ISSN:0069-3030    

DOI:10.1039/OC98683FX001

出版商:RSC    

年代:1986

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC98683BX003

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

3 Theoretical Chemistry By M. GODFREY Department of Chemistry The University Southampton SO9 5NH 1 Introduction In recent years it has become common for the results of applications of standard computational methods to problems in specialized fields to be included in reports on those fields. Consequently my main criterion for selecting items for this chapter has been the perceived interest to organic chemists as a whole. Most of the relevant material divides quite well into two main categories (i) that which concerns innova- tions in and criticisms of theoretical models the concepts used in them and rules generated from them and (ii) that which gives information on molecular structures and reaction mechanisms through the application of established models.Occasionally a particular aspect of organic chemistry catches the imagination of theoreticians. This year it was the aromaticity of a C60 cluster Buckminsterfullerene or footballene a species which may have been formed in the laser vaporization of graphite and by natural processes in stars. An amusing account of the background to this problem has been given by Kroto.’ My philosophical highlight of the year was an article in which Turro’ explored the intellectual and scientific foundations of organic chemistry and of the methods that provide the field with a platform for making rapid conceptual and experimental advances. It was proposed that these methods involve a geometric and topological approach to scientific reasoning within the framework of scientific paradigms that guide experimental design and execution.2 Models Concepts and Rules Computational Models.-Many organic chemists are confused by the wide variety of basis sets used in MO calculations. Davidson and Feller3 have reviewed basis sets of the type known as ‘contracted Cartesian Gaussians’ from the point of view of the non-specialist who is interested in a practical guide to what is generally available and of the pitfalls to avoid. Ichikawa and his co-workers4 have compared 22 different basis sets for the calculation of molecular electronic structures. They conclude that polarization functions must be added to both heavy atoms and hydrogen atoms in order to produce well-balanced wave functions. Marriott and Topsom’ have found that calculations of barriers to rotation in some mono-’ H.Kroto Roc. R. Znst. 1986 58 45. N. J. Turro Angew. Chem. Znt. Ed. Engl. 1986 25 882. E. R. Davidson and D. Feller Chem. Rev. 1986 86 681. H. Ichikawa K. Sameshima and Y. Ebisawa Bull. Chem. SOC.Jpn. 1986 59 2729. S. Marriott and R. D. Topsom Aust. 1. Chem. 1986 39 1157. 17 18 M. Godfrey substituted benzenes are in better agreement with experiment when minimal basis sets are used for both energy and geometry optimization than when split-valence basis sets are used. Progress made before 1986 on the problem of reducing the errors associated with basis set truncation has been reviewed by Wilson.6 The efficient computation of electron correlation effects is a continuing challenge. Developments include a relatively simple method for calculating correlation energies in large organic molecules which offers a good physical insight into the phenomenon of electron ~orrelation,~ and the application of a novel method to acetylene ethylene and ethane which shows that specific correlation patterns arise from different kinds of bond.8 Locating transition states on potential energy surfaces is also a difficult computa- tional problem.Baker’ has designed a new algorithm for use within the GAUSSIAN 82 program package. It is capable of locating transition states even if the search is started in the wrong region of the surface. Semi-empirical MO methods involving the complete neglect of differential overlap (CNDO) are now rarely used. However some methods involving a degree of NDO are still quite popular.Their usefulness relative to ab initio methods continues to be questioned. Baird and Hadley” have claimed that the apparent superiority of MNDO over ab initio in predicting molecular energetics disappears when the methods are compared on the same basis and McKee Shevlin and Rzepa” have concluded that MNDO and MNDOC cannot be relied upon for the energetics of proton transfer between oxygens or between nitrogens. More sympathetically Lewis” has reviewed the MIND0/3 method Dewar and Reynold~’~ have reported an improved set of MNDO parameters for sulphur and Dewar and DieterI4 have claimed that AM1 seems to be an effective method for studying processes involving deprotonation or protonation of neutral molecules.Schroder and Thiel” have provided some general guidelines for MNDOC studies of thermal organic reactions following a comparative study of correlation effects on activation energies and transition state structures. Although parametrized for neutral closed-shell molecules both MIND0/3 and MNDO methods work well overall in reproducing experimental heats of formation of closed-shell and open-shell cations containing C H N and 0; there are however failures with certain types of structure.16 Regarding other methods for computing molecular structure Lifson” has reviewed the theoretical foundation of the Empirical Force Field approach and Saunders and Jarret18 have described a new method for optimizing molecular structures in which the terms involving bond angles and torsional angles used in the force fields S.Wilson Adu. Chem. Phys. 1987 67 439. A. M. Oles F. Pfirsch P. Fulde and M. C. Bohrn J. Chem. Phys. 1986 85 5183. G. Stollhoff and P. Vasilopoulos J. Chem. Phys. 1986 84 2744. J. Baker J. Comput. Chem. 1986 7 385. 10 N. C. Baird and G. 0. Hadley Chem. Phys. Lett. 1986 128 31. M. L. McKee P. B. Shevlin and H. S. Rzepa J. Am. Chem. Soc. 1986 108 5793. 12 D. F. V. Lewis Chem. Reu. 1986 86 1111. l3 M. J. S. Dewar and C. H. Reynolds J. Comput. Chem. 1986 7 140. 14 M. J. S. Dewar and K. M. Dieter J. Am. Chem. Soc. 1986 108 8075. 15 S. Schroder and W. Thiel J. Am. Chem. SOC.,1986 108 7985. 16 H. Halim N. Heinrich W. Koch J. Schmidt and G. Frenking J. Comput. Chem. 1986 7 93. 17 S.Lifson Gazz. Chim. Ztal. 1986 116 687. 18 M. Saunders and R. M. Jarret J. Comput. Chem. 1986 7 578. Theoretical Chemistry 19 of conventional molecular mechanics are replaced with two-body central forces between atoms with considerable computational advantage. Bonding.-The nature of the covalent bond is not as simple as most textbook discussions s~ggest.'~~~' The accumulation of electron density appears weak or even absent in certain covalent bonds. An explanation for this anomaly is that the structures of some atoms change dramatically as a first step in the bond-formation process.21 Valence bond calculations2' without the imposition of any orthogonality constraints show the equivalent hybrid (banana) description of the double bond in ethylene to be more stable than a u plus 7r bond description.Theories of bonding in charge-transfer complexes have been reviewed.23 Linear conjugation is preferred to cross conjugation for systems of four p-orbitals containing four 7r Studies of the structures and stabilities of fluorinated carbanions provide evidence for negative hyperconjugation by the CF3 group.2s It is known that in pentalene and heptalene an alternating bond structure is more stable than a delocalized bond structure whereas in each corresponding radical anion the opposite is the case. It has been demonstrated26 that electron-donating substituents at some sites tend to relax bond alternation but such substituents at other sites enhance bond alternation. The concept of bond fixation provides no help in understanding the geometry of cyclopropabenzene a molecule which consists of fused cyclopropene and benzene rings.27 Molecular Shape and Size.-Meyer28 has reviewed some of the procedures used to estimate molecular size andz9 has extended his own contribution to the field by proposing new shape and bulk descriptors to deal with steric effects of substituents on reaction rates.Richards3' has developed an approximate method for calculating molecular similarity based on the notion of standard electron densities for molecular fragments. Theory of Reactions.-Papers given at an international conference on the theory of organic reactions held at Gargnano Italy in June 1985 have been published under the editorship of Bernardi.31 Bernardi and Robb3' have analysed the cycloaddition of two ethylene molecules in terms of their own diabatic surface model and have shown that the behaviour of the constituent surfaces can be easily rationalized by using simple MO energy expressions.19 N. C. Baird J. Chem. Educ. 1986 63 660. 2o K. Jug N. D. Epiotis and S. Buss J. Am. Chem. SOC.,1986 108 3640. 21 K. L. Kunze and M. B. Hall J. Am. Chem. SOC.,1986 108 5122. 22 W. E. Palke J. Am. Chem. SOC.,1986 108 6543. 23 C. J. Bender Chem. SOC.Rev. 1986 15 475. 24 S. Inagaki K. Iwase and N. Goto J. Org. Chem. 1986 51 362. 2s D. A. Dixon T. Fukunaga and B. E. Smart J. Am. Chem. SOC.,1986 108 4027. 26 M. Kataoka T. Ohmae and T. Nakajima J. Org. Chem. 1986 51 358. 2' Y. Apeloig and D. Arad J.Am. Chem. SOC.,1986 108 3241. 28 A. Y. Meyer Chem. SOC.Rev. 1986 15 449. 29 A. Y. Meyer J. Chem. SOC.,Perkin Trans. 2 1986 1567. 30 E. E. Hodgkin and W. G. Richards J. Chem. SOC.,Chem. Commun. 1986 1342; P. E. Bowen-Jenkins and W. G. Richards Int. J. Quantum Chem. 1986 30 763. 31 THEOCHEM 1986 31 Nos. 1/2. 32 F. Bernardi M. Olivucci M. A. Robb and G. Tonachini J. Am. Chem. SOC.,1986 108 1408. 20 M. Godfrey An alternative to the FMO method for predicting regiochemical preferences has been presented by Hehre and his co-worker~.~~ Measures of differential reactivity of the various sites in nucleophiles towards electrophiles and in electrophiles towards nucleophiles are obtained by allowing the test electrophile H+ and the test nucleophile H- to interact with the electron density surfaces of the substrates.Preferred sites of interaction between actual nucleophiles and electrophiles are then predicted by matching these differential reactivities. Alston and his co-~orkers~~ have demonstrated that the regio-selectivity in the Diels- Alder reaction of 1 -substituted- 1,3-butadienes can be completely explained by FMO theory when the FMOs of the reactants in the concerted transition state as opposed to the ground state are considered. Bachrach and Streitwieser3’ have concluded that the FMO approximation of HOMO-LUMO interactions dominating the transition state is too severe HOMO-HOMO interactions are also important. The configuration mixing model of Pross and Shaik36 has been used by Pros3’ to classify polar reactions as ‘allowed’ and ‘forbidden’.Thus direct nucleophilic attack is forbidden with respect to radical cations but allowed with respect to dications. The same model has been used by Shaik3* to give a unified understanding of the factors controlling the mechanistic choice of a given reactant pair the variation of the reaction barriers and the geometries of the transition states in a set of nucleophilic substitution reactions. The dynamical excitation of high vibrational states in the direct scattering process has been given as the most probable reason for the low efficiency of gas-phase SN2 reactions with no activation barriers.39 Increasing understanding of biological redox systems has led to the need for detailed information regarding the effects of mutual orientation and separation distance of the redox partners on the rate of electron transfer.Marcus4’ has developed a semi-classical model for orientation effects and4’ has given a theoretical treatment for the effects of intramolecular vibrational and diff usive solvent orientational motions. War~hel~~ has developed a semi-classical trajectory approach to the micro- scopic simulation of electron transfer reactions in polar solvents. Aromaticity.-One of the most nebulous concepts in organic chemistry is aromaticity. Everyone is agreed that benzene is highly aromatic but even in this case the electronic basis of the property is uncertain. Cooper Gerratt and Rairn~ndi~~ have argued that the T electrons of benzene are essentially localized and that the aromatic characteristics arise from the symmetric coupling of the electron spins around the 33 S.D. Kahn C. F. Pau L. E. Overman and W. J. Hehre J. Am. Chem. SOC.,1986 108 7381; S. D. Kahn C. F. Pau and W. J. Hehre ibid. 1986 108 7396; S. D. Kahn and W. J. Hehre ibid. 1986 108 7399. 34 P. V. Alston R. M. Ottenbrite 0. F. Guner and D. D. Shillady Tetrahedron 1986 42 4403. 35 S. M. Bachrach and A. Streitwieser J. Am. Chem. Soc, 1986 108 3946. 36 A. Pross and S. S. Shaik Acc. Chem. Res. 1983 16 363. 37 A. Pross J. Am. Chem. SOC.,1986 108 3537. 38 D. Cohen R. Bar and S. S. Shaik 1. Am. Chem. SOC.,1986 108 231. 39 M. V. Basilevsky and V. M. Ryaboy Chem. Phys. Lett. 1986 129 71. 40 R. J. Cave S. J. Klippenstein and R.A. Marcus J. Chem. Phys. 1986 84 3089. 41 H. Sumi and R. A. Marcus J. Chem. Phys. 1986 84,4894. 42 A. Warshel and J.-K. Hwang J. Chem. Phys. 1986 84 4938. 43 D. L. Cooper J. Gerratt and M. Raimondi Nature (London) 1986 323 699. Theoretical Chemistry 21 carbon ring framework. BairdU has argued against the conclusion of Hiberty Shaik Ohanessian and Lefour which I reported last year that the symmetric structure for benzene is preferred because of the a-bond energy but the latter authors have disagreed with his arg~ment.4~ Buckminsterfullerene appears to be a spherical aromatic molecule. The many reported calculation^^^ on this species illustrate the difficulties in establishing a precise definition of degree of aromaticity. By the Huckel rule planar cis-[ 12lannulene is anti-aromatic but high level ab initio MO calculations surprisingly indicate a small positive resonance energy.47 The concept of o-aromaticity helps in explaining why cyclopropane has a very similar strain energy to cycl~butane.~~ The role of homoaromaticity in stabilizing appropriate species has been further explored.49 SINDO/ 1 calculations have been used to establish that excited states of antiaromatic molecules can exhibit aromatic ~haracter.~' Finally it has been shown that aromatic transition-state theory and the general rule of the principle of conservation of orbital symmetry can be regarded as the same concept described in different termin~logies.~' Linear Free Energy Relationships and Substituent Effect Analysis.-The disputation between Wold and Sjostrom who regarded LFERs as locally valid linearizations of complicated functional relationships and Kamlet and Taft who believe that LFERs reflect fundamental and rather simple physiochemical relationships con- tinue~.~~ A chemometric investigation of substituent effects on chemical and spectro- scopic data sets leads to the conclusion that individual components of the two effects cannot be determined q~antitatively.~~ There is still little understanding of short-range substituent effects.A statistical analysis54 has demonstrated that Mullay's group electronegativity scale (reported last year) linearly correlates with (J,which is widely regarded as a good measure of the field effect of a substituent.The apparent dissimilarity of the two scales is due to a large constant term in the electronegativity scale. There is no precise relationship between a,and the HCC bond angles at the ips0 carbon in monosub- stituted ethylenes as determined by ab initio MO calculation^.^^ This result is in 44 N. C. Baird J. Org. Chem. 1986 51 3907. 45 P. C. Hiberty S. S. Shaik G. Ohanessian and J.-M. Lefour J. Org. Chem. 1986 51 3908. 46 R. L. Disch and J. M. Schulman Chem. Phys. Lett. 1986 125 465; P. W. Fowler and J. Woolrich ibid. 1986 127 78; R. C. Haddon L. E. Brus and K. Raghavachari ibid. 1986 125 459; 1986 131 165; A. D. J. Haymet J. Am. Chem. Soc. 1986 108 319; B. A. Hess and L. J. Schaad J. Org. Chem. 1986 51 3902; D. J. Klein T. G. Schmalz G. E. Hile and W.A. Seitz J. Am. Chem. Soc. 1986 108 1301; D. S. Marynick and S. Estreicher Chem. Phys. Lett. 1986 132 383; M. D. Newton and R. E. Stanton J. Am. Chem. Soc. 1986 108 2469; A. J. Stone and D. J. Wales Chem. Phys. Lett. 1986 128 501. 47 R. C. Haddon hre Appl. Chem. 1986 58 129. 48 D. Crerner and J. Gauss J. Am. Chem. Soc. 1986 108 7467. 49 P. v. R. Schleyer E. Kaufmann A. J. Kos H. Mayr and J. Chandrasekhar J. Chem. SOC. Chem. Commun. 1986 1583; A. B. McEwen and P. v. R. Schleyer J. Org. Chem. 1986 51 4357. 50 E. J. P. Malar and K. Jug Tetrahedron 1986 42 417. '' Z. Hua-ming and W. De-xiang Tetrahedron 1986 42 515. 52 S. Wold and M. Sjostrom Acta Chem. Scand. Ser. B 1986,40 270; M. J. Kamlet and R. W. Taft ibid. 1986 40 619. 53 S. Alunni S.Clementi C. Ebert P. Linda G. Masumarra U. Edlund M. Sjostrom and S. Wold Gazz. Chim. Ital. 1986 116 679. 54 E. Sacher Tetrahedron Lett. 1986 42 4683. 5s S. Marriott and R. D. Topsom THEOCHEM 1986 32 101. 22 M. Godfrey accord with earlier work on monosubstituted benzenes. An MNDO indicates that inductive effects of a-substituents have no special importance in determining substituent stabilization effects on carbocations. The Marcus relationship between free energy of activation and free energy of reaction has been applied extensively to electron proton and group transfer reac- tions in organic chemistry over the years. A special issue of the Journal of Physical Chemistry” to commemorate the contributions of Marcus to chemistry includes papers from several leading physical organic chemists.This year Form~sinho~~ has presented an extension of the Marcus relationship that involves two new independent variables. Within this extended relationship it is possible to describe the progress of sigmatropic shifts and cycloadditions in terms of one progress variable. Marcus theory breaks down when the bond order of the transition state varies with the nature of the reaction and/or when the effect of the configuration entropy is significant. Elsewhere59 Formosinho has proposed a general inter-relationship between transition state bond extensions and the energy barrier to reaction. The model introduces the concept of a variable bond order over the reaction path if reactants or products have anti-bonding or non-bonding electrons which can have a bonding character at the transition state.That Marcus theory can sometimes be successful in reproducing quantum mechanical data has been demonstrated in an MO study6’ of the effects of a-alkyl substituents on proton transfers between pairs of nitrogen atoms and between pairs of oxygen atoms. Another probe into the relationship between transition state structures and reac- tivities through an MO study of specific reactions this time the additions of amines to carbonyl compounds gives support to the BEP (Bell-Evans-Polanyi) theory in that the activation energy falls as the reaction becomes more exothermic.61 On the other hand transition state structures and kinetic isotope effects are virtually invariant in spite of a wide variation in reactivity.The significance of the Bransted parameter for transition state structure remains a subject for conjecture. Shaik6* has defined a new intrinsic selectivity factor for identity S,2 reactions which yields information about (a) the average looseness of the transition state geometry in a reaction series; and (b) the sensitivity of the reaction series to geometric loosening. Lee and S~hn~~ have given mechanistic significance to values of cross interaction constants pij in an extended Hammett relationship for simultaneous variation of two substituents in different part of a reaction complex. The relative gas-phase acidities and basicities of substituted amines mercaptans alcohols etc. are believed to be strongly dominated by charge/induced-dipole stabilization of the ion formed by protonation or deprotonation.A scale of substituent effects on this factor has been obtained64 from ab initio MO calculations on a model 56 A. M. Aissani J. C. Baum R. F. Langler and J. L. Ginsburg Can. J. Chem. 1986 64 532. 57 J. Phys. Chem. 1986,90 No. 16. 58 S. J. Formosinho Tetrahedron 1986 42 4557. 59 A. J. C. Varandas and S. J. Formosinho J. Chem. SOC.,Faraday Trans. 2 1986 82 953. 6o S. Scheiner and P. Redfern J. Phys. Chem. 1986 90 2969. 61 H. Yamataka S. Nagase T. Ando and T. Hanafusa J. Am. Chem. SOC.,1986 108 601. 62 S. S. Shaik Can. J. Chem. 1986 64 96. 63 1. Lee and S. C. Sohn J. Chem. SOC.,Chem. Commun. 1986 1055. 64 W. J. Hehre C. F. Pau A.D. Headly R. W. Taft and R. D. Topsom J. Am. Chem. Soc. 1986,108 1711. The0retica1 Chemistry 23 system. The variation of the gas-phase basicities of amines can be analysed by using two parameters one global and one local.65 Other Electronic Effects.-It has been concluded66 that merostabilization of carbon- centred radicals is important in media of high dielectric constant but less so in the gas phase. In the gas phase only this merostabilization (or capto-dative) effect has been ~alculated~~ to be greater in nitrogen-centred radicals than in carbon-centred analogues. Ab initio studies68 have indicated that intramolecular long distance electron transfer between A and A2 in [A1-G-A2]- proceeds mostly by through-bond interaction involving the spacer G and does so in a very stereospecific manner.Other ab initio studies69 indicate that relay orbitals play an important role in the determination of the energy levels in molecules containing a pair of perpendicular T systems (e.g. spiropentadiene). New interpretations have been reported for the antiperiplanar effect in eliminations from ethane derivatives and for the cis effect in difluoroethylenes. In the former case,7o continuity of phase of the bonding and anti-bonding orbitals of the antiperi- planar bonds and the bonding orbital of the intervening C-C bond is the key factor. In the latter case,’ attraction of one fluorine nucleus for electrons of the other fluorine atom is considered to be relatively very important. 3 Studies of Molecular Structures and Reaction Paths General.-Applications of computational methods to the study of biological systems have been revie~ed.~~,~~ have continued to produce their Ohno and M~rokuma~~ annual bibliography of ab initio calculations.Ab initio Structures.-The ability to perform calculations with sophisticated basis sets and with allowance for electron correlation permits the reinvestigation of structural problems concerning stable molecules. The preference of 1,2-difluoroethane for the gauche rather than the trans conformation can be explained at the MP2/6-31G** level but not at the Hartree-Fock Polarization functions in the basis set reduce the rotational barriers in formamide and acetamide by about 5 kcal mol-’ at the Hartree-Fock level; electron correlation yields less than 1 kcal-mol-’ further red~ction.~~ The effect of including polarization functions on the geometrical parameters for pyridine has been determir~ed.~’ 65 W.Yang and W. J. Mortier J. Am. Chem. SOC.,1986 108 5708. 66 A. R. Katritzky M. C. Zerner and M. M. Karelson J. Am. Chem. SOC.,1986 108 7213. 67 D. Kost M. Raban and K. Aviram J. Chem. SOC.,Chem. Comrnun. 1986 346. 68 K. Ohta G. L. Closs K. Morokuma and N. J. Green J. Am. Chem. Soc. 1986 108 1319. 69 K. Kanda T. Koremoto and A. Imamura Tetrahedron 1986 42 4169. 70 S. Inagaki K. Iwase and Y. Mori Chem. Lett. 1986 417. 71 M. M. Heaton and M. R. El-Talbi THEOCHEM 1986,32 61. 12 ‘Theoretical Chemistry of Biological Systems’ ed. G. Naray-Szabo Elsevier Amsterdam 1986.73 Y.B. Luzhkov and G. N. Bogdanov Russ. Chem. Rev. (Engl. Transl.) 1986 55 272. 74 THEOCHEM 1986 33 Nos. 3/4. 75 G. F. Smits M. C. Krol P.N. Van Kampen and C. Altona THEOCHEM 1986 32 247. 76 P. G. Jasien W. J. Stevens and M. Krauss THEOCHEM 1986 32 197. 17 D. A. Dixon T. Fukunaga and B. E. Smart J. Am. Chem. SOC.,1986 108 1585. 24 M. Godfrey Molecules containing second row atoms can now be studied by ub initio methods. It has been that d polarization functions on sulphur play an essential role in the formation of the disulphide bond in CH3SSCH3. The conformational behaviour of bithienyls is similar to that of bif~ranyls.'~ Methyl and trifluoromethyl hyperconjugation," and the stabilization of a-substituted carbocations" and car- banions,82 with substituents based on second-row atoms have also been studied.Other species investigated include fluorine substituted phosphonium ylidess3 and the thioxyallyl radi~al.'~ Dicationic species have attracted much attention. The linear structure of C4H22f is markedly less stable than the 4-membered ring.85 Back donation of fluorine lone-pair electrons is very important in determining the shape of fluorine-substituted ethylene dications.86 Bipyridine dications have markedly twisted conformations while the corresponding radical cations are nearly planar this may be significant for herbicidal action.87 Barriers to the dissociation of ylide dications H2C=XH2+ (X = NH, OH F PH2 SH and C1) are substantial and hence these species may be observable.88 Lischka and KarpfenS9 have begun a systematic study at different levels of sophistication of electronically excited states in the polyene and polyyne series.A study of the low-lying electronic states of ketene has added to the understanding of the dissociation of ketenes to carbenes." There has been continuing interest in carbenes" and diradi~als,~ and in solvent- solute interaction^.^^ Ab initio Potential Energy Surfaces Transition States and Mechanisms.-Bernardi and R~bb~~ have published an essay on transition state structure computations and their analysis covering the pre- 1986 literature. The mechanisms of pericyclic reactions have continued to attract interest. There is more evidence for the synchronous concerted mechanism in the Diels-Alder reaction of butadiene with eth~lene.9~ The cycloaddition of HF to ethylene is easier 78 M.Honda and M. Tajuna THEOCHEM,-1986,29,93. 79 V. Barone F.Lelj N. Russo and M. Toscano J. Chem. SOC.,Perkin Trans. 2 1986 907. 80 E. Magnusson J. Am. Chem. SOC.,1986,108,11. F. Bernardi A. Bottoni and A. Venturini J. Am. Chem. SOC. 1986 108 5395. 82 F. Bernardi A.Bottoni A. Venturini and A. Mangini J. Am. Chem. SOC.,1986 108 8171. D. A. Dixon and B. E. Smart J. Am. Chem. SOC.,1986 108 7172. 84 T. Furuhata and W. Ando Tetrahedron Lett. 1986,27 4035. 85 K. Lammertsma J. A. Pople and P. v. R.Schleyer J. Am. Chem. SOC.,1986,108 7. 86 G. Frenking W. Koch and H. Schwarz J. Comput. Chem. 1986,7,406. H.-J. Hofmann R.Cimiraglia and J.Tomasi THEOCHEM,1986,32,213. 88 B. F.Yates W. J. Bouma and L. Radom. J. Am. Chem. Soc.. 1986 108 6545. 89 H.Lischka and A. Karpfen Chem. Phys. 1986 102,77; A. Karpfen and H. Lischka ibid. 1986,102.91. 90 W. D. Allen and H. F. Schaefer J. Chem. Phys. 1986,84 2212. 91 E.A.Carter and W. A. Goddard J. Phys. Chem. 1986,90,998;D. A.Dixon ibid. 1986,90 54; G. E. Scuseria M. Duran R.G. A. R.Maclagan and H. F. Schaefer J. Am. Chem. SOC.,1986,108 3248; H. Tomioka T. Sugiura Y. Masumoto Y. Izawa S. Inagaki and K. Iwase J. Chem. Soc. Chem. Commun. 1986 693; J. S. Yadav and J. D. Goddard J. Chem. Phys. 1986,85 3975. 92 P. Du D. Hrovat and W. T. Borden J. Am. Chem. SOC.,1986 108 8086. 93 C. A. Deakyne M. Meot-Ner C. L. Campbell M. G. Hughes and S. P. Murphy J.Chem. Phys. 1986 84 4958;J. Gao D. S. Gamer and W. L. Jorgensen J. Am. Chem. SOC.,1986 108 4784; P. G.Jasien and W. J. Stevens J. Chem. Phys. 1986,84 3271. 94 F. Bernardi and M. A. Robb Adu. Chem. Phys. 1987 67 155. 95 K. N. Houk Y.-T. Lin and F. K. Brown J. Am. Chem. SOC.,1986,108,554. Theoretical Chemistry 25 with the H-Fs-aH-F dimer than with a single H-F m01ecule.~~ There is no barrier in the gas phase to the symmetry forbidden [3 + 21 cycloaddition of the butadiene radical cation to eth~lene.~' Dewar's suggestion which I reported last year that tunnelling from a twisted form of the reactant should play an important part in the mechanism of the thermal [1,5]H shift in cis-1,3-pentadiene is strongly supported the reaction is found most likely to proceed via a transition state of C2 symmetry.98 Ab initio MO calculations support the predictions of resonance theory for the preferred protonation sites in furan and in vinyl alcohol.99 The proton-transfer properties of C=O in the carboxyl group of formic acid are very similar to those of C=O in formaldehyde.The primary effect of the OH group is to increase the proton affinity of the C=O. The proton affinity of OH is lowered by its association with C=O.loo Formic acid pyrolyses to yield carbon monoxide and carbon dioxide by competing processes. It appears that the water molecules produced along with the carbon monoxide catalyse the formation of carbon dioxide."' Calculated substituent effects on neutral and ionized C=C and C=O bonds imply that the variation of the keto :enol ratio for first-row substituents ought to be very different with radical cations than with neutral compounds.'"2 The enhanced rate of sN2 displacement of chloride ions due to neighbouring group effects is similar in origin in a-chloroacetaldehyde and in ally1 ch10ride.l'~ A PMO analysis of ab initio results for identity &2 reactions involving various a-substituents and various nucleophiles/leaving groups indicates that the T interac-tions between the a-substituent and an occupied orbital associated with the reaction co-ordinate axis are of major importance in governing the transition state energy.lo4 The activation energy for 0-alkylation of acetaldehyde enolate by methyl fluoride is lower than that for C-alkylation even though the latter is favoured thermodynami- cally.This and other results imply that a free enolate reacts exclusively at oxygen regardless of the hardness or softness of the alkylating agent or whether the transition state is early or late. The preference for C-alkylation of metal enolates in solution must arise from co-ordination of the enolate oxygen by metal cations which is known to decrease the reactivity of the oxygen site relative to the carbon site.'" Arylcarbenes readily undergo intramolecular reactions with nucleophilic groups in ortho substituents whereas simple benzyl cations do not in spite of similar intermolecular reactivities of carbenes and cations. This dramatic difference has been attributed to considerably lower barriers to rotation about the bond connecting the sp2 carbon atom to the ring in the arylcarbenes.'06 96 C.Clavero M. Duran A. Lledos 0. N. Ventura and J. Bertran J. Am. Chem. Soc. 1986 108 923. 97 D. J. Bellville and N. L. Bauld Tetrahedron 1986 42 6167. 98 G. J. M. Dormans and H. M. Buck 1.Am. Chem. Soc. 1986 108 3253. 99 M. T. Nguyen A. F. Hegarty T.-K. Ha and G. R. De Mare J. Chem. Soc. Perkin Trans. 2 1986 147. 100 E. A. Hillenbrand and S. Scheiner J. Am. Chem. Soc. 1986 108 7178 101 P. Ruelle U. W. Kesselring and H. Nam-Tran J. Am. Chem. SOL 1986 108 371. 102 N. Heinrich W. Koch G. Frenking and H. Schwarz J. Am. Chem. SOC.,1986 108 593. 103 R. D. Bach B. A. Coddens and G. J. Wolber J. Org. Chem. 1986 51 1030. 104 D. Kost and K. Aviram J.Am. Chem. SOC.,1986 108 2006. K. N. Houk and M. N. Paddon-Row J. Am. Chem. Soc. 1986 108 2659. 106 W. Kirmse. K. Kund E. Ritzer A. E. Dorigo and K. N. Houk J. Am. Gem. SOC. 1986 108 6045. 26 M. Godfrey Studies of potential energy surfaces indicate that the dication of formic acid is not stable and that C(OH):+ is the global minimum;'07 that H2NCH2+ and H3NC2+ are the stable species on the NCH3'+ surface;lo8 and that CH=CH-C=O' is a stable species on the C3H20t s~rface.''~ Calculations with biological significance include the reaction of hydroxyl radical with cytosine;"' and the oxidation of triose reductone which has the same functional group as L-ascorbic acid."' Semi-empirical.-The emphasis in reported semi-empirical MO calculations has been on mechanism rather than structure.The main methods used have been MIND0/3 MNDO MNDOC and AM1. Cycloadditions have been studied with the following results. The Diels- Alder reaction of butadiene cannot be synchronous with cyanoethylenes but the mechanism remains uncertain with ethylene itself."' The transition states for the Diels- Alder reaction of acrolein with cyclopentadiene and several monosubstituted derivatives of butadiene have been located there is a possibility of a two-step mechanism where charge-transfer is great. The results are in good agreement with experimental observa- tions regarding selectivity and substituent effects on reaction rate.' l3 The thermal 2,5-cycloaddition of alkenes to phenols can occur only when strained cyclic alkenes are empl~yed."~ An asynchronous mechanism has been proposed for the 1,3-dipolar cycloaddition of substituted cyclic azomethine ylides to chloroacrylonitrile the minimum potential energy surface explains the observed regioselectivity.' l5 The cycloaddition of cyclopentyne to ethylene proceeds via a very short-lived diradical intermediate.lI6 In the tetrahedral intermediate in the BAc2 hydrolysis of an ester acyl-oxygen bond dissociation preceeds hydroxylic hydrogen tran~fer."~ In the acid-catalysed hydrolysis of acetamide rate-determining nucleophilic attack of water at the carbonyl group occurs in the N-protonated species rather than in the 0-protonated tautomer.The resulting tetrahedral species are not at the energy minima but at or near the saddle points."* The mechanism for ips0 attack in the nitration of certain aromatic molecules involves radical pair recombination rather than classical electrophilic substitution.' l9 Calculations of potential energy surfaces for the interaction between peroxyformic acid and ethylene or substituted ethylenes do not support the electrophilic mechan- isms that are currently favoured.Instead they suggest that peroxyformate anions should add to olefins. With electron-withdrawing substituents in the olefins there is lo' W. Koch and H. Schwarz Chem. Phys. Lett. 1986 125 443. W. Koch N. Heinrich and H. Schwarz J. Am. Chem. SOC.,1986 108 5400. 109 G. Bouchoux Y. Hoppilliard J.-P. Flament J. K. Terlouw and F. van der Valk J. Phys. Chem. 1986 90 1582.110 B. G. Eatock W. L. Waltz and P. G. Mezey Can. J. Chem. 1986 64 914. 111 Y. Abe H. Horii S. Taniguchi S. Yamabe and T. Minato Can. J. Chem. 1986 64,360. 112 M. J. S. Dewar S. Olivella and J. J. P. Stewart 1.Am. Chem. SOC.,1986 108 5771. 113 V. Branchadell A. Oliva and J. Bertran THEOCHEM 1986 29 25. 114 J. Amau J. Fernandez and P. Yianni J. Chem. SOC.,Perkin Trans. 2 1986 2013. M. C. Cardozo M. T. Pizzorno S. M. Albonico and A. B. Pierini Tetrahedron 1986 42 5857. 116 S. Olivella M. A. Pericas A. Riera and A. SolC J. Chem. SOC.,Perkin Trans. 2 1986 613. 117 J. J. Maraver E. S. Marcos and J. Bertran J. Chem. SOC.,Perkin Trans. 2 1986 1323. 118 I. Lee C. K. Kim and H. S. Seo Tetrahedron 1986,42 6627. J. Feng X. Zheng and M.C. Zerner J. Org. Chem. 1986 51 4531. Theoretical Chemistry no activation energy. With electron-donating substituents a two-step mechanism is predicted involving the formation of a metastable intermediate and rate-determining epoxide ring closure.'2o The MIND0/3 potential energy surface'21 for the ethylene dication is not similar to the ab initio surface.'22 Other Computational Procedure~.-Jorgensen'~~has used a novel combination of ab initio quantum mechanics and statistical perturbation theory to study the effect of hydration on the structure of the transition state for the SN2exchange reaction of C1- and CH,Cl. The effect is found to be very small. In earlier work on this reaction he had found that the activation barrier induced by hydration results primarily from reduction in strength rather than reduction in the number of solute- water hydrogen bonds upon proceeding to the transition state.This year he has obtained a similar result for nucleophilic attack of hydroxide ion on the carbonyl carbon of f0rma1dehyde.l~~ Stimulated by the importance of -NH,+ and -COO- groups in molecules of biological interest and the role of solvation by water in influencing the interactions of these groups K01lman'~~ has initiated a Monte Carlo simulation study of the solvation of these groups using CH3NH3' and CH3COO- as models. The nature of the water structure around the methyl group of CH,NH,+ is significantly different from that around the methyl group in CH,COO-. The calculations reported in this sub-section involve considerable amounts of computer time and approach the limit of what can reasonably be attempted at the present time.I20 J. Kaneti Tetrahedron 1986 42 4017. 121 M. J. S. Dewar and C. H. Reynolds THEOCHEM 1986 29 209. 122 K. Lammertsma M. Barzaghi G. A. Olah J. A. Pople A. J. Kos and P. v. R. Schleyer J. Am. Chem. Soc. 1983 105 5252. 123 W. L. Jorgensen and J. K. Buckner J. Phys. Chem. 1986,90,4651. 124 J. D. Madura and W. L. Jorgensen J. Am. Chem. SOC.,1986 108 2517. 125 G. Alhgona C. Ghio and P. Kollman J. Am. Chem. SOC.,1986 108 185.

ISSN:0069-3030    

DOI:10.1039/OC9868300017

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (i) Pericyclic Reactions By D. W. JONES Department of Organic Chemistry The University Leeds LS2 9JT 1 General The two most cited reviews published in Angewandte Chemie (ht. Ed. Engl.) over the twenty-five years of its existence both deal with pericyclic reactions. In first place with 1821 citations comes Woodward and Hoffmann's famous review 'The Conservation of Orbital Symmetry'.'" Huisgen's article '1,3-Dipolar Cycloadditions -Past and Future'lbSC follows with 1449 citations. It is a tribute to Woodward and Hoffmann that not only their theory but the language they invented to describe it have largely survived the test of time. One troublesome point of semantics not discussed by them arises for concerted (one-step) but asynchronous reactions in which at the transition state (TS) not all bond-making and bond-breaking processes have proceeded to the same extent.It has been suggested that the term two-stage be used when some of the changes in bonding take place mainly before the TS and the remainder between the TS and the The description of such TS's as biradicals is inappropriate if there is interaction between the formal radical centres which confers a degree of cyclic conjugation; the term biradicaloid TS is preferable." 2 Cycloaddition Reactions Evidence for the concertedness of the addition of butadiene to ethylene has been obtained by addition of (1) to cis-dideuterioethylene (2) which gives the cis-adduct (3) and less than 1 % of its trans-isomer.2a Since the barrier to rotation in a biradical intermediate (4) would be expected to be only 0-0.4 kcal mol-' extensive loss of stereochemistry would have been expected if (4) were an intermediate.The reverse Diels-Alder reaction of an adduct derived from two aromatic molecules should most closely approach the ideal synchronous reaction.2b In such adducts both addends lack the two singly occupied p-orbitals required for aromaticity and only simultaneous generation of these allows the TS to acquire part of the aromatic ' (a) R. B. Woodward and R. Hoffmann Angew. Chem. Znt. Ed. Engl. 1969 8 781; (6) ibid. 1986 25 A-3; (c) R. Huisgen ibid. 1963 2 565; (d) M. J. Goldstein and J. L. Thayer J. Am. Chem. Soc. 1965 87 1925; (e) M. J. S. Dewar S. Olivella and J. J. P. Stewart ibid.1986 108 5771. '(a) K. N. Houk Y.-T. Lin and F. K. Brown J. Am. Chem. SOC.,1986 108 554; (6) A. Bertsch W. Grimme and G. Reinhardt Angew. Chem. Znt. Ed. Engl. 1986 25 377; (c) R. Engelke J. Am. Chem. SOC.,1986,108,5799; (d) F.-G. Klarner B. M. Dogan 0.Ermer W. von E. Doering and M. P. Cohen Angew. Chem. Znt. Ed. Engl. 1986 25 108; (e) H. D. Roth M. L. M.Schilling and C. J. Abelt J. Am. Chem. Soc. 1986 108 6098; Tetrahedron 1986 42 6157; (f)S. D. Kahn C. F. Pau L. E. Overman and W. J. Hehre J. Am Chem. Soc. 1986 108 7381. 29 D. W. Jones D stabilization. For a series of five adducts made up from two arenes e.g. (5) and (6) the reduction in the TS state energy for cycloreversion was 43% of the resonance energy gained. The activation free-energy for the cycloreversions extended over a range of 13 kcal mol-'.Since rate-determining single bond cleavage to a biradical would result in a variation of only 2kcalmol-' in the resonance energies of the intermediates a synchronous mechanism is indicated. A theoretical study on the other hand predicts an asynchronous mechanism for the formation of (5) from two benzene molecules.2c The thermal dimerization of 1,3-cyclohexadiene gives the endo (7) and em (8) Diels-Alder dimers as well as the syn (9) and anti (lo) (2 + 2)-dimers and the threo (6 + 4) ene product (1 1). The activation volumes and energies for the formation of these products suggest concerted mechanisms for (7) and (11) and two-step mechanisms for (8) (9) and (10). Here the concerted processes are less than 4 kcal mol-' more favourable than the two-step processes.The novel (6 + 4)-ene process (12; arrows) showed a KIE (kH/kD) of 2.42 similar to that found for the normal (4 + 2) ene reaction.2d Spiro[2,4]heptadiene undergoes easy (4 + 2)-dimerization to (13) via photo-chemical electron-transfer to strong electron acceptors. Time-resolved CIDNP effects Reaction Mechanisms -Part (i) Pericyclic Reactions 4 -4 ,+; indicate the radical cation (14) is present during the addition2' so that at least a part of the reaction is two-step. Whilst the FMO model correctly predicts the major regioisomer from the reaction of mono-substituted dienes with mono-substituted dienophiles the theory overesti- mates the directing ability of a 2-substituent on the diene in competition with a 1-substituent.Experimentally even strong donors like alkoxyl at C-2 are dominated by weak donors like methyl at C-1 and if the same group is present at both C-1 and C-2 of the diene it is the C-1 substituent which directs the addition. An alternative approach which partly overcomes this problem uses complementary reactivity sur- faces for the diene and dienophile.2f The electrophilic surface of an electron-poor dienophile and the nucleophilic surface of an electron-rich diene are derived by calculating the interaction of hydride ion and a proton with the respective surfaces; the results are displayed in colour code for matching. It is still not possible to predict accurately which diastereotopic face of a diene will be preferentially involved in a Diels- Alder addition; the undesired arrangement (15)dominated in an approach to actinobolin although related allylically oxygenated dienes had shown the opposite facial ~electivity.~" The solid-state conformation (16) ZHN-/=+ I -SiO+ 7 I ' CHzOAcAcO H H- (15) (a) A.P. Kozikowski T. Konoike and T. R. Nieduzak J. Chem. SOC.,Chem. Commun. 1986 1350; A. P. Kozikowski and T. R. Nieduzak Tetrahedron Lett. 1986 27 819; (b) R. C. Gupta A. M. Z. Slowin R. J. Stoodley and D. J. Williams J. Chem. Soc. Chem. Commun. 1986 1116; (c) S. D. Kahn and W. J. Hehre Tetrahedron Lett. 1986 27 6041; (d) G. H. Posner and D. G. Wettlaufer J. Am. Chem. Soc. 1986 108 7373; Tetrahedron Lett. 1986 27 667; (e) D. L.Boger and M. Patel Tetrahedron Lett. 1986 27 683; (f)T. R. Kelly A. Whiting and N. S. Chandrakumar J. Am. Chem. Soc. 1986 108 3510; K. Maruoka M. Sakurai J. Fujiwara and H. Yamamoto Tetrahedron Lett. 1986,27,4895; (8)S. G. Davies and J. C. Walker J. Chem. SOC.,Chem. Commun. 1986 609; (h) J. W. Herndon J. Org. Chem. 1986 51 285; (i) P. G. Lenhert C. M. Lukehart and L. Sacksteder J. Am. Chem. SOC.,1986 108,793; (j)K. Furuta K. Iwanaga and H. Yamamoto Tetrahedron Lett. 1986 27 4507. D. U? Jones is consistent with an approximately sp2-hybridized 0-1 whose lone pair can both conjugate with the diene system and participate in an exo-anomeric effect with the C-1'-0-1' bond. Diene attack from above upon the cisoid conformer of (16) derived by the 180" bond rotation shown accounts for the useful facial selectivity exhibited by this diene.,' Vinyl sulphoxides add dienes via the cisoid conformer shown in (17).Electron-rich dienes select the face opposite the sulphur lone pair even at the expense of steric clash with a bulky R group.3c The enol ether (18) reacts with the electron-deficient diene (19) with good diastereoface selectivity despite the separ- ation of the stereogenic centre in (18) from the double bond by a freely rotating ether link.," Both butadiene and 1-methoxy-3-trimethylsilyloxybutadiene add exclusively syn to the heteroatom bridge of the olefins (2O).," Diels- Alder additions to naphthoquinones like (21) proceed with high asymmetric induction when conduc- ted in the presence of chiral Lewis acids prepared in sitw31 The (S)-( + )-acryloyl complex (22) adds cyclopentadiene in the presence of zinc chloride to give mainly (23) derived by addition to the face of the double bond away from the PPh ligand.Oxidative removal of the iron (Ce'") gave endo-norbornene-2-carboxylicacid characterized as the optically pure iod~lactone.~~ The related acyl-iron complexes (24; R = Hor Me) add smoothly to dienes at 25 "C under ethylaluminium dichloride catalysis.3h Formulation of the reacting species as (25) agrees with the known dienophilic reactivity of related Fischer carbene complexes like (26) which react 0-A1C1 E t OMe / C' H~C=CH' +cr(co) (a) M. E. Jung and K. R. Buszek Tetrahedron Lett. 1986,27 6165; (b) S. J. Danishefsky and C. Vogel J.Org. Chem. 1986 51 3915;(c) P. A. Grieco S. D. Larson and W. F. Fobore Tetrahedron Lett. 1986 27 1975; (d) P. A. Grieco and S. D. Larsen J. Org. Chem. 1986,51,3553; (e) P. G. Gassman and D. A. Singleton J. Org. Chem. 1986 51 3075; (f)K. Hayakawa S. Ohsuki and K. Kanematsu Tetrahedron Lett. 1986,27,947; K. Hayakawa T. Yasukouchi and K. Kanematsu ibid. 1986,27,1837; (g)R. Sigrist M. Rey and A. S. Dreiding J. Chem. SOC., Chem. Commun. 1986,944. Reaction Mechanisms -Part (i) Pericyclic Reactions with simple dienes ca. lo4 times more rapidly than methyl acrylate with improved regio- and stereo-~electivity.~' For the addition of dimenthyl fumarate to several dienes Et2AlC1 is much superior to AlC13 in the diastereoisomeric excesses ~btained.~' ,Other novel dienophiles include the vinylpyridinium salts (27; Z = CN CO,Me H) which react with cyclopentadiene in MeOH-H,O to give exclusively the adducts (28) with endo-pyridinium and the imine (29) which reacts with (30) (BF,.Et,O catalyst) as a key step in the synthesis of ipalbidine!b Iminium salts derived from a number of a-dicarbonyl compounds e.g.(31) react with cyclo- pentadiene in water at 25°C to give good yields of adducts e.g. (32):' The intramolecular version of this process is also successful; heating (33) with aqueous MeNH,.HCl gives (34).4d Ally1 cations can be regarded as double bonds made strongly dienophilic by attachment to a carbonium ion centre. In agreement with this view the allylalcohol (35) and CF3S03H at -23°C give (36) (77'/0).~~Allenes appear to be reactive dienophiles in intramolecular addition^.^^ A particularly pleasing example4g involves reaction of the mixture of allylic bromides (37) with (38) to give (39) en route to sativen.H' (35) (36) (37) D. W Jones Although the intramolecular Diels- Alder reaction commands extremely wide use in synthesis' there are few systematic studies which reveal useful general information about the effect of changes in the 'handle' between diene and dienophile upon the ease and stereoselectivity of the process. The influence of the length of the carbon chain connecting diene and dienophile has been explored for the intramolecular additions depicted in (40) for values of n from 5-11.6" When n = 6 z.e.the new left-hand ring was 6-membered addition occurred at 20 "C but when n = 10 or 11 the thermal reaction failed and catalysis by Me,AlCl was required. For n = 5 and 7 heating at >140 "Cwas needed. The failure of (40; n = 5) to undergo catalysed addition is attributed to the preference of the aluminium complex for an s-trans conformation unsuitable for the addition. Only the addition of (40; n = 5 or 6) showed high stereoselectivity (for a cis ring-junction) and here the stereoselectivity was greater than for the intermolecular reaction. 0 The now well recognized beneficial effect of running some Diels-Alder reactions in water is not accounted for by well established solvent parameters; the accelerating effect of water is too great. However a new solvophobicity parameter set Sp based on the energy changes of noble gases alkanes etc.for transfer from gas to a given solvent successfully correlates the rate of addition of dimethyl fumarate with cyclo- pentadiene in a range of solvents including water.6b The same authors note that whereas P-cyclodextrin inclusion strongly promotes the addition of diethyl fumarate to cyclopentadiene the addition of ethyl acrylate to the same diene is actually retarded by P-cyclodextrin; the result may be due to preferred binding of two molecules of either the diene or the dienophile. Pools of water in clays accelerate additions to furans,6c and the addition of butyl acrylate and acrylonitrile to cyclopen- tadiene is speeded in micelles with accompanying increased endo-selectivity.6d Aqueous Diels- Alder reaction in the presence of P-cyclodextrin provided a vital rate enhancement in the intramolecular addition (41;arrows) allowing preparation of the kinetic product (42) in 96% yield.6' The hetero-Diels-Alder reaction in natural product synthesis has been reviewed.6f Two conditions might be expected to give rise to two-step 1,3-dipolar cycloaddi- tion.When both HO-LU interaction energies are similar the addition is slowest and e.g. P. A. Brown and P. R. Jenkins J. Chem. Soc. Perkin Trans. 1 1986 1303; H. Dyke R. Sauter P. Steel and E. J. Thomas J. Chem. Soc. Chem. Cornmun. 1986 1447; H. J. Reich E. K. Eisenhart R. E. Olson and M. J. Kelly J. Am. Chem. Soc. 1986 108 7791; M. Ladlow P. M. Cairns and P. Magnus J. Chem.Soc, Chem. Cornmun.,1986 1756; S. Handa K. Jones and C. G. Newton ibid. 1986 1797; D. L. Boger and R. S. Coleman J. Org. Chem. 1986 51 3250; K. Shishido K. Hiroya Y. Ueno K. Fukumoto T. Kametani and T. Honda J. Chem. Soc. Perkin Trans. 1 1986 829; K. Fischer and S. Hunig Chem. Ber. 1986 119 2590 3344; K. J. Shea and J. J. Svoboda Tetrahedron Lett. 1986,27 4837. (a) D. A. Smith K. Sakan and K. N. Houk Tetrahedron Lett. 1986,27,4877; H.-J. Schneider and N. K. Sangwan J Chem. Soc. Cbem. Cornmun. 1986 1787; (c) P. Laszlo Acc. Chem. Res. 1986,19,121; (d) R. Brown F. Schuster and J. Sauer Tetrahedron Lett. 1986 27 1285; (e) W. M. Grootaert and P. J. DeClerq Tetrahedron Lett. 1986 27 1731; (f)R. R. Schmidt Acc. Chem. Rex 1986 19 250. Reaction Mechanisms -Pert (i) Pericyclic Reactions a biradical path is expected in the presence of stabilizing substituents.Alternatively if the HO (1,3-dipole)-LU (dipolarophile) interaction is very dominant the other FMO interaction will be very weak and in the extreme it should be overcome by the more favourable entropy of a two-step process. The 1,3-dipole (43) has a high energy HO due to the absence of electronegative atoms and steric effects favour two-step addition. Addition of (43) to the very electron-deficient dipolarophile (44) (low energy LUMO) shows marked non-stereospecificity which increases with sol- vent polarity. The zwitterion (45) is suggested as intermediate and the related zwitterion from (43) and tetracyanoethylene can be trapped with methan01.~" H 'OH (411 (42) (431 Me02C ,CN NC Ji C02Me COzMe (44) (45) Reaction between CD2N and CH20 has been carried out both thermally and phot~chemically.~~ Both reactions give CD20 which is believed to arise via the 1,3-dipole (46).The related dipoles (47) are generated by heating arylchlorodiazirines in acetone and are trapped in the presence of acetylenic ester^.'^ Although secondary interaction would be expected to favour endo-addition of dipolarophiles to nitrones only maleates behave in this way. The exo-adducts are the main products of the kinetically controlled addition of cyclic nitrone (48) to mono-substituted dip~larophiles.~~ Related additions provide useful routes to simple alkaloids7' '(a)R. Huisgen G. Mloston and E. Langhals J. Am.Chem. SOC.,1986,108,6401; R. Huisgen E. Langhals and H. Noth Tetrahedron Lett. 1986 27 5475; (b) G. K. S. Prakash R. W. Ellis J. D. Felberg and G. A. Olah J. Am. Chem. SOC.,1986 108 1341; (c) T. Ibata M. T. H. Liu and J. Toyada Tetrahedron Lett. 1986 27 4383; (d)J. J. Tufariello and J. M. Puglis ibid. 1986 27 1265; (e)J. J. Tufariello and K. Winzenberg ibid. 1986 27 1645; J. J. Tufariello H. Meckler and K. Winzenberg J. Org. Chem. 1986 51 3556; (f)D. L. Boger and C. E. Brotherton J. Am. Chem. SOC.,1986 108 6695; 1986 108 6713; Tetrahedron 1986,42 2777; (g) E. Vedejs and J. W. Grisson J. Am. Chem. SOC.,1986 108 6433; (h) A. Padwa and J. R. Gasdanska ibid. 1986 108 1104; (i) A. Padwa J. R. Gasdanska M. Tomas N. J. Turro Y. Cha and I. R. Could ibid.1986 108 6739. D. W. Jones The fascinating species formulated as (49) arises upon heating the cyclopropenone acetal (50) at 75 "C.In the presence of ketones adducts of type (51) are formed and the related adduct (52) is obtained from dimethyl methoxymethylenemalonate. With methyl acrylate on the other hand the product (53) of carbene-type addition is observed. As befits a highly strained olefin (high energy HO and low energy LUMO) (50) adds 1,4 to dienes substituted with either donor or acceptor groups. Steric effects are held responsible for the failure of (50) to add to a-pyrones at sufficiently low temperature to avoid addition of the ring-opened form (49) which leads to adducts of the type (54) from the Eschenmoser intermediate (55) in the synthesis of colchicine.High-pressure stimulated addition of (50) to a-pyrones proceeds without the intervention of (49).7f A The dihydrooxazolines (56; R" = H) open spontaneously to the azomethine ylides (57). In contrast if R = alkyl aryl etc. eclipsing effects in the planar dipole inhibit ring-opening; the heating of aziridines (58) then gives (56) as stable products.7g With silver fluoride the indoles (59) are believed to give the 1,3-dipoles (60) which can be trapped e.g. with acrylonitrile to give the adducts (61) which then lose Ago and a proton (61; In related work" the nitrile ylide (62) has been generated by AgF-induced elimination of PhSSiMe from the silylthioimidate (63). R RwAkR' 0 R"' (58) (57) R I CH2SiMe CHY Reaction Mechanisms -Part (i) Pericyclic Reactions Pha Me CH,-CAI-CH The bromonitrile oxide (64) can be slowly generated from (65) using solid sodium hydrogen carbonate in ethyl acetate.Trapping is consequently efficient e.g. (66) and its regio-isomer are formed in a CQ. 4 :1 ratio in 86%yield. Even trisubstituted olefins react well8" The method has been used to make epipodophyllotoxin.8b 0-h X-Ray structure determination shows that protonated Ruhemann's purple is the stable N-protonated 1,3-dipole (67) which reacted with several dipolarophiles to give the expected adducts in high yield.8' Reaction of ninhydrin with a-amino-acids in the presence of N-phenylmaleimide gives the adduct type (68) of the N-protonated 1,3-dipole (69) providing evidence for such 1,3-dipoles in the ninhydrin reaction.Sulphinylaminomethanide anions (70) rather than protonated species like (69) are believed to be intermediates in the reaction of thionylaniline with a-amino-acids.8d Ph *(a)P. Caldirola M. Ciancaglione M. DeAmici and C. DeMichaeli Tetrahedron Lett. 1986 27 4647; (b) D. M. Vyas P. M. Skonezny T. A. Jenks and T. W. Doyle ibid. 1986 27 3099; (c) R. Grigg J. F. Malone T. Mongkolaussavaratana and S. Thianpatanagul J. Chem. SOC.,Chem. Commun. 1986 421; (d) R. Grigg M. Dowling and V. Sridharan ibid. 1986 1777; (e) E. Vedejs and C. K. McClure J. Am. Chem. SOC.,1986,108,1094; (f)K. N. Houk,H.-Y. Duh Y.-D. Wu and S. R. Moses ibid. 1986,108,2754. D. W Jones Hyperconjugative effects of allylic substituents were found to be unimportant in determining facial selectivity in the osmylation of allylic silanes sulphones sul- phides silyl ethers and acetates.8e Osmium ligand effects are suggested as being important and for 2-double bonds an alkoxy-anti alkyl-outside conformation is preferred.These results conflict with earlier suggestions made by Houk about the preference of an alkoxy-group for the inside position in addition TS's. The latter group have now studied the addition of nitrile oxides to the olefins (71) where R' is larger than R2;the adduct (72) was more important than (73). If (71) reacted in its ground-state conformation (shown) this would require preferred approach to the more hindered face and increasing selectivity for this face as the size of R' increased.The major product is therefore believed to arise via the staggered TS (74) with the largest group (L) anti and the medium-sized.group in the inside position. The minor product arises via TS (75). For allylic ethers the alkoxy-group takes the place of M in (74) although this probably occurs to minimize electron repulsion between the allylic oxygen and the nitrile oxide oxygen rather than to reduce electron withdrawal from the double bond as postulated earlier.*J y-/H R' H-C R2 The formal (4 + 4)-dimerization of (76; R = R' = H) to (77) is probably a two-step process with a biradical (78) as intermediate; (76; R = D R' = H) dimer- izes ca. six times more slowly than (76; R = H R' = D).9a A similar biradical intermediate is proposed for formation of both the formal (4 + 2)-and (4 + 4)-dimers of 0-q~inodimethane.~' Intramolecular (6 + 4)-addition to the tropone nucleus has been studied with a view to the synthesis of Ingenane diterpenes.Like the intermolecular reaction the intramolecular one is exo-selective (79) giving (SO)." Both intramolecular (6 + 4)-9d and (8 + 6)-addition9" can be observed with fulvenes as 67r components. Vinylogous urethanes like (81) lose ethanol upon FVP at ca. (a)C. H. Chou and W. S. Trahanovsky J. Am. Chem. SOC., 1986 108,4138; (b)W. S. Trahanovsky and J. R. Macias ibid. 1986 108 6820; (c) R. L. Funk and G. L. Bolton ibid. 1986 108 4655; J. H. Rigby T. L. Moore and S. Rege J. Org. Chem. 1986 51 2398; (d) Y. N. Gupta R. T. Patterson A. Z. Bimanand and K.N. Houk Tetrahedron Lett. 1986 27 295; (e) C.-Y. Liu D. A. Smith and K. N. Houk ibid. 1986 27 4881; (f)F. Arya J. Bouquant and J. Chuche ibid. 1986,27 1913; (g) J. Mann Tetrahedron 1986 42 4611; (h) H. R. Seikaly and T. T. Tidwell ibid. 1986 42 2587; (i) H. D. Roth Editor ibid. 1986 42. Reaction Mechanisms -Part (i) Pericyclic Reactions R 400 "C to give vinylketenes which undergo intramolecular (2 + 2)-addition (82; arrows).9f The synthetic utility of oxyallyl cationsgg and the addition reactions of ketenesgh have been reviewed and the structure and reactivity of organic radical cations has been the subject of a Symposium in Print.g' 3 Sigmatropic Reactions A non-randomized biradical intermediate (83) in the thermolysis of deuterium labelled ( -)-(S)-a-pinene (84) will explain the D-distribution in the products [( f )-limonene alloocimene and a little (R)-a-pinene] as well as the effect of the label in reducing the quantity of ( * )-limonene formed whilst not slowing the disappearance of (84).''' Biradical intermediates have also been suggested for D3cr D3C CH3 0 several other apparent 1,3-shifts.lob Although walk rearrangement in the bicyclo[2.1 .O]pentane system proceeding with inversion at C-5 could involve a biradical intermediate (85) this would have to be different from the biradicals generated by photolysis of pyrazolines like (86); the biradical (87) formed from the latter undergoes bonding between C-5 and both C-1 and C-3 and in both cases the side of C-5 originally bonded to nitrogen is (a) J.J. Gajewski and C. M. Hawkins J. Am. Chem. SOC., 1986 108 838; (b) J. W. Barton and M. K. Shepherd J. Chem. SOC.,Perkin Trans. 1 1986 961; X. Creary and M. E. Mehrsheikh-Mohammadi J. Org. Chem 1986,51 1110; B. Miller and J. Bagdadchi J. Chem. SOC.,Chem Commun. 1986 1257; M. Christl C. Herzog and P. Kemmer Chem. Ber. 1986 119 3045; (c) F.-G. Klarner V. Glock and H. Frigge ibid. 1986 119 794; (d) R. M. Jarret M. Saunders S. Pikulin and J. A. Berson J. Am. Chem. SOC.,1986 108 2768; (e) P. de Mayo and G. Wenska J. Chem. SOC.,Chem. Commun. 1986 1626. D. W. Jones MeOCH2 D The cation (88) undergoes walk rearrangement (1,4-sigmatropy) much more rapidly than (89). This may be associated with a dicyclopropylcarbinyl cation (90) as intermediate or TS; the failure of (88) to give the benzyl cation is presumably due to the requirement of a conrotatory electrocyclic ring-opening.lod Irradiation (A > 420nm) of (91) and suspended CdS induces a 1'3-hydrogen shift to (92).loe This presumably involves the radical-cation of (91 ) produced by electron-transfer to a 'hole' photogenerated in the semi-conductor.dH2 Arrhenius parameters and a primary kinetic isotope effect (kH/kD = 6.3-7.6) for the fast 1'5-hydrogen shift to the central carbon of an allene (93; arrows) points the similarity of this process to simple 1,Shydrogen shifts."" The sulphone (93; R' = SO,Ph R = H) and the sulphoxide (93; R' = SOPh R = H) rearrange ca. 700 and ca. 100 times more rapidly than (93; R' = R = H).Moreover a But group and a sulphoxide favour migration of hydrogen to different faces of the allene double bond; the But group favours migration to the lower face [Hb migration in (93)] to give (94) whilst the SOPh group favours migration to the upper face (Ha migration) to give (95),llb Although generated at 0 "C (96) is not detectable. Instead (97) the product of an extremely easy 1,Sbenzyl shift is obtained.'lc The order of migratory aptitude RSO > RS -H > RS02 > RCO > C0,Et has been deter- mined for the 1,5-shift in e.g. the transient species (98).'ld In related carbocyclic systems formyl and acetyl groups migrate faster than hydrogen and direct conversion '' (a) S. A. Barrack and W. H. Okamura J. Org. Chem. 1986 51 3201; (6) W.H. Okamura G.-Y. Shen and R. Tapia J. Am. Chem. SOC.,1986 108 5018; (c) B. Miller and J. Baghdadchi J. Chem. Soc. Chem. Commun. 1986 511; (d) R. S. Gairns C. J. Moody and C. W. Rees J. Chem. SOC.,Perkin Trans. 1 1986 501; (e) M. J. Collett D. W. Jones and S. J. Renyard ibid. 1986 1471; P. J. Battye and D. W. Jones ibid. 1986 1479; (f)J. J. Gajewski A. M. Gortfa and W. T. Borden J. Am. Chem. SOC.,1986 108 1083. Reaction Mechanisms -Purr (i) 'Pericyclic Reactions of (98; Y = H) into product (99) by prototropy rather than via 1,5-sigmatropy is a possible explanation. Full papers have appeared dealing with the very different relative migratory aptitudes of doubly and triply bonded groups about cyclopen- tadiene and cycloheptatriene systems.'le.Thermolysis of (100) gives first the products of formal 1,5-shift (101) and its C-7 epimer in a ratio of 3 1; (101) involving forbidden inversion of the migrating carbon is dominant. Accordingly it is proposed that rearrangement involves a biradical intermediate.' Substitution of deuteriums at the terminal methylene carbons of (102) allowed measurement of a bond-making KIE in the boat-like Cope process (102; arrows). This indicated 25% bond-making at the TS. This value compares with one of cu. 67% in chair-like acyclic rearrangement and rules out significant intervention of the biradical (103) as intermediate or TS.'*" Attempts to prepare sulphoxides of type (104) by oxidation of the related sulphides gave instead the sulphines (105) derived Me$T"2-j .-&/ & Me' f.-CH2 Me b (102) (103) (104 (105) (a) J.J. Gajewski and J. L. Jimenez J. Am. Chem. Soc. 1986 108 468; (b) E. Block S. Ahmad J. L. Catalfamo M. K. Jain and R. Apitz-Castro ibid. 1986 108 7045; J. R. Hwll and D. J. Anderson Tetrahedron Lett. 1986 4965; (c) K. J. Shea S. C. Greerley S. Nguyen P. D. Beauchamp D. H. Aue and J. S. Witzeman J. Am. Chem. Soc. 1986 108 5901; (d) N. Eisen and F. Vogtle Angew. Chem. Int. Ed. Engl. 1986 25 1026. D. W. Jones by rearrangement (104; arrows). Although (104) could use the accelerating effect of both the sulphonium salt and anionic oxy-Cope rearrangements it rearranges only 45 times faster than the sulphide in the absence of acid.'2b Cope rearrangement of systems of the type (106) where m is 1 or 2 and n is 3 or 4 provides a route to several meso-bridged dienes (107).The rearrangement rates do not correlate with relief of strain. More likely the high HOMO energy of the bridgehead bond when rn = 1 or 2 is an important factor.12' On the other hand ring-strain is believed to induce the Cope-rearrangement (108; arrows) converting an 11-membered into a 15-membered ring.'2d The stereochemistry of Claisen and related processes has been explored'3a and contrary to the general view some tertiary allylic alcohols participate in such rearrangements with good stereochemical contr01.'~ The Ireland-Claisen rearrange- ment (109; arrows) is a key step in a synthesis of q~adrone'~' and the use of large-ring lactones in these reactions has been explored'3d en route to dicotyl diterpenes.Amusingly the planned conversion of (1 10) into (1 11) via Claisen rearrangement failed. Instead (1 10) underwent reverse (4 + 2)-addition to (1 12) which then gave (1 11) by intramolecular (4 + 2) additi~n!.'~' RO,C 02 Ro2ca R3si0& IH'Et \ /i 'Et Et Whilst the lithium enolate (1 13; M = Li) undergoes 2,3-sigmatropic shift to (114) the silylketene acetals (1 13; M = SiMe,Bu') undergo 3,3-shift (1 13; The l3 (a) G. W. Daub and D. A. Griffith Tetrahedron Lett. 1986 27 6311; G. W. Daub P. L. Shanklin and C. Tata J. Org. Chem. 1986 51 3402; C. S. Wilcox and R. E. Babston J. Am. Chem. SOC.,1986 108 6636; (6) A. H. Davidson and I. H. Wallace J. Chem. SOC.,Chem. Commun. 1986 1759; (c) R. L. Funk and M.M. Abelman J. Org. Chem. 1986,51,3247; (d) N. J. Begley A. G. Cameron and D. W. Knight J. Chem. SOC.,Perkin Trans. 1 1986 1933; A. G. Cameron and D. W. Knight ibid. 1986 161; (e)S. D. Burke D. A. Armistead and K. Shankaran Tetrahedron Lett. 1986 27 6295. (a) S. Raucher and L. M. Gustavson Tetrahedron Lett. 1986 27 1557; (6) M. C. Pirrung and J. A. Werner J. Am. Chem Soc. 1986 108 6060; E. J. Roskamp and C. R. Johnson ibid. 1986 108 6062; (c) K. Mikami 0.Takahashi T. Tabei and T. Nakai Tetrahedron Lett. 1986,27,4511; (d)T. Takahashi H. Nemoto Y. Kanda and T. Tsuji J. Org. Chem. 1986 51 4315; J. A. Marshall T. M. Jenson and B. S. DeHoff ibid. 1986 51 4316; (e) M. Uchikawa T. Hanamoto T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1986 27 4577 Reaction Mechanisms -Part (i) Pericyclic Reactions 0 oxygen ylides (1 15) generated by Rh" catalysed decomposition of the diazoketones (116) undergo 2,3-shift (115; arrows) to 5- 6- and 8-membered oxygen heterocycle^.'^^ Similar oxygen ylides may be intermediates in the reaction of the ally1 ethers (117) with trimethylsilyl triflate-Et,N which gives the Wittig rearrange- ment products (1 18).14' A 2,3-Wittig ring-contraction (1 19; arrows) has been explored in routes to cembranoids and cost~nolide.'~~ Asymmetric 2,3-rearrange- ments of the related amides (120) proceed with high syn-diastereo and diastereo-face ~e1ection.l~~ 0.!OMOM 4 Electrocyclic Reactions The preference of a wdonor substituent for outward rotation in cyclobutene ring- opening has been examined for (121).The conrotatory mode-1 [see arrows in (121)] involves inward rotation of only one fluorine atom whilst mode-2 involves inward rotation of two fluorine atoms. The first mode is favoured over the second by ca. 13 kcal mol-' in good agreement with a predicted value of 13 kcal mol-' for the activation energy difference for outward and inward rotation of a single fluorine High temperature equilibrium constants for the valence tautomerism of l5 (a) W. R. Dolbier H. Koroniak D. J. Burton and P. Heinze Tetrahedron Lett. 1986 27 4387; (b) M. E. Squillacote and A. Bergman J. Org. Chem. 1986 51 3910; (c) K. Schishido K. Hiroya K. Fukumoto and T. Kametani Tetrahedron Lett. 1986,27,971; (d) K. Schishido K. Hiroya H.Komatsu K. Fukumato and T. Kametani J. Chem. SOC.,Chem. Commun. 1986,904; (e)A. Hassner and S. Naidorf Tetrahedron Lett. 1986 27 6389; (f)L. S. Leibskind S. Iyer and C. F. Jewell J. Org. Chem. 1986 51 3065; S. T. Perri L. D. Foland 0. H. W. Decker and H. W. Moore J. Org. Chem. 1986 51 3067; (g) R. L. Danheiser S. K. Gee and J. J. Perez J. Am. Chem. Soc. 1986 108 806. D. W. Jones cyclo-octatetraene and bicycle[ 4.2.0loctatriene have been determined by rapid cool- ing of high temperature mixtures. Extrapolation of the results to 100 "Cgives a AGO value of 7.1 kcal mol-' in good agreement with an earlier indirect estimate (AGO 6.8 kcal m~l-').'~~ Heating (122) at 180 "C results in a fascinating sequence of electrocyclic ring-opening to (123) ring-closure to ( 124) and Claisen rearrangement to (125).lSc The general scheme has been used in alkaloid ~ynthesis.'~~ \ Me The thermal ring-opening of cyclobutenones to vinylketenes is well established.The corresponding photo-reaction has now been shown to have advantage^.'^^ Irradiation of (126) (A = 300 nm) gives the vinylketene (127) which is long-lived and may be efficiently trapped several minutes after irradiation has ceased. Trapping with isopropene is now successful whereas in the thermal process polymerization intervened. Adduction is regiospecific but mixtures of stereoisomers are formed. Whereas .rrf + 7:approach of ketene and olefin should give mostly cis-product e.g. (1 28) from cyclohexa- 1,3-diene the thermal reactions give mostly trans-products.The photogenerated ketene gave mostly (128) which was shown to be converted in c1 c1 C15 \ Ph Phb c15ph 0 o+C Reaction Mechanisms -Part (i) Pericyclic Reactions part into its 2,3-trans isomer on heating. Cyclobutenone ring-opening provides a useful route to q~inones.'~~ Thus the derivatives (129) ring-open with well preceden- ted outward rotation of the donor group (OH) to give the vinylketenes (130) which ring-close to (131); tautomerism and oxidation then gives naphthoquinones. The Ar group in (129) may be replaced by a vinyl group or a heterocyclic substituent. Pride of place for ingenuity in the use of vinylketenes must go to Danheiser and his collaborator^.'^^ The vinylketene (1 32) generated from the related cyclobutenone at 120 "C adds to the electron-rich acetylene (133) to give cyclobutenone (134) which ring-opens to (135).Electrocyclic ring-closure (135; arrows) and prototropy then gives (136) which can be readily converted into mycophenolic acid in 17-19'/0 overall yield. R 0 ,I,f II Me0I CH20CH20Me L+ CH,OCH,OMe (133) (132) (134) Me (135) (136) R = E-CH,CH=C(Me)(CH,),OSiMezBu'

ISSN:0069-3030    

DOI:10.1039/OC9868300029

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (ii) Polar Reactions By D. J. McLENNAN Department of Chemistry University of Auckland Auckland New Zealand 1 Introduction Several of the most notable 1986 contributions appeared in Symposia-imprint. An issue of Israel Journal of Chemistry (with a 1985 dateline) was devoted to the reactivity-selectivity principle (RSP) whilst Tetrahedron featured an issue on hydride transfer. The Journal ofPhysical Chemistry dedicated an issue to Ruldoph A. Marcus and Arthur N. Bourns was similarly honoured by the Canadian Journal ofchemistry. Discussion of relevant papers will be deferred to the appropriate mechanistic section. If Pross and Shaik have their way there may well be no Polar Reactions subsection in Annual Reports in the near future.Their configuration mixing (CM) model blurs the distinction between ‘polar two-electron’ shifts and radicaloid one-electron trans- fers. Pross has comprehensively reviewed the field and has applied the qualitative theory to a wide variety of reaction types.’ Radical intermediates are not a necessary consequence of the emphasis on one-electron shifts but it is noteworthy that further evidence has been adduced for radical and radical ion intermediates in what were hitherto regarded as ionic reactions. The quantitative aspects of the CM model addressed by Shaik will be covered elsewhere. Even on this basis the concept of effective charge on an atom in a transition state (TS) is still valid insofar as this is the charge ‘seen’ by substituents and solvent.Thea and Williams discuss ways of measuring such charges.2 Ionic reactions are of course not constrained to condensed media and a considerable body of work on gas-phase nucleophilic displacement reactions has been re~iewed.~ Douglas has presented an account of work on elimination-addition pathways for chemical and biochemical reactions of thiol esters4 Nature has played a nasty trick on researchers in this area since some thiol chemistry will always be necessary. Having once dabbled with thiols himself the Reporter appreciates perhaps more than most the apt Shakespearian epilogue to Douglas’s paper. Seeman has reviewed in practical terms the integration of the Curtin-Hammett and Winstein-Holness concept^.^ ’ A. Pross Adu. Phys. Org. Chem. 1985,21,99.’ S.Thea and A. Williams Chem. SOC.Reu. 1986,15,125. J. M. Riveros,S. M. Jose and K. Takashima Adu. Phys. Org. Chem. 1985,21 197. K.T.Douglas Acc. Chem. Rex 1986,19,1986. ’ J. I. Seeman J. Chern. Educ. 1986,63,42. 47 D. J. McLennan Heterolysis of carbon-carbon bonds yields carbanions and carbocations. Arnett and Molter continue their work in this area and have developed a master equation for predicting solution heterolysis energies and re-emphasize that the energetics of anion-cation combination reactions are dominated by ion solvation factors. It is therefore not surprising that a spectacular failure of the RSP is found confirming a Pross prediction of some years ago. Zwitterions are also best discussed in a general mechanistic section.It is somewhat ironic that the debate over one-step (concerted pericyclic) us. two-step 1,3-dipolar cycloaddition reactions previously focused attention on the possibility of biradical intermediates in the stepwise cases. The first clearcut evidence for the stepwise mechanism presented equally ironically by Huisgen is interpreted in terms of zwitterionic intermediates for cases involving high HOMO (1,3-dipole) and low LUMO (dipolarophile) energies.' The cycloadditions in question are non-stereos- pecific7" and intermediates have been intramolecularly tra~ped.~ The rich diversity of mechanistic pathways in nucleophilic vinylic substitution is exemplified in a comprehensive review by Rappoport.8 The search for alternative catalytic methods for routine organic reactions has progressed from the laboratory to the kitchen.The use of microwave ovens acceler- ates common polar reactions in solution by factors up to 250-f0ld.~ Pressure solvent superheating and even solvent boiling point seem to be of importance in determining the magnitude of the accelerations. While kinetic and mechanistic investigations will undoubtedly continue the applicability of the method to large-scale preparations is mandated. Cook-book chemistry may well acquire a new and less derisory dimension. 2 Solvolysis and Carbocations Proton loss from carbocations to yield alkenes and/or fragmentation products is a commonplace occurrence. Loss of a methyl group when for instance (1) yields (2) plus (3) (12 1) in FS03H-S02 at -60°C is less expected." Carr and Whittaker claim that methyl loss as CH3+ competes with methyl migration prior to cyclization and support their proposal by observing that (a) the medium is non-nucleophilic (b) the TS for a shift of methyl from a gem-dimethyl group is highly crowded and (c) CH,03SF has been observed in a similar case.The stability of ethers in super-acid apparently rules out direct attack by the hydroxyl oxygen on methyl. E. M. Arnett and K. Molter J. Phys. Chem. 1986,90 383. '(a) R. Huisgen G. Mloston and E. Langhals J. Am. Chem. SOC.,1986 108 6401; (b) J. Org. Chem. 1986,51 4085. Z. Rappoport Recl. Trau. Chim. Pays-Bas 1985 104 309. R. Gedge F. Smith K. Westaway H. Ali L. Baldisera L. Laberge and J. Rousell Tetrahedron Lett. 1986 27 279.lo G. Cam and D. Whittaker J. Chem. Soc. Chem Commun. 1986 1245. Reaction Mechanisms -Part (ii) Polar Reactions 49 Organic non-carbocations of interest have been reported. The triphenylsilyl cation has been prepared according to equation 1 and the trivial name sityl has been proposed." The methoxydiazonium cation CH30N2+ has been prepared by methyla- tion (MeF-SbF in S02F2 or S02C1F) of N20 and acts as a methylating agent rather than a methoxylating agent towards toluene.12 Attempts to prepare the hydroxy analogue HON2+ were unsuccessful but in any case this cation lacks an essential feature for mention in Section B of Annual Reports. Ph3SiH + Ph3C+C104-+ Ph3Si+C104-+ Ph3Cl (1) Diary1 carbocations destabilized by an a-carbonyl group (4) have been prepared from alcohois using C1S03H and have a reasonable lifetime at low temperature.'' 13 C N.m.r.parameters suggest that the 0x0 structure (5) is not a significant resonance contributor. At ambient temperature these ions form benzofurans or fluorenes by 6 T electrocyclization. Long-range 19F n.m.r. isotope shifts due to y-deuteration in carbocations are upfield whereas the corresponding P-deuterium shifts are d0wnfie1d.I~ This corre- sponds to the situation met with for kinetic and equilibrium isotope effects in carbocation-forming solvolysis which are normal for P-deuterium and inverse for y-deuterium in spite of the differing mechanisms governing the two types of isotope effects. Laser flash photolysis of Ph3COAc allows generation of ground-state Ph3C+ in solution (1:2 MeCN-H20) and reactions of the free carbocation with nucleophiles can be st~died.'~ Water reacts with a rate constant of 1.5 x lo5s-' whilst azide ion is the most reactive of the nucleophiles studied with a rate constant of 4 x lo91 mol-' s-I which is close to the diffusion limit (and close to the indirectly determined calibration value of 5 x lo91 mol-' s-l employed by Jencks and co-workers for the 1-phenylethyl cation).Surprisingly the rate constants for a wide range of nucleophiles do not concur with the pattern established earlier for more stable cations by Ritchie in his development of the N+ nucleophilicity scale. Only azide approaches the diffusional limit. Other good N+ nucleophiles may well be levelling but at rates lo2 below the limit.In any case the RSP is followed when the less reactive An3C+ is compared with Ph3C+. The directly observed azide :water rate ratio is within an order of magnitude of (some of) those established by product analyses. Since azide is the most frequently used of probe nucleophiles for carbo- cation capture its unusual behaviour warrants further attention. '*J. B. Lambert J. A. McConnell and W. J. Schulz J. Am. Chem. SOC.,1986 108 2842. 12 G. A. Olah R. Herges K. Laali and G. A. Segal J. Am. Chem. SOC.,1986 108 2054. 13 L. H. Dao M. Maleki A. C. Hopkinson and E. Lee-Ruff J. Am. Chem. SOC.,1986 108 5237. 14 D. A. Forsythe J. S. Puckace and F. E. Shawcross Tetrahedron Lett. 1986 27 3569. l5 R. A. McClelland N.Banait and S. Steenken J. Am. Chem. SOC.,1986 108 7023. 50 D. J. McLennan Carbonate ion is only 1.7 times less reactive towards (pmethoxypheny1)tropylium cation than is hydroxide ion,I6 which suggests caution in the use of C032-HC03- buffers in the investigation of reactive electrophiles. When more reactive nucleophiles are involved there is no problem but it is still an open question as to whether desolvation ion pair formation or covalent bond formation is the rate-limiting step in anion-cation reactions. In the case of methoxide reaction with 2,6-di-t-butyl-4- arylthiopyrylium cations adduct formation appears to be rate-limitir~g,’~ but this may not be a general rule. The solvolysis chemistry of the 1-phenylethyl system continues to be of interest even though the pioneering studies date back to the work of Ingold and Hughes in the 1930s.A paper entitled ‘Anatomy of an SN1 Reaction’ receives the 1986 award for the most eye-catching title although it will not enjoy the readership of other anatomical studies commonly featured on page three of tabloid newspapers. It does however extend the studies of Jones and Kirby on the relationship between crystal structure parameters and reactivity in solution to the S,1 reactions of ArCH(CH3)0X systems wherein aryl and X substituents are varied.18 The response of crucial bond lengths and angles to substitution allows a picture of the early stages of C...OX heterolysis to be described. Two simple and general rules arising from earlier work of a similar nature remain valid (i) the longer the bond in a given system the faster it breaks and (ii) the more reactive the system the more sensitive is the length of the bond to structural variation.In past decades structure and mechanism have been viewed as almost separate concepts although biochemists and catalysis researchers have long known otherwise. The attentions of chemists have been increasingly directed towards a unification in recent years and the time may well come when the diffractometer is viewed as being as much an instrument for mechanis- tic studies as is the fixed-wavelength multi-cell spectrophotometer. A more traditional study of chlorine kinetic isotope effects (KIEs) in the solvolysis of substituted 1-phenylethyl chlorides is reported.” Values of k35/k37 are largely insensitive to the electronic demands of ring substituents and to the polarity of ethanol-water solvent mixtures.The results are either a negation of the Hammond postulate or an indication that a multistep mechanism is operative. The authors favour the latter alternative and propose that a substituent- and solvent-induced variation in the extent of internal ion pair return tends to level the leaving group KIEs. A diminution in k35/k37with CF3CH20H-H20 solvents is evidence for stronger electrophilic solvent participation. While ArCH(CH3)C1 is some 4 x lo5 $me more reattive in solvolysis than ArCH(CF3)Cl (Ar = p-MeOC,H,) the ArCHCH3 and ArCHCF cations are cap- tured equally rapidly by water (k = 5 x lo7s-’ based on equal diffusional rates of capture by N3- see also ref.15).20 This is unexpected in view of the markedly differing stabilities of the cations. Richard argues that the a-CF3 destabilization in the latter is off set by a greater degree of p-Me0 resonance charge delocalization and thus provides a further example of TS imbalance with respect to resonance and 16 C. D. Ritchie and Y. Tang J. Org. Chem 1986,51 3555. 17 M. L. Di Vona G. Doddi G. Ercolani and G. Illuminati J. Am. Chem. SOC.,1986 108 3409. 18 M. R. Edwards P. G. Jones and A. J. Kirby J. Am. Chem. SOC. 1986 108,7067. 19 D. J. McLennan A. R. Stein and B. Dobson Can. J. Chem. 1986 64 1201. *’ J. P. Richard J. Am. Chem. SOC. 1986 108 6819. Reaction Mechanisms -Part (ii) Polar Reactions 51 inductive interactions.In a similar vein Tidwell shows that double destabilization of carbocations by the introduction of two CF groups is markedly attenuated with respect to the large destabilization effected with just one CF, and that in the former case the charge is largely delocalized on to an a-aryl group.21 His studies have been extended to polycyclic 1-arylethyl systems,22 where ion pair pathways are again operative. Maskill has used azoxytosylates to investigate solvolytic intermediates with much success in recent years (equation 2). Heterolytic fragmentation occurs for R = PhCH2 but concurrent nucleophilic attack by the basic nucleophiles OAc- and imidazole occurs at the tosyloxy sulphur atom.23 0- I R-N+=N-OTs + [R+.N,O.OTs-] + [R+OTs-] + N,O .c products A careful study of the rates of reaction of benzyl tosylate in the presence of added solutes in 1 :1 CF3CH20H-H20 reveals the operation of nothing other than &2 reactions for solvent-derived products and those arising from attack by external nu~leophiles.~~" Thus attack on ions or ion pairs is excluded.A parallel study of solvolysis rates in a variety of solvents concurs solvent nucleophilicity is almost as important a determinant of reactivity as is polarity.24b Katritzky's continuing research into the mechanisms of nucleophilic substitutions wherein heterocycles act as leaving groups demonstrates that at the borderline dividing rate-limiting nucleophilic trapping of intimate ion-molecule pairs from formation of free carbocations the pathways are independent.Likewise there is no merging of mechanisms when rate-limiting nucleophilic attack on an ion-molecule pair is contrasted with formation of the pair. The idea of an SN2-intermediate mechanism is not supported by these re~u1t.s.~' The rates of SN1solvolysis of t-alkylpyridinium cations are almost independent of solvent over a wide range of solvent polarity and nucleophilicity.26 The possibility of nucleophilic solvent assist- ance is dismissed as are earlier suggestions that the solvolysis of t-butyl chloride is assisted. In the pH-independent solvolysis of p-methoxystyrene oxide a reversibly-formed intermediate must intervene since the trans-P-deuterio isomer suffers deuterium scrfmbling during rea~tion.~' The intermediate is identified as the zwitterion ArCH-CH2-0-.An unusual cyclization accompanies solvolysis of trimesitylvinyl tosylate (6; Mes = 2,4,6-Me,C,H2). Formation of indene (7) is proposed to result from hydride transfer from a P-mesityl methyl to the cationic centre in the vinyl cation followed by cyclization of the resulting benzylic cation or from electrophilic attack by a methyl C-H bond on a P-mesityl group.28 21 A. D. Allen V. M. Kanagasabapathy and T. T. Tidwell J. Am. Chem. Soc. 1986 108 3470. 22 A. D. Allen R. Girdhar M. P. Jansen J. D. Mayo and T. T. Tidwell J. Org. Chem. 1986 51 1324. 23 H.Maskill J. Chem. Soc. Chem. Commun. 1986 1433. 24 (a) H. Maskill J. Chem. SOC.,Perkin Trans. 2 1986 1241; (b) D. N. Kevill and T. J. Rissrnann J.Chem. Res. (S),1986 252. 25 A. R. Katritzky and B. Brycki Can. J. Chem. 1986 64,1161. 26 A. R. Katritzky and B. Brycki J. Am. Chem. SOC.,1986 108 7295. 27 V. C. Ukachukwu J. J. Blurnenstein and D. L. Whalen J. Am. Chem. Soc. 1986 108 5039. S. E. Biali and 2. Rappoport J. Org. Chem. 1986 51 964. D. J. McLennan Mes\ Mes\ C=C-Mes + /c=c \ /Mes -bMes / Mes OTs Mes Me Mes Non-classical ion matters are hardly new but novel angles continue to be explored. H.C. Brown announces his retirement from the field with two concluding papers of a monumental provocative and stimulating series. In the first the behaviour of U-shaped systems in solvolysis is re-e~amined,~~ and solvent participation in the solvolyses of the non-norbornyl model systems (absent in secondary norbornyl solvolyses) is suggested to account for earlier discrepancies.In the second a direct search for the reputed non-classical stabilization energy is undertaken -the 6-8 kcal mol-' required to explain the exo-endo rate ratio for solvolyses of secondary norbornyl derivatives on the basis of a delocalized intermediate in the ex0 case.3o Solvolytic data (again corrected for solvent participation) are compared with heats of ionization under stable ion conditions and again the stabilization fails to appear. Yet even these papers may not mark Brown's last words on the subject matters may continue to be argued by public corre~pondence.~' Kirmse has summarized experimental and theoretical studies of cations on the C7HT energy surface.For once attention is focused not on the 2-norbornyl cation but on metastable isomers protected from immediate decay by potential barriers.32 These are considered to be bridged. Studies on nucleophilic capture of isotopically labelled 2-bicyclo[2.1. llhexyl cations are consistent with the intermediacy of equili- brating bridged ions.33 These are believed to be more strongly solvated than has been previously thought to be the case for delocalized cations. Last year was reported a new world record for the ex0 :endo rate ratio in solvolysis of a norbornyl system. In contrast exo- and endo-5-brexyl brosylates acetolyse at almost the same rate and produce predominantly inverted acetates.34 Relative to norbornyl exo-solvolysis is retarded whilst endo-solvolysis is enhanced.These findings are also of relevance to the stereochemical preference of 1,2-migrations in carbenes. An earlier report on the bromination of stereospecifically deuteriated cyclopropane concluded that the reaction stereospecificity demanded the intermediacy of a corner- brominated cyclopropane containing a formal pentacoordinate carbon. Battiste and Coxon now show that the observed result specifically excludes such a symmetrical intermediate and interpret the results in terms of both the degenerate HOMOS of cyclopropane interacting with the ele~trophile.~~ 29 H. C. Brown I. Rothberg and J. Chandrasekharan J. Org. Chem. 1985 50 5574. 30 H. C. Brown M.-H. Rei J. Chandrasekharan and V. Somayiji J. Org. Chem. 1985,50 5578.31 H. C. Brown Acc. Chem. Rex 1986 19 34. 32 W. Kirmse Acc. Chem. Rex 1986 19 36. 33 W. Kirmse V. Zellmer and B. Goer J. Am. Chem. SOC.,1986 108 4912. 34 A. Nickon and R. C. Weglein Tetrahedron Lett. 1986 27 2675. 35 M. A. Battiste and J. M. Coxon Tetrahedron Lett. 1986 27 517. Reaction Mechanisms -Part (ii) Polar Reactions 53 3 Other Nucleophilic Substitutions Our interest in the formation of the first C-C bond in the ZSM-5 zeolite-catalysed methanol-to-gasoline process continues. The world's first commercial plant is now operating successfully in New Zealand using natural gas as the feedstock but while the chemical engineering problems have been overcome the economics (in the light of current low prices for Middle East crude oil) are reputed to be disastrous.Olah reinforces his conviction in favour of the oxonium ylide mechanism by paradoxically questioning earlier evidence provided by others in support of it.36 Ethylene was reported last year to arise from treatmyt of Me30+BF4- with weak bases but Olah now concludes that it comes from Me,OEt present as an impurity. A rival mechanism involving singlet methylene insertion into C-H bonds of an oxonium species is not supported by model laboratory studies. However the novel technique of monitor-ing the reaction by in situ FT-IR fails to provide evidence for detectable concentra- tions of Me30+ under catalytic condition^.^^ Instead an Al-0-Me species is detected whose formation correlates with the onset of hydrocarbon formation and which acts as a methylating agent towards alkenes and aromatics.The possibility that it also methylates dimethyl ether to form transient Me30+ cannot be dismissed. As mentioned earlier the detection of radicals or radical-derived products is not a necessary prerequisite for the operation of a single electron-transfer S mechanism. A better criterion is that the substitution rate is comparable with a reliably calculated electron-transfer rate and this is successfully applied to the reactions of sterically hindered alkyl halides and the anion of 1,4-dihydro-4-methoxycarbonyl-1-methyl-~yridine.~' Radical cations are singularly unreactive with nucleophiles in contrast to carbocations and an extremely simple application of CM theory by Pross shows The concept of 'allowed' and 'forbidden' polar reactions is introduced but the categories are based on energetics rather than orbital symmetry as is the case for pericyclic reactions.Substrate and solvent KIEs in SNreactions have been widely studied but entering group KIEs are rare. The k14/k15values for methyl transfer to pyridines in water fall in the range 0.995-0.998 and are virtually independent of the identity of the nucleophile or leaving Preliminary model calculations and comparison with equilibrium isotope effects for pyridine prot~nation~~~ suggest that early TSs with N-..C bond orders in the 0.2-0.3 range are involved. Interestingly interaction of solvent with free amine in the initial state appears to be a prerequisite. Similar results are obtained for the reactions of substituted dimethylanilines with benzylic arene~ulphonates,~' a system in which substrate KIEs have previously been found to be remarkably substituent-sensitive.Jencks continues his search for intermediates for simple secondary substrates solvolysing in solvents of moderate nu~leophilicity.~~ However rates of reaction of 36 G. A. Olah G. K. Surya Prakash R. W. Ellis and J. A. Olah J. Chem. SOC.,Chem. Commun. 1986 9. 37 T. R. Forester S.-T. Wong and R. F. Howe J. Chem. Soc. Chem. Commun. 1986 1611. 38 T. Lund and H. Lund Tetrahedron Lett, 1986 27 95. 39 A. Proos J. Am. Chem. Soc. 1986 108 3537. 40 (a) J. L. Kun M.W. Daniels K. S. Cook and M. M. Nasr J. Phys. Chem. 1986 90,5357; (b) J. L. Kurz J. E. Pantano D.R.Wright and M.M. Nasr ibid. 1986 90,5360. Earlier results on entering nitrogen KIEs (J. Am. Chem. Soc. 1982 104 5823) have been repudiated. 41 T. Ando H. Yamataka and E. Wada Isr. J. Chem. 1985 26 354. 42 P. E. Dietze and W. P. Jencks J. Am. Chem. SOC.,1986 108 4549. 54 D. J. McLennan p-N02C6H4CH2CHXCH3(X = Br I OTs) with solvent fall on the same Swain- Scott correlation line as do rates of reaction with bonaJidesN2 anionic nucleophiles and it is concluded that the solvolyses are also concerted sN2 albeit through a TS possessing carbocation character. Significantly there is a symbiotic effect when both nucleophile and nucleofuge are polarizable (‘soft’) which indicates coupling in a concerted TS. Jencks acknowledges that much of the controversy regarding solvolysis mechanisms is semantic and points out that substitution reactions at carbon will be stepwise if they can be and will be concerted or will show nucleophilic participation when the carbocation has too short a lifetime to exist in the presence of surrounding nucleophiles.In the Reporter’s view these are wise words. However a case of the Sneen mechanism (a rate-limiting attack of a nucleophile on an ion pair formed in a pre-equilibrium) may have been uncovered. As so elegantly demonstrated in the 1930s by Hughes and his collaborators the second- order rate constant for racemization of one enantiomer of an alkyl bromide in the presence of Br- should be exactly twice the second-order rate constant for isotopic exchange between organic and inorganic bromide if a classical sN2 mechanism is operating.Stein and Moffatt indeed find k,,J k, = 2.0 for ArCHBrCH + LiBr in acetone (Ar = Ph p-BrC6H4 p-N02C6H4).43 But for Ar = p-MeC6H4 the rate ratio is 2.36 f0.24 suggesting the presence of an ion pair intermediate sufficiently stable to suffer internal return with racemization. Expecting the Ar = 3,4-Me2C,H3 com- pound to yield an even higher ratio the authors found instead a value of 1.59 * 0.39 and proposed that frontside exchange of Br- with retention in a loose ion pair was conceivable. Although the authors took pains to minimize the effects of concurrent bromide-induced dehydrobromination the fact remains that concurrent elimination followed by back-addition of HBr could complicate the results.It would be interest- ing to establish the racemization-to-exchange ratios in media containing a non- nucleophilic HBr scavenger. The putative intermediacy of free metaphosphate anion in phosphate ester hydro- lysis is a question similar to those raised on behalf of carbocations. Volume of activation results are consistent with an associative mechanism for aqueous hydroly- sis of 2,4-dinitrophenylphosphatedianion.44 The secondary l60/l80KIE for hydro- lysis of glucose-6-phosphate monoester (non-bridging oxygens) is 1.0046 which is consistent with a dissociative mechanism but does not allow distinction between free metaphosphate and the loose sN2 TS advocated in other recent ~tudies.4~ On the other hand phosphoryl transfer from adenosine 5’-diphosphate to ROH in dry MeCN proceeds with racemization at phosphorus.Free metaphosphate intermediacy is one interpretation but it is not possible to rule out preassociative phosphoryl transfer to a~etonitrile.~~ Indeed positional isotope exchange in the ‘*O-labelled diphosphate is consistent with the latter process.47 A salt containing the sulphur analogue of metaphosphate namely PS; has been prepared.48 43 A. R. Stein and E. A. Moffatt Can. J. Chem. 1985,63 3433. 44 F. Ramirez J. Marecek J. Minore S. Srivastava and W. J. le Noble J. Am. Chem. SOC.,1986,108 348. 45 P. M. Weiss W. B. Knight and W. W. Cleland J. Am. Chem. SOC.,1986 108 2761. 46 P. M. Cullis and A. J. Rous J. Am. Chem. SOC.,1986 108 1298. 47 G. Lowe and S. P.Tuck J. Am. Chem. SOC.,1986 108 1300. 48 H. W. Roesky R. Ahlrichs and S. Brode Angew. Chem. Int. Ed. Engl. 1986 25 82. Reaction Mechanisms -Part (ii) Polar Reactions 55 Heavy-atom KIEs are usually (and tediously) measured by competitive methods. The methanolysis of p-nitrostyrene oxide under basic and acidic conditions has been examined by direct kinetics as far as ring l80and 13C KIEs are concerned. Base-catalysed methanolysis occurs primarily at the unhindered carbon and yields KIEs consistent with SN2 ring-opening by OMe-. In contrast acid-catalysed methanolysis results in attachment of the nucleophile to the benzylic carbon of the 0-protonated epoxide. A high value of k16/kl* is indicative of a well-broken C.s.0 bond in the TS but the less than maximal a-k,/k value supports concurrent nucleophilic participation by MeOH rather than a free carbocationic intermediate.49 4 Elimination Reactions Studies of conventional eliminations from halides and 'onium salts are decreasing at such a rate that this area can hardly be regarded any longer as the mainstream of elimination chemistry.Nevertheless two such papers justify citation. Discovery and exploration of the anti-syn dichotomy have given rise to concern about the earlier interpretation of results pertaining to influences on orientation etc. The 2-phenylethyl system has been a mechanistic template in this regard and the reaction of stereospecifically deuteriated PhCHDCHDNMeT with OEt-EtOH has been confirmed as wholly anti. The oxide of the corresponding amine eliminates exclus- ively by a syn path~ay.~' There are strong suggestions that the p-nitro analogue of the ammonium ion eliminates by an ElcB pathway but the stereochemical con- sequences could not be examined since the deuteriated p-nitrostyrene suffers label scrambling under the conditions employed for elimination.Unimolecular (E 1) reactions of 'onium salts are rare in view of the diminished nucleofugality of say the NMe; group. It is thus doubly surprising to find that 9-benzylfluoren-9- yltrimethylammonium ions undergo E 1 eliminations since the carbocation is anti- aromatic. Nevertheless the reaction clearly occurs in this way and ring substituent effects substantiate the claim that initial state steric repulsions aid expulsion of the bulky nucleof~ge.~~ The elimination of FINO2 from ArCH2C(N02)MeR (Ar = p-NO&H4; R = Me or But) appears to be a polar concerted E2 reaction in OMe-MeOH-Me2S0.52 The nucleofugality order Br- > NO > C1-is established.At a time when polar mechanisms are being increasingly re-assigned as radical ion pathways it is a pleasure to find such a strong electron acceptor acting in a polar fashion. Imine-forming eliminations equation 3 are generally E2,like their less facile alkene-forming counterparts. An investigation of ArCH2N(X)Me+ R2NH -+ ArCH=NMe + R,kHX-(3) responses to substituent base nucleofuge and isotopic variation shows however that the TS is symmetrical rather than carbanionic or carbocationic in ~haracter.~~ A rare example of the Melander-Westheimer k,/k maximum is found for a base strength variation covering only 2 pK units.49 S. P. Jacober and R. P. Hanzlik J. Am. Chem. SOC.,1986 108 1594. 50 B. R. Dohner and W. H. Saunders Can.J. Chem. 1986 64 1026. 51 P. J. Smith and J. Pradhan Can.J. Chem. 1986 64 1060. 52 R. K. Noms and T. A. Wright Aust. 1 Chem. 1986 39 281. 53 B. R. Cho S. K. Namgoong and R. A. Bartsch J. Org. Chem. 1986 51 1320. 56 D. J. McLennan On the other hand eliminations from isonitriles CN-CH2CH2-Z by OEtC-EtOH are ElcB in cases where loss of CNH competes with removal of HP4 While isonitrile is not a highly ranked nucleofuge it is at least 10" better than cyanide. The E 1cB mechanism of ester hydrolysis is now well-established.Another mechanistic criterion is available since volumes of activation are markedly different from those for the more usual BA,2 me~hanism.~~ Mechanistic variation within the ElcB spectrum from (ElcB) to can be brought about by introduction of a bulky substituent in the acyl moiety.56 The existence of a neutral sulphonylamine intermediate in the alkaline hydrolysis of aryl sulphamate esters has been established. The pH-rate profile however requires another intermediate and the unprecedented involvement of a dianion (Scheme 1) is ~uggested.~' -2-H2NS02-OAr HNSO,-OAr Y NSO2-0Ar I-... HN=S02 \p~oductsj=102 Scheme 1 The full paper on the enormous stereoelectronic effect of the nitrogen lone pair in promoting chloride loss from the anions of (E)-and (2)-benzohydroxyimoyl chlorides has appeared.58 This effect is not universally accepted as far as lone pairs on neighbouring oxygens are concerned but the results here assert a clear antiperi- planar preference for a single lone pair on nitrogen.5 Addition Reactions The +first direct measurement of rate constants for addition of carbocations (Ar,CHBCl in CH2C12 at -20 to -9OOC) to alkenes has been rep~rted.'~ The reactions are second-order and ion association effects are negligible. The results should be of assistance in understanding the initial step(s) in cationic alkene polymerization. An investigation of the bromination of 3-substituted cyclohexenes by Br and Br in CH2CI2 and CHC13 substantiates the mechanistic proposals reported last year.60 Charge transfer complexes are essential intermediates but different mechanisms operate for the two reagents and this is reflected in markedly different diaxial :diequatorial product ratios.61 In particular Bu4NBr3 is a most suitable reagent for stereoselective anti-diaxial addition irrespective of the 3-substituent.54 B. A. Jones M. Varma and C. J. M. Stirling J. Am. Chem. SOC.,1986 108 3153. 55 N. S. Isaacs and T. S. Najem Can. J. Chem. 1986 64 1140. 56 M. Inoue and T. C. Bruice J. Org. Chem. 1986 51,959. 57 S. Thea G. Cevasco G. Guanti and A. Williams J. Chem. SOC. Chem. Commun. 1986 1582. 58 A. F. Hegarty and M. Mullane J. Chem. SOC. Perkin Trans. 2 1986 995. 59 R. Schneider U. Grabis and H. Mayr Angew. Chem. Int. Ed. Engl.1986 25 89. 6o D. J. McLennan Annu. Rep. bog Chem. Sect. B Org. Chem. 1985 82 67. Note in ref. 66a read J. Org. Chem. for J. Am. Chem. Soc. and in ref. 666 read J. Am. Chem. SOC.,1985 108 2464. 61 G. Bellucci R. Biachini and S. Vecchiani J. Org. Chem. 1986 51 4224. Reaction Mechanisms -Part (ii) Polar Reactions Electrophilic bromination of micelle-associated alkenes (fatty acids esters and alcohols) has been used to probe micellar structure and action.62 A segment pro- trusion model is used to account for exclusively anti-addition and rates slower than those in aqueous solution. A bromonium ion intermediate is believed to be formed and trapped in a polar region of the micelle and it is proposed that the double bond initially enters this reactive region by protrusion of a chain segment from a non-polar region.The small probability of this is offset by the high rate of reaction with bromine once the protrusion occurs. Unexpected participation by sulphone groups during alkene bromination has been reported. Bromination of (8) yields a substantial proportion of cis-dibromide and a long-range Coulomb interaction between sulphonyl oxygen and an open carbocationic centre is ~uggested.~~" Even nucleophilic interaction is possible bromi- nation of (9) in CH2C12 yields a product thought to be ( Clearly the inherently low nucleophilicity of sulphone oxygen is offset by proximity to the reaction site in (9). 6 Aromatic Substitution and Rearrangements Genuinely electrophilic processes are hard to find this year.The reactivity of electrophiles does not seem to be as seriously attenuated by solvent as is the case for nucleophiles. Gaseous t-butyl cation shows normal temperature-dependent intermolecular (benzene us. toluene) and intramolecular positional selectivity (within toluene).64 Thus these ion-molecule reactions are essentially thermal processes at the high pressure limit. 2-Nitro- rn-xylene and some nitrophenols undergo a first-order 1,3-nitro-group rearrangement in CF3S03H at 100 "C,giving the lie to the idea that nitration products are universally formed under kinetic control.65 Mechanistic details are as yet unclear but reversible protonation to yield a Wheland intermediate seems likely. Direct evidence for a nitro-nitrito rearrangement following ips0 nitration of a phenol has been presented.& The nitrite is unstable and loses oxides of nitrogen in the presence of water.A similar suggestion made late last year but based on indirect evidence6' has apparently been confirmed. A homolytic mechanism has been tentatively pro- posed. 62 R. B. Lennox and R. A. McClelland J. Am. Chern. SOC.,1986 108 3771. 63 (a) J. I. G. Cadogen D. K. Cameron I. Gosney R. M. Highcock and S. F. Newlands J. Chem. SOC. Chem. Commun. 1985 1751; (b) ibid. 1986 766. 64 F. Cacace and G. Ciranni J. Am. Chem Soc. 1986 108 887. 65 P. Barrow J. V. Bullen A. Dent T. Murphy J. H. Ridd and 0.Sabek J. Chem. SOC.,Chem. Commun. 1986 1649. 66 M. R. Amin L. Dekker D. B. Hibbert J. H. Ridd and J. P. B. Sandall J.Chem. SOC.,Chem. Commun. 1986 658. 67 M. P. Hartshorn R. J. Martyn W. T. Robinson K. H. Sutton J. Vaughan and J. M. White Aust. J. Chem. 1985 3,1613. 58 D. J. McLennan Electrophilic mechanisms for the HN02-catalysed nitration of p-nitrophenol by aqueous HN03 are abandoned in favour of an electron-transfer radical process in the light of new evidence presented by Ali and Ridd.68 The proposal is that p-nitrophenoxide ion is oxidized by NO+ to the radical which then couples with nitrogen dioxide itself generated by reduction of NO;. However the mechanism( s) of nitration of some methylnaphthalenes under various conditions do not involve coupling between the free arene-radical cation and NO2 formed in a SET step.69 Both the electron transfer and proton transfer aspects of the Marcus equation are used in analysing the energetics of electron transfer from methylarenes to Fe"' complexes and consequent proton loss from the resulting radical cations.70 On the nucleophilic substitution side a surprise comes with a report of proton sponge [1,8-bis(dirnethylamino)naphthalene]acting as a carbon n~cleophile.~~ With strongly electrophilic substrates such as 4,6-dinitrobenzofuroxan proton sponge reacts through C-4 of the naphthalene ring to form zwitterionic adducts which at least preserves the reputation of the amino nitrogens as centres of low nucleophilicity towards anything but protons.7 Carbanions and Proton Transfer Kinetic and KIE anomalies in proton transfer reactions involving carbon acids have often been attributed to the intermediacy of hydrogen-bonded carbanions capable of suffering internal return without exchange.Direct evidence ('H n.m.r. and i.r.) has now been presented to substantiate the existence of such species.72 The spectra of suitable hydroxy-substituted fluorenide and indenide anions can be interpreted in terms of intramolecular c..-HO bonds. The synthetic utility of 1,3-dithiane anion as an acyl anion equivalent will be most marked if it is generated under ion-pairing conditions rather than in Me2S0 as solvent.73 This does not apply however to carbanions with highly delocalized charge. The aqueous pK of toluene is of interest in anchoring carbon acid acidity scales and in comparing scales derived from various basic media.The latest estimate based on isotope exchange measurements and the rate constant for reaction of benzyl anion with water (albeit in THF media) is 39.6 per hydrogen.73 The acetylide anion is apparently not stabilized by resonance.74 The role of base solvation and solvent reorientation in proton transfer has been examined in terms of the principle of imperfect synchr~nization.~~ Intrinsic rate constants for deprotonation of 1,3-indandione by carboxylate ions increase as the Me2S0 content of Me2SO-H20 solvent mixtures increases and this can be inter- preted in terms of desolvation occurring ahead of proton transfer with enolate ion solvation lagging far behind.75" On the other hand the intrinsic rate constants for deprotonation of 9-cyanofluorene by amine bases are independent of Me2S0 content.75 6a M.Ali and J. H.Ridd J. Chem. SOC.,Perkin Trans. 2 1986 327. 69 L. Eberson and F. Radner Acta Chem. Scond. Ser. B 1986 40 71. 70 C. J. Schlesener C. Amatore and J. K. Kochi J. Phys. Chem. 1986 90 3747. 71 F. Terrier J.-C. Halle M.-J. Pouet and M.-P. Simonnen J. Org. Chem. 1986 51 409. 72 P. Ahlberg B. Johnson I. McEwan and M. Ronnqvist J. Chem. SOC.,Chem. Commun. 1986 1500. 73 A. Streitwieser and J. X.Ni Tetrahedron Lett. 1985 26 6317. 74 A. J. Kresge and M. F. Powell J. Org. Chem. 1986 51 819. 75 (a) C. F. Bernasconi and P. Paschalis J. Am. Chem. SOC.,1986 108 2969; (6) C. F. Bernasconi and F. Terrier Can. J. Chem. 1986,64 1273. Reaction Mechanisms -Part (ii) Polar Reactions 59 A full account of Stirling's remarkable findings on cyclization of stabilized car- banions has appeared.76 Cyclopropane rings are the most readily formed by several orders of magnitude despite their inherently greater strain and this enhanced reactivity has an entropic rather than an enthalpic origin.These results are consistent with TS structures wherein the nucleofuge is well on its way out with ring formation lagging well behind. A model for prediction of diastereoselectivity in reactions of prochiral carbanions (or their equivalent) with prochiral ketones in the absence of chelation control has hitherto been lacking. This deficiency is now remedied by an empirical model based on a Burgi-Dunitz trajectory and the assumption of an early TS structure (steric approach 8 Carbonyl Derivatives and Tetrahedral Intermediates A landmark study on the mechanism and stereochemistry of the Wittig reaction has been published in full.Direct observation of diastereomeric 1,2-0xaphosphetanes by low-temperature n.m.r. allows rationalization of 'stereochemical drift' in that correspondence between the proportions of cis- and trans-intermediates prior to alkene formation and the final proportion of (E)-to (2)-alkene is lacking.78 Selective reversibility of oxaphosphetane formation appears to be responsible and in light of this evidence for an element of thermodynamic control it is not possible to define the stereochemistry of the Wittig reaction in terms of alkene products alone. Unfortunately the reactions of stabilized phosphorus ylides were not amenable to n.m.r.observation. The authors are candid in conceding that many important details remain unclear. Not so elusive are details on the hydroxide-promoted chlorination of acetone. A complete kinetic analysis involving the evaluation or estimation of 27 rate and 16 equilibrium constants describing the formation of 25 unstable or metastable inter- mediates and products has been described.79 The situation is therefore somewhat more complex than that presented in organic textbooks and the principal product is lactate rather than chloroform plus acetate. The former appears to arise from a complex pair of pathways involving hydration of mono- and dichloro-acetone. More quantitative work on enols and enolates has appeared.The equilibrium constant for the phenol 2,4-cyclohexadienone equilibrium is around lo-" at 80 0C.80The acidity constant for isobutyraldehyde enol and the keto-enol equilibrium constant have been evaluated,81' and a Marcus equation analysis of the acid- catalysed ketonization of both the enolate and enol has been performed.81b In the latter study the RSP holds in that the Bronsted a is significantly lower for the more reactive enolate. Unexpected catalysis by HSO in aqueous H,SO solutions used in earlier work has forced revision of figures for the enolization of acetophenone 76 F. Benedetti and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1986 605. 77 A. R. Bassindale R. J. Ellis J. C.-Y. Lau and P. G. Taylor J. Chem. SOC.,Chem.Commun. 1986 98. 78 B. E. Maryanoff A. B. Reitz M. S. Mutter R. R. Inners H. R. Almond R. R. Whittle and R. A. Olofson J. Am. Chem. SOC.,1986 108 1664. 79 J. P. Guthrie and J. Cossar Can. J. Chem. 1986,64 1250. 80 M. Capponi I. Gut and J. Win Angew. Chem. Int. Ed. Engl. 1986 25 344. 81 (a) Y. Chiang A. J. Kresge and P. A. Walsh J. Am. Chem. SOC.,1986 108 6314; (b) P. Pruszyniski Y. Chiang A. J. Kresge N. P. Schapp and P. A. Walsh J. Phys. Chem. 1986 90,3760. 60 D. J. McLennan (pKE = 7.96) and for its ionization as a carbon acid (pK = 18.31)in dilute aqueous solution.82 Last year it was shown that base-catalysed ring-opening of a cyclic hemiacetal having a phenolate leaving group occurs by a stepwise mechanism. When an even more stable carboxylate leaving group is involved as with the conversion of 3-hydroxyphthalide into p-formylbenzoic acid a concerted mechanism is enforced by the instability of the conjugate base of the substrate relative to the product,83 to the point where the existence of the conjugate base (the tetrahedral intermediate in attack of H-on phthalic anhydride) is doubtful.The acid-catalysed hydrolyses of acetals and thioacetals of p-Me2NC6H4CH0 have been investigated in detail for the opposite reason the oxocarbocationic intermediate should be so stable that a diversity of rate-limiting steps should be observed. This has been realized. Depending on the pH and the functionality undergoing hydrolysis general acid-catalysed breakdown of protonated acetal to the oxocarbocation or attack of water on this stabilized intermediate can be detected as the rate-limiting step.84 But in no case is hemiacetal breakdown rate-limiting.The remarkable bond length-reactivity correlation earlier observed with respect to leaving group variation in R-OX compounds has now been successfully extended to hydrolysis of acetals (R = R'O-CHR') in which R is varied.85 Thus the more stable is the cation R+ the longer is the R-OX bond and the more reactive is the compound. Lengthening a bond in a crystal correlates with the ease of breaking it heterolytically in solution. The stereochemistry of reaction of ester enolates bearing a P-oxygen with elec- trophiles,86" and of alkylation of 2-t-butyl-5-X-1,3-dioxanes (X = EWG)86bhave been rationalized in terms of stereoelectronic control (or rather control by antiperi- planar lone pairs).But the theory of such stereoelectronic effects has come under close scrutiny. Bennet and Sinnott have described a monumental KIE study of the acid-catalysed hydrolyses of methyl a-and P-glucopyranosides (seven isotopic positions with 3 primary and 4 ~econdary).~' The rate-limiting step is unimolecular scission of the (protonated) exocyclic C-0 bond. Primary KIEs allow evaluation of the extent of bond-breaking and nucleophilic assistance by the endocyclic oxygen. The known conformational dependence of some of the secondary KIEs then allows several TS bond angles to be estimated and the remainder of the TS structure has been deduced by molecular mechanics calculations.The minimum energy structures obtained flatly contradict the antiperiplanar lone pair hypothesis which in any case is not expected to apply to systems reacting through late TSs. Four years ago Perrin provided evidence in support of the theory based on the regioselectivity of hydrolysis of cyclic amidines. He now concedes that the system studied was biased as far as differential leaving group abilities were concerned and has now reinvestigated the situation with a less biased substrate.88 The conclusion which applies to the forma- 82 J. R. Keefe A. J. Kresge and T. Toullec Can. J. Chem. 1986 64 1224. 83 R. A. McClelland and P. E. Sgrensen Can. J. Chem. 1986 64 1196. 84 T. H. Fife and R. Natarajan J. Am. Chem. SOC.,1986 108 2425. 85 P.G. Jones and A. J. Kirby J. Chem. SOC.,Chem. Commun. 1986 444. 86 (a) M. Caron T. Kawamata L. Ruest P. Soucy and P. Deslongchamps Can. J. Chem. 1986,64 1781; (b) A. Ndibwami and P. Deslongchamps ibid. 1986 64 1788. 87 A. J. Bennet and M. L. Sinnott J. Am. Chem. SOC.,1986 108 7287. 88 C. L. Perrin and 0. Nufiez J. Am. Chem. SOC.,1986 108 5997. Reaction Mechanisms -Part (ii) Polar Reactions 61 tion of the tetrahedral intermediate is that the stereoelectronic hypothesis is barely consequential in the case of 6-membered cyclic amidinium ions and of no import as far as the 5-and 7-membered analogues are concerned. 9 Some Probes of Polar Mechanisms In claiming last year that their linear solvation energy relationship was so widely applicable as to approach the status of a law of nature Kamlet and Taft challenged those wedded to a system-specific statistical approach.The chemometricians of UmeH have responded in kind but alas no reconciliation of views is yet apparent. The latter reinforce their arguments that within the framework of any statistical model lies a distinction between goodness of fit and predictive power and that such models must of necessity be local rather than universal.*’ The diversity of views expressed in other work to be cited in this section would tend to bear this out. The a-effect on nucleophile reactivity has been critically scrutinized by Hoz and Buncel who conclude that none of the theories proposed so far accounts for all of the facts.” An unusual solvent effect on the a-effect’” and a rationalization in terms of initial state destabilization by lone-pair repulsion” are testimony to the fact that much remains to be understood.Last year it was proposed that the a-effect had a thermodynamic rather than a kinetic origin. Experimental evidence is now available -a-eff ect nucleophiles exhibit enhanced equilibrium constants but normal rate constants for addition to benzylidene Meldrum’s acid.’* Lewis has reviewed his work on methyl transfer reaction^'^ and shows that although the Marcus equation (a quantitative expression of the RSP) is applicable selectivities are almost constant. The general Marcus relationship is compatible with linear free energies over wide rate ranges. The need for a loose VB contribution X-Me+Y-to the TS hybrid is emphasized which concurs with conclusions from methyl transfers to water.94 Here little O..C bonding has occurred at the TS as a result of solvational and bonding coordinates being only partially coupled.Methyl transfer data for equilibrium cases where arenesulphonates are the mobile groups are used as a basis to set up Bronsted plots for leaving group departure. The slopes are as would be intuitively e~pected.’~ Nevertheless it has been evident for a number of years that all is not well as far as using a Bronsted a or p as an index of the degree of bonding in a TS or as a selectivity parameter in an RSP context is concerned. Jencks and co-workers report a case where increasing basicity of amines results in decreasing reactivity in phosphoryl tran~fer.’~ In the terminology of Bernasconi partial desolvation of the stronger bases runs ahead of proton transfer at the TS (imperfect synchr~nization).’~ Over-89 s.Wold and M. Sjostrom Acfa Chem. Scand. Ser. B 1986 40,270. 90 S. Hoz and E. Buncel Isr. J. Chem. 1985 26 313. 91 (a) E. Buqcel and I.-H. Um J. Chem. SOC.,Chem. Commun. 1986 595; (b)S. Oae and Y. Kadoma Can. J. Chem. 1986 64,1185. 92 C. F. Bernasconi and C. J. Murray J. Am. Chem. SOC.,1986 108 5251 93 E. S. Lewis T. A. Douglas and M. L. McLaughlin Isr. J. Chem. 1985 26 331; E. S. Lewis J. Phys. Chem. 1986,90 3756. 94 J. L. Kurz and L. C.Kurz Zsr. J. Chem. 1985 26 339. 95 R. V. Hoffman and J. M. Shankweiler J. Am. Chem. Soc. 1986 108 5536.96 W. P. Jencks M. T. Haber D. Herschlang and K. L. Nazarentian J. Am. Chem. SOC.,1986 108,479. 97 C. F. Bernasconi and R.D. Bunnell Zsr. J. Chem. 1985 26 420. 62 D. J. McLennan whelming solvation sensitivity is held responsible. Bordwell has been concerned for some time that results of his extensive studies involving reactions of carbon elec- trophiles do not accord with the RSP (or with the Bema Hapothle model -see last year p. 73).98 A detailed study of the response (or lack of it) of PNuand PLGto substituent vfriation elsewhere in the system comprising fluorenide anions reacting with ArCH2NMe2Ar' substrates in Me2S0 is reported. In only a few cases do the experimental results accord either with this theory or with the Pross-Shaik CM Having conceded that the RSP may well be valid in cases where a low activation barrier accompanies a true single-step reaction,97 Bordwell now dissects an sN2 reaction in solution into ion-dipole complex formation followed by bond- making and -breaking in an activated process.Such complexes respectable in gas-phase SN2reactions should survive in polar aprotic solvents. Parameters such as PNureflect charge transfer in complex formation whilst PLGis manifested in the second step and is independent of the basicity of the nucleophile. The central carbon p value presumably reflects variation in balance between complex formation and destruction giving rise to the familiar U-shaped Hammett plots in benzylic systems. In terms of the CM model the explanation is that in systems such as benzyl where intermediate configurations are of importance at higher energy levels but not in reactants or products p and p values are not valid indices of TS bonding.'.''' Given that charge transfer is an essential component of the CM model the similarities between the two explanations are more important than the differences.A search for charge-transfer complexes in SNArreactions involving carbanionic nucleophiles in Me2S0 was even though PNuis larger here than in sN2 processes. Imperfect synchronization or the importance of intermediate configurations yields a Bronsted a of infinity [p(rate) = 0.27; p(equi1ibrium) = 01 for the reactions of j3-nitrostyrenes with amines.'02 Anomalies associated with nitro -* nitronate conversions are thus not confined to the deprotonation of nitroalkanes.The principle of imperfect synchronization also explains why the addition of amines to benzylidene acetylacetone has an abnormally high intrinsic barrier.lo3 Steric inhibition of reson- ance in the TS leading to the adduct appears to run ahead of C-.N bond formation to the extent that extended n-overlap is absent in the substrate itself as evidenced by a crystallographic determination. Other work on reactivity and selectivity s~pports''~ or denieslo5 the reality of the RSP. Together with the work cited in the preceding paragraphs this suggests that the RSP area is chaotic. Perhaps as suggested by an anonymous referee to the Israel Journal of Chemistry issue devoted to the problem it would be best to talk about reactivity-selectivity efects rather than a principle.An effect is permitted to be distinguished by its absence. Isotopic selectivity (i.e.KIEs) should be more well-behaved and less controversial. However the TS for hydride transfer remains in doubt in that there is yet no.genera1 98 F. G. Bordwell J. C. Branca and T. A. Cripe Isr. J. Chem. 1985 26,357. 99 F. G.Bordwell and D. L. Hughes J. Am. Chem. Soc. 1986 108 7300. 100 A. Pross Zsr. J. Chem. 1985 26 390. 101 F. G.Bordwell and D. L. Hughes J. Am. Chem. Soc. 1986 108 5991. 102 C. F. Bernasconi R. A. Renfrow and P. R. Tia J. Am. Chem. SOC.,1986 108 4541. 103 C. F. Bernasconi and A. Kanavariotti J. Am. Chem. Soc. 1986 108 7744. 104 D. J. Hupe and E. R.Pohl lsr. J. Chem. 1985 26,395; M.-F. Ruasse ibid. 1985 26,414. 105 N.C.J. Chokotho and C. D. Johnson Isr. J. Chem. 1985 26,409. Reaction Mechanisms -Par? (ii) Polar Reactions agreement as to whether the donor-..H--acceptor TS is linear or bent. Studies on transfer promoted by NAD( P)H models suggest a bent TS,lo6 on the grounds that isotope effects are temperature-independent in an intramolecular case in accordance with the Kwart hypothesis. But Kwart's suggestion has no theoretical foundation and an alternative practical proposal concerning the observance of apparently temperature-independent isotope effects has been made.'" Calculations at the ab initio level demonstrate a linear TS for hydride transfer between CH3NH2 and CH2NHl,108nand while tunnelling contributions are non-negligible neither are they of great importance.'0sb The tendency of genuine hydride transfers to mimic behaviour expected of SET processes is analysed in terms of the CM model.'06 Full details of the scope and precision of the measurement of kinetic deuterium isotope effects by natural abundance deuterium n.m.r.are now a~ailable.'~' The method obviates the need to synthesize specifically deuteriated substrates although gram quantities of material may be required. Even small secondary effects can be observed provided that primary KIEs are absent. 106 J. W. Verhoeven W. van Gerresheim F. M. Martens and S. M. van der Kerk Tetrahedron 1986,42,975. 107 D. J. McLennan and P. M. W. Gill Zsr. J. Chem. 1985 26 378. 108 (a) B.G. Hutley A. E. Mountain I. H. Williams G. M. Maggiora and R. L. Schowen J. Chem. SOC. Chem. Commun. 1986 267; (b) 1303. 109 R. A. Pascal M. W. Baum C. K. Wagner L. R. Rodgers and D.-S. Huang J. Am. Chem. Soc. 1986 108;6477.

ISSN:0069-3030    

DOI:10.1039/OC9868300047

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Free-radical Reactions By D. CRICH Department of Chemistry University College London 20 Gordon Street London WC1H OAJ 1 Introduction The material included in this chapter reflects to a large extent the author's interest in the use of free radicals as reactive intermediates in preparative organic chemistry and is divided into two sections. The first section contains a summary of the more interesting uses of free-radical intermediates in synthesis published in the past year and the second a description of those mechanistic studies and physical measure- ments published during the same period which will prove useful to chemists planning the incorporation of free-radical steps into their own reaction sequences. The use of physical methods for the observation of free radicals per se and the measurement of thermochemical data pertaining to free radicals their formation and their reactions has been omitted.2 Synthesis Intramolecular Processes.-One of the most interesting developments in the field of free-radical cyclizations in 1986 was the macrocyclization of alkyl radicals generated by the action of tri-n-butyltin hydride on alkyl halides onto crp-unsaturated ketones and esters (Scheme l).' Best yields were obtained for the formation of 14-and 20-membered rings. The inclusion of an E-alkene or a triple bond into the alkyl chain had no detrimental effect upon the cyclization yields. A more cumbersome approach to macrocyclic ketones involved photochemical or thermal decomposition of cyclic tetraacyl diperoxides in the absence of solvent.* Bu,SnH AlBN wc Scheme 1 Nicolaou established an ingenous route to some brevetoxin model compounds involving the sodium naphthalenide mediated transannular cyclization of macrodithionolides (Scheme 2).3 ' N.A. Porter D. R. Magnin and B. T. Wright J. Am. Chem. SOC.,1986,108 2787. * M. Feldhues and H. J. Schafer Tetrahedron 1986,42 1285. K. C. Nicolaou C.-K. Huang M. E. Duggan K. B. Reddy B. E. Marron and D. G. McGarry J. Am. Chem. Soc. 1986 108 6800. 65 66 D. Crich a% Me - . .. I I1 0 0 0 H H H SMe H Reagents i sodium naphthalenide; ii Me1 Scheme 2 With the exception of these highlights the now familiar 5/6-exo-trig/ dig processes continued to dominate the field of free-radical cyclizations.Nevertheless some significant advances were made in this area. Parsons et al. have succeeded in fusing a five-membered ring onto a p-lactam by means of a free-radical cyclization (Scheme 3).4 Interestingly the inclusion of a methyl group at the azetidione 4-position led to higher yields of carbapenam possibly due to a Thorpe-Ingold effect. Winkler and Sridar made elegant use of the original Julia observation of the reversibility of the cyclization of 5-hexenyl radicals stabilized by two-electron withdrawing groups to obtain a good yield of cis-anti-cis linear triquinanes from an appropriately functionaliZed 1,5-~yclooctadiene (Scheme 4).' The use of a simple alkyl radical generated from an iodide with tri-n-butyltin hydride led to mixtures of cis-and trans-bicyclo[6,3,0]undec-3-enesand linear triquinanes.68% (@/a= 5.8/1) 10% Scheme 3 CN H n 45 "/o 15 '/o Scheme 4 Curran introduced the cyclization of 5-hexynyl iodides to iodomethylene cyclo- pentanes (Scheme 5).6 This process which relies on the very rapid (3lo9mol-' dm3 s-' at 80 "C) and efficient abstraction of an iodine atom from the substrate by a vinyl radical has the significant advantage of requiring only a catalytic quantity of stannane as initiator. In a similar manner 5-hexenyl iodides were cyclized to iodomethylcyclopentanes although these reactions were not so clean reflecting the less efficient chain-transfer step.' Use was made of the fact that 2-sila-5-hexenyl J. Knight P.J. Parsons and R. Southgate J. Chem. Soc. Chem. Commun. 1986 78. -5 J. D. Winkler and V. Sridar J. Am. Chem. Soc. 1986 108 1708. 'D. P. Curran M.-H. Chen and D. Kim.J. Am. Chem. Soc. 1986 108 2489. ' D. P. Curran and D. Kim Tetrahedron Lett. 1986 27 5821. Reaction Mechanisms -Part (iii) Free-radical Reactions radicals cyclize predominantly in the 6-endo-trig mode to effect a stereoselective synthesis of steroidal side-chains from 17-alkylidene-16-(bromomethyl)dimethyl-silyloxy steroids.' 5-Hexenyl radicals can be generated and subsequently cyclized by the treatment of homoallylic iodides with tri-n-butyltin hydride in the presence of an excess of a Michael acceptor such as acrylonitrile (Scheme 6).9 Scheme 5 I Scheme 6 Tandem cyclizations have again been put to good use by Curran.This time for the preparation of angular triquinanes (Scheme 7)." The influence of minor modifications to the substitution pattern of the precursor on cyclization stereochemistry is noteworthy here. Tsang and Fraser-Reid demonstrated that appropriately placed aldehydes can function as internal traps for alkyl radicals in the presence of tri-n-butyltin hydride (Scheme 8).11 The popular a-methylene- y-lactones can be prepared by 5-exo-dig cyclization of homopropargyloxycarbonyl radicals generated from the phenylseleno carbonate with tri-n-butyltin hydride (Scheme 9).12 It was also possible to cyclize a homoallyloxycarbonyl radical in the 5-exo-trig mode leading to a y-lactone after chain tran~fer.'~ X X Bu,SnH b + AIBN 80°C Br I I x=o 66% 1 3 X = OCH2CH2O 65% 2.5 1 Scheme 7 M.Koreeda and I. A. George J. Am. Chem. SOC.,1986 108 8098. 2. CekoviE and R. SaiEiE Tetrahedron Lett. 1986 27 5893. 10 D. P. Curran and S. C. Kuo J. Am. Chern. SOC.,1986 108 1106. R. Tsang and B. Fraser-Reid J. Am. Chem. SOC.,1986 108 2116; 1986 108 8102. 12 M. D. Bachi and E. Bosch Tetrahedron Lett. 1986 27 641. 13 D. H. R. Barton and D. Crich J. Chem. SOC.,Perkin Trans. 1 1986 1603. 68 D. Crich phT'% 0 Bu,SnH OMe ____,Ho{& OMe !%oMe H k I 1 8O/O 73'/o Scheme 8 Scheme 9 A novel approach to radical cyclizations involved the fragmentation of tertiary alkoxy radicals generated from hydroperoxides with ferrous sulphate giving sub- stituted 5-hexenyl radicals which subsequently underwent ring closure (Scheme lO).I4 The main problem with this entry into the 5-hexenyl system was the lack of regioselectivity in the fragmentation of the alkoxy radical.OOH MeC0,H W 3 8 '10 30% 8Yo 18% Scheme 10 A key step in the synthesis of isoamijiol by the Pattenden group was the generation of a ketyl radical anion from a ketone with sodium naphthalenide and its subsequent cyclization onto an w-acetylenic bond (Scheme 1 l)? Ketyl radical anions generated in the same manner were cyclized onto allenes by Crandall and Mualla.I6 Various cobalt complexes have again been demonstrated to be efficient in promoting the cyclization of alkyl and aryl halides onto appropriately placed double bonds." The Reagent i sodium naphthalenide Scheme 11 Z.CekoviE and R. SaiEiE Tetrahedron Lett. 1986 27 5981. Is G. Pattenden and G. M. Robertson Tetrahedron Lett. 1986 27 399. 1b J. K. Crandall and M. Mualla Tetrahedron Lett. 1986 27 2243. " H. Bhandal G. Pattenden and J. J. Russell Tetrahedron Lett. 1986 27 2299; V. F. Patel G. Pattenden and J. J. Russell ibid. 1986 27 2303. Reaction Mechanisms -Part (iii) Free-radical Reactions cobalt complexes need only be present in catalytic quantities with regeneration by either chemical or electrochemical means. The use of a cobalt complex in stoicheiometric amounts leads after cyclization to an organocobalt( 111) species which can be transformed with oxygen and sodium borohydride to the corresponding alcohol.In the field of remote functionalization Breslow has been able to functionalize for the first time on the P-face of a steroid using a 6P-ester (Scheme 12)." In this manner it was possible after elimination and ozonolysis to effect cleavage of the cholesterol side-chain to the 20-ketone. Three papers" describing the use of excep- tionally active catalysts for the remote functionalization of various steroidal alcohols and esters were later retracted.20 Reagents i PhlCl2 CH2C12 Bu'OH NaHCO, hv; ii -HCI; iii O3 Scheme 12 Intermolecular Processes.-Several interesting developments have been made in the field of carbon-carbon bond formation by intermolecular radical addition to multiple bonds. The use of a catalytic quantity of tri-n-butyltin chloride and sodium cyanoborohydride as overall reductant enabled Stork to employ a variety of activated alkenes including methyl and phenyl vinylsulphone and diethyl vinylphosphonate as radical traps in his radical cyclization with subsequent intermolecular carbon- carbon bond forming sequence.21 Particularly noteworthy was the use of an a-trimethylsilyl-aP-unsaturated ketone as radical trap in this sequence leading to an a-silyl ketone which was subsequently rearranged to give a regiospecific trimethyl- silyl enol ether (Scheme 13).22 It has been demonstrated that 2-carboethoxyallyl-tri-n-butylstannane( 1) under-goes SH2' reactions with alkyl radicals much more rapidly than simple allyl-tri-n- b~tylstannane.~~ The N-tertiary butyl carboxamide group also proved to be a good U.Maitra and R. Breslow Tetrahedron Lerr. 1986 27 3087. 19 R. Breslow and M. P. Mehta J. Am. Chem. Soc. 1986 108 2485; 1986 108 6417; 1986 108 6418. 2o R. Breslow Chem. Eng. New; December 8 1986 p. 2; J. Am. Chem. Soc. 1987 109 1605. G. Stork and P. M. Sher J. Am. Chem. Soc. 1986 108 303. 22 G. Stork P. M. Sher and H.-L. Chen J. Am. Chem. Soc. 1986 108 6384. 23 J. E. Baldwin R. M. Adlington D. J. Birch J. A. Crawford and J. B. Sweeney J. Chem. Soc. Chem. Commun. 1986 1339. 70 D. Crich OEt Q-(OEt I + 'I OSiMe3 Reagents i 10% Bu3SnCI NaBH3CN CH,=CH(SiMe3)CO(CH2)4Me; ii 140 "C Scheme 13 activating group for the S,2' reactions of allylstannanes. At the same time it was demonstrated that 1 -or 3-substituted allylstannanes are scrambled under free-radical conditions.In the reaction of carboxylic/thiohydroxamic mixed anhydrides (which this author proposes to call 0-acyl thiohydroxamates) with allylic sulphides the presence of an activating group as in (2) was found to be f~ndamental.~~ COzEt ASCMe, / Tertiary-butyldiphenylmethylhydrazones have been shown to be superior to triphenylmethylhydrazones for the formation of alkyl radicals by a deprotonation alkylation and subsequent azo decomposition sequence.25 In order to form the radical the intermediate azo-compound was heated in benzene at reflux. Diphenyl diselenide N-bromo- and N-chloro-succinimide and P-nitrostyrene were used to trap radicals formed in this manner. Low-temperature deprotonation of triphenyl- methylhydrazones and treatment of the resulting anion first with an aldehyde or ketone and then phosphorus trichloride prior to warming to room temperature results in the formation of alkenes possibly via a 4-membered ring (Scheme 14).26 24 D.H. R. Barton and D. Crich J. Chem. SOC.,Perkin Trans. I 1986 1613. 25 J. E. Baldwin R. M. Adlington and I. M. Newington J. Chem. Soc. Chem. Commun. 1986 176. 26 J. E. Baldwin R. M. Adlington J. C. Bottaro J. N. Kolhe I. M. Newington and M. W. D. Perry Tetrahedron 1986 42 4235. Reaction Mechanisms -Part (iii) Free-radical Reactions Reagents i MeLi THF/TMEDA -55 "C; ii PhCHO; iii XI, -78°C; iv -104 20°C Scheme 14 With the aid of alkylmercury(I1) chlorides as radical sources Russell has carried out the substitution of phenylacetylenes themselves containing an appropriate radical leaving group at the terminal position by a proximal addition elimination sequence (Scheme 15).27 The irradiation of alkylmercury( 11) chlorides in the presence of an activated terminal alkene results in the formation of a bishomoalkylmercury( 11) chloride via a radical chain-reaction (Scheme 16) .28 Similarly alkylmercury( 11) chlorides can be added across activated acetylenes.Ph-CEC-I + R-Hg-ClZ Ph-C=C-R Scheme 15 0 Scheme 16 Dicyanogen triselenide was introduced as an efficient trap for alkyl radicals leading to the formation of alkyl selen~cyanates.~~ Homolytic substitution of nitrogenous heterocycles was a popular subject in 1986.The importance of protonation of the heterocycle in increasing the rate of addition and in drastically changing the regioselectivity of addition was demonstrated by Mini~ci.~' Thus phenyl radicals generated from dibenzoyl peroxide add to 4-cyanopyridine giving a 0.23/1 ratio of ortho/ meta substitution products whereas addition to the 4-cyanopyridinium cation gave an ortho/ meta ratio of 1.71/ 1. Formylation of heteroaromatic bases can be 27 G. A. Russell and P. Ngoviwatchai Tetrahedron Lett. 1986 27 3479. 28 G. A. Russell W. Jiang S. S. Hu and R. K. Khanna J. Org. Chem. 1986 51 5498. 29 D. H. R. Barton D. Bridon Y. HervC P. Potier J. Thierry and S. Z. Zard TetrcLedron 1986,42,4983. 30 F. Minisci E. Vismara F. Fontana G. Morini M.Serravalle and C. Giordano J. Org. Chem. 1986 51 441 1. 72 D. Crich achieved by reaction of the base hydrochloride with trioxane tertiary butyl- hydroperoxide and ferrous ion followed by an aqueous work-~p.~' The dibenzoyl peroxide-initiated substitution of the lepidinium cation with cyclohexene leads not to the 243'-cyclohexenyl)lepidinium cation but rather to the (241'-cyclo-hexeny1)lepidinium cation.32 A mechanistic rationale for this observation involving addition of the benzoyloxy radical to cyclohexene substitution of the lepidinium cation by the adduct and finally elimination of benzoic acid was proposed. Homolytic substitution of protonated heteroaromatic bases was also achieved by photolysis in the presence of 0-acyl thiohydroxamates as radical sources (Scheme 17).33 The efficiency of substitution of protonated heteroaromatic bases with benzyl radicals is temperature-dependent.34 The ratio of dibenzyl to benzylated base increases significantly with temperature leading to the speculation that the addition of benzyl radicals to protonated bases is reversible.NHCOPh NHCOPh + G[-O-N? S Reagents camphor-10-sulphonic acid DMF hv Scheme 17 3 Mechanism and Physical Aspects The kinetic product of vinyl radical cyclization onto a 6-alkene is the 5-exo-trig At high stannane concentration the a-methylenecyclopentylmethyl radical so formed can be effectively trapped. At lower stannane concentration this radical undergoes rearrangement via a cyclopropylmethyl radical to the thermodynamically more favoured P-methylenecyclohexyl radical the product of an apparent 6-endo-trig process (Scheme 18).First-order rate constants were measured for steps a and b (Scheme 18) and found to be 1.2 x 10' and 1.6 x lo5s-' respectively at 60 "C. Aryl radicals were also found to cyclize rapidly in a 5-exo-trig mode onto 8-alkenes (5 x lo's-' at 50°C for the parent 2-(3'-buteny1)phenyl radical).36 Here again however in certain cases the kinetic 5-exo-trig cyclized radicals have been shown to undergo rearrangement by a pathway analogous to that outlined in Scheme 18 to the apparent 6-endo-trig produ~t.~' The nature of substituents at position-6 on the aromatic ring had a pronounced effect on the efficiency of this rearrangement. 31 C.Giordano F. Minisci E.Vismara and S. Levi J. Org. Chem. 1986 51 536. 32 E. Vismara M. Serravalle and F. Minisci Tetrahedron Lett. 1986 27 3187. 33 D. H. R. Barton B. Garcia H. Togo and S. Z. Zard Tetrahedron Lett. 1986 27 1327; E. Castognino S. Corsano D. H. R. Barton and S. Z. Zard ibid. 1986 27 6337. 34 F. Minisci E. Vismara G. Morini F. Fontana S. Levi M. Serravalle and C. Giordano J. Org. Chem. 1986 51 476. 35 A. L. J. Beckwith and D. M. O'Shea Tetrahedron Lett. 1986 27 4525; G. Stork and R. Mook ibid. 1986 27 4529. 36 A. N. Abeywickrema and A. L. J. Beckwith J. Chem. Soc. Chem. Commun. 1986,464. 37 K. A. Parker D. M. Spero and K. C. Inman Tetrahedron Lett. 1986 27 2833. Reaction Mechanisms -Part (iii) Free-radical Reactions b Ilow[Bu,SnH] Scheme 18 Thus with a 6-formyl group the rearrangement product was the only one observed whilst with a 6-hydroxymethyl group no rearrangement was found.Giese has studied the rate of 1,2-formyl migration in P-formyl radicals and found it to be of a similar order to 1,2-vinyl migration in P-vinyl radicals3* Two useful papers describing the relative reactivities of variously substituted alkyl halides alkyl phenyl sulphides and alkyl phenyl selenides towards tri-n-butylstannyl radicals and tri- n-butylgermyl radicals were published.39 In general it was found that for a specific alkyl group the order of reactivity is Br > PhSe > C1 > 4-NC-C6H4S > PhS > 4-Me-C6H4S > MeS and that for a given halide or chal- cogen X the order of reactivity of the alkyl fragment is EtOCOCH2X > RCH,0CH2X > RC02CHzX> RCH2X.It was also found that the tri-n-butyl- germyl radical abstracts halogen (with the exception of chlorine) and chalcogen more rapidly than the tri-n-butylstannyl radical and adds more rapidly to alkenes. Nevertheless with the possible exception of reactions involving a radical rearrange- ment or cyclization step the use of germanes instead of stannanes does not necessarily lead to higher yields in chain reactions due to the relatively poor hydrogen-donor capability of germanes. Pentamethyldisilane has been proposed as a hydrogen donor in radical chain-reactions with alkyl halides;40 in terms of reactivity towards alkyl radicals it was found to be intermediate between tri-n-butylgermanium hydride and triethylsilane.The rate of inversion of the parent cyclopropyl radical has been estimated by means of specific deuterium labelling to be greater than 10” s-l at 71 0C.41 Pyramidal alkyl radicals show similar selectivity towards alkenes in addition reactions as planar alkyl radicals.42 The selectivity of addition of a series of alkylated ethyl bromoacetates to two pairs of alkenes has been ~tudied.4~ With the exception of the parent radical it was found that the carboethoxyalkyl radicals added more rapidly to propyl-2-propenyl ether than to 1-octene but also more rapidly to 1-methylcyclohexene than to 1-octene. Both selectivities increased with increasing steric bulk at the radical centre which was explained in terms of increased radical persistance and hence lower exothermicity of addition.38 B. Giese N. Heinrich H. Horler W. Koch and H. Schwarz Chem. Ber. 1986 119 3528. 39 A. L. J. Beckwith and P. E. Pigou Aust. J. Chem. 1986 39 77; 1986 39 1151. 40 J. Lusztyk B. Maillard and K. U. Ingold J. Org. Chem. 1986 51 2457. 41 L. J. Johnston and K. U. Ingold J. Am. Chem. Soc. 1986 108 2343. 42 B. Giese and J. A. Gonzalez-Gomez Chem. Ber. 1986 119 1291. 43 V. Ghodoussi G. J. Gleicher and M. Kravetz J. Org. Chem. 1986 51 5007. 74 D. Crich The reaction of alkylcobaloximes with various radicals has been portrayed for some years now as an example of SH2 at carbon; two more examples of this process involving the reaction of propargy14 and benzylcobaloximes4’ with sulphonyl chlorides have appeared.Evidence has been presented however for an alternative mechanism involving addition of the attacking radical onto a ligand giving a resonance-stabilized nitroxide radical followed by elimination to give the apparent S,2 product (Scheme 19).46The reaction of small strained propellanes with bromotri- chloromethane tetrachloromethane and aldehydes in the presence of dibenzoyl peroxide does however appear to be a good candidate for a reaction involving an SH2 step at carbon.47 Interestingly the use of acetaldehyde led to a 2/1 adduct (Scheme 20). A review on the homolytic reactions of small strained bicycloalkanes has appeared.48 Beckwith has demonstrated that SH2 at sulphur in chiral sulphoxides takes place with complete inversion of c0nfiguration.4~ I I OH OH Scbeme 19 OH (PhCO,), + MeCHO -Me~&c!H-Me Scheme 20 Benzyl vinyl ethers are formed on reaction of 1-aryl-2-bromomethyloxiranes with tri-n-butyltin hydride and a radical initiator.” By means of 180-labelling studies the 1,2-acetoxy migration in 2-acetoxyalkyl radicals was shown to be a 1,2-shift involving only the acetoxy oxygen as opposed to a 2,3-shift involving the carbonyl oxygen.’l A particularly interesting example of this radical rearrangement is the formation of 2-deoxyglucose tetraacetate upon treatment of acetobromoglucose with tri-n-butylstannane (Scheme 2 1).52 This particular example appears to have gone pre- viously unnoticed and doubtless depends on the order and rate of addition of the reactants.The mechanism of addition of tri-n-butylstannyl iodoacetates to alkenes giving y-lactones has been in~estigated~~ and shown to proceed via two discrete 44 B. D. Gupta and S. Roy Tetrahedron Lett. 1986 27 4905. 45 B. D. Gupta M. Kumar 1. Das and S. Roy Tetrahedron Lett. 1986 27 5773. 46 R. C. McHatton J. H. Espenson and A. Bakac J. Am. Chem. Soc, 1986 108 5885. 41 K. B. Wiberg S. T. Waddell and K. Laidig Tetrahedron Lett. 1986 27 1553. 48 K. U. Ingold and J. C. Walton Acc. Chem. Rex 1986 19 72. 49 A. L. J. Beckwith and D. R. Boate J. Chem. SOC.,Chem. Commun. 1986 189. 50 M. Cook 0.Hares A. Johns J. A. Murphy and C. W. Patterson J. Chem. SOC.,Chem. Commun. 1986 1419. P. KoEovski I. Sta~,and F. TureEek Tetrahedron Lett.1986 27 1513. 52 B. Giese Silicon Germanium Tin and Lead Compounds 1986 9 99. 53 M. Degueil-Castaing B. De Jaso G. A. Kraus K. Landgrebe and 9. Maillard Tetrahedron Leu. 1986 27 5927. Reaction Mechanisms -Part (iii) Free-radical Reactions Scheme 21 steps; a radical chain-process involving addition of the carbon-iodine bond across the alkene followed by a two-electron cyclization of the so-formed stannyl y-iodocarboxylate to the lactone. Unlike their acyclic counterparts which are quenched by oxygen at the terminal position six-membered cyclic pentadienyl radicals react with molecular oxygen at the central position leading eventually to cross-conjugated cyclohexadienone~.~~ This disparity was explained in terms of reduced steric strain in the adduct radical.Newcomb and Park used 0-acyl thiohydroxamates in the measurement of rates of hydrogen abstraction by alkyl radicals from various hydrogen donors and found them to be a clean and convenient radical source for use in this kind of quantitative Beckwith measured the rates of reaction of primary alkyl radicals with the stable nitroxide (3) and found them to be of the order 8.9 x lo8mol-' dm3 s-' at 60 0C.56 Warkentin used the same nitroxide (3) to calibrate the rate of ring-opening of the cyclopropylmethyl radical in the range 30-90 0C.57 X The capto-dative effect continues to be a subject of much interest. Newcomb investigated the effect of captodative substituents on the rate of cyclization of 5-hexenyl radicals (4).58 Thus it was found that at 50°C the 6-cyano-5-hexenyl radical [(4) X = H Y = CN] and the 6-methoxy-5-hexenyl[(4) X = H Y = OMe] cyclized 275-and 2.4-times more rapidly respectively than the standard 5-hexenyl radical whilst in the capto-dative substituted radical [(4) X = CN Y = OMe] cyclization was accelerated by a factor of 41 5 at 50 "C providing some slight evidence for a capto-dative effect.Neumann on the other hand found little or no evidence for merostabilization of 4,4'-disubstituted triarylmethyl radicals as measured by the extent of change in the position of the radical-dimer equilibrium according to the 54 A. L. J. Beckwith D. M. O'Shea and D. H. Roberts J. Am. Chem. Soc. 1986 108 6408. 55 M. Newcomb and S.-U. Park J. Am. Chem.SOC.,1986 108 4132. 56 A. L. J. Beckwith V. W. Bowry M. O'Leary G. Moad E. Rizzardo and D. H. Solomon J. Chem. Soc. Chem. Commun. 1986 1003. 57 L. Mathew and J. Warkentin J. Am. Chem. Soc. 1986 108 7981. 58 S.-U. Park S. K. Chung and M. Newcomb J. Am. Chem. SOC.,1986 108 240. 76 D. Crich nature (capto dative and capto-dative) of the aryl sub~tituents.~~ Viehe et al. noticed a significant drop in the minimum temperature required for the cleavage of symmetri- cally substituted 1,Shexadienes to ally1 radicals when the substituents were capto- dative in nature rather than simply one or the other.60 Katritzky et al. made the interesting suggestion that merostabilization is likely to be much more pronounced in polar media than in non-polar media as a result of the higher polarization of capto-dative substituted radicals as compared to more symmetrically substituted ones.61 The 'reverse effect' is a concept introduced by Ballester to describe the accelerating effect of persistent radicals in a molecule upon the reactions of other substituents in the same molecule.62 For example benzylic bromination with bromine and AIBN in tetrachloromethane at reflux of the di( pentachlorophenyl)-4-methyltetra-chlorophenylmethyl radical was found to be approximately eight times more rapid than bromination of the analogous triarylmethane under the same conditions.Similarly the reaction of diethylmalonate and potassium carbonate in dioxane at 90 "C with the di(pentachlorophenyl)-4-bromomethyltetrachlorophenylmethyl radical was nine times faster than with the triarylmethane.Finally the controversial idea of there being two types of chemistry associated with the succinimidyl radical one belonging to a .rr-type radical and one to a a-type radical has now been withdrawn.63 59 W. P. Neumann W. Uzick and A. K. Zarkadis J. Am. Chem. SOC. 1986 108 3762. 60 M. Van Hoecke A. Borghese J. Penelle R. MerCnyi and H. G. Viehe Tetrahedron Letl. 1986 27,4569. 61 A. R. Katritzky M. C. Zerner and M. M. Karelson J. Am. Cbem. SOC.,1986 108 7213. 62 M. Ballester J. Veciana J. Riera J. Castacer C. Rovira and 0.Armet J. Org. Chem. 1986 51 2472. 63 P. S. Skell U. Luning D. S. McBain and J. M. Tanko J. Am. Cbem. Soc. 1986 108 121.

ISSN:0069-3030    

DOI:10.1039/OC9868300065

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (i)Hydrocarbons By 6. V. SMITH Department of Chemistry King's College London (KQC) Kensington Campus Campden Hill Road London W8 7AH 1 Alkanes Protonolysis of trialkylboranes (RC0,H-diglyme) affords alkanes in variable yields; thus (C6H&B gave C6HI4(91% 2 h) whereas the borane with the hindered 2,4,4-trimethylpentyl structure gave only 5% of alkane.' Since this is a mild method it may be applied safely to sensitive compounds with sulphur halogen or nitrogen functions. Evidence was secured to confirm retention of stereochemistry during protonolysis. Sodium cyanoborohydride -zinc iodide is a unique and selective reducing agent for a range of compounds (aldehydes ketones and benzylic and tertiary alcohols) yielding the corresponding hydrocarbon (and in the former examples some alcohols).' gem-Dialkylation of carbonyl groups (ArCHO ArCOR) by sequential steps (Scheme 1)has been used for synthesis of arylalkane~.~ Tertiary alkyl radicals generated from alcohols via homolytic attack of RS' on (l),formed hydrocarbons in the presence of a thiol; some addition of the radical to an alkene was ob~erved.~ ArCOR' 2ArC(OH)R'R* 5ArC(SeMe)R'R2 iii I ArCR'R2R3 Reagents i RZM-EtzO;ii MeSeH-ZnC1,-CICHzCH,C1; iii BuLi-THF-hexane then R3X -78 "C Scheme 1 The extremely hindered hydrocarbon 2,3-di( l-adamantyl)2,3-dimethylbutanehas been prepared by a Wurtz reaction (0.6%yield in the final stage!).X-Ray diffraction showed deformation arising from torsional strain and lengthening of certain bonds as shown in (2).Theholysis (PhMe-PhSH 180°C 5 h) gave 1-AdCHMe as the major product.A negligible quantity of adamantane (<0.1%)was formed.' Coupling ' H. C. Brown and K. J. Murray Tetrahedron 1986,42 5497. C. K. Lau C. Dufresne P. C. Bilanger S. PiCtri and J. Scheigetz J. Org. Chem. 1986 51 3038. A. Krief M. Clarembeau and P. Barbeaux J. Chem. Soc. Chem. Commun. 1986 457. D. H. R.Barton and D. Crich J. Chem. SOC.,Perkin Trans. I 1986 1603 1613. M. A. Flamm-ter-Meer H.-D. Beckhaus K. Peters H.G. von Schnering H. Fritz and C. Ruchardt Chem. Ber. 1985 118 4665. 77 B. V. Smith of 1-adamantyl-1,l-dibromo-2,2-dimethylpropanewith magnesium gave three diastereoisomeric hydrocarbons (3) separable by crystallization. Structure determi- nation showed that they are a meso-and a d I-pair; it is notable that interconversion of rotamers does not take place at or above room temperature the first reported examples of simple aliphatic compounds which show this property.6 Energy barriers to rotation were measured; e.g.for meso-(3) the barriers for gauche- anti and gauche +gauche interconversions were 217 and 184 kJ mol-' respectively. Ther- molysis of (3) as for (2),gave 2 mols of 1-neopentyladamantane per mol of (3). 163.9 pm ROZC-COZ-N 164.7 pm- Ad S (1) Ad76.4MaLd 40.8 41.2 AdCH( But) CH(But)Ad (Torsional angles) (3) (2) Photolysis of trans-tetra-t-butylazomethane,in C6H6 or C6H5C1 gave a quantita- tive yield of 1,1,2,2-tetra-t-butylethane.' Reports have appeared of the 'Gif' system for functionalizing saturated hydrocar- bons.After some variations in conditions used in earlier experiments,8 the Gif'" system has evolved. It was shown to require an iron-containing catalyst oxygen zinc acetic acid and pyridine. An in-depth study revealed evidence for the role of superoxide (from one-electron reduction of 302). The Gif'" system is not a mimic of cytochrome oxidase (although it was thought that it could be) and does not epoxidize alkenes or oxidize sulphides. Selectivity in the oxidation (of for example adamantane) depends on the partial pressure of oxygen. The proposed mechanism (Scheme 2) is consistent with all observations made so far.' Although this scheme refers to a cyclic hydrocarbon the method will presumably allow of application to acyclic systems.It was shown that zinc could be replaced by an electrochemical cell with improvement in yields." M. A. Flamm-ter-Meer H.-D. Beckhaus K. Peters H.-G. von Schnering H. Fritz and C. Ruchardt Chem. Ber. 1986 119 1492. W. Bernlohr M. A. Flamm-ter-meer J. H. Kaiser M. Schmittel H.-D. Beckhaus and C. Ruchardt Chem. Ber. 1986 119 1911. D. H. R. Barton J. Boivin M. Gastiger J. Morzycki R. S. Hay-Motherwell W. B. Motherwell N. Ozbalik and K. M. Schwartzentruber J. Chem. SOC.,Perkin Trans. I 1986 947. D. H. R. Barton J. Boivin W. B. Motherwell N. Ozbalik K. M. Schwartzentruber and K. Jankowski Now. J. Chim. 1986 10 387. G. Balavoine D. H. R. Barton J. Boivin A. Gref N. Ozbalik and H. Rivibre Tetrahedron Lett.1986 27 2849; J. Chem. SOC.,Chem. Commun. 1986 1727. Aliphatic Compounds -Part (i) Hydrocarbons 79 In the presence of H202 a manganese porphyrin catalyst and imidazole alkanes are oxidized to a mixture of alcohol and ketone." 'Shape-selective hydroxylation' relies on highly hindered iron and manganese porphyrins and unprecedented enhancement of primary hydroxylation was observed in this chemical process.12 Reaction of alkanes with CO-H20 in HF-SbF5 under pressure gave a different product distribution from that obtained by the Koch-Haaf reaction. Thus c5-c6 alkanes with a tertiary hydrogen gave secondary carboxylic acids (from skeletal isomerization) and straight-chain alkanes gave extensive fragmentation judged by the mixtures f~rmed.'~ Activation of alkane C-H bonds by organometallics has been re~iewed.'~ Fe"' eFell ;o2,e-Fe"'OOH H+ =CHR I + ,e",/OH F I -Fe"=O (Major)=Y (Minor) OH Fe"=C / >kH Fen\ / I I 0-0-CH I I I O2 \ \ O=C / C-,CHOOH + ,CH-OH Notes; i n is variable; ii no ligands are shown on Fe atom Scheme 2 2 Alkenes Synthesis.-A stereospecific synthesis of (S)-3-methylpent- 1-ene from L-isoleucine has been achieved (e.e.98.6%).15 Protonolysis of alkenyldialkylboranes forms the basis of a simple stereospecific synthesis of z-alkenes.I6 Some acid catalysis may be needed; the process was applied to preparation of terminal and internal double bonds. In a closely related process lithium(1-alkyny1)tryialkylborates were iodinated to afford an alkyne which was reacted with 9-BBN; the adduct was transformed into a 2-alkene by protonoly~is.'~ Such routes are valuable in synthesis of pheromones or their precursors.A comparative study of stereoselective syntheses of E-trisubstituted alkenes has been published.'* P. Battioni J.-P. Renaud J. F. Bartoli and D. Mansuy J. Chem. SOC.,Chem. Commun. 1986 341. 12 B. R. Cook T. J. Reinert and K. S. Suslick J. Am. Chem. SOC.,1986 108 7281. 13 N. Yoneda Y. Takahashi T. Fukuhara and A. Suzuki Bull. Chem. SOC.Jpn. 1986 59 2819. 14 M. Ephritikhine Nouu. J. Chim. 1986 10 9. V. Schurig U. Leyrer and D. Wistuba J. Org. Chem. 1986 51 242. 16 H. C. Brown and G. A. Molander J. Org. Chem. 1986 51 4512. 17 H. C. Brown and K. K. Wang J.Org. Chem. 1986 51 4514. 18 A. Bernardi W. Cabri G. Poli and L. Prati J. Chem. Res. (S).,1986 52. 80 B. V. Smith E/Z-Selectivity was cu. 1 :1 for the reaction of a-phenylthiosilyl anions with ketones followed by Peterson elimination to form alkenes.” uic-Diols have been converted into alkenes stereospecifically by elimination of C02 AcOH and MeOAc in refluxing Ac,O from the intermediate 2-rnethoxy- 1,3-dioxolanes (4).20Iododesily-R’ lation of vinyl silanes has been used in ‘tuneable’ alkene synthesis with variable stereoselectivity. The intermediate (5) can form Z- or E-vinyl iodide (6) according to the conditions in which control is mediated by a Lewis acid (Scheme 3). Indications from the literature implies retention of stereochemistry in iododesily- ation and hence formation of the Z-vinyl iodide was unexpected.In a further step I I I Scheme 3 the formed vinyl iodide gave an alkene with e.g. RMgBr-Li,CuCl,; wide variation in the E/Z-ratio of the final product is possible by selection of the appropriate Lewis acid in the first step.21 By this approach pheromone synthesis was neatly achieved. Terminal allylic carbonates and acetates afforded terminal alkenes when reacted with formates and a Pd catalyst.22 Elimination from primary alkyl bromides and iodides by a new method gave principally a terminal alkene; the transformation 19 D.J. Ager J. Chem. Soc. Perkin Trans. I 1986 183. 2o M. Ando H. Ohhara and K. Takase Chem. Lett. 1986 879. 21 T. H. Chan and K. Koumaglo Tetrahedron Lett.1986 27 883. 22 J. Tsuji I. Minami and I. Shimizu Synthesis 1986,. 623. Aliphatic Compounds -Part (i) Hydrocarbons 81 was brought about by adding a mixture of RCH2X and 1,8-diazabicyclo[5.4.O]undec-7-ene in THF to C1,(PPh3)2Ni-PPh3-BuLi in THF.23 With HO(CH2),'Br 82% of alk-1-ene was obtained (together with 14% of internal alkene). Elimination of hydrogen bromide or hydrogen chloride from 5-halogeno-4-hydroxypent-1-enes furnished 4,5-epoxypent-l-ene in a short efficient process.24 A regioselective syn- thesis of a terminal alkene is shown in Scheme 4.25 Fe(CO) CP.BF i,ii R~POH +R1p RZ -RIP Reagents i (Pr'0)2POCI;ii Fe(CO)2Cp then HBF,; iii NaI Me2C0 0 "C Scheme 4 Three variations on the Wittig reaction have been reported.A molybdenum metalloazine (8) was generated from (7) and R'R2CN2; reaction of (8) with Ph3P=CR3R4 gave high yields of R'R2C=CR3R4 (Z/E ratio = 1.25 when R' = R3 = H R2 = Ph R4 = Bu).~~ Decomposition of the Wittig-like intermediate gave Ph3P(!) and N2. kine (8) reacted with Bu'NH2 forming an imine. Tungsten alky- 0 :Mo'"(S~CNR,)~ (7) lidene complexes W( =CR'R2)X2Y2 were shown to react with carbonyl groups to form alkenes bearing two three or four substituents. Enol ethers and enamines were also prepared by this method. The tungsten derivatives reacted with esters amides and lac tone^.^^ Carbonyl compounds reacted cleanly with C1CH2Li (from C1CH21-MeLi) forming alkenes.28 The use of mesyltriflone (9) for alkene synthesis has been developed further.29 As shown in Scheme 5 sequential deprotonation -alkylation led to di- tri- and tetra-substitution in the formed alkene.The process is characterized by clean regiospecific reaction and smooth Ramberg-Backlund elimination; it is possible to carry out one-pot operations. Stereospecificity is not controlled since for (lo) a 1:1 mixture of diastereoisomers was formed. Acylation of the sulphone was also examined and shown to be satisfactory; a short convenient synthesis of artemisia ketone (11) was devised (89% yield). 23 S. Jeropoulos and E. H. Smith J. Chem. SOC.,Chem. Commun.,1986 1621. 24 A. De Camp Schuda P. H. Mazzochi G. Fritz,. and T. Morgan Synthesis 1986 309. 25 S. Araki M. Hatano and Y. Butsugan J. Org. Chem. 1986 51 2126.26 J. A. Smegal I. K. Meier and J. Schwartz J. Am. Chem. SOC.,1986 108 1322. 27 A. Agnero J. Kress and J. A. Osborn J. Chem. SOC.,Chem. Commun. 1986 31. 28 J. Barluenga J. L. Fernandez-Simon J. M. Concell6n and M. Yus J. Chem. Soc. Chem. Commun. 1986 1665. 29 J. B. Hendrickson G. J. Boudreaux and P. S. Palumbo J. Am. Chem. Soc. 1986 108 2358. B. V. Smith Tf-S02 TfVS02 2Tf-SO2 TfVSO2 '-2-ii 1 ii 1 I TfYSo2vR2 R' ii li "X TfY TfYso2vR2 R' R4 R' iii 1 I R2 R'I ii ii R' TfXSo2vR2 )= R' R4 R4 iii iii I 1 R' [Tf = CF3S0 -3 )=-R2 RkR2 R4 R4 R3 Reagents i BuLi; ii R'X R2X R3X or R4X; iii KOBUI-THF OT,or K2C03-THF-A or NaOHaq-CH~CI~-BU.,N+HSO; Scheme 5 The addition of lithium to simple cyclic and acyclic alkynes led to formation of ~ic-dilithioalkenes.~~ Thus oct-3-yne by metallation and quenching with MeOD- Et20 gave (12) with isotope distribution of 77%-D2 18%-D1 and 5%-D0.A practical synthesis of methylated alkenes was achieved by quenching the dilithiated oct-3-yne with Me2S04 affording E-3,4-dimethyloct-3-ene (62% ). It was surmised that a cis -* trans isomerization has occurred in such processes since cycloalkynes (and PhCECH) formed cis-lithiated derivatives. An ab initio study of the isomers of 1,2-dilithioethene has a~peared.~' Synthetic applications of tellurium reagents including alkene synthesis and stereomutation of alkenes have been reviewed.32 Reactions.-Multiphoton laser-induced isomerization/fragmentations of alkenes have been 30 A.Maercker T. Grade and V. Girreser Angew. Chem. Int. Edn. Engl. 1986 25 167. 31 P. von R. Schleyer E. Kaufmann A. J. Kos T. Clark and J. A. Pople Angew. Chem. Int. Edn. Engf. 1986 25 169. 32 N. Petragnani and J. V. Comasseto Synthesis 1986 1. 33 F. D. Lewis P. Teng and E. Weitz J. Am. Chem. Soc. 1986 108 2818. Aliphatic Compounds -Part (i) Hydrocarbons 83 Some revision of earlier estimates of regioselectivity of hydroboration has been ~ndertaken.~~ It was recognized that in the addition of the HBBr2.SMe2 reagent to alkenes some addition of HBr may have occurred. Consequently during the alkaline oxidation to form alcohol some alcohol may have been obtained via the bromide. With modified experimental technique such spurious addition is avoided and the true regioselectivity of the reagent can be assessed.Thus 2-methylbut-2-ene and hex-1-ene were shown to form only 1% of Markownikov product. These results now compare with those obtained by the use of ultrasound-promoted hydrobora- ti~n.~~ Asymmetric hydroboration of prochiral alkenes has been exploited in a sequence leading to amines R*NH2 with very high (>99%) optical purity.36 Secon- dary deuterium kinetic isotope effects have been analysed in enantioselective hydro- borations; it was concluded that substituents in the allylic position are crucial for enantioselection. Alkenes ( 13)-( 16) were prepared reacted with di-isopinocam- pheylborane and then aqueous Na202 to form the alcohol(s). Analysis of the mixture of e.g.EtCH(OH)CH(D)Et and EtCH,CD(OH)Et [from (13)] was carried out with LIS n.m.r. to enable calculation of k,/ k to be made. The lack of secondary isotope effect with (13) was taken as evidence for absence of steric compression of vinylic hydrogen in the transition state.37 D H -a$%:DHfi: H H n D D n H H H Electrophilic addition of bromine to micelle-associated alkenes has been used as a probe of micelle structure; variation in micellar components reveals a product dependence arising from attack of the counterion on the bromonium ion.38 Regioselectivity in addition of BrCl and the dichlorobromate ion to alkenes has been analysed in terms of contribution from polar and steric effects.39 Fluorine in aqueous MeCN reacts rapidly with alkenes forming epoxides; thus dodec-1-ene gave >go% yield.40 The mechanism is not certain but perhaps HOF is involved; this pathway offers fast selective reaction in high yield and at low temperatures.In the addition of elemental fluorine to alkenes in CHC13-CFC13 mixture addition of a proton donor suppresses radical processes (and tar formation) and encourages ionic addition?l The process appears to take place via syn-addition and it is proposed that rapid collapse of an ion pair involving an a-fluorocarbocation accounts for observed stereochemistry. Yields of difluoro-adducts are 50-55%. 34 H. C. Brown and U. S. Racherla J. Org. Chem. 1986 51 895. 35 H. C. Brown and U. S. Racherla Tetrahedron Lett. 1985 26 2187. 36 H. C. Brown K.-W.Kim T. E. Cole and B. Singaram J. Am. Chem. SOC.,1986 108 6761. 37 B. E. Mann P. W. Cutts J. McKenna J. M. McKenna and C. M. Spencer Angew. Chem. Int. Edn. Engl. 1986 25 577. 38 R. B. Lennox and R. A. McClelland J. Am. Chem. SOC,1986 108 3771. 39 T. Negoro and Y. Ikeda Bull. Chem. SOC.Jpn. 1986 59 2547. 40 S. Rozen and M. Brand Angew. Chem. Int. Edn. Engl. 1986 25 554. 41 S. Rozen and M. Brand J. Org. Chem. 1986 51 3607. 84 B. V. Smith Photoirradiation of a methanolic solution of an alkene (containing EuC13) led to formation of hydroxymethylalkane the dihydrodimer of the alkene hydrogen and HOCH2CH20H. A photo-initiated redox system [Eu"'-Eu"] was impli~ated.~~ Diacylation of alkenes with acid catalysis has been used in synthesis of pyrylium salts and thus of pyridine~.~~ Terminal alkenes add HSiEt, in the presence of Ru,(CO),~ to afford E-RCH=CHSiEt,; for substitution patterns of the type R'R2CH-CH=CH2 some allylic silane and alkane were produced simultaneously.44 Regioselective formation of 1 -or 2-p-toluenesulphonylalk-1-enes was achieved by either iodosulphonylation or sulphonylmer~uration.~~ A synthesis of alk-1-enyl azides from trans- 1,2-epoxy- silanes (18) gave the 2-isomers (17) with Z/E-specificity of 93-95% when R was alkyl; for R = Ph low yield (8%) was reported but the product was a single (Z)-i~omer.~~ A simple route to nitroalkenes (19) is based on an addition-elimination Rt_jN02 f-7 R2 R3 sequence starting with R'R2C=CHR3 and NaN0,-12-EtOAc-H20.Yields were variable (49-82%) in this alternative to the Henry rea~tion.~' Alkenes add Hg(N03)2,forming P-nitrato-alkyl mercury( 11) nitrates (probably by trans-addition) which with bromine formed P-bromoalkylnitrates?* 2-But-2-ene thus formed a single diastereoisomeric mixture differing from that obtained with E-but-2-ene. The complex involved in catalytic hydrocyanation of ethene has been identified as (20); L is a phosphorus-containing ligand.49 An improved procedure for metallation of 2-and E-but-2-enes gave stereochemi- cally pure 2-and E-cr~tylpotassiums.~~ Subsequent boration and reaction with RCHO was employed in a route to erythro-or threo-P-methylhomoallylalcohols with very high diastereo- and enantio-selectivities. Metallation of 2,3-dimethylbut-2- ene leads preferentially to a cross-conjugated dianion agreeing with prediction." The mono- and di-anions were shown to undergo elimination a novel reaction for such systems.Allylic zinc halides react with metallated alkenes (RCH=CHMet; R = C6HI3 Met = Li or MgBr) forming (21) which was transformed further by reaction with electrophiles R'X and R2X to afford (22). In an alternative scheme (21) was transformed into (23) and hence (24) with CH2=CH(R)CH2X.52A wide range of polyfunkional compounds may be prepared by these routes illustrated in the examples cited. 42 A. Ishida S. Yamashita S. Toki and S. Takamuku Bull. Chem. SOC.Jpn. 1986 59 1195. 43 H. G. Rajoharison and C. Roussel Bull. Chem. SOC.Fr. 1986 307. 44 Y. Seki K. Takeshita K.Kawamoto S. Murai and N. Sonoda J. Org. Chem. 1986 51 3890. 45 K. Inomata T. Kobayashi S. Sasaoka H. Kinoshita and H. Kotake Chem. Lett 1986 289. 46 S. Tomoda Y. Matsumoto Y. Takeuchi and Y. Nomura Bull. Chem. SOC.Jpn. 1986 59 3283. 47 S. Jew H. Kim Y. Cho and C. Cook Chem. Lett. 1986 1747. 48 A. J. Bloodworth and P. N. Cooper J. Chem. SOC.,Chem. Commun. 1986 709. 49 R. J. McKinney and D. C. Roe J. Am. Chem. SOC.,1986 108 5167. 50 H. C. Brown and K. S. Bhat J. Am. Chem. SOC.,1986 108 5919. 51 N. S. Mills and A. R. Rusinko 111 J. Org. Chem. 1986 51 2567. 52 P. Knochel and J. F. Normant Tetrahedron Letf. 1986 27 4427. 4431 5727. AIiphatic Compounds -Part (i) Hydrocarbons L-Ni-CN Et RqMet I- ZnBr E2 ZnBr (20) (21) Allylic dimethylphenylsilanes show remarkable regioselectivity in reactions of their carbanions with C02 or MeI.s3 Despite the known tendency for y-selectivity in reaction of CH2=CHCH2SiR3 methylation or carboxylation occurred at the a-position.The a-carboxylated allylic silanes form useful synthetic equivalents for 3-carboxylated ally1 anions. Two general accounts of the Sharpless reaction have appeared.54 Interest in applications and modifications of the process has been maintained. The role of water has been discussed and it was shown that as little as 15 mol% of Ti(OPr') was sufficient to convert geraniol into the epoxide (99'/0 yield 91% optical purity).55 Ally1 alcohols are smoothly converted into epoxides in a process of high regio- and stereo-selectivity which is based on Bu~S~O-BU'OOH.~~ A new approach to structure-selectivity relationships in epoxidation has explored the use of a novel family of peracids chosen in order to magnify steric effects at the expense of electronic effects." Since selectivity arising from the transition state in the Prilaschajew reaction [written as (25)J is low for cisltrans-pairs of alkenes an attempt was made to prepare a peracid (U-shaped) in which steric bulk could modify the ease of approach of the alkene to the site of oxygen transfer.Such an acid (26) R I showed low selectivity and even when the bridge across the cyclohexane ring contained a naphthalene residue there was negligible selectivity. The C-shaped peracid (27) showed greater selectivity; thus for (27b) Bu'CH=CHEt gave kcis/kfrans = 7.8.These results are consistent with a transition state in which the C=C bond is parallel to the 0-H bond of the peracid. Chiral sulphamyloxaziridines have been used in the asymmetric oxidation of non-functionalized alkenes. Thus (R,R)-(28)with PhCH=CHPh gave syn-stereo- specific epoxidation. Reaction was fastest in MeCN but some selectivity was lost.'* 53 H. Uno Bull. Chem. SOC.Jpn. 1986 59 2471. 54 K. B. Sharpless Chem. Brit. 1986 38; A. Pfenninger Synthesis 1986 89. 55 R. M. Hanson and K. B. Sharpless J. Org. Chem. 1986 51 1922. 56 S. Kanemoto T. Nonaka K. Oshima K. Ultimoto and H. Nozaki Tetrahedron Lett. 1986 27 3387. 51 J. Rebek jun. L. Marshall J. McManis and R. Wolak J. Org. Chem. 1986 51 1649.F. A. Davis and S. Chattopadhyay Tetrahedron Lett. 1986 27 5079. B. V. Smith Me 0 '. / 0 \ CsF5 (27a) R = Me (27b) R = Et [a = (S)-( -)-N-benzyl-1-phenylethylamine] A dinuclear iron peroxide complex has been described which can epoxidize e.g. 2-stilbene; the yield is very low (2.5%) but the product was claimed to have a cis/ trans-ratio of 5 :95.59 Dinuclear copper complexes do not epoxidize terminal alkenes and give modest yields with di-or tetra-substituted alkenes; thus Me,C=CMe gave 41% and PhCH=CHPh 23% (E) and 8% (2)of epoxide. In the latter example some PhCHO was also formed.60 Novel vanadium( v) complexes epoxidize alk-1-enes in addition to other types e.g. oct-1-ene gave 40% and Me2C=CMe2 yielded 98% of product.61 A system based on mimicking mono- oxygenase action which used Mn"'-NaOC1 has been the subject of a study of rates and products of reaction.62 A theoretical analysis of epoxidation by v2-peroxo- complexes of Group VI transition metals has analysed the interactions in terms of frontier orbitals.62 The unusual alkene (29) prepared from reductive coupling of (30) (TiCl3-LiA1H4-THF) is very easily oxidized (Eo= 0.7V) and yet forms a normal ep~xide.~~ The chiral ligand ( -)-(&R)-N,N,N',N'-tetramethylcyclohexane-1,2-truns-diamine allows high levels of asymmetric hydroxylation of alkenes by OSO~.~~ Thus hept-1-ene gave (R)-heptan-1,2-diol (75% 86% e.e.) in 2 h at room temperature.With PhCH=CH2 reaction was slower and the e.e. was much lower (34%).Chalcone did not react in three days. A review of allylic oxidation brought about by stoicheiometric or catalytic quantities of metal complexes has been published.65 Amongst+other work on additions to alkenes reports have appeared of addition of Ar-CEN-0 to (3R)-but-l-ene in which addition seems to occur from attack 59 B. P. Murch F. C. Bradley and L. Que jun. J. Am. Chem. SOC.,1986 108 5027. 60 A. F. Tai L. D. Margerum and J. S. Valentine J. Am. Chem. Soc. 1986 108 5006. 61 H. Mimoun M. Mignard P. Brechot and L. Saussine J. Am. Chem. SOC.,1986 108 3711. 62 J. A. S. J. Razenberg R. J. M. Nolte and W. Dreuth J. Chem. SOC.,Chem. Commun. 1986 277; K. A. J~rgensen and R. Hoffman Acra Chem. Scand. (B) 1986,40 411. 63 H. Wenck A. de Meijere F. Gerson and R.Gleiter Angew. Chern. Znr. Edn. Engl. 1986 25 335. 64 M. Tokles and J. K. Snyder Tetrahedron Lett. 1986 27 3951. 65 J. Muzart Bull. Chem. SOC.Fr. 1986. 65. Aliphatic Compounds -Part (i) Hydrocarbons 87 on the more hindered face of the preferred conformation of the alkene,66 addition of SO3-PhIO forming cyclic ~ulphates,~~ and halogenocyclopropanation via MeLi- CH2C12-LiBr.68 In the latter reaction allylic alcohols containing a methyl group cis to the hydroxyl gave rise to an unexpected syn-stereoselection which was attributed to a synergic interaction between the groups. Thus (31) gave only trans-(32) (X = Cl or Br; Cl/Br = 77/23) whereas (33) gave (34) (X = C1 c/t = 76/24 X = Br c/t = 97/3; Cl/Br = 75/25). .r PT' Me ..OH OH X Me Alkanes add to alkenes in a thermally initiated process with characteristics of a radical chain.69 Addition of carbocations of the type Ar2CH+ to alkenes R'R2C=CR3R4 was the subject of analysis of rates and products. A conclusion which was drawn from the data suggests that the transition state is scarcely bridged. A second paper refers to reaction with diene~.~' It is believed that the nickel-promoted addition of a perfluoroalkyl iodide to an alkene proceeds via single-electron transfer since scavenging experiments gave positive results.71 The complex Cl,(MeOCH,OMe)( WECCMe,) with alkenes gave disproportion- ation and dimerization; thus oct-1-ene gave ethene and tetradec-7-ene. In this way 40% conversion of oct-1-ene was realized in 30 minutes at room ternperat~re.~' Cationic nickel complexes containing dithio-P-diketonate and chelating diphos- phine ligands serve as effective catalysts for oligomerization and double-bond migration of olefins.The product mix is rich in dimers with a high proportion of linear or near-linear isomers; e.g. propene gave ca. 75% methylpentenes and 16% hexene~.~~ A substantial review of transition metal-catalysed dimerization of small alkenes has appeared.74 Stereoregulation of ionic polymerization of alkenes has been reviewed.75 It has been observed that the cyclization of 1-methylhex-5-enyl halides (Na or Na-C$8 in THF or DME) is suppressed by Bu'NH2. Cyclization of the radical is unaffected however and this method is shown to be a valid probe for the radical and to distinguish between radical and polar pathways.76 Double-bond migration in alk-1-en-3-yl acetates can be effected by N~OH-ACOH.~~ 66 K.N. Houk H.-Y. Duh Y.-D. Wu and S. R. Moses J. Am. Chem. SOC.,1986 108 2754. 67 N. S. Zefirov V. D. Sorokin V. V.Zhdankin and A. S. Koz'min J. Org. Chem U.S.S.R,1986,22,398. 6a R. Barlet R. Baharmast and M. Vidal C. R Hebd. Seances Acad. Sci Ser. C 1986 303,289. 69 J. Hartmanns K. Klenke and J. 0.Metzger Chem. Ber. 1986,119,488; J. Hartmanns and J. 0.Metzger ibid. 1986 119 500; J. Hartmanns J. 0. Metzger and D. Eisermann ibid. 1986 119 508. 70 H. Mayr and R. Pock Chem. Ber. 1986 119 2473. 71 Q.-Y. Chen and Z.-Y. Yang J. Chem. SOC.,Chem. Commun. 1986 498. 72 K. Weiss Angew. Chem Int. Edn.Engl. 1986 25 359. 73 K. J. Cavell and A. F. Masters Aust. J Chem 1986 39 1129. 74 S. M. Pillai M. Ravindranathan and S. Sivaram Chem. Rev. 1986 86 353. 75 K. S. Minsker M. M. Kapasas and G. E. Zaikov Russ. Chem. Rev. 1986 55 17. 76 J. F. Garst J. B. Hines jun. and J. D. Bruhnke Tetrahedron Lerr. 1986 27 1963. I7 A. G. Martinez M. 0. Ruiz and J. L. Contelles Synthesis 1986 125. B. V. Smith New applications of tetracyanoethene have been reviewed.78 3 Polyenes Synthesis.-A practical stereoselective synthesis of 1,3-dienes is shown in Scheme 6.79Carbocupration of ethyne by lithium dialkylcuprates leads to 12,3Z-dienyl cuprates intermediates in the synthesis of Z,Z-dienes; this methodology was used to synthesize llZ,13Z-hexadecadienal the pheromone of the navel orange worm.8o r 1 SiPh3 -R& SiPh3 I I OH \ I 1 vi vii x\ 4 \ Reagents i BuLi-THF; ii Ti(OPr'), -78 "C; iii RCHO -78 "C;iv -78 "C lh -P 30 "C,3h; v HCI-H20; vi H,SO,-THF; vii KOBU' Scheme 6 Cu' iodide-catalysed cross-coupling of 2-( 1-trimethylsily1)alk- 1 -enyl dicyclohexyl boranes with ally1 bromide (or 1-bromohex-1-yne) gave rise stereoselectively to 2-1,4-dienes (or conjugated 2-enynes) having the trimethylsilyl group on the internal position of the double bond.Thus BuC-CSiMe gave via the above steps Z-BuCH=C(SiMe3)CH2CH=CH2 stereospecifically.81 A route to E,Z-1,3-dienes is outlined in Scheme 7; the product was obtained in modest yield (51%) but was 97% pure.82 A regiospecific free radical addition of a-halogenoalkanesulphonyl bromides (RCHBrS02Br or ICH2S02Br) to alkenes e.g.oct-1-ene gave a single adduct which copld be transformed into a bromoalkenyl sulphone or a diene. In this latter pathway nona-1,3-diene (59%) was formed with 83 :17 Z/E-rati~.~~ In a similar way hex-3-yne gave oct- 1 -ene-3-yne. An improved method for preparation of 2,Z-1-bromo-l,3-dienes shown in Scheme 8 is efficient and E-and 2-1 -hydroxybuta-1,3-diene have been obtained from the retro-Diels-Alder reaction of the corresponding 3-exovinyl-78 A. J. Fatiadi Synthesis 1986 249. 79 Y. Ikeda and H. Yamamoto Bull. Chem. SOC. Jpn. 1986 59 657. 8o M. Furber R. J.K. Taylor and S. C. Burford J. Chem. SOC.,Perkin Trans. 1 1986 1809. 81 M. Hoshi Y. Masuda and A.Arase Bull. Chem. SOC.Jpn. 1986 59 659. 82 S. Hyuga S. Takinami S. Hara and A. Suzuki Tetrahedron Lett. 1986 27 977. 83 E. Block M. Aslam V. Eswarakrishnan K. Gebreyes J. Hutchinson R. Iyer J.-A. Lafitte and A. Wall J Am. Chem. SOC.,1986 108 4568. 84 S. Hyuga S. Takinami S. Hara and A. Suzuki Chem. Lett. 1986 459. Aliphatic Compounds -Part (i) Hydrocarbons 89 R2 R' R2 R'C=CR 2R' -w A 7 H BBr Br-BUBr A H R3 I iv H R3 H R3 U R? c-v R-Br -7 HA R2 R2 Reagents i HBBr,.SMe2; ii BBr,; iii HCFCR3; iv I, KOAc; v Bu'Li MeOH Scheme 7 R / UH BrmR2 Reagents i BBr, ii R'C-CR' iii I, KOAc Scheme 8 OTMS / R-. P=C ,OTMS P=C Bu' .=+But (35) Bu' (36) bicycl0[2,2,l]hept-5-en-2-01(35) by FVP (750"C t~rr).~~ 2-2-Hydroxy-2,4-dienes (2-dienols) were implicated in photoenolization of P-alkyl-a$-unsaturated ketones since trapping by a silylating reagent was achieved.86 The first stable open-chain 1,3-diphosphabutadiene (36) has been synthesized." 85 F.TureEek Z. Havlas F. Maquin N. Hill and T. Gaumann J. Org. Chem. 1986 51 4061. 86 C. S. K. Wan A. C. Weedon and D. F. Wong J. Org. Chem. 1986,51 3335. 87 R. Appel P. Folling W. Schuhn and F. Knoch Tetrahedron Lett. 1986 27 1661. B. V. Smith Allene formation from propargyl ethers has been intensively investigated. Scheme 9 sets out the details of this transformation a valuable route to chiral allenes.88 l-Bromo-3-methylpenta-l,2-diene with Bu'M( M = Al Zn Mg) gave reduction Bu I p BuMgBr L.--3 I Bu +I ii Tv Bu Cu u B'uMgX -y Bu Bu Me0 Me0 Reagents i 5% CuBr ligand [l or 2 eq.PR3 P(OR), or P(NMe,),] and HCZC-C' ; ii CuBr I 'Bu ,H Me0 Me,S Et,O then H-CEC-C' ; iii I,; iv Bu"Li Et20 -78 "C then MgX, Et,O -78 "C; Me0I \Bu V -78 + +5 "C X = I anti-elimination 68% opt. yield X = CI syn-elimination 35% opt. yield Scheme 9 elimination or alkylation with chemo- and regio-selectivity governed by the organometallic reagent used.89 So,it was noted that BuiM and Et(Me)C=C=CHBr gave mainly Et(Me)C=C=CHBu' whereas BuiZn gave less allene and MeCH=C( Me)CrCH in slightly greater yield. 1H-Allene-l,3-dicarboxylicacid monoesters have been prepared from Ph3P=C(R)C02Me (R = Me,Ph) and AcCl; the formed H2C=C=C(R)C02Me was lithiated and treated with C02 to form the product.By reacting R'CH(C02R2)COC1 and Ph3P=CHC02R3 the desired half ester was also available provided R3 was But (cleaved by acid) or CH2CC13 (cleaved by zinc) and that R2 was unreactive under these conditions. This alternative method extends the scope of reaction since the lithiation-carboxylation sequence only works for H2C=C=C( Ph)C02Me.90 Porcine liver esterase-catalysed hydrolysis of racemic allenic esters showed moderate-high selectivity; thus Ph( Me)C=C=C( Me)CO,Me gave modest yield (33%) of the ( -)-acid but the e.e. was 90% .91 The bis-phosphaal- lene (37)has been synthesized and reactions of phosphorus (e.g.oxidation thiation methylation) take place normally.92 1.Marek P. Mangeney A. Alexakis and J. F. Normant Tetrahedron Lett. 1986 27 5499. 89 A. M. Caporusso L. Lardicci and F. Da Settimo Gazz. Chim. Ital. 1986 116 599. 90 F. W. Nader A. Brecht and S. Kreisz Chem. Ber. 1986 119 1196. 91 S. Ramaswamy R. A. H. F. Hui and J. B. Jones J. Chem. SOC,Chem. Commun. 1986 1545. 92 M. Schmidbaur and T. Pollok Angew. Chem. Inf. Edn. EngL 1986 25 348. Aliphatic Compounds -Part (i) Hydrocarbons But Ph ,c=c=c=c=c/ 4 (Ph,P),C=C=C( PPh,) EtO2C 'C02H (37) (38) 1H-Allene-l,3-dicarboxylic acid monoester acid chlorides are precursors of buta- 1,2,3-trienone which by Wittig olefination can be transformed into l-t-butyl-5- phenylpenta-l,2,3,4-tetraene- 1,5-diesters. Cleavage of the t-butyl ester group in the above type of compound gave the first synthesized derivative of the tetraene acid ( 38).93 Reactions.-Reactions of E,E- E,Z- and Z,Z-1,4-di-t-butoxybuta-1,3-diene with singlet oxygen have been st~died.9~ 1,3-Dienes with NH4N03-(CF3C0)20-HBF4 gave nitrotrifluoroacetate adducts which via elimination gave l-nitr0-1,3-dienes.~' With NOZBF, in MeCN conjugated dienes gave nitroacetamidation in a process showing 1,2- and 1,Caddition.The products could be transformed into dihy- droirnidaz~les.~~ 1,3-Butadiene will add ketones ( Me2C0 PrCOMe Pr'COMe) under catalysis by ceric ammonium nitrate; 1,2- and 1,4-adducts were obtained. A free-radical pathway for reaction was propo~ed.~' Coupling of C02 and butadiene has been achieved by using the complex (39); the products (see Scheme 10) are L3Fe 0 0Iiii \ ./-=CC02H HO2CnCO?H \ + + -P-CO2H HozcL Reagents i CO,; ii H30+;iii COz H,O; iv FeCI, H,O+ Scheme 10 dependent on the conditions used.98 Buta-1,3-diene forms a zirconacycle (40) on reaction with the product from C1,ZrCp2 and 2 eq. RM (containing Li or Mg).99 The structure of an allenyl sodium derivative has been discussed in terms of competition between carbanion resonance delocalization and gegenion charge 93 F. W. Nader A. Brecht and S. Kreisz Chem. Ber. 1986 119 1208. 94 E. L. Clennan R. P. L'Esperance and K. K. Lewis J. Org. Chem. 1986 51 1440. 95 A. J. Bloom and J. M. Mellor Tetrahedron Lett. 1986 27 873. 96 A. J. Bloom M. Fleischmann and J. M. Mellor J.Chem. SOC.,Perkin Trans. I 1986 79. 97 E. Baciocchi and R. Ruzziconi J. Org. Chem. 1986 51 1645. 98 H. Hoberg K. Jenni C. Kriiger and E. Raabe Angew. Chem. Int. Edn. Engl. 1986 25 810. 99 E. Negishi F. E. Cederbaum and T. Takahoshi Tetrahedron Lett 1986 27 2829. B. V. Smith Na+( tmeda) I\ -119 -144 -\ Me [Bond lengths/pm] I-localization.'00 For Bu'C=C-(Me)C-C-CBu' a localized charge depiction is favoured with the Na(tmeda)2 counter-ion; when the Li derivative was examined it was extensively dimerized. The structure shown (41) reflects the localization. Reduction of allenes [HMn(CO)5 or HCO(CO)~] was monitored by CIDNP which supports the mechanism shown in Scheme 11."' Allenes and phenyl-substituted Me +HM 7 Meb.4 -1 Me*Me M.1 Me* / \ Me Me Me bde + HM Me Me Me Me Scheme 11 allenes add (PhMe,Si),CuLi in THF at -78 "C to form an E-vinylsilane.lo2 Di- and tri-alkylallenes gave a 3 :1 mixture of (allyl-/vinyl-silane; reaction at -78 "C gave only allylsilane whereas warming to 0°C for one hour before quenching gave a mixture of vinylsilane and allylsilane.Allenes add Me,SiCN in the presence of palladium or nickel catalyst; C6H13CH=C=CH2 gave mostly E-C6H13CH=C(SiMe3)CH2CN(95%) together with 5% of Z-isomer (66% overall yield).lo3 Ally1 azides can undergo [3,3] sigmatropic rearrangement. However with IN3 allene itself formed a bis-adduct with a gem-diazide structure.'o4 Bromine azide behaved similarly. A novel allene-ene reaction was observed with e.g.2,5,5-trimethylocta-l,6,7-triene-4-one which gave products of [2 + 21 thermal addition. Two other examples were noted for substituted n~natrienones."~ The cycloaddition of chloro- cyano- methoxy- and phenylthio-allenes with 1,l-dichloro-2,2-difluoroethene has been investigated.'06 Other (dienophile) addends were also used. 100 C. Shade P. von R. Schleyer M. Geissler and E. Weiss Angew. Chem. Znt. Edn. Engl. 1986 25 902. 101 J. F. Garst T. M. Bockman and R. Batlaw J. Am. Chem. Soc. 1986 108 1689. 102 I. Fleming and F. J. Pulido J. Chem. SOC.,Chem. Commun.. 1986 1010. 103 N. Chatani T. Takeyasu and T. Hanafusa Tetrahedron Lett. 1986 27 1841. 104 A. Hassner and J. Keogh J. Org. Chem. 1986 51 2767. 105 L. Skattebcil Y. Stenstram and E.Uggerud Acta Chern. Scand. Ser. (B) 1986,40 363. 106 D. J. Pasto and S. N. Yang J. Org. Chem. 1986 51 1676 3611. Aliphatic Compounds -Part (i) Hydrocarbons Shifts in 'H n.m.r. of chiral allenes induced by chiral silver and ytterbium complexes have been measured and this approach is recommended for 1,3-disub- stituted allenes. Results for ( -)-trideca-6,7-diene and ( -)-2,2-dimethyldeca-3,4-diene are the first application of an absolute method via this technique.'" It was concluded that butatrienone does not have a 'kink' in the structure.'08 Pentatetraenes show some lengthening of the terminal double bonds with respect to 'central' bonds whereas cumulenes with an odd number of double bonds differ in structure from those with an even number.Representative examples are shown in (42) (43) and (44).'09 Ph Ph 1.327 1.27A (42) 4 Alkynes Synthesis. Lithium acetylides react smoothly with organoboranes in THF to form lithium( 1-a1kynyl)organoborates;iodination of the latter compounds at low tem- perature gives an alkyne with good yields in some instances. By this method hex-1-yne afforded dec-5-yne in high yield. The lithium acetylide-ethylenediamine complex was found to give superior results in some cases. The method is versatile and allows of preparation of a wide range of alkynes with or without functional groups."' An improvement in the synthesis of unsymmetrical alkynes was secured by iodination of the 'ate' complexes formed from thexylalkylborinates. It was shown that whilst compounds such as (45) gave BuC_CC8H, and MeC=CC,H, by an iodination/oxidation sequence the use of (46) gave an improved yield of the desired product (47)."' It was further shown that this route was compatible with the presence Me -,Bu CaH17-/ -B-C=CBuH\OMe H,,C,CrCBu &ccnH'7(45) (46) (47) of other functional groups as shown by the synthesis of CI(CH,),CFCBu in 53% yield.An enantioselective synthesis of disubstituted alkynes is possible uia the same route but with the use of the 'ate' complex from diisopinocampheyl s-butyl borane [from 2-but-2-ene and (ip~)~BH)l. Optical activity of 95% was preserved in the 107 A. Mannschreck W. Munninger T. Burgemeister J. Gore and B. Cazes Tetrahedron 1986 42 399. 108 R. D. Brown P.D. Godfrey M. J. Ball S. Godfrey D. McNaughton M. Rodler B. Kleibomer and R. Champion J. Am. Chem. SOC.,1986 108 6534. I09 H. lrngartinger and W. Gotzmann Angew. Chem. Int. Edn. Engl. 1986 25 340. I10 A. Suzuki N. Miyaura S. Abiko M. Itoh M. M. Midland J. A. Sinclair and H. C. Brown J. Org. Chem. 1986 51 4507. Ill J. A. Sikorski N. G. Bhat T. E. Cole K. K. Wang and H. C. Brown J. Org. Chern.. 1986. 51. 4521. B.V. Smith formed alkyne.' l2 Iodination/oxidation of complexes formed analogously from 1-alkynyl lithiums and B-alkoxyborinanes gave alkynols with 1-iodoalk-1-ynes; increase of the steric bulk of the alkoxy-group gave more alkynol at the expense of the iodo-compound. The best result from this point of view was obtained with the triphenylmethoxy-group leading to alk-6-yn-1-01 (85% ).Modifications to the method led to alk-7-yn- 1-01s and by using complexes from dialkylmethylboranes unsymmetrical alkynes could be obtained.' l3 In the equilibrium set up between RC-CM and MeSOMe competition existed between regeneration of RCECH and alkylation of RCrCM by added R'X; the presence of inductively stabilizing groups favoured alkylation.' l4 The products from such reactions are useful intermediates especially when R = -CH,OTHP or -CH(OEt) . Thexylalkenylalkynylboraneswith I,-KOMe form E-1,3-enynes in acceptable yields and good stereochemical purity (295%).l15 The route was used to prepare Z-E-dodeca-5,7-diene-l-ol, a caterpillar pheromone. The palladium-catalysed cross- coupling shown in Scheme 12 showed a preference for reaction of E-isomers.'16 R Br i R Br :+ + mw-:+* + m\"=/ Br SiMe Reagents i n CIZnC=CSiMe, (PPh,),Pd THF Scheme 12 Fluorinated alkenyl iodides couple with RCECZnCl in a palladium-promoted reaction to yield fluoro-substituted enynes.'" Peracid oxidation of (48)gave 1,3- diynes in good yield (R = Ph R' = Et or Ph) but failed when R = Bu and R' = Ph.'18 During attempted alkylation of PhCECH in a two-phase system oxidative dimerization to 1,4-diphenylbuta-l,3-diyneand 1,4-diphenylbut-l-en-3- yny was noted.Products of alkylation with cg. ally1 bromide were unconjugated and conjugated phenyl-substituted pentenynes.' l9 Oligomerization of ethyne (Cu' NH4C1) forms E-and Z-o~ta-1,3,7-trien-5-yne.*~~ A phosphaalkyne (P-CR R = 1-adamantyl) has been obtained by elimination from (49) of Me,SiOSiMe .12' The product shows intense absorption at 1520 cm-' OSi Me Me,Si -P = C,/ C.A. Brown M. C. Desai and.P. K.Jadhav J. Org. Chem. 51 162. '13 H. C. Brown D. Basavaiah and N. G. Bhat J. Org. Chem. 1986 51 4518. J. M. Chong and S. Wong Tetrahedron Lett. 1986 27 5445. H. C. Brown N. G. Bhat and D. Basavaiah Synthesis 1986 674. B. P. Andreini A. Carpita and R.Rossi Tetrahedron Lett. 1986 27 5533. F. Tellier R. Sauvetre and J.-F. Normant Tetrahedron Lett. 1986 27 3147. I18 J. V. Comasseto V. Catani J. T. B. Ferreira and A. L. Braga J. Chem. Soc. Chem. Commun. 1986,1067. 119 S. L. Paravyan G. D. Torosyan and A. T. Babayan J. Org. Chem. USSR. 1986 22 631.H. Hopf L. Eisenhuth V. Lehne and L. Emst Chem. Ber. 1986 119 1105. 121 T. Allspach M. Regitz G. Becker and W. Becker Synthesis. 1986 31. Aliphatic Compounds -Part (i) Hydrocarbons 95 ( vpSc) and readily undergoes [3 + 21 cycloaddition with a nitrile oxide to give a 1,2,4-0xazaphosphole. Aminoacetylene was identified as the product of decarbonyla- tion of HCECCONH in a mass spectrometer.'22 Alkyne-forming eliminations have been studied from a theoretical aspect.123 Reactions.-Rates of base-catalysed hydrogen exchange of 13 terminal alkynes have been reported and ana1y~ed.l~~ The effect of added triphenylphosphine and metal loading and/ or dispersion on product distribution from reduction of hex-3-yne and di-t-butylacetylene by palladized alumina has been studied.'25 Some enhanced cis-selectivity was found when dispersion increased.Addition of dichlorobromate and bromine monochloride to alkynes shows anti-stereospecificity (but non-regios- pecificity except for PhCECH).126 Iodine fluoride and bromine fluoride add to alkynes forming adducts CF2CX2 (X = 1,Br). Reaction is rapid at low temperature (<5 min at -75 "C) and yields are good (e.g. but-2-yne gave 85% MeCF2C12Me). Aryl alkynes also react; thus PhCECH gave PhC(F)=CHX (1 eq. of FX; E/Z-ratio = 1:1) and with an excess of reagent PhCF2CHX2. Triple bonds which are a,P-related to ester functions also react.12' Alkynes react with bis-pyridine-iodine( I) tetrafluoroborate in the presence of nucleophiles (Hal- SCN OAc etc.) to yield R'C( Nu)=C( I)R2.'28Chlorosulphamation of alkynes (R2NC1-S03) gives a mixture of adducts of the form R'C(Cl)=C(OS02NR2)R2.'29 An account of hydrocyanation of alkynes has appeared.13' Addition of thiocyanic acid to alkynes is a two-step process; in the first Hg(SCN)2 and the alkyne generate an adduct which in a second step undergoes acid-promoted demercuration thus forming a vinylic is~thiocyanate.'~' The Hg"-promoted hydration of oct-4-yne in methanol afforded octan-4-one as major product with small amounts of 4- methoxyoct-4-ene and the dimethyl ketal of the 0ctan0ne.l~~ Addition of H~(OAC)~ in AcOH which gave vinylic acetoxymercuric acetates has been studied for a range of a1k~nes.l~~ Phenol (and thiophenol) add to PhC_CCF3 under base catalysis and with thermodynamic control; with PhOH the principal adduct was Z-Ph( PhO)C_CHCF,;-with PhSH the E-adduct was formed.The differing pathways were rati0na1ized.l~~ An expedient route to either E-or 2-alkenyl bromides is shown in Scheme 13.13' The selectivity associated with formation of hexa-l,5-dien-3-ols has been attributed to chemodiff erentiation in reaction between R'CECBR and (50).136 122 B. van Baar W. Koch C. Lebrilla J. K. Terlouw T. Weiske and H. Schwarz Angew. Chem Int. Edn. Engl. 1986 25 827. 123 R. D. Bach and J. C. Evans J. Am. Chem SOC. 1986 108 1374. 124 A. J. Kresge and M. F. Powell J. Org. Chem. 1986 51 819 822. 125 S. Siege1 and J. A. Hawkins J. Org. Chem. 1986 51 1639. 126 T. Negoro and Y.Ikeda Bull. Chem. SOC.Jpn.1986 59 3515. 127 S. Rozen and M. Brand J. Org. Chem. 1986 51 222. 128 J. Barluenga M. A. Rodriguez J. M. Gonzllez and P. J. Campos Tetrahedron Lett. 1986 27 3303. 129 N. S. Zefirov N. V. Zyk S. I. Kolbasenko and E. M. Itkin J. Org. Chem. USSR 1986 22 397. 130 W. R. Jackson and P. Perlmutter Chem. Brit. 1986 338. 131 M. Giffard J. Cousseau L. Gouin and M.-R. Crahe Tetrahedron 1986 42 2243. 132 M. Bassetti and B. Floris Gazz. Chirn. Ital. 1986 116 595. 133 M. Bassetti and B. Floris J. Org. Chem. 1986 51 4140. 134 C. L. Bumgardner J. E. Bunch and M.-H. Whangbo Tetrahedron Lett. 1986 27 1883. 135 H. C. Brown N. G.Bhat and S. Rajogopalan Synthesis 1986 480. J.-M. Mas J. Gore and M. Malacria Tetrahedron Lett. 1986 27 3133. 13' B.V. Smith R1 R2 R'-CeC-R2 2R' R2 iiw n n H BBr2.SMe2 H 1B(OMe)2 iv 1 (R2=Br) iii R' Br R' Br u W n H BBr2.SMe2 I I R2 ii (E) Reagents i BHBr2.SMe2,CH2C12;ii MeOH; iii Br2 CH2C12 -40°C; iv R2BHBr.SMe2 Scheme 13 R' R2 n H SiMe2 J-u 0 I PhMe,SiZnR:Li Ph (51) (52) R' R2 u n Me2Si H I PhMe,SiZnBu; Li Ph (53) (54) Addition of (51) to an alkyne (silylzincation) gave with C,,H,,C~CH exclusive formation of vinylsilane (52). Silylalumination gave a similar result. However (53) gave principally (99 :1)the adduct (54).'37 Terminal alkynes react with silylstannanes in the presence of catalytic amounts of Pd( PPh3)4 to give regio- and stereo-selective cis-addition (55) in which the tin atom is attached at the 'internal' po~ition.'~' Further reaction with e.g.MeCOCl-AICI leaves the tin in place; thus PhCECH gave Ph(SnBu,)C=CHCOMe in 30-50% yield. However iodination of (55) gave (56) (83% ).Reaction between bis-(trimethylsily1)acetyleneand NOlBF gave 70% of the nitroalkyne 02NC~CSiMe3.'39 Nitryl fluoride at low temperature gave a low yield of the above product together with the product of addition of NOzF to 137 K. Wakamatsu T. Nonaka Y. Okuda W. Tuckmantel K. Oshima K. Ultimoto and H. Nozaki Tetrahedron 1986 42 4427. 138 B. L. Chenard and C. M. Van Zyl J. Org. Chem. 1986 51 3561. 139 R. J. Schmitt and C. D. Bedford Synthesis. 1986 132. Aliphatic Compounds -Part (i) Hydrocarbons the 7-system. Acetylenic ketones with Me,SiI gave iodovinyl ketones and hence alkenyliodides.140 Disilenes add to alkynes with formation of disilacy~lobutenes.'~' Trimethylsilyl acetylenes with Os04-B~'OOH-R'OH gave a-ketoesters RCOC02R1.142 Stannylated aminoalkynes R'R2NC=CSnRi react with a triarylmethyl halide Ar3CCl to form triarylmethylynamines R'R2NC=C -CAr3 which by hydration form tertiary amides R' R2NCOCH2CAr3 .143 Stannylated alkynes RC_CSnMe3 with Pb(OAc) in chloroform generate the species RC_CPb(OAc) an alkynyl lead triacetate.In the presence of 2-ethoxycarbonylcyclopentanone,alkylation occurs; the lead derivative may thus be considered to function as an equivalent for an alk-1-ynyl carbocation.'44 In the presence of a palladium catalyst the alkynyl zinc RC-CZnCl reacts preferentially with E-1,2-dibromoethene (even in the pres- ence of the 2-isomer).The formed endiyne (57) is obtained in a high state of purity.'45 R / Vanadium derivatives of alkynes have been obtained from reaction of RCECM (M = Li or MgBr) and VC13 in CH2C12 at -78 "C; they react with RCHO to afford an acetylenic ketone.'46 Phenylacetylene with MtI-CO-Mn( CO)5Br under phase- transfer catalysis (CH2Cl2-H20-Na0H-PhCH2NEt3C1-) gave a mixture of 4- methyl-2-phenylbutyrolactone(47% trans- 31O/O cis-isomer). Such a simple novel approach seems a promising method for synthesis of this class of compound. With other alkynes yields were variable (17-78% ).147 With saturated or unsaturated acids in the presence of RuC13 or ruthenium complexes phenylacetylene gave regioselective enol ester f~rmation.'~~ Diphenylacetylene has been shown to form a triphenylazulene derivative by a process of photo-oxidation rearrangement and dimeri~ati0n.l~~ 140 S.H. Cheou W. J. Christ L. D. Hawkins H. Jin Y. Kishi and M. Taniguchi Tetrahedron Lett. 1986 27 4759. 141 D. J. De Young and R. West Chem. Lett. 1986 883. 142 P. C. B. Page and S. Rosenthal Tetrahedron Lett. 1986 27 1947. 143 G. Himbert and R. Giesa Liebigs Ann. Chem. 1986 292. 144 M. G. Moloney J. T. Pinhey and E. G. Roche Tetrahedron Lett. 1986 27 5025. 145 A. Carpita and R. Rossi Tetrahedron Lett. 1986 27 4351. 146 T. Hirao D. Misu and T. Agawa Tetrahedron Lett. 1986 27 933. 147 J.-X. Wang and H. Alper J. Org.Chem. 1986,51 273.148 C. Ruppin and P. H. Dixneuf Tetrahedron Lett 1986 27 6323. 149 C. J. Cooksey J. L. Courtneidge A. G. Davies J. C. Evans P. S. Gregory and C. C. Rowlands J. Chem. SOC.,Chem. Commun. 1986 549. B. V. Smith In the process of reductive ester homologation,'50 it has now been shown that lithium hydride adds to an ynolate anion in the key Cyclohexadiene used in the earlier experiments is thus not needed and its role would seem to be to generate LiH from BuLi. The prediction of Houk that LiH should add to the ynolate is thus justified. A dianion is invoked as the intermediate in such additions with support from deuterium incorporation experiments. It was judged that Z-PhCH=CHOLi did not form the E-isomer. Quenching the ynolate with R3SiCl gave RC=C-OSiR (-78 "C); warming to room temperature gave R3Si(R)C=C=0.'52 Alkynyl tosylates RCGC-OTs react with two equivalents of MeLi forming an ynolate (and Ts2CH2); as before trapping gave an expected (and an unexpected) result.whilst R,MCl (R = Et M = Ge; R =.Bu,M = Sn) gave R3M( R)C=C=O only with Bu'Me2SiC1 0-trapping was observed with forma- tion of RCEC-OS~M~~BU'.'~~ This is the first recorded example of 0-trapping in such a system. Palladium-mediated alkylation of lithium alkynoates with ally1 chloride has been re~0rted.l~~ Addition of organolithiums to 1-thiomethyl (or l-thiophenyl)-3-methylbut-3-en-l-yne gives rise to a-lithiated allenic sulphides which could be transformed into a$-unsaturated aldehydes; alkylation prior to protonolysis gave corresponding ketones.'55 But-1-en-3-yne with CO-H2-Rh,(C0)12 under pressure gave formyl dienes cyclopentenones and unsaturated lactones.The 1,4-diphenyl analogue gave 91% conversion into products in this way.'56 Chiral alkynyl acetals have been used to generate optically pure propargyl alcohols by reaction with organoaluminium compo~nds.'~' Regioselective reduction of pro- pargyl acetates. (Sm12-Pdo-THF) gives rise to allene and alkene. Thus CH3(CH2)17C-CCH20Ac gave 85% of allene and in the presence of an alcohol as a proton source the allene alkyne ratio was as high as 20 1.'58 150 C. J. Kowalski and M. S. Haque J. Am. Chem. SOC.,1986 108 1325. C. J. Kowalski and G. S. Lal J. Am. Chem. SOC.,1986 108 5356. I52 C. J. Kowalski G. S. Lal and M.S. Haque J. Am. Chem. SOC.,1986 108 7127. 153 P. J. Stang and K. A. Roberts J. Am. Chem. SOC.,1986 108 7125. 154 N. Yanagihara C. Lambert K. Iritani and H. Nozaki J. Am. Chem. SOC.,1986 108 2753. 155 E. Guittet C. B. Ekogha and S. A. Julia Bull. SOC.Chim. Fr. 1986 325. 156 K. Doyama T. Joh and S. Takahashi Tetrahedron Lett. 1986 27,4497. 157 K. Isihara A. Mori I. Irai and H. Yamamoto Tetrahedron Lett. 1986 27,983. 158 T. Tabuchi J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1986 27,5237.

ISSN:0069-3030    

DOI:10.1039/OC9868300077

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By P. F. GORDON ICI Organics Division Blackley Manchester M9 3DA 1 Introduction The following discussion highlights only a small proportion of the enormous number of eligible publications and so some areas are unfortunately neglected whilst others can be covered only scantily. Nevertheless the major theme of stereocontrol in the synthesis of 'other aliphatic compounds' is reflected by the number of references included in the sections which follow. 2 Alcohols and Ethers The preparation of stereodefined alcohols and ethers has engaged the interest of synthetic organic chemists for many years and particularly those involved in natural product synthesis. This year has proved to be no exception with several useful additions to the literature.The reduction of P-hydroxyketones to provide diols has received considerable attention no doubt because of the ready availability of the starting materials. Several papers have revealed new methods and new reagents to effect this useful step as shown by the reduction of (chiral) hydroxyketone (1) by lithium triethylborohydride.'" The diastereoselectivity is high regardless of the nature of the substituents and the configuration at C-3 of the starting material. By com-parison other reducing agents e.g. DIBAL give lower selectivities and are much more affected by the stereochemistry at C-3. Interestingly omission of the silyl groups leads to a complete reversal in the stereochemistry of the reduction reaction.' The diols derived from (1) have been eventually elaborated to avenaciolide and isoavenaciolide.A related reducing reagent the triacetoxyborohydride [Me4NHB(OAc),] also reduces hydroxyketones in high yield to give the anti-1,3-diol with diastereoselectivities approaching 99%.*Simple substituents at the 2-position of the hydroxyketone appear to have little effect on the stereochemical outcome of the reaction. The same stereochemistry is observed when the less common reducing agent diisopropylchlorosilane is used.3 Once again the diastereoselectivity is very high (95% ) with intermediate formation of (2) followed by intramolecular transfer of hydrogen suggested by the high selectivity. ' (a) K. Suzuki M. Shimazaki and G.4. Tsuchihashi Tetrahedron Lett. 1986,27 6233;(b) K.Suzuki M.Miyazawa M. Shimazaki and G.4. Tsuchihashi ibid. p. 6237. D.A. Evans and K. T. Chapman Tetrahedron Lett. 1986,27 5939. S.Anwar and A. P. Davis J. Chem. Soc. Chem. Commun. 1986 831. 99 100 P. E Gordon Of course the interest in chiral reductions is not just limited to P-hydroxyketones since there is still much interest in reducing isolated ketones to chiral alcohols. The efficient asymmetric reduction of unsymmetrical ketones (R'COR2) in which R' and R2 have similar steric requirements is difficult to attain as testified by the paucity of reagents capable of effecting the reaction. However it now appears that borolane (3) is such a reagent and will reduce various ketones such as 2-propanone 2-methyl-4- octanone etc.in good chemical and asymmetric yield."" A rationale for the very high asymmetric induction observed is also pre~ented.~' H. C. Brown and co-workers have continued their studies in this area and have developed a convenient route to (3) (4) the new chiral borohydride reagent (4) which is generally effective in the asymmetric reduction of alkylphenylketones and hindered aliphatic ketones as well as ket~esters.'",~(-)-Diisopinocampheylchloroborane which is known to reduce (hetero)aralkyl ketones. will also reduce a-tertiary aliphatic ketones to the alcohol with enantiomeric excesses frequently exceeding 90%." Significantly many of the ketones studied resist reduction by many other reagents described previously. Boron reagents are not restricted merely to reductions but have wider application as demonstrated in the synthesis of all four possible stereoisomers of &methyl-homoallylalcohols e.g.(5).6 The key step in the synthesis is the addition of crotyl-diisopinocampheylboron to aldehydes (RCHO) whereby any of the four stereoisomers can be specifically prepared by choosing the appropriate geometrical isomer of the crotyl group (2 or E) and the enantiomer of the isopinane. Enan- tioselectivities are in the region of 95% and diastereoselectivities greater than 99%. A rather similar approach to the synthesis of chiral homoallylalcohols (6) involves (a) T. Imai T. Tamura A. Yamamuro T. Sato T. A. Wollmann R. M. Kennedy and S. Masamune J. Am. Chem. Soc. 1986 108 1402; (b)S. Masamune R. M. Kennedy and J.S. Petersen ibid. p. 1404. (a) H. C. Brown W. S. Park and B. T. Cho J. Org. Chem. 1986 51 1934; (b) ibid. p. 3396; (c) H. C. Brown J. Chandrasekharan and P. V. Ramachandran ibid. p. 3394. H. C. Brown and K. S. Bhat 1.Am. Chem. SOC.,1986 108 293. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 101 the addition of chiral allylic tin( 1v)-diethyltartrate complexes to aldehydes.' Enan- tiomeric excesses are at best reasonable however the route is simple and various substituents a to the alcohol group are tolerated. Tartrates have also been used as chiral auxiliaries in modified E-crotylboronates which add to chiral aldehydes (7) and (8) to produce alcohols (9) and (lo) respectively.8 ?3 OHC/I/O R HO HO OH Many of the alcohols just mentioned are intermediates in synthetic sequences and so apart from having defined stereochemistry at the alcohol centre they must also contain other functional groups capable of further synthetic manipulation.Hence homoalkynylalcohols (11) fall in this general category since they can be prepared by reaction of allenylboronic acid with chiral p-hydroxyketones and can then be converted into chiral lactones by manipulation of the alk~ne.~ Complete 1,3-asymmetric induction is observed in this reaction and as might be expected chemical yields are good. Addition of organometallic reagents to aldehydes either or both of which contain a chiral centre has proved popular in the enantioselective synthesis of alcohols and the next few examples further illustrate the point.Mulzer and his group have investigated the stereochemical course of reactions between organometallic reagents and glyceraldehyde derivatives and have shown that chromium(I1) salts of crotyl bromide will add with high enantiofacial and low diastereofacial selectivity whereas dilithium propionate shows quite the opposite behaviour.'O"Tb Furthermore condi- tions have been worked out leading to the elaboration of all four stereoisomers of brevicomin with enantiomeric excesses approaching 100°/~ ; a corrected value for the optical rotation of (+)-exo-brevicomin is also given in the same paper. 2-Methylfuran adds to glyceraldehyde acetonide to give after ring-opening of the furan and reduction 'carbohydrate'-like multifunctionalized chains such as alcohols (12) and (13)." A high yielding route to various related alditols such as D-lyXitOl ' G.P. Boldrini E. Tagliavini C. Trombini and A. Umani-Ronchi J. Chem. Soc. Chem. Cornrnun. 1986 685. W. R. Roush and R. L. Halterman J. Am. Chem. SOC.,1986 108 294. N. Ikeda K. Omori and H. Yamamoto Tetrahedron Lett. 1986 27 1175 lo (a) J. Mulzer P. de Lasalle and A. Freissler Liebigs Ann. Chem. 1986 1152; (b) J. Mulzer A. Angermann and W. Munch ibid. p. 825. 'I J. Jurczak S. Pikul and K. Ankner Tetrahedron Lett. 1986 27 1711. 102 I? E Gordon ribitol and xylitol also relies upon a highly stereospecific addition to glyceraldehyde acetonide.12 Thus vinyl copper reagents derived from Grignard reagents (14) add to give the syn-diols (15) whereas vinyl cuprates provide anti-diols.The alditols are then produced by epoxidation of the double bond and ring-opening of the epoxide. Likewise optically active a-hydroxy and a$-dihydroxy aldehydes useful intermediates for the synthesis of arachidonic acid metabolites can be synthesized starting from glyceraldehyde a~etonide.'~ Interestingly by the use of the appropriate organometallic reagent and epoxidation conditions all four possible isomers of the epoxide (16) can be obtained. Nucleophilic attack at the epoxide then leads to diols (17) which cleave to either a-hydroxyaldehyde (18) and the starting glyceraldehyde acetonide if (17 R' = H) or a,P-dihydroxyaldehyde (19) from (17 R = H). OSiBu' Phz OBDM OHC&Nu OR' OHC OR' Titanium reagents appear particularly effective at promoting asymmetric induc- tions when chiral auxiliaries are present.For instance chiral benzylic alcohols can be made in very high enantiomeric excess from benzaldehydes and norephedrine- modified tetramethyltitani~rn.'~~ Unfortunately unacceptably low levels of asym- metric induction occur with aliphatic aldehydes. The same authors have explored the chemistry of titanium reagents further and have found that by careful selection of the titanium reagent Le. RTi(OPri) extremely high non-chelation controlled addition to chiral a-siloxyketones occurs.'4b Thus starting from a-siloxyketone (20) a very high ratio (99:l) of alcohols (21) to (22) is obtained; in complete contrast Grignard reagents and alkyl lithium reagents complexed with titanium tetrachloride provide the opposite stereochemistry.Most of the organometallics discussed thus I' M. Kusakabe and F. Sato J. Chem. SOC.,Chem. Commun. 1986 989. S. Okamoto T. Shimazaki Y. Kitano Y. Kobayashi and F. Sato J. Chem. SOC.,Chem. Commun. 1986 1352. (a) M. T. Reetz T. Kukenhohner and P. Weinig Tetrahedron Lett. 1986 27 5711; (b) M. T. Reetz and M. Hullmann J. Chem. SOC..Chem. Commun. 1986 1600. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds far are used in stoicheiometric amounts. However in the addition of dialkylzinc reagents to aldehydes catalytic quantities of the chiral auxiliary (23) suffice to give high asymmetric ind~ction.'~ R'SiO R'SiO R'SiO The chemistry of 2,3-epoxy alcohols is particularly interesting in view of their ready access by Sharpless oxidation of the corresponding alkene.Scheme 1 illustrates some of the useful transformations carried out this year characterized by high yields and high stereocontro1.'6 RIA ~2 R1& R3 CHO JI OH X'" i II OH R2 OH OH OH Reagents i Ref. 16a; ii Ref. 166; Ref. 16c; iv Ref. 16d Scheme 1 Organoyttrium and organolanthanoid reagents are observed to alkylate epoxides with regioselectivities complementary to organocuprate reagents currently the stan- dard reagent for epoxide alkylation." For example epoxide (24) is alkylated to give alcohol (25) by the above reagents whereas alcohols (26) result from alkylation by organocuprate reagents.Is M Kitamura S. Suga K. Kawai and R. Noyori J. Am. Chem. Soc. 1986 108 6071. (a) Y. Takeda T. Matsumoto and F. Sato J. Org. Chem. 1986,51,4728; (b)Y. Kitano T. Matsumoto and F. Sato J. Chem. SOC., Chem. Commun. 1986 1323; (c) J. M. Palazbn B. Ahorbe and V. S. Martin Tetrahedron Lett. 1986 27 4987; (d) L.-x. Dai B.-L. Lou Y.-z. Zhang and G.-z. Guo ibid. p. 4343. 1. Mukerji A. Wayda G. Dabbagh and S. H. Bertz. Angew. Chem. lnt. Ed. Engl.. 1986. 25 760. 104 P. E Gordon Recently several different groups have investigated the selective cleavage of chiral acetals as a route into chiral alcohols. In this way optically pure propargylic alcohols (27) can be obtained in excellent yield and selectivity by reductive cleavage of the ketal(28) with organoaluminium reagents.18 A more facile ring-opening is observed when dioxolanes (29) are opened with nucleophiles e.g.by organocopper reagents or silylated organometallics to yield chiral secondary alcohols (30).'9"7bThe ready availability of the chiral auxiliary from polyhydroxybutyrate used in the dioxolane makes this an attractive route to such chiral alcohols. Chiral tetrahydrofurans (31) can also be cleaved by Me2BBr to produce syn-1,3-diols (32).20This route therefore represents an easy method for generating one extra chiral alcohol centre since the tetrahydrofurans are themselves obtained from 4-alken- 1,2-diols containing a chiral centre at the 2 position. A Scheme 2 illustrates a novel and efficient entry into cyclic ether C-glycosides and relies on a polarity inversion at the anomeric carbon.2' Yet another reference to cyclic ethers involves their preparation by rhodium carbenoid cyclization.22 Thus rhodium(1r) acetate catalyses the cyclization of diazo compounds (33) to seven and eight membered cyclic ethers (34) in good yield.An interesting study of metal exchange reactions in chiral alkenylcarbamates (35) reveals that deprotonation occurs with retention of configuration whereas lithium- titanium exchange occurs with inversion. This reaction presents the intriguing possibility of a hitherto unobserved inversion at an sp3 carbon during electrophilic substitution although this remains to be proven c~nclusively.~~ l8 K. Ishihara A. Mori I. Arai and H. Yamamoto Tetrahedron Lett. 1986 27 983.19 (a) D. Seebach R. Imwinkelrkd and G. Stucky Angew. Chem. Int. Ed. Engl. 1986 25 178; (b)S. L. Schreiher and J Reapn. Tetrahedron Lett. 1986 27. 2945. 20 Y. Guindon Y. St. Denis S. Daignealt and H. E. Morton Tetrahedron Lett. 1986 27 1237. 2' S. Hanessian M. Martin and R. C. Desai J. Chem. SOC.,Chem. Commun. 1986 926. 22 J. C. Heslin C. J. Moody A. M. 2.Slavin and D. J. Williams Tetrahedron Lett. 1986 27 1403. 23 D. Hoppe and T. Kramer Angew. Chrm. Int. Ed. Engl. 1986 25 160. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 105 RO’. a Y OR OR OCH2Ph I P h CH 20**v.*0 H OCH2Ph Reagents i BuOK BuLi Bu,SnCI; ii Bu,NF PhCH,Br; iii BuLi MeI; iv BH,Me2S NaOH H202 Scheme 2 Although several references to stereocontrolled carbonyl reductions have been included chemoselective carbonyl reductions still remain of interest to the synthetic chemist.In this context lithium borohydride in mixed solvents containing methanol (1 equivalent) is reported to be effective in reducing esters lactones and epoxides to the corresponding alcohol whereas carboxylic acids chloro nitro and carbamoyl groups remain unaff e~ted.~~ If larger quantities of methanol are used (4 equivalents) then nitro nitrile as well as primary and tertiary amide groups can be reduced. However secondary amides and metal carboxylates still remain unscathed and so a useful differentiation between functional groups especially in the amide series is available. A ‘universal’ high yielding route to vicinal diols appears to be the reductive coupling of aldehydes and ketones using magnesium on graphite at ambient tem- perat~re.~~ This reagent seems to emulate other commonly used reagents and has a wider scope.Quite often monoprotection of a.symmetrica1 diol is desired in a synthetic sequence and this has now been achieved using a combination of sodium hydride and t-butyldimethylsilylchloride.26 Finally in this section the preparation and n.m.r. analysis of o-methylmandelate esters is cited as an excellent method for establishing the absolute configuration of a secondary alcoh01;~’ full details are provided in the reference. 24 K. Soai and A. Ookawa J. Org. Chem. 1986 51 4000. 25 R. Csuk A. Fiirstner and H. Weidmann J. Chem. Soc.Chern. Cornmun. 1986 1802. 26 P. G. McDougal J. G. Rico Y.-I. Oh and B. D. Condon J. Org. Chem. 1986 51 3388. 27 B. M. Trost J. L. Belletire S. Godleski P. G. McDougal and J. M. Balkovec J. Org. Chern. 1986 51 2310. 106 I? E Gordon 3 Alkyl Halides New and improved syntheses of alkyl halides are always worth noting especially because of their role in so many synthetic sequences. The synthesis of asymmetric alkyl halides may be considered a bonus and is illustrated by the synthesis of chiral a-bromoacetals and hence ketones from the corresponding chiral acetal (36).28 A particularly noteworthy aspect is the high selectivity observed at room temperature. A different sort of selectivity i.e. chemoselectivity is observed in the monochlorina- tion of ketones uia the intermediacy of monoorganothallium derivative^.^^ The monothallium compound is produced from the ketone using an aqueous solution of thallium trichloride and thence gives specifically the product derived from thallation of the methyl group in a methyl ketone.Replacement of the thallium then gives specifically the chloromethylketone. An important route to organofluorine compounds is by displacement of other halogens with KF-sulpholane. It now seems that simple addition of calcium fluoride to potassium fluoride considerably enhances the yield in this displacement rea~tion.~’ Me0 0 R2 2cxco2Me II / I\ OX0 R R’ (36) (37; Z =C02R3;CN) One of the classic reactions of alkyl halides is their hydrolysis to the alcohol.Electrolysis has now been applied to this reaction in the form of a single cell with sacrificial magnesium electrode^.^^ Good yields of alcohols are possible in common solvents such as DMF and acetonitrile. Alkyl halides (R’X)also provide access to the ketones (37) via a palladium-catalysed carbonylative cross-coupling with active methylene compounds.32 Unfortunately the reaction is restricted to aryl and vinyl halides. 4 Aldehydes and Ketones The synthesis of hydroxyketones has again been the focus of intense activity reflecting their importance in natural product synthesis. In this context ketones (38) are derived from !-lactic acid uia an acylation-reduction sequence employing lithium bis-p-tolylthiomethanide; ketones (38) can then be enantioselectively reduced and deprotected to yield chiral aldehydes (39).33 On the other hand chiral epoxy silyl ethers (40) rearrange to chiral p-hydroxyketones (41) stereo~pecifically.~~ In this case titanium tetrachloride proves to be the most effective Lewis acid catalyst for the rearrangement and migratory aptitudes prove to be fairly typical of pinacolone- type rearrangements.28 G. Castaldi S. Cavicchioli C. Giordano and F. Uggeri Angew. Chem. Inf. Ed. Engl. 1986 25 259. 29 J. Glaser and I. Toth J. Chem. Soc. Chem. Commun. 1986 1336. 30 J. H. Clark A. J. Hyde and D. K. Smith J. Chem. SOC. Chem. Commun. 1986 791. 31 S. Sibille E. d’Incan L. Leport and J. Perichon Tetrahedron Leff. 1986 27 3129. 32 T. Kobayashi and M. Tanaka Tetrahedron Lett.1986 27 4745. 33 G. Quanti L. Banfi and E. Narisano J. Chem. Soc. Chem. Commun. 1986 136. 34 K. Maruoka M. Hasegawa and H. Yamamoto J. Am. Chem. SOC.,1986 108. 3827. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds The aldol reaction is probably the method of choice for producing P-hydroxy- ketones and certainly work continues apace in this important area of research. For instance the Lewis acid (42)proves to be an effective catalyst for enantioselective additions of enolsilanes (and trimethylsilylcyanide) to aldehydes.35 The rhodium complex [(CO)Rh(DPPB)+X-] and IUI(CO)~will also catalyse aldol reactions between silyl enol ethers and aldehydes; surprisingly this is the first example of the use of rhodium catalysis in such reactions.36 A more unusual type of aldol reaction has been reported to give unsaturated ketones (43).37In this case 1,4 addition of iodide ions to an a,P-acetylenic ketone yields an allenolate which will then add to aldehydes (R'CHO) to give (43).A high 2-stereoselectivity is achieved if the reaction is maintained at -78 "Cwhereas at 0 "C the E-isomer predominates.Ph G-Ph I Cl (42) SiMe3 (43) RMew Me %Me3 In turn unsaturated acetylenic ketones are readily prepared by treatment of aldehydes with vanadium acetylides via an oxidative nucleophilic addition.38 The synthesis is a versatile one since alkyl and aryl acetylides as well as aryl alkyl and vinyl aldehydes will undergoe the reaction in good chemical yield. In contrast the synthesis of chiral acetylenic ketones such as (44) depends on the facile aluminium- catalysed pinacol rearrangement of alcohols (45).39 The rearrangement occurs with very high selectivity with the acetylenic group acting as the non-migrating one.The same paper also describes the stereospecific reduction of the acetylenic ketones (44) to chiral alcohols with high threo selectivity. A useful route to a$-unsaturated ketones has been detailed and involves the palladium-catalysed decarboxylative cross-condensation of aryl halides.40 The yield 35 M. T. Reetz F. Kunisch and P. Heitmann Tetrahedron Lett. 1986 27,4721. 36 S. Sato I. Matsuda and Y. Izumi Tetrahedron Lett. 1986 27,5517. 37 M. Taniguchi and T. Hino Tetrahedron Lett. 1986 27,4767. 38 T. Hirao D. Misu and T. Agawa Tetrahedron Lett.1986 27,933. 39 K. Suzuki T. Ohkuma M. Miyazama and G.4. Tsuchihashi Tetrahedron Lett. 1986 27,373. 40 M.Kadokura T.-a. Mit and Y. Watanabe J. Chem. SOC.,Chem. Commun. 1986 252. 108 I? E Gordon of products are high in the examples quoted but so far examples appear limited to arylketones. Michael addition of ketones to unsaturated esters occur with high enantioselectivity (e.e. > 92% ) and antidiastereoselectivity (d.e. > 90% ) if they are converted first into the SAMP or RAMP hydra zone^.^' After formation of the lithium salt the addition to the unsaturated esters provides the ketoester (46) with either the S or R configuration depending upon the configuration of the starting hydrazone. Copper-catalysed conjugate additions of Grignard reagents to a,@-unsaturated ketones in the presence of trimethylchlorosilane-HMPA occur in higher yield and with enhanced regio stereo and chemoselecti~ity.~~~*~ It appears that the silyl chloride is more than a simple enolate trap and genuinely accelerates the addition reaction.Paquette and his group have reported on n-facially controlled nucleophilic additions of chiral vinyl organometallic reagents to chiral @ y-unsaturated ketones.43 Although limited in scope so far the paper demonstrates the feasibility of attaining n-facially controlled nucleophilic addition of chiral vinyl organometallics to chiral unsaturated ketones. The reaction is illustrated in Scheme 3 and is one of seven examples. MeO-OMe OMe + Scheme 3 Several other examples of selective nucleophilic additions of Grignard reagents have been reported.In what is claimed to be the first example of a highly stereoselec- tive addition of Grignard reagents to chiral open-chain a-ketoacetals (47) chiral a-hydroxyacetals (48) have been obtained both in high chemical yield and with high diastereo~electivity.~~~*~ This particular route has been used to prepare various chiral a-hydroxyketones after unmasking (48) and thence (R)and (S)-mevalolac- tone.44aIn the case of the a,@-unsaturated acetal (49) nucleophilic attack by phenyl copper reagent takes place exclusively at the &position to give chiral @-substituted 41 D. Enders K. Papadopoulos and B. E. M. Rendenbach Tetrahedron Lett. 1986,27 3491. 42 (a)E.Nakamura S. Matsuzawa Y. Horiguchi and 1. Kuwajima Tetrahedron Lert. 1986 27 4029; (b) Y. Horiguchi S. Matsuzawa E. Nakamura and I. Kuwajuma ibid. p. 4025. L. A. Paquette and K. S. Learn J. Am. Chem. SOC.,1986 108 7873. 43 44 (a) Y. Tamura T. KO H. Kondo H. Annoura M. Fuji R. Takeuchi and H. Fujioka Tetrahedron Lert. 1986 27 2117; (h)M. P. Heitz F. Gellibert and C. Mioskowski ibid. p. 3859. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 109 aldehyde (50) after deprotection and recovery of the chiral auxiliary.45The reaction therefore provides an alternative to a Michael addition reaction and avoids the problem of the competing 1,2-addition; unfortunately the reaction is of rather limited scope as it stands. A quite different use of chiral acetals can be seen in the specific and aluminium-catalysed cleavage of 2-and 4-substituted cyclohexanone acetals to give chiral2-and 4-substituted cyclohe~anones.~~ Since the cyclohexanone acetals are obtained from the cyclohexanone the overall procedure represents an effective method for converting achiral cyclohexanones into chiral ones.Me02C Me02C 77 '2C02Me 0 R' 0 RqR1 0 HU K' (47) (48) X I N,-C-COR YCHO I Y 'Ph R Apart from the above there have been a host of references to the synthesis and reactions of aldehydes and ketones. For instance a synthesis of a new class of chiral ketone derivative (51) has been published in which the a-carbon contains four different labile groups chosen from halogens (X) oxygen and sulphur groups (Y) and nitrogen functions such as azide amino and nitro group (Nf).47These com-pounds should be particularly useful as intermediates.Scheme 4 illustrates some further transformations in which higher yields or better selectivities are attainable with the reagents des~ribed.~~-~' Finally in this section there have been a number of reports dealing with enan-tioselective deprotonation. In the first chiral lithium bases (52) give chiral enol ethers upon deprotonation and trapping of the enolate derived from 4-alkylcyc-lo hex an one^.^^ Thus enantiomeric excesses in the region 80-97O/0 have been achieved with the base (52; R' = Ph X = 4-methylpiperidyl). A similar approach uses the chiral base (53) with symmetrical ketones so far limited to cyclohexanones; after trapping of the enolate enantiometric excesses approaching 74% have been obtained.54 4s P.Mangeney A. Alexakis and J. F. Normant Tetrahedron Lett. 1986,27 3143. 46 Y. Naruse and H. Yamamoto Tetrahedron Lett. 1986,27 1363. 47 Y. Takeuchi M. Asahina A. Murayama K. Hori and T. Koizium J. Org. Chern. 1986,51 955. 48 J. A. Soderquist and E. L. Miranda Tetrahedron Lett. 1986,27 6305. 49 T.Hirao D.Misu K. Yao and T. Agawa Tetrahedron Lett. 1986,27 929. so G. A. Molander and G. Hahn J. Org. Chern. 1986,51 1135. " T. Sato H. Matsuoka T. Igerashi and E. Murayama Tetrahedron Lett. 1986,27 4339. 52 T. Satoh S. Motoheshi and K. Yamakawa Tetrahedron Lett. 1986,27 2889. 53 R. Shirai M.Tanaka and K. Koga J.Am. Chern. SOC.,1986,108,543. N. S.Simpkins J. Chern. SOC.,Chern. Cornmun. 1986.88. 54 110 P. F. Gordon RMgBr + RCOCl c):-(-xi R 2.0 Ri v R' = R' = -CH=CH-R 0 iv R'= Me I II RCCHR' I RC02R' R~*OH X 0 %Me2 ; ii VCI,; iii SmI,; iv R3SnCH2; v Ph.!!CHR2 MCPBA Reagents i CI (-> I Scheme 4 A completely different approach to chiral ketones relies upon the asymmetric oxidation of 1,3-dithiolanes to the S-oxide followed by separation of the diastereoisomers and thence deprotection to the resolved ketone.55 This therefore provides a convenient method for resolving carbonyl compounds. 5 Carboxylic Acids and their Derivatives The formation of a and P-hydroxyacids with defined stereochemistries has been an important synthetic target for some years now because of their importance as subunits in natural products.p-Hydroxyacids can be prepared by exploiting the aldol reaction and useful references to this methodology can still be found. For example chiral ferrocenyl-gold (I) complexes catalyse the asymmetric aldol reaction of isocyanates with aldehydes producing optically active 5-alkyloxazoline carboxy- late^.'^ The oxazolines can then be hydrolysed to the corresponding a-amino-p- hydroxy carboxylic acid esters in high yield. An alternative route into chiral hydroxy acids much used in recent years requires the presence of a chiral auxiliary. Usually the auxiliary is treated with the acid prior to the aldol reaction. This route has again proved a popular oiie as exemplified in the reactions of the new thiones (54).The latter react viu their tin enolates with a$-unsaturated aldehydes and 4-acetoxyazetidinones to give a-hydroxy-y,6-unsaturated acids and 4-substituted-P- '' 0. Bortolini F. Di Furia G. Licini G. Modena and M.Rossi Tetrahedron Lett. 1986 27 6257. Y. Ito M. Sawarnura and T. Hayashi J. Am. Chem. Soc. 1986. 108 6405. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds lactams respectively with enantioselectivities approaching 100°/o.57a1b Further studies with the known chiral auxiliary (55) have yielded rather interesting results. For example the acid derivatives (55 R = -COCH2R) can be converted readily into the triisopropoxy tin enolate which then reacts with aldehydes to give aldol products (56) possessing the opposite diastereoselectivity than that obtained with boron enolate~.~'~ Thus use of either titanium or boron permits convenient access to both stereoisomers starting from the same chiral auxiliary.The same chiral auxiliary can be used in crotonate imides [56 R = C(O)C=CR] which then react with aldehydes to give vinyl compounds (57) with high diastereoselectivity. If the chiral auxiliary (58) is used products with the opposite diastereochemistry are obtained.58bA variation on the use of titanium enolates utilizes triphenyl phosphine as complexing agent whereupon a dramatic enhancement of the anti-syn ratio is observed.59 Chiral iron complex e.g. (59) is a more unusual chiral auxiliary that has excited much interest in the last two or three years.In the presence of Lewis acids these enolates (59) undergo highly stereoselective aldol reactions with ketones and imines to give the corresponding hydroxycarboxylic acids and P-aminoacids respectively after removal of the iron.60 In the same (full) paper the latter have been converted into p-lactams thus providing a useful extension to this area of chemistry. P-Silylenolates (60) will also participate in diastereoselective aldol reac- tions and depending upon the stereochemistry of the enolate erythro products from (60;X = Me Y = Li) or threo products from (60;X = Li Y = Me) are obtained.6' xcJJRl (59) a-Hydroxycarboxylic acids can also be synthesized conveniently by hydroxylation of the enolate of the carboxylic acid.The chiral auxiliaries used in the enantiospecific aldol reactions described above function equally well in this hydroxylation reaction. 57 (a) Y. Nagao Y. Hagiwara T. Kurnagai M. Ochiai T. Inoue K. Hashirnoto and E. Fujita J. Org. Chem. 1986 51 2391; (b)Y. Nagao T. Kurnagai S. Tarnai T. Abe Y. Kurarnoto T. Taga S. Aoyagi Y. Nagase M. Ochiai Y. Inoue and E. Fujita J. Am. Chem. SOC.,1986 108 4673. 58 (a) M. Nerz-Stormes and E. R. Thornton Tetrahedron Lett. 1986 27 897; (b) D. A. Evans E. B. Sjogren J. Bartroli and R. L. Dow ibid. 1986 27 4957. 59 C. Palazzi L.Colombo and C Gennari Tetrahedron Lett.. 1986 27 1735. 60 L. S. Liebeskind M. E. Walker and R. W. Fengl J. Am. Chem. SOC.,1986 108 6328. 61 I. Fleming and J. D. Kilburn 1.Chem.SOC.,Chem. Commun. 1986 305. 112 €? E Gordon Thus the protected hydroxylated acid derivatives (61) are synthesized from the corresponding acid derivative upon treatment with dibenzyl peroxydicarbonate.62" Specificity can be as high as 99% and the method can be considered a viable alternative to several of the existing procedures. In a related reaction DBAD (Boc-N=N-Boc) gives the chiral hydrazines (62) in equally high yield which can be used further or cleaved to the amine constituting a very useful route to chiral a-amino acids.62b An alternative to using an achiral oxidizing agent and chiral substrate as described above is to generate a chiral oxidizing agent capable of a-hydroxylating the enolate. This has been done with the chiral oxaziridine (63).63The chemical yields are very good but enantiomeric excesses are somewhat variable.Chiral a-substituted-a- hydroxycarboxylic acids can also be synthesized by first taking an achiral hydroxyacid and then enantiospecifically alkylating it. This has been demonstrated via the intermediacy of chiral dioxolanones (64) which can be alkylated in excellent yield and with good ~pecificity.~~ Hydrolysis then yields the chiral substituted a-hydroxyacid and starting chiral auxiliary. In contrast to these routes to chiral a-hydroxyacids are others proceeding by way of a rearrangement reaction. Thus chiral ester (65) undergoes an auxiliary directed diastereoselective Claisen rearrange- ment to hydroxyacid (66) following a hydrogenation step.65 Similarly the chiral esters (67) rearrange to a-hydroxyesters (68) in good yields and with high diastereoselectivities.66a9Particularly noteworthy here is that zirconium enhances considerably the enantioselectivity observed in the rearrangement.Theene reaction of chiral glyoxylates with alkenes also leads to chiral a-hydroxy esters (69) in which the enantiospecificity is controlled during the rearrangement step.67 In particular 62 (a) M. P. Gore and J. C. Vederas J. Org. Chem. 1986 51 3700; (6) D. A. Evans T. C. Britton R. L. Dorow and J. F. Dellaria J. Am. Chem. Soc. 1986 108 6395. 63 F. A. Davis M. S. Haque T. G. Ulatowski and J. C. Towson J. Org. Chem. 1986 51 2402. 64 W. H. Pearson and M.-C. Cheng J. Org. Chem. 1986 51 3746. 65 J. Kallmerten and T.J. Gould J. Org. Chem. 1986 51 1152. 66 (a) M. Uchikawa T. Hanamoto T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1986 27,4577; (6) M. Uchikawa T. Katsuki and M. Yamaguchi hid. p. 4581. 67 J. K. Whitesell R. M. Lawrence and H. H. Chen J. Org. Chem. 1986. 51 4779. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds OMOM R' /I1 0 R2 R3 OMOM ,OMOM LPh R' OH (68) (69) (70) the nature of the chiral auxiliary used for the reaction has been carefully examined and of the thirteen auxiliaries tried the cyclohexane (70) appears the best with induction levels claimed to be better than 99.9 to 0.1. In their turn chiral P-hydroxyesters derived from tartaric acid have been converted into chiral epoxyesters (71) uia bromination and ring-closure.68 By suitable manipu- lation of reaction conditions and substrate all four possible stereoisomers are attainable in both a diastereoisomeric and enantiomeric pure state.Likewise esters derived from the chiral isobornyl alcohol (72) can be chlorinated and brominated highly enantiospecifically to give chiral a-halogenoesters which furnish azidoesters upon treatment with sodium azide.6' A simple hydrogenation step then leads to chiral a-aminoacids (73) in what constitutes a simple high-yield route to these important materials. Another synthesis of chiral a-aminoacids proceeds by a different strategy and starts from the benzophenone imine of the methyl ester of glycine." The asymmetric induction occurs during the allylation reaction catalysed by pal- ladium co-ordinated to a chiral ligand.Although the phosphorus ligand (+DlOP) appears the best of the ligands tried optical yields are still only of the order of 60%. V (so, t(l>) (71) (72) (73) In the highly diastereoselective a-alkylation of a,@-unsaturated esters (74) to P,y-ester (75) no new asymmetric centres are induced instead an almost complete (>95%) 1,3-transfer of chirality is observed upon treatment with an organocopper- 68 S. Saito Y. Nagao M. Miyazaki M. Inaba and T. Moriwake Tetrahedron Lett. 1986 27 5249. 69 W. Oppolzer R. Pedrosa and R. Moretti Tetrahedron Lett. 1986 27 831. 'O J. P. Genet D. Ferroudl S. Juge and J. R. Montes Tetrahedron Lett. 1986 27 4573. 114 P. F.Gordon Lewis acid complex.71 In contrast iron complexes such as (76) are usually synthe- sized with the purpose of inducing new or additional chiral centres into a suitable substrate. A series of papers has been published dealing with various aspects of asymmetric inductions involving such chiral iron ligands. In particular conditions have been worked out for improved stereochemical control in the alkylation of enolates derived from (76) resulting in an amelioration in the observed selectivities to greater than 200 1.72a In this case it seems that addition of an aluminium reagent followed immediately by the alkylating agent is beneficial. A most unusual synthesis of a pentanoic acid also uses the same type of iron complex and proceeds by an iterative homologation process involving alternate carbonylation and reduction steps.72bThus all the carbon atoms in the pentanoic acid are derived from carbon monoxide and this paper therefore represents an interesting model study of building carbon chains from simple precursors i.e.synthesis gas. Because of their good electron-accepting ability the carboxylic acid group and certain of its derivatives are efficient promoters of the Michael reaction. In several areas of carboxylic acid chemistry the accent has been on asymmetric induction reactions and this is certainly the case for the Michael reaction. In conjugate additions to alkylidene malonates the chiral enamines (77) add to give chiral triesters with excellent enantiomeric exce~s.~~~.~ As might be expected the level of asymmetric induction depends critically on reaction temperature and solvent and in this case toluene-HMPA at -95°C gives best results.An alternative method for promoting asymmetric inductions in Michael reactions is to convert the unsaturated carboxylic acid group into a chiral amide with a chiral amine. This method works well with amine (78) since Grignard reagents add to the resulting chiral a,p-unsaturated amide with enantiomeric excesses in the range 80-90% .74 Simple hydrolysis then releases the chiral auxiliary for further use. Several references to chiral iron com- plexes have already been noted and the following two demonstrate further their versatility in asymmetric synthesis. a-Alkyl-a,p-unsaturated acyl groups attached directly to the chiral iron centre c$ (76) undergo asymmetric Michael additions to yield E-enolates which can then be trapped to yield quaternary carbon centres highly ~tereo~electively.~~~~~ If amines are used as nucleophiles then chiral p-aminoacids are formed which can be cyclized to give stereodefined 2,3-disubstituted- p-lactams in good yield.75b 71 T.Ibuka T. Nakao S. Nishii and Y. Yamamoto J. Am. Chem. SOC., 1986 108 7420. 72 (a) S. L. Brown S. G. Davies D. F. Foster J. 1. Seeman and P. Warker Terrahedron Lett. 1986 27 623; (b) S. L. Brown and S. G. Davies J. Chem. SOC.,Chem. Commun. 1986 84. 73 (a) K. Tomioka K. Ando K. Yasuda and K. Koga Tetrahedron Lett. 1986,27,715; (6) K. Tomioka K. Yasuda and K. Koga ibid. p. 4611. K. Tomioka T.Suenaga and K. Koga Tetrahedron Lett. 1986 27 369. (a) S. G. Davies and J. C. Walker J. Chem. SOC., 74 75 Chem. Commun. 1986,495; (b) S. G. Davies I. M. Dordor-Hedgecock. K. H. Sutton and J. C. Walker Tetrahedron Lett. 1986. 27 3787. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Finally in this section two reports have been published referring to efficient methods for transesterification. In the first distannoxane is found to be an efficient catalyst for transesterification of methyl esters with various alcohols,76a whereas in the second butyl lithium in tetrahydrofuran catalyses the In this latter case the process works for aromatic and @-unsaturated methyl esters with primary secondary and (particularly) tertiary alcohols.6 Lactones Just as in previous sections an important theme running through many lactone syntheses is one of asymmetric induction. For instance acid-catalysed ring-opening of epoxide (79) takes place at C-1 with complete retention of configuration at C-2 to form ethers (80). However in base nucleophiles attack at C-2 with inversion to give lactols (81). Both lactols (80) and (81) may be oxidized to the corresponding y-lactones and so the overall route represents a useful synthesis of highly substituted stereodefined y-lactone~.~~ Ziegler and his group have studied the synthesis and use of y- butyrolactones as templates in the preparation of invictolide (+)-methyl-Prelog- Djerassi lactone and other homochiral tripropionate Thus the 3-methyl-y- butyrolactone (82) can be converted into enolethers (83) which then rearrange to lactones (84).Lactones (84) can then be transformed to lactones (85) by a Baeyer- 76 (a) J. Otera T. Yano A. Kawabata and H. Nozaki Tetrahedron Lett. 1986,27,2383;(6)0.Meth-Cohn J. Chem. SOC.,Chem. Commun. 1986 695. 77 L. Lussmann D. Hoppe P. G. Jones C. Fittschem and G. M. Sheldrick Tetrahedron Lett. 1986,27,3595. 78 (a) F. E. Ziegler E. P. Stirchak and R. T. Wester Tetrahedron Lett. 1986 27 1229; (b) F. E. Ziegler A. Kneisley and R. T. Wester ibid.,p. 1221; (c) F. E. Ziegler and R. T. Wester ibid. p. 1225. 116 P. F. Gordon Villiger reaction. An iterative process is then used to access (+)-methyl-Prelog- Djerassi lactone.Similarly the S-isomer of (82) has been used to generate (+)-invictolide and no doubt various related systems such as (86) can be obtained by a similar sequence.78b Achiral monosubstituted lactones can be kinetically resolved by an enantioselec- tive partial neutralization with (1S)-(+)-10-camphorsulphonic acid following an initial alkaline hydrolysis of the lactone ri11g.7~ In this way (R) or (S) isomers can be obtained in good enantiomeric excess. Chiral lactones have also been obtained by acid-catalysed cyclization of ketone dithioacetals (87) leading to protected lac- tones (88) with the stereochemistry known at ~-2.~' (87) It is by no means true that all the interesting work carried out in the lactone area is concerned with stereocontrolled reactions since there is considerable scope for useful lactone ring synthesis.a-Methylene- y-lactones (89) are of great topical interest and can be prepared from tin reagents (90) via a Lewis acid-catalysed reaction with aldehydes (R'CHO) followed by acid-catalysed cyclization.81 Alterna- tively la2tones (89) are formed when cyclopropanes (91) are added to iminium salts (CH2=NMe2C1-) followed by ring-closure.82 Both routes are characterized by good yields of desired product. Radical reactions have been the subject of renewed interest ' to synthetic chemists and several applications to lactone synthesis can be found this year. For example alkenoyloxymethyl iodides or selenides are readily cleaved with tributylstannane to radicals such as (92) concomitant with ring-closure to the corresponding 5-or 6-membered lac tone^.^^ Ketyl radicals (93) also undergo facile ring-closure onto alkynes giving rise to a-methylene- y-butyrolactones (94) in excel- lent yield.84 The possible intermediacy of radicals in the samarium iodide-induced l9 K.Fuji M. Node and M. Murata Tetrahedron Lett. 1986 21 5381. 8o K. Suzuki T. Masuda Y. Fukazawa and G.4. Tsuchihashi Tetrahedron Lett. 1986 27 3661. J. E. Baldwin R. M. Adlington and J. B. Sweeney Tetrahedron Lett. 1986,27 5423. 82 H.-A. Reissig and H. Lorey J. Chern. SOC.,Chem Comrnun. 1986 269. 83 A. L. J. Beckwith and P. E. Pigou J. Chern. SOC.,Chern. Cornrnun. 1986 85. 84 M. D. Bachi and E. Bosch Tetrahedron Lett. 1986 21 641. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds reductive coupling of ketones or aldehydes (R3COR4) to a,P-unsaturated esters (R'CHCHR2COEt) must also be con~idered.'~" In this case good yields of the y-lactone (95) result and the coupling reaction may also be extended to other electron-deficient alkenes.Similarly samarium iodide promotes the cyclization of bromoaldehyde (96) to medium and large ring lactones (97) and would therefore appear to be a versatile reagent for lactone synthesis.85b Bu3Sn E .7&t3 RHNOC R' R' Ac Y. Most of the preceding discussion has dealt with building lactone rings; however one paper discusses the chiral functionalization of lactone rings. Thus lactone enolates will react with chiral enamines (98) via an addition-elimination reaction yielding chiral lactones (99) in reasonable enantiomeric excess.86 This is therefore claimed to be the first example of a chiral induction through a one-pot addition- elimination sequence in an aliphatic system.7 Phosphorus and Sulphur Chiral sulphur groups have proved extremely useful in asymmetric inductions and so new or improved routes to preparing chiral sulphur groups are always to be welcomed. This is the case for the oxidation of sulphide to chiral sulphoxides via 85 (a)S.4. Fukuzawa A. Nakanishi T. Fujinami and S. Sakai J. Chem Soc. Chem. Commun. 1986,624; (b)T. Tabuchi K. Kawamura J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1986 27 3889. 86 K. Fuji M. Node H. Nagasawa Y. Naniwa and S. Terada J. Am. Chem. SOC.,1986 108 3855. 118 P.F. Gordon the chiral iodine oxidizing agent (loo).*’ Fair levels of asymmetric induction are observed and good chemical yields can be expected. Chiral sulphoxides have been the most exploited of the chiral sulphur groups and several references demonstrating their versatility are again to be found. Thus the sulphoxide (101) rearranges to provide the (R)-hydroxyenoates (102) with fairly good optical purity (70%) and in acceptable yields (>68’/0 ).88 In a completely different reaction chiral P-ketosul- phoxides have been enantiospecifically reduced to the corresponding P-hydroxysul-phoxides followed by conversion into butenolides (103) via oxidation to the sulphin- ate and treatment with the sodium salt of iodoacetic acid.*9 Because the nature of the reducing agent ultimately determines the stereochemistry of the hydroxysul- phoxide both enantiomers of (103) are accessible upon demand merely by altering the reducing agent.In the synthesis of (+)-pentalene a chiral vinyl sulphoxide is used in a highly enantiospecific Michael reaction to give the 5,5 ring system (104 X = O).90Interestingly reduction of the sulphoxide gives the sulphide (104 X = :) which is then ring-closed hydrolytically in good yield by a mixture of formic and trifluoroacetic acids. This reagent combination seems to circumvent the problems previously experienced in hydrolysing vinyl sulphides with an a carbon-hydrogen bond. 02+);*.. RCO; R1-’C02Me 0 (101) (102) Although used less frequently chiral sulphones will also function as useful chiral auxiliaries and have been prepared in high enantiomeric excess from achiral sulphin- ates by a palladium-catalysed rearrangement in the presence of chiral phosphorus ligands.” Chiral sulphur groups have also been applied to asymmetric inductions in the Michael reaction because of their strong electron acceptor properties.Thus in conjugate additions of organometallic reagents to vinyl sulphoximines (105) high asymmetric induction is observed (>90Y0).~~ The Michael adducts can then be transformed to various interesting compounds by simple manipulation of the sul- phoximine group; for instance sulphoximine (105 R = C02R) can be readily cleaved to give chiral 2-alkylalkanoic acids. ” T. Imamoto and H. Koto Chem. Letr. 1986 967.88 H. Kosugi M. Kitaoka A. Takahashi and H. Uda J. Chem. SOC.,Chem. Commun. 1986 1268. 89 G. Solladie C. Frechou G. Demailly and C. Greck J. Org. Chem. 1986 51 1912. 90 D. H. Hua J. Am. Chern. SOC.,1986 108 3835. 91 K. Hnroi and K. Makino Chem. Lett. 1986 617. 92 S. G. Pyne J. Org. Chem. 1986 51 81. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 119 Several efficient routes to thiolesters have again been published. Nucleophilic attack by sulphur in thiolacids upon alcohols is catalysed by zinc iodide and yields the corresponding thiolesters in high yield.93" The reaction appears quite general with primary secondary tertiary allylic and benzylic alcohols all reacting well. An alternative route to thiolesters also yields satisfactory results and involves the reaction of anhydrides or acid chlorides with thiols catalysed by cobalt(I1) chloride.93b Once again the reaction appears quite general.In their turn thiols have been prepared under the mildest conditions presently available by desilylation of the appropriate a-trimethylsiloxy sulphides which can be made by standard literature meth0ds.9~ Warren and his group have continued their studies of the synthetic utility of the Homer-Wittig reaction and have now devised a route to Horner-Wittig intermediates (106) stereoselectively; the latter can then be used to generate 2-a,P-unsaturated acids in high yield.95" Similarly Horner-Wittig adducts (107) are prepared by reduction of the corresponding ketone with cerium trichloride catalysis and the resultingdcohols converted into the E-isomer of the unsaturated hydroxya~ids.~'~ R' Ph2P+ I HO-PRI C0,Bu' H (106) (107) (108) Several new chiral phosphines such as (108) have been developed and found to be highly effective ligands in the catalytic asymmetric synthesis of (R)-(-) -pantolac-tone.96 The phosphines find application in the hydrogenation step and will presum- ably have wider application.Finally in this section it has been shown that triethyl- phosphine advantageously replaces triphenylphosphine tributylphosphine and other such phosphorus( 111) reagents in phosphazene reactions (amide and phthalimide formation) and disulphide cleavage-based reactions such as found in reduction of disulphides thioester formation and some hydroly~es.~' 8 Amines and Related Functional Groups As in many of the other sections asymmetric inductions in amine chemistry is of topical interest though perhaps not a dominating theme.An elegant route to chiral amines in high asymmetric yield has been developed by Brown and co-workers using organoboron reagents. Thus borinanes (R*B0,Me3) of essentially 100% optical purity prepared by asymmetric hydroboration of readily available prochiral olefins followed by removal of the chiral auxiliary can be converted into borinic ester derivatives (R*MeBOMe30Ac).98 Elaboration of these esters to the primary amine is then easily accomplished by treatment with hydroxylamine o-sulphonic 93 (a) J. G. Ganthier F. Bourdon and R. N. Young Tetrahedron Lett.1986 27 15; (b) S. Ahmad and J. Iqbal ibid. p. 3791. 94 D. N. Harpp and M. Kobayashi Tetrahedron Lett. 1986 27 3975. 9s (a)D. Levin and S. Warren Tetrahedron Lett. 1986,27,2265; (b)N. Greeves and S. Warren ibid.,p. 259. 96 H. Takahashi M. Hattori M. Chiba T. Morimoto and K. Achira Tetrahedron Lett. 1986 27 4477. 97 F. Urpi and J. Vilarrasa Tetrahedron Lett. 1986 27 4623. 98 H. C. Brown K.-W. Kim T. E. Cole and B. Singaram. J. Am. Chem. SOC.,1986 108 6761. 120 P. I? Gordon acid. An alternative approach starts from a chiral imine which provides the amine (109) after treatment with an allylic boron compound. The high 1,2 asymmetric induction is rationalized via a six-membered chair-like transition state.99 A totally different approach to chiral amines is demonstrated in Scheme 5.'O0 Noteworthy aspects of this route are the hindered nature of the amines in which two tertiary carbons can be constructed (Y to the nitrogen.Since chiral hindered amines are frequently used in chiral induction reactions this then constitutes a valuable route to some potentially novel and synthetically useful systems. R3 R R3 i R / 3-NH2+0=( -)rN=C, R' RZ R4 R' R2 R4 Reagents i TiCl,; ii H2-Pt/C; iii PbO,; iv Na Scheme 5 Scheme 6 outlines a new general high yield synthesis of primary amines."' Although one group (Y to the amino function must be aryl the second group (R') can be varied depending only upon the accessibility of the organometallic reagent. ArCHO + NHzSOzNH2 -(ArCH=N)#02 \ii iii R I ArCHNHz Reagents i RM; ii H202-Py; iii NaOH Scheme 6 Protection and deprotection of amines is a vitally important process in organic synthesis.In this context 4-trimethylsilylethanesulphonylchloride is reported to be a new reagent for the protection of amines as the corresponding sulphonamide.lo2 99 Y. Yamamoto S. Nishii K. Maruyama T. Komatsu and W. Ito J. Am. Chem. SOC.,1986 108 7778. 100 E. J. Corey and A. W. Gross J. Org. Chem. 1985,51 5391. 101 F. A. Davis M. A. Giangiordano and W. E. Starner Tetrahedron Lett. 1986 27 3957. 102 S. M. Weinreb D. M. Demko T. A. Lessen and J. P. Demars Tetrahedron Lett. 1986 27 2099. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 121 Although amines have previously been protected as sulphonamides a major problem has often been the vigorous conditions required for deprotection.In this case deprotection can be carried out simply by treatment with fluoride ions. The t- butyldiphenylsilyl group is another good amine protecting group notably stable to chromatography basic and hydrolytic reagents as well as alkylating and acylating reagents yet it is cleaved readily by mild acid and pyridine-HF.lo3 Regarding the cleavage of protecting groups tellurolates have been proposed as efficient reagents for the removal of the trichloro-t-butyloxycarbonyl moiety and complements the alternative methods of deprotection.lw One of the most important reactions involving the amine group is the acylation reaction as used in peptide synthesis.In this context fluorenylmethoxycarbonylamine acid derivatives of 3-hydroxy-4-oxodihydroben-zotriazene are particularly effective acylating agents in solid-phase peptide syn- thesis.''' An important advantage with these reagents is their self-indicating ability since upon completion of the coupling reaction the transient yellow colour fades. One of the conventional routes to primary amines particularly aromatic amines is via reduction of the corresponding nitro group; occasionally however the reverse reaction is desired. Dimethyldioxirane appears to be an excellent reagent if not the reagent of choice for converting amines of all types into the corresponding nitrocom- pound with yields typically better than 80%.'O6 A more conventional synthesis of nitroaliphatics proceeds by nitrotrifluoroacetoxylation of 1,3 dienes.'07 Elimination of the acetoxy group is induced easily to yield 1 -nitro- 1,3-dienes in fair to good yields.Finally mesyl azide appears to be a superior reagent for the diazo transfer reaction."* It is relatively cheap and facilitates easy work-up of the reaction products. 9 Reviews The Table below lists some of the reviews relevant to this chapter. Title Reference (1) Asymmetric epoxidation of allylic alcohols the Sharpless 109 epoxidation (2) The application of elemental fluorine in organic synthesis 110 (3) R-and S-(2,3)-o-lsopropylideneglyceraldehydesin stereo- 11 1 selective organic synthesis (4) The chiroptical properties of carbonyl compounds 112 (5) a-Oxoketene dithioacetals and related compounds 113 103 L.E. Overman M. E. Okazaki and P. Mishra Tetrahedron Lett. 1986 27 4391. 104 M. V. Lakshmikantham Y. A. Jackson R. J. Jones G. J. O'Mallay K. Ravichandran and M. P. Cava Tetrahedron Lett. 1986 27 4687. 105 E. Atherton L. Cameron M. Meldal and R. C. Sheppard J. Chem. Soc. Chem. Commun. 1986 1763. 106 R. W. Murray R. Jeyaraman and L. Mohan Tetrahedron Lett. 1986 27 2335. 107 A. J. Bloom and J. M. Mellor Tetrahedron Lett. 1986 27 873. D. F. Taber R. E. Ruckle jun. and M. J. Hennesey J. Org. Chem. 1986 51 4077. 109 A. Pfenninger Synthesis IY86 89. 'lo S. T. Purrington B. S. Kagen and T. B. Patrick Chem. Rev. 1986 86 997. J. Jurezak S. Pikul and T. Bauer Tetrahedron 1986 42 447.112 D. N. Kirk Tetrahedron 1986 42 777. 113 R. K. Dieter Tetrahedron 1986 42 3029. 122 P. E Gordon Title Reference Oxazoles in carboxylate protection and activation 114 The synthesis of mevinic acids 115 N-Hydroxy-a-amino acids in organic chemistry 116 Advances in the synthesis of a-methylene lactones 117 Multiple convergent syntheses via conjugate-addition 118 reactions to cycloalkenyl sulphones Recent advances in the chemistry of chlorosuiphonyl 119 isocyanate Organic synthesis with a-chlorosulphides 120 Synthesis of sulphoxides by oxidation of thioethers 121 Conjugated nitroalkenes versatile intermediates in organic 122 synthesis Reductive cleavage of aliphatic nitro-groups in organic 123 synthesis Silyl-substituted cyclopropanes as versatile synthetic reagents 124 II4 H.H. Wasserman K. E. McCarthy and K. S. Prowse Chern. Reu. 1986 86 845. 115 T. Rosen and C. H. Heathcock Tetrahedron 1986 42 4909. 116 H. C. J. Ottenheiim and J. D. M. Herscheid. Chem. Reu. 1986 697. 117 N. Petragnani H. M. C. Ferrdz and G. V. J. Silva Synthesis 1986 157. I in P. L. Fuchs and T. F. Braish Chem. Rev. 1986 86 903. 119 D. N. Daher and K. S. K. Murthy Synthesis 1986 437. 120 B. D. Dilworth and M. A. McKerven Tetrahedron 1986 42 3731. 12’ M. Madesclaire Tetrahedron 1986 42 5459. 122 A. G. M. Barrett and G. G. Graboski Chern. Reu. 1986 86 751. 123 N. Ono and A. Kaii Synthesis 1986 693. 124 L.A. Paquette Chem. Rev. 1986 86 733.

ISSN:0069-3030    

DOI:10.1039/OC9868300099

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

6 Alicyclic Chemistry By N. S. SlMPKlNS Department of Chemistry Queen Mary College Mile End Road London E14NS 1 General An issue of Chemical Reviews has been devoted to 'Emerging Organic Reactions' and covers many topics relevant to alicyclic synthesis.' Meyers has developed a number of chiral bicyclic lactam systems which are suitable for synthesis of alicyclic compounds in optically pure form. The versatility of this method has now been further demonstrated by synthesis of chiral 4,4-disubstituted cyclohexenones,2 cycl~pentenones,~ and cyclobutanones? e.g. (-)-grandisol (Scheme 1). yp&MeL@p2+ 05 Me MeOzC "1 IMe H 0 H 0 (93%) 12 1 ratio iii *--Me02C I Ho be Me (-) -grandisol iv v . Ph 0 &7 -i";l Rl R diastereoisomeric ratio 4748% 75~25to 97:3 >95% e.e.Reagents i CH,=CH2 hv -78 "C; ii H2S04 MeOH; iii Ph,P=CH2; iv LDA RX;v LDA HMPA R'X; vi Red Al;vii Bu4NH2P04 Scheme 1 ' See Chem. Rev. 1986,86 No. 5. A. I. Meyers B. A. Lefker K. T. Wanner and R. A. Aitken J. Org. Chem. 1986 51 1936. A. I. Meyers and B. A. Lefker J. Org. Chem. 1986 51 1541. A. I. Meyers and S. A. Fleming J. Am. Chem. Soc. 1986 108 306. 123 124 N. S Simpkins Another asymmetric synthesis of grandisol also involves the use of an easily detachable chiral auxiliary and allows for synthesis of both enantiomers.' A new general method for synthesis of cycloalkenones involves cyclization of dialkylamides bearing a vinyl iodide appendage using Bu'LL6 The method gives good yields and is especially suitable for preparation of a-silylenones.A Lewis acid mediated version of the Nicholas reaction yields cobalt-complexed cycloalkynes of varying ring sizes.7 Decomplexation to give the cycloalkyne is not yet possible however subsequent Pawson-Khand reaction provides an elegant and stereoselective route to polycyclics with potential for natural product synthesis (Scheme 2).CO benzene 75 % 8 85% Scheme 2 A facile Lewis acid rearrangement of epoxy silyl ethers allows for 1-carbon ring-expansion of suitable cyclic systems.8 Another ring-expansion method uses the reaction between a cyclic P-hydroxyselenide and TlOEt (5.5 eq.)' (e.g. Scheme 3). &J PhSef ___, '8"" 95:5 Scheme 3 Contrary to the usual trend migration of an alkyl group in preference to a vinyl group is observed although the outcome is somewhat substituent-dependent.Other new general methods which have been largely illustrated using cyclic compounds include a regioselective entry to vinyl tins via enol triflates," and a method for P-functionalization of enones involving 'phosphoniosilylation'." M. Demuth A. Palomer H.-D. Sluma A. K. Dey C. Kruger and Y.-H. Tsay Angew. Chem. Int. Ed. Engl. 1986 25 1117. H. Sawada M. Webb A. T. Stoll and E. Negishi Tetrahedron Lett. 1986 21 775. 'S. L. Schreiber T. Samrnakia and W. E. Crowe J. Am. Chem. Soc. 1986 108 3128. K. Maruoka M. Hasegawa H. Yarnarnoto K. Suzuki M. Shimazaki and G. Tsuchihashi J. Am. Chem. Soc. 1986 108 3827. A. Krief and J. L. Laboureur J.Chem. Soc. Chem. Commun. 1986 702. 10 W. D. Wulff G. A. Peterson W. E. Bauta K.4. Chan K. L.Faron S.R. Gilbertson R.W. Kaesler D. C. Yang and C. K. Murray J. Org. Chem 1986,51 277. 11 A. P. Kozikowski and S. H. Jung J. Org. Chem. 1986 51 3400. Alicyclic Chemistry A report covering the synthesis of non-natural products has appeared,12 and another review which discusses strained molecules has also been p~b1ished.l~ Interest in novel cumulenes continues particularly in the synthesis of strained compounds which are stabilized by incorporation of bulky groups. Amongst compounds recently synthesized are the t-butyl-8-membered ring allene (1),14 the first ever bicyclic cumulatriene (2)," and the tetramethyl benz-fused cyclooctatrienyne (3).16 The first known bicyclo[l.l.l]pentane with sp2 carbon atoms at each bridge is the very strained ketone (4) with a half-life of 90 min at -30 'C.17 Me Me Me he hu 260nm hu 334 nm ___c_, -10 K 17 K Sensitizer Matrix Photolysis of (4) at 10K in the presence of a photosensitizer produces the ground-state triplet hydrocarbon (5),'* as does photolysis of (6).19Similarly cyclopro- pen-3-yl has been generated at low temperature in a matrix and characterized by e.p.r.spectroscopy.20 Addition of an alkyne to a cyclobutylidene results in formation of several novel products (Scheme 4).21 I Scheme 4 l2 P. E. Eaton (ed.) Tetrahedron 1986 42 No. 6. l3 K. B. Wiberg Angew. Chem Znt. Ed. Engl. 1986 25 312. 14 J. D. Price and R.P. Johnson Tetrahedron Lett. 1986 27 4679. 1s R. S. Macomber and T. C. Hemling J. Am Chem. SOC.,1986 108 343. 16 T. L. Chan T. C. W. Mak C.-D. Poon H. N. C. Wong J. H. Jia and L. L. Wang Tetrahedron 1986 42 655. P. Dowd and Y. H. Paik Tetrahedron Lett. 1986 27 2813. P. Dowd and Y. H. Paik J. Am. Chem SOC.,1986 108 2788. 19 G. J. Snyder and D. A. Dougherty J. Am. Chem SOC.,1986 108 299. 2o G. L.Closs and 0.D. Redwine J. Am Chem. Soc. 1986 108 506. 21 U. H. Brinker and J. Weber Tetrahedron Lett. 1986 27 5371. 126 N. S. Simpkins Studies on strained pyramidalized olefins have resulted in successful matrix isolation and characterization of (7),22whilst (8) has been detected by trapping with diphenylisoben~ofuran.~~ (7) n = 2 6 8% McMurry has published further details concerning the synthesis and properties of the unusual cyclic olefins (9) and (10).Whilst in (9) there appears to be little interaction between the carbon-carbon double bonds,24 (10) forms a static silver olefin 7r-complex when treated with AgOTf.25 2 Three-membered Rings Schollkopf has reported a straightforward synthesis of 1 -amino- l-cyclopropanecar- boxylic acids which involves reaction of t-butylisocyanoacetate with epoxides26 (Scheme 5). But02C' 2. BF,.OEt 2. KOBu' A 4 CNC02Bu' CN C02Bu' Scheme 5 In another paper from the same group these products are again prepared stereoselectively using a carbene derived from a chiral bislactim-ether.27 Dichlorocar- bene cyclopropanation of allylic alcohols is possible in highly stereoselective fashion regardless of the olefin substitution pattern.28 The use of homochiral ketals for asymmetric cyclopropane synthesis has been extended to bicyclic and applied to large rings in a synthesis of (R)-m~scone.~' Asymmetric cyclopropanation of olefins using diazo-compounds catalysed by chiral copper semicorrin complexes has also received more attenti~n.~' Vinylcyclopropanes have been prepared by a new method which relies on conju-gate addition of a-bromoester dienolates to enones3* (Scheme 6).22 J. E. Radziszewski T.-K. Yin F. Miyake G. E. Renzoni W. T. Borden and J. Michl J. Am. Chem. SOC.,1986 108 3544. 23 G. E. Renzoni T.-K. Yin and W. T. Borden J. Am. Chem. Soc. 1986 108 7121. 24 J. E. McMurry G.J. Haley J. R. Matz J. C. Clardy G. V. Duyne R. Gleiter W. Schafer and D. H. White J. Am. Chem. Soc. 1986 108 2932. 25 J. E. McMurry G. J. Haley J. R. Matz J. C. Clardy and J. Mitchell J. Am. Chem. Soc. 1986 108 515. 26 U. Schollkopf B. Hupfeld and R. Gull Angew. Chern Znt. Ed. Engl. 1986 25 754. 27 U. Schollkopf M. Hauptreif J. Dippel M. Nieger and E. Egert Angew. Chem. Znt. Ed. EngL 1986 25 192. 28 F. Mohamadi and W. C. Still Tetrahedron Lett. 1986 27 893. 29 E. A. Mash and K. A. Nelson Tetrahedron Lett. 1986 27 1441. 30 K. A. Nelson and E. A. Mash J. Org. Chem. 1986 51 2721. 31 H. Fritschi U. Leutenegger and A. Haltz Angew. Chem. Znt. Ed. Engl. 1986 25 1005. 32 T. Hudlicky L. Radesca H. Luna and F. E. Anderson 111 J. Org.Chem. 1986 51 4746. Alicyclic Chemistry The products such as (11) have considerable synthetic application including the well known pyrolysis to furnish cyclopentenes (1 2). High-temperature chemistry such as this has been recently reviewed.33 New and useful applications of vinylcyclopropane chemistry include a radical- mediated stereoselective ~xygenation~~ (Scheme 7) and a convenient synthesis of substituted cycl~heptenones~~ (Scheme 8). 63% Scheme 7 / R 0Si.-Scheme 8 Et,AlCl effectively mediates the aminolysis of activated cyclopropanes allowing regioselective opening of suitable substrates even with primary amine~.~~ A sequence combining stereoselective cyclopropanation of an allylic alcohol followed by regioselective oxymercuration offers an attractive route to systems having alternating hydroxyl and methyl substituents (Scheme 9).37 Scheme 9 33 M.Karpf Angew. Chem. Int. Ed. Engl. 1986 25 414. 34 K.S. Feldman R.E. Simpson and M.Parvez J. Am. Chem. Soc. 1986 108 1328. 35 E.Piers M.S.Burmeister and H. V. Reissig Can. J. Chem. 1986 180. 36 L. A. Blanchard and J. A. Schneider J. Org. Chem. 1986 51 1372. ’’ D. B. Collum W. C. Still and F. Mohamadi J. Am. Chem. SOC.,1986 108 2094. N. S. Simpkins The Ni( CO),-induced reductive carbonylation of gem-dibromocyclopropanes is a versatile method for the synthesis of cyclopropanecarboxylic acid derivative^^^ (Scheme 10). 0 Br Br PrNH Ni(CO), 75 "C Ph Ni(CO), DMF ,PhYEpr gyHa. Br 82Yo 78% mixture of cis and trans Scheme 10 A tetracyclic intermediate related to lycorine has been synthesized by an elegant application of the cyclopropyl iminium ion rearrangement39 (Scheme 11).Scheme 11 Thermal rearrangement of a cyclopropene azide (13) has allowed the preparation of the first kinetically stable azacyclobutadiene (14)? cycZo-C,I is a readily prepared and explosive compound which appears to be a salt-like halogenocarbon best formulated as (15):l 38 T. Hirao Y. Harano Y. Yamana Y. Hamada S. Nagata and T. Agawa Bull. Chem. SOC.Jpn. 1986 59 1341. 39 R. K. Boeckman jun. J. F.Sabatucci S. W. Goldstein D. M. Springer and P. F. Jackson J. Org. Chem 1986 51 3740. U. J. Vogelbacher M. Regitz and R Mynott Angew. Chem Int.Ed. EngL 1986 25 842. 41 R. Weiss G.-E. Meiss A. Haller and W. Reinhardt Angew. Chem Inr. Ed. EngL 1986 25,103. Alicyclic Chemistry 3 Four-membered Rings A number of reports have concerned intramolecular [2 + 21 cycloadditions as a method of cyclobutane constyction. Pirrung has investigated photolysis of cyclooc- tenes such as (16) and obtained mixtures of products in rather low yield?2 In related studies the use of an acetal as a link between enone and olefin was found more ~atisfactory~~ (Scheme 12). The regiocontrol in such cycloaddition reactions of carbonyl-substituted 144- alkeny1)-1-cyclopentenes has been thoroughly examined,44 allowing some generaliz- ations concerning the favoured mode of ring-closure. A strategy involving intramolecular [2 + 21 photocycloaddition and subsequent cyclobutane fragmenta- tion has proved effective for the synthesis of a number of angular triquinanes4’ (Scheme 13).F02R (*)-pentalenene % *zo2Et __* --, hu (*)-pentalenic acid CO2Et ,t Mew 73% (and minor isomer) Scheme 13 Another method utilizes a copper-catalysed photobicyclization followed by cationic rearrangement as a general stereoselective and high yielding route to fused norbornanes.& Lewis acid mediated [2 + 21 cycloadditions have also been examined. Di-t-butylmethylenemalonateadds effectively to vinyl ethers at low temperature in the presence of ZnBr2.47 Allenic esters also undergo this type of reaction with simple alkenes (reaction times 1-25 days) to give mixtures of stereoisomeric products and again the intramolecular version has been examined48 (Scheme 14).Johnson has examined the generation and rearrangement of oxonium ylides. Thus treatment of substituted diazo-ketones with Rh(OAc) gives a mixture of products in which cyclobutanones often pred~minate~~ (Scheme 15). 42 M. C. Pirrung and N. J. G. Webster Tetrahedron Lett. 1986 27 3983. 43 M. C. Pirrung and S. A. Thomson Tetrahedron Lett. 1986 27 2703. 44 A. R..Matlin C. F. George S. Wolff and W. C. Agosta J. Am. Chem. SOC,1986 108 3385. 4s M. T. Crimmins and J. A. DeLoach J. Am. Chem SOC.,1986 108 800. 46 K.Avasthi and R G. Salomon J. 0%.Chem. 1986 51 2556. 47 M. R. Baar P. Ballesteros and B. W. Roberts Tetrahedron Lett. 1986 27 2083.48 B. B. Snider and E.Ron J. Org. Chem 1986 51 3643. 49 E. J. Roskamp and C. R. Johnson. J. Am. Chem. SOC.,1986 108,6062. 130 N. S. Simpkins CO2Et CO2Me CH,CI 25 "C "i 56% 21O/o and a bridged adduct (16%) Scheme 14 0 A0 PN2 Rh(OAc) 1 mol% + &OM' benzene RT OMe 45O/O 10% Scheme 15 Applications of the cyclobutenyl phosphorane (17) appear limited to reaction with two equivalents of an aromatic aldehyde." Danheiser has nicely demonstrated his cyclobutenone strategy for preparation of polysubstituted aromatics with a total synthesis of mycophenolic acid (18p (Scheme 16). Another elegant use of cyclobutanes in synthesis involves titanium reagents in a synthesis of A9*'2-capnellene52 (Scheme 17).A total synthesis of (-)-punctatin A has been accomplished in which the cyclo- butane ring was formed by a photolytic Norrish type I1 processs3 (Scheme 18). 4 Five-membered Rings Details have appeared concerning a number of five-membered ring-forming reactions which are mediated by silicon groups. Denmark has further examined the stereocon- trol possible in the silicon-directed Nazarov cyclization thus treatment of j3-silyl enone (19) with FeCl gives predominantly the bicyclic enone (20)54(Scheme 19). 50 T. Minami N. Harui and Y. Taniguchi J. Org. Chem. 1986 51 3572. 51 R. L. Danheiser S. K. Gee and J. J. Perez J. Am. Chem SOC.,1986 108 806. 52 J. R. StiIIe and R. H. Grubbs J. Am. Chem. Soc. 1986 108 855. 53 L. A. Paquette and T.Sugimura J. Am. Chem. SOC.,1986 108 3841. 54 S. E. Denmark K. L. Habermas G. A. Hite and T. K. Jones Tetrahedron 1986.42 2821. Alicyclic Chemistry 131 / -SiO + benzene-(sealed120tube)"C-14 h @%-% Me0 O,,OMe 73'/o Me <OOMe COiH ,' 4 steps Me0 Me (18) Scheme 16 I + % TiCp 9 steps (*)-A9.''Capnellene +- - - - - - -81% overall Reagents i Cp2TiAA1Mel DMAP; ii HO/\/OH p-TSA benzene A \/ c1 Scheme 17 M& -Hfl hv 254nm --+ II SEMO SEMO 49yo (-)-Punctatin A Scheme 18 N. S. Simpkins + P R ‘H R R (19) R = Me CH=CH, Ph erc. (20) major minor combined yields 40-99% Scheme 19 In a study of the reactions of cis-silyl tin olefins such as (21) it was found that BF,-promoted Nazarov cyclizations occurred with retention of the bulky silicon group” (Scheme 20).(21) R = (CH2)3CI 80% Scheme 20 More details of the intramolecular cyclizations of allylS6 and propargyl” silanes to give five-membered ring products have appeared. Allylsilanes also feature in an annulation sequence described by Lee.58 A silyl enol ether is reacted with reagent (22) to produce an intermediate which then cyclizes under harsher Lewis acid conditions (Scheme 21). The method suffers from lack of regioselectivity in most OMe YOMe TMSOTf @+ & OSiMe3 I. (22) + 2. TiCl, -78 “C OMe 48% combined yield Scheme 21 cases but is interesting in that TMSOTf is shown selectively to activate an enol silane in the presence of an allylsilane.A highly stereocontrolled addition of the iodinated allylsilane (23) to 1,2-diones has been described by M01ander~~ (Scheme 22). 55 B. L. Chenard C. M. Van Zyl and D. R. Sanderson Tetrahedron Lett. 1986 27 2801. 56 G. Majetich R. W. Desmond jun. and J. J. Soria J. Org. Chem. 1986 51 1753. 57 D. Schinzer J. Steffen and S. Solyom J. Chem SOL Chem Commun. 1986 829. T. V. Lee K. A. Richardson and D. A. Taylor Tetruhedron Lett. 1986,27 5021. 59 G. A. Molander and D. C. Shubert J. Am. Chem. Soc. 1986 108,4683. 133 Alicyclic Chemistry II Scheme 22 Intramolecular olefin cyclization of hmmerer reaction products is possible yielding sulphur-substituted cyclopentanones which can then be further transformed into dienonesm (Scheme 23).The method appears limited to substrates having a fairly nucleophilic double bond and can lead to other products resulting from carbocation capture by CF3C02-,although some general applicability to five- six- and seven-membered rings is evident. 0 &,Me II 0 CH,CI, 0 "C 7 8 '10 72'/o Scheme 23 Snider has disclosed details of the EtAlC1,-catalysed reaction of alkenes with electrophilic cyclopropanes which gives good yields of cyclopentane products.61 In an extension of earlier work Canonne has used bis-Grignard reagents having one secondary terminus in a high yielding and stereoselective preparation of cylopen-tanols6 (Scheme 24). + FMe R = H alkyl aryl I minor major combined yields 70-88% Scheme 24 A similar sequence using an homologous bis-Grignard reagent gave disappointing yields of cyclohexanols.Polyfunctionalized cyclopentanes are obtained when suitably activated olefins are treated with (2-carbamoylallyl)lithium reagents63 (Scheme 25). Significant propor- tions of uncyclized products are also usually formed. Vinyl lithiums generated from aryl sulphonyl hydrazones undergo efficient and highly stereoselective cyclization onto olefinic appendages. Subsequent in situ inter-molecular quenching of the resulting cyclized alkyl lithium has been accomplished 60 H. Ishibashi S.Harada M. Okada M. Ikeda K.Ishiyama H. Yamashita and Y. Tamura Synthesis 1986 847. R.B. Beal M. A. Dombroski and B. B. Snider J. Org. Chem. 1986 51 4391. 62 P.Canonne and M.Bernatchez J. Org. Chem 1986,51 2147. 63 P.Beak and K. D. Wilson J. Org. Chem 1986,51,4627. N. S. Simpkins R' R2N I 8-8 1Yo EWG = CONR Scheme 25 for the first time,@ thus offering an attractive alternative to the analogous radical sequence (Scheme 26). A review highlights the utility of cy -chlorosulphides in organic synthesis,65 includ- ing Ramberg-Backlund reactions of cyclic a-chlorosulphones to give cyclic olefins. A new variant of this approach constitutes a useful multistep route to substituted ~yclopent-3-enones~~ (Scheme 27). IE+ x?' H 49-6 1Yo Tris = triisopropylbenzene E = Br CHO CO,H CH2CH20H Scheme 26 n n ___ 02 02 R R 83% Reagents i NCS py; ii TolSO,Na HCI EtOH; iii HOkoH H+ benzene; iv rn-CPBA; v base RX;vi NaH KH; vii p-TSOH-py HzO acetone Scheme 27 64 A.R. Chamberlin and S. H. Bloom Tetrahedron Lett. 1986 27 551. " B. M.Dilworth and M. A. McKervey Tetrahedron 1986,42 3731. 66 H. Matsuyama Y. Miyazawa and M. Kobayashi Chem. Lett. 1986 433. Alicyclic Chemistry An intramolecular nitrone-alkene cycloaddition yields a stereoisomeric mixture of bicyclic isoxazolidines (24) which can then be cleaved to give substituted aminocycl~pentanols~~ (Scheme 28). The method appears to offer a direct and operationally simple route to a variety of prostanoid analogues although as yet the cycloaddition is not stereoselective. NHPh H I H OSiPh3 (24) and diastereomer Scheme 28 Full details have appeared concerning the photoreductive cyclization of a,&-unsaturated ketones including stereochemical aspects and comparison with chemical methods?* The reaction has the advantage of being conducted under homogeneous conditions and will tolerate additional functionality as in conversion of ketoester (25) (Scheme 29).solvent = HMPA (80%) Scheme 29 = tt,N-MeCN (86%) Several papers have dealt with the application of cobalt reagents to the preparation of cyclopentenones for example in a synthesis of cyclocolorenone (26),69initially thwarted by an unexpected ‘mislocation’ in cyclopropanation of ketal (27).70 Br Br Br (27) (26) A rhodium cluster effects catalytic hydroformylation and hydrocarboxylation of certain enynes giving mixtures of products including cyclopentenones and b~tenolides.~’ A more selective method which utilizes a catalytic amount of Pd(OAc) allows oxidative cyclization of hexa-l,Sdienes as in Scheme 30.72 67 J.R. Hwu and J. A. Robl J. Chem. SOC.,Chem. Commun. 1986 704. D. Belotti J. Cossy J. P. Pete and C. Portella J. Org. Chem. 1986 4196. 69 M. Saha B. Bagby and K. M. Nicholas Tetrahedron Lett. 1986 915. 70 M. Saha S. Muchmore D. Van der Helm and K. M. Nicholas J. 0%.Chem. 1986 1960. ” K. Doyama T. Joh S. Takahashi and T. Shiohara Tetrahedron Left. 1986 27 4497. 72 T. Antonsson A. Heumann and C. Moberg J. Chem. Soc. Chem. Cornmun. 1986 518. N. S. Simpkins 70‘/o (> 95 % stereoselective) Scbeme 30 The area of cyclopentane annelation has been reviewed.73 Annulating reagents utilized very recently include the sulphone (28),74 the phosphonate (29),” the dithiane (30) and the iodide (31) in which the vinyl silane acts as a masked ketone.76 OEt Vinyl tin compounds are attractive reagents in a variety of ring-forming reactions.Piers has investigated several applications to preparation of cyclopentanoid systems77 and succeeded in synthesizing the dolostane diterpene (32) Scheme 31.78 1. LDA THF HMPA FL.1 2. PhN(SO,CF,) 3. (Ph,P),Pd steps Scbeme 31 73 B. M. Trost Angew. Chem Int. Ed. EngL 1986 25 1. 74 S. De Lombaert I. Nemery B. Roekens J. C. Carretero T. Kimmel and L. Ghosez Tetrahedron Lett. 1986 27 5099. 75 S. C. Welch J.-M. Assercq and J.-P. Loh Tetrahedron Lett. 1986 27 1115.76 D. R. St. Laurent and L. A. Paquette J. Org. Chem. 1986 51 3861; L. A. Paquette R. A. Galemmo jun. J.-C. Caille and R. S. Valpey ibid. p. 686. 77 E. Piers and R. T. Skerlj .IChem. Soc. Chem. Commun. 1986 626. E. Piers and R. W. Fnesen J. Org. Chem 1986,51 3405. Alicyclic Chemistry 5 Six-membered Rings Cytochalasins G and H,79(+)-compactin,80 and 3-oxosilphinenes1 are recent examples of molecules which have succumbed to total synthesis uia application of the intramolecular Diels-Alder reaction. Asymmetric Diels-Alder chemistry also continues to attract interest; Davies has nob illustrated the use of an unsaturated chiral iron acyl to obtain a Diels- Alder adduct in useful diastereoisomeric excess.82 A new and elegant approach to this problem involves mediating the cycloaddition process with a chiral Lewis acid.Kelly has found that the chiral quinone complex (33) undergoes highly selective reaction with diene (34) to give the expected product in 98% enantiomeric excess83 (Scheme 32). OMe 0 98% e.e. (33) Scheme 32 The reaction worked equally well with several other reaction partners allowing an enantioselective synthesis of (-)-bostrycin. A chiral titanium reagent also effects asymmetric Diels- Alder reactions to give products in high e.e. Remarkably this reagent works equally well in catalytic (10%) quantities providing the reaction is carried out in the presence of 4A molecular sieves84 (cJ the Sharpless epoxidation). A full paper concerns the use of chiral Lewis acids to effect cationic cyclization of unsaturated aldehyde^.^' Further examples of the Posner 2 + 2 + 2 one-pot construction of cyclohexane systems have appeared.86 In another method involving 79 H.Dyke R. Santer P. Steel and E. J. Thomas J. Chem. Soc Chem Commun.,1986,1447; E. J. Thomas and J. W. F. Whitehead ibid. p. 727. 80 G. E. Keck and D. F. Kachensky J. Org. Chem. 1986 51 2487. 81 M. Ihara A. Kawaguchi M. Chihiro K. Fukumoto and T. Kametani J. Chem. SOC Chem. Commun. 1986 671. '* S. G. Davies and J. C. Walker J. Chem Soc. Chem. Commun. 1986 609. 83 T. R. Kelly A. Whiting and N. S. Chandrakumar J. Am. Chem. Soc. 1986 108 3510. 84 K. Narasaka M. Inoue and N. Okada Chem Lett. 1986,1109; K. Narasaka M. Inoue' and T. Yamada ibid p.1967. 85 S. Sakane K. Maruoka and H. Yamamoto Tetrahedron 1986 42 2203. 86 G. H. Posner S.-B. Lu E. hirvatham E. F. Silversmith and E. M. Schulman J. Am Chem. SOC.,1986 108 511; G. H. Posner S.-B. Lu and E. Asirvatham Tetrahedron Lett. 1986 27 659. N. S. Simpkins a double Michael reaction Mukaiyama has reacted siloxydienes with a,P -unsatur-ated ketones in the presence of trityl perchlorate" (Scheme 33). The method has the advantage of operating under very mild conditions and gives products of kinetic control. 55% Scheme 33 The problem of stereoselective construction of exocyclic tetrasubstituted double bonds has been addressed allowing the first stereospecific synthesis of E-y-bisabolene" (Scheme 34). The key feature of this synthesis is a stereospecific 84% overall isomerically pure Reagents i BuLi B U I 3 ; ii TMSOTf; iii BuLi CuI; (MeO),P-HMPA-Mel; iv TBAF; TiCI,-methylaniline complex Scheme 34 T.Mukaiyama Y. Sagawa and S. Kobayashi Chem. Lett. 1986 1821. an E. J. Corey and W. L. Seibel Tetrahedron Lett. 1986 27 905. Alicyclic Chemistry 139 migration of a carbon chain from boron to carbon. Similar chemistry also allows for preparation of Z-y-bisabolene but with lower ~electivity.'~ In a series of papers Livinghouse has described new procedures for arene-alkene carboannulati~ns~~ (Scheme 35). These methods appear limited to systems having the right combination of nucleophilic arene and/or alkene groups. OMe OMe OMe PhS+BF,-NC y or PhSCl then AgBF /R R OMe NC X NC Meo&R R R = H or Me R = Me 30:l (combined yield 48%) Scheme 35 The two conformers of the fully substituted cyclohexane (35) are separable by chromatography have distinct melting points and are stable indefinitely in solution at room temperature." The barrier to cyclohexane inversion is much higher than any hitherto observed.6 Larger Rings In a continuation of studies on trans cycloalkenes 1-methoxy- trans-cyclooctene has been synthesized by a Peterson elimination route.92 89 E. J. Corey and W. L. Seibel Tetrahedron Lett. 1986 27 909. YO E. Edstrom and T. Livinghouse J. Chem. Soc. Chem. Commun. 1986 279; E. D. Edstrom and T. Livinghouse Tetrahedron Lett. 1986 27 3483; E. D. Edstrom and T.Livinghouse J. Am Chem. SOC. 1986 108 1334. 91 D. Wehle and L. Fitjer Tetrahedron Lett. 1986 27 5843. 92 M. J. Prior and G. H. Whitham. J. Chem. Sac.. Perkin Trans. I 1986 683. 140 N. S. Simpkins A new method for the synthesis of polycycles incorporating 8-membered rings has been described by Wender; thus nickel-catalysed [4 + 41 cycloaddition of suitable substrates gives cyclooctadienyl products in stereoselective fashiong3 (Scheme 36). 100% cis :trans 19 1 70% yield C02Me H Reagents i base Brw 84% ;ii 11% Ni(COD)2 33% Ph,P toluene 60 "C Scheme 36 The use of chemically modified KH (using iodine to remove potassium metal) improves yields in oxy-Cope rearrangement^.^^ Acetylenic oxy-Cope rearrangements feature in recent total syntheses of Phoracantholide 1 Poitediol and Dactylolgs (Scheme 37).Ireland ester enolate-type ring contraction of macrocyclic lactones to give car- bocycles and heterocycles has been more fully described.% This method has now MEMoG -O ***\ 170°C Me --_ ~ -..& OMEM HO 0 Phoracantholide 62% Dactylo1 Scheme 37 93 P. A. Wender and N. C. Ihle J. Am. Chem. SOC.,1986 108,4678. 94 T. L. Macdonald K. J. Natalie jun. G. Prasad and J. S. Sawyer J. Org.Chem. 1986,51 1124. 95 T. Ohnuma N. Hata N. Miyachi T. Wakamatsu and Y.-Ban Tetrahedron Lett. 1986 27 219; R. C. Gadwood R. M. Lett and J. E. Wissinger J. Am. Chem. SOC 1986 108 6343. % A. G. Cameron and D. W. Knight J. Chen SOC.,Perkin Trans. I 1986,161; R. L. Funk M.M. Abelman and J. D. Munger jun. Tetrahedron 1986,42 2831. Alicyclic Chemistry enabled the synthesis of a known quadrone precursor.97 A similar strategy has now been applied to 13- and 17-membered ring ethers. Thus low-temperature [2,3] Wittig rearrangement of compounds (36) and (37) is effected on treatment with alkyllithiums at low temperature (Scheme 38). OH '1 94% from (E,E) 96% from (Z,Z) major isomer 4.5 :1 mixture 85% combined yield Scheme 38 7 Bicyclic Compounds There is continued interest in methods for the rapid assembly of cyclic systems of various types involving sequential Michael additions.w The first three-component triple conjugate addition process gives fair yields of substituted bicyclo[2.2. llhep- tanones in stereoselective fashion'"" (Scheme 39).,C02Me [I p-Qo Ph Ph Me02C Ph 68% NU =-SPh Scheme 39 40% Nu =fCo,Me The use of an allylic alcohol or ether as an allylic cation precursor allows control of regioselectivity in the 'ionic Diels- Alder reactions' described by Gassman"' (Scheme 40). 97 R L. Funk and M. B. Abelman J. Org. Chem 1986,51 3241. 98 T. Takahashi H. Nemoto Y. Kanda J. Tsuji and Y. Fujise J. Org. Chem. 1986 51 4315; J. A. Marshall J. M. Jenson and B. S. DeHoff ibid. p. 4316. H. Hagiwara and H. Uda J. Chem Soc Perkin Trans. I 1986,629; M. Ihara M. Toyota K. Fukumoto and T. Kametani ibid p. 2151. C. Thanupran C. Thebtaranonth and Y. Thebtaranonth Tetrahedron Lett. 1986 27 2295. lo' P. G. Gassman and D. A. Singleton J.Org. Chem. 1986 51 3075. N. S. Simpkins I 31% I I TI known y-cadenane precursor Scheme 40 Although the reaction is stereospecific the yields appear variable and the reaction conditions have been adjusted for each substrate. An efficient strategy for the synthesis of stereodefined exocyclic alkenes has been described by Negishilo2 (see also the Corey example above) and uses a combination of organometallic reactions developed previously. Thus regio- and stereospecific introduction of an ally1 group to a propargyl alcohol allows preparation of vinyl iodides (38),which are then further reacted with organozinc halides using catalytic Pd(PPh3)4 to give (39) (Scheme 41). Further transformation then gives the desired bicyclic enones such as (40) in stereospecific fashion.iii iv R-C-CCH20H R)=qo +L R;G \ __ -%Me3 R2 SiMe3 (40) Reagents i eMgBr* 10% CuI; ii 12; iii Bu'Me2SiCl imidazole; iv R'ZnX 1% Pd(PPh3)o; v C12ZrCp2 BuLi; CO Scheme 41 8 Polycyclic Compounds Decarbonylation of tricyclic bridgehead acid chlorides can be effected under remark- ably mild conditions to give alkene products presumably uia bridgehead alkeneslo3 (Scheme 42). A re-examination of the decomposition products of diazo ketone (41) confirms the identity of the strained cyclopropanobicyclo[3.2.l]octanone (42),'O" although 102 E. Negishi Y.Zhang F. E. Cederbaum and M. B. Webb J. Org. Chem. 1986 51 4080. 103 K. Hori M. Ando N. Takaishi and Y. Inamoto Tetrahedron Lett. 1986 27 4615.'04 P. Ceccherelli M. Curini M. C. Marcotullio and E. Wenkert J. Org. Chem. 1986 51 738. Alicyclic Chemistry 1% Pd". Bu,N 130 "C Scheme 42 (42) 41% Scheme 43 the product of subsequent reaction with Li-NH3 is (43) and not (44) as previously described (Scheme 43). The direct formation of a tricyclic cycloheptanone-containingsystem has been observed when cyclopropanone hemiacetal (45) is treated with MeMgBr followed by cyclohexanone lithium en~late'~' (Scheme 44). -78" +25 "C 14% Scheme 44 Cationic rearrangement of [3.3.3]propellanes furnishes mixtures of tricyclic enones suitable for further elaboration to natural products including quadrone.'06 Further synthetic activity in the area of linear triquinane natural products has resulted in the first total synthesis of (-)-c~riolin,'~' and two A9('2)-Capnellanes,'08 as well as other members of this family synthesized previo~sly.'~~ A very nice example in this area is a simple four-step synthesis of hirsutene'" (Scheme 45).More Diels-Alder chemistry aimed at synthesis of taxane targets has appeared."' The synthesis of mevinic acids has been the subject of a tetrahedron report."* Two lo' J. T. Carey C. Knors and P. Helquist J. Am. Chem SOC.,1986 108 8313. G. Mehta K. Pramod and D. Subrahmanyam J. Chem. SOC.,Chem..Commun. 1986 247. 107 M. Demuth P. Ritterskamp E. Weigt and K. Schaffner J. Am Chek Soc. 1986 108 4149. 108 M. Shibasaki T. Mase and S. Ikegami J. Am. Chem Soc. 1986 108 2090. 109 P. F. Schuda J.L. Phillips and T. M. Morgan J. Org. Chem. 1986,51,2742; G. Mehta A. N. Murthy D. S. Reddy and A. V. Reddy J. Am Chem. SOC 1986 108 3443. 110 M. Iyoda T. Kushida S.Kitami and M. Oda 1.Chem. SOC.,Chem. Commun. 1986 1049. Ill P. A. Brown and P. R Jenkins J. Chem. Soc. Perkin Trans. 1 1986 1303; K. J.' Shea J. W. Gilman C. D. Haffner and T. K. Dougherty J. Am. Chem. SOC.,1986 108 4953; A. S. Kende S. Johnson P. Sanfilippo J. C. Hodges and L. N. Jungheim J. Am. Chem. SOC,1986 108,3513. T. Rosen and C. H. Heathcock Tetrahedron 1986 42 4909. 144 N.S. Simpkins @-Me,SiI H H 0 80% Ph,P=CH -H H H 47 % Scheme 45 73% R = Me 92% 58% R = Pr' (46) Scheme 46 examples of Lewis acid catalysed intramolecular heterocycloaddition reactions have been explored"' (Scheme 46).These constitute relatively rare examples in which ketones (rather than aldehydes) participate effectively in this type of process subsequent cleavage of the oxygen bridge to give (46) was cleanly effected using lithium in methylamine. Wender has described another application of his arene olefin cycloaddition reaction,' l4 which constitutes the first total synthesis of the antileukaemic pseudoguaianolide Rudmollin (47) (Scheme 47). Both isomeric products from the photocycloaddition are efficiently converted through into the same tricyclic ketone by the use of Hg(OAc);?. The synthesis is then completed by a rather lengthy sequence involving a further ring fragmentation. Several groups have disclosed chemistry involving cycloaddition reactions of tropone derivatives.The intramolecular [6 + 21 photocycloaddition of alkenyl tropones such as (48) has been examined with mixed res~lts"~ (Scheme 48). None of the desired adduct could be isolated on irradiation of (48) in aprotic solvents. Mixtures of products resulting from [6 + 21 and [8 + 21 cycloaddition could be obtained in acidic medium thus implicating the hydroxytropylium ion (49) as the effective 67r component. Unfortunately yields in all cases were rather low- ca. 20% isolated. By contrast the thermal [4 + 21 and [6 + 41 cycloadditions of tropone 113 J. H. Rigby J. Z. Wilson and C. Senanayake Tetrahedron Lett. 1986 27 3329. 114 P. A. Wender and K. Fisher Tetrahedron Lett. 1986 21 1857. K.S. Feldman J. H. Come A. J. Freyer B. J. Kosmider and C. M. Smith J. Am. Chem. SOC.,1986 108 1327. Alicyclic Chemistry 145 I I -SiO -SiO '+ '+ 63% combined vield \H.~(oA~),,~~.THF H\ +________ -sid Ho OH /I (47) Rudmollin -I-Scheme 47 mR1 H+,McOH --, / R' RZ *. R3 RZ -r mR1 + @, R2 R3 [6 +21 Scheme 48 derivatives appear facile and high yielding especially in intramolecular examples. Intermolecular reaction of dienes with tropone gave mainly [4 +21 addition however 1-acetoxybutadiene gave the [6 +41 adduct (5O)ll6 in 55% yield. The intramolecular process favours [6 +41 addition (51) being the only product obtained from the diene-substituted tropone (52). Funk examined these intramolecular reactions in some detail,"' obtaining high (67-92% ) yields and J.H.Rigby T. L. Moore,and S. Rege J. Org. Chem 1986,51 2398. R. L. Funk and G. L. Bolton J. Am. Chem. SOC.,198% 108,4655. 146 N. S. Simpkins (50) (52) (51) finding that more substituted olefinic appendages will react smoothly if 0.1 eq. of Et,AlCl is included (Scheme 49). This strategy appears ideally suited for the synthesis of several polycyclic natural products notably those of the ingenane group. Vollhardt has extended his cobalt-mediated method for steroid synthesis to allow direct one-step preparation of B-ring aromatic steroids from acyclic precursors' '* (Scheme SO). Two other publications indicate the potential of this chemistry for synthesis of fused indole ~ystems.''~ -y 80°C.6h (92%) ' a-; OSi-X 20O0C 60h (86%) or llO"C 36h (79%) 0.1 eq. Et,AICI d? OSi-X without Et,AlCl a :p ratio 3 :1 with Et,AICl a :p ratio >20 1 Scheme 49 80-90% Scheme 50 118 S. H. Lecker N. H. Nguyen and K. P. C. Vollhardt J. Am. Chem. SOC.,1986 108 856. 119 G. S. Sheppard and K. P. C. Vollhardt J. Org. Chem. 1986 51 5496; D. B. Grotjahn and K. P. C. Vollhardt J. Am. Chem. Soc. 1986 108 2091.

ISSN:0069-3030    

DOI:10.1039/OC9868300123

出版商:RSC    

年代:1986

数据来源: RSC

摘要:

7 Aromatic Compounds By R. McCAGUE Drug Development Section Institute of Cancer Research Clifton Avenue Sutton Surrey SM2 5PX 1 General and Theoretical Studies Benzene.-There is controversy over the fundamental problem of the origin of the exceptional stability of aromatic compounds. Cooper et al. challenge the molecular orbital description that the r-electrons in benzene are delocalized. Using a spin- coupled valence bond description they arrive at six non-orthogonal orbitals each highly localized about a carbon nucleus. The aromatic stabilization is then explained by a particularly favourable symmetric coupling of the electron spins around the carbon framework.' A further area of dispute concerns the distortive propensity of the .rr-system of benzene.In reply to criticisms2 regarding the validity of chosen bond lengths Hiberty et al. consolidate their argument by comparison with a hypothetical molecule H6 that the symmetrical r-components of benzene are unstable with respect to distortion towards a Kikult type of ~tructure.~ The observed symmetrical structure of benzene is then explained by the tendency of the 0-framework to achieve bond equalization being greater than the tendency of the r-system to cause distortion. This latter tendency is weak in aromatic systems but strong in non-aromatic olefins. A real and strong KCkulC type distortion of benzene is observed using electron diffraction when it is co-adsorbed with carbon monoxide onto the surface of a rhodium cry~tal.~ Each benzene molecule is bonded to three rhodium atoms the extent of distortion (C-C bond lengths 1.81 and 1.33 A) indicating partial transfor- mation into three molecules of acetylene.It is thought that the electron acceptance by the co-adsorbed carbon monoxide promotes the distortion of the benzene molecule and hence that carbon monoxide might catalyse the benzene-acetylene interconversion on rhodi~m.~ Low-temperature photolysis of the benzene trimer (1)5 generated the benzene dimer (2) which has a lifetime of ca. 0.5 s at ambient temperature. Flash photolysis studies of dimer (2) give a free energy of activation AG* = 15.7 kcal mol-' for its decomposition into benzene. Kinetics of the decomposition of the more stable adducts of benzene with anthracene and naphthacene revealed A G values extending over a range that indicated a synchronous bond-breaking proce~s.~ This,conclusion ' D.L. Cooper J. Gerratt and M. Raimondi Nature (London) 1986 323 699. N. C. Baird J. Org. Chem. 1986 51 3907. P. C. Hiberty S. S. Shaik G. Ohanessian and J.-M. Lefour J. Org. Chem. 1986 51 3908. M. A. Van Hove R. F. Lin and G. A. Somorjai 1.Am. Chem. Soc. 1986 108 2532. A. Bertszh W. Grimme and G. Reinhardt Angew. Chem. Int. Edn. Engl. 1986 25 377. 147 148 R McCague is in apparent conflict with MNDO calculations6 that predict the dimerization of benzene would occur by a pathway with asynchronous formation of the new a-bonds. The benzene-carbon monoxide adduct (3) has also been synthe~ized.~ It decomposes into benzene and carbon monoxide with a similar activation energy as that for the dimer (2).The decompositions of compounds (2) and (3) have the lowest energies yet observed for a retro-Diels- Alder reaction. Measurements of gas-phase heats of formation of the keto tautomers of phenol (4) and (9,show the linearly conjugated dienone (4) to be the more stable by 4 kcal mol-'.8 Kinetic measurements of the conversion of the dienone (4) into phenol revealed that (4) is a strong carbon acid pK -3 f 1 the tautomerization being dominated by protonation of water although below pH 3 the tautomerism is acid catal ysed.' b Calculated geometries of phenyl and benzyl radicals (see Figure 1) show that in the phenyl radical (6) the bonds to the carbon bearing the unpaired electron are shortened relative to those in benzene and in the benzyl radical (7)the ring bonds to the substituted carbon are lengthened." The unusual bonding in benzynes and cyclopropabenzenes attracts theoretical study.Ab initio molecular orbital calculations give the bond lengths shown in Figure 1 for o-benzyne (8) the short C-1 to C-2 bond length indicating extensive overlap of the in-plane sp2-type orbitals. The similarity of the remaining C-C bond lengths is evidence against wbond fixation in o-benzyne." In addition to evidence for the existence of free o-benzynes," m-and p-benzynes have been generated by thermoly- ses of polymer-bound diaryliodonium carboxylates followed by trapping onto a R. Engelke J. Am. Chem SOC.,1986 108 5799. D. M. Birney and J.A. Berson Tetrahedron 1986 42 1561. * C. S. Shiner P. E. Vorndam and S. R. Kass J. Am. Chem. Soc. 1986 108 5699. M. Capponi I. Gut and J. Win Angew. Chem. Int. Edn. Engl. 1986,25 344. J. Pacansky B. Liu and D. DeFrees J. Org. Chem. 1986 51 3720. 10 " L. Radom R. H. Nobes D. J. Underwood and W.-K. Li Pure Appl. Chem 1986 SS 75. '* F. Gavina S. V. Luis A. M. Costero and P. Gil Tetrahedron 1986 42 155. Aromatic Compounds 1 49 second resin containing a bound n~cleophile.’~ The results support the expected biradical structure for m-and p-benzynes. Molecular orbital calculations (both semi-empirical and ab initio methods) have been made for cy~lopropabenzene.’~ The semi-empirical methods gave erroneous geometries but the geometries calculated by ab initio methods are in good agreement with experiment a calculated structure being given in Figure 1.The bond angles around the bridge are severely distorted but there is little 7r-bond fixation. The observed reactivity at the bridge carbon atoms is explained by the localization of the HOMO at the bridge bond. 1.387 \H 1.384\H 1.493 1.390 1.380 - H 1.371 1.071 1.396 1.073 1.392 1.383 Figure 1 Calculated geometries ofthe phenyl radical (6),the benzyl radical (7) o-benzyne (8) and cyclopropabenzene (9). Bond lengths are in A A variety of papers lead to an improved understanding of the effect of substituents on the benzene nucleus. A simple algorithm for the calculation of nionization energies in polysubstituted benzenes based on the HOMO approach has a~peared.’~ Calculations on benzyl-type carbanions have led to a re-emphasis of the concept of resonance saturation whereby the electron release of CH2- and OMe is not additive the effect being particularly important if the substituents are para.16 Mag-netic circular dichroism (MCD) of the benzene bond has been shown to give a measure of the net 7r-electron donor and acceptor properties of a substituent and proves particularly useful as a probe for hyperconjugative power.” Evidence for negative hyperconjugation by methyl groups in anilines and anisoles (i,e +B Ar-X-CH3 Ar-X+=CH2 H-; X = 0 NH NMe) has been found from the long-range deuterium isotope shifts observed for a para fluorine in the fluorine-19 n.m.r.spectrum.18 Studies of encumbered symmetrically hexasubstituted benzenes c6&,have been reported by Mislow et al.Hexaisopropylbenzene has been shown to have an excep- tionally rigid structure with gear-meshed isopropyl groups requiring 35 kcal mol-’ for their rotation.” Hexakis(dimethylsily1)benzene on the other hand has a much lower rotational barrier of 14.2 kcal mol-’ indicating a stepwise mechanism for its homomerization.” Unlike hexaisopropylbenzene which has essentially c6 sym-metry in the crystal the trimethylgermyl analogue R = Ge(CH,) had a slightly l3 F. Gavina S. V. Luis V. S. Safont P. Ferrer and A. M. Costero Tetrahedron Lett. 1986 27 4779. 14 Y. Apeloig and D. Arad J. Am. Chem. SOL,1986 108 3241. 1s J. Cioslowski A. Baranski and T.Juska Tetrahedron 1986 42 4549. 16 G. Vanermen S. Toppet M. Van Beylen and P. Geerlings J. Chem SOC.,Perkin Trans. 2 1986 699. 17 G. H. Weeks W. Adcock K. A. Klingensmith J. W. Waluk R. West M. Vasak J. Downing and J. Michl Pure Appl. Chem. 1986 58 39. 18 D. A. Forsyth and J.-R. Yang J. Am. Chem. SOC,1986 108 2157. 19 J. Siegel A. Gutierrez W. B. Schweizer,0.Ermer and K. Mislow J. Am. Chem. SOC.,1986 108 1569. 20 I. I. Schuster W. Weissensteiner and K. Mislow J. Am. Chem. SOC.,1986 108 6661. 150 R. McCague puckered benzene ring with germanium atoms located alternately above and below the average ring plane.21 Calculations on the unsynthesized hexa-t-butyl and hexakis( trimethylsilyl) analogues predict that these will also have a D3 symmetry.21 Homoaromaticity.-Homoaromaticity in Cations.The homotropylium ion ( 10) with its cyclic 6.n conjugated system can be regarded as the archetypal homoaromatic system. Scott and Hashemi have addressed the question of whether it has an ‘open’ form with through-space overlap of p-orbitals at the homoconjugation gap or whether it is ‘closed’ with the conjugation completed by cyclopropane Walsh orbitals.22 The close similarity of the physical properties of this ion with the synthesized bridged homotropylium ion (11)that is constrained into a ‘closed’ form has led to their conclusion that the unconstrained ion (10) must have a relatively small homoconjugation gap of 1.5-1.7 A.22In contrast the ethoxyhomotropylium ion (f2) the structure of which has been solved by X-ray diffraction has an ‘open’ conformation with a C1-C7 internuclear distance of 2.28 8 and bond length alterna- tion suggesting that this ion is better represented as a linear 1-ethoxyoctatrienyl cation than as an aromatic system.23 Nonetheless the presence of ring current in the n.m.r.spectrum of (12) shows that there is still homoconjugation. The use of one-bond 13C-13C coupling constants as a measure of carbon atom hybridization has been demonstrated and applied to the bis-homotropylium ion (13); the results support an earlier conclusion that the ion is homoaromatic having partial three- membered rings rather than being a localized ally1 cation (14).24 The formulation of certain radical cations as bis-homoaromatic has been made for the first time by Roth and Abelt for structures such as (15)25and (16).26In the case of (16) the neutral hydrocarbon undergoes retrocyclization to generate the tetraene (17) from which it was originally prepared.Neutral Homoaromaticity. The evidence for cyclic homoconjugation by its imparting non-alternant character to alternant hydrocarbons has been reviewed.” However 21 W. Weissensteiner I. I. Schuster J. F. Blount and K. Mislow J. Am. Chem. Soc. 1986 108 6664. 22 L. T. Scott and M. M. Hashemi Tetrahedron 1986 42 1823. 23 R. F. Childs R. Faggiani C. J. L. Lock and M. Mahendran J. Am. Chem. Soc. 1986 108 3613. 24 G. Jonsall and P. Ahlberg J. Am. Chem. Soc. 1986 108 3819. 25 H. D. Roth and C. J. Abelt J. Am. Gem. Soc. 1986 108 2013.26 C. J. Abelt and H. D. Roth J. Am. Chem. Soc. 1986 108 6734. 27 L. T. Scott fire Appl. Chem. 1986 58 105. 151 Aromatic Compounds whether homoaromaticity can be used to describe a neutral system has remained a matter of debate. Although n.m.r. spectroscopy shows that the 9-phosphabarbaralene (18) has a localized structure the closeness of the bond lengths of C-2-C-8 and C-4-C-6 (1.949 and 2.054 A respectively) as found by X-ray diffraction was taken as evidence for this being the closest approach to a neutral bis-homoaromatic system yet found.28 Neutral bis-homoantiaromaticity has been claimed for the biphenylene (19) on the basis of spectral evidence which points to significant homoc~njugation.~~ The possibility of tris-homoaromaticity in structure (20)has been discounted since its photoelectron spectrum can be accounted for by the large separation (2.60A) between the doubly bonded carbon atoms (as revealed by X-ray cry~tallography).~~ The prevention of adequate .rr-orbital overlap by the a-framework in this and similar structures has been recognized in a computational eval~ation.~~ However using thermochemistry rather than spectroscopy to detect aromaticity comparison of the heat of hydrogenation of triquinacene (21) with its partially saturated analogues indicates that triquinacene has a significant albeit small degree of homoaromatic- Lastly the possibility of homoaromaticity in hexaethynylbenzene owing to overlap of the orthogonal ethynyl .rr-orbitals has been raised but there is as yet no experimental evidence to support such an interacti01-1.~~ Homoaromaticity in Anions.There has been active debate concerning whether the anion from bicyclo[3.2.l]octa-2,6-diene (22) owes its stability to bis-homo- aromaticity. New support for a homoaromatic structure has been based on n.m.r. data34 and gas-phase physical measurement^.^^ The crystal structure of the 28 S. A. Weissman and S. G. Baxter J. Am. Chem. Soc. 1986 108 529. 29 C. F. Wilkox Jr. D. A. Blain J. Clardy G. Van Duyne R. Gleiter and M. Eckert-Maksic J. Am. Chem. SOC.,1986 108 7693. 30 J. E. McMurry G. J. Haley J. R. Matz J. C. Clardy G. Van Duyne R. Gleiter W. Schafer and D. H. White J. Am. Chem. SOC.,1986 108 2932. 31 A. B. McEwen and P. von R. Schleyer J.Org. Chem. 1986 51 4357. 32 J. F. Leibman L. A. Paquette J. R. Peterson and D. W. Rogers J. Am. Chem. SOC.,1986 108 8267. 33 R. Diercks J. C. Armstrong R. Boese and K. P. C. Vollhardt Angew. Chem. Int. Edn. Engl. 1986 25 268. 34 M. Christ1 and D. Bruckner Chem. Ber. 1986 119 2025. 35 R. E. Lee and R. R. Squires J. Am. Chem. SOC.,1986 108 5078. 152 R. McCague tetramethylethylenediamine complex of the lithium salt has been solved and shows co-ordination of the lithium cation to both the olefinic bond and ally1 anion as depicted in (23) and in doing so reduces the homoconjugation distance to 2.37 On the basis of these observations it is all the more interesting that an independent MCSCF molecular orbital study has predicted that the stability could be due to electrostatic association with the cation rather than to hom~aromaticity.~' More recent MNDO calculations agree with this hypothesis but it has been pointed out that even in the absence of a lithium gegenion the stabilization of the anion can be accounted for by negative hyperconjugation and inductive effects as are docu- mented for the homoallyl anion (24).38 Thus it seems unlikely that there is any significant homoaromaticity in (23).Capitalizing on this controversy Huber and Mullen claim in a review" that their 10~ dianion (25) represents a better case for homoaromaticity than does (23). 2 Synthesis of Substituted Benzenes From Non-aromatic Precursors.-In a series of papers Vollhardt et al. have applied their cobalt complex catalysed cyclization of acetylenic units.For example trimeriz- ation of diisopropylacetylene gave hexais~propylbenzene.'~ Linear [4]phenylenes of interest for their alternation between 4n and 4n + 2 total T electrons with increasing length were prepared as shown in Scheme 1. Since the trialkyltin groups could be converted into ethynyl functions the reaction sequence could in principle be continued indefinitely possibly to give polymers with useful electrical conducting proper tie^.^' A similar strategy gave angular [4]phenylene~.~'~~* Probably the most elegant application has been a single step assembly of a B-ring aromatic steroid framework from an acyclic precursor.43 Scheme 1 36 N. Hertkorn F. H. Kohler G. Muller and G. Reber Angew.Chen Int. Edn. Engl. 1986 25 468. 37 R. Lindh B. 0. Roos,G. Jonsall and P. Ahlberg J. Am. Chem Soc. 1986 108 6554. 38 P. von R. Schleyer E. Kaufmann A. J. Kos H. Mayr and J. Chandrasekhar J. Chem SOC Chem. Commun. 1986 1583. 39 W. Huber and K. Mullen Acc. Chem Res. 1985 19 300. M.Hirthammer and K.P. C. Vollhardt J. Am. Chem. SOC 1986 108 2481. 41 R. Diercks and K. P. C. Vollhardt Angew. Chem. Int. Edn. EngL 1986 25 266. 42 R. Diercks and'K. P. C. Vollhardt J. Am. Chem. Soc. 1986 108 3150. 43 S.H.Lecker N. H. Nguyen and K. P. C. Vollhardt J. Am. Chem. SOC. 1986 108 856. Aromatic Compounds 153 Diels-Alder cyclization is an obvious route for the synthesis of benzene rings but is relatively little used for monocyclic systems. However Diels- Alder reaction with methyl propiolate has been used in a novel benzannulation sequence (Scheme 2).44 Scheme 2 Biomimetic polyketide condensations such as that shown in Scheme 3;’ are proving attractive for the synthesis of aromatic rings in precursors of antitumour antibiotics such as Frederi~amycin.~~ ] -COzMe _&C02Me [&zMe &2Me c-COzMe COzMe COZMe Scheme 3 Cyclocondensations related to the Robinson annelation followed by aromatization have been used to synthesize aryl ~ulphides~~ and the fully substituted benzene ring in certain phenolic natural products:* In a curious synthesis of metu-substituted aromatic compounds addition of an alkyllithium to a tricyclic ketone is followed by Lewis acid catalysed rearrangement of the carbinol and then oxidative aromatiz- ation (Scheme 4).49 0 0 xqR-;bQL CHO CHO Scheme 4 Electrophilic Substitution.-Mechanistic Studies.Remarkably the detailed mechan- ism of as fundamental a reaction as aromatic nitration is still not fully established. According to MNDO calc~lations,~~ for compounds such as toluene and xylene the Wheland intermediate is formed by way of an electron transfer (i.e. ArH + NO2++ArH+’ + NO;) followed by radical-pair combination and only when the aromatic ring bears electron-withdrawing groups is the classical direct electrophilic attack by NO2+the only mechanism. However there is the conflicting experimental 44 R.L. Snowden and M. Wust Tetrahedron Lett. 1986 27 703. 45 M. Yamaguchi K. Hasebe and T.Minami Tetrahedron Lett. 1986 27 2401. 46 K. A. Parker and G. A. Breault Tetrahedron Lett. 1986 27 3835. 47 T. H. Chan and C. V. C. Prasad J. Org.Chem. 1986 51 3012. 48 H. Saimoto and T. Hiyama Tetrahedron Lett. 1986 27 597. 49 J. Adams and M. Belley J. Org.Chem 1986 51 3878. 50 J. Feng X.Zheng and M.C. Zerner J. Org. Chem. 1986 51,4531. 154 R. McCague evidence that independently-generated arene radical cations react with nitrogen dioxide to give a different isomer product distribution than is observed during normal nitration suggesting a radical-pair mechanism is not in~olved.~’ Moreover only with radical cations having an electron potential >1.7 V (e.g. naphthalene but not perylene) can a successful (exergonic) coupling with nitrogen dioxide take place.Nonetheless in the case of nitrous acid-catalysed nitration of p-nitrophenol the proposed mechanism is oxidation of the substrate to the phenolate radical which then combines with nitrogen dioxide.52 The discovery that nitration can be accom- plished in the gas phase using protonated methyl nitrate will hopefully assist experimental studies of nitration mechani~rns.~~ The matter of merging stepwise (electron transfer) and concerted (electrophilic) mechanisms is also a feature of the reaction of arenes with the active electrophiles Hg(OAc) or Tl(O,CCF,),+. These reactions have been shown to proceed via observable ~r-complexes.~~ Synthetic Procedures. ips0 -Protonation by sufficiently strong acids can effectively redirect an electrophilic substitution reaction allowing the rearrangement of nitrocompounds by [1,3] shifts to thermodynamically more stable isomers55 and allowing the acylation of arenes by transfer of the acetyl function from acetylpen- tamethylben~ene.~~ The specific reduction of unhindered nitro-groups by sulphide allows the synthesis of nitroarenes which cannot be prepared dire~tly,~’ such as the synthesis of hexanitrobenzene from trinitrotol~ene.~~ Electrophilic attack can be redirected by blocking the favoured site of attack with a t-butyl group that can be later removed by transalkylation with excess benzene and aluminium chloride.59 With the increasing demand for specifically fluorinated arenes new reagents have emerged for aromatic fluorination and.these have been reviewed.60 Iodoarenes can be prepared by replacement of trimethylsilyl using iodine and silver tetrafluoro- borate.61 Regiospecific p-halogenation of phenols has been achieved using tetrabutyl- ammonium tribromide6 or halodimefiylsulphonium halides.63 In a useful synthesis of aromatic aldehydes N,N-dimethylbenzylamines (ArCH2NMe2) are prepared either by reaction of phenols with formaldehyde- dimethylamine,@ or from aryltributylstannanes with Eschenmoser salts (Me N+=CH2 Cl-),65 and are then treated with hexamethylenetetraamine and acid.@ 51 L.Eberson and F. Radner Acta Chem. Scand. Ser. B 1986,40 71. 52 M. Ali and J. H. Ridd J2 Chem. SOC.,Perkin Trans. 2 1986 327. 53 M. Attina and F. Cacace 1. Am. Chem SOC,1986 108 318.54 W. Lau and J. K. Kochi J. Am. Chem SOC.,1986 108,6720. 55 P. Barrow J. V. Bullen A. Dent T. Murphy J. H. Ridd and 0.Sabek J. Chem SOC Chem. Commun. 1986 1649. 56 T. Keumi T. Mortia T. Shimada N. Teshima H. Kitajima and G. K. S. hakash J. Chem Soc. Perkin Trans. 2 1986 847. ” T. E. Nickson J. Org. Chem. 1986 51 3903. 58 R. L. Atkins R. A. Hollins and W. S. Wilson J. Org. Chem. 1986 51 3261. 59 S. Kajigaeshi T. Kadowaki A. Nishida and S. Fujisaki Bull. Chem. SOC. Jpn. 1986 59 97. 69 S. T. Pumngton B. S. Kagen and T. B. Patrick Chem. Rev. 1986 86 997. 61 S. R. Wilson and L. A. Jacob J. Org. Chem 1986,51 4833. J. Bethelot C. Guette M. Ouchefoune P.-L.Desbene and J.-J. Basselier J. Chem. Res. (S),1986 381. 63 G. A. Olah L.Ohannesian and M. Arvanaghi Synthesis 1986 868. 64 M. T. Clark and D. D. Miller J. Org. Chem 1986 51 4072. 65 M. S. Cooper and H. Heaney Tetrahedron Lett. 1986,27 5011. Aromatic Compounds 155 Direct chemical hydroxylation of arenes can be difficult. Anilines have been hydroxylated using hydrogen peroxide in superacid the electrophile being H302+.66 Benzene has been converted into phenol by electroreduction of dioxygen in tri- fluoromethanesulphonic acid,67 and under conditions of hydroxyl radical gener- ation.6s Microbial oxidation can also sometimes take place readily and regioselective para-hydroxylation by the fungus Beauoeria sulfurexens has been reported.69 Intramolecular electrophilic cyclization using aryliodonium tetrafluoroborates has been used to prepare dihydr~naphthalenes~' and functionalized tetrahydronaph- thalenes the latter by using episulphoni~m~' intermediates or episelenoni~m~~ derived from alkenes.Nucleophilic Substitution.-Mechanistic Studies. The nucleophilic substitution reac- tion has attracted many kinetic studies. In the reaction of l-chloro-2,4-dinitrobenzene with piperidine hydrogen bonding between the 2-nitro-group and the nucleophile favours the reaction so that increasing the hydrogen-bond-donating ability of the solvent decreases the reaction rate.73 When amines are the nucleophiles it has been found that non-nucleophilic bases catalyse the reaction indicating that the rate- limiting step is then deprotonation of the initial reversibly-formed zwitterionic a-~omplex.~~ Furthermore it has been suggested that a significant decrease in rate when a bulkier amine is the nucleophile is likely to be due to a lower rate of this proton-transfer rather than to a lower rate of the initial nucleophilic attack.75 Consequently the use of a hydrogen-bond-accepting solvent such as DMSO can increase the rate of such a reaction.An alternative viewpoint is that the effective nucleophile could consist of a hydrogen-bonded dimer (or higher ~ligomer).'~ Nucleophilic aromatic substitution can be catalysed by P-cyclodextrin the rate enhancement being due to reversible nucleophilic displacement by the cyclodextrin in addition to formation of an inclusion complex.77 It is now well established that metal carbonyl rr-complexation dramatically increases the rate of nucleophilic attack on the aromatic ring.A relationship has been reported connecting the reactivity with the stretch force constant of the carbonyl bonds in the metal carbonyl having the arene replaced by carbon monoxide.78 Synthetic Procedures. Nucleophilic attack is often fastest at unsubstituted ring posi- tions. Exploitation of this feature has led to the most significant latest developments in nucleophilic aromatic substitution since a change in the substitution pattern of the ring can be brought about. In the case of arenetricarbonylchromium complexes 66 J.-C. Jacquesy M.-P. Juannetaud G. Morellet and Y. Vidal Bull. SOC.Chim. Fr. 1986 625. 67 R.Ohnishi and A. Aramata J. Chem. Soc. Chem. Commun. 1986 1630.68 A. Kunai S. Hata S. Ito and K. Sasaki J. Am. Chem. SOC.,1986,108,6012; J. Org. Chem. 1986,51,3471. 69 B. Vigne A. Archelas J. D. Fourneron and R. Furstoss Tetrahedron 1986,42 2451. 70 M. Ochiai Y.Takoaka K. Sumi and Y. Nagao J. Chem. SOC.,Chem. Commun. 1986 1382. 71 E. D. Edstrom and T. Livinghouse J. Chem. Soc. Chem. Commun. 1986,279; J. Am. Chem. Soc. 1986 108 1334. 72 E. D. Edstrom and T. Livinghouse Tetrahedron Lett. 1986 27 3483. 73 R. D. Martinez P. M. E. Mancini L. R. Vottcro and N. S. Nudelman J. Chem. SOC.,Perkin Trans. 2 1986 1427. 74 E. Buncel C. Innis and I. Onyido J. Org. Chem. 1986 51 3680. 7s N. S.Nudelman and S. Cerdeira J. Chem. SOC.,Perkin Trans. 2 1986 695. 76 0. Banjoko and C. Ezeani J. Chem. SOC.,Perkin TrunJ.2 1986 531. 77 R.H. de Rossi M. Barra and E. B. de Vargas J. Org. Chem. 1986,51 2157. 78 R. C. Bush and R. J. Angelici J. Am. Chem. Soc. 1986 108 2735. 156 R. McCague acid treatment of the initial adduct causes elimination of the proton at the attack site together with a leaving group. Accordingly tele-and cine-substitutions have been achieved (Scheme 5).79 The leaving group can be benzylic as in the reaction of benzyl alcohol tricarbonylchromium with alkyllithiums to give o-alkyltoluenes.80 Replacement of hydrogen ortho to a nitro-group in nitrobenzenes by the nucleophile Me3 SiCH2 MgCl is accomplished after DDQ oxidation of the initial adduct.’* R R Y tele-Substitution cine-Substitution favoured if X is electron-favoured if X is electron-releasing (e.g.OPh) withdrawing (e.g. C1) X-= leaving group Y-= nucleophile Scheme 5 Radical Substitution.-Radical cyclization by aryl radicals onto a double bond in the same molecule was observed following treatment of the arenediazonium tetra- fluoroborates with copper saltsg2 or by U.V. photolysis of the aryl iodide^.'^ The 2-nitropropane anion has been shown to be a powerful nucleophile in its addition to electrochemically generated aryl radicals giving overall replacement of halide.84 Homolytic arylation of aromatic compounds to give biphenyls has been reviewed.” Substitution uia Transition Metal a-Complexes.-The use of transition metal com- plex catalysis for bringing about selective substitutions at sp2 centres has made a very significant contribution to the advancement of organic synthesis in recent years.Typically using palladi~m-~’~~~’~ catalysts useful features and cobalt-9~g6complex of the methodology are the ready route to carbonyl-substituted arene~’~*’~-’~ (owing to a facile insertion of carbon monoxide into the initially formed aryl-metal a-bond) and the fact that in addition to halides triflates can be di~placed~~.’~ allowing overall ’9 F. Rose-Munch E. Rose and A. Semra J. Chem. SOC.,Chem. Commun. 1986 1108 and 1551. SO J. Blagg S. G. Davies C. L. Goodfellow and K. H. Sutton J. Chem. SOC.,Chem. Commun. 1986 1283. 81 G. Bartoli M. Bosco R. Dalpouo and P. E. Todesco J. Org. Chem. 1986,51 3694. 82 G. F. Meijs and A. L. J. Beckwith J. Am Chem. SOC. 1986 108 5890. 83 A. N. Abeywickrema and A.L. J. Beckwith Tetrahedron Lett. 1986 27 109. 84 C. Amatore M. Gareil M. A. Oturan J. Pinson J.-M. Saveant and A. Thiebault J. Org. Chem. 1986 51 3757. 85 R. Bolton and G. H. Williams Chem SOC.Reu. 1986 15 261. 86 Q.-Y. Chen Y.B. He and Z.-Y. Yang J. Chem SOC.,Chem. Commun. 1986 1452. 87 N. Miyaura T. Ishiyama M. Ishikawa and A. Suzuki Tetrahedron Lett. 1986 27 6369. ’* D. A. Widdowson and Y.-Z. Zhang Tetrahedron 1986 42 2111. 89 T. R. Bailey Tetrahedron Lett. 1986 27 4407. 90 A. Dondoni M. Fogagholo G. Fantin A. Medici and P. Pedrini Tetrahedron Lett. 1986 27 5269. 91 V. P. Baillargeon and J. K. Stille J. Am Chem. SOC 1986 108 452. 92 E. Neigichi and J. M. Tour Tetrahedron Lett. 1986 27 4869. 93 S. Cacchi P.G. Gattini E. Morera and G. Ortar Tetrahedron Lett. 1986 27 3931. 94 T. Kashimura K. Kudo S. Mori and W. Sugita Chem. Lett. 1986 851. 95 T. Kashimura K. Kudo S. Mori and N. Sugita Chem. Lett. 1986 299. % M. Miura F. Akase and M. Nomura J. Chem. SOC.,Chem. Commun. 1986 241. Aromatic Compounds 157 replacement of the hydroxyl group of phenols. An outline of the course of these reactions is shown in Scheme 6. Examples of groups that can be introduced in this way are H,86 alk~l,~~ heter~aryl,~~ for-ary1,88 alkyn~l?~ 2,2-dimethyloxazolinyl~0 my1?* alko~ycarbonyl~~*~~ carboxylic acid,95 and methyl ketone?6 In addition the method has been used in a cyclization to form naphthoq~inones.~' .,-ArCO-[MI-X 2ArCOY ArX -% Ar-[MI-X where X = halogen or triflate and [MI represents the transition metal and associated ligands Scheme 6 Metallation with a manganese carbonyl complex has been used to introduce electrophiles into the ring position adjacent to a methyl ketone gr0up.9~ Phenylation of amines phenols and enols has been reported using triphenylbismuth diacetate?* Substitution vita Lithiation.-Several advances have been made in the area of regiocontrol of lithiation.Reaction of tetramethyldopamine with alkyllithium gives selective lithiation at either of the two vacant ring positions depending on whether the treatment is at -78°C or room temperature.- The remaining position can be specifically substituted using palladium acetate mediated cyclometallation.99 Regio- specific lithiation ortho to fluorine in tricarbonylchromium-complexed fluoroanisoles has allowed the synthesis of a range of polysubstituted arenes.Im In contrast the uncomplexed arenes give preferred lithiation ortho to the methoxy group.'o' The use of tertiary P-aminobenzamides [ArCON( Me)CH2CH NMe,] for directed lithiation has the advantages that the amide function is easily hydrolysed or can be treated to give improved yields of aldehydes or ketones compared with other dialkylamides.'02 Lithiation of N-monoalkylanilines can be achieved by prior in situ conversion into the N-carb~xylate.'~~ A procedure for substitution ortho to the amino group in N,N-unsubstituted anilines is via the lithium salt of the formamide the formyl group being readily removed by hydrolysis.'" Substitution uh Arynes.-The formation of a substituted benzyne by elimination of iodine and fluorine from the readily prepared 2-iodo-3-fluoroanisole has found use in the synthesis of conformationally defined tricyclic tyramine analogue^.'^^ Jung and Lowen have demonstrated the intramolecular coupling of anions and benzyne both generated using lithium diisopropylamide (LDA).The method was used in a direct synthesis of an intermediate for podophyllotoxin synthesis.'06 Buchwald et 97 L. H. P. Gommons L. Main and B. K. Nicholson J. Chem. SOC Chem Commun.,1986 12. 98 D. H. R. Barton J.-P. Finet J. Khamsi and C. Pichon Tetrahedron Lett. 1986 27 3615 and 3619; D. H. R. Barton N. Y. Bhatnagar J.-P. Finet and W. B. Motherwell. Tetrahedron 1986 42 3111. 99 C.D. Liang Tetrahedron Lett. 1986 27 1971. loo J. P. Gilday and D. A. Widdowson Tetrahedron Lett. 1986 27 5525. 101 J. P. Gilday and D. A. Widdowson J. Chem. SOC,Chem. Commun. 1986 1235. 102 D. L. Comins and J. D. Brown J. Org. Chem. 1986. 51. 3566. 103 A. R. Katritzky W. Q. Fan and K. Akutagawa Tetrahedron 1986,42,4027. 104 I. Fleming M. A. Loreto I. H. M. Wallace and J. P. Michael J. Chem. SOC.,Perkin Trans. I 1986,349. 105 G. L. Grunewald H. S. Arrington W. J. Bartlett T. J. Reitz and D. J. Sall J. Med. Chem. 1986,29 1972. lo6 M. E. Jung and G. T. Lowen Tetrahedron Lett. 1986 27 5319. 158 R. McCague al. have begun to uncover a rich chemistry of the zirconocene-benzyne complex (26); examples showing its great promise as a precursor to substituted benzenes are its coupling reactions with acetone and diethylacetylene (Scheme 7).'07 E:m a ,EtCECEt CP2Q I PMe3 Et (26) Scheme 7 Other Reactions.-Treatment of arenediazonium salts with formamide has been shown to effect reduction to the arene the proposed mechanism being cleavage of the formyltriazene in a six-membered ring transition state resulting in the elimination of nitrogen and HNC0.'08 3 Benzene Derivatives for the Synthesis of Non-aromatic Compounds Reductions.-The application of the Birch reduction for the synthesis of natural products has been reviewed."' In contrast to previous observations benzonitriles and N,N-dialkylbenzamides have been shown to be excellent substrates for the Birch reduction and reductive alkylations.' lo Phenyl radical cations generated by electroreduction have been trapped intramolecularly by a ketone function to give cyclized products with high diastereoselectivity; Scheme 8 gives an example."' Scheme 8 A reversal of the regi9selectivity of the Birch reduction has been achieved using photolysis in the presence of an electron acceptor 1,3-dicyanobenzene and sodium borohydride.Typically the least substituted 1,4-diene is formed. The mechanism for this 'Photo-Birch' reduction of p-xylene is illustrated in Scheme 9.112 H Me Me Me Me 04.0 -22% Q /. 0 \ DCB DCB*--DCB-^ DCB + H+ Me Me H Me H Me DCB = 1,3-dicyanobenzene Scheme 9 107 S. L. Buchwald B. T. Watson and J. C. Huffman J. Am. Chem. SOC.,1986 108 7411.108 M. D. Threadgill and A. P. Gledhill J. Chem. Soc. Perkin Trans. I 1986 873. 109 J. M. Hook and L. N. Mander Nut. hod. Rep. 1986 3 35. 110 A. G. Schultz and M. Macielag J. 0%.Chem. 1986 51 4983. Ill T. Shono N. Kise T. Suzumoto and T. Morimoto J. Am. Chem. SOC.,1986 108 4676. 112 G. A. Epling and E. Florio Tetrahedron Let?. 1986 27 1469. Aromatic Compounds meto-Photocyc1oaddition.-Mechanistic studies of the meta-cycloaddition to arenes have been concerned with rationalizing the observed regioselectivity in terms of a dipolar intermediate. Investigation of the isotope effects of deuterium incorporation into the arene indicate that the electron cloud of the photoexcited arene becomes polarized on approach of the alkene as postulated in Scheme the stabilization of this induced charge separation influences the regi~selectivity."~-' l4 Alternatively the regioselectivity can be explained by orbital symmetry consideration^."^ Scheme 10 The stereocontrol found in the final ring formation when the 2v-component is trans- 1,2-dichloroethene is attributed to distortion of the biradical bicyclic inter- mediate induced by the chlorine atoms.' l6 The rneta-cycloaddition reaction has been employed in a total synthesis of the complex seven-membered ring anti-leukaemic agent rudmollin."' Thermal Cyc1oaddition.-Benzene derivatives do not normally undergo Diels- Alder reactions with olefins but following observations that addition of N-phenyl-maleimide to phenols can take place a theoretical approach has predicted that the reaction will occur only if the olefin is strained."' Interestingly a remarkably facile Diels-Alder addition to a benzene ring has been found (Scheme 11) where intramolecular hydrogen bonding holds the molecule in a favourable conformation for cycl~addition."~ C0.NHR' 80 "C ___ R' Scheme 11 4 Polyhalogenoarenes One of the characteristics of polyhalogenoarenes is the ease with which they form radical species; this is considered to be an important factor in the environmental 113 P.de Vaal G.Lodder and J. Cornelisse Tetrahedron 1986 42 4585. 114 J. Mattay J. Runsink J. Gersdorf T. Rumbach and C. Ly,Helv. Chem. Acta 1986 69 442. I15 D. Bryce-Smith A. Gilbert and J. Mattay Tetrahedron 1986 42 6011.I16 J. Cornelisse A. Gilbert and P.W. Rodwell Tetrahedron Lett. 1986 27 5003. 117 P.A. Wender and K. Fisher Tetrahedron Lett. 1986 27 1857. 118 J. Arriau J. Fernandez and P. Yianni J. Chem. SOC. Perkin Trans. 2 1986 2013. 119 K. Diehl and G. Himbert Chem. Ber. 1986 119 3812. 160 R. McCague problems associated with polychloroarenes. Oxidation of perfluoroarenes by dioxy- genyl tetrafluoroarsenate (02+ASF6-) gives radical cation salts; that formed from perfluoronaphthalene is stable.’” Radical cations of polychlorinated biphenyls have been observed under pulse irradiation conditions.’” Studies of the radical anion of perchlorobenzene [PCB-Cl+’] reveal two pathways of its fragmentation to PCB’ and C1- or to PCB- and Cr.’” Photolysis of pentafluorophenyl ally1 ether gives intramolecular [2+ 21cycloaddi-tion to form a tricyclic str~cture.’’~ Such tricyclic compounds might be intermediates in the photo-Claisen rearrangement.Although a characteristic of perfluoroarenes is their propensity to attack by nucleophiles displacement of fluorine by certain nucleophiles that are ‘soft’ in hard-soft acid-base theory is not favoured. Thus Grignard reagents displace cyanide and from 1,4-dicyan0-2,3,5,6-tetrafluorobenzene~~~ do not affect perfluorotolyl ethers.’25u Also octafluorotoluene arylates the caesium enolate of androst-Cene- 3,17-dione at oxygen instead of at carbon.’25b 5 Condensed Polycyclic Aromatic Compounds Theoretical Studies.-MNDO calculations on closed-loop odd-alternant polycyclic polyenes such as the phenalenyl system show that there is a genuinely non-bonding frontier .rr-orbital and consequently the Huckel (4n+ 2) rule does not apply for these systems.’26 Early in the year a report by Haymet appeared re-emphasizing the predi~tion’~~ that the intriguing hypothetical icosohedral c60 hydrocarbon ‘footballene’ (‘Buck- minsterfullerene’) would be stable with a spherically delocalized 7r-system having a high Huckel delocalization energy (DE) of 0.55P/carbon compared to a value of 0.33Plcarbon for benzene.’’* Other calculations have also been reported’29a and predicts that the molecule would not undergo bond distortions to optimize energy and would therefore maintain a symmetrical structure.However it has been pointed out that the Huckel DE used by Haymet is not a good criterion for stability.A better one is resonance energy per welectron (REPE) for which footballene gives a value of 0.031p compared to 0.065 for benzene 0.038 for pentacene and 0.022 for an infinite polyacene so that an REPE of the size found does not guarantee stability.’30 MNDO calculations for the automerization of naphthalene indicate that tetracyclic ‘valene’ derivatives are probably not involved and a new mechanism in which benzofulvenes are intermediates has been I?”. T. J. Richardson F. L. Tanzella and N. Bartlett J. Am. Chem Soc. 1986 108 4937. 121 J. Monig K.-D. Asmus L. W. Robertson and F. Oesch J. Chem. Soc. Perkin Trans. 2 1986 891. P. K. Freeman R. Srinivasa J.-A. Campbell and M.L. Deinzer J. Am. Chem. Soc. 1986 108 5531. 123 B. Sket N. Zupancic and M. Zupan Tetrahedron 1986 42 753. 124 D. J. Milner 1. Organomet. Chem. 1986 302,147. 125 (a) R. McCague J. Chem. Res. (S) 1986 58; (b) M. Jarman and R. McCague J. Chem. Soc. Chern. Commun. 1986 635; (c) C. Glidewell and D. Lloyd J. Chem Rex (S) 1986 106. ’*’ D. A. Bochvar and E. G. Gal’pern Dokl. Akad. Nauk SSSR 1973 209 610. 12* A.D. J. Haymet J. Am. Chem Soc. 1986 108 319. 129 (a) D. J. Klein T. G. Schmalz G. E. Hite and u’. 4. Seitz J. Am Chem. Soc. 1986 108 1301; (b) M. D. Newton and R. E. Stanton J. Am. Chem. SOC,1986 108,2469; (c) M. Kataoka and T. Nakajima Tetrahedron. 1986. 42. 6437. 130 €4. A. Hess jun. and L. J. Schaad J. Org. Chem. 1986 51 3902.13‘ M. J. S. Dewar and K. M. Merz jun. J. Am. Chem. SOC.,1986 108 5146. Aromatic Compounds 161 Synthesis of Condensed Aromatic Compounds.-From Acyclic Precursors. The total synthesis of the E-rhodomycinone racemic anthracyclone has been accomplished by way of a polyketide c~ndensation.'~~ A useful feature of the reaction (shown in Scheme 3) is that the product is like the starting material a glutarate and the reaction sequence can be repeated to give polyoxygenated polynuclear linear a~enes.4~ Using Diels- Alder Reactions. Utilization of the Diels-Alder approach to polycyclic systems is currently very popular much of the work having been aimed at the synthesis of anthracycline antibiotic^'^^-'^^ such as daunomycine. Frequently used When quinones 2n-components are the and benzyne~.'~-'~~ are used regioselectivity can be brought into the cyclization by substitution of the quinone double bond with such groups as CN SPh or C1.Typical 4n-components and furans136~138~139~144-'47.'50 used are quin~dimethanes'~~.'~~ although a variety of polarized simple butadienes have also been an example being 3-chloro-l-methoxy-1,3-butadiene which has been used in an efficient synthesis of the naphthalene 5-lipoxygenase inhibitor RS-43 179.l4O The use of 1,2-dimethyl- enecyclohexanes has also been rep~rted.'~~ The basic components can be benzo- fused allowing highly convergent syntheses of structures having several rings to be undertaken. Thus naphtho[ 1,2-c]furan and naphtho[2,3-c]furan which have now been ~ynthesized'~~.'~~ can be used for annelation of a phenanthrene and anthracene unit respectively.Also a 1-(dialky1amino)isobenzofuranreacts with a variety of 27r-components allowing direct aromatic-ring annul at ion^.'^^ Other Methods of Ring Construction. A novel sequence for 2,3-naphthalene annula- tion from acyclic or cyclic ketones is illustrated in Scheme 12.'51 0-Allylbenzamides cyclize on formation of the anion with methyllithium to give a regioselective synthesis 132 K. Krohn and W. Priyono Liebigs Ann. Chem. 1986 1506. 133 Y. Tamura M. Sasho S. Akai and H. Kishimoto Tetrahedron Lett. 1986 27 195; R. A. Russell R. W. Irvine and R. N. Warrener J. Org. Chem. 1986 51 1595. 134 G.A. Kraus and J.A. Walling Tetrahedron Lett. 1986 27 1873. 135 D. W. Cameron C. Conn. M. J. Crossley G.I. Feutrill M. W. Fisher P. G. Griffiths B. K. Merrett and D. Pavlatos Tetrahedron Lett. 1986 27 2417; D. W. Cameron G. I. Feutrill P.G. Griffiths and B. K. Merrett ibid. p. 2421. 136 R. W. Franck V. Bhat and C. S. Subramaniam J. Am. Chem. Soc. 1986 108,2455. 137 A. A. Abdallah J.-P. Gesson J.-C. Jaquesy and M. Mondon BulL SOC.Chim Fr. 1986,93; A. Bekaert J. Andrieux. and M. Plat ibid. 314. 138 J.-G. Smith P. W. Dibble and R. E. Sandborn J. 0%.Chern. 1986 51 3762. I39 W. C. Christopfel and L. L. Miller J. Org. Chem. 1986 51 4169. 140 D. L. Flynn and D. E. Nies Tetrahedron Lett. 1986 27 5075. 141 M. S. Newman and V. K. Khanna J. Org.Chem 1986,51 1921.142 A. D. Thomas and L. L. Miller J. Org. Chem 1986,51,4160; L. L. Miller A. D. Thomas C. L. Wilkins and D. A. Weil J. Chem. SOC.,Chem. Commun. 1986 661. 143 G.A. Kraus and S. H.Woo,J. Org. Chem 1986 51 114. 144 F. Gavina S. V. Luis P. Ferrer A. M.Costero and P. Gil Tetrahedron 1986 42 5641. 145 D. J. Pollart and B. Rickborn J. Org. Chem 1986 51 3155. 146 R. Camezind and B. Rickborn J. Org. Chem. 1986 51 1914; J. Netka S. L. Crump and B. Rickborn ibid. p. 1189. 147 H. Hart and D. Ok J. Org. Chem. 1986 51,979. 148 J. Makayama M. Kuroda and M. Hoshino Heterocycles 1986,24,1233; R. G.Carlson K. Srinivasachar R. S. Givens and B. K. MatuszEwski J. Org.Chem. 1986 51 3978. 149 R. D.Bach and R. C. Klix Tetrahedron Lett. 1986 27 1983. 1so C.-W.Chen and P. Beak J. Org. Chem. 1986 51 3325. M. A. Tius and J. Gomez-Galeno Tetrahedron Lett. 1986 27 2571. 162 R. McCague of naphthols and naphthoq~inones.'~~ 9-Phenanthrols are obtained on ring-expansion of (a-bromobenzyl)fluorenols.'53A rapid synthetic approach to sub- stituted chrysene derivatives involves alkylation of the lithium salt of 1,Cdime- thoxycy~lohexadiene.~~~ Reagents i PhCH2MgC1 -55 "C; ii pyridinium tosylate; iii TiC14 CH2C12 Scheme 12 Preparation of SpecificaZZy Substituted Products. One approach to the substitution of arenes at certain sites that are unaffected by electrophilic reagents is to functionalize a precursor of the arene having different positional reactivity. This strategy is employed in the synthesis of 2,7-dibromopyrene via electrophilic substitution in 4,5,9,10-tetrahydr0pyrene'~~ and in a synthesis of 2,3-disubstituted anthracenes by electrophilic substitution in 9,10-ethano-9,10-dihydroanthracenefollowed by flash vacuum thermolytic elimination of eth~1ene.l~~ The observed reactivity in the ethanoanthracene is attributed to hybridization changes at the ring junction owing to ring strain.A new synthesis of 2,3-dibromonaphthalene useful as a synthon for extended trypticines from 1,2,4,5-tetrabromobenzenevia the potentially versatile intermediate (27) is shown in Scheme 13.'57 Reagents i Bu"Li (1 equiv.) furan; ii TiC14 Zn THF Scheme 13 Carcinogenicity of Polycyclic Aromatic Hydrocarbons (PAH).-It is now established that bay region diol epoxides are the ultimate carcinogenic metabolites of PAH.In a review of the structural requirements favouring tumourigenicity of methylated PAH generalizations made are that a methyl group in a bay region adjacent to an unsubstituted ring increases tumourigenicity (+B effect) whereas substitution of a peri-position adjacent to the angular ring decreases it (-P effe~t)."~ Following a synthesis of diol epoxides of 5-methylchrysene the diol epoxide (28) has been 152 M. P. Sibi. J. W. Dankwardt. and V. Snieckus. J. Org. Chem. 1986 51 271. A. Tantivanich and D. Supatimusro Tetrahedron Lett. 1986 27 5301. I54 R. G. Harvey J. Pataki and H. Lee J. Org. Chem. 1986 51 1407. 155 H. Lee and R. G. Harvey J. Org. Chem. 1986 51 2847. I56 J. E. Baldwin A.G. Swanson J. K. Cha and J. A. Murphy Tetrahedron 1986.42 3943. 15' H. Hart A. Bashir-Hashemi. J. Luo. and M. A. Meador Tetrahedron 1986 42 1641. 158 S. S. Hecht A. A. Melikian and S. Amin Acc. Chem. Res. 1986 19 174. Aromatic Compounds confirmed to be the Jltimate carcinogen from the hydrocarbon; n.m.r.studies show the hydroxyl groups to prefer a diequatorial on formation.'^^ Similarly diol epoxides (29) have been synthesized and shown to be the principle active carcinogenic metabolites of 7,12-dimethylbenz[ ~lanthracene.'~~ A review has also appeared on the synthesis of oxidized metabolites of PAH including the dihydrodiols.'60 Resolution and absolute-configuration determinations of various PAH dihy-drodiols and epoxides reveal that usually the dihydrodiols having RR-stereochemistry are dextrorotatory in the case of K-region diols and laevorotatory in the case of bay-region diols and that these are the preferred enantiomers formed metabolically by rat liver rnicrosomes.l6' Novel Polycyclic Structures.-Planar Structures.The cycloarene (30) has been synthe- sized. The chemical shift of the inner protons (8 9.56) shows that despite the inner and outer 4n + 2 welectron peripheries there is no annular ring-current although the localization of aromatic sextets is thought to be less than in kekulene.'62 The cyclohexa[ cdlperylium ion [31] a higher homologue of the phenalenium ion showed a strong induced n.m.r. ring-current indicating an extensively delocalized struct~re.'~~ The hexagonal planar 13-ring hydrocarbon hexaperibenzocoronene has been suggested as being abundant in interstellar media and a new synthesis has been pre~ented.'~~ (30) (31) 159 H.Lee and R. G. Harvey J. Org. Chem. 1986 51 3502. 160 R. G. Harvey Synthesis 1986 605. 161 J. M. Sayer P. J. van Bladeren H. J. C. Yeh and D. M.Jerina J. Org. Chem. 1986 51 452; S. K. Balani P. J. van Bladeren N. Shirai and D. M. Jerina ibid. p. 1773; M. Schollmeir H. Frank F. Oesch and K. L. Platt ibid. p. 5368. 162 D. J. H. Funhoff and H. A. Staab Angew. Chem. Znt. Edn. Engl. 1986,25 742. 163 K. Yamamura H. Miyake and I. Murata J. Org. Chem. 1986 51 251. 164 W. Hendel Z. H. Khan and W. Schmidt Tetrahedron. 1986 42 1127. 164 R. McCague Triptycenes.Extended triptycenes (iptycenes) have been of interest for their high melting points (with consequent possibilities for use as thermoresistant materials) and because their molecular cavities should allow complexation of other molecules. A variety of iptycenes have been ~ynthesized.'~~~'~~ Helicenes. Some elegant work on helicenes has been published by Katz et al. The synthesis of [7]helicenes has been improved by the use of a bromine-substituted precursor (32). The bromine atom directs photocyclization in the manner required to give the helicene.'66 In an asymmetric synthesis of a helicene the configuration of the carbon marked by an asterisk in precursor (33) controls the wind of the helix in the resulting photocyclization the bulky silyl group becoming placed outside the heli~.'~' Cobalt complexation of helicenes terminating in cyclopentadienyl units could lead to optically active polymers possibly with unusual electrical magnetic and optical properties.16' Twisted Hydrocarbons.The diphenyltetrabenzanthracene (34) has been shown by X-ray diffraction to be twisted by 66" spread along the anthracene structure. The helicity of (34)along the planes of the rings is in contrast to the helicenes where the twist is perpendicular to the ring ~1anes.l~~ Distortion of the geometry of the anthracene rings in 1,8-diarylanthracenes causes unexpectedly low barriers to rota- tion of the aryl gro~ps."~ 16' A. Bashir-Hashemi H. Hart and D. L. Ward J. Am. Chem. Soc. 1986 108 6675. 166 A. Sudhakar and T. J. Katz Tetrahedron Lett.1986,27 2231. 167 A. Sudhakar and T. J. Katz J. Am. Chem. Soc. 1986 108 179. A. Sudhakar. T. J. Katz. and B.-W. Yang J. Am. Gem. Soc.. 1986 108 2790. 169 R. A. Pascal jun. W. D. McMillan and D. Van Engen J. Am. Chem. Soc. 1986 108 5652. 170 H. 0. House J. A. Hrabie and D. VanDerveer J. Org. Chem 1986,51 921. Aromatic Compounds 165 6 Cyclophanes Distortion of the Benzene Ring.-Probably the best compounds for studying the effects of distortion of aromatic rings are the simple [nlparacyclophanes preparable by U.V. irradiation of corresponding Dewar benzenes. [SIParacyclophane (35 n = 5) is a highly unstable species but substitution by ester and methyl groups increases the ~tabi1ity.l~~ The X-ray crystal structure of a derivative of [6]paracyclophane reveals the expected severe distortion of the benzene rings into a boat c~nformation.'~~ A consequence of this distortion in [6]paracyclophane itself are the facile addition reactions with N-phenyltriazolinedione or bromine oxidation with m-chloroperoxy- benzoic acid and thermal rearrangement to a spirotriene (36 n = 6) presumably uia benzylic bond horn~lysis,'~~ In contrast conditions of flash vacuum thermolysis can be used to prepare [7]- and [8]-paracyclophane from the appropriate spirotrienes (7 and 80% yields respecti~ely).'~~ 2-[6]Paracyloph-3-ene (37) has been prepared; U.V.evidence suggests an increase in the benzene ring distortion compared with [6lparacyclophane.174 Using a new method for establishing the degree of aromaticity based on measure- ments of quadrupolar couplings in the deuterium n.m.r.spectrum [5lmetacyclo-phane is shown to be fully aromatic despite its strongly distorted ring.'75 Ring Interactions.-U.v. irradiation of quadruple-layered cyclophanes gave revers- ible formation of a cage structure between the central rings. The outer rings are thought to stabilize the cage ~tructure.'~~ Syntheses have been reported of syn- [2.2]metacyclophanes (38) and (39). The former was prepared from trithia p3]-(1,3,5)~yclophane'~~ and the latter by ring-contraction of a chromium-complexed dithia prec~rsor.'~~ Both rearrange to the anti-conformer with an activation energy of ca. 20 kcal mol-'. A strong anchimeric assistance to the ionization of the tosylate (40) during acetolysis has been attributed to a T-T interaction between the rings as indicated.179 171 G.B. M. Kostermans W. H. de Wolf and F. Bickelhaupt Tetrahedron Lett. 1986 27 1095. 172 Y. Tobe K.-I. Ueda K. Kakiuchi Y. Odaira Y. Kai and N. Kasai Tetrahedron 1986 42 1851. 173 L. W. Jenneskens W. H. de Wolf and F. Bickelhaupt Tetrahedron 1986,42 1571. 174 Y. Tobe K.-I. Ueda K. Kakiuchi and Y. Odaira Angew. Chem. Znt. Edn. Engl. 1986 25 369. 175 P. C. M. van Zijl L. W. Jenneskens E. W. Bastiaan C. MacLean W. H. de Wolf and F. Bickelhaupt J. Am. Chem. Soc. 1986 108 1415. 176 H. Higuchi E. Kobayashi Y. Sakata and S. Misumi Tetrahedron 1986 42 1731. 177 Y. Fujise Y. Nakasato and S. Ito Tetrahedron Lett. 1986 27 2907.178 R. H. Mitchell Pure Appl. Chem. 1986 58 15. '79 J. Nishimura Y. Okada and A. Oku J. Org. Chem. 1986 51 1838. 166 R. McCague Macrocyclophanes.-[2.2.2]Paracyclophane (41) forms a stable dianion but which is neither paratropic nor diatropic since steric requirements force one ring at any given time to be out of plane of the remaining delocalized system."' Large-ring [9 to 151 paracyclophanes have been prepared by the photolysis of large-ring 2-phenylcycloalkanones the mechanism being homolysis adjacent to the carbonyl group and recombination at the para-position on the benzene ring.'81 Encapsulation within a zeolite matrix can improve this process.'** Macrocyclophanes have been of interest for the synthesis of [3]~atenanes,'~~ and those with three linking chains for the study of conformational interconversions of the chain position which can occur by a chain passing either between or over the aromatic rings.'84 Other Studies.-Features of the absorption spectra of cyclophanes have been re~iewed.'~'The possibility of forming organic electrical conductors by linking [2n] cyclophane units to give a one-dimensional polymer has been explored using ruthenium copper or silver complexation to link the units.'86 Also by connecting together anthracene units the resulting v-orbital interactions between adjacent units might enable the construction of organic erni icon duct or^.'^^ [2.2]Metacyclophanes where one chain is longer than the other owing to heteroatom substitution have helicity.The enantiomers are separable and may be useful for chiral induction of chemical reactions.'" 7 Non-benzenoid Aromatic Systems Theoretical Studies.-Haddon has demonstrated using v-orbital axis vectors analy- sis (POAV) that rehybridization of the orbitals in bridged annulenes can improve v-bonding overlap.189 The rehybridization is particularly large at the 4-position of 180 D.Tanner 0.Wennerstrom U. Norinder K. Mullen and R. Trinks Terrahedron 1986 42 4499. 181 X. Lei C. Doubleday jun. and N. J. Turro Tetrahedron Lett. 1986 27 4675. X.-G. Lei C. E. Doubleday jun. M. B. Zimmt and N. J. Turro J. Am. Chem. Soc. 1986 108 2444. K. Rissler G. Schill H. Fritz and W. Vetter Chem. Ber. 1986 119 1374. I84 A. B. Brown and H. W. Whitlock jun. J. Am. Chem.Soc. 1986 108 3509. 185 J. Ferguson Chem. Rev. 1986 86 957. 186 R. T. Swann A. W. Hanson and V. Boekelheide J. Am. Chem. Soc. 1986 108 3324; R. H. Voegeli H. C. Kang R. G. Finke and V. Boekelheide ibid. p. 7010; V. Boekelheide Pure Appl. Chem. 1986 58 1; H. Schmidbaur W. Bublack B. Huber G. Reber and G. Muller Angew. Chem. IN. Edn. Engl. 1986,25 1089. 187 J. Fiedler W. Huber and K. Mullen Angew. Chem. Znt. Edn. Engl. 1986 25 443; D. Bender H. Unterberg and K. Mullen ibid. p. 444. 188 F. Vogtle J. Struck H. Puff P. Woller and H. Reuter J. Chem. Soc. Chem. Commun. 1986 1248. 189 R. C. Haddon J. Am. Chem. Soc. 1986 108 2837; R. C. Haddon and L. T. Scott Pure Appf. Chem. 1986 58 137. Aromatic Compounds 1,4,7-methino[ l01annulene (42) and explains the high degree of aromaticity in this annulene.For cyclic 4n-anions a relationship has been established between the proton n.m.r. ring-current anisotropy with the ratio of carbon-1 3 n.m.r. chemical shifts and charge.'" Ab initio molecular orbital calculations of 4n-annulenes by Haddon indicate that only cyclobutadiene exhibits a strong resonance destabilization and surprisingly the hypothetical planar cis-[ 12lannulene would have a small positive resonance energy.'" Interestingly heat of hydrogenation measurements of the fused system (43) a [4n]annuleno[4n)annulene indicate a positive resonance energv. suggesting delocalization around the [4n + 21 periphery in variance with theoretical predi~tions.''~ Studies of [4n + 2]annuleno[4n + 2lannulenes such as (44) indicate that delocalization in the neutral hydrocarbons is governed by the two subunits but by the monocyclic perimeter in ionic Non-alternant Fused-ring Systems.-A new mechanism for the azulene to naphthalene rearrangement proposed by Dewar and Men.from MNDO and MIND0 calculations is shown in Scheme 14.'94 Scheme 14 Studies by Hafner et al. on the 127r hexamethylheptalenes e.g. (45) which exist as optical isomers owing to twisting by the eclipsed methyl groups have shown them to exhibit a barrier to both racemization and bond rearrangement in the order of 20-30 kcal m~l-'.'~~ Derivatives of cyclohepta[ eflheptylene reveal a similar bond rear rang ern en^'^^ (45) (46) 190 B. Eliasson U. Edlund and K. Mullen J.Chem. Soc. Perkin Trans 2 1986 937. 191 R. C. Haddon Pure Appl. Chem. 1986 58 129. I92 W. D. Roth H.-W. Lennartz E. Vogel M. Leiendecker and M. Oda Chem. Ber. 1986 119 837. 193 W. Huber. K.Mulllen C. Schneiders M. lyoda and M. Nakagawa Helu. Chim. Am 1986. 69 949. 194 M. J. S. Dewar and K.M. Merz,jun. J. Am. Chem. SOC.,1986 108 5142. 195 K. Hafner and G. L. Knaup Tetrahedron Lett. 1986 27 1665. 196 K. Hafner G. L. Knaup and H. J. Linder Angew. Chem. Int. Edn. Engl. 1986 25 633. 168 R. McCague Small-ring Aromatic Cations.-Despite the inherent stability of the cyclopropenyl cation it is stabilized by welectron donating substituents such as amino or hydroxyl groups. Electron-withdrawing groups are de~tabilizing.'~~ The cyclopropenyl cation is also stabilized by out-of-plane cyclopropyl substituents and in-plane phenyl groups.19* The remarkably stable pagodane dication (46) is obtained simply by prolonged chlorosulphonylfluoride-antimony pentafluoride treatment of the hydro- carbon.Its structure can be rationalized as a 2-electron aromatic system with the worbitals in the plane of the ring. Calculations indicate a rectangular structure with bond orders of ca. 1.5 and 0.5.'99 Higher Annu1enes.-The anion of the bridged biphenylene (19) is found to possess a 10~ aromatic system the inner proton resonating at S -2.79.200 9b-Methyl-9bH- benz[ cdlazulene (47) a 12.rr-electron system has been synthesized the methyl group having been introduced by methylation of 4,5-dihydro-3H- benz[ cdlazulene.Antiaromaticity is evident from the S 4.75 resonance of the central methyl group.*'' Reductive methylation of aceheptylene occurs at the inner angular carbon allowing the synthesis of a range of annulenes with novel .rr-perimeters; examples are the strongly diatropic hydrocarbons (48) and (49).202 A consequence of the asymmetry of hydrocarbons such as (47)-(49) is that one of the bond-shift forms can be favoured over the other. Thus the form (47) is that favoured and bond fixation reduces the diatropicity of (48). Vogel et al. have reported the synthesis of syn-and anti-bismethano[ 14lannulenes which have a phenanthrene perimeter.203 The syn-isomer (50) is diatropic but less so than the anthracene analogue; the anti-isomer has olefinic properties owing to the high torsional angles.Quinones of homoazulene (1,5-methano[ l01annulene) had U.V. spectra like those of quinones derived from azulene rather than an alternant hydrocarbon illustrating the homoconjugative interaction in these quinones.2" Properties of the radical anion of 1,5-methano[ lO]annulene are also attributed to a homoconjugative intera~tion.~~' 197 A. C. Hopkinson and M. H. Lien J. Am. Chem. SOC.,1986 108 2843. 198 R. A. Moss S. Shen K. Krogh-Jespersen J. A. Potenza H. J. Schugar and R. C. Munjal J. Am. Chem. SOL,1986 108 134. 199 G. K. S. F'rakash V. V. Krishnamurthy R. Herges R. Bau H. Yuan G. A. Olah W.-D. Fessner and H. Prinzbach J. Am. Chem. SOL,1986 108 836. 200 C. F. Wilcox jun. and D. A. Blain Tetrahedron 1986 42 6389.20 I K. Hafner and V. Kuhn Angew. Chem. Znt. Edn. En@ 1986 25 632. 202 G. Neumann and K. Mullen J. Am. Chem. SOC.,1986 108 4105; K. Mullen Pure Appl. Chem. 1986 58 177. 203 E. Vogel W. Puttmann W. Duchatsch T. Schieb H. Schmicker and J. Lex Angew. Chem. Znt. Edn. Engl. 1986 25 720; E. Vogel T. Schieb W. H. Schulz K. Schmidt H. Schmickler and J. Lex ibid. p. 723. 204 L. T. Scott and M. Oda Tetrahedron Lett. 1986 27 779. 205 F. Gerson J. Knobel A. Metzger L. T. Scott M. A. Kirms M. Oda and C. A. Sumpter J. Am. Chem SOC.,1986 108 7920. Aromatic Compounds The paratropic doubly bridged [24]annulene (51) has been synthesized uia Wittig condensations and reductive coupling.206 A series of related methano-bridged bis- dehydro [181 [ZO] [22] and [24]-annulenes were found to be paratropic or diatropic depending on the number of ~-electrons,~~~ but a series of bisdehydrodibenzo-annulenes were neither dia- nor paratropic,208 presumably owing to bond fixation by the benzo-fusion.The [24]annulene (52) was prepared by a nickel complex induced tetramerization of byclopr~pabenzene.~~~ 206 K. Yamamoto M. Shibutani S. Kuroda E. Ejiri and J. Ojima Tetrahedron Lett. 1986 27 975. 207 J. Ojima E. Ejiri T. Kato S. Kuroda S. Hirooka and M. Shibutani Tetrahedron Lett. 1986,27 2467. 208 J. Ojima K. Yamamoto T. &to and K. Wada Bull. Chem Soc J~R,1986,59,2209. *09 R. Mynott R. Neidlein H. Schwager and G. Wilke Angew. Chem Inr. an. EngL 1986,25 367.

ISSN:0069-3030    

DOI:10.1039/OC9868300147

出版商:RSC    

年代:1986

数据来源: RSC