ISSN:0069-3030    

DOI:10.1039/OC97976FX001

出版商:RSC    

年代:1979

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC97976BX003

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (ii) X-Ray Crystallography By S. NEIDLE Department of Bioph ysics Kings College (University of London 1 26-29 Drury Lane London WC2B 5RL The literature of organic crystal structures continues to grow at a steady pace of about 2000 newly reported structures per annurn. As in previous years the reader is referred to the latest extensive bibliographies from the Cambridge Crystallographic Data Centre.’ The detailed files of the Data Centre are now available on computer installations world-wide and are extensively used for speedy access to details of all published organic molecular structures.2 As detailed below this powerful facility is being utilised as a structural tool in its own right capable of extracting new and meaningful data by means of structural correlations.Several trends in organic crystallography have become apparent during the past several years. The power of spectroscopic methods is now such that X-ray crystal- lography only rarely needs to be called upon as a determinant of molecular structure its traditional role in organic chemistry. Thus crystallographers are increasingly defining new areas for their attention. Studies relating structure to theoretical calculation and prediction either for bonding geometry or molecular conformation are of particular interest at present as are analyses involving solid-state reactivity uis h uis structure. It is also increasingly apparent that small-molecule as well as protein crystallography can provide important data on biological molecules and such molecules serve as models for biological systems.Thus organic crystallography is now moving rapidly into the phase of its development where the crystallographer himself defines his problems and performs his own chemistry and biochemistry as well as solving and analysing his structures. 1 Molecular Structure and Bonding A number of studies have been concerned with the influence of crystal structure (i.e. non-bonded forces including inter-molecular hydrogen bonds) on molecular con- formation. In one approach the conformational polymorphism of N-(p-chloro-benzy1idene)-p- chloroaniline has been e~amined,~ by combining molecular orbital calculations with an analysis of the molecular packing in the two space groups found ‘Molecular Structures and Dimensions’ Crystallographic Data Centre Cambridge University 1978 Vol.9; 1979 Vol. 10. * F. H. Allen S. Bellard M. D. Brice B. A. Cartwright A. Doubleday H. Him,T. Hummelin B. G. Hummelink-Peters,0.Kennard W. D. S. Motherwell,J. R. Rodgers and D. G. Watson Acra Cryst. 1979 B35.2331. J. Bernstein and A. T. Hagler J. Amer. Chem. Soc. 1978,100,673. 14 S. Neidle for this molecule. Extensive conformational polymorphism has been noted in the three crystal forms of iminodiacetic acid with each showing a distinct molecular conf~rmation.~ Intermolecular forces in hydrogen-bonded crystals of carboxylic acids and amides have been examined' with consistent-force-field calculations. Ab inifio molecular orbital calculations of hydrogen bonds in carbohydrates6 suggest that for 0-H -* 0systems the energy minimum is not at a 180" bond angle but at -163"; neutron-diffraction data gives an average of 166".The Cambridge data files have been used for an alternative approach to the problems of conformational variability in crystals based on the examination of all structures determined and employing standard statistical methods to analyse the data.7 In one instance the geometry of the p-1'-aminofuranoside ring (in nucleic acids and their constituents) was examined in some 100 structures and statistically meaningful correlations among several geometric parameters were noted.' The geometry of substituent- induced deformation of bond length in cyclopropane-containing structures has recently been investigated;' the trends found are not large but support the predic- tions of molecular orbital theory.The structure analysis of 10,10-dimethyl-3,4- dioxatricyclo[5.2.1 .0'*5]decane-2-spiro-2'-adamantane(1)has led to a comparison of C-0 and 0-0 bond lengths in small rings as a function of ring size." The exploration of reaction pathways via examination of relevant crystal struc- tures is proving to be most instructive. Dunitz and his colleagues have approached the problem by examining related compounds that all react in the same manner but say with varying rates. A crystallographic study of four compounds that display aspects of the keto-acid-hydroxy-lactoneisomerization (2) has shown two to be on OQ OH the ring-opened side but with short 0 --C=O distances.The two ring-closed compounds have lengthened C-0 bonds.' ' Explorations of solid-state reactions continue to be a fruitful area; for example a plausible explanation in terms of differences in molecular packing has been advanced for the racemic +chiral thermal conversion of 2,6-dimethyl-4-(a,a-diphenylmethylene)cyclohexa-2,5-dien-1-one.12 X-Ray data on eight derivatives of cis-4a,5,8,8a-tetrahydro-l,4-naphtho-quinone have been correlated with their solid-state phot~chemistry.'~ J. Bernstein Actu Cryst. 1979 B35 360. 'S. Lifson A. T. Hagler and P. Dauber J. Amer. Chem. Soc. 1979 101,5111. M. D. Newton G. A. Jeffrey and S. Takagi J. Amer. Chem. Soc. 1979,101,1997. 'P.Murray-Rust and W. D. S. Motherwell Acfu Cryst.,1978 B34 2518 2527.a P.Murray-Rust and W. D. S. Motherwell Actu Cryst. 1978 B34,2534. F. H. Allen Actu Cryst. 1980 B36 81. lo P. B. Hitchcock and I. Beheshti J.C.S. Perkin IZ 1979 126. l1 D.J. Chadwick and J. D. Dunitz J.C.S.Perkin ZZ 1979 276. l2 T.W.Lewis I. C. Paul and D. Y. Curtin Actu Cryst.,1980 B36,70. l3 J. R. Scheffer and A. A. Dzakpasu J. Amer. Chem. Soc. 1978,100,2163. Physical Methods and Techniques -Part (ii) X-Ray Crystallography 15 It is not uncommon for crystal structures to provide the theoretician with new phenomena to explain. This is well illustrated by for example [3]-and [4]-rotane (3)and (4) both of which have abnormally short mean central C-C bond distances of 1.470 A suggesting that there are v-bonding contributions in these structure~.'~ The central C-C bond length in 9,9-bitriptycyl has been found to be shorter than predicted by force-field calculations even though these correctly predicted other aspects of the ge~metry.'~ An authentic example of an intramolecular 0-H * -v hydrogen bond has been reported in the crystal structure of 2,6-diphenylphenol.l6 2 Natural Products and Biological Molecules The natural world continues to cause surprises with the bizarre nature of the secondary metabolites of plants. Noteworthy among these crystal structures are mintsulphide (9 a sulphur-containing sesquiterpene from peppermint oil," and solanscone (6) a novel sesquiterpene ketone from Nicotiana tabacum (as the oxime).18 DL-Bi-( 0-trimethyl-cis- brazilane) (7) a derivative of brazilin has an H (8) (7) l4 C.Pascard T. Prange A. de Meijer W. Weber and J.-P. Barnier J.C.S. Chem. Comm. 1979,425. lS M. H. P. Ardebili D. A. Dougherty K. Mislow L. H. Schwartz and J. G. White J. Amer. Chem. SOC. 1978,100,7994. l6 K. Nakatsu H. Yoshioka K. Kunimoto T. Kinugasa and S. Ueji AcfaCryst. 1978 B34 2357. '' T. Yoshida S. Muraki K. Takahashi T. Kato C. Kabuto,T. Suzuki T. Uyehara andT. Ohnumen J.C.S. Chem. Comm. 1979,512. 18 T. Fujimori R. Kasuga H. Kaneko S. Sakamura M. Noguchi A. Furusaki N. Hashiba and T. Matsumoto J.C.S. Chem. Comm. 1978 563. 16 S. Neidle expected staggered conformation; however the three central bonds C-10-C-11 C-11-C-1 l’ and C-ll’-C-lO‘ are all longer than normal C(sp3-sp3) bonds with the central one of length 1.61 This is most likely a result of the steric overcrowding in the molecule.An important code of recommended practice and standardized procedures for the assignment of absolute configurations has been established.20 The use of the principles laid down in this code has led to the revision of the chirality originally assigned for clerodin,2’ one of two errors found so far among the ca. 900 absolute configurational assignments derived by X-ray crystallography that are in the lit- erature. The analysis of steroid structures continues to be an active topic. The two independent molecules of 3p-acetoxy-l6/3-methylpregn-5-en-20-one have their side-chains in very different conformations;22 energy calculations show that the minimum is a broad one. The careful analysis of the structures of four oestranes in the light of conformational data on other 1,3,5(10)-oestratriene structures has shown the role of conformational transmission in that exocyclic non-bonded interactions are crucial factors in determining conf~rmation.~~ The structures of three 4,4,14a-trimethyl-19(10 -B 9)-abeo- 5P,9p,lOa-pregnane-6,1 l-diols [typified by (8)] have been dete~mined.~~ Their conformations are as predicted by force-field methods which have also been used to analyse puckering parameters and steric energies.Interest in structural studies of small peptides has been revitalized by the dis- covery and subsequent intensive biochemical study in many laboratories of the enkephalins. These are pentapeptides that occur naturally in animal brains that mimic the action of morphine and which bind to the opiate receptor.Several crystallographic analyses of enkephalin fragments have been reported. The N-terminal tripeptide residue Tyr-Gly-Gly exists as a zwitterion with an a-helix-like conformati~n,~~ although no intramolecular hydrogen bonds were observed. The structures of two tetrapeptide enkephalin fragments Tyr-Gly-Gly-Phe and Gly- Gly-Phe-Leu have been determined.26 Their conformations are quite distinct; the former has a Gly-Gly @-turn whereas the latter has a bent conformation without intramolecular head-to-tail interaction. As the p-turn has been suggested to occur for enkephalin itself in solution it has been proposed that Tyr-Gly-Gly-Phe is the biologically active sequence.This and other possible biologically important features have been reported in the crystal structure of [Leus]enkephalin itself .27a However it has now transpired2” that the original diffraction data recorded (from small thin crystals) corresponded to a small sub-cell of the true unit cell. Although it is now apparent that the crystal structure is in fact an average from four closely l9 M. F. MacKay and N. W. Isaacs Tetrahedron 1979,35 1893. ’O D.Rogers and F. H. Allen Acta Cryst. 1979 B35,2823. ’’ D. Rogers G. G. Unal D. J. Williams S. V. Ley G. A. Sim B. S. Joshi and K. R. Ravindranath,J.C.S. Chem. Comm. 1979,97. 22 H.Campsteyn 0.Diderberg L. Dupont and J. Lamotte Actu Cryst.,1979 B35 2971. 23 W. L. Duax D. C. Rohrer R. H. Blessing P.D. Strong and A. Segaloff Actu Cryst. 1979 B35,2656. 24 J. C.A. Boeyens J. R. Bull A. Tuinman and P. H. Van Rooyen J.C.S. Perkin 11 1979 1279. ’’ W. M.Carson and M. L. Hackert Acta Cryst. 1978 B34 1275. 26 T. PrangC and C. Pascard Actu Cryst. 1979 B35 1812. ” (a)G. D. Smith and J. F. Griffin Science 1978,199,1214;(b)T. L.Blundell L. Hearn I. J. Tickle R. A. Palmer B. A. Morgan G. D. Smith and J. F. Griffin Science 1979,205,220. Physical Methods and Techniques -Part (ii)X-Ray Crystallography related molecules it has not as yet been possible to solve the true structure and hence unequivocally to define all the conformational features especially those of the side-chains. Among the several structures of cyclic peptides published during the period under review two are especially worthy of note.The structure of the cyclic decapeptide gramicidin S (as a complex with urea) has finally been solved,28 after many years of effort. It has many of the features predicted in an early as well as some unexpected ones such as an intramolecular hydrogen bond. The conformation of the cyclic decapeptide antamanide is the same as that found in several solvents as well as in several derivatives with variants in the ~ide-chains.~' It has thus been concluded that the conformation found is an intrinsic property of the molecule. The crystal structures of several fragments of the nucleic acid DNA have attracted much attention. The tetranucleotide d(pApTpApT) forms Watson-Crick base-pairs in the solid but not as a continuous fragment of double-stranded DNA.Instead two short segments of base-pairing are formed by each tetranucleotide by means of hydrogen-bonding to two other molecules in the crystal structure. On the other hand the hexanucleotide d(CpGpCpGpCpG) crystallizes as a double-helical Watson-Crick base-paired duplex.32 This structure has a number of remarkable and unexpected features which may well have considerable biological implications; for example the helicity is left-handed rather than right-handed as in the classical model of DNA. ** S. E. Hull R. Karlsson P. Main M. M. Woolfson and E. J. Dodson Nature 1978 275 206. 29 D. C. Hodgkin and B. M. Oughton Biochem. I. 1957,65,752. 30 I. L. Karle,T. Wieland D. Schemer andH. C. Ottenhegm Proc. Nu?.Acad. Sci. U.S.A.,1979,76,1532. 31 M. A. Viswamitra,P. Kennard P.G. Jones G. M. Sheldrick S. Salisbury L. Falvello and Z. Shakked Nature 1978,273 687 32 A. H.-J. Wang G. J. Quigley F. J. Kolpak. J. L. Crawford J. H. van Boom,G. van der Marel and A. Rich Nature 1979,282,680.

ISSN:0069-3030    

DOI:10.1039/OC9797600013

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (iii) N.M.R. Spectroscopy By J.K. M. SANDERS University Chemical Laboratory University of Cambridge Lensfield Road Cambridge CB2 1EW 1 Introduction Last year's Report' was both long and concentrated describing major advances published during 1976-78 in a variety of areas of n.m.r. spectroscopy. This Report on the 1979 literature retains the same format as before but concentrates on the development of those ideas and techniques as tools for solving chemical problems. No attempt has been made to restrict examples to specifically organic applications each section contains illustrations from physical inorganic or biological appli- cations chosen because they are instructive and interesting. 2 Spin-Lattice Relaxation For organic molecules in solution the dominant relaxation mechanism for both 'H and 13Cis dipole-dipole relaxation induced by nearby protons.The relaxation time is given by equation (l),where r is the distance from neighbouring protons and 7,is a correlation time for molecular motion. Thus Tl gives information about mobility or about inter-nuclear distances and both effects have been put to good effect this year in assigning spectra. For example the methine protons of frangulanin (1)are expected to experience similar tumbling rates and so they can be distinguished on the basis of their different distances from neighbouring protons; the methyls which all have the same geometry (and hence the same Cr-6) can be assigned through their differing mobilities.2 Similarly C-18 in asperdiol(2) is the most mobile methylene carbon and has a significantly longer Tl than the ring methylene~.~ As expected from equation (l),the ring methine carbons of (2) relax at half the rate of the methylenes.More quantitatively equation (1)can be used to extract detailed geometrical information particularly when substitution by or selective pulse experiments6 allow the contribution of a particular proton to the relaxation of J. K.M. Sanders Ann. Reports (B) 1978,75 3. * E. Haslinger and W. Robien Monatsh. 1979,110 1011. G. E. Martin J. A. Matson and A. J. Weinheimer Tetrahedron Letters 1979 2195. L. D. Hall K. F. Wong W. E. Hull and J. D. Stevens J.C.S. Chem. Comm. 1979,953. L. M.Jackman and J. C. Trewella J.Amer. Chem. SOC.,1979,101,6428. L. D. Hall K. F. Wong and H. D. W. Hill J.C.S. Chem. Comm. 1979,951. Physical Methods and Techniques -Part (iii) N.M.R. Spectroscopy :H, Ph OR RO @OROR UPh 0 (4) R=COCD3 (3) another nucleus to be determined. In the case of (3) 13Cand "N relaxation rates enabled precise measurement of the hydrogen (deuterium) bond geometry and demonstrated its asymmetry rather c~nvincingly,~ whilst substitution by deuterium at C-5 in (4) gave values for all the inter-proton distances that were in complete agreement with those from neutron-diffraction mea~urements.~All the above examples report suitable control experiments which ensure that indeed dipole- dipole interactions are responsible for the observed effects and all are for molecules that are essentially rigid.More difficult is the determination of mobility given an essentially known geometry. For example interpretation of 13Crelaxation data is crucially dependent on choosing an appropriate value for the C-H bond length in both small organic molecules7 and proteins.* Even then detailed interpretation of relaxation rates in terms of molecular motion is fraught with problem^,^ and should be attempted only by the brave. Paramagnetics are very efficient inducers of relaxation and therefore should be removed from solutions where Tl measurements are contemplated. The most common approach for aqueous solutions is to add EDTA but when this was tried with a solution containing Fe3' and phosphate the Tl of 31P actually shortened because of the formation of ternary EDTA-Fe-Pi complexes.lo An alternative approach that is sometimes successful is extraction with 8-hydroxyquinoline," but the important point is that care must be exercised.Of course paramagnetic effects on Tl may be exploited and one fine example of this -inadvertently omitted from last year's Report [Vol. 75 p. 31 -is the determination of the bound conformation of propionyl-CoA on the metal-containing enzyme transcarboxylase.'2 'R. K. Harris and R. H. Newman Mol. Phys. 1979,38 1315. K. Dill and A. Allerhand J. Amer. Chem. SOC.,1979,101,4376. P.Stilbs and M. E. Moseley J. Magn. Reson. 1979,33,209. lo G. A. Elgavish and J. Granot J. Magn. Reson. 1979,36 147. *' D. H.Live H.R. Wyssbrod A. J. Fischman W. C. Agosta C. H. Bradley and D. Cowburn J. Amer. Chem. SOC.,1979,101,474. C. H.Fung R. J. Feldmann and A. S. Mildvan Biochemistry 1976,15,75. J. K. M. Sanders Experimental Methods.-The search continues in many laboratories for an ideal way of measuring TI values in any given sample. One problem has always been the generation of a good 180” pulse to invert all the nuclear spins but Levitt and FreernanI3 have described T. composite ‘sandwich’ pulse which self-compensates for any errors and which should therefore make the null-point method more reliable. The variable-flip-angle approach to measurement of Tl has been extended into two variants one employing fixed delays between the perturbing and monitoring pulses’4 and the other allowing simultaneous nulling of an interfering HOD ~igna1.l~ A completely different way of removing unwanted resonances is to use spin echoes in TI sequences.16*17 Spin echoes are discussed in detail in Section 5 of this Report.Spin-lattice relaxation in the rotating frame a hitherto rather obscure subject has proved to have a simple application in the study of rapid internal motions and it may well become popular.’* The Nuclear Overhauser Effect.-This has experienced a revival in the guise of n.0.e. difference spectroscopy and is now proving to be perhaps the most subtle and powerful manifestation of spin-lattice relaxation phenomena in organic chemistry. The ‘traditional’ n.0.e. experiment is very powerful and it has been exploited skilfully to determine the structure conformation and absolute configuration of the polypeptide antibiotic ristocetin (mol.wt. 3000),19but it is limited in scope because the signal to be observed must be resolved and because the minimum credible effect using integration is ca. 5%. In n.0.e. difference spectroscopy a control spectrum without n.0.e. is subtracted from the spectrum with n.O.e. so that only spectral changes appear. The signal of interest need no longer be resolved in the normal spectrum and the lower limit of observable effect is determined only by instrument stability. Thus all the protons of the steroids 1-dehydrotestosterone (5) and llp-hydroxyprogesterone (6) have been resolved and assigned using n.O.e.3 in the 0.5-5% range (to ‘see’ between and across rings) in combination with a difference decoupling technique (see Section 9.’’ The same combination of techniques has been used to resolve and assign the protons of tyrocidine A a decapeptide.” l3 M.H. Levitt and R. Freeman J. Magn. Reson. 1979 33,473. l4 R. K. Gupta G. H. Weiss J. A. Ferretti and E. D. Becker J. Magn. Reson. 1979 35 301. R. K. Gupta and P. Gupta J. Magn. Reson. 1979 34 657. l6 J. Hochmann R. C. Rosanske and G. C. Levy J. Magn. Reson. 1979,33,275. D. L. Rabenstein T. Nakashima and G. Bigam J. Magn. Reson. 1979 34,669. l8 D. M. Doddrell M. R. Bendall P. F. Barron pd D. T. Begg J.C.S. Chern. Cornm. 1979,77. l9 D. H. Williams V. Rajananda G. Bojesen and M. P. Williamson J.C.S. Chem. Cornrn.,1979,906 and refs. therein. *’ L.D. Hall and J. K. M. Sanders J.C.S. Chern. Cornrn. 1980,368. *’ M. Kuo and W. A. Gibbons J. Biol. Chem. 1979,254,6278. Physical Methods and Techniques -Part (iii) N.M.R. Spectroscopy 21 Nuclear Overhauser effect difference spectroscopy has also been used22 to assign non-equivalent protons in the primary amide group-CONH2 to study the con- formation of trimethoprim bound to dihydrofolate red~ctase,~~ and to characterize the interaction of ADP with creatine kina~e.~~ Most n.0.e. experiments are carried out under steady-state conditions but in large proteins where spin diffusion eventually dilutes the useful r-6 dependence of the n.O.e. it is helpful to acquire ‘truncated’ n.O.e.’s just after the saturation has begun to build up.25 Alternatively ‘transient’ n.O.e.’s arising from the selective inversion of a single resonance can be useful in geometry measurements9 or spectral assign- ments2’ for organic molecules.Since the build-up of transient and truncated effects depends on the relaxation rates of both nuclei involved the rates of build-up can be used to measure TI values of signals that are otherwise inaccessible because they have large negative n.0.e.’s.26 Finally we come to Chemically Induced n.O.e. or deceptive CIDNP,27an elegant technique for generating enhancements in a small part of the molecule of interest that molecule must (for the present) contain an exchangeable OH or NH proton. To the solution is added an aromatic acceptor and a suitable tertiary amine. Irradiation with light in the probe leads to electron transfer [equation (2)] and the resulting amine radical cation exchanges its now acidic protons (H) with the molecule under study hv Acceptor + R2NCH2Me AT (R2NCHzMe)t (2) The exchanged protons carry into their ‘host’ CIDNP which then imparts negative enhancements to any nucleus that is J-coupled to them and a positive enhancement to protons that are dipolar-coupled to them.This trick has promise both as an assignment tool and as a sensitivity-enhancement method for nuclei such as 15N. 3 Other Nuclei Deuterium,’H.-Direct observation of 2H spectra can be a very powerful way of studying reaction mechanisms and one of this year’s finest examples is the deter- mination of the mechanism and of the conformation of the transition state of the vitamin-D3-previtamin-D3equilibrium.28 Direct comparison of proton deuterium and tritium chemical shifts in intramolecular hydrogen bonds gives a detailed picture of the shape of the potential well easily distinguishing a symmetrical hydrogen bond from two unsymmetrical rapidly interconverting bonds.29 This approach nicely complements Jackman’s,’ which was described in Section 2.Deuterium is an almost ideal nucleus owing to the ease of incorporation into biological molecules the 22 A. G. Redfield and S. Waelder J. Amer. Chem. SOC.,1979 101,6151. 23 P. J. Cayley J. P. Albrand J. Feeney G. C. K. Roberts E. A. Piper and A. S. V. Burgen Biochemistry 1979,18,3886. 24 M. Vasik K. Nagayama K. Wuthrich M. L. Mertens and J.H. R. Kagi Biochemistry,1979,18,5050. 25 G. Wagner and K. Wiithrich J. Magn. Reson. 1979 33 675; A. A. Bothner-By and J. H. Noggle J. Amer. Chem. SOC. 1979,101,5152. 26 S. J. Opella R. A. Friedman M. C. Jarema and P. Lu J. Magn. Reson. 1979 36 81. 27 J. Bargon and G. P. Gardini J. Amer. Chem. Soc. 1979,101,7732. M. Sheves E. Berman Y. Mazur and Z. V. 1. Zaretskii J. Amer. Chem. SOC. 1979,101 1882. 29 L. J. Altman D. Laungani G. Gunnarsson H. Wennerstrom and S. Forsen J. Amer. Chem. SOC. 1978 100,8264. J. K. M. Sanders simplicity of the ensuing spectra and the straightforward interpretation of its relaxation parameters. For example the histidine of lysozyme has been labelled with deuterium by exchange and the 2H nucleus then used to study aggregation of the enzyme;3o deuterium has been incorporated by chemical modification into proteins and glycopro teins for n .m.r. studies. 3' More important for the organic chemist are the isotope effects of deuterium on 'H and 13Cchemical shifts (relaxation effects having been discussed in Section 2). Anet and Dekmezian have very carefully distinguished between equilibrium isotope effects which are due to a change in the population of two or more equilibrating species (usually conformations) and intrinsic effects that are observed in single species.32 As an example of the latter they describe a shift of 0.0137 p.p.m. in H* of the half-cage (7) when X is changed from H to D. Isotope effects on 13Cshifts of carbohydrates in H20 us. D20provide an elegant assignment method,33 and small deuterium effects are strongly amplified at pH values near the pK, allowing extraction of all the microscopic pK values.34 A similar amplification effect has long been known with lanthanide shift reagents3' Nitrogen-15.-Last year's Report stated that this nucleus was probably after 'H and 13 C the most interesting nucleus for many chemists and biochemists its main drawback being low sensitivity.Section 5 describes several methods which may increase its effective sensitivity sufficiently to make "N a reasonably accessible nucleus; chemically induced n.0.e. may also help in this regard. Meanwhile it is possible (with patience and adequate access to spectrometers) to acquire natural- abundance spectra of e.g. reserpine and related alkaloids and to draw up all the expected correlations of chemical shift with structure and c~nformation.~~ Most "N spectra are taken with molecules that have been highly enriched synthetically [see for example (3)] or biosynthetically.Thus measurements of Tl and of the n.0.e. of labelled oxytocin yield information on its conformation," and the mechanism of action of a serine protease has been thoroughly investigated using "N-labelled histidine in the 'catalytic triad'.37 Perhaps most remarkable of all are the "N spectra of biosynthetically labelled bacterial cell walls which supply extra- ordinarily detailed pictures of the chemical and physical similarities and differences 30 J. B. Wooten and J. S. Cohen Biochemistry 1979,18,4188. 31 M.A. Bernstein L. D. Hall and W. E. Hull J. Amer. Chem. SOC. 1979,101 2744. 32 F. A. L.Anet and A. H. Dekmezian J. Amer. Chem. SOC. 1979,101,5449. 33 P. E. Pfeffer K. M. Valentine and F. W. Parrish J. Amer. Chem. SOC. 1979,101 1265,7438. 34 J. J. Led and S. B. Petersen J. Magn. Reson. 1979,33 603. 3s J. K.M.Sanders and D. H. Williams J.C.S. Chem. Comm. 1972,436. 36 S. N. Y.Fanso-Free G. T. Furst P. R. Srinivasan R. L. Lichter R. B. Nelson J. A. Panetta and G. W. Gribble J. Amer. Chem. SOC. 1979,101 1549. 37 W. W. Bachovchin and J. D. Roberts J. Amer. Chem. SOC. 1978,100 8041. Physical Methods and Techniques -Part (iii) N.M.R. Spectroscopy 23 between one species and another.38 It is worth noting that I5Nseems to be far more sensitive to the presence of paramagnetics than are 'H and l3C.'' The great potential in biosynthetic investigations of detecting 15N through its coupling with the common nuclei was discussed in last year's Report.It should be emphasized that the couplings looked for in such experiments must be reliably known or estimated from model experiments; the dangers are stressed in a study of labelled adenine which found that some 'JNcare actually very small indeed and may not be see also Section 5. 'Other' Other Nuclei.-Phosphorus-31 continues to be a powerful probe of intact biological entities. It has been used to monitor the internal pH of the chromaffin granules of adrenal gland and to determine the co-ordination state of the ATP within those granules,4o and also to monitor release of ATP in blood platelet^.^' More exciting possibilities include the simultaneous acquisition of 31P and I3C spectra from a single sample using a probe that is quadruply tuned to both these frequencies and to 'H (for decoupling) and to 2H (lock),42 and obtaining n.m.r.spectra from parts of bodies using probes which simply lie on the skin.43 Isotope effects of l80on 13C and 31Pchemical shifts are proving to be very useful mechanistic tools the former has only been used in organometallic chemistry44 as yet but it should be generally applicable. The latter has rather quickly become an established method in enzyme chemistry.'*45 This year such isotope effects have been used to show that purine nucleotide phosphorylase catalyses exchange of phosphate on a-D-ribose 1-phosphate with C-0 cleavage (rather than the expect- ed P-0 cleavage)46 and to show that in two amino-acyl tRNA synthetases the nucleotidyl-transfer step takes place with inversion at phosph~rus.~~ Oxygen-17 has much organic chemical potential this year's most intriguing example being the direct observation of H30+(quartet JOH= 106 Hz) in cold wet; acidic carbon tetra~hloride.~~ Finally we should note that it is relatively easy to observe 113Cd-113 Cd coupling in suitably labelled samples of the protein metallo- t hionein.50 4 Paramagnetics Shift Reagents and Metal Complexes.-It is a measure of the maturity of the field that there is relatively little of novelty to report on shift reagents. Reuben" has developed a system for the n.m.r.resolution of chiral molecules in aqueous solutions 38 A. Lapidot and C. S. Irving Biochemistry 1979,18,704. 39 M. Kainosho J. Amer. Chem. Soc. 1979,101 1031. 40 H. B.Pollard H. Shindo C. E. Creutz C. J. Pazoles and J. S. Cohen JBiol. Chem. 1979,254 1170. 4.' K. Ugurbil H. Holmsen and R. G. Shulman Roc. Natl. Acad. Sci. USA 1979,76,2227. 42 P.Styles C. Grathwohl and F. F. Brown J. Magn. Reson. 1979 35 329. 43 J. J. H. Ackerman T. H. Grove G. G. Wong D. G. Gadian and G. K. Radda Nature 1980,283,167. 44 D.J. Darensbourg and B. J. Baldwin J. Amer. Chem. SOC., 1979,101,6447. 4s M. C.Summers,Ann. Reports (B),1978,75 391. 46 F.Jordan J. A. Patrick and S. Salamone Jr. J. Biol. Chem. 1979 254 2384. 47 S.P. Langdon and G. Lowe Nature 1979,281,320.48 See for example M. Katoh T. Sugawara Y. Kawada and H. Iwamura Bull. Chem. SOC. Japan 1979,52 3475and refs. therein. 49 G. D. Mateescu and G. M. Benedikt J. Amer. Chem. SOC.,1979,101,3959. J. D. Otvos and I. M. Armitage J. Amer. Chem. SOC.,1979,101,7734. '' J. Reuben J.C.S. Chem. Comm. 1979,68. 24 J. K.M. Sanders a-hydroxy-carboxylic acids form 2 :1complexes with lanthanide ions so the addi- tion of a 1:1 mixture of e.g. D-mandelate [PhCH(OH)COJ and lanthanide to another optically impure a-hydroxy-acid will result in the formation of dia- stereoisomeric complexes with different stabilities an& geometries. Alternatively enantiotopic groups in a prochiral molecule (the methyls of a-hydroxybutyrate or the methylene protons of glycollate HOCH2C02-) can be rendered non-equivalent.’I The fitting of shift data to geometrical models is perhaps becoming less risky as both the models and their statistical evaluation improve.Thus for adamantan-2-one the goodness of fit improves dramatically as the model is refined from a single metal-binding site that is collinear with the carbonyl group to a chemically sensible model with two sites along the carbonyl lone pairs and improves again in a four-site model that minimizes steric interactions between reagent and s~bstrate.’~ The standard Hamilton R test for the statistical evaluation of such geometrical models has been shown to be quite inappropriate and simple alternatives have been propo~ed.’~ Indeed the apparent failure of shift reagents to distinguish diastereo- isomers which was discussed in last year’s Report (p.14 ref. 125) turns out to be only a failure of the statistical method -the use of valid statistics shows that the diastereoisomers were distinguishable after all. It is a matter of taste whether one wants chemical problem-solving to be reduced to such statistics particularly when ‘significance testing [can] only test whether one mathematical model of a real situation fits the data better than another such model. . .. [It] can never determine whether such a model is corre~t.”~ The temperature dependence of €anthanide-induced shifts has given rise to some controversy (see last year’s Report p. 13) but McGar~ey’~ has now confirmed theoretically that the dependence should indeed be approximately and not exactly TP2.However in cases where reagent-substrate binding is bi- or ter-dentate the exchange rate becomes so low that it is directly observable in the form of line broadening and separate free/bound spectra.In such cases it is possible not only to measure temperature dependences of the shifts directly but also to determine whether the exchange mechanism is associative or dissociative.” Biologically oriented applications of paramagnetic effects include the deter- mination of conformation of enzyme-bound propionyl-CoA already referred to12 and the assignment of the five indole N-H resonances of hen egg-white ly~ozyme.’~ N.m.r. spectroscopy of haems has now developed to the point where it is detecting localized conformational flexibility in cytochromes using a methyl group attached to the haem as reporter,” and is giving exquisite detail of electronic structure co- ordination chemistry and geometry of complexes in model porphyrins and real proteins.’* 52 R. J. Abraham D. J. Chadwick L. Griffiths and F. Sancasson Tetrahedron Letters 1979,4691. s3 M. F. Richardson,S. M. Rothstein and W.-K.Li J. Magn. Reson. 1979,36 69. s4 B. R. McGarvey J. Magn. Reson. 1979 33,445. ” L. F. Lindoy and H. W. Louie J. Amer. Chem. SOC.,1979 101,841. 56 R. E. Lenkinski,J. L. Dallas and J. D. Glickson J. Amer. Chem. Soc. 1979,101 3071. ” P. D. Burns and G. N. LaMar J. Amer. Chem. SOC.,1979,101. 5844. 58 D. L. Budd G. N. LaMar K. C. Langry K. M. Smith and R. Nayyir-Mazhir J.Amer. Chem. SOC.,1979 101 6091 and references therein. Physical Methods and Techniques -Part (iii) N.M. R. Spectroscopy 25 C1DNP.-Three contributions have captured this Reporter’s imagination. Chem- ically Induced n.0.e. has been described in detail in Section 2 of this report. The detection of CIDNP with a time resolution of microseconds after a laser flash was achieved” by first saturating the equilibrium magnetization by a series of pulses then a laser flash of several ns duration is followed by a variable delay (to allow evolution of CIDNP) and an r.f. pulse to give the n.m.r. signal. Only pure CIDNP responses are observed and they can be monitored from 1gs after the flash. The potential for mechanistic chemistry is clearly very significant.Finally a series of papers from Kaptein’s laboratory developing laser photo-CIDNP as a way of simplifying protein spectra (see last year’s Report p. 15) has culminated in selective detection of the single tryptophan in bovine pancreatic phospholipase A2and the use of that tryptophan to characterize a pH-dependent conformational change.60 5 New Experimental Methods Last year’s Report highlighted two-dimensional (2-D) n.m.r. and high-resolution solid-state n.rn.r. as fundamental developments that would soon have a great impact on many areas of chemistry and indeed the application of these techniques is already moving from physics into organic chemistry Thus all the geminal and vicinal proton coupling constants in a steroid have been resolved by 2-D J spectroscopy; the sensitivity of ”N n.m.r.has been increased in some cases by one hundred fold using population-transfer tricks; solid-state chemical reactions at catalyst surfaces have been observed. This is only the beginning of a new phase in n.m.r. spectroscopy which will develop rapidly in the next few years as the implications are digested by the organic chemist. Two-dimensional (2-D) and Spin-echo Techniques.-As explained more fully in last year’s Report 2-D spectra display the response of the nuclear spins to two different sets of frequencies in contrast to l-D(traditional) spectra which are a function of only one frequency. As a bonus most 2-D techniques are based on spin-echo methods which means that all effects due to inhomogeneity of the magnetic field are removed and thus that linewidths are determined only by the spin-spin relaxation time T2.2-0 J Spectroscopy. A simple pulse sequence i.e. 9OO-delay-180°-delay-collect FID gives spin-echo spectra in which the signal phases depend on the size and number of J couplings. Repetition of the sequence with a set of different delays gives after suitable manipulation of the data,’ spectra in which chemical shifts and coupling constants are separated in different dimensions (for weakly coupled systems). This leads of course to the resolution of signals that are otherwise hopelessly overlapping. The most spectacular use of proton-proton 2-D J spectro-scopy known to the Reporter (in January 1980)is shown in Figure 1 the spectrum allowed the measurement of all the chemical shifts and the geminal and several long-range couplings of the steroid l-dehydrotestosterone (5),61 but others will 59 G.L. Closs and R. J. Miller J. Amer. Chem. SOC.,1979,101 1639. 6o E.H.J. M. Jansen G. J. M. van Scharrenburg A. F. Slotbloom G. H. de Haas and R. Kaptein J. Amer. Chem. SOC.,1979,101,7397. 61 L. D. Hall J. K. M. Sanders and S. Sukumar J.C.S. Chem. Comm. 1980,366. J. K.M. Sanders / I / Figure 1 Partial spectra (400MHz) of 1-dehydrotestosterone (5) (data are from unpublished spectra and from ref. 61). (a) Normal one-dimensional spectrum. (6) Two-dimensional J spectrum of the same region. (c) ‘Proton-decoupled’ proton spectrum obtained by summing all the two-dimensional cross-sections onto the chemical-shift axis.(d)Some representative cross-sections showing the multiplet structure of individual proton resonances surely follow. In addition as heteronuclear couplings behave like chemical shifts in the spin-echo experiment it is possible to remove (without a decoupler) either all the homo- or all the hetero-nuclear couplings from a proton at will merely by changing the angle of projection of the proton in the 2-D spectrum.62 It is possible also to achieve 13C-lH 2-D J spectros~opy,~~ in which all the JCHappear in one dimension and the 13Cchemical shifts in the other? There are several technical problems associated with 2-D J spectroscopy some of which have yet to be solved satisfactorily. The most important (apart from the difficulty of second-order spectra) is that the spectra experience a ‘phase twist’ around each peak.In early work this was dealt with by plotting absolute value (AV) mode? spectra but these have the disadvantage of inducing line broadening and generating long ‘tails’ around intense peaks. One way round the problem is to use a * Other nuclear pairs are possible of course. t AV = (real2+imaginary*)‘ 62 L. D. Hall and S. Sukumar J. Arner. Chem. Soc. 1979,101,3120; J. R. Everett D. W. Hughes A. D. Physical Methods and Techniques -Part (iii) N.M.R. Spectroscopy Lorentzian to Gaussian transformation for the AV another is to plot the power spectrum (AV’) which cuts off tails but also distorts multiplets so that a 1 :2 1 triplet becomes 1:4 :l.65Better for the ‘H-’H experiment one can phase each signal of interest although some distortions and for the I3C-lH experiment several other possibilities are also available.63 It is possible to remove interfering solvent signals that have long Ti's by a standard 180” pulse followed by a delay before the spin-echo sequence,67 or to decouple during a 2-D J acquisition; the latter turns out to be an experiment fraught with complications and it looks unlikely that it will be of general applicability in organic chemistry.68 Finally 2-D J spectra contain extra spinning side-bands but these are (fortunately) at predictable places.69 2-0 Correlation Spectroscopy.In this form of 2-D spectroscopy both frequency axes contain chemical shifts in the heteronuclear variants suitable pulsing of both the proton and another nucleus yields 2-D spectra in which just one signal appears in the map at the co-ordinate for chemical shifts corresponding to the heteronucleus and its coupled proton (Figure 2a).The advantages of this technique are that the 1 2 3 4 (a) I 23 4 ‘H d ’H Figure 2 (a) Schematic two-dimensional correlation spectrum showing a carbon (8 30) coupled to a proton at S 1.5 and a carbon (6 50) coupled to a proton at S 3.5. (b) Schematic two-dimensional exchange-correlation spectrum showing a proton (X)at S 3 exchang-ing with a proton (Y)at S 2 the latter also exchanging with a proton (2)at S 1.5. heteronucleus is observed with a sensitivity approaching that of protons (by virtue of a cross-polarization effect) that the shifts of coupled nuclei are automatically correlated abolishing many assignment problems and that only the nuclei involved in such coupling will appear in the spectrum.Thus in the 31P-1H correlation experiment only ‘local’ protons that are coupled to 31Pare seen provided that the proton spectrum is fir~t-order.~’ Examples of 13C-lH correlation experiments were given in last year’s Report (refs. 174-176) once the technique becomes established it could eventually be a routine way of acquiring spectra of rare spins. The basis of these experiments is well described by Bodenhausen and Freeman with an intuitive approach that employs a relatively simple physical picture of population levels.” 64 J. C. Lindon and A. G. Ferridge J. Magn. Reson. 1979,36,277. 65 L.D. Hall S. Sukumar and G. R. Sullivan J.C.S. Chem. Comm. 1979,292. 66 M. H. Levitt and R. Freeman J. Magn. Reson. 1979,34,675; L. D. Hall and S. Sukumar ibid. 1980 38,555. 67 L. D. Hall and S. Sukumar Carbohydrate Res. 1979 74 C1. 68 K. Nagayama J. Chem. Phys. 1979,71,4404. 69 G. Bodenhausen S. P. Kempsell R. Freeman and H. D. W. Hill J. Magn. Reson. 1979,35,337. 70 P. H. Bolton and G. Bodenhausen J. Amer. Chem. SOC.,1979,101 1080. 71 G. Bodenhausen and R. Freeman J. Magn. Reson. 1979,36,221. 28 J. K.M. Sanders Homonuclear 2-D correlation methods allow the unambiguous elucidation of chemical exchange pathways72 or assignments of coupling constants.73 As with almost all the 2-D experiments mentioned above and several 1-D experiments that are described at the end of this section these techniques were developed by Ernst in a series of definitive and brilliant papers.In the chemical-exchange experiment7* the slowly exchanging peaks are ‘labelled’ by a 90”pulse allowed to evolve and then are monitored by further pulses. The resulting spectrum (Figure 2b) has two identical axes for proton chemical shift with the main peaks appearing on a diagonal. Peaks representing exchanged magnetization are off -diagonal and instantly show (in this example) that X exchanges with Y and Y with Z. The technique seems to this Reporter to have an appealing simplicity which will make it most valuable. In its present form at least the closely related coupling-correlation-pulse sequence73 gives by contrast spectra that are highly complex and low in effective sensitivity thus limiting its general applicability.Other Spin-echo Techniques. Even without resort to 2-D methods the spin echo can be very useful as it removes effects arising from inhomogeneity of the magnetic field and allows the separation of resonances that have the same chemical shift but different multiplicity or different values of T,. A simple description of these ideas has been published by Raben~tein,~~ and examples of their use include the elimina- tion of both broad17 and sharp7’ interfering resonances (see also last year’s Report p. 17). It is also possible to arrange the spin-echo experiment so that the resulting spectra depend only on instrumentally determined More importantly heteronuclear couplings can be eliminated or scaled down by flipping the abundant spins by 180”between acquisitions of the rare spin (i.e.”C).” This can provide an alternative to decoupling -see also page 29.A spin-echo sensitivity-enhancement technique is described in the following paragraph. Sensitivity Enhancement.-A series of have described methods for greatly increasing the effective sensitivity of nuclei such as 13C 15N,and 29Si. Morris and Freeman78 employed spin echoes to give a cross-polarization effect between protons and the insensitive nucleus. This is the same effect that operates in the 2-D correlation experiments described above; it requires an estimate of the H-X coupiing constant and enhances all X with that (or similar) coupling. The other papers79 employ a selective population transfer from one proton at a time giving a time saving for the coupled ”N of lo2-to lo4-fold.Both techniques allow the pulse rate to be determined by the proton TIrather than the slower X spin TI,and neither is (in principle) very demanding of hardware or software. N.M.R. of Organic Solids.-Last year’s Report described how a combination of ‘magic-angle’ spinning high-power (dipolar) decoupling and cross-polarization ” B. H. Meier and R. R. Ernst J. Amer. Chem. SOC.,1979,101,6441;J. Jeener B. H. Meier P. Bachmann and R. R. Ernst J. Chem. Phys. 1979,71,4546. ’’ K. Nagayama K. Wuthrich and R. R. Emst Biochem. Biophys. Res. Comm. 1979,90,305. 74 D.L.Rabenstein and T. T. Nakashima Anulyt. Chem. 1979,51 1465A. ” D.L.Rabenstein and A.A. Isab J. Mugn. Reson. 1979,36 281. 76 A.Bax A. F. Mehlkoff and J. Smidt J. Magn. Reson. 1979 35 167. ’‘ R.Freeman S. P. Kempsell and M. H. Levitt J. Mugn. Reson. 1979 35,447. 78 G.A.Morris and R. Freeman J. Amer. Chem. SOC.,1979,101,762. 79 H.J. Jakobsen and W. S. Brey J. Amer. Chem. SOC.,1979,101,774;J.C.S. Chem. Comm. 1979,478. Physical Methods and Techniques -Part (iii)N.M.R. Spectroscopy 29 techniques rendered high-resolution 13C spectra accessible from organic solids. Applications published this year include the demonstration of conformational preferences in the solid diethoxycarbonium ion [HC(OEt)2]' by observation of non-equivalent methylene carbons," the observation of solid-state organometallic fluxional processes,81 and a study of the gelation of sickle-cell haemoglobin.82 Significant industrial potential is clearly indicated in observations of toluene adsor- bed on Styrene can be manufactured by alkylation of toluene with methanol over zeolite catalysts and n.m.r.experiments revealed the identity of at least some of the intermediates involved. A neat and simple modification of the standard cross-polarization experiment has allowed Opella's group to observe non-protonated carbons in all that is required is to turn off the proton decoupler very briefly before FID acquisition and the protonated carbons almost instantly broaden. The technique is not only applic- able to solid amino-acids sugars steroids and other organics but sometimes turns out to be quicker for solid proteins than for protein solutions giving linewidths of ca.20 Hz. Finally it should be noted that it is possible to carry out double cross-polarization experiments from 'H to 13C to 15N (or from 'H to "N to "C) enabling either the observation of the natural-abundance 13C nuclei that are directly attached to a 15N label or the direct measurement of the relative concentration of 1sN-13C and lSN-l2C pairs without separation or purification of the solid This has opened the way for some fine biosynthetic and metabolic as the experiment monitors the history of a bond rather than an atom in an even more direct way than the 13C-2H methods discussed in last year's Report (p. 8). Miscellaneous.-Selective excitation of a single resonance using DANTE was described in last year's Report on p.19. Extensions this year include its use to generate transient n.0.e.'s2' and a slight modification to yield off -resonance de- coupled ~pectra.~ An alternative named CASS" has been described which does not require such modern computer control but instead needs a rather good decoupler system.86 Other new data-acquisition methods include coils for body surfaces,43 the simultaneous observation of 13C and 31P,42and improved ways of noise-decoupling which do not cause overheating of the ample.'^*^^ The flow of data-processing tricks also continues. A simple resolution-enhance- ment routine which requires no programming has been proposed,88 and Marshall has shown that a plot of absorption us. dispersion for a broad line will give valuable information on the broadening mechanism Two groups have used * A clever allusion to the senior author's history.J. R. Lyerla C. S. Yannoni D. Bruck and C. A. Fyfe J. Amer. Chem. SOC. 1979,101,4770. J. R. Lyerla C. A. Fyfe and C. S. Yannoni J. Amer. Chem. SOC. 1979,101 1351. J. W. H. Sutherland W. Egan A. N. Schecter and D. A. Torchia Biochemistry 1979,18 1797. M. D. Sefcik J. Amer. Chem. SOC. 1979,101,2164. 84 S. J. Opella M. H. Frey and T. A. Cross J. Amer. Chem. SOC.,1979,101 5856. 85 (a)J. Schaefer R. A. McKay and E. 0.Stejskal J. Magn. Reson. 1979,34,443; (6)J. Schaefer E. 0. Stejskal and R. A. McKay Biochem. Biophys. Res. Comm. 1979 88 274. 86 G. T. Andrews I. J. Colquhoun B. R. Doggett W. McFarlane B.E. Stacey and M. R. Taylor J.C.S. Chem. Comm. 1979,89. " V. J. Basus P. D Ellis H. D. W. Hill and J. S. Waugh J. Mugn. Reson. 1979 35 19. 88 B. Clin J. de Bony P. Lalanne J. Blais and B. Lemanceau J. Magn. Reson. 1979,33,457. A. G. Marshall and D. C. Roe J. Mugn.Reson. 1979,33 551. 30 J. K.M. Sanders decoupling difference spectroscopy to simplify and assign spectra 20,21 a spectrum with decoupling is subtracted from one without leaving responses only from the decoupled nuclei. This is particularly useful when the resonances are not otherwise resolved. ‘Conventional’ flow n.m.r. has proved to be useful for studying reactions that are too fast for standard n.m.r. techniques but which are slow on the time-scale of FID collection for example it is possible at -4O”C to see intermediates in the nucleophilic substitution of 2,4,6-trinitroanisole by b~tylamine.’~ Ernst has now developed a theory and tested it experimentally for stopped-flow n.m.r.when chemical evolution is occurring on the time-scale of one FID collectton i.e. rates of around 50-100 1mol-’ s-’.~’ Characteristic line shapes quite different from those seen in exchange equilibria were predicted theoretically and then observed experimentally. The beautifully designed apparatus achieved a dead time of only ca. 2 ms by abandoning the idea of a sample tube the receiver coil was simply wound around the mixing chamber.” The determination of molecular geometry by dissolving a compound in a nematic solvent to restore some dipolar coupling interactions is a well-established technique.However in a definitive paper from Diehl et al. the structure of [l-13C]benzene has been determined with a precision of better than 0.001Angstroms for all the inter- atomic ?;his paper discusses lucidly and in great detail all the problems which may arise from for example vibrational motion. Ernst has shown that geometrical information can be re-introduced into nematic-phase proton-decoupled 13 C spectra by the selective introduction of 2H or 15N. These added nuclei induce splittings in the 13C signals that can be directly converted into distance inf~rmation.~~ In the same paper a 2-D J technique is also described that was used to give geometrical inf~rmation.~~ The principles of spin imaging (also called spin mapping or Zeugmatography) were outlined in last year’s Report.The technique is potentially of medical importance if it can be made sufficiently sensitive that it can map portions of the body in a short time. To this end Ernst has carried out a detailed theoretical study of the potential sensitivity characteristics of the various different imaging methodsg4 An imaging method has been described which is based on 2-D n.m.r. and n.m.r. images have been obtained both from water flowing in the pores of ceramics96 and from solids.97 90 C. A. Fyfe S. W. H. Darnji and A. Koll J. Amer. Chem. Soc. 1979,101,951. 91 R. 0.Kuhne T. Schaffhauser,A. Wokaun and R. R. Ernst J. Magn. Reson. 1979,35,39. 92 P. Diehl H. Bosiger and H. Zirnrnerrnann J.Magn. Reson. 1979,33 113. 93 A. Hohener L. Muller and R. R. Ernst Mol. Phys. 1979,38,909. 94 P. Brunner and R. R. Emst J. Magn. Reson. 1979 33 83. 95 D. I. Hoult J. Magn. Reson. 1979 33 183. 96 R. J. Gumrnerson C. Hall W. D. Hoff R. Hawkes G. N. Holland and W. S. Moore Nature 1979,281 56. 97 R. A. Wind and C. S. Yannoni J. Magn. Reson. 1979 36 269.

ISSN:0069-3030    

DOI:10.1039/OC9797600018

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

3 Theoretical Chemistry By H. S. RZEPA Department of Chemistry Imperial College of Science and Technology (University of London) London SW72AY 1 Introduction The activity in this field is illustrated by the citation in volumes 89-91 of Chemical Abstracts of about 420 references to ab initio calculations alone! This necessarily selective report reviews recent advances in quantum-mechanical methods and the application of these techniques to the electronic structure and geometry of molecules and to dynamic processes and reaction hypersurfaces. A new journal concerned with computational chemistry is appearing,’ and recent advances have been summarized in excellent series on the theory and application of quantum-mechanical methods2 and in the Specialist Periodical Reports of the Chemical S~ciety.~ Particularly characteristic of the past few years has been the use of standard computer programs distributed by QCPE,4 which has greatly facilitated the direct comparison of the results of different investigations.2 Advances in Theoretical Techniques Geometry Optimization.-Despite misgivings by Woolley’ concerning the Born- Oppenheimer approximation and whether or not the geometry of a molecule can be usefully defined much effort has been expended in this area. The desirability of complete geometry optimization and the characterization of stationary points in a potential surface by inspection of the corresponding force-constant (Hessian) matrix has been amply demonstrated by amongst others Dewar and co-workers who have concentrated in their studies on the use of computationally fast semi-empirical methods.6 Efficient optimization at the ab initio level was not feasible until the development of analytical methods for obtaining the first derivatives of the energy with respect to the nuclear co-ordinates.Pulay has been prominent’ in the development of these gradient methods and recently a number of programs have ’ J. Computational Chem. Wiley-Interscience 1980. (a) J. A. Pople W. J. Hehre L. Radom and P. von R. Schleyer ‘Ab initio Molecular Orbital Theory. 11 Assessment and Applications’ Academic Press New York 1979; (b) ‘Modern Theoretical Chemistry’ ed. H. F. Schaefer Plenum New York 1977 Vols. 3 and 4;ibid. ed. G. A. Segal 1977 Vols. 7 and 8. ‘Theoretical Chemistry’ ed.R. N. Dixon and C. Thompson (Specialist Periodical Reports) The Chemical Society London 1978. Vol. 3. Quantum Chemistry Program Exchange Indiana University Bloomington In. R. G. Woolley J. Amer. Chem. SOC., 1978,100 1073. (a) M. J. S. Dewar M. L. McKee and H. S. Rzepa J. Amer. Chem. SOC.,1978,100,3607; (b) M. J. S. Dewar and G. P. Ford ibid. 1979,101 5558. ’(a) P. Pulay in ref. 26 Vol. 4 pp. 152-185; (b) P. Pulay Theor. Chim. Acra 1979 50 299. H. S. Rrepa been reported which are capable of carrying out geometry optimization more or less automatically. Several groups have now published algorithms for the calculation of first deriva- tives of spin-restricted SCF wave-functions of doublets triplets open-shell singlets quartets and multiconfigurational (MCSCF) wave-f~nctions.~ The time taken in calculating the derivatives is between one and two times that for a SCF calculation but the use of these in efficient optimization algorithms such as that of Davidon-Fletcher-Powell6 is expected to be more efficient and reliable than the commonly used method of cyclic optimization of individual geometrical variables.Electron Correlation.-Handy et ul.'' have suggested that whilst the 1970's will be viewed as the decade in which variational SCF wave-functions of up to almost Hartree-Fock quality came to be applied to a broad range of chemical problems the 80's will see the routine application of methods which go beyond the Hartree-Fock approximation. The major problem is the calculation of the electron-correlation energy of a system defined as the difference between the energy calculated at the Hartree-Fock level and that obtained from the exact solution of the non-relativistic Schroedinger equation.An approach has been outlined for a 'standard' direct configuration interaction (CI) procedure which includes all single and double excitations and which is expected to recover about 95%of the correlation energy for a small molecule such as water and rather less for larger molecules. The price to be paid however is considerably increased computing time which may show a depen- dence on the basis set of between n5 and n6 (where n is the size of the basis set) compared with the usual n dependence of single-configuration ab initiu calculations and the n2 dependence of the NDO semi-empirical methods! Procedures have recently been developed based on the graphical unitary group approach to CI," which can reduce the computing time two- or three-fold.Papers from a recent symposium concerned with this problem have appeared. l2 Improvements in the use of pseudo-core or effective core potentials for elements of high atomic weight have been reported.13 Morokuma has described his energy charge and spin decomposition analysi~,'~ which enables the evaluation of charge and spin redistributions at the transition state and along the reaction pathway. The importance of charge-transfer interactions in chemical reactions was emphasized. Lipscomb et ul. have given a detailed comparison of the PRDDO method with the STO-3G CND0/2 INDO and several other procedure^.'^ PRDDO was about 6 times slower than CND0/2 and eliminated 90% of the error of the latter as compared with reference SCF calculations.Relative energies were only moderately (a) D. Poppinger Chem. Phys. Letters 1975,34,332; (b) H. B. Schlegel S. Wolfe and F. Bernardi J. Chem. Phys. 1975,63 3632; (c) M. Dupuis and H. F. King ibid. 1978,68,3998; (d) A. Komornicki and R. L. Jaffe ibid. 1979,71 2150. (a) J. D. Goddard N. C. Handy and H. F. Schaefer J. Chem. Phys. 1979,71,1525;(b) S. Kato and K. Morokuma Chem. Phys. Letters 1979 65 19. lo N. C. Handy J. D. Goddard and H. F. Schaefer J. Chem. Phys. 1979,71,426. (a) P. E. M. Siegbahn J. Chem. Phys. 1979,70,5391; (b)B. R. Brooks and H. F. Schaefer ibid.1979 70 5092. l2 Internat. J. Quantum Chem. 1978 Vol. 14. l3 P. A. Christiansen Y. S. Lee and K. S. Pitzer J. Chem. Phys. 1979,71,4445. l4 S. Nagase and K. Morokuma J. Amer. Chem. SOC.,1978,100,1666. l5 T. A. Halgren D. A. Kleier J. H. Hall L. D. Brown and W. N. Lipscomb J. Amer. Chem. SOC.,1978 100,6595. Theoretical Chemistry 33 well predicted by PRDDO. Dewar and Ford report that the MNDO method,6 whilst only slightly slower than the CNDO/2 method is about three times more accurate than PRDDO or STO-3G for the calculation of relative energies and has about the same accuracy for the calculation of ionization potentials and dipole moments. Schweig et a1.16 have developed the LNDO/S method. It is parameterized on the electronic transition energies (ETEs) and vertical ionization potentials (VIPs) of a number of small molecules and not surprisingly it gives very good estimates of these two quantities for a large number of hydrocarbons appearing to be superior to the CNDO/S method.The HAM/3 method has given rise17 to several polemics concerning the rigour of its theoretical foundations It provides a fast and apparently reliable method of predicting ionization energies. The MIND0/3 method has now been tested with some success for a range of properties although a number of defects have been reported.'* LCAO-MO theory continues to be combined with force-field calculations. An interesting combination of extended Huckel theory with an empirical force field is a useful adjunct to existing molecular-mechanics methods and represents an improved method for the study of arenes.I9 3 Electronic Structure and Geometries of Molecules Although the success of SCF-MO methods in reproducing molecular geometries has been amply demonstrated there remain a few problem areas.Pople and co- workers2' have investigated the effect of electron correlation at the ab initiu level. Using the MP2/6-3lG* method they found that the only major improvement was in bonds to electronegative elements such as F and 0. A number of groups have analysed substituent effects in organic molecules. Wiberg2' has shown that substituent effects in CH3-X can be separated into u-and wcomponents in a manner analogous to those in aromatic compounds and cal- culations have been carried out which show that strain energies in small ring systems are decreased by a-donating and T-withdrawing or .Ir-donating substituents (e.g.Li or 0).22 The role of d-orbitals in species such as H3N0 or H3P0 has been re-investi- gated.23 The results of calculations using a basis set of double-zeta quality and with the inclusion of electron correlation suggest that these molecules are best considered as bipolar species and that there is no justification in describing the d-functions as valence orbitals although they are necessary if molecular energies are to be predicted accurately. l6 G. Lauer K. W. Schulte and A. Schweig J. Amer. Chem. SOC.,1978 100,4925. '' L. Asbrink C. Fridh E. Lindholm and S. de Bruijn Chem. Phys. Letters 1979 66 43. l8 (a) T.J. Zielinski D. L. Brean and R. Rein J. Amer. Chem. SOC.,1978 100 6266; G. Klopman P. Andreozzi A. J. Hopfinger 0.Kikuchi and M. J. S. Dewar ibid. 1978,100,6267; (6) S. P. McManus and M. R. Smith Tetrahedron Letters 1978 1897; (c)S. Bantle and R. Ahlrichs Chem. Phys. Letters 1978 53 148; (d) G. Frenking H. Goetz and F. Marschner J. Amer. Chem. SOC.,1978 100 5295. l9 D. A. Dougherty and K. Mislow J. Amer. Chem. SOC.,1979,101 1401. 20 D. J. DeFrees B. A. Levi S. K. Pollack W. J. Hehre J. S. Binkley and J. A. Pople J. Amer. Chem. SOC. 1979,101,4085. 21 K. B. Wiberg J. Amer. Chem. SOC.,1979,101 2204. 22 J. D. Dill A. Greenberg and J. F. Liebman J. Amer. Chem. SOC.,1979 101 6814. 23 H. Wallmeier and W. Kutzelnigg J. Amer. Chem. SOC.,1979.101 2804. H.S. Rzepa Neutral Species.-The replacement of H by Li or of C by Si has been rich grazing ground for theoretical studies. A 'state of the art' calculation on dilithiomethane re-affirms it to have nearly degenerate singlet and triplet ground states in both tetrahedral and planar config~rations.~~ Schleyer's group continue to predict unusual structures for lithiated species e.g. -(1)-(3).25 They used the popular method of carrying out geometry optimizations with a STO-3G basis set and evaluating relative energies with a 4-31G basis set (STO-3G/4-31G). They found (3) that (3) is best considered as a carbene complex with LiF the lone pair on the carbene overlapping with an empty orbital on the metal and back donation occurring from the fluorine into the unoccupied carbene p-orbital.There is some support for the structure of (3)from n.m.r. studiesz6 Dilithioethylene (4) has been studied using a double-zeta basis set plus CI,27 the conclusion being that the twisted triplet is the most stable state. The planar triplet is 5 kJ mol-' and the planar singlet is 123 kJ mol-' higher in energy. Calculations at the STO-3G/4-31G level have also been reported for a number of lithio derivatives of allene propyne and cyclo- propene.28 In most cases the most stable isomer has a non-classical structure involving Li bridging. The reaction between acetylene and an aluminium atom is predicted to be exothermic by 84 kJ m01-l.~~ These studies at the ab initio level using basis sets of double-zeta quality suggest that the 7r-complex is not bonding and that instead the most stable isomer involves a hydrogen shift to form (5).Interest in the ability of silicon to replace carbon in organic molecules is unabated. The analogue of ethylene Si2Hs was calc~lated,~' using a STO 4-31G basis to favour the silylene structure (6) rather than the double-bonded form (7). A similar conclusion was reached by Schaefer and co-workers3' concerning CSiH4. Using a very large orbital basis set and what they describe as almost a complete CI they found that (8)and (9) were essentially degenerate in energy. Ab initio calculation^^^ suggest that the silylene (10) has a singlet ground state and is a relatively stable species unlike its carbon analogue which has a triplet ground 24 W.D. Laidig and H. F. Schaefer J. Amer. Chem. SOC., 1978,100 5922. 2s T. Clark and P. von R. Schleyer (a)J.C.S. Chem. Comm. 1979 883; (b) Tetrahedron Letters 1979 4963;(c) J. Amer. Chem. SOC.,1979,101,7747. 26 D. Seebach H. Siege] K. Mullen and K. Hiltbrunner Angew. Chem. Znternat. Edn. 1979 18,784. *' W. D.Laidig and H. F. Schaefer J. Amer. Chem. SOC., 1979,101,7184. 28 E.D.Jemmis J. Chandrasekhar and P. von R. Schleyer J. Amer. Chem. SOC., 1979,101,2848. 29 M. Trenary M. E. Casida B. R. Brooks and H. F. Schaefer J. Amer. Chem. SOC., 1979 101 1638. 30 L.C.Snyder and Z. R. Wasserman 1. Amer. Chem. SOC.,1979 101,5222. 31 H. F.Schaefer Accounts Chem. Res. 1979,12,288. 32 J. C.Barthelat G. Trinquier and G. Bertrand J. Amer. Chem. SOC., 1979 101 3785.Theoretica1Chemistry state. Another molecule of great interest silabenzene (1l),has been calculated by Schlegel et al.33 to have as much as f of the resonance energy of benzene itself. Whether this will be reflected in its properties remains to be seen. Further papers have appeared34 on cyclobutadiene (12). The vibrational frequencies of the rectan- gular ground-state singlet have been calculated using an ab initio method,34a and were found to be in good agreement with those reported for matrix-trapped (12). Lipko~itz~~' has studied the possibility that complexes of (12) with CO HCN or benzene might be formed. CND0/2 predicts the formation of all three complexes to be considerably exothermic whereas STO-3G predicts that none of the complexes is stable.In a similar study using MND0,34c the complex with CO was found to form exothermically but on relaxing the C4"symmetry restraint the system was found to collapse to bicyclopentenone. Schweig and Thiel report that the optimized geometry of tetra-t-butyltetrahedrane using MNDO has only T symmetry with the impli- cation that the molecule is chiral. However a very low barrier to racemization was predicted. 35 Higher annulenes have been studied by the semi-empirical MIND0/3 method,36 which was found to over-estimate the amount of bond alternation. Possible reasons for this were discussed including the inadequate treatment of electron correlation in the method. A remarkable series of anti van't Hoff compounds have been postulated on the basis of STO 4-31G calculation^.^^ By substituting two geminal hydrogens on a carbon atom with the cyclic -BH-BH- unit Schleyer and his co-workers have suggested that compounds (13)-( 15) exist preferentially in planar perpendicular and planar forms respectively.Isomers with conventional van't Hoff stereochemistry were calculated to be as much as 84 kJ mol-' higher in energy! Although little optimism was expressed for the synthesis of (13)-(15) a more hopeful candidate (16) was suggested which might be expected to display similar properties. TxH HB T>c<H ,*I H*fH mH HB HB H cpco-cocp (13) (14) (15) (16) The benzynes continue to attract attention.38 The vibrational spectrum of o-benzyne has been calculated using MND0,38" and ab initio GVB calculations suggest that the meta-and para-isomers have singlet ground states and exist as biradical~.~~' Although the calculations suggested that bicyclic isomers are higher in energy Washburn has apparently characterized bicyclo[3.1 .O]hexatriene (m-ben-~yne).~~' 33 H.B. Schlegel B. Coleman and M. Jones J. Amer. Chem. SOC., 1978,100,6499. 34 (a) L. J. Schaad B. A. Hess and C. S. Ewig J. Amer. Chem. SOC.,1979,101,2281 (b) K. B. Lipkowitz, ibid. 1978 100 7535; (c)A. Schweig and W. Thiel Tetrahedron Letters 1978 1841. 35 A. Schweig and W. Thiel J. Amer. Chem. SOC., 1979 101,4742. 36 (a) H. Vogler J. Mol. Strucf. 1979,51,289; (6) H. Baumann J. Amer. Chem. SOC., 1978,100 7196. 3'7 K. Krogh-Jespersen D. Cremer D. Poppinger J. A. Pople P. von R.Schleyer and J. Chandrasekhar J. Amer. Chem. SOC., 1979,101,4843. (a) M. J. S. Dewar G.P. Ford and H. S. Rzepa J. Mol. Strucf.,1979,51,275; (b) J. 0.Noell and M. D. Newton J. Amer. Chem. SOC.,1979 101 51; (c)W. N. Washburn R. Zahier and I. Chen ibid. 1978 100,5863. H. S. Rzepa The structures of crucial intermediates involved in ozonolysis have been investi- gated. The 'Criegee intermediate' (17) is calculated to have a high barrier to synlanti isomerization (134 kJ mol-') with the syn form favoured by 12-17 kJ mol-'. This is consistent with many experimental observations. Two isomeric species (18) and (19) have been calculated to be considerably lower in energy (by 139 and 113 kJ mol-' respectively) and the possible involvement of such species in ozonolysis cannot be excluded.39 A closely related study by Harding and Goddard4' came to very similar conclusions.Cremer41 has published an important series of papers on the conformations of primary (20) and final ozonides (21). Ab initio calculations find the rings to be puckered in each case. The oxygen envelope (E) is the most stable for the primary ozonide and an explanation is offered for the contrasting stereochemical behaviour of cis- and trans-alkenes upon ozonolysis. The novel dipolar species (22) was predicted by STO 4-31G calculations to be a good candidate for detection particularly if the hydrogens are replaced by electron- withdrawing sub~tituents.~~ A study of several amides using the TEXAS ab initio gradient program with complete geometry ~ptimization,~~ appears to have settled the vexed question of whether the nitrogen is pyramidal or planar in favour of the latter.The same conclusion was reached in a related study of f~rmamide.~~ Conformations.-Pople and his co-workers have applied their GAUSSIAN 70 ab initio program to the study of conformational analysis with some success. One unexpected result was their prediction that certain cyclic alkenes such as (23) are puckered and not planar.45 Conformational effects in pyranosides were modelled with dimethoxymethane. Although complete geometry optimization was not possible at the time of the study the 4-31G method correctly predicted46 that the molecule has the preferred conformation (24). This is in excellent agreement with the anomeric effects observed in pyranosides.This study has subsequently been 39 D. Cremer J. Amer. Chem. SOC.,1979,101 7199; K. Karlstom S. Engstrom and B. Jonsson Chem. Phys. Letters 1979 67 343. 40 L. B. Harding and W. A. Goddard J. Amer. Chem. SOC.,1978,100,7180. D. Cremer J. Chem. Phys. 1979 70 1898 1911 1928. 42 R. Cimiraglia M. Persico and J. Tomasi Theor. Chim. Acru 1978,49 13. 43 G. Fogarasi P. Pulay F. Torok and J. E. Boggs J. Mol. Sfruct. 1979 57,259. 44 N. R. Carlsen L. Radom N. V. Riggs and W. R. Rodwell J. Amer. Chem. Soc. 1979,101 2234. " H.-U. Wagner 0.Szeimies,J. Chandrasekhar P. von R. Schleyer J. A. Pople and J. S. Binkley J. Amer. Chem. SOC.,1978,100 1210. 46 G. A. Jeffrey J. A. Pople J. S. Binkley and S. Vishveshwara J.Amer. Chem. SOC.,1978,100 373. Theoretical Chemistry 37 extended to methoxymethyl fluoride and chloride as models for the study of glycosyl halide^.^' Fluoride was found to have a greater anomeric effect than chloride with OH having an intermediate value. An apparent disagreement between the predicted (STO4-3 1G) conformation of glycine and microwave results appears to have been resolved.48 Complete geometry optimization at the 4-21G level using the TEXAS program agrees with earlier calculations in predicting (25) to be more stable than (26) by 9 kJ mol-' although the microwave results had suggested that the predominant conformer was (26). However since only (26) is predicted to have a large dipole moment [6.54 D us. 1. 1D for (25)] it seems probable that only microwave transitions from (26) were detected experimentally.Pople and co-~orkers~~ report 4-3 1G cal- culations which suggest that the zwitterionic form of glycine is a shallow minimum in the potential-energy surface a barrier of only 2 kJ mol-' separating it from (26) which is 121 kJ mol-' more stable. On the basis of these results a hydration energy of at least 209 kJ mol-' has been proposed. Other conformational studies have been carried out on vinyl thioether~,~'" ester~,~" peroxyformic acid,50' n-b~tane,"~ substituted thi~phens,~" and bia~etyl.~" Charged Species.-Schleyer et al? have studied ions of the type CH3MZ+ (M = Li BeH Na or MgH) which are interesting as models for electrophilic substitution reactions. Whilst the most stable structure for CH5+ has C,symmetry (27),those when M is Li or BeH have DShsymmetry (28) suggesting a fine balance between retention and inversion of configuration in SE2reactions.The combination of using MIND0/3 for rapid optimization of the geometry and an ab inifio 4-31G basis for energy calculations has been successful in a study of numerous carbo-~ations.~~ Corrections for zero-point energies were made using thermodynamic quantities evaluated from MIND0/3 calculations. Hehre et a~,'~ on the basis of 4-31G/6-31G* calculations have proposed that two forms of the cyclobutylcarbinyl cation may be stable; i.e.one form with C,symmetry (29) and an alternative isomer which is structurally very similar but does not have the plane of symmetry and which is twisted to some extent.Since this latter species is only 47 G. A. Jeffrey and J. H. Yates J. Amer. Chem. SOC., 1979,101 820. 48 H. L. Sellers and L. Schafer J. Amer. Chem. SOC.,1978,100,7728. ''Y.-C. Tse M. D. Newton S. Vishveshwara and J. A. Pople J. Amer. Chem. SOC.,1978 100,4329. " (a) J. Kao J. Amer. Chem. SOC.,1978,100,4685; (b) J. R. Larson N. D. Epiotis andF. Bernardi ibid. 1978,100 5713; (c) R. D. Bach C. L. Willis and T. J. Lang Tetrahedron 1979 35 1239; (d) M. R. Peterson and I. G. Csizmadia J. Amer. Chem. SOC.,1978 100 6911; (e) J. Kao and L. Radorn ibid. 1979 101 311; (f) J. Tyrell ibid. 1979 101 3766. " E. D. Jemrnis J. Chandrasekhar and P. von R. Schleyer J. Amer. Chem. SOC.,1979,101 527. " H. J. Kohler and H. Lischka J.Amer. Chem. SOC.,1979,101 3479. B. A. Levi E. S. Blurock and W. J. Hehre J. Amer. Chem. SOC.,1979,101 5537. '3 H. S. Rzepa 2 kJ mol-' higher in energy than (29) it is difficult to be certain that this result is not an artifact of either the method or the geometry optimization. Using the same method it was found that cyclobutyl cation was not a stable species collapsing without activation to (29). H- ,H "\ ,SH M-c'-M "-,%A I H H H On the basis of STO-3G calculations but without geometry optimization Greenbe~g'~ has made the fascinating prediction that the central bond in bicyclo- butane is comparable to the vinyl group in its ability to stabilize a carbo-cation centre. The rotational barrier about the C-C bond in (30) was calculated to be as high as 133 kJ mol-'.Further studies using a higher quality basis set and complete geometry optimization would be desirable. Substitution of a methyl group in the terminal position was calculated (STO-3G) to stabilize an ally1 cation by 71 kJ mol-' whereas substitution on the central carbon atom has a much smaller effect (21 kJ m~l-').~~ The stabilization was found to be related to the rate of solvolysis. The cyclobutadienyl dication may naively be expected to be aromatic and planar on the basis of the Huckel4n +2 rule. It has been reported that in fact a puckered form is 31 kJ mol-' more stable as a consequence of destabilizing 1,3- interactions and the results of orbital mixing and re~rientation.'~ Chandrasekhar and Schleye?' have studied 1,2-shifts in cyclic carbonium ions.Both the MIND0/3 and STO-3G methods predict that the activation energy increases with decreasing ring size [e.g.by 64 kJ mol-' (MIND0/3) or 93 RJ mol-' (STO-3G) for cyclopropyl cation relative to ethyl cation]. The effect has been attributed to increasingly poor orbital overlap in the smaller rings. A re-investiga-tion of the protonation of benzene using the MIND0/3 and STO-3G methods suggests that previously found differences between the two methods may have been a result of inadequate optimization of the ge~metry.'~ The structure corresponding to a rr-complex was found to represent the transition state for a 1,2 hydrogen shift. Another interesting predictions9 is of two-fold aromaticity for (31). It has been suggested that this ion which is known from mass spectral studies is especially stable by virtue of (a)having six 7r-electrons and (b) having two cr-electrons occupying the symmetric Walsh orbital.Lischka and Kohler6' have published a detailed comparison of the results of MIND0/3 and ab initio CEPA/PNO calculations for small carbo-cations. Both methods predict non-classical bridging structures to be slightly more stable than the classical forms. MIND0/3 however was found to predict excessive stability for cyclic halonium ions (32). McLafferty and co-workers have discovered some " A. Greenberg. Tetrahedron Letters 1978 3509. " H. Mayer W. Forner and P. von R. Schleyer J. Amer. Chem Soc. 1979,101,6032. 56 K. Krogh-Jespersen P. von R. Schleyer J.A. Pople and D. Cremer J. Amer. Chern. Soc. 1978 100 4301. '' J. Chandrasekhar and P. von R. Schleyer Tetrahedron Letters 1979,4057. T. Sordo J. Bertrln and E. Canadell J.C.S. Perkin 11 1979 1486. 59 J. Chandrasekhar E. D. Jemmis and P. von R. Schleyer Tetrahedron Letters 1979,3707. 6o H. Lischka and H. J. Kohler J. Amer. Chern. Soc. 1978 100 5297. Theoretical Chemistry H interesting differences in the behaviour of oxygen and sulphur.61 Both (33) and (34) were deduced to be stable on the basis of mass spectral studies and STO 4-31G calculations verified this predicting (33) to be a triplet. In contrast the methoxy cation is predicted to be unstable and does not seem to have been detected experimentally although there is evidence of a weak complex between H2 and HCO'.Radom and co-workers have calculated that eleven isomers of C2H40tare stable of which five as yet unknown species are proposed as reasonable candidates for identification.62 The most stable isomer corresponded to ionized vinyl alcohol. There have been several investigations of C2H50+as a model for the electrophilic addition of HO' to an alkene. Various methods63 are in agreement that the bridging ion (35) is more stable than the open form (36) by 92 kJ mol-' (a6 initio/CEPA) 30 kJ mol-' (STO 4-31G) 21 kJ mol-' (MNDO) or 100 kJ mol-' (MIND0/3). A high barrier has been predicted for the isomerization of (35) to (36) (25 kJ m01-l)~~ and an alternative isomer (37) is predicted by all the methods to be considerably more H O+ (35) Carbenes Triplets and Excited States.-A review on singlet-triplet separations in carbenes and biradicals has appeared.6s There is now sufficient confidence in the reliability of the calculated singlet-triplet energy separation in methylene that when an anomalous experimental result is reported it is confidently concluded that the experimental interpretation and not the calculations must be erroneous!66 The theory has now reached the stage where a small difference in the latest experimental value (=33 kJ mol-') and the latest calculations (-42 kJ mol-') can be attributed to the neglect of relativistic effects in the latter.66 The triplet states of a number of carbene~~~~ have been shown to and nitrene~~~" be stabilized relative to the singlet by u-donating substituents (e.g.Li) and to be destabilized by w-donors (e.g.F OR NR2 or CR2-).Cyanocarbene has proved rather mysterious. Experimental evidence suggests that it is linear i.e. (38) and calculations at the STO4-31G/small CI level appeared to support this conclusion.67c 61 J. D. Dill and F. W. McLafferty J. Amer. Chem. Soc. 1979,. 101 6526. 62 W. J. Bouma J. K. MacLeod and L. Radom J. Amer. Chem. Soc. 1979,101,5540. 63 A. C. Hopkinson M. H. Lien I. G. Csizmadia and G. Yates Theor. Chim. Acta 1978 43 97. 64 H. Lischka and H. J. Kohler Chem. Phys. Letters 1979 63 326. 65 W. T. Borden and E. R.Davidson Ann. Rev. Phys. Chem. 1979,30 125. 66 D. Feller and E. R. Davidson Chem. Phys. Letters 1980,69,201. 67 (a) N. C. Bairdand K.F.Taylor J.Amer. Chem. Soc. 1978,100,1333; (b) J. F. Harrison R. C. Liedtke and J. F. Liebman ibid.,1979,101,7162;(c) J. F. Harrison A. Dendramis and G. E. Leroi ibid. 1978 100,4352; (d) M. F. Zandler J. D. Goddard and H. F. Schaefer ibid. 1979 101 1072. 40 H.S.Rzepa A re-investigation using a more extensive basis set and a larger CI suggests that the species is bent with an angle of about 135 O and that the linear form is 18 kJ mol-' higher in energy.67d Hydroxycarbene (39) has been implicated in the photochemistry of formalde- h~de.~' A significant delay between the decay of the S1state and the appearance of CO photoproduct suggested that an intermediate might be involved. Goddard and Schaefer,68 on the basis of extensive CI calculations found that (39) was energetic- ally accessible although there appears to be no low barrier to the conversion of (39) into H2 and CO.It was concluded3' that although (39) may be 'visited' in the course of photodissociation of HzCO it does not play an important role. OH H-C.. / Cyclopropenylidene (40) is of interest because the singlet state can be regarded as aromatic in the Huckel4n +2 sense. Indeed CI studies suggest that configurations which violate the 4n +2 rule contribute relatively less to the wave-function than they do in other carbene~.~~ If the equilibrium geometry is distorted by lengthening the C-C single bond a singlet-triplet crossing was found to occur and was felt to be significant in rationalizing the non-stereospecific addition of singlet carbenes of this type to alkene~.~~ Cyclopropylchlorocarbene is apparently less selective (more reactive) towards alkenes than was e~pected.~' STO 4-3 1G calculations offer an interesting rational- ization The preferred conformation (41) is stabilized by interaction of the vacant carbenic p-orbital with the cyclopropyl u-bonds but this does not allow sterically favourable overlap with the n-orbitals of an approaching alkene.This problem does not occur with the alternative conformation (42) which however is predicted to be 40 kJ mol-' higher in energy and would be expected to show less selectivity. H+-&C A 'state of the art' double-zeta basis set/CI calculation on trimethylenemethane (43) suggests that the elusive (3A,'-1B1) energy separation is not less than 59 kJ rn~l-',~'~ while a much less extensive calculation on Closs's biradical (44) suggests that in this case the singlet and triplet energies are almost equal."' Salem has reviewed the phenomenon of sudden p~larization.~~ Calculations using a large basis set and extensive CI suggest that if one of the CH groups in the 68 J.D. Goddard and H. F. Schaefer J. Chem. Phys. 1979,71,5117. 69 R. Shepard A. Banerjee and J. Simons J. Amer. Chem. SOC. 1979,101,6174. 70 R. A. Moss M. Vezza W. Guo R. C. Munjal K. N. Houk,and N. G. Rondan J. Amer. Chem. SOC. 1979 101,5088. 71 (a) D. M. Hood,H. F. Schaefer and R. M. Pitzer J. Amer. Chem. SOC. 1978 100 8009; (b) M. P. Conrad R. M. Pitzer and H. F. Schaefer ibid. 1979,101 2245.72 L. Salem Accounts Chem. Res. 1979,12,87. 41 Theoretical Chemistry 0 H orthogonal SIstate of ethylene becomes pyramidal a large amount of charge separation will occur,73 e.g. as in (49 by as much as 0.5 e for 10 O of bending. Salem speculates that such an effect could be important in the mechanism of vision (Scheme l).72 + ’H H Scheme 1 4 Dynamic Processes and Reaction Hypersurfaces An instructive and entertaining paper by Muller dealing with reaction hypersur- faces is recommended to anyone who has had difficulties in locating a transition state! Several new ways of locating stationary points in a potential surface are reviewed and illustrated with examples.74 The ability to predict accurately the rate constants of organic reactions entirely from first principles has come closer to reali~ation.~~ Morokuma and co-worker~~~~ have calculated rate constants and kinetic isotope effects for the reaction of hydrogen radicals with ethylene using a STO 4-31G basis set and obtained excellent agreement with experiment.In general however such accuracy is not to be expected although the calculation of kinetic isotope effects a priori using SCF-MO methods for a variety of reactions has been shown to give reasonably good res~lts.~~’*~ Pericyclic Reactions.-Radom and co-w~rkers~~ have found that the calculated STO-3G/4-31G barrier to the ‘forbidden’ suprafacial 1,3-shift in propene is slightly lower than that for the ‘allowed’ 1,3-antarafacial shift. In the transition state located for the former the migrating hydrogen atom is essentially directly bonded to the central carbon atom resulting in a biradical-like structure (46).There remains doubt whether (46) truly represents a transition state for a 1,3-hydrogen shift or whether it is the transition state for propene-cyclopropane isomerization. The same method was found to predict the barrier to the 1,Sshift in pentadiene to be 259 kJ mol-’; much lower than for the 1,3-shift but still in error by a large amount. An excelletlt account of theoretical calculations concerned with 1,2-shifts has a~peared.~’ 73 B. R. Brooks and H. F. Schaefer J. Amer. Chem. SOC.,1979,101 307. 74 K. Miiller Angew. Chem. Internat. Edn. 1980 19 1. 75 (a) S. Nagase T. Fueno andK. Morokuma J. Amer.Chem. SOC.,1979,101,5849; (b) S. B. Brown M. J. S. Dewar G.P. Ford D. J. Nelson and H. S. Rzepa ibid. 1978,100,7832; (c) D. J. McLennan Ausr. J. Chem. 1979,32,1869. 76 W. J. Bouma M. A. Vincent and L. Radom Int. J. Quantum Chem. 1978,14,767. H. S. Rzepa Hy* H' . Reudenberg and co-workers have concluded7' that the dimerization of singlet ('Al) methylene to give ethylene in its excited (lA,*) state occurs with no barrier despite being formally an orbital-symmetry-forbidden reaction! Calculations show that several other reactions that are symmetry-forbidden occur with no activation energy by adopting least-energy pathways that involve no symmetry (e.g. 'Al CH2 +H2; 'A CH2+eth~lene).'~ The study of such reactions which may involve avoided orbital crossings is best carried out using MCSCF methods or with very large Theoretical studies of the cyclodimerization of ethylene to give cyclobutane have produced conflicting conclusions.8o Jug and Kruger using their semi-empirical SINDO method find that the reaction is concerted but involves an unsymmetrical transition state.80a According to CI applied after geometry optimization a biradical should be encountered along the reaction path but this should not affect the concerted nature of the reaction.This does not preclude the possibility that CI applied during geometry optimization would lead to the biradical as a definite minimum on the reaction pathway. In contrast Burke and Leroygob used the STO-3G/CI method and found that the symmetric [dS + 7r2,] forbidden reaction has a lower barrier (345 kJ mol-') than the [T*~ +T*,] allowed reaction (447 kJ mol-') but that both are much higher in energy than the stepwise biradical pathway (177 kJ mol-').The Diels-Alder reaction between ethylene and butadiene continues to be Previous STO 4-31G/CI studies with partial geometry optimization suggested a symmetrical addition although an alternative pathway involving a biradical intermediate was at most 17 kJ mol-' higher in energy.*ln More recently Jug and Kruger have suggested that the reaction is concerted but involves an unsymmetrical transition state.goa Dewar et aZ.,81busing MIND0/3 and applying CI during geometry optimization found it to be stepwise and to involve a biradical intermediate. Kinetic isotope effects often cited as evidence for a concerted reaction were shown to be consistent with this mechanism.However the MIND0/3 method has been criticized"" and a more complete calculation involving complete optimization of the geometry and extensive CI might help to resolve this problem. Studies using STO 4-31G find that the reduction of ethylene with cis-di-imide is concerted and involves a symmetrical transition state.g2 77 L. M. Cheung K. R. Sundberg and K. Ruedenberg Int. J. Quantum Chem. 1979,16,1103. 78 (a) H. Kollmar and V. Staemmler Theor. Chim. Acta 1979 51 207; (6) B. Zurawski and W. Kutzelnigg J. Amer. Chem. SOC.,1978 100 2654. 79 S. Yarnabe T. Minato and Y. Osaniura J. Amer. Chem. SOC.,1979,101,4525. (a) K. Jug and H. W. Kruger Theor.Chim. Acta 1979,52,19;(b) L. A. Burke and G.Leroy Bull. SOC. chim. belges. 1979 88 379. (a) R. E. Townshend G. Ramunni G.Segal W. J. Hehre and L. Salem J. Amer. Chem. SOC.,1976,98 2190; (b) M. J. S. Dewar S. Olivella and H. S. Rzepa ibid. 1978,100 5650. 82 (a) D. J. Pasto and D. M. Chiprnan J. Amer. Chem. Soc. 1979 101 2290; (b) E. Flood and P. N. Skancke Chem. Phys. Letters 1978 54 53. Theoretical Chemistry Other Reactions.-Nucleophilic addition to a triple bond is known to proceed with trans stereochemistry. Two theoretical studies using the ab initio approach have used the addition of H-to acetylene as a model for the reaction.83 The calculated structure of the transition state (47) shows that the nucleophile and the developing negative charge are indeed trans with respect to each other.It was also demon- strated that acetylene is less sensitive than ethylene to changes in the angle of approach of the nucleophile. Although the preferred angle is about 127 O and not 60 O (as implied by Baldwin’s rules) deformation to achieve the latter angle is more facile in the case of acetylene than ethylene. Very similar transition states were reported for nucleophilic addition to nitrile and for the addition of a hydrogen atom to acetylene.84b H 0-H (47) (48) The reaction between peroxyformic acid and alkenes or imines has been studied using a STO-4G basis set with the conlusion that an intermediate adduct may be involved.85 Since no calculations of the reaction path were carried out and transition states were not located as saddle points in the potential surface this conclusion can only be qualitative.The same is true of a study of the photochemical transformation of oxaziridine to formamide,86 in which the N-0 bond is thought to cleave first followed by a decay to the So ground state and subsequent migration of hydrogen. Bigot et al. haw come to similar conclusions on the basis of rather more detailed calc~lations.~~ A thorough STO-3G study of the HF-catalysed ring-opening of oxirad8 suggests that initial protonation on oxygen is followed by rearrangement to give the cis-fluorohydrin. It was predicted that the gas-phase reaction should occur with no formation of the trans-isomer. Gorenstein and co-w~rkers~~ have studied the hydrolysis of dimethyl phosphate by hydroxide ion.Using a STO-3G basis set which does not include &functions they concluded that the energy of the dimethoxyphosphorane transition state (48) was critically dependent upon the orientation of the basal ester bonds but not of the leaving group. 83 (a) C. E. Dykstra A. J. Arduengo andT. Fukunaga J. Amer. Chem. SOC.,1978,100,6007;(b) R. W. Strozier P. Caramella and K. N. Houk ibid. 1979,101 1340. 84 (a) G. Leroy M. T. Nguyen M. Sana K. J. Dignam and A. F. Hegarty J. Amer Chem. SOC.,1979,101 1988; (b) S.Nagase and C. W. Kern ibid. 1979,101,2544. 85 A. Aiman J. Koller and B. Plesnifar J. Amer. Chem. SOC.,1979,101 1107. 86 E. Oliveros M. Riviere J. P. Malrieu and C. Teichteil J. Amer. Chem. SOC., 1979 101 318.B. Bigot D. Roux,A. Sevin and A. Devaquet J. Amer. Chem. SOC.,1979,101 2560. G. Algona E. Scrocco and J. Tomasi Theor. Chim. Actu 1979 51 11. 89 D. G. Gorenstein B. A. Luxon and J. B. Findlay J. Amer. Chem. SOC., 1979 101 5869.

ISSN:0069-3030    

DOI:10.1039/OC9797600031

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (i) Pericyclic Reactions By R. J. BUSHBY Department of Organic Chemistry The University Leeds LS2 9JT 1 Introduction The pericyclic reactions of singlet oxygen' and of the photoexcited states of organic anions2 have been reviewed. The effect of substituents on pericyclic reactions has long remained a source of difficulty. This year two interesting approaches to the problem have been described. Carpenter and Wilcox3 have used a simple HMO model. They have shown that for electrocyclic reactions 1,5-hydrogen shifts cyclopropane stereomutations and reactions involving carbon-carbon bond homolysis there is a linear relationship (1) between AAH* (the measured effect of the substituent on the enthalpy of activation in kcal mol-l) and AAE (the calculated difference between the effect of the substituent on the HMO .rr-energy of the substrate and that of a suitable model for the transition state both in units of p.Mobius cyclobutadiene is taken as a model for the transition state in the conrotatory opening of cyclobutene). AAP = 19.31AAE (1) In most cases deviations from linearity are small. For example the effects of phenyl substituents on the enthalpy of activation for opening the cyclobutenes (2) (3) and (4)[relative to the parent system (l)] are calculated from equation (1)to be -7.0 -12.0 and +7.0 kcal mo1-l respectively whereas the measured values are -6.3 -11.2 and +6.4 kcal mo1-l. The treatment is limited to hydrocarbon systems and breaks down for reactions such as 3,3-sigmatropic rearrangements where the substituents themselves drastically alter the position and nature of the transition state.This variable nature of the transition state in Cope/Claisen rearrangements is 4 phj-yph A. A. Frimer Chem. Rev. 1979,79,359. M. A.Fox Chem. Rev. 1979,79,253. C. F. Wilcox and B. K. Carpenter,J. Amer. Chem. SOC.,1979,101 3897. R. J. Bushby deliberately built into the model developed by Gaje~ski.~ He makes use of the simplest equation for an energy surface with a saddle point; namely equation (2) in which for 3,3-sigmatropic shifts x and y refer to the fraction of 1,6-bond formation and 3,4-bond breaking and a b c and d are constants. AG = ax +by +cxy +d (2) Application of suitable boundary conditions and solution for the position of the saddle point gives rise to equation (3) in which AG* is the desired free energy of activation AG’(BB) and AG’(BM) are the calculated free energies for forming the (appropriately substituted) bond-broken and bond-made species (5) and (6) AGr is the free energy of reaction and p is an empirically derived parameter which is found to be constant for a given series of reactions.For a value of p = 1.5 this equation leads to predicted free energies of activation for the 3,3-sigmatropic rearrangements of the dienes (7) (8) and (9) of 41.2 36.3 and 30.1 kcal mol-’ respectively whereas the experimental values are 41,35.5 and 31 kcal mol-’. A similar treatment was applied successfully to the Diels-Alder reaction of cyano-substituted dienophiles.0 ;c; w (5) (6) (7) (8) Ph (9) 2 Cycloadditions and Cycloreversions Charge-transfer complexes are frequently formed between compounds which undergo cycloaddition reactions but it is difficult to decide whether these are intermediates [equation (4)] or just a dead end [equation (5)]. Reactants $Charge-transfer complex +Cyclo-adducts (4) Charge-transfer complex ++Reactants -+Cyclo-adducts (5) Hence one study of the addition of tetracyanoethylene to vinyl ethers suggests that the charge-transfer complex is a true intermediate5 and another very similar study that it is Perhaps the best evidence for the intermediacy of a charge-transfer complex comes from the reaction of tetracyanoethylene with 9,lO-dimethylanth- racene where the observed ‘overall’ enthalpy of activation is negative.’ This can only be reconciled with equation (4) and a more recent study of the reaction of tetracyanoethylene with a range of anthracene derivatives has shown a correlation J.J. Gajewski J. Amer. Chem. SOC.,1979 101,4393. M. Sasaki H. Tsuzuki and M. Okamoto J. Org. Chem. 1979,44,652. J. von Jouanne H. Kelm and R. Huisgen J. Amer. Chem. SOC.,1979,101,151. ’V. D. Kiselev and J. G. Miller J. Amer. Chem. SOC.,1975 97 4036. Reaction Mechanisms -Part (i) Pericyclic Reactions between the 'overall' free energy of activation and that for formation of a charge- transfer complex. This has also been interpreted as evidence that the charge-transfer complex is a true intermediate.8 The formation of zwitterionic intermediates in certain cycloaddition reactions has continued to attract attention and Moore9 has discussed the use of furanone azides for the independent generation of such intermediates.For example the furanone (10) can be used to generate the zwitterion (ll),which is thought to be an intermediate in the addition of cyanochloroketen to benzaldehyde." Evidence has also been provided for a zwitterionic intermediate in the addition of tetra-cyanoethylene to thioenol ethers," and the zwitterionic intermediate (12),formed by the addition of bromoketen diethyl acetal to an electron-poor olefin is trapped internally to give (after work-up) the cyclopropane (13).'* 0-CO),Et N3 cl)j$ Ph C0,Et (13) Several investigations have been reported of the 2 +2 Lewis-acid-catalysed addition of propiolate esters to alkene~.'~ Whilst the mechanism of this reaction is still uncertain the observed stereospecificity as well as the parallels with keten reactivity suggest a concerted 7~2s+7~2a process.[Perhaps the keten analogy is best seen if the intermediate complex is written as in formula (14)].However the reaction with norbornene gives both normal (15) and rearranged (16)products showing that a zwitterionic intermediate can be formed when the carbonium ion is sufficiently stable. Some 2 +4 cycloaddition reactions are also catalysed by Lewis acids; when the chiral menthol derivative (17)is employed quite high asymmetric induction can be ~btained.'~ RO ,OAlCI II &C0,Me C C /I +CH M.Lofti and R. M. G. Roberts Tetrahedron 1979,35 2131 2137. H. W. Moore Accounts Chem. Res. 1979,12,125. lo H. W. Moore F. Mercer D. Kunert and P. Albaugh J. Amer. Chem. SOC.,1979,101,5435; but compare 0.Krabbenhoft,J. Org. Chem. 1978,43,1305 and E. Schaumann and J. Ehlers Chem. Ber. 1979,112 1000. l1 R. Huisgen and H. Graf J. Org. Chem. 1979,44 2594 2595. l2 H. K. Hall A. B. Padias A. Deutschmann and I. J. Westerman J. Org. Chem. 1979,44,2038. l3 B. B. Snider and D. M. Roush J. Amer. Chem. SOC.,1979,101,1906; B. B. Snider D. J. Rodini R. S.E. Conn and S. Sealfon ibid. p. 5283; R. D. Clark and K. G. Untch J. Org. Chem. 1979 44 248; H. Fienemann and H. M. R. Hoffmann ibid p. 2802. l4 S. Hashimoto N. Komeshina and K. Koga J.C.S. Chem. Comm. 1979,437.R. J. Bushby The energetics for the gas-phase retro-Diels-Alder reactions of 3,6-dihydro-2H- pyrans seem to exclude the possibility that biradicals are intermediates." For example the observed energy of activation for the parent compound (18) is 49.7 kcal mol-l whereas formation of biradical (19) would require ca. 66.0 and of the biradical(20) ca. 69.3 kcal mol-'. OAc 1 The stereochemistry of the product (2 1)obtained by allowing 1-acetoxybutadiene and dimethyl fumarate to react had been explained in terms of secondary orbital interactions. However investigation of addition reactions of a range of fumaric acid derivatives shows exceptions to the expected stereochemical pattern. It has there- fore been concluded that if the secondary orbital effects are ever significant in these systems then they are small and easily over-ridden by other factors.16 On the other hand the preference of N=N dienophiles for the syn face of propellane (22) [leading to adducts such as (23)] and of C=C dienophiles for the anti face [leading to adducts such as (24)] has been plausibly explained in terms of a secondary orbital interaction between the antisymmetrical combination of the lone-pair orbitals of the N=N and the .;rr*-orbitals of C=O which attracts this dienophile to the syn side." 0 (22) X = 0,NH or NR (23) 0 (24) Two investigations of the Diels-Alder reaction have been made in which it is claimed that reactivity is related to the C-1-C-4 distance in the diene as well as to the ionization potential of the diene.'* Similar studies of 1,3-dipolar cycloadditions have nicely illustrated how the electron-rich/-poor nature of the 1,3-dipole influences the relationship between ionization potential and reactivity of the alkene.Whereas diazomethane is of 'type 1'in Sustmann's classification (reaction being controlled by the HOMO of the 1,3:dipole and the rate increasing roughly as the ionization potential of the alkene increases) in diazoacetic ester (25b) 'type 2' behaviour is H. M. Frey R. Pottinger H. A. J. Carless and D. J. Lingley J.C.S.Perkin II,1979,1460; H. M. Frey and S. P. Lodge ibid. p. 1463. W. B. T. Cruse I. Fleming P. T. Gallagher and 0.Kennard J. Chem. Res. (3, 1979,372. l7 M. Kaftory M. Peled and D. Ginsburg Helv. Chim. Acta 1979,62 1326.H.-D. Scharf H. Plum J. Fleischhauer and W. Schleker Chem. Ber. 1979,112,862;R. Sustmann M. Bohm and J. Sauer ibid. p. 883. l9 (a) J. Geittner R. Huisgen and R. Sustmann Tetrahedron Letters 1977 881; (b) W. Bihlmaier R. Huisgen H.-U. Reissig and S. Voss ibid. 1979 2621. Reaction Mechanisms -Part (i) Pericyclic Reactions observed [interactions with the HOMO and the LUMO of the 1,3-dipole are both important leading to a U-shaped plot of log (rate) vs. (ionization potential of the alkene)] and the introduction of further electron-withdrawing groups as in dimethyl diazomalonate (25c) or methyl diazo(phenylsulphony1)acetate (25d) leads to behaviour intermediate between ‘type 2’ and ‘type 3’”’ (Sustmann ‘type 3’ behaviour involves domination by the LUMO of the 1,3-dipole and a rate of reaction which increases as the ionization potential of the alkene decreases).A similar difference is seen between benzene nitrile oxide (26a) which shows ‘type 2’ behaviour and the more electron-deficient benzenesulphonyl nitrile oxide (26b) which shows behaviour intermediate between ‘type 2’ and ‘type 3’.20 R’ \-+ O-&fC-R R2/c-N=N (25) a; R’=R2=H (26) a; R=Ph b; R’ =H R2 = C02Me b; R=SO;?Ph c; R’ = R2= C02Me d; R’ = C02Me R2= S02Ph Retro- 1,3-dipolar additions2’ and the cycloaddition reactions of triazines2* have been reviewed. Katritzky and co-workers have continued their extended studies of aromatic ring 1,3-dipoles. 1-Substituted-3-oxido-pyridiniums (27)give adducts (28) with alkenes and it has been shown that reactivity and selectivity can be rationalized in terms of FMO Ab initio MO calculations (STO-3G and 4-31G) on the thermal elimination of nitrogen from A’-pyrazolines suggest a non-synchronous breaking of the two carbon-nitrogen bonds and (probably) a nitrogen-containing biradical inter- mediate.24 The pyrolysis of tetrahydropyridazines (29) and N-pyrrolidine nitrenes (30) as well as the thermal rearrangement of cyclobutanes has generally been interpreted in terms of a common 1,4-biradical although there is also evidence for a direct retro-(2+2 +2) fragmentation of the dia~ines.~’ 2o P.A. Wade and H. R. Hinney Tetrahedron Letters 1979 139. ” G. Bianchi C. De Micheli and R. Gandolfi Angew. Chem. Internat. Edn. 1979,18,721.22 J. Bourgois M. Bourgois and F. Texier Bull. SOC. chim. France 1978,1I 485. 23 A. R. Katritzky N. Dennis M. Chaillet C. Larrieu and M. El Mouhtadi,J.C.S. Perkin I 1979,408 and related papers. 24 P. C. Hiberty and Y. Jean J. Amer. Chem. SOC. 1979,101,2538. 2s P. B. Dervan T. Uyehara. and D. S. Santilli J. Amer. Chem. Soc. 1979,101,2069; P. B. Dervan and T. Uyehara ibid. p. 2076; P. B. Dervan and D. S. Santilli ibid. p. 3663. R. J. Bushby 3 Sigmatropic Rearrangements The stereochemistry of 2,3-sigmatropic rearrangements has continued to attract and has been reviewed,28 as has anchimeric assistance by silicon and its relevance to the mechanism of dyotropic rearrangement^.^' The phototranspositions of cyano-thiophens [for example the conversion of compound (31) into its isomer (32)] have been shown to involve 5-thiabicyclo- [2.1.0]pent-2-ene intermediates [(33) and (34) in the example given] which Me CN MP MeMcNMe interconvert via a sulphur ‘walk’.In some cases it has been shown that these intermediates can be trapped as their 2+4 furan adducts or as in the case of compound (33) isolated from the reaction mixture so that the sulphur ‘walk’ can be studied in i~olation.~’ An interesting related carbon ‘walk’ [bicyclopentene (35) to its isomer (36)] has also been reported.31 This thermal 1,3-shift involves inversion at the migrating centre as expected for an orbital-symmetry-controlled process. However the 1,3-shift in compound (39 the related 1,5-shifts in compounds (37) and (38) 32 and the 1,7-shift in compound (39)33 all apparently involve inversion at the migrating centre whether this is ‘allowed’ or not.The simplest view of these results is that the stereochemistries are determined by ‘least motions’ factors and that the distinction between ‘allowed’ and ‘disallowed’ processes is found not in the stereochemistries but in the activation energies which are 21.7 37.1 ca. 35 and 28.8 kcal mol-’ for compounds (33 (37) (38) and (39)respectively. However by using a specifically deuteriated 3,7-dimethyl-7-methoxymethylcycloheptatriene Baldwin claims to have shown that the 1,5-shift occurs by a two-step (C-7 epimerization) + (1,5-shift with retention) ‘allowed’ It is also found that ($C02Me -Ma#co2Me R2Me / & Me Me 26 E.Vedejs M. J. Arnost and J. P. Hagen J. Org. Chem. 1979,443230; V. Cert C. Paolucci,S. Pollicino E. Sandri and A. Fava ibid. p. 4128. ’’ E. Vedejs M. J. Arco D. W. Powell J. M. Renga and S. P. Singer J. Ore. Chem. 1978.43.4831; V. Cer6 C. Paolucci S. Pollicino E. Sandri and A. Favo ibid. p. 4826. 28 R. W. Hoffmann Angew. Chem. Internat. Edn. 1979,18,563. 29 M. T. Reetz Angew. Chem. Internat. Edn. 1979,18 173. 30 J. A. Barltrop A. C. Day and E. Irving J.C.S. Chem. Comm. 1979 881 966. 31 F.-G. Klarner and F. Adamsky Angew. Chem. Internat. Edn. 1979,18,674. 32 (a)F.-G.Klarner S. Yaslak and M. Wette Chem. Ber. 1979,112 1168; (b) J. E. Baldwin and B. M. Broline J. Amer. Chem. SOC.,1978,100 4599. Reaction Mechanisms -Part (i) Peric yclic Reactions 51 the photochemical rearrangements of compounds (37) and (38) like their thermal analogues involve overall inversion of the migrating Here epimerization at C-7 certainly competes with the 1,5-shift and the results have been interpreted in terms of a triplet biradical intermediate (40) which can either close or in which rotation about the C-6-C-7 bond occurs.Me 7 X Y (39) (40) X = C02Meor CN Migratory aptitude in 1,5-sigmatropic shifts seems to be determined by a number of factor^.^'-^^ Dolbier and his co-workers have shown that the isoindenes (41) [normally encountered as short-lived intermediates in the rearrangement of indene~~~] can be generated by eliminating N,O from the corresponding bicyclo- azoxy-system (42).35*39 They have studied the relative migratory aptitudes of the substituents R in these compounds seeking for evidence of a radical-pair mechanism.Whilst on quantitative grounds they demonstrated that the extent of radical development cannot be very great they did find a correlation between migratory aptitude and the stability of the radical (R). In other systems secondary orbital interactions seem to be important; for example in the migration of carbonyl groups. Whereas 1$shifts of alkyl groups in cyclopentadienes frequently require temperatures above 300 "C the rate of rearrangement of the formyl-substituted compound (43)is rapid (k= 90 s-l) at room tempe~ature.~' Here the transition state can be stabilized by an interaction between (1/3 of the pentadienyl system and T*of the formyl group (44).A complementary situation is seen in the rapid 1,5-shift of the carbanionic centre in compound (49 where a similar interaction may be written between t,h4 of the pentadienyl system and a filled p-orbital of the carbanion (46).38 33 F.-G. Klarner and M. Wette Chem. Ber. 1978,111 282. 34 F.-G. Klarner and S. Yaslak Chem. Ber. 1979,112 2286. 35 W. R. Dolbier K. E. Anapolle L. McCullagh K. Matsui J. M. Riemann and D. Rolison J. Org. Chem. 1979,44,2845. 36 D. J. Field and D. W. Jones J.C.S. Perkin I 1979 1273. 37 R. J. Bushby and D. W. Jones J.C.S. Chem. Comm. 1979,688. 38 G. Boche and D. Martens Chem. Ber. 1979,112 175. 39 W. R. Dolbier K. Matsui H. J. Dewey D. V. Horik and J. Michl J. Amer. Chem. Soc. 1979,101,2136.R. J. Bushby Li CN CN There have been several attempts to demonstrate carbon analogues (47) of the Claisen rearrangement.4043 Such reactions can be facilitated by incorporating a cyclopropane ring into the system as in compound (48).41 The general difficulty of these reactions and the need to add a base catalyst had been attributed to a mechanism in which the rate-determining step is prototropic rearrangement of the intermediate (49). However the lack of scrambling of the isotopic label in compound (50) has been taken to indicate that the first step (3,3-shift) and not the second step (prototropy) is rate-determini~~g.~~ Evidence for a 1,4-diyl(52) in the Cope rearrangement of the en-yn-ene (51)has been provided by isolating products from the 1,2-silicon shift shown in (52).44 However secondary isotope effects for and aliphatic46 Claisen rear- rangements do not support the notion of a 1,4-diyl in these reactions.Rather they suggest a non-synchronous concerted process in which bond breaking is in advance of bond making. As expected they indicate that the transition state comes early in the more exothermic aliphatic rearrangement but later in the aromatic case. 40 G. Maas and M. Regitz Angew. Chem. Internat. Edn. 1977,16,711. 41 E. N. Marvell and C. Lin J. Amer. Chem. SOC., 1978 100 877; E. N. Marvell and S. W. Almond Tetrahedron Letters 1979,2777 2779. 42 J. B. Lambert D. M. Fabricius and J. A. Hoard J. Org. Chem. 1979,44 1480. 43 J. B. Lambert D. M. Fabricius and J.J. Napoli J. Amer. Chem. SOC.,1979,101 1793. 44 G. C. Johnson J. J. Stofko T. P. Lockhart D. W. Brown and R. G. Bergman J. Org. Chem. 1979,44 4215. 45 K. D. McMichael and G. L. Korver J. Amer. Chem. SOC., 1979,101,2746. 46 J. J. Gajewski and N. D. Conrad J. Amer. Chem. SOC.,1979 101 2747,6693. Reaction Mechanisms -Part (i) Pericyclic Reactions 53 Me3s$3Bu Bu‘ Stereochemical and regioselective aspects of the photochemical di-T-methane rearrangement have continued to excite interest:’ and the interconversion of compounds (53)and (54) has provided the first example of a thermal reaction of this type.48 D 4 Electrocyclic Reactions The electrocyclic reactions of 1,5-dipoles have been reviewed49 and those of radical cations discussed in some detail.50 The 16~-electron vinylogous heptafulvene (55)51cyclizes thermally in a conro- tatory manner to give compound (56).Whilst this is the stereochemistry expected for an ‘orbital-symmetry-controlled’ process the related l4r-electron and 12~-elec- tron compounds (57)52and (58)53also cyclize in a conrotatory sense despite the fact (57) (58) 47 H.E. Zimmerman and D. R. Diehl J. Amer. Chem. SOC.,1979 101 1841; H. E. Zimmerman T. P. Gannett and G. E. Keck J. Org. Chem.,1979,44,1982;R. L. Coffin,W. W. Cox R. G. Carlson andR. S. Givens J.Amer. Chem. SOC.,1979,101,3261;L. A. Paquette A. Y. Ku C. Santiago M. D. Rozeboom and K. N. Houk ibid.,p. 5972; A. Y. Ku L. A. Paquette M. D. Rozeboom and K. N. Houk ibid. p. 5981; A. Padwa and T.Brookhart J. Org. Chem. 1979,44,4021. 48 M. Demuth U. Burger H. W. Mueller and K. Schaffner J. Amer. Chem. SOC.,1979 101 6763; M. Demuth C. 0.Bender S. E. Braslavsky H. Gorner U. Burger W. Amrein and K. Schaffner Helu. Chim. Actu 1979,62 847. 49 E. C. Taylor and I. J. Turchi Chem. Rev. 1979,79 181. E. Haselbach T. Bally and Z. Lanyiova Helu. Chim. Actu 1979 62 577; E. Haselbach T. Bally Z. Lanyiova and P. Baeryschi ibid.,p. 583. 51 H. Bingmann L. Knothe D. Hunkler and H. Prinzbach Tetrahedron Letters 1979 4053. ’* H. Prinzbach H. Babsch and D. Hunkler Tetrahedron Letters 1978,649. 53 H. Prinzbach H. Sauter and B. Gallenkamp Chem. Ber. 1977,110 1382. R. J. Bushby that compound (57) ‘should’ cyclize in a disrotatory manner. Since all three sub- strates probably adopt a spiral conformation the products obtained in each case are those expected on a ‘least motions’ basis.Probably the stereochemistries of these reactions are therefore the result of ‘least motions’ rather than ‘orbital symmetry’ control. There may however be some evidence for a weak alternation between what is ‘allowed’ and what ‘disallowed’ in the Arrhenius activation energies which are 20.0 24.4 and 22.1 kcal mol-’ for compounds (55)’ (57),and (58)respectively. It has been claimed that the cyclopropyl anion opens photochemically in a disrotatory manner.54 However the tendency of the products to undergo (photo- chemical) cis-trans isomerization renders the result open to some doubt. Similar problems have frustrated attempts to observe directly the stereochemistry of the thermal ring-opening The apparently ‘disallowed’ cyclization product (60) obtained by allowing the cyclononatetraenyl anion (59) to react with elec- trophiles RX has now been shown to arise in an ‘allowed’ manner from the trans-isomer of the anion.56 (59) 54 1979,101,4008.M. A. FOX,J. Amer. Chem. SOC. 55 G. Boche K. Buckl D. Martens D. R. Schneider and H.-U.Wagner Chem. Ber. 1979,112,2961. 56 G. Boche M. Bernheim D. Lawaldt and R. Ruisinger Tetrahedron Letters 1979,4285.

ISSN:0069-3030    

DOI:10.1039/OC9797600045

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (ii) Polar Reactions By H.R. HUDSON Department of Chemistry The Polytechnic of North London Holloway Road London N7 8DB 1 Introduction The mechanisms of polar organic reactions are inevitably influenced by the medium in which they occur. Considerable effort is therefore being directed to the investiga- tion of intrinsic properties of solvent-free reactions by the study of ion-molecule reactions in the gas phase.’ At the same time attempts are being made to rationalize the polar effects of solvents on rates equilibria heats and free energies of solution or transfer and spectroscopic properties through linear solvation-energy relation- ships2 Earlier work in this field has been re~iewed.~ The effects of changes of medium on rate processes and structures of transition states have also been examined from the viewpoint of thermodynamic transfer functions and the effects of micellar catalysts on the rates and mechanisms of a variety of reaction types have been st~died.~ The following report deals with some novel aspects of the year’s work on the basic types of polar organic reaction and reaction intermediate.A fuller account is published elsewhere.6 2 Solvolytic Reactions Solvolysis of Saturated Alkyl Substrates.-A novel approach to the analysis of solvolytic reaction mechanisms has been based on a multi-parameter optimization procedure.’ The method was used to interpret solvolytic data for the substitution and elimination reactions of cyclopentyl p-bromobenzenesulphonate (1)and its a-’H ‘Gas Phase Ion Chemistry,’ ed.M. T. Bowers Academic Press New York 1979. * M. J. Kamlet and R. W. Taft J.C.S. PerkinII,1979,337;M. J. Kamlet M. E. Jones R. W. Taft and J.-L. Abboud ibid. p. 342; M. J. Kamlet and R. W. Taft ibid. p. 349; R. W. Taft and M.J. Kamlet ibid. p. 1723; M. J. Kamlet A. Solomonovici and R. W. Taft J. Amer. Chem. SOC., 1979 101 3734; M. J. Kamlet T. N. Hall J. Boykin and R. W. Taft J. Org. Chem. 1979 44 2599. C. Reichardt Angew. Chem. Internat. Edn. 1979,18 98. E. Buncel and H. Wilson Accounts Chem. Res. 1979 12,42. D. C. Bredt N. Utrapiromsuk and S. S. Jaglan J. Org. Chem. 1979,44,136;G. B. van de Langkruis and J. B. F. N. Engberts ibid. p. 141; A. Pillersdorf and J. Katzhendler ibid. p. 549; W. Tagaki D. Fukushima T.Eiki and Y.Yano ibid.,p. 555; A. Pillersdorf and J. Katzhendler ibid. p. 934; A. Finiels and P. Geneste ibid. p. 2036; M. Croce and Y. Okamoto ibid. p. 2100; Y. Yano Y. Yoshida A. Kurashima Y. Tamura and W. Tagaki J.C.S. Perkin II 1979 1128; T. Kunitake Y. Okahata S. Tanamachi and R. Ando Bull. Chem. SOC. Japan 1979,52,1967; H. Fujii T. Kawai and H. Nishikawa ibid. p. 1978; T. Kunitake and T. Sakamoto,’ibid.,p. 2624. ‘Organic Reaction Mechanisms 1979’ ed. A. C. Knipe and W. E. Watts Wiley London 1980. ’V. J. Shiner jnr.. D A. Nollen and K. Humski J. Org. Chem. 1979,44 2108. H. R. Hudson cis-p-*H and p-2H4 analogues in eight different solvent systems consisting of ethanol-water trifluoroethanol(TFE)-water and hexafluoroisopropyl alco- hol(HF1P)-water.Assuming the possibility of product formation from both contact and solvent-separated ion-pairs the total number of mechanistic parameters required to define the system is 78. This number was reduced to 46 by assuming that isotope effects are independent of the solvent used and are identical for certain steps of the reaction and that anti-/syn-elimination ratios are identical under specified conditions. To fit the reaction parameters to 95 experimental observations the simplex method of optimization was used (see e.g. S. N. Deeming and S. L. Morgan Analyt. Chem. 1973 45 278A; 1974 46 1170) this being apparently the first application of the method to the correlation of rates product distributions and isotope effects. The outcome of the analysis was that significant fractions of ion-pair return were shown to occur in most solvents nucleophilic solvation was not apparently involved and the secondary p-2H effects on elimination of a proton from the tight ion-pair suggested a twisted-envelope transition-state structure for this process.The interpretation differs from that of Bentley and Schleyer who consider borderline solvolyses of secondary sulphonates to occur via the rate-determining formation of nucleophilically solvated ion-pairs for which return is kinetically insignificant [Ann. Reports (B) 1976,73 55; 1974,71 1161. The importance of nucleophilic solvation for simple s-alkyl cations has been stressed in a comparative study of heats of ionization (AHi)for alkyl chlorides in SbF and their corresponding free energies of limiting solvolysis in ethanol.* The results confirm the view that rates of limiting solvolysis are a good measure of stabilities of carbonium ions.For simple secondary alkyl chlorides the solvolytic data correlated well with AHiafter a correction for nucleophilic solvation had been made. In the case of secondary or tertiary 2-norbornyl substrates (2) a good correlation was obtained for the exo-isomer indicating that the solvolytic transition state is closely related to the resulting carbo-cation. The result is in keeping with 0-delocalization in this case and it is interesting to note that a similarly good correlation was not found for the endo-isomer. Other evidence in favour of a steric interpretation of high exo-/endo- rate ratios in 2-norbornyl solvolyses has been provided by the relative rates for some 2-substituted exo-or endo-5,6-trimethylene-2-norbornyl p-nitrobenzenesul-phonates (3) in which the 5,6-trimethylene bridge provides steric interference to cr-interaction in the exo-isomer.’ exo-/endo-Rate ratios of 118 (2-phenyl) 286 [2-(5’-coumaranyl)] and 420 (2-methyl) were nevertheless observed.Evidence has been presented for unexpected examples of nucleophilic solvent assistance in the solvolysis of t-butyl halides. The conclusions were based on a comparison of reaction rates with those of adamantyl substrates in aqueous ethanol and HFIP and indicated a mechanistic change for the t-butyl halides as the medium E. M. Arnett C. Petro and P. von R. Schleyer J. Amer.Chem. SOC.,1979,101 522. H. C. Brown C. G. Rao and D. L. Vander Jagt J. Amer. Chem. SOC.,1979,101 1780. Reaction Mechanisms -Part (ii) Polar Reactions Y Y (2) X = C1 Y = H or substituent (3)X = OBs Y = substituent Y = C1 X = H or substituent Y = OBs X = substituent became more nucleophilic." It was also shown that trifluoroacetic acid (TFA) is more nucleophilic than HFIP towards simple s-alkyl tosylates although trifluoroacetolyses of the latter are normally regarded as good models for SN1 (limiting) reactions. A new scale of solvent nucleophilicities based on the two-term Grunwald- Winstein equation has been set up by the use of first-order rate coefficients obtained for the solvolysis of triethyloxonium hexafluorophosphate in various organic or aqueous-organic solvent mixtures." By the use of a positively charged substrate contributions from the solvent ionizing power (Y) are reduced to less than 10%of those for an initially neutral substrate and can be estimated from data available for solvolysis of t-butyldimethylsulphonium ion.The new 'NKL'values [based on equation (l)]were applied to previously studied solvolyses of alkyl tosylates and NKL=log (k/ko)Et30+-0.55 Y (1) alkyl chlorides and were shown to be applicable to both RX- and RX'-type substrates. The reactivity selectivity principle (r.s.p.) has continued to attract atten- tion in the study of solvolytic reactions although there are circumstances under which it does not hold. Some possible reasons for its failure have been discussed in terms of More O'Ferrall plots [cf.J.Chem. SUC.(R) 1970,2741 which illustrate the possibility of movement of the transition state over a potential surface without significant change in the nucleophile-carbon distance. l2 The lack of a relationship between reactivity and selectivity in the reactions of octyl 1-methylheptyl and benzyl derivatives with m-chloroaniline and ethanol has led to the conclusion that selectivity values derived from two unrelated nucleophiles (i.e. those not having a common nucleophilic atom) cannot be utilized as a measure of structure of the transition ~tate.'~ Selectivity was also found to be dependent on the nature of the substrate and the solvent. The results were rationalized by perturbation molecular orbital theory and it was suggested that the differential HOMO-LUMO gap governs selectivity.The range of applicability of the r.s.p. to SN2reactions in which a series of related nucleophiles and related leaving groups is involved is still not clear. In the solvolytic reactions of 1-adamantyl bromide picrate 2,4-dinitrophenolate and tosylate in aqueous ethanol the variation of selectivity with substrate and with solvent composition was attributed to the differing abilities of the various ion-pair intermediates to select a molecule of water or of ethanol in the formation of a solvent-separated ion-pair. l4 lo T. W. Bentley C. T. Bowen W. Parker and C. I. F. Watt J. Amer. Chem. Soc. 1979,101 2486. '*D. N. Kevill and G. M. L. Lin J. Amer. Chem. Soc. 1979 101 3916.J. M. Harris S. G. Shafer J. R. Moffatt and A. R. Becker J. Amer. Chem. Soc. 1979,101 3295. l3 Y.Karton and A. Pross J.C.S. Perkh II 1979 857. l4 P. R. Luton and M. C. Whiting J.C.S. Perkin 11 1979 646. H. R. Hudson A new treatment of the solvolysis of t-butyl chloride employs Me4" C1- as a model for the transition state because of its similar size and high p01arity.l~ Twelve solvents were considered including hydroxylic solvents (in which both substitution and elimination can occur) and aprotic media (which lead only to elimination). The free energy of cavity formation in each solvent IG,,,I, was calculated for the reactant R the activated complex AC and the model M; by taking methanol as the reference solvent relative cavity terms I Gcavlzl, were obtained.These were combined with free energies of transfer from gas phase to solvent IG,] to give the relative solvent- solute interaction terms I Giatlzl. The linear correlation obtained between terms for AC and those for M indicates that the charge separation in the transition state remains approximately constant for all the solvents studied whilst the slope (0.73) confirms the highly polar nature of the activated complex. Solvolysis of Vinyl Substrates.-The first comparison of titrimetric (k,)and polari- metric (k,) rate constants for the solvolysis of a vinyl substrate has been made for 9-(cy-bromoanisylidene)-l0-hydroxy-9,10-dihydroanthracene(4)in 2,6-lutidine- buffered TFE at 49.5OC.16 The extent of rate depression by a common ion and the identity of ky and k values showed that a free vinyl cation (5)was involved.Product formation from ion-pairs and ion-pair return with racemization in TFE were excluded. Some caution must however be exercised in the application of the k,/k probe to systems such as this in which alternative rate-determining ionization steps are available. Although C-Br heterolysis was rate-determining in good ionizing and relatively non-acidic solvents (TFE or 80% ethanol) it was found that the initial site of reaction was solvent-dependent. l7 In acetic acid for example the initial cleavage was of the bond between C-10 and oxygen and alternative reaction pathways were introduced (Scheme 1).In either case the carbo-cation that is formed is non-chiral and optical activity is lost.An Br ,An I n c+ + products @JJ \ \ H-OH H OH (4) (5) H+Jr Br ,An Br ,An Br +,An C C @J-J -&J \ \ I H + products Scheme 1 J. J. M. Ramos R. Reisse and M. H. Abraham Canad. J. Chem. 1979 57 500. l6 Z. Rappoport and J. Greenblatt J. Amer. Chem. SOC.,1979 101 1343. " Z. Rappoport and J. Greenblatt J. Amer. Chem. SOC.,1979,101 3967. Reaction Mechanisms -Part (ii) Polar Reactions The solvolysis of (bromocyclopropylmethy1ene)cyclopropane(6) in aqueous ethanol of TFE has been shown to proceed via a vinyl cation (7) in which stabilization by both the cyclopropyl and the cyclopropylidene rings is possible.18 The effects of added salts (KBr LiC104 or LiCl) together with product analyses indicated a reaction scheme which involves rearrangement to the 2-cyclo-propylcyclobutenyl (8) and 4-cyclopropylhomopropargyl (9) cations and in which intimate ion-pairs [(7) (8) and (9)] solvent-separated ion-pairs [(7) and (S)] and dissociated ions [(7) and (S)] may occur.In aqueous ethanol Grunwald-Winstein m values of 0.92 or 1.00 (the highest so far obtained for a vinyl derivative) showed the solvolysis to be almost a pure k process. Rearrangement among cyclobutenyl cyclopropylidene and homopropargyl cations has also been reported in the solvolyses of a series of 2- or 3-substituted cyclobutenyl nonaflates (10-12; R = Me or aryl).” The rates of solvolysis of cyclic vinyl nonaflates have previously been shown to increase with ring size in the range C5-C9 a reflection of the preferred linear geometry of the vinyl cation.Much higher reactivity for the four-membered cyclobutenyl derivatives is therefore attributed to the formation of stabilized non- classical intermediates (13)-( 15) respectively. e,(10) ONf R (11) ONf RQ(12) ONf R An unusual example of complete rearrangement with substitution in the reaction of a substituted 1-cyclohexenyl substrate has been provided by the solvolysis of the steroidal derivative 5a -cholest-1-en-1-yl triflate (16).20 The reaction in a sodium- acetate-buffered mixture of acetone and water yielded substitution products (17)- (20) presumably via an ally1 cation intermediate (21) which was formed in a concerted ionization and migration process. R. Kopp and M. Hanack Chem.Ber. 1979,112,2453. lg M. Hanack E. J. Carnahan A. Krowczynski W. Schoberth L. R. Subramanian and K. Subramanian J. Amer. Chem. SOC.,1979,101 100. G.Ortar and E. Morera Tetrahedron Letters 1979 4881. H. R. Hudson (17) R' =OH R2 = Me (19) R' = H R2= OH (21) (18) R' =Me R2= OH (20) R' =OH R2= H 3 Nucleophilic Substitution in Non-solvolytic Reactions Substitution in Saturated Aliphatic Substrates.-In the SN2 reaction of thio-phenoxide ion with benzyldimethylphenylammonium ion (Scheme 2; Ar' = Ar2= Ar3= Ph) in DMF at 0 "C an unusually large secondary a -deuterium kinetic isotope effect was observed (1.179*0.007 i.e. 1.086 f0.003 per Q-D).~~ This is significantly higher than the normal values for SN2reactions (kH/kD= 1.082 or 1.04 per a-D) and indicates that maximum values are more dependent on the bulk of the leaving group than was previously supposed.Such values should therefore be established for each leaving group before being used as a criterion of mechanism. In an analogous Ar'S- + Ar2CH2kMe2Ar3 -+ Ar'S--C--NMe2Ar3 -+ Ar'SCH2Ar2 + Me2NAr3 L \A 1 Scheme 2 study (Scheme 2; Ar'=p-MeOC6H4 p-MeC6H4 Ph or p-C1C6H4;Ar2=Ph; Ar3= p-MeOC6H4 Ph or p-ClC6H4),heavy atom (N) kinetic isotope effects secondary a-deuterium isotope effects and Hammett p values showed that a change to a better leaving group resulted in a more product-like transition state.22 Secondary a-deuterium kinetic isotope effects have also been used to study the symmetrical Finkelstein reaction (Scheme 3) but were complicated in dipolar XC6H4YCZ2Cl + Et4NCl' $ XC6H4YCZ2Cl' + Et4NCl X = H p-C1 p-Me p-MeO p-NO2 rn-C1 or m-Me Y=O S CHLCH none (i.e.benzyl) or CH2 Z=HorD Scheme 3 aprotic solvents by the formation of a substrate-nucleophile complex.23Specific association was demonstrated (Scheme 4) by the observation of a low-field shift of absorption in the 'H n.m.r.spectrum and it was seen to be strongest in the case of the most electronegative anion i.e. The effect was observed in aceto-nitrile DMSO and DMF but was retarded by the addition of methanol because of competitive hydrogen-bonding. Complex formation was thought to involve " K. C. Westaway and S. F. Ali Canad. J. Chem. 1979,57,1089. 22 K. C. Westaway and S. F. Ali Canad. J. Chem.1979 57 1354. 23 J. Hayami N. Hihara N. Tanaka and A. Kaji Buff. Chem. SOC.Japan 1979,52,831. 24 J. Hayami T. Koyanagi N. Hihara and A. Kaji Buff.Chem.SOC. Japan 1978,51,891 and cited papers. Reaction Mechanisms -Part (ii) Polar Reactions ArXCH2C1 + Y-+ ArXCH2C1Y-Ar = Ph or substituted Ph X = none S SO SO2,or CO Y = C1 Br or I (as R,NY; R = Et or Bu) Scheme 4 hydrogen-bonding of the nucleophile to the 'acidic' a-methylene protons thus locating it in the close neighbourhood of the rear side of the C-Cl bond in a site of potential SN2 attack. The overall observed secondary a-deuterium isotope effects were therefore dissected into equilibrium isotope effects of bimolecular association (KH/KD)and kinetic isotope effects for unimolecular scrambling of the complex (kr/&y),such that ky/ky = (ky/ky)x (KH/KD).23For activated systems the analysis leads to a fairly large and uniform kinetic isotope effect (1.127-1.147) approaching that for limiting solvolysis whereas the value for the 2-arylethyl chlorides is nearer to unity.The investigation was also extended to substrates of extremely low reactivity uiz. p-nitroarylsulphonyl-chloromethanes,p-nitroaryl-sulphinyl-chloromethanes and 2-chl0ro-l-ethanones.~~ For the halogeno-ketones the association mechanism leads to an a-deuterium effect of ca. 1 suggesting the intermediacy of a very tight ion-pair. The positive entropies of activation for these highly deactivated substrates do not accord with steric hindrance to reaction but the overall interpretation is still not clear.The association-scramble mechanism is a possibility that requires further investigation. The intriguing possibility of an SN2reaction with retention of configuration has been theoretically predicted for substitution in small ring compounds (P. D. Gilles-pie and I. Ugi Angew. Chem. 1971 83,493; W. D. Stohrer and K. R. Schneider Chem. Ber. 1976 109 285). Unfortunately an attempt to demonstrate such a process by diazotization of syn-or anti-11-aminotricyclo[4.4.1 .O1.']undec-3-ene (22) in the presence of sodium bromide failed.26 As reported for the decomposition of exo-7-norcaranediazonium ions [Ann. Reports (B) 1978 75 571 retentive substitution results when disrotatory cyclopropyl-ally1 rearrangement is initiated but it cannot be completed for reasons of ring strain.A partly opened cyclopropyl cation is therefore most probably involved as described previously. Q (22) Preponderant retention of configuration has long been known to occur in the formation of alkyl chloride by the thermal decomposition of an optically active s-alkyl chloroformate in the liquid phase. A mechanism which involves the forma- tion and collapse of an ion-pair intermediate is most likely. Extensive alkyl rearrangement in the case of primary alkyl chloroformates shows that these 25 J. Hayami T. Koyanagi and A. Kaji Bull. Chem. SOC.Japan 1979,52,1441. 26 W. Kirmse and T. Engbert Angew. Chem. Internat. Edn. 1979 18,228. H. R. Hudson decompositions also have considerable carbonium-ion chara~ter.~~ Products are obtained resulting from competitive 1,2-hydride 1,2-alkyl and 1,3-hydride shifts the latter being thought to proceed via protonated cyclopropane intermediates.An example has been reported of what is claimed to be a directly observable model of an sN2 transition state (23).28 The central carbon atom in the structure shown is R I Ph (23) X=MeorF R = H or But associated with five ligands which contribute ten electrons to the bonding unlike pentaco-ordinate 'onium species (e.g. CH,') in which only eight electrons are involved. The species was prepared in liquid SO2or S02-S02C1F at -80 "C and was distinguished from other non-symmetrical possibilities in which one of the C-S bonds is absent by 'H and "F n.m.r.spectroscopy. Allylic Substitution.-Although the precise timing of bond-making and bond- breaking in the sN2' process has been the subject of controversy the stereochemical outcome is open to direct investigation. Both syn- and anti-attack have been reported previously according to conditions. It has now been that the attack of diethylamine on (-)-(R)-and (+)-(S)-3-chloro-(Z)-[ l-2H]but-l-ene proceeds with ~95% syn -stereospecificity (Scheme 5). This is a relatively simple allylic system which has no built-in conformational preference for syn-attack and yet the degree of stereospecificity is much higher than that reported previously for the amminolysis of (R)-or (S)-[l-2H]alk-l-en-3-yl 2,6-dichlorobenzoates [Ann. Reports (B) 19'78 75 511. Most theoretical analyses predict a preference for syn-attack and the role of hydrogen-bonding between the attacking and leaving groups is still not clear.An intramolecular displacement with concerted allylic rearrangement by carbanion has however been shown to proceed with an anti- relationship between the attacking and departing groups (Scheme 6),30this paral- lelling a previous result with sulphide as the internal nucleophile. It is likely that the nature of the counter-ion the leaving group and the medium are all important factors in determining the course of the reaction. The reactions of a-,0-, and y-methylallyl chlorides with silver nitrate in aceto-nitrile have been shown to exhibit kinetics which are first-order in substrate and of 27 H. R. Hudson A.J. Koplick and D. J. Poulton J.C.S. Perkin 11 1979 57. '* T.R.Forbus jnr. and J. C. Martin J. Amer. Chem. Soc. 1979 101,5057. 29 R.M. Magid and 0.S. Fruchey J. Amer. Chem. Soc. 1979,101,2107. 30 G.Stork and A. R. Schoofs J. Amer. Chem. Soc. 1979,101 5081. Reaction Mechanisms -Part (ii) Polar Reactions (-)-(R)-chloride 1 1 (E)-isomer (95%) (2)-isomer (5%) C1 H (+)-(.$)-chloride (€)-isomer (100%) Scheme 5 0 c1 -NaH THF-DMF -aH;. E 5540 "C VHACH, EE / CH E = CO2Et EE Scheme 6 order 1.5 in silver nitrate.31The results indicate that either nucleophilic assistance by nitrate ion is involved in a rate-determining attack on a pre-formed ion-pair intermediate or that synchronous SN2'attack is more important in the presence of silver ion than was previously believed for similar anionic substitutions in its absence.4 Carbo-cations Detailed information on the structures and properties of carbo-cations continues to be obtained from studies in super-acid media and in the gas phase. Also reported this year are the first high-resolution I3Cn.m.r. spectra of carbo-cations in the solid state determined for diethoxycarbonium hexachloroantimonate (24) and heptamethyl-benzenonium tetrachloroaluminate (25) by 'magic-angle' spinning.32 Preparation and Properties in Super-acid Media.-The 'H and 13Cn.m.r. spectra of secondary cycloalkyl cations derived from 1-chloro-cycloalkanes (C8-Cll) in SbFS/SO2C1F-SO2F2at ca. -140"Creveal hydrido-bridged structures (26)-(29).33 These correspond to those cycloalkyl systems in which transannular hydride shifts 31 D.N. Kevill and C. R. Degenhardt J. Amer. Chem. Soc. 1979,101,1465. 32 J. R. Lyerla C. S. Yannoni D. Bruck and C. A. Fyfe J. Amer. Chem. Soc. 1979,101,4770. 33 R. P. Kirchen and T. S. Sorensen J. Amer. Chem. Soc. 1979 101 3240 and cited references. H.R. Hudson (25) occur in the course of nucleophilic substitution. The cyclo-octyl cation (26) was the least stable of the series and rearranged rapidly to 1-methylcycloheptyl (tt ca. 17min at -142°C). Ring contraction occurred more slowly in the case of the cyclononyl (27) and cycloundecyl (28) ions whilst the hydrido-bridged cyclodecyl ion (29) lost hydrogen to give cyclodecalyl. Attempts to prepare cycloheptyl and cyclohexyl cations invariably result in the immediate formation of the ring-contrac- ted products presumably because hydrido-bridging does not occur in these cases.(26) (27) (28) (29) In a study of highly strained bicyclo[l.l.l]pentyl cations it was found that the parent species (30) could not be detected in SbF5/SO2C1F even at -140 0C.34 The carbo-cation centre appears to interact strongly with the C-C c+-bonds of the bicyclic ring system with consequent rearrangement to 3-cyclopentenyl (31). The 4-cyclopentenyl cation was assumed to occur as a transient inter-mediate. The presence of a phenyl substituent at position 2 i.e. as in (32) had a stabilizing effect on the carbo-cation which could then be observed at -140 "C although rearrangement to the allylic structure (33) was quantitative at -30 "C.The first examples of the previously unknown chloromethylhalonium ions have been rep~rted.~' Bis(chloromethy1)chloronium ion (34)was obtained by the inter- action of dichloromethane with an excess of SbF in S02CIFat -130 "C and it was found to be a powerful chloromethylating agent which reacted with sulphur dioxide monohalogeno- and dihalogeno-alkanes and ethers as shown (Scheme 7). Gas-phase Studies.-Heats of formation (AHf)for simple alkyl cations (Me+ Et' i-Pr+ and t-Bu') have been determined uia photoelectron spectroscopy of the corresponding radicals.36 The value for t-butyl (162.9f1.2 kcal mol-') agrees well with a recent figure derived by photoionization mass spectrometry of isobutane and 34 G.A. Olah G. K. Surya Prakash and G. Liang J. Amer. Chem. SOC.,1979,101,3932. 35 G.A.Olah and M. R. Bruce J. Amer. Chern. SOC,1979,101,4765. 36 F.A.Houle and J. L. Beauchamp J. Arner. Chem. SOC.,1979 101,4067. Reaction Mechanisms -Part (ii)Polar Reactions [CH3XCH*CI]+ [CICH2CICH2Cl]' -S [ClCH2-O=S=O]+ (34) iiil + ;CH3\ + [C1CH2XCH2CI]+ XC&-0 H*C=O-CH2Cl \ CH2CI Reagents i CH,X; ii ClCH,X; iii XCH,OCH,; iv ClCH,OCH,Cl; v SO Scheme 7 the t-butyl halides (162.1f8 kcal m~l-l),~' and indicates that a currently accepted value is 6-7 kcal mol-1 too high (cf. F. P. Lossing and G. P. Semeluk Cunad. J. Chem. 1970,48,955).A new value for AHffor (2-norbornyl') (182f2 kcal mol-') determined from a study of proton-transfer equilibria agrees well with previous data and shows this cation to be more stable than other cyclic secondary cations by cu.6 kcal m01-l.~~ The 2-adamantyl cation (39) has been detected as a stable species in the gas phase for the first time.39 Dissociative ionization of the corresponding bromides gave the l-adamantyl (40) and 2-adamantyl (39) ions which did not rearrange and which were distinguished by collision activation spectroscopy. Bromide-transfer reactions have confirmed the order of stabilities indicated for ions (35)-(40) and have shown that (37) and (40) differ in stability by no more than 4 kcal m~l-'.~' The l-adamantyl cation is therefore to be regarded as a normal tertiary cation but 2-adamantyl appears to be more stable than might be expected for a classical secondary cation.A A Photoionization mass spectrometry has shown that two non-interconverting halonium ions (41) and (42) can exist in the gase phase these being produced by photoionization of the corresponding 1,l -dihalogeno- and 1,2-dihalogeno-alkanes re~pectively.~~ Heats of formation were calculated for each species and it was shown that the cyclic isomer (42)is more stable by 1.4 kcal mol-' if X is Br but less stable by 5.6 kcal mol-' if X is C1. The relative stabilities of other 'onium ions (X = OH SH NH2,or PH2) were found by the use of ion cyclotron resonance spectroscopy which enabled the preferred direction of exchange [equation (2)] to be determined. Other C2H4X+ + HY + C2H4Y+ + HX (2) gas-phase studies have included a photoionization investigation of the structures of the c8H8+ cations obtained from the isomeric compounds styrene cyclo-octa- tetraene and barrelene (43).42Rearrangement to a common structure was not 37 R.G. McLoughlin and J. C. Traeger J. Amer. Chem. SOC.,1979 101 5791. 38 P. P. S. Saluja and P. Kebarle J. Amer. Chem. SOC.,1979 101 1084. 39 C. Wesdemiotis M. Schilling and H. Schwarz Angew. Chem. Internat. Edn. 1979,18,950. 40 R. Houriet and H. Schwarz Angew. Chem. Internat. Edn. 1979,18,951. 41 D. W. Berman V. Anicich and J. L. Beauchamp J. Amer. Chem. SOC.,1979 101 1239. 42 R. C. Dunbar M. S. Kim and G. A. Olah J. Amer. Chem. SOC.,1979,101,1368. H.R. Hudson observed and in the case of styrene and barrelene at least the original structure appeared to be retained.Protonation however caused relatively rapid rearrange- ment to the most stable gas-phase form of C8H9+,which is thought to be the styryl cation. The first clear evidence for the existence of cyclopropylcarbinyl and cyclobutyl cations in the gase phase has been provided by allowing multi-tritiated cyclobutane to undergo P-decay [equation (3)] in the presence of water or ammonia in the dilute &decay c-C4Hs-,T -c-C4H7-,,Tn + 3He + p-(3) gaseous In addition to products derived from skeletal rearrangement cyclobutanol (or cyclobutylamine) and cyclopropylcarbinol (or cyclopropylamine) were formed presumably by interaction of the nucleophilic water or ammonia with the corresponding cyclic cations. 5 Carbanions Spectrophotometric studies of (triphenylmethy1)lithium and (triphenyl-methy1)potassiumin dimethoxyethane (DME) THF and diethyl ether have shown that contact ion-pairs or solvent-separated ion-pairs may exist according to the solvent and the The addition of 18-crown-6 ether converted the contact ion-pairs into complexes whose absorption maxima were closely similar to those for the solvent-separated species.A similar effect has been noted previously for fluorenylsodium in THF but this is the first report of such a complexing effect when the counter-ion is lithium. Ion-pairing has been shown to increase the stability of the fluoradenide ion (FD-) (44) with respect to its electron-transfer equilibrium with nitr~benzene.~~ The ion was generated in the presence of methoxide ion in methanol which can stabilize both MeO- and PhNO2; by hydrogen-bonding.Although hydrogen-bonding between methanol and the FD- ion might also occur this is a highly delocalized carbanion and it is energetically favourable to replace such solvation by ion-pairing provided that a large cation is available. Ion-pairs were shown to be formed with cations such as R4N+or Cs+,and with smaller cations in the presence of crown ethers. M+ -:::ig (44) \/ (45) n = 0 1,or 2 43 F. Cacace and M. Speranza J. Amer. Chem. SOC.,1979 101 1587. 44 E. Buncel and B. Menon J. Org. Chem. 1979,44,317. 45 R. D. Guthrie and N. S. Cho J. Amer. Chem. SOC.,1979,101,4698. Reaction Mechanisms -Part (ii) Polar Reactions To obtain information on the role of neighbouring sulphur as a stabilizing group for carbanions the oxidation number of sulphur was varied in a series of alkali-metal fluorenyl carbanions (45) that were substituted with phenyl-sulphur groups in the 9-po~ition.~~ At +20 to -78 "Cthe electronic absorption spectrum of the sulphenyl carbanion (45; n = 0) corresponded to the solvent-separated species PhSFl-IIM' or to the free anion and a stabilization due to the phenylsulphenyl substituent of ca.5.5 kcal mo1-I was calculated. The sulphinyl carbanion (45; n = 1)existed as contact ion-pairs even in MTHF at 77 K and its greater stability was explained on the basis of electrostatic interaction between the sulphinyl oxygen and the counter-cation. A completely different type of absorption spectrum in the case of the sulphonyl derivative (45; n = 2) was attributed to intramolecular charge transfer which places the negative charge on the sulphonyl oxygen atoms in the excited state.Proton n.m.r. spectra oxidation potentials and electron-transfer reactions for the three types of carbanion were also reported and it was concluded that the stabilizing influence of the phenyl-sulphur groups can be correlated with their inductive effects. The role of pT-d interaction was not clear. Selenium-stabilized carbanions have also been reported as intermediates in the reactions of enolates with 3-methylallyl br~mide.~' New information on rotational barriers for allyl carbanions in solution has been obtained from n.m.r. exchange rates for the terminal protons of allyl-alkali-metal compounds in THF.48 The results provide the first reliable evidence on the simple allyl anion and give a new lower limit for AG' of 18 kcal mol-' determined for allylcaesium.Quantitative data were also given for the rotational barriers in alkyl- substituted allyl carbanions. Gas-phase Studies.-A new method for the generation of carbanions in the gas phase involves the reaction of the corresponding trimethylsilyl derivative with fluoride ion (Scheme 8).49This has the advantage over methods based on proton F-+ CH3C=CSiMe3 CH3CGC-+ FSiMe3 F-+ HCECCH2SiMe3 + HC=CCHz-+ FSiMe3 Scheme 8 abstraction that the desired anion is produced unambiguously. The possibility of base-catalysed rearrangement of the anion is also obviated. Reaction with molecular oxygen in either its triplet or singlet state appears to be a potentially valuable method for the gas-phase degradation of organic anions and for the determination of their Specific cleavage is induced reflecting the site of negative charge; e.g.the 2,4-hexadienyl anion reacted with triplet oxygen at the non-terminal negative sites to give enolate anions (Scheme 9). CH,CH=CHCHO + -OCH=CHz s-6-6-/-CH~-CH-CH=CH=CHECHZ + 302 + CH3CH=CH-O-+ OCHCH=CH2 CH3CH0 + -OCH=CHCH=CHz Scheme 9 46 S. Nishi and M. Matsuda J. Amer. Chem. SOC.,1979,101,4632. 47 H.J. Reich and M. L. Cohen J. Amer. Chem. SOC., 1979,101 1307. 48 T. B.Thompson and W. T. Ford J. Amer. Chem. SOC., 1979,101 5459. 49 C. H. Depuy V. M. Bierbaum L. A. Flippin J.J. Grabowski G. K. King and R. J. Schmitt J. Amer. Chem. SOC.,1979,101,6443. R. J. Schmitt V. M. Bierbaum and C. H. Depuy J. Amer. Chem. SOC., 1979,101,6443. 68 H. R. Hudson 6 /3 -Elimination The structures of E2 transition states have been discussed in the context of elimination reactions of substituted benzyldimethylcarbinyl chlorides in the presence of methanol methoxide and mercaptide Hammett p values of -0.9 for methanolysis and of +1.2 for the formation of ArCH=CMe2 from the methoxide-induced eliminations of the 3,5-dichloro- and p-nitro-derivatives51 can be rationalized on the basis of a transition state which may vary between the paenecarbenium and paenecarbanion extremes [(46)-(48)]. A similar variation in E! H :I -7-c-X (47) (48) transition-state structure is consistent with the U-shaped Hammett plot which was obtained for mercaptide-ion-induced eliminations and in this case a competing (E2)ip mechanism might also be The E2CIE2H hypothesis [cf.Ann. Reports (B) 1977,74,82] was discussed in some detail particularly with respect to the relative rates of eliminations induced by EtS- and MeO- but was considered to provide a less satisfactory explanation of the experimental results. The influence of attacking base on positional orientation has been studied for various s-alkyl substrates [equation (4)] in their reactions with oxyanions nitrogen bases or carbanions in DMSO. Previous investigations had shown that the relative proportions of terminal and internal alkenes obtained from 2-iodobutane (49; X = I R = Me) were controlled by base strength rather than size in the case of attack by oxyanions unless extremely bulky species such as 2,6-di-t-butylphenoxide were In general a stronger base yields more of the alk-1-ene and a similar variation with base strength has been observed for amide anions derived from substituted anilines amides and sulphonamides.The effects of methide ions were more dependent on base type and ion-pairing was seen to be an important factor in eliminations promoted by dimsyl anion. The level of complexity of the base at which its steric influence becomes significant was found to depend on the size of the P-substituent R but it was independent of the leaving group X.54 For R=Pr' steric effects became apparent with t-butoxide.Anomalous results in the formation of 4,4-dimethylpent-2-ene from (49; R = But,X = OTs) were interpreted in terms of a syn -elimination which is forced on the system by the unfavourable steric interactions which would occur between the t-butyl and tosylate moieties in the transition state for anti-elimination. RCH2CHXCH3 %RCH=CHCH3 + RCHzCH=CH:! (4) (49) 51 J. F. Bunnett and S. Sridharan J. Org. Chem. 1979,44 1458. 52 J. F. Bunnett S. Sridharan and W. P. Cavin J. Org. Chem. 1979,44 1463. 53 R. A. Bartsch D. K. Roberts and B. R. Cho J. Org. Chem. 1979 44,4105. " R. A. Bartsch R. A. Read D. T. Larsen D. K. Roberts K. J. Scott and B. R. Cho J. Amer. Chem. Soc. 1979,101,1176. Reaction Mechanisms -Part (ii) Polar Reactions ‘Complex bases’ such as NaNH2-Bu‘ONa are known to favour syn-elimination from trans-l,2-dibromo-alkanes (C,-C,) (P.Caubere Accounts Chem. Res. 1974 7,301). Investigations with compounds containing two different halogens have now shown that the normal order of leaving-group ability for dehydrohalogenations (I > Br > C1>>F) is reversed in reactions of this type; e.g. trans-1-bromo-2-fluoro- and trans- 1-chloro-2-fluoro-cyclohexane each gave 85 YO yields of 1-bromo- or 1-chloro-cyclohexene with none of the corresponding fl~oro-alkene.~ The result was attributed to the dominant role played by metal-halogen interaction in the syn-transition state (50; B=base M = metal ion) as opposed to the importance of carbon-halogen bond strength in conventional /3 -eliminations.Comparisons of rates of syn- and anti-elimination have been made for the sterically constrained trans-2,3- dihalogeno- (5 1)and cis-2,3-dihalogeno-2,3-dihydrobenzofurans (52) respectively; the anti-elimination was favoured by a factor of ca. 33 000 for sodium ethoxide and of ca. 10000 for potassium t-buto~ide.,~ Together with the kinetic effects of a 3-deuterio-or a 5-chloro-substituent in the trans-2,3-dibromo-compound the results suggested that the transition state for syn-elimination is affected significantly by association of the base but not by the basicity of the medium. The synlanti dichotomy has also been investigated for the alkoxide-catalysed eliminations of two homologous series of positionally isomeric alkyl-trimethylammonium +salts RCH2CHXCsH11 and RCHXCH2C,H11 (R = H Me Et Pr” Pr’ or But;X = NMe3 Cl-).’ Overall rates were dissected into their syn- and anti-components and it was concluded that the steric factors are more important in controlling the stereochemi- cal (syn- or anti-) outcome whilst polar effects are overriding in determining the orientation of products (Hofmann us.Saytzeff). 7 Electrophilic Addition A claim that the kinetic effects of methyl substitution in styrene on its rate of bromination more closely resemble those of sulphenylation than of hydration [cf. Ann. Reports (B) 1978 75 641 and that a bridged bromonium ion is therefore involved in the rate-determining step,” has been challenged on the grounds that the overall rate constants in protic solvents include terms for both free bromine and tribromide ions [equation (S)].” The use of corrected values for kBrz,together with kex,,(l+ K[Br-]) = kBrz+ KkBrj[Br-] (5) ’’ J.G. Lee and R. A. Bartsch J. Amer. Chem. SOC. 1979,101,228. ’‘ E. Baciocchi and G.V. Sebastiani J. Org. Chem. 1979 44 28. ’’ J. Zavada and M. Pankova Coll. Czech. Chem. Comm. 1979,44,1273. ’’ G. H. Schmid J. Org. Chem. 1978,43,777. 59 M. F. Ruasse J. E. Dubois and A. Argile J. Org. Chem. 1979 44 1173. H. R. Hudson an enlarged body of data led to the conclusion that a-and B-methyl substituent effects are both large for additions to RCH=CH2 where R is an alkyl group but that the a-effect is small and the &effect is large where R is phenyl as in hydration.An open carbenium-ion-like transition state is therefore indicated for the bromination of styrene as reported previously. The basis of comparison with arenesulphenylation has also been criticized on the grounds that log k uersus log k correlations are poor and that steric interactions in the rate-determining steps of the two processes are so different that a linear free-energy relationship over a wide range of substituents cannot be expected.60 Relative rates of reaction (kc,,/ kc,c) for pairs of phenyl-substituted alkynes and alkenes with diphenylmethyl or 1-phenylethyl cations are mainly in the range 0.2-3.5 and are consistent with a transition state having an open cation structure in each case.61 Steric factors appear to dominate the effect of structure on reactivity.What are described as ‘bizarre reactions’ of but-2-yne have been shown to occur with anhydrous hydrogen chloride at room temperature.62 Apart from the expected addition products thirteen compounds were identified as chlorinated and non- chlorinated cyclic and acyclic dimers and trimers of but-2-yne resulting from electrophilically induced cycloadditions. Key intermediates in the proposed reaction scheme were formed as shown in Scheme 10. Cyclodimerization products having 1,3-dialkyl-1,3-dibromocyclobutanestructures were likewise obtained by the interaction of anhydrous hydrogen bromide with alkyne~.~~ HC -+ Scheme 10 8 Nucleophilic Addition to Alkenes Suitably activated carbon-carbon double bonds may undergo nucleophilic addition by a two-step process the first step of which consists in the rate-determining formation of an association complex.The rate of attack is frequently too fast for conventional kinetic studies but temperature-jump and stopped-flow techniques have now been successfully applied to the reactions of substituted benzylidene- Meldrum’s acids (53) and substituted benzylidene-NN’-dimethylbarbituric acids (54) with amines in acetonitrile or chlor~form.~~ The zwitterionic structure assigned to the association complex (55) is in agreement with its lower stability in chloroform 6o M. F. Ruasse A. Argile E. Bienvenue-Goetz and J. E. Dubois J. Org. Chem. 1979 44 2758. 61 F. Marcbzzi G. Melloni and G. Modena J. Org. Chem. 1979 44 3022. 62 H. Schneider and K.Griesbaum J. Org. Chem. 1979 44 3316. 63 K. Griesbaum W. Seiter H. Schneider M. El Abed and Z. Rehman Annalen 1979 1137. 64 B.Schreiber H. Martinek P. Wolschann and P. Schuster J. Amer. Chem. SOC.,1979,101,4708. Reaction Mechanisms -Part (ii) Polar Reactions 71 0 ?. ,co-0 \ / CO-N \ /Me H \ 45 Ar-C-C-R3 FMe2 ArCH=C \ co / $. J ArCH=C / R'-N+ C \co-0 CO-N \ R2/ \ 4, H...O (53) (54) Me (55) R3= OCMe20 or N(Me)CON(Me) and with the fact that tertiary amines which provide no hydrogen atom for intramolecular hydrogen-bonding in the complex associate more weakly than primary or secondary amines. Electron-withdrawing substituents in the aromatic ring afford stabilization. Some unusual examples of nucleophilic addition are provided by the base- catalysed reactions of certain tricylic derivatives (%) which yield ethers (57) by intramolecular attack of the carbon-carbon double bond by alkoxide ion derived from the neighbouring hydroxyl group.65 In those cases in which R2+R3= 0 (i.e.a carbonyl group is present) the reaction was thought to proceed by virtue of the stabilizing effect of an intermediate homo-enolate (58) but steric compression appears to be the sole driving force for reaction when R2 and R3are H and/or MeO.R' R' R' R2$ 9 R2 R3 0' R3 (57) 9 Nucleophilic Reactions of Carbonyl Compounds A new correlation for the reactivities of carbonyl compounds with nucleophiles (BH,- CN- S032- NH20H and RS-) has been derived €or twenty-six ketones [equation (6); k is the rate constant for a given ketone; ko is the rate constant for cyclohexanone as ~tandard].~~ The slope of the line is approximately unity and the relationship can therefore be simplified to log (klk,) = B.log k = A log ko + B (6) The intramolecular transesterifications of some o-hydroxyalkyl thionobenzoates and thionoacetates have been shown to give rise to a novel class of thermally stable anionic tetrahedral intermediate (Scheme 1l).67The compounds were obtained as stable solids which were insoluble in aprotic solvents such as acetonitrile or dichloromethane but which reacted with water to yield the starting materials. 65 R. A. Pfund and C. Ganter Helv. Chim. Acta 1979 62 228. " A. Finiels and P. Geneste J. Org. Chem. 1979 44 1577.'' F. Khouri and M. K. Kaloustian J. Amer. Chem. SOC.,1979 101 2249. H. R. Hudson I1 S R=PhorMe,n=2or3 Scheme 11 Gas-phase Reactions.-Pulsed ion cyclotron resonance spectroscopy (ICR) has been used to investigate the behaviour of acyl compounds towards nucleophiles in the gas phase. RCOY + X-+ RCOX + Y-(7) Acyl halides undergo displacement reactions [equations (7)] although a number of competitive processes may also occur viz. proton transfer base-induced complexation and base-induced elimination.68 Nucleophilicity of the attacking group decreased in the order MeO- 5F-> CN-> SH-> C1- which is the same as for gas-phase basicities and is essentially the same as is found in protic solvents. This contrasts with the behaviour of nucleophiles in displacements at sp3 carbon for which the order of nucleophilicity is very susceptible to solvation effects.Reaction rates suggested that displacement occurs via a double-minimum potential well with loose association complexes (59) and (60),at the minima (Scheme 12) and an intervening saddle point which possibly corresponds to the tetrahedral intermediate structure. X-+ RCOY $ [X--RCOY]-$ [Y--RCOXI-$ Y-+ RCOX Scheme 12 The relatively unstable character of tetrahedral intermediates in the absence of solvation has been made clear by the gas-phase interactions of phenyl acetate with a range of nucleophiles (OH- MeO- CN- SH- MeS- and PhO-).69 In spite of the reluctance of the phenyl ring to undergo SN2attack this mode of reaction [equation (S)] occurred exclusively in preference to the displacement of phenoxide by the BAc2 mechanism [equation (9)].However reaction by the BAc2 route occurred X-+ PhOCOCH3 + XPh + -0COCH3 (8) X-+ PhOCOCH3 + XCOCH3 + PhO-(9) when partially solvated nucleophiles (obtained e.g.from the reaction X-+ HC02Me+ X---. HOMe + CO) were used. It is clear that charge delocalization by even a single solvent molecule is extremely important for the stabilization of transition states for processes proceeding uia tetrahedral intermediates. " 0.I. Asubiojo and J. I. Brauman J. Arner. Chern. SOC.,1979,101 3715. 69 E. K. Fukuda and R. T. McIver jnr. J. Arner. Chem. Soc. 1979,101,2498.

ISSN:0069-3030    

DOI:10.1039/OC9797600055

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Free-Radical Reactions By A. G. DAVIES Department of Chemistry Urliversity College London 20 Gordon Street London WClH OAJ 1 General A useful introductory text on organic free radicals has been published.’ Other general reviews include articles on the mechanisms of free-radical reactions,2 anchimerically assisted bond homoly~is,~ vibrational spectroscopy of free radical^,^ fluorine-containing free radicals,’ directive effects in gas-phase radical addition reactions homolytic aromatic ipso-substitution reactions,’ and the capto-dative stabilization of radicals carrying both an electron-acceptor and an electron-donor group.’ An interesting development in technique is the application of e.s.r. spectroscopy to the direct observation of the radicals that are formed during the pyrolysis of hydrocarbons.’ The compounds in benzene solution are passed slowly through the cavity at temperatures up to 566 “C and pressures up to 140 kg cm-2 usually well above their critical temperatures but the high density of the fluid quenches the angular momentum of molecular rotation and sharp well-resolved spectra are observed.As yet the technique has been applied mainly to radicals of the benzyl type. 2 Carbon-centred Radicals Electron spin resonance spectroscopy continues to be the technique that is used most widely to investigate the structures of free radicals. In an sp2-hybridized alkyl radical (1)the a-carbon atom is in the nodal plane of the p-orbital containing the unpaired electron and hence the hyperfine coupling to this carbon is low (about 40 G).On the other hand an sp3-hybridized radical (2) has a finite s-electron density at the carbon nucleus and the hyperfine coupling is large. The temperature dependence of 4°C) can further be used to determine the out-of-plane bending frequency of the radical. D. C. Nonhebel J. M. Tedder and J. C. Walton ‘Radicals’ Cambridge University Press 1979. C. Ruchardt Uspekhi Khim. 1978,47,2014. M. T.Reetz Angew. Chem. Internat. Edn. 1978 17 594. R. E.Hester Adv. Infrared Raman Spectrosc. 1978,4,1. ‘Fluorine-containing Free Radicals’ ed. J. W. Root A.C.S. Symposium Series 1978,Vol. 66. J. M. Tedder and J. C. Walton Adv. Phys. Org. Chem. 1978,16,51. J. C. Traynham Chem.Rev. 1979,79 323. H.G.Viehe R. Merknyi L. Stella and Z. Janousek Angew. Chem. Internat. Edn. 1979,18,917. R.Livingston H.Zeldes. and M. S. Conradi J. Amer. Chem. SOC.,1979,101,4312. A. G.Davies In the ethyl" and isopropyl radicals," the value of a("C,) increases monotoni- cally with temperature. These radicals have a planar structure at the minimum of the potential-energy curve and the out-of-plane bending frequencies which are derived (541 and 380 cm-' respectively) are in good agreement with the values obtained from i.r. spectroscopy.'* In contrast the t-butyl radical [a("C,) ca. 45 GI appears to be most stable when it is bent by 11.5" from planarity. The trineopentylmethyl radical13 [a(13Ca) ca. 40.5 GI shows the lowest value of a ("CC,) of any t-alkyl radical and is presumably forced nearer to planarity by steric repulsion between the neopentyl groups Below -85 "C the spectrum shows that the hydrogen atoms on the P-carbon atoms become non-equivalent as the neopentyl groups are frozen into specific conformations.Steric repulsion between pairs of these radicals also confers on them a high persistence in solution in benzene at 20 "C their half-life is 11minutes. Steric effects are also the basis of the persistence of (RS),C' radi~a1s.l~ Hexakis(trifluoromethylthiy1)ethanedissociates at room temperat~re.'~ The C-C bond length is 1.7 nm (compared with 1.54 nm in ethane) and the bond dissociation energy is only 13.7 kJ mol-l. The value of a(13C,) in the radical (3)is 40.09 G confirming that the radical is approximately planar [cf.(l)]; in contrast the radical (MeO),C' has a("C) = 154 G,showing that it is pyramidal [cf.(2)]. (CF3S)3C-C(SCF3)3 $ 2(CF3S)3C. (31 The value of a(H,) in an alkyl group can similarly give evidence regarding the conformation about the C -Cp bond. Hyperconjugative coupling will be largest when the P-C-H bond eclipses the semi-occupied p-orbital i.e. (4) and least when it is in the nodal plane as shown in (5). H Br (4) (5) (6) By this type of argument the P-bromoalkyl radical Me2CCH2Br about which there has been some controversy has been shown to have the preferred con-formation (6).16 Other spectra that can be observed when isobutyl bromide in an adamantane matrix is subjected to X-radiolysis apparently result from the inter- action of the radicals Me2CHCH2' and Me3C' with Br-.16*17 lo D.Griller P. R. Marriott and K. F. Preston J. Chem. Phys. 1979 71 3703. l1 D. Griller and K. F. Preston J. Amer. Chem. SOC.,1979 101 1875. l2 J. Pacansky D. E. Home G. P. Gardini and J. Bargon J. Phys. Chem. 1977,81,2149. l3 K. Schluetter and A. Berndt Tetrahedron Letters 1979 929. l4 R. Schecker U. Henkel and D. Seeback Chem. Ber. 1977,110,2880. A. Haas K. Schlosser and S. Steenken J. Amer. Chem. SOC., 1979,101,6282. l6 M. C. R. Symons and I. G. Smith J.C.S. Perkin ZZ,1979 1362. l7 R. V. Lloyd D. E. Wood andM. T. Rogers J. Amer. Chem. SOC., 1974.96.7130. Reaction Mechanisms -Part (iii) Free-Radical Reactions The first well-defined e.s.r. spectrum of an alkane radical cation (7) has been reported from the y-irradiation of 2,2,3,3,-tetramethylbutanein the presence of a carbon tetrahalide as an electron scavenger at 77 K.18 It is suggested that the two Me3C groups which are held together by a one-electron bond are approximately planar (7); six C-H bonds lie parallel with the singly occupied 0-orbital and by hyperconjugation show a large hyperfine coupling constant of 32 G and the other twelve hydrogen atoms show a=4.5 G.In the absence of the carbon tetrahalide electron return gives the alkane in an excited state and fragmentation occurs. The first long-lived mono-olefin radical cation (8)has also been ob~erved,'~ from the electrolytic oxidation of adamantylideneadamantane in an e.s.r. cell. It is thought to owe its persistence to the fact that the p-carbon atoms are all located at bridgeheads from which loss of a proton is forbidden by Bredt's rule.E.s.r. spectroscopy has also been used to show the existence of two isomeric forms of the pentadienyl radical that are not interconvertible on the time-scale of the technique. Photolysis of di-t-butyl peroxide in the presence of penta- 1,4-diene above -60 "C shows the presence of only one species which has been identified as the (Em-isomer (9) but at -120 "C the predominant radical that is formed is the (EZ)-isomer (1o).",~~ -.. Bu'O. .<. and/or &./,.-..--.- (9) (10) One of the more satisfying aspects of Huckel MO theory is its success in interpreting quantitatively the e.s.r. spectra that are observed when a substituent interacts with the 7-electron system of an annulene radical.It is inevitable that most studies should have been carried out on the benzene radical anions (C6H5R7) but the cyclopentadienyl radicals (C5H4K) would have certain advantages because the 7-electron system is concentrated over fewer nuclei (so that the observed effects are often larger) and because the radicals are uncharged and the unpaired electron resides in a bonding rather than an antibonding orbital. There has previously been no satisfactory route to the cyclopentadienyl radicals because the substituted cyclopentadienes C5H5R react with alkoxyl radicals by addition rather than hydrogen abstraction (except when R is a trialkylsilyl group)." M. C. R. Symons and I.G.Smith J. Chem. Res. (S),1979,382; J. T. Wang and F. Williams Chem. Phys. Letters 1979,67 202; M. C. R. Symons ibid. 1980,69 198. l9 S. F. Nelson and C. R. Kessel J. Amer. Chem. SOC.,1979 101 2503. 2o D. Griller K. U. Ingold and J. C. Walton J. Amer. Chem. Soc. 1979,101 758. R. Sustman and H. Schmidt Chem. Ber. 1979,112 1440. 22 M. Kira M. Watanabe and H. Sakurai J. Amer. Chem. Soc. 1977,99,7780. A. G. Davies The general routes to the radicals C5H4R'shown in Scheme 1 have now been developed and the e.s.r. spectra can be analysed to identify the substituent effects of the groups R.23s24 R R r R-I (R =Hor D) (R = H or alkyl) (R= H alkyl or R3Si) Scheme 1 The forms of the degenerate symmetrical ($s) and antisymmetrical (t+hA) wave-functions for the cyclopentadienyl radical are shown in (11) and (12).These are equally populated by the unpaired electron in the CsH5*radical resulting in an equal spin density at each carbon centre and an e.s.r. spectrum which consists of a binomial sextet; a(5H) =5.98 G. If the ring carries an electron-releasing substituent at position 1 the MO will be destabilized because of the high electron density at C-1 but $A will be unaffected because it has a node passing through this position. Two electrons will therefore enter the t+hA orbital and the unpaired electron will occupy the t,bS orbital. The value of a(Hj)will be given by c; (5 x 5.98) G where cjis the Huckel coefficient at position j; this predicts that u(H2,5)= 1.1G and a(H3,4)=7.8 G. Conversely an electron-attracting substituent should stabilize CLs which will be doubly occupied leaving the unpaired electron in JIA so that a(H2,5) = 10.8 G and a (H3,4)=4.1 G.When R is Me Et Pr' or But the e.s.r. spectrum that is observed shows that the unpaired electron is wholly in the $s orbital; for example for C5H4Me*radical a(H2,5) = 1.10 G and a(H3,4) =7.73 G at 24 "C. This is compatible with the accepted behaviour of alkyl groups acting as electron-releasing substituents. On the other hand the spectrum of C5H,.,SiMe3* shows that the Me3Si group weakly attracts electrons leaving the unpaired electron principally (but not wholly) in the t+hA orbital. 23 A. G. Davies and M.-W. Tse J.C.S. Chem. Comm. 1978 353; P. J. Barker A. G. Davies and J. D. Fisher ibid.1979 587. 24 M. Kira. M. Watanabe and H. Sakurai Chem. Letters 1979 973. Reaction Mechanisms -Part (iii) Free-Radical Reactions Penta-alkyldisilyl substituents R3SiR2Si however act as weakly electron-releasing groups in the cyclopentadienyl radical whereas in the benzene radical anion they act as electron-attracting substituents. The spectrum of the C5H4D* radical shows that the +A MO is higher in energy than $rS. This is ascribed not to a Coulombic effect but to the difference in the vibrational frequencies of the C-H and C-D bonds acting upon the resonance integral of the t,hs M0,24,25or upon the various Jahn-Teller-distorted isomers of the The above correlations between structure stability and e.s.r. spectra all relate to carbon-centred 7-radicals (1).Relatively little is known about such relationships for a-radicals partly because the e.s.r.spectra of two of the most important classes of these radicals namely the vinyl and aryl radicals are difficult to observe in fluid solution and the spectra of most of the small number of acyl a-radicals (13)that have been observed in the past have shown broad lines with no resolvable str~cture.~' The intramolecular interactions and the conformations which they impose are similar in the acyl radicals and their parent aldehydes. Further the n.m.r. couplings 3J(CH-CHO) in the aldehydes (14) and the e.s.r. couplings a(HB) in the acyl radicals (15) me similar functions of the dihedral angle 8 being largest when 8 = 0" [p-C-H bond trans to the (+-C(0)-H bond or singly occupied a-orbital] and least when 8 is 90-270".When R is a small alkyl group (Cl-C5) the most stable conformation of the aldehydes RCH2CH0 and of the acyl radicals RCH2C0 is that in which the R-C bond eclipses the carbonyl group [8 in (14) and (15) is 120 or 240'1. The n.m.r. coupling constant 3J(CH-CHO) is small (<1.8 Hz) and the e.s.r. coupling is unresolvable accounting for the broad signals that have been observed previously. If R is larger than C5 8 is reduced probably because of steric hindrance between R and the carbonyl group; the n.m.r. coupling increases (to ca. 2 Hz) and the e.s.r. coupling becomes resolvable (2-3 G). In the extreme di-t-butylacetaldehyde which is most stable in the conformation (16) in which the P-C-H bond is trans to the aldehydic C-H bond shows a large n.m.r.coupling 3J(CH-CHO) = 6 Hz and the cor- responding acyl radical with a similar conformation (8 = 0) shows a(H,) =ca. 11G.28 In 2,3-unsaturated aldehydes interaction between the 7-system of the carbonyl group and that of the double bond stabilizes the molecule in the s-trans con-formation and 3J(CH-CHO) = 6 Hz. The corresponding unsaturated acyl radicals adopt the same conformation (17) in which 8 = 60"and a(H,)= 19 G. H H 25 P. J. Barker and A. G. Davies J.C.S. Chem. Comm. 1979,815. 26 T. Clark J. Chandrasekhar and P. von R. Schleyer J.C.S. Chem. Comm. 1980,266. '' H. Paul and H. Fischer Helv. Chim. Actu 1973 56 1575. 2a A. G. Davies and R. Sutcliffe,J.C.S. Chem. Comm. 1979,473; J.C.S.Perkin ZZ 1980 819. A. G.Dauie9 Similarly the interaction of the r-system of the carbonyl group with the Walsh .rr-orbitals of the cyclopropyl ring restricts rotation about the C,-CB bond in cyclopropylcarbaldehyde but now the two conformations have approximately equal stability. Below -9O"C the aldehyde reacts with t-butoxyl radicals to show the spectra of the two radicals (18) in which 8 = 0" and a(H,) = 18.2 G and (19),where 8= 180",and a (HB)= 0.5 G. Above about -90 "C rotation about the C -Cp bond is rapid on the e.s.r. time-scale and a single time-averaged spectrum is observed; a(H,) = ca. 9 G. Simulation of the spectra over the region of intermediate exchange rates gives a barrier to rotation of 17.5 kJmol-' close to the value of 18.4* 1.7 kJ mol-' that has been obtained by microwave spectroscopy for the parent aldehyde." Similar considerations may be expected to apply to the a-imidoyl radicals (21).Previously their spectra had been observed only from the radicals obtained from the corresponding imines (20; R2=alkyl).30 A wider variety of imidoyl radicals (21a) H have now been prepared by the addition of radicals X*[e.g. ButO* Me3SiO* (Et0)2P0 Mesa and Me&] to alkyl isocyanides (R2= Me Bun But Me3Si et~.).~~ When X is Bu'O or Bu'S the imidoyl radicals undergo cleavage within X to give the radicals But- and OCNR' or SCNR' as appropriate but when X is MeS Et3Si or Ph the N-R2 bond breaks to give R2and XC=N. An unusual case of a radical existing in two distinct electronic configurations has been detected in the reaction of t-butoxyl radicals with the phosphorus(II1) iso- cyanate (22)32 (the proposed ?r and a-N configurations of the succinimidyl radical are a second example33).Two e.s.r. spectra are observed one being ascribed to the conventional trigonal-bipyramidal phosphoranyl radical (23) and the other to its isomerization product (24) where the electron occupies a a-orbital on the isocyanate ?? -0 NLV (23) 29 P. M. Blum A. G. Davies and R. Sutcliffe J.C.S. Chem. Comm. 1979 217. 30 W. C. Danen and C. T. West J. Amer. Chem. SOC.,1973,95,6872. 31 P. M. Blum and B. P. Roberts J.C.S. Perkin 11 1978 1313. 32 J. A. Baban and B. P. Roberts J.C.S. Chem. Comm. 1979 537. 33 See Ann. Reports (B), 1978,75,74. 79 Reaction Mechanisms -Part (iii) Free-Radical Reactions ligand.The large value of the I3Cahyperfine coupling (136.1 G) and the low g value (2.0009) are characteristic of acyl radicals. 3 Sulphur-centred Radicals The e.s.r. spectra of the RS*radicals and the RO-radicals (which were discussed in last year's cannot be detected unless a specific electronic interaction breaks the degeneracy of the doubly occupied and singly occupied orbitals on the heteroatoms. In the ROO-radicals this is accomplished by interaction with an electron pair on the P-oxygen atom. A similar interaction occurs in the RSS. radicals and the spectrum of Bu'SS' (g=2.025 AH, = 4 G) has now been detected from the photolysis of t-butylthiosulphenyl chloride Bu'SSCl. At -86 "C the rate constant for its second-order decay (2 x lo81mol-' s-') is about lo8times greater than that of the Bu'OO.The degeneracy can also be broken by nitrogen and a variety of dialkylaminothiyl radicals for example Et,NS. [a(N) = 10.7 G a(4H) = 6.1 G g = 2.01561 have recently been identified.36 On the other hand the persistent radicals that are observed when tetrasulphur tetranitride is photolysed in the presence of alkenes are not the sulphur-centred radicals (25) as was originally belie~ed,~' but are instead nitrogen-centred radicals [e.g. (26); a(N)= 13.11 G a(2H)= 3.49 G ~(2~~s) = 2.89 G g = 2.0064].38 Again the degeneracy can be broken by interaction with the r-electron system of an aromatic ring and the arylthiyl radicals ArS* have been detected when the products of the photolysis of diary1 disulphides were condensed on a cold finger at 77 K.39 Alkylthiyl radicals can react with alkenes either by addition to the double bond or by abstraction of allylic hydrogen.In the reaction between methylthiyl radicals and cyclopentene the balance between these two processes is strongly temperature- dependent. At -100 "C only the spectrum of the adduct (27) is observed; at -60 "C only the cyclopentenyl radical (28) is detect~d.~' Sylphides also fairly readily lose an electron to reagents such as HOS,~~ NO',42 Bu'OH,~~ or NH3t,44or electrochemically,43 to give the radical cations R2St.45These 34 See Ann. Reports (B) 1978 75 76. 35 J. E. Bennett and G. Brunton J.C.S. Chem. Comm. 1979,62.36 W. C. Danen and D. D. Newkirk J. Amer. Chem. SOC.,1976,98,516; B. Maillard and K. U. Ingold ibid. p. 520; J. A. Baban and B. P. Roberts J.C.S. Perkin 11,1978 678. 37 S. A. Fairhurst W. R. McIlwaine and L. H. Sutcliffe J. Mugn. Resonance 1979 35 121. 38 S. Rolfe D. Griller K. U. Ingold and L. H. Sutcliffe J. Org. Chem. 1979,44 3515. 39 W. Moerke A. Jezierski and H. Singer Z. Chem. 1979,19 147. 40 L. Lunazzi G. Placucci and L. Grossi J.C.S. Chem. Comm. 1979 533. 41 K.-D. Asmus D. Bannemann C.-H. Fischer and D. Weltwisch J. Amer. Chem. SOC.,1979,101,5322. 42 T. L. Wolford and P. B. Rousch J. Amer. Chem. Soc. 1978,100,6416. 43 W. B. Gara J. R. M. Giles and B. P. Roberts J.C.S. Perkin II 1979 1444. 44 B. C. Gilbert and P. R. Marriott J.C.S. Perkin 11,1979 1425.45 Reviewed by K.-D. Asrnus Accounts Chem. Res. 1979,12,436. A. G.Davies -100 MeS-+ 0 X60 OC 0+ MeSH (28) may be stabilized +sterically or electronically as the monomers; e.g. Bu',St (Me2N),S" and PhSMe. Otherwise they react (inter- or intra-molecularly) with a second sulphur centre giving the dimer cation radicals (R2SSR2)" with an equill- brium constant of 103-104 1 mol-' [e.g. Me,SSMe,'; a(12H) =6.3 GI. The unpaired electron is probably contained in a a*-orbital with the optical absorption due to a a+ a* transition (29). R R R 11; oso oso -0saPSa 'R I 'h R R (29) The sulphuranyl radicals 'SX3,e.g. CF3SSMe; and Me3SiOSMe; which occur as intermediates in SH2reactions at sulphur probably also have the unpaired electron confined in a orbital.^^'^^ A variety of sulphur-containing radicals are known in which the sulphur carries oxygen ligands put the unpaired electron appears to be centred mainly on sulphur (e.g.R2NS0 RSO, and RSO).47p48 The structures of the arenesulphonyl radicals ArS02 have been re-investigated. These are a-radicals with the unpaired electron in the plane of the benzene ring and (like the benzoyl radical) the hyperfine coupling constants are in the sequence a (H-rn)>a (H-o) a(H-p) and not o >p >rn as had previously been 4 Nitrogen-centred Radicals The detection of R2N' radicals by e.s.r. spectroscopy is not beset with the problems associated with orbital degeneracy that are encountered with RO' and RS' radicals and the variety of nitrogen-centred radicals which have been studied is increasing rapidly.The reactions often involve addition of a radical to a multiple bond to nitrogen. Thus aminyl radicals e.g. (30) have been prepared by the addition of alkyl radicals to imine~~~ and hydrazyl radicals e.g. (31) by addition to azodicarboxy- lates." Azo-compounds which carry an electronegative substituent X in the a-position similarly undergo addition by trialkylmetallic radicals (R3M) but this is 46 J. R. M. Giles and B. P. Roberts J.C.S. Chem. Comm. 1978,623. 47 C. Chatgilialoglu B. C. Gilbert C. M. Kirk and R. 0.C. Norman J.C.S. Perkin IZ 1979 1084; B. C. Gilbert and P. R. Marriott ibid.,p. 1425. 48 C. Chatgilialoglu B. C. Gilbert and R. 0.C. Norman J.C.S. Perkin 11,1979,770.49 B. P. Roberts and J. N. Winter J.C.S. Chem. Comm. 1978,960. 50 B. P. Roberts and J. N. Winter TetrahedronLetters 1979 3575. Reaction Mechanisms -Part (iii) Free-Radical Reactions But Me3CN=CH2 + R' + Me3CNCH2R EtO,CN=NCO,Et + But. + Et02CI!J-NC02Et (30) (31) followed by elimination of R3MX,then fl -scission of the resulting nitrogen-centred radical to give an azine (M = R3Si or R3Sn;X = C1 PhS or PhO) as shown in Scheme 2.5i R3M RM ClMe2CN=NCMe2CI 3C1Me2Ck-NCMe2CI .1 -CI. Me2C=NN=CMe2 t-Me2C=NNCMe2Cl Scheme 2 Photolysis of the azines gives the iminyl radicals (32),which can also be formed by the photolysis of di-t-butyl peroxide in the presence of primary or secondary alkyl azides. The iminyl radicals recombine to form the azines at diffusion-controlled rates.52 Bu'O' + H-CR2-NN2 + Bu'OH + N2 + R2C=N' + R2C=NN=CR2 (32) h" Iminyl radicals can also be prepared by addition to a nitrile.The 4-cyanobutyl radical (33)undergoes irreversible ring closure with a rate constant of 4.5 x lo2s-' at 259 K,52but photolysis of cyclobutanone azine (34) shows only the spectrum of the ring-opened radical. A reversible ring-closure of this type has been proposed to account for the 1,4-homolytic transfer of a cyanide group,53 as shown in Scheme 3 and an intermolecular addition provides the basis for the peroxide-initiated cyana- tion of hydrocarbons by methyl cyanoformate (Scheme 4).54 CSN No C-N I II 1 HOCCH,CH,kMe -Me -* HO&H,CH,CMe, I 1 Me Me "*OMe Me Scheme 3 C.Grugel and W. P.Neumann Annalen 1979,1675. B. P. Roberts and J. N. Winter J.C.S. Perkin ZZ 1979 1353. D. W. Watt J. Amer. Chem. SOC.,1976,98,271. D. D. Tanner and P. M. Rahimi J. Org. Chem. 1979,441674. A. G. Davies Bu'O' + RH + Bu'OH + R' R' + MeOCOCEN + MeOCOC-N' + MeOeO + RCrN R (>70°/o ) Scheme 4 Under the same conditions 2,4-dimethylpentane gave an azacyclopentene (35)by a sequence of reactions that includes the cycloaddition of an alkyl radical to the nitrogen of an imine. MeOCOC=NH J MeOCOC =N MeOCOc-NH (35) For use in chemical synthesis iminyl radicals can conveniently be generated by the oxidation of imino-oxyacetic acids with persulphate or thermolysis of the cor- responding t-butyl peroxy-esters e.g.as shown in Scheme 5." Ph2C=NOCH2C02H -CH20 ih2C=NO&12 +Ph2C=N' -+ (Ph2C=N)2 Ph2C=NOCH2C03But Y Scheme 5 If the structure of the arylimino moiety is varied these reactions can provide useful routes to a variety of compounds such as phenanthrolines quinolines pyridines pyrimidines and tetra lone^.^^ Examples are shown in Scheme 6. If hexabutylditin is photolysed in the presence of a 3-alkyl-3-bromodiazine the bromine is abstracted to give a new family of diazirinyl radicals (36).56Correlation of the results from 13Clabelling of the ring atom with INDO calculations shows that these are n-radicals in which a("C) has a negative sign and arises principally by spin polarization from nitrogen through the C-N bonds. The radical is therefore best represented by the valence-bond structures (37a) and (37b) with (38) making no significant contribution.-This structure is analogous to that of the aziridinyl (CR2CR2N) diaziridinyl -(CR2NRN) and oxaziridinyl (WN')<adicals but differs from that of the tri-t- butylcyclopropenyl radical (BU'C=CBU'CBU'') which has a 0-configuration. In contrast if a mixture of a bis(trimethylmeta1)mercurycompound (Me3M)zHg (M = Si or Ge) and a 3-alkyl-3-chlorodiazine is thermolysed or photolysed the R3M " A. R. Forrester M. Gill D. J. Meyer J. S. Sadd and R. H. Thompson J.C.S. Perkin I,1979,606; A. R. Forrester M. Gill J. S. Sadd and R. H. Thompson ibid. p. 612; A. R. Forrester M. Gill and R. H. Thompson ibid. pp. 616,621; A. R. Forrester M. Gill R.J. Napier and R. H. Thompson ibid.,p. 632; A. R. Forrester M. Gill C. J. Meyer and R. H. Thompson ibid. p. 637. 56 Y. Maeda and K. U. Ingold J. Amer. Chem. SOC.,1979,101,837. Reaction Mechanisms -Part (iii)Free-Radical Reactions /\ /\ C=NOCH $02H C=N* / Me/ Me (60%) Me NOCH,CO,H d)-0-m J 0 NH Scheme 6 radical is added at nitrogen to give a 2-metallated diaziridinyl radical (39).57When M = Si the two nitrogen atoms are non-equivalent but when M = Ge they are rendered equivalent presumably by a rapid 1,2-migration of Me3Ge. These di- aziridinyl radicals may then react further to give N-metallated 1,2,3,5-tetrazinyl radicals (40) which are in equilibrium with their corresponding dimers. Trialkylsilyl radicals similarly add to the nitrogen multiple-bond system of a variety of organic azides to give either 1,3- or 3,3-triazenyl radicals.52 The available evidence suggests that these are the 3,3-triazenyls (41) in which the unpaired electron is mainly associated with the central nitrogen in a 0-orbital that is in the N-N-N plane.R$i' + R2N3 + R:Si(R2)N-N=N' or R2N=N-NSiR (41) s7 C. Grugel and W. P.Neumann Annulen 1979,870. 84 A. G.Davies 5 Transition-MetalCompounds The ability of transition metals with univariant valence to act as good homolytic leaving groups gives rise to a variety of direct (R=R)or conjugated (R#R') bimolecular homolytic displacement processes at organic ligands on the metal. When these reactions are coupled into a chain process with a second step which regenerates the radical reagent they may be useful in organic synthesis.x' + R-M~ -+ XR'+ 'M~-' Stage (1) X-Y + OMN-' -+ X'+ Y-MN Stage (2) x-Y + R-M~-+ XR'+ Y-M~ Overall result There is some precedent for these processes in the chemistry of the Main-Group metals such as tin. Most of the work on transition-metal derivatives has been carried out with cobalt(II1) compounds but there are also examples of similar reactions which involve ligands on other metals; e.g. rhodium iridium and iron. Alkyl-cobalt complexes react with reagents X-Y such as Cl3C-C1 (NC)Cl,C-Cl (Et02C)2CH-Br and ArS02-Br by a conjugative displacement (SH2'or SH2y);e.g.,58*59 (42) yields (43) and allenyl-cobalt complexes react similarly to give propargyl derivatives; e.g.,57 (44)provides (45).Butenyl compounds e.g. (46) undergo ring-closure giving a useful route to cyclo-propylmethyl derivatives,60 and the reactions with benzylcobalt compounds e.g. (47) appear to provide examples of the elusive process of bimolecular homolytic substitution at saturated carbon.6l c13c'+ Co"'(dmgH);?L + C13C+" + [C~"(dmgH)~Ll (43) (dmgH = dimethylglyoximato) [Coi1(dmgH)2L] (44) (45) C13C' + -Co11'(dmgH)2(py)-+ 'I3'-+ [Co"(dmgH)2(~~ )I (46) C13C' + [ArCH2Co"'(dmgH)(imid)] + ArCH2CC13+ [Co"(dmgH)~(imid)] (47) (imid = imidazole) A. Bury C. J. Cooksey T. Funabiki B. D. Gupta and M. D. Johnson J.C.S. Perkin ZI 1979 1050. 59 A. E. Crease B. D. Gupta M. D. Johnson A. Bialkowska K. N. V. Duong and A. Gaudemar,J.C.S.Perkin I,1979 261 1. 6o A. Bury M. R. Ashcroft and M. D. Johnson J. Amer. Chem. SOC.,1978,100,3217. 61 B. D. Gupta T. Funabiki and M. D. Johnson,J.C.S. Chem. Comm. 1977,653.

ISSN:0069-3030    

DOI:10.1039/OC9797600073

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

5 Arynes Carbenes Nitrenes and Related Species By D. W. KNIGHT Department of Chemistry The University Nottingham NG7 2RD 1 Arynes Ab initiu calculations have established that 0- rn- and p-benzynes have singlet ground states although some doubts still exist in the case of p-benzyne.' The total energies of the isomers increase in the order o < rn <p with the equilibrium structures of the latter two isomers showing considerable diradical character in contrast to the aryne nature of o-benzyne. Although the bicyclic structure of p-benzyne may represent an energy minimum this is far above the monocyclic structure. An analysis of the products arising from the thermolysis of hexa-1,5-diyn- 3-enes e.g. (l) suggests that the reaction proceeds via 1,4-dehydrobenzyne diradi- cals which rearrange to 1,3-dehydrobenzenes by [1,2] shifts of the trimethylsilyl groups presumably reflecting the greater stability of rn -benzynes.* Treatment of the indene derivative (2) with a strong base at 0°C gives a large number of products whose formation can be rationalized by assuming the intermediacy of 2-chloro-l,3- dehydronaphthalene in both the bicyclic (diradical) and tricyclic form^.^ u-Benzyne can be generated photochemically from the u -nitrobenzaldehyde derivative (3),4 and a full report has appeared on the generation of polymer-linked benzyne.' Ab initiu calculations suggest that the high electrophilicity of benzyne is due to a significant lowering of its LUMO energy level relative to the LUMO of linear but-2-yne while the HOMO energies of the two molecules are approximately the same.6 The synthetic utility of this electrophilicity continues to be exploited.Thus a J. 0.Noel1 and M. D. Newton J. Amer. Chem. SOC., 1979,101 51. * G.C. Johnson J. J. Stofko Jr. T. P. Lockhart D. W. Brown and R. G. Bergman J. Org. Chem. 1979,44 4215. ' W.E.Billups J. D. Buynak and D. Butler J. Org. Chem. 1979 44,4218. Y. Maki T. Furuta and M. Suzuki J.C.S. Perkin I 1979,553. S. Mazur and P. Jayalekshmy,J. Amer. Chem. SOC., 1979,101,677;c6 J. Rebek Jr. and J. E. Trend ibid. p. 737. N. G.Rondan L. N. Domelsmith K. N. Houk A. T. Brown and R. H. Levin Tetrahedron Letters 1979 3237. D. W.Knight Japanese group have reported a potentially useful route to polycyclic alkaloids (Scheme 1)7 while a new route to pyrrolo[3,4-~]pyridines probably proceeds via a pyridyne intermediate (Scheme 2).* Scheme 1 Scheme 2 Phthalide enolates add to benzyne to provide a simple if not very efficient route to anthraquinones (Scheme 3)9 and in a similar type of reaction enolates of cyclic cup -unsaturated ketones condense with benzyne (Scheme 4) affording ultimately the tricyclic alcohols e.g.(4) which are useful as precursors of benzocyclo-octenones.10 0- Scheme 3 0, +-0/o:--+Q \ HO Scheme 4 Some evidence of the existence of the heteroaryne species (5) is the isolation of (6) its (formal) Diels-Alder adduct with anthracene." H. Iida Y. Yuasa and C. Kibayashi J. Org. Chem. 1979,44 1074; cf ibid.,p.1236. I. Ahmed G. W. H. Cheeseman and B. Jaques Tetrahedron 1979,35,1145; see also M. Mallet and G. Qutguiner ibid. p. 1625. P. G. Sammes and D. J. Dodsworth J.C.S. Chem. Comm. 1979,33. lo M. Essiz G. Guillaumet J.-J. Brunet and P. Caubkre J.C.S. Chem. Comm. 1979,276; see also M. L. Viriot J. Chem. Res. (S) 1979,324;H. Iida Y. Yuasa and C. Kibayashi J. Org. Chem. 1979,44,3985. l1 M. G. Reinecke and H. H. Ballard Tetrahedron Letters 1979,4981. 87 Arynes Carbenes Nitrenes and Related Species m&\ \ (6) 2 Nitrenes A useful review has appeared concerning advances in the synthetic applications of aryl and heteroaryl nitrenes.'* Chapman et al. have summarized recent studies on the low-temperature photochemistry of C6H5N specie^;'^ it now seems clear that under these conditions triplet phenylnitrene and triplet 2-pyridylmethylene inter- convert via l-aza-l,2,4,6-~ycloheptatetraene Ab initio calculations predict that an energetically favourable pathway in the reduction of ethylene by trans-di-imide proceeds by way of ethylamin~nitrene.'~ The reaction between cyanamide and iodobenzene diacetate produces cyano- nitrene which can be trapped by a variety of reagents." The nitrene (7) obtained by oxidation of the corresponding arylsulphenamide adds to electron-rich olefins to give aziridines in 38-64% yield.16 The stereoselec- tivities of the additions imply that the singlet and triplet states of (7) are in equilibrium and that the addition of triplet (7) to olefins is reversible.A milder method for the generation of phthalimidonitrene is by thermolysis in refluxing benzene of the sulphimide (8).17 The nitrene so produced is a relatively stable singlet species which adds to olefins stereoselectively to give aziridines.OS-N N-N=SMe OZN \ (7) A study of the reactions between alcohols and ethoxycarbonylnitrene generated thermally or photolytically from ethyl azidoformate indicates that only the singlet species is capable of inserting into the O-H bonds of alcohols.18 The photolysis of pyridine N-oxides leading to formyl-pyrroles (Scheme 9,gives considerably improved yields when performed in the presence of copper(I1) ~a1ts.l~ l2 B. Iddon 0.Meth-Cohn E. F. V. Scriven H. Suschitzky and P. T. Gallagher Angew. Chem. Infernat. Edn.1979,18,900. l3 0.L. Chapman R. S. Sheridan and J.-P. LeRoux Rec. Trav. chim. 1979,98,334;0.L. Chapman and R. S. Sheridan J. Amer. Chem. SOC. 1979,101,3690. l4 D. J. Pasto and D. M.Chipman J. Amer. Chem. SOC. 1979,101,2290. J. E. G. Kemp D. Ellis and M. D. Closier Tetrahedron Letters 1979 3781. l6 R. S. Atkinson and B. D. Judkins J.C.S. Chem. Comm. 1979,832 833. " M. Edwards T. L. Gilchrist C. J. Harris and C. W. Rees J. Chem. Res. (S) 1979 114. '* N. Torimoto T. Shingaki and T. Nagai J. Org. Chem. 1979 44 2585; see also L. D'Epifanio L. Pellacani and P. A. Tardella ibid. p. 3605. l9 F. Bellamy and J. Streith J. Chem. Res. (S) 1979 18. D. W. Knight I 0- Scheme 5 A highly practical route to pentaco-ordinate phosphoranes consists of treatment of a suitable azide with a phosphine*' (Scheme 6).(::+ PR'R2R3 + (EPR'R2R3 -* Z=OorNH Scheme 6 Previous studies with imidoylnitrenes (9; R = H) revealed that a major reaction pathway was attack by the nitrene at the ortho-position of the aromatic ring followed by re-aromatization. It has now been found that when the ortho-positions are blocked e.g. (9; R=Me) a rather different set of rearrangements occurs via 3aH-benzimidazoles (lo) leading to cyclopenta[d]pyrimidines by sequential [1,5]vinyl- imidoyl- and hydride-shifts (Scheme 7).*l Also isolated from thermally generated (9; R = Me) were low yields of benzimidazoles e.g. (1l) which could have arisen from (10) by extremely rare but thermally allowed [1,9] alkyl shifts. Scheme 7 J.I. G. Cadogan I. Gosney E. Henry T. Naisby B. Nay N. J. Stewart and N. J. Tweddle J.C.S. Chem. Comm.,1979 189; J. I. G. Cadogan N. J. Stewart and N. J. Tweddle ibid.,p. 191. T. L. Gilchrist C. J. Moody and C. W. Rees J.C.S. Perkin I,1979,1871;T. L. Gilchrist P. F. Gordon,D. F. Pipe and C. W. Rees ibid.,p. 2303. 89 Arynes Carbenes Nitrenes and Related Species Some evidence that intramolecular insertion of an arylnitrene into thiophenes proceeds via a ring-opened form is the isolation of one such compound (12) (see Scheme 8);22however it is still uncertain that (12) is a true intermediate and not a by-product. Scheme 8 A second example of a bis-nitrene metal complex C~S-[MO(NP~),(S,CNE~~)~], has been reported. X-Ray analysis at -130 "C reveals that the two phenylnitrene ligands are not identical one being nearly linear while the second is bent at nitrogen (LMoNC= 139.4 ") with a longer Mo-N bond than the former.23 Phenylphosphinidine (PhP:) thermally generated from (PhP)5 inserts into Ge-X bonds (X = H C N 0,or P) to provide a route to germylph~sphines.~~ 3 Carbenes The stable isolable salt (13) serves as a useful source of methylene for the stereospecific conversion of olefins into cyclopropanes in good yields2' The formation of cyclopropanes from carbenes and olefins when thought of in Frontier Orbital terms is generally carried out with an electrophilic carbene (e.g.:CC12) where the dominant orbital interaction is between the LUMO of the carbene and the HOMO of the olefin and less commonly using a nucleophilic carbene e.g.zC(OM~)~. This spectrum of reactivity has been summarized,26 and it has also been demonstrated that methoxychlorocarbene (14) is an ambiphilic species in that although its additions to electron-rich olefins may be characterized as electrophilic (14) is a nucleophilic species in the reactions with electron-poor ole fin^.^' The preparation of (14) by thermolysis of diazirine (15) both in solution and in the gas phase involves a direct two-bond cleavage to the exclusion of the alternative pathway via one-bond rupture to give a diazo intermediate; a process which operates when various other substituents (e.g.Ph or alkyl) are present.28 co + C1 OMe YMe I Cp-Fe -CH2SMe2 N=N 's' I '* G. Jones C.Keates I. Kladko and P. Radley Tetrahedron Letters 1979,1445; see also G.Jones and W. H. McKinley J.C.S. Perkin I 1979 599. 23 B. L. Haymore E. A. Maatta and R. A. D. Wentworth J. Amer. Chem. SOC. 1979,101,2063. 24 J. Escudit C. Couret and J. Satgt Rec. Trav. chim. 1979,98,461. '' S. Brandt and P. Helquist J. Amer. Chem. SOC. 1979 101 6473. 26 R. A. Moss and R. C. Munjal Tetrahedron Letters 1979,4721. " R. A. Moss M. Fedorynski and W.-C. Shieh J. Amer. Chem. SOC.,1979,101,4736; N. P. Smith and I. D. R. Stevens J.C.S. Perkin ZI 1979 1298. ''N. P. Smith and I. D. R. Stevens J.C.S. Perkin ZI 1979 213. D. W.Knight The generation of dibromocarbene from bromoform under phase-transfer condi- tions is successful when cetyltrimethylammonium bromide is used as catalyst whereas benzyltriethylammonium chloride favours the formation of -CBr3 only.29 A careful choice of reagents is also necessary for the generation of bromo-chlorocarbene from HCBr2Cl by phase-transfer methods.30 Dihalogeno-carbenes generated in this way can be added sequentially to all of the olefinic bonds in bullvalene and cyclo-octatetraene to give (16) and (17) re~pectively.~’ The preparation and chemistry of 1,2,2-trifluoroethylidenehas been investigated; reactions with alkanes lead mainly to C-H insertion products with the usual order of reactivity (3’ >2’> 1’) being Halogenocarbenes thermally generated from chloroform add to pyrrole and some methyl-pyrroles to give surprisingly high yields of chloro-pyridine~.~~ Interest in Simmons-Smith-type reactions continues.Conventional conditions using gem -dihalides and zinc or copper-based catalysts are usually only successful when applied to electron-rich olefins. It has now been found that by employing a nickel catalyst i.e. [Ni(PPh3)4] in the presence of sodium iodide and zinc electron- poor olefins (e.g. vinyl ketones or acrylates) can be efficiently converted into cycl~propanes.~~ When copper powder is used in these reactions the addition is highly stereoselective indicating the intermediacy of organo-coppers rather than free carbene~.~~ Indeed ab initio calculation^^^ support this view and suggest that the true intermediates in the Simmons-Smith reaction may have considerable metallocarbenium character. Such species’ have been directly observed using 13C n.m.r.37 Furthermore in the reaction between dibromocyclopropane (18) and methyl-lithium products are found which attest to the intermediacy of (19)as well as of cyclopropylidene (20).38 29 M.S. Baird A. G. W. Baxter B. R. J. Devlin and R. J. G. Searle J.C.S. Chem. Comm. 1979 210. 30 E. V. Dehmlow and M. Slopianka Annalen 1979 1465. 31 E. V. Dehmlow and M. Lissel Annalen 1979 181. 32 R. N. Haszeldine R. Rowland J. G. Speight and A. E. Tipping J.C.S. Perkin I 1979 1943; R. N. Haszeldine C. Parkinson P. J. Robinson and W. J. Williams J.C.S. Perkin IZ 1979,954. 33 R. E. Busby M. Iqbal M. A. Khan J. Parrick and C. J. G. Shaw J.C.S. Perkin I 1979 1578. 34 H. Kanai and N. Hiraki Chem. Letters 1979 761. 35 N. Kawabata I.Kamemura and M. Naka J. Amer. Chem. SOC.,1979 101 2139; N. Kawabata M. Tanimoto and S. Fujiwara Tetrahedron 1979 35 1919. 36 T. Clark and P. von R. Schleyer J.C.S. Chem. Comm. 1979,883; Tetrahedron Letters 1979,4963. 37 D. Seebach H. Siegel K.Miillen and K. Hiltbrunner Angew. Chem. Internat. Edn. 1979,18,784;H. Siegel K. Hiltbrunner and D. Seebach ibid. p. 785. 38 M. S. Baird and A. G. W. Baxter J.C.S. Perkin I 1979 2317. Arynes Carbenes Nitrenes and Related Species Br%k Br CONRz Br* Li CONRZ CONR Cyclopropylidenes usually undergo ring-opening reactions to give allenes unless these would be highly strained or unless insertion pathways are readily available. An example of the latter phenomenon is the formation of (22) and (23) from the anti-3-vinylbicyclo[4.1.0]heptane (21),39by insertion into the C-3-H and C-5-H bonds respectively.Similar treatment of the syn isomer of (21) at low temperatures results in addition to the vinyl group. The dual pathway in the reactions of cyclopropylidene (24)to give allenes (25) and insertion products (26)has been investigated. A Hammett plot gives p = -0.5 indicating little build-up of charge at the benzylic carbon during insertion assuming that changes in the para -substituent have little effect on the rate of formation of a11ene.40 Vinylcyclopropylidenes usually undergo [1,3] shifts to give 3-cyclo-pentenylidenes; it has now been suggested that the cis-dienylcyclopropylidene (27) reacts by a novel [1,5] shift to give (28) ultimately isolated as cycloheptatriene (29).41Alternative mechanistic rationales (e.g.insertion into vinylic C-H or into the terminal double bond) seem to be energetically unfavourable.39 M. S. Baird J.C.S. Perkin I 1979 1020; see also R. M. Cory L. P. J. Burton and R. G. Pecherle Synth. Comm. 1979,9,735;M. S. Baird P. Sadler J. Hatem J.-P.Zahra and B. Waegell J.C.S. Chem. Comm. 1979,452. 40 M.S. Baird J.C.S. Chem. Comm. 1979,776. 41 U.H. Brinker and I. Fleischhauer Angew. Chem. Internar. Edn.,1979 18 396. D. W.Knight MIND0/3 calculations indicate that the initial step in the transformation of cyclobutylidene into methylenecyclopropane involves electrophilic attack by the empty p-orbital of the carbene carbon onto the methylene group at C-3 to produce a bicyclobutane-type intermediate a formulation which represents a ‘non-classical’ ~arbene.~* 2-Vinylcyclobutylidenes (30) in contrast to vinylcyclopropylidenes (cf.ref. 41) do not undergo carbene-carbene rearrangements but instead give mainly allyl- idenecyclopropanes (3 1)by C-2-C-3 bond cleavage.43 Isopropylidenechlorocarbene when generated in the presence of olefins under- goes mainly intramolecular rearrangement whereas under similar conditions cyclopropylidenechlorocarbeneadds to the alkenes although lower selectivities are found than those theoretically predicted. These observations can be explained by assuming that the latter carbene is stabilized by interaction between the cyclopropyl a-bonds and the empty p-orbital of the carbene carbon (32) and that this stability is lost when the incoming olefin causes the molecule to adopt a less crowded twisted conformation (33).44 The greater stability and longevity of (32) contrasts with the cyclobutyl analogue (34) which undergoes intramolecular rearrangement and cyclopropanation reactions in approximately equal amo~nts.~’ The aluminium-carbon bond energy in the vinylidene complex Al-C=CH2 has been calculated to be ca.20 kcal mol-’ showing the profound influence that a metal can have on such reactive intermediate^.^^ A novel thermal rearrangement termed the ‘a-alkynone cyclization’ involves the formation of 2-cyclopentenones (37) from a-alkynones (39 probably via alkylidenecarbenes (36).47 A general route to alkylidenes is by a facile loss of nitrogen from diazoalkenes these being prepared by Wadsworth-Emmons reactions between dimethyl diazomethylphosphonate and aldehydes or alkyl aryl ketones.48 Ab initio calculations on the C4H2system have shown that the two arrangements butatrienylidene (38) and ethynylvinylidene (39) are of almost the same energy and 42 W.W. Schoeller J. Amer. Chem. SOC., 1979,101,4811. 43 U. H. Brinker and L. Konig J. Amer. Chem. SOC., 1979,101,4738. 44 R. A. Moss M. Vezza W. Guo R. C. Munjal K. N. Houk andN. G. Rondan J. Amcr. Chem. SOC., 1979 101,5088. 4s R. A. Moss M. E. Fantina and R. C. Munjal Tetrahedron Letters 1979 1277. 46 M. Trenary M. E. Casida B. R. Brooks and H. F. Schaefer 111 J. Amer. Chem. SOC., 1979,101,1638. 47 M. Karpf and A. S. Dreiding Helv. Chim.Acta. 1979 62 852. 48 J. C. Gilbert U. Weerasooriya and D. Giamalva Tetrahedron Letters 1979,4619. Arynes Carbenes Nitrenes and Related Species that the energy difference between them and the stable structure buta-1,3-diene is similar to the difference between vinylidene and acetylene.49 A brief report has appeared on the generation of the 4,4-dimethyl derivative of (38) by base-induced y-elimination of triflate from (40).” An authoritative review has appeared on [1,2]-hydrogen shifts involvingcarbenes and nitrene~.’~ A detailed study of such [1,2] rearrangements in non-rigid cyclo-hexylidenes e.g. (41),amplifies previous work in leading to the conclusion that for such conformations an axial hydrogen is more likely to migrate as its bonding orbital is nearly parallel with the empty p-orbital of the carbene and perpendicular to the filled non-bonding ~rbital.’~ In contrast to earlier findings with methylene the energy gap between the singlet and triplet ground states in simple alkylcarbenes (42) appears53to be considerably less than 20 kcal mol-’.Ar R-C IH (41) (42) R =But or Pr’ (43) (44) PadwaS4 has discussed the probable intermediacy and subsequent reactions of vinylcarbenes (44) in photochemical reactions of cyclopropenes (43). Photo-chemically generated vinylsulphinylcarbene (45) undergoes a novel rearrangement to give vinyl-sulphines (46) which can be trapped or isolated as the corresponding ap-unsaturated ketone.” 1,l-Dichloroallyl-lithium serves as a useful source of chlorovinylcarbene (47) which reacts with simple olefins to give 1-chloro-1 -vinyl-cyclopropanes in 1842%yield.56 0 t s-0 9 CI (47) (45) 49 C.E. Dykstra C. A. Parsons and C. L. Oates J. Amer. Chem. SOC.,1979,101 1962. ’O P. J. Stang and T. E. Fisk J. Amer. Chem. SOC., 1979,101,4772; Synthesis 1979,438. ” H. F. Schaefer 111 Accounts Chem. Res. 1979,12,288. 52 L. S. Press and H. Shechter J. Amer. Chem. Soc. 1979 101,509. 53 K.-T. Chang and H. Shechter J. Amer. Chem. SOC., 1979,101,5082. ”A. Padwa Accounts Chem. Res. 1979,12 310; A. Padwa T. J. Blacklock and R. Loza Tetrahedron Letters 1979 219 1617. ”M. Franck-Neumann and J. L. Lohmann Tetrahedron Letters 1979 2397. 56 R. A. Moss and R. C. Munjal Synthesis 1979 425.D. W. Knight In a rather odd reaction 1-chloro-2-alkyl-cyclohexenesreact with organo- lithiums to give bicyclo[4.1.O]heptanes (Scheme 9) probably via the carbene (48) and the cyclopropene (49).” Reactions of (presumably) singlet pyrrolylidene (50) with substituted benzenes proceed via two pathways depending on the electronic properties of the substituent (Scheme 1O);58 not surprisingly triplet (50)gives only the substitution products (52) without the participation of spironorcaradiene (51). Z = CN or NOz (52) Z = OMe or Me Scheme 10 The thermal rearrangement of benzocyclopropane to ethynylcyclopentadiene (Scheme 11)is well known but the final product has always eluded proper charac- terization. This has now been achieved with the naphthalene analogue (53),obtained from naphth0[2,3]cyclopropane.~~The preparation of benzvalene via cyclo-pentadienylcarbene could proceed by a conventional cyclopropanation reaction or by an overall [1,4] addition (Scheme 12).Compelling evidence for the latter pathway is the isolation of only (55)from the rearrangement of the 1-methyl analogue (54).60 Full details for the preparation of p-tolylcarbene have been published together with some useful notes on the generation of carbenes.6l Arylcarbenes photo- 57 P. G. Gassman J. J. Valcho and G. s.Proehl J. Amer. Chem. SOC.,1979 101 231. ” M. Nagarajan and H. Shechter J. Amer. Chem. SOC.,1979,101,2198. ’’ C. Wentrup. E. Wentrup-Byrne P. Muller and J. Becker Tetrahedron Letters 1979,4249. 6o U. Burger and G.Gandillon Tetrahedron Letters 1979 4281. 61 C. M. Dougherty and R. A. Olofson Org. Synth. 1978,58 37. Arynes Carbenes Nitrenes and Related Species (53) Scheme 11 4d ;dl _[1,21 ’@ [1,4] 5 41 2 5 Scheme 12 chemically generated in rigid matrices of alkanes preferentially insert into primary C-H bonds in contrast to the propensity for reaction with secondary and tertiary C-H bonds in liquid alkanes at room temperature. This effect is probably due to the steric constraints imposed by the rigid matrix.62 These constraints can also cause the reactivity of arylcarbenes to be dependent on the precursor. Thus determinations of singlet/triplet ratios by an analysis of the products arising from carbenes generated in Thermally matrices at low temperatures (e.g.-196 “C) can be ~nreliable.~~ generated a-substituted arylcarbenes such as (56) mainly undergo intramolecular insertion reactions to give five- and six-membered rings (Scheme 13);64a-alkoxy-arylcarbenes also react by a formal double proton abstraction to give the cor- responding vinyl although labelling studies reveal that this reaction does not occur via a geminal abstraction followed by a [1,2] hydride shift. X = CH2 NR 0,or S Scheme 13 It is known that the bivalent carbon in p-tolylcarbene is capable of migration to give styrene and benzocyclobutene. Good evidence has been found for the occur- rence of a similar process in icosahedral carbaboranes;66 it is interesting to note that other analogies between benzene and carbaboranes have been made in the past.62 H. Tomioka J. Amer. Chem. SOC., 1979,101,256. 63 H.Tomioka G. W. Griffin and K. Nishiyama J. Amer. Chem. SOC.,1979,101,6009. 64 W.D.Crow and H. McNab Austral. J. Chem. 1979,32 89,99 123. ” W.D.Crow and H. McNab Austral. J. Chem. 1979 32,111. 66 S.Chari G. K. Agopian and M. Jones Jr. J. Amer. Chem. SOC., 1979,101,6125. D. W. Knight Further progress towards understanding the role of copper in catalysing the decomposition of diazodiphenylmethane has been made.67 It seems that copper(I1) is involved in a chain reaction with radical cations as carriers whereas copper(1) reacts via unknown complexes. The mechanism of the reactions between carbenes and metal carbonyls to give ketens has remained obscure for many years.It now seems that this occurs not by addition of carbon monoxide to a metal-carbene complex but rather by addition of carbene across the metal-CO bond.68 More evidence has been found to support the idea that olefin metathesis reactions proceed via metal-carbenoid complexe~.~~ The specific formation of vinylcyclopropanes (58) can be achieved under mild conditions from diazo-ketones (57) by intramolecular carbenoid insertion reactions; good yields are obtained only for small rings (n = 2,3 or 4).70 Thermolysis of compounds (58) leads to cis-fused cyclopentenes. Surprisingly the effects of conformation on the Wolff rearrangement of a-diazo-ketones to ketens have not until recently been investigated. It has now been shown7' that under aprotic thermal or photochemical conditions an S-2 conformation with the migrating group trans to the nitrogen is necessary for keten formation suggesting that the Wolff rearrangement is a concerted reaction rather than one involving ketocarbenes (Scheme 14).Set against this conclusion are some further studies'* on the photo-Wolff reaction of a-diazo-ketones using 13C labelling which indicate the occurrence of a carbene-carbene rearrangement via an oxeten inter- mediate in line with previous work. 0 S-Z Mainly S-E Bu' Scheme 14 It has long been known that ketocarbenes (59; R = H) react by insertion into the endo-C-H bond at C-5. When this position is blocked by an acetate group i.e. (59; 67 D. Bethell K. L. Handoo S. A.Fairhurst and L. H. Sutcliffe J.C.S.Perkin ZZ 1979,707,D. Bethell M. F. Eeles and K. L. Handoo ibid. p. 714. 68 W. A. Herrmann J. Plank M. L. Ziegler and K. Weidenhammer J. Amer. Chem. SOC.,1979,101,3133. 69 R. H. Grubbs and C. R. Hoppin J. Amer. Chem. SOC.,1979,101,1499; F. N. Tebbe G.W. Parshall and D. W. Ovenall ibid. p. 5074; see also C. O'Donohoe J. K. A. Clarke and J. J. Rooney J.C.S. Chem. Comm. 1979,648. 70 T. Hudlicky J. P. Sheth V. Gee and D. Barnvos Tetrahedron Letters 1979,4889. 71 F. Kaplan and M. L. Mitchell Tetrahedron Letters 1979 759. 72 K.-P. Zeller Chem. Ber. 1979,112 678; Annalen 1979 2036; Monatsh. 1979,110 393. 97 Arynes Carbenes Nitrenes and Related Species R =OAc) insertion into the C-R bond is replaced by reaction with the carbonyl group of the acetate followed by rearrangement to (60).73When R is OMe the carbene inserts into a C-H bond of the methoxy-group to give (61).a-1minocarbene (62) when photochemically generated in methanol largely undergoes rearrangement to the ketenimine (63)before being trapped by the solvent (Scheme 15).74 The intermediate (63) can be trapped by other reagents; for example with benzylideneanilide when the p -1actam imide (64) can be isolated. N2 Ph2NpH & Ph2NyeH __* MeOH Ph2NYcH20Me NCN NCN NCN (62) ca. 25% 'I Ph Ph2N OMe 'CScSNCN MeOH Yt'ph I +P~~NANCN Ph2N NCN H ca. 75% (64) (63) Scheme 15 The reaction of carbene (65) with alcohols leads to a number of products the most notable of which is the methoxysilane (66); its formation may involve a silene i~~termediate.~' A A MeOH Me3Si C02Et __* Me2Si C02Me PhAP(OMe), I II (65) Me0 0 (66) (67) Photolytically generated phosphorylcarbenes (67) insert into the hydroxy-group of simple alcohols at 27 "C but into the C-H bonds at -196 "C As the sensitized photolytic generation of (67) at 27°C leads to an increase in products of C-H insertion these results may be rationalized by assuming that 0-H insertion products arise via the singlet carbene (cf.ref.18) whereas C-H insertion products involve the intermediacy of the triplet carbene. The triplet carbene probably reacts by proton abstraction followed by combination of the resulting radicals.76 73 P. Yates and G. F. Hambly Canad. J. Chem. 1979,57 1668. 74 B.Arnold and M.Regitz Angew. Chem. Internat. Edn. 1979,18,320. 75 W.Ando A. Sekiguchi T. Hagiwara T. Migita V. Chowdhry F. H. Westheimer S. L. Kammula M. Green and M. Jones Jr. J. Amer. Chem. SOC.,1979,101 6393. 76 H. Tomioka T. Inagaki S. Nakamura and Y. Izawa J.C.S. Perkin I 1979 130. 98 D. W. Knight Further reports have appeared on the reactions of thiophen with various diazo- compounds in the presence of rhodium(I1) (Scheme 16).77 The remarkably stable ylide (68) serves as a good source of bis-methoxycarbonyl-carbene (69) which can be used to prepare aryl malonates from electron-rich aryl~.'~ The conversion of (68) into (69) requires the presence of Cu" or Rh" catalysts as simple thermolysis of the ylide leads to (70). Carbenoids derived from diazomalonates by Cu"-induced decomposition react with 1,l -dicyclopropylethylene to give only the addition product; this suggests ihat the singlet rather than the triplet carbenoid is involved as the latter would be expected to give rise to rearrangement HH iii 1 0 AMeO,CACO,Me 1 (69) Me0,C C02Me (70) (68) Reagents i N,CHCO,Me; ii PhCOCHN,; iii N,C(CO,Me),; iv A; v Cu" Scheme 16 [2,3]-Sigmatropic rearrangements of dithiocarbenes (7 l),generated from the corresponding tosylhydrazone by base-induced elimination give only the trans product (72) probably due to the intermediate adopting a 'folded envelope' con- formation in which the substituent R occupies a pseudo-equatorial position." Theoretical calculations indicate that in contrast to cyclopropylidene which is considerably less stable than its neutral acyclic isomers (i.e.allene propyne) silacyclopropylidene (73) is much more stable than 2-sila-allene and 2-silapr0pyne.~~ Also a singlet ground state is predicted for (73) again in contrast to cyclo- propylidene which has a triplet ground state. The elusive dimethylsilylene (74) has been detected by U.V. and i.r. spectroscopy in hydrocarbon glasses at -196 "C; the 77 R. J. Gillespie and A. E. A. Porter J.C.S. Perkin I 1979 2624; R. J. Gillespie J. Murray-Rust P. Murray-Rust and A. E. A. Porter J.C.S. Chem. Comm. 1979,366. 78 R. J. Gillespie and A. E. A. Porter J.C.S. Chem. Comm. 1979 50. 79 M. E.Alonso and M. G6mez. Tetrahedron Letters 1979,2763. 80 T. Nakai and K. Mikami Chem.Letters 1979 1081. J.-C. Barthelat G. Trinquier and G. Bertrand J. Amer. Chem. SOC.,1979 101,3785. Arynes Carbenes Nitrenes and Related Species species appears to be stable under these conditions and can be trapped by various reagents to give ca. 60% yields of the expected products.82 Dimethylsilylene (74) can also be generated by photolysis of (Me2Si), and it adds to a-diketones to give silacyclopent-4-enes such as (75).83Further support for the existence of silylenes is the isolation of (77)from the co-thermolysis of (76)with anthracene; presumably the silylenes dimerize to disilenes prior to reaction with the anthracene. If the latter is replaced by 2,3-dimethylbuta-1,3-diene,then the 1-silacyclopentene (79) is iso- lated the silylene probably being trapped as the silacyclopropane (78) before it can dimeri~e.~~ ,SIRR'R2Si I 'R2 R 1.R' \/ (77) R2 82 T.J. Drahnak J. Michl and R. West J. Amer. Chem. Soc. 1979 101 5427. 83 W.Ando and M. Ikeno J.C.S. Chem. Comm. 1979,655. 84 Y.Nakadaira T. Kobayashi,T. Otsuka and H. Sakurai J. Amer. Chem. Soc. 1979,101,486; H.Sakurai Y. Nakadaira and T. Kobayashi ibid. p. 487.

ISSN:0069-3030    

DOI:10.1039/OC9797600085

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

6 Electro-organic Chemistry By R. LINES Ra ychem Limited Farada y Road Dorcan Swindon SN3 5HH 1 Introduction This review is organized as in previous years according to the nature of the species which is believed to participate in the initial electrode reaction. Of general interest is a report by a Swedish group' on the advantages and use of a capillary-gap cell for large laboratory-scale organic electrosyntheses. 2 Anodic Processes The Anodic Oxidation of Carboxy1ates.-A procedure for the conversion of a-(pheny1thio)carboxylic acids into the corresponding aldehydes or acetals (Scheme 1) under mild conditions has been described by a Japanese group.2 CH3(CH&CHO +(PhS)2 CH3(CH&CH(SPh)C02H mc91O/O CH3(CH2)7CH(OCH3)2+PhS(O)OCH3 Reagents i aq.NaOH; ii MeOH LiClO 95% Scheme 1 The Kolbe reaction has also been used to advantage for the preparation of cyclic and semi-cyclic N-acyl NO-a~etals.~ The definition of semi-cyclic and cyclic N-acyl NO-acetals has been given by Nyberg quoted in ref. 3. Such compounds are precursors of N-acyl-immonium ions which in turn are key intermediates in the synthesis of some amino-acids and alkaloids. The starting materials are N-acyl- prolines or N-acyl-pipecolic acids and these are smoothly converted into the acetals in high yield by anodic oxidation in alcoholic solution (Scheme 2). COR ' COR' Scheme 2 L. Eberson J. Hlavaty L. Jonsson K.Nyberg R. Servin H. Sternrup and L.-G. Wistrand Acta Chem. Scand. (B),1979,33 133. J. Nokami M. Kawada and R. Okawara Tetrahedron Letters 1979 1045.'T. Iwasaki H. Horikawa K. Matsumoto and M. Miyoshi J. Org. Chem. 1979,44 1552. 102 R. Lines The finding that malonic acid derivatives can function as ketone synthons has been applied by a Japanese group4 to the synthesis of jasmones in 43% overall yield starting from diethyl malonate (Scheme 3). R' ' "ZH Pt electrodes ____ R~'CO,H 10-12Fmol~' R2 Scheme 3 The synthetic utility following the electrolytic decarboxylation of 1-alkyl-2-cycloalkene-1-carboxylic acids' is well demonstrated by the preparation of dl-muscone (1; R'= Me n = 12) outlined in Scheme 4. The reaction involves a regiospecific acetoxylation at the a-position of the unsaturated acids and this is used to advantage in the synthesis of dl-muscone by serving as a means of introducing a methyl group at the p -position of the cyclopentadecanone precursor.OAC Reagents i HOAc Bu'OH Scheme 4 The Anodic Oxidation of Neutral Organic Compounds.-The synthetically useful organic intermediates benzoquinone bis-acetals have been found to be readily prepared by the anodic oxidation of 2-substituted 1,4-dimethoxybenzenes in methanolic KOH solution.6 Many of these compounds were also found to undergo selective monohydrolysis at the acetal remote from the 2-substituent to give a good yield of the equally useful mono-acetals. The anodic oxidation of methoxy-naph- thalenes has also been studied in methanolic KOH solution7 and found to be a convenient route to methoxylated naphthalenes and 1,2-naphthoquinone mono- ace tals.The electro-acetoxylation of 4-methylphenyl acetate to 4-acetoxybenzyl acetate has formed the basis of a synthesis of vanillin described by Torii and co-workers.8 A detailed study of the electro-acetoxylation conditions revealed that the products in which the side-chain was oxidized could be obtained in high yield (90%) and with high selectivity (88%)by the addition of metal acetates especially copper(I1) acetate to the acetic acid-t-butyl alcohol electrolyte. The metal ions are thought' to promote the smooth oxidation of the benzyl radicals to benzyl cation intermediates. J. Nokami T. Yamamoto M. Kawada M. Izumi N. Ochi and R. Okawara Tetrahedron Letters 1979 1047. S. Torii T. Inokuchi K. Mizuguchi and M. Yamazaki J.Org. Chem. 1979,442303. D. R. Henton B. L. Chenard and J. S. Swenton J.C.S. Chem. Comm. 1979,326. 'M. G. Dolson D. K. Jackson and J. S. Swenton J.C.S. Chem. Comm. 1979,327. S. Torii H. Tanaka T. Siroi and M. Akada J. Org. Chem. 1979,443305. Elec tro -organic Chemistry Methanolic NaCN appears to be an excellent medium for the anodic cyanation of pyrroles' and methyl-naphthalenes. lo For a series of 1-alkyl-pyrroles,' substitution was found to take place pfeferentially at a vacant 2- or 5-position while the 1,2,5-triaIkyl-derivativesunderwent cyanation in the side-chain to form dialkyl- pyrrole-2-acetonitriles. An interesting feature of this reaction is that in contrast to the anodic cyanation of cyclohexene in the same reaction medium [see Ann.Reports (B) 1977 74 1551 no isocyanides or methoxylated products were observed.' Oxidation of some methyl-naphthalenes in methanolic NaCN resulted in a variety of naphthonitriles." The orientation of attack was found to be directed by the substituent effect of the methyl groups rather than by any steric factors. In many cases the yields of products from the cyanation of pyrroles and methyl-naphthalenes are sufficient to make the methods preparatively attractive; e.g. Scheme 5. CN Reagents i MeOH NaCN Scheme 5 A novel anodic dimerization has been discovered" in which the enamine (2) undergoes coupling between the @-carbon atom and the 4-position of the phenyl ring (see Scheme 6). Until now all of the reported oxidative dimerizations of enamines have occurred predominantly at the ethylenic carbon p to the nitrogen atom.Scheme 6 Another novel observation this time concerning a cleavage reaction relates to the stereoselective oxidation of (dl)-4,4'-dihydroxyhydrobenzoin to 4-hydroxy-benzaldehyde at a mild steel anode.'* Under the electrolysis conditions (aqueous NaOH pH 13.5 2-3 V us. SCE) the meso-form was found to be completely electro-inactive. An explanation advanced by the author'* is that a complex between the oxide coating on the steel anode and the hydroxy-groups of the glycol is a necessary prerequisite for charge transfer. For the meso-compound the phenyl rings prevent a favourable alignment of the hydroxy-groups thus inhibiting oxida- tion. Some preliminary findings have been published on the oxidation of a series of strained polycyclic hydrocarbons.l3 An excellent correlation was found between the E; potentials and the HOMO's of the compounds studied. For these compounds the HOMO's are associated with a carbon-carbon rather than a carbon-hydrogen bond K. Yoshida J. Amer. Chem. SOC.,1979,101 2116. '' K. Yoshida and S.Nagase J. Amer. Chem. SOC.,1979 101 4268. M. Masui T. Michida C. Ueda and H. Ohrnori Chem. and Ind. 1978,922. l2 J. H. Wagenknecht J. Electrochem. SOC.,1979,126,983. l3 P. G. Gassrnan and R. Yamaguchi J. Amer. Chem. SOC.,1979,101 1308. 104 R. Lines and indeed on oxidation in pyridine-methanol tricyclo[4.1.1 .0.02*7]heptane for example gave predominantly the acetal (3). A study has been made of the oxidation of a series of mono- and di-thioethers and of a number of mesocyclic dithioether~.'~ The latter compounds underwent facile (3) (4) reversible oxidation in contrast to the irreversible oxidation of the non-cyclic derivatives.The difference in behaviour was attrib~ted'~ to transannular inter- actions between the sulphur atoms of the products of the oxidation of the mesocyclic compounds. From their observations the author~'~ concluded that transannular interaction depended on the fulfilment of two conditions viz. the formation of two five- or six-membered rings coupled with geometric constraint. Thus for example 1,5-dithiacyclo-octane gave the dication (4) whereas dibenzo-dithiacyclododecane underwent irreversible oxidation. 3 Cathodic Processes The Cathodic Reduction of Organic Cations.-Following last years report of the formation of a pyrrolodiazepine from the electrolysis of a dihydrodiazepine salt [see Ann.Reports (B) 1978 75 1391 the reduction of the NN'-disubstituted dihy- drodiazepine salt (5) has been studied." The presence of the substituents on the nitrogen atoms precludes the reaction pathway reported previously and instead three products were isolated viz. (6) and the meso and racemic forms of (7). It has yet to be ascertained whether the formation of (6)precedes or follows the dimeriza- tion of (5) to (7). The Cathodic Reduction of Neutral Organic Compounds.-The cleavage of diary1 sulphones in aprotic solvents to the corresponding aryl sulphinate ion and aromatic hydrocarbon has until now been thought to proceed entirely uia charged inter- mediates i.e.anion radicals and dianions. Evidence has now been presented to suggest that radical intermediates are involved.16 Thus reduction of (8) in DMF gave (9) by cleavage of a carbon-sulphur bond in the anion radical of (8),followed by an intramolecular radical substitution on the adjacent phenyl ring. l4 G. S. Wilson D. D. Swanson J. T. Klug R. S. Glass M. D. Ryan and W. K. Musker J. Amer. Chem.SOC. 1979,101,1040. '' D. Lloyd C. A. Vincent and D. J. Walton Bull. SOC. chim. belges 1979,88 113. l6 J. Grimshaw and J. Trocha-Grimshaw J.C.S. Perkin I 1979,799. Elec tro-orga n ic Chemistry The electroreduction of a number of ao-9,9'-dianthryl-ethanes[m(CH2),,7r]has been st~died,'~ with a view to determining how the interactions between the aromatic centres affected the reversible electrode potentials.The results showed that strong interactions operated for the compounds with n = 0 and n = 2 but decreased as the length of the methylene chain increased. At n = 6 the two successive charge transfers (anion radical to dianion) merged into a single wave with a peak width close to that of a reversible one-electron transfer confirming the independence of the electro-active centres. In a separate study of bianthryl (i.e. n = 0),l8fragmentation into anthracene and 9,lO-dihydroanthracene was observed upon electrolysis at the potential of the second wave and above. This represents the first example of the direct electrochemical cleavage of a biaryl into the corresponding monomer.A very useful example of the selective protection of the primary or secondary hydroxy-group in a diol has been presented by van der Stouwe and Schafer." The authors found that tritylone ethers can be cathodically cleaved in high yield and under mild conditions to the corresponding alcohols. By taking advantage of the different reduction potentials of the tritylone and p -cyanobenzyl ether protecting groups the selective protection of the hydroxy-groups of pentane- 1,4-diol was demonstrated. The electroreduction of some cyclic ethers namely epoxides of structure (lo) has also shown interesting behaviour.20 The direct reduction of the epoxides in DMF at mercury afforded products (alchohols and hydrocarbons) by a two-electron pathway.Ph R2 \ / c-c R \0/ \R3 The same products were also obtained by indirect reduction using electrogenerated reducing agents and autocatalysis was observed in some cases. Thus for (10; R2= Ph) ring opening followed by elimination of OH-generated trans-stilbene which was then able to form a stable anion radical and thereby once a suitable concentration of it had been attained undergo homogeneous electron exchange with the substrate. " K. Itaya and A. J. Bard 2.Phys. Chem. (Frankfurt) 1978,112 1. l8 0.Hammerich and J.-M. Saveant J.C.S. Chem. Comm. 1979,938. l9 C. van der Stouwe and H. J. Schafer Tetrahedron Letters 1979 2643. *' K. Boujlel and J. Simonet Electrochim. Acta 1979,24,481. 106 R. Lines Two have appeared that describe an improved synthesis of retinal pinacol(l1) by the reductive dimerization of retinal (12).One of the methods22 uses CrC13.6H20 as a modifier whilst _the other21 uses carbon acids such as diethyl malonate as the proton donor. Both procedures seem to owe their success to the abilities of the additives to form complexes with retinal or its anion radical and thereby to direct the coupling reaction towards pinacol formation. Retinal pinacol (1 1) provides an entry into the C40 carotenoids and as such an efficient method of electrochemically cleaving allylic hydroxy-groups would be of great synthetic value. The leaving ability of such a group is however rather low. It seems appropriate then that the methyl ester of abscisic acid (13) has been chosen as a model compound for the study of the conditions required for hydroxyl cleavage.23 The hydroxy-group attached to C-6 is activated both by the enone and by the unsaturated side-chain ester.Contrary to expectations it was found that upon reduction the bicyclic ester (14) was obtained in good yield. It appears that the hydroxy-group by preventing conjugation throughout the molecule allows selective transfer of electrons to the side-chain. The radical anion that is so formed isomerizes and undergoes rapid cyclization. 0m 0 2 M e The formation of alkenes following the reductive elimination of acetate from vicinal diacetates can be rationalized either by a stepwise or a concerted process. The observation of hydrogenolysis of one of the acetate groups of diacetoxystilbene upon reduction in aqueous DMF24 has provided good evidence for the stepwise mechanism.In contrast with dry DMF where diphenylacetylene is the major product the aqueous medium is sufficiently acidic that the intermediate carbanion is protonated. Reduction of 9,lO-diacyloxy-phenanthrenesled to an unexpected acyl-oxygen fission.24 Phenanthraquinone and the appropriate carboxylic acid were isolated. Following a previous report of the formation of NO-dialkyl-hydroxylamines from the electrochemical reduction of nitro-compounds in the presence of alkyl halides ” L. A. Powell and R. M. Wightman J. Amer. Chem. SOC.,1979,101,4412. ’’ D. W. Sopher and J. H. P. Utley J.C.S. Chem. Comm. 1979 1087. 23 B. Terem and J.H. P. Utley Electrochim. Actu 1979,24 1081. 24 C. Adams N. M. Kamkar and J. H. P. Utley J.C.S. Perkin ZI 1979 1767. Electro-organic Chemistry 107 [see Ann. Reports (B) 1977 74 1583 a description of the efficient synthesis of NO-diacetyl-hydroxylamines has been published.25 The method'consists of directly reducing aliphatic or aromatic nitro-(and nitroso-)compounds in the presence of acetic anhydride. Isolated yields range from 40 to 80%. Another efficient transformation concerns the selective reduction of aliphatic alcohols to alkanes via the methanesulphonate esters.26 The method appears effective even when the alcohol contains other functional groups such as ester alkene nitrile or epoxide. A variety of 1,l-dichloro-alkenes have been ~ynthesized,~~ in good yields by the reduction of diethyl trichloromethylphosphonate and the appropriate carbonyl compounds (Scheme 7).The method has the advantage of avoiding the strongly basic and expensive alkyl-lithium reagents. 0 0 II Hg cathode R'R~CO C12CP(OEt)2-R'R2C=CC12 C13CP(0Et)2 -1.2 V 0s. SCE ' -11 Scheme 7 The electroreduction of some N-ethyl-maleimides has led to the discovery of a hydrodimerization reaction in aqueous Normally aprotic conditions are required for the formation of hydro-dimers from diactivated alkenes where pro- tonation of the intermediate anion radicals competes with their dimerization. In the present example a radical-radical coupling mechanism is thought to operate. Two papers have appeared on the synthesis of substituted barbaralane~.~~*~~ The first paper29 reports on the reduction of bridged 1,5-benzodiazepines (15) in acetonitrile to give substituted barbaralanes (16) in good yield.In the second paper,3o substituted barbaralanes e.g. (17) were obtained by the reduction of bicyclo[3.3. llnonadienediones (18) in the presence of acetic anhydride at the potential of the second wave. Reduction of the substrates at the first wave gave dimeric products only. Aco&Ac (17) X Y =H C1 or Me (18) 25 L. Christensen and P. E. Iversen Acta Chem. Scand. (B),1979,33,352. '.s T. Shono Y. Matsumura K. Tsubata and Y. Sugihara Tetrahedron Letters 1979 2157. '' F. Karrenbrock H. J. Schafer and I. Langer Tetrahedron Letters 1979 2915. 28. H. Zoutendam and P.T. Kissinger J. Org. Chem. 1979 44 758. 29 J. M. Mellor B. S. Pons and J. H. A. Stibbard J.C.S. Chem. Comm. 1979,761. 30 J. M. Mellor B. S. Pons and J. H. A. Stibbard J.C.S. Chem. Comm. 1979 759. 108 R. Lines Evidence has been presented for the reversible formation of the tetranegative ion of the aromatic hydrocarbon de~acyclene.~~ Cyclic voltammetry of the hydrocarbon in dimethoxyethane at 0 "C gave four reversible one-electron waves the fourth being located at -3.35 V (u.s.Agl Ag'). This ion represents the most reduced form of an aromatic hydrocarbon yet reported. Both electrogenerated anions32 and radical diani~ns~~ have been cited as electron- transfer reagents in solution. 1-Ethyl-4-methoxycarbonylpyridinium iodide32 furnished the anion upon reduction whilst the radical dianion was generated33 from the conjugated phenol (19)in the presence of a strong base.In each case a solution electron transfer was demonstrated by cyclic voltammetry for the reduction of a benzylic chloride. HoecH=CH-coR (19) Fritz and Kornr~mpf,~~ by the electrolysis of CF2Br2 at platinum electrodes in dichloromethane containing Bu4NBr are the first investigators to obtain the carbene CF electrochemically. Current efficiencies of up to 60% were recorded for the trapping of the carbene by various alkenes. Contrary to some statements that the reduction of allyl bromides and iodides proceeds in two distinct one-electron steps compelling evidence has now been presented3' to show that in fact the reduction follows a single two-electron pathway.Detailed electro-analytical studies of various allyl halides in acetonitrile revealed that peaks that had previously been attributed to the separate reduction of the allyl radical to the anion were the result of specific surface interactions of the allyl halides with the electrode materials. The reductions can thus be formalized as an elce2 process where I?; <Ey. The reduction of organic halides this time of benzene and pyridine is also the subject of a comprehensive paper by French researcher^.^^ Initial electron transfer to these compounds is slow thus placing the electrochemical reaction under kinetic control and this limits the amount of information that can be obtained from the system. The describe how by the analysis of the homogeneous redox catalytic processes occurring during the electrochemical reductions a more complete characterization of the system can be achieved.Following on from last years' report of electrochemically induced nucleophilic substitution [see Ann. Reports (B) 1978 75 1411 two paper^^'.^^ describe the reaction when conducted in liquid ammonia By this means H-atom abstraction by the intermediate aromatic radicals was suppressed so that attention could be 31 T. Saji and S. Aoyagui J. Electroanalyt. Chem. Interfacial Electrochem. 1979,102 139. 32 H. Lund and L. H. Kristensen Acta Chem. Scand. (B),1979,33,495. 33 A. M. Martre and J. Simonet J. Electroanalyt. Chem. Interfacial Electrochem. 1979,97,287. 34 H. P. Fritz and W. Kornrumpf J.Electroanalyt. Chem. Interfacial Electrochem. 1979 100 217. 3s A. J. Bard and A. Merz J. Amer. Chem. Soc. 1979,101,2959. 36 C. P. Andrieux C. Blooman J. M. Dumas-Bouchiat and J.-M. Saveant I.Amer. Chem. Soc. 1979,101 343 1. 37 C. Amatore J. Chaussard J. Pinson J.-M. Saveant and A. Thiebault J. Amer. Chem. Soc. 1979,101 6012. C. Amatore and J.-M. Saveant J. Electroanalyt. Chem. Interfacial Electrochem. 1979,103 303. Electro-organic Chemistry 109 focussed on the other major competing process to substitution viz. electron transfer to the radicals. A detailed analysis of the kinetics of the competitive electron- transfer process using cyclic voltammetry gave good evidence for the correctness of the SRNlmechanism (Scheme 8). ArX + e-$ ArF ArX7 + Ar' + X- (E; = electrolysis potential) Ar' + Y-+ ArYS ArY7 -e- $ ArY (E;,if E; > E;) Scheme 8 4 Miscellaneous Interest continues to be shown in modifying electrode surfaces by applying polymeric films.Two communications have appeared on the electrochemical polymerization of pyrrole~.~~*~~ in acetonitrile containing Et4NBF4 gave a tough Oxidation of pyrr01e~~ film of conductivity 100 R-' cm-'. Elemental analysis suggested a structure containing polymerized pyrrole units and BF ions in the ratio 4:1. The polymer could be modified further by e.g. nitration. Polymer films of N-methylpyrr~le~~ exhibited much lower conductivities n-'cm-') and thus by co-electrolysis of solutions of pyrrole and N-methylpyrrole films of intermediate conductivities could be obtained.The potentialities of using the charge-transfer complex TTF/TCNQ (tetrathiafulvalene/tetracyanoquinodimethane)as an electrode material in aqueous solution have been explored by Jaeger and Bard.41 The complex was found to be stable over a potential span of 0.9V and the oxidation and reduction of redox couples e.g. Curl/Cul could be carried out. Beyond the potential limits insoluble compounds of TTF or TCNQ with the ions of the supporting electrolyte were formed. A further application of the poly(4-nitrostyrene)-coatedelectrode referred to in last years' report [see Ann. Reports (B) 1978 75 1451 has been found for the reduction of 1,2-dibromo-1,2-diphenylethaneto tr~ns-stilbene.~~ Like the reduc- tion of oxygen on this electrode electron transfer to the dibromide via the charged polymer was found to take place 0.4V less cathodically than at a clean platinum surface.The electrode was also found to be sufficiently stable for preparative-scale electrolyses. Catalyst turnover was of the order of lo4. Chemically modified electrodes as well as being able to catalyse charge transfers can also alter isomer ratios a case in point being the selective chlorination of anisole at a cyclodextrin-modified electr~de.~~ At a graphite anode the chlorination of anisole in aqueous NaCl gave a para :ortho ratio of about 5 :1. Chemically bound a-cyclodextrin on the graphite changed the ratio to 18:1 while adsorbed cyclo- dextrin on the electrode surface increased the ratio to >25 :1.In these cases it is that the ortho-positions of anisole are blocked by the cyclodextrin struc- ture leading to preferential para -chlorination. 39 A. F. Diaz and K. K. Kanazawa J.C.S. Chem. Comm. 1979,635. 40 K. K. Kanazawa A. F. Dim R. H. Geiss. W. D. Gill J. F. Kwak J. A. Logan J. F. Rabolt and G. B. Street J.C.S. Chem. Comm. 1979 854. 4 C. D. Jaeger and A. J. Bard J. Amer. Chem. SOC. 1979,101 1690. 42 J. B. Kerr and L. K. Miller J. Electroanalyt. Chem. Interfacial Electrochem. 1979,101 263. 43 T. Matsue M. Fujihira and T. Osa J. Electrochem. Soc. 1979,126 500. 110 I?. Lines Turning to more conventional electrolytic procedures the almost quantitative conversion of 3-substituted sydnones into their 4-chloro- or 4-bromo-derivatives has been dis~overed.~~ The success of the method appears to lie with the mild conditions of the electrolysis (MeOH NaBr or Me4NCl) which minimizes any tendency for ring opening.Attempts at fluorination and iodination of 3-substituted sydnones by this method were unsuccessful. A preparatively significant synthesis of esters and ketones from primary and secondary alcohols has been accomplished by the use of iodide ions as catalytic current carriers.45 Typically electrolysis of an aqueous solution of the alcohol and KI (4 :1ratio) yields the ketone or ester in up to 84% yield. Although the authors4' suggest the iodonium ion as the key intermediate (Scheme 9) it seems unlikely that this species would be generated in an aqueous environment and at the low anode potential (0.6-0.8 V us.SCE). 0 Scheme 9 Liquid SOz as an electrochemical solvent has been re-examined by two group^.^^*^' Liquid SOz has many advantages from an electrochemical viewpoint e.g. high dielectric constant (ca.20) low nucleophilicity and high solvating ability for covalent compounds. Contamination by water can be a problem however and the solubility of most inorganic salts in the solvent is low. Anhydrous liquid SO2can be obtained by vacuum-line techniques46 or by using AlCI as a supporting ele~trolyte.~~ In the latter case the solutions are oxidizing and the cation radicals of a number of aromatic hydrocarbons can be obtained directly. Further electrochemical oxidation to the dications is also possible. In contrast anhydrous liquid SO containing Bu4N'C10i was found to have a very wide anodic range46 (ca.3.4 V us. SCE) and the dications of a variety of aromatic compounds could easily be generated. Halide ions particularly bromide (as sodium bromide) have been found to be excellent promoters of the electrolytic cross-coupling of disulphides with imide~~~ and with dialkyl (or diary]) ph~sphites~~ (Scheme 10). The mechanism is thought to involve electrogenerated bromine which reacts with either the imide or the phos- phite to give an intermediate (N-bromo-imide or phosphorobromide) that is capable of reacting with the disulphides and regenerating bromide ions. 2R1(C0),NH b 2R'(C0)2NSR + H2 2Fio,-l 2(R1O),P(O)H b 2(R10),P(0)SR + H2 2 F mol-I Reagents i RSSR,NaBr Scheme 10 44 Tien T.Nonaka and T. Sekine Chem. Letters 1979 283. H.-J. 45 T. Shono Y.Matsumura J. Hayashi and M. Mizoguchi Tetrahedron Letters 1979 165. 46 L. A. Tinker and A. J. Bard J. Amer. Chem. Soc. 1979,101,2316. 47 P.-C. Lacaze J.-E. Dubois and M. Delamar J.Electroanalyt. Chem. Interfacial Electrochem. 1979,102 135. 48 S. Torii H. Tanaka and M. Ukida J. Org. Chem. 1979,44 1554. 49 S. Torii H. Tanaka and N. Sayo J. Org. Chem. 1979,44,2938 Electro-organic Chemistry Finally an unusual mixed-valence ferrocene compound (20) has been synthesized by the reaction of ferrocenyl-lithium with boron trifl~oride.~' Structure deter- minations revealed that the complex contains one sterically and one electronically distinct ferrocene group; these are not coincident.The electronic absorption spectrum showed bands characteristic df inter-valence charge-transfer transitions and these were attributed" to a through-space rather than to a through-bond mechanism. Cyclic voltammetry of the complex in dichloromethane gave one reversible reduction wave and three reversible one-electron oxidation waves (Scheme 11). Fc = (.rr-CloH&Fe Scheme 11 50 D. 0.Cowan P. Shu F. L. Hedberg M. Rossi,andT. J. Kistenmacher J. Arner. Chern. SOC.,1979,101 1304.

ISSN:0069-3030    

DOI:10.1039/OC9797600101

出版商:RSC    

年代:1979

数据来源: RSC