ISSN:0069-3030    

DOI:10.1039/OC98582FX001

出版商:RSC    

年代:1985

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC98582BX003

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (ii) Mass Spectrometry By M. A. BALDWIN rtment of Pharmaceutical Chemistry School of Pharmacy University of London 29/39 Brunswick Square London WClN 7AX 1 Introduction ; spectrometry is more than just an analytical technique those of us who practise spectrometry however are well aware that it is primarily the analytical cations that justify the existence of our mass spectrometers and we have learned most organic chemists are more interested in the analytical applications than e structures and reactions of gas-phase ions. Nevertheless the analytical tech- es have emerged through fundamental research and this must continue LObe orted. In fact the state of analytical mass spectrometry has never been livelier lore dynamic than it is at the present time.The last few years have seen endous growth in the range of compounds amenable to mass spectrometry and e range of techniques available giving ever higher sensitivity with increasing ficity. As a new-comer to this series the author has decided that this review Id document this analytical development. is review cannot attempt to be comprehensive for fuller coverage the reader erred to the two most recent issues in the series Specialist Periodical Reports in Spectrometry,’.’ and the Analytical Chemistry review by Burlingame et aL3 I of the original literature can be found in the specialist journals Organic Mass rometry Biomedical and Environmental Mass Spectrometry (previously Biomedi-fuss Spectrometry) International Journal of Mass Spectrometry and Ion Processes iously International Journal of Mass Spectrometry and Ion Physics) and Mass rometry Reviews.Valuable assistance in locating the many relevant papers shed in non-specialist journals is provided by the Mass Spectrometry Bulletin4 CA Selects Mass Spectrometry.’ The proceedings of the 5th International osium on Mass Spectrometry in Life Sciences held in Ghent 1984 have been shed in Biomedical Mass Spectrometry.6 The 10th International Mass Spec- s Spectrometry’ ed. R. A. W. Johnstone A Specialist Periodical Report The Royal Society of nistry London 1984 Vol. 7. s Spectrometry’ ed. M. E. Rose A Specialist Periodical Report The Royal Society of Chemistry Ion 1985 Vol. 8. Burlingame J. 0.Whitney and D. H.Russell Anal. Chem. Rev. 1984 56,417R. ;Spectrometry Bulletin’ The Royal Society of Chemistry London. selects Mass Spectrometry’ Chemical Abstracts Service Columbus Ohio U.S.A. eedings of the Fifth International Symposium on Mass Spectrometry in Life Sciences’ ed. A. P. de leer Biomed. Muss Specrrom. 1985 12,437-576. 15 16 M. A. Baldwin trometry Conference was held in Swansea at the end of the period under review the proceedings of which will be published in 1986.7Many books have been published for specialists during the review period but at this point reference will only be made to 'Practical Organic Mass Spectrometry' by Chapman which is informative for non-specialists and provides comprehensive lists of compound classes that have been analysed by particular techniques although it must be said that the rate of development of the newest techniques has left this somewhat out-of-date.* 2 Fast Atom Bombardment Two years ago the equivalent review on mass spectrometry referred to the explosive growth in the use of the soft ionization technique of fast atom bombardment (FAB).9 This technique has established itself as a general ionization method in widespread use unlike field desorption (FD) and an alternative soft ionization technique for involatile materials.FD has never become easy to use and has remained a 'black art' whereas FAB is quick and easy to use and has proved to be extremely versatile particularly with the range of matrix media that have been developed." It also does not suffer from memory effects and in the reviewer's laboratory the speed and simplicity of FAB is causing it to displace chemical ionization and even electron impact ionization for many analyses.The techniques of FAB and FD have been compared;" FD still has an important role to play as compounds ionized by this technique give strong molecular ions and undergo little fragmentation thereby aiding unambiguous assignment of molecular masses in cases where FAB gives considerable fragmentation. The most important contribution made by FAB is its ability to produce ions directly from the solid or liquid phase without the need for prior evaporation and this has greatly extended the range of materials amenable to analysis. Mass spec- trometric analysis of involatile materials of relative molecular mass of several thousand daltons is now commonplace and in one respect this has brought mass spectrometry full circle for those of us who have been practising the art for a long time.The 1960s saw the introduction of high resolution mass spectrometers that accurately measured ion masses ( f 1 p.p.m.) and allowed the determination of atomic compositions. This gave a new dimension of information for analysis of organic molecules of masses of several hundreds but broke down in the kilodalton range. The number of possible atomic compositions at each integer mass number increases dramatically as the accuracy of the mass measurement decreases (1 p.p.m. equals 0.0001 mass units at m/z 100 but only 0.01 mass units at m/z 10000). Furthermore high resolution can only be attained at the expense of sensitivity which is at a premium for the analysis of biomolecules of masses up to 10000 daltons.It has been recommended that the ion current is maximized by opening wide the mass spectrometer resolving slits thereby obtaining an unresolved peak envelope for the various isotopic versions of the protonated molecular ion incorporat- ing (M + l)+,(M + 2)+ (M + 3)+ etc. To calculate the anticipated mass of the ' 'Advances in Mass Spectrometry' ed. J. F. J. Todd Wiley Chichester 1986. 'Practical Organic Mass Spectrometry' J. R. Chapman Wiley Chichester 1985. M.Jarman Annu. Rep. Prog. Chem Sect. B 1984 80 19. 10 J. L. Gower Biomed. Muss Spectrom. 1985 12 191. " M. Przybylski Fresenius' Z.Anal. Chem. 1983 315 402. Physical Methods and Techniques -Mass Spectrometry 17 centroid of such an envelope the chemical masses are used rather than the isotopic masses familiar in mass spectrometry e.g. carbon is 12.011 instead of 12.0000 and chlorine becomes 35.5 again (or more accurately 35.453). For large molecules this gives an average molecular mass which is several mass units higher than the monoisotopic mass.12 The use of this technique has been described for bovine proinsulin I of molecular mass 8680 and proinsulin I1 of mass 8696; the mass difference of 16 corresponding to replacement of leucine by pr~line.’~ A discrepancy of one mass unit between the calculated and measured masses was attributed to a significant contribution from the molecular ion as well as the protonated species and this exposes a weakness of the technique which relies on there being no such interfering species present.Nucleosides and other molecules with basic sites and low-lying unoccupied molecular orbitals have been reported to give M + 2H and M + 3H ions,I4 and partial reduction of protein disulphide bridges could introduce similar problem^.'^ Consequently the technique of low-resolution studies on high mass samples should be used with caution. It has been reported that the sensitivity of FAB can be enhanced by the incorpora- tion of a heated filament in the ion source. Many neutral species are sputtered from the liquid matrix and chemical ionization of these occurs under the pressure condi- tions pertaining in the FAB source greatly enhancing ~ensitivity.’~”~ A problem with FAB is the evaporation of the liquid matrix which leads to loss of signal and prevents operation at elevated temperature.It has been reported that the use of sugars as the matrix medium allows the sample to be heated with a consequent increase in ion current and sensitivity for several involatile compounds. This tech- nique also minimizes the interference due to ions corresponding to the matrix a problem which normally makes FAB unsatisfactory for analysis of compounds of lower molecular mas1* The applications of FAB are now too numerous to list in a general mass spec- trometry review. An area of rapid growth which has been reviewed,” is the analysis of inorganic organometallic and co-ordination compounds.Sequencing of biologi- cal polymers remains a major area of interest. The FAB analysis of modified oligonucleotides not amenable to conventional sequencing has been described2’ and strategies for measuring molecular masses of high mass compounds have been Signal averaging allows excellent quality spectra to be obtained for high mass ions.23FAB mass spectrometry has been widely used for peptide sequenc- ing but it has been noted that it does not always give sufficiently comprehensive fragmentation for unambiguous sequence determinati~n;~~ the use of tandem mass spectrometry may resolve this problem (vide infra). 12 C. Fenselau J. A. Yergey and D. N. Heller Int. J. Muss Spectrom. Zon Phys. 1983 53 5. 13 J. S. Cottrell and B.H. Frank Biochem. Biophys. Res. Commun. 1985 127 1032. 14 R. L. Cerny and M. L. Gross Anal. Chem. 1985 57 1160. l5 H. R. Moms and P. Piero Biochem. Biophys. Res. Commun. 1985 126 1122. 16 J. E. Campana and R. B. Freas J. Chem. SOC.,Chem. Commun. 1984 1414. 17 R. B. Freas M. M. Ross and J. E. Campana J. Am. Chem. SOC. 1985 107 6195. 18 B. L. Ackemann J. T. Watson and J. F. Holland Anal. Chem. 1985 57 2656. 19 J. M. Miller Adv. Znorg. Chem. Radiochem. 1984 28 1. 20 L. Grotjahn H. Blocker and R. Frank Biomed. Muss Spectrom. 1985 12 514. 21 A. Bateman A. Dell and H. R. Moms J. Appl. Biochem. 1985 7 126. 22 R. J. Cotter B. S. Larsen D. N. Heller J. E. Campana and C. Fenselau Anal. Chem. 1985 57 1479. 23 L. Grotjahn and L.C. E. Taylor Org. Mass Spectrom. 1985 20 146. 24 P. Roepstorff P. Hojrup and J. Moller Biomed. Mass Spectrom. 1985 12 181. 18 M. A. Baldwin Mass spectrometry has traditionally provided a means of studying gas-phase phenomena but FAB allows direct observation of solution phenomena by mass spectrometry as was referred to in the previous report in this series.’ This topic has now been reviewed by Caprioli the major contributor to systematic studies of this type and some previously unpublished results are pre~ented.~’ Ideally such studies use FAB to observe solution chemistry but not to change it. In practice chemical modification of analytes in the liquid matrix is not uncommon and is not surprising as the matrix is bombarded by high energy particles.Transamidation between analyte molecules has been reported,26 Lehmann has demonstrated a decomposition product of glycerol to be methanal which may undergo addition reactions with the anal~te,~’ and a series of substitution and elimination reactions have been identified in nucleoside cylophosphates.28 3 Other Soft Ionization Techniques As was explained in the previous review in this ~eries,~ FAB is one of several desorption techniques able to produce gas-phase ions from involatile materials. Secondary ion mass spectrometry (SIMS) has largely been associated with analysis of inorganic materials but there is increasing use of SIMS in organic and biological chemistry. Like FAB SIMS can be used with a liquid matrix but high yields of secondary ions have been reported for analysis of biomolecules deposited in pmole amounts on silver and gold supports.29 SIMS studies from liquid matrices include those on gluc~ronides~~ and pep tide^.^^ Laser desorption (LD) has also undergone rapid growth stimulated partly by the need for a technique to be used with fourier transform (FT) mass spectrometers that does not produce the high ion source pressure associated with FAB.Such systems have been described and results presen- ted on high mass compounds.32 Analysis of oligosaccharides can be assisted by doping them with alkali metal halides or silver oxide to produce cationized species,33 and it has been reported that LD of sugars from a matrix containing glycerol aids formation of cationized species without the troublesome glycerol cluster ions associ- ated with FAB.34 Some reasons for the rapid growth in the use of FAB were outlined above; a further advantage that FAB SIMS and LD all possess is the ease with which these techniques can be used with conventional sector mass spectrometers.By contrast californium-252 plasma desorption mass spectrometry can only be used with pur- pose-built time-of-flight instruments and has not yet achieved wide acceptance 25 R. M. Caprioli in ‘Mass Spectrometry’ ed. M. E. Rose A Specialist Periodical Report The Royal Society of Chemistry London 1985 Vol. 8 p. 184. 26 L. Kurlanski T. J. Williams J. E. Campana B. N. Green L. W. Anderson and J. M. Strong Biochem. Biophys. Res. Commun. 1983 111 478. 27 W. D.Lehmann Biomed. MQSSSpectrom. 1984 11 217. 28 H.-M. Schiebel P. Schulze W.-D. Stohrer D. Leibfritz B. JastorlT and K. H. Maurer Biomed. MQSS Spectrom. 1985 12 170. 29 A. Benninghoven E. Niehuis T. Friese D. Greifendorf and P. Steffens Org. MQSSSpeclrom. 1984 19 346. 30 P. P. Wickramanayake M. L. Deinzer and A. L. Burlingame Biomed. MQSSSpectrom. 1985 12 127. 31 D. F. Hunt J. Shabanowitz R. T. McIver Jnr. R. L. Hunter and J. E. P. Syka Anal. Chem. 1985 57 765. 32 C. L. Wilkins D. A. Weil C. L. C. Yang and C. F. Ijames Anal. Chem. 1985 57 520. 33 M. L. Coates and C. L. Wilkins Biomed. Mass Spectrum. 1985 12 424. 34 L. G. Wright R. G. Cooks and K. V. Wood Biomed. Mass Spectrom. 1985 12 159. Physical Methods and Techniques -Mass Spectrometry 19 although commercial instruments are now available.Some very high mass species can be studied by this technique but with lower resolution than can be obtained with sector mass spectrometers:’ but studies on lower mass species (= 1000 dalton) show that molecular masses can be assigned with satisfactory pre~ision.~~ It has been reported that plasma desorption and FAB yield very similar data for sequence determination in pep tide^.^' 4 Liquid Chromatography-Mass Spectrometry Having been responsible for some of the early development work on interfaces for high performance liquid chromatography-mass spectrometry (LC-MS) the reviewer feels qualified to say that until recently LC-MS was another ‘black art’ that could in no way be described as a routine technique despite the availability of a variety of LC-MS systems from instrument companies.Evidence that this situation has changed was provided by the large number of papers at the 10th International Mass Spectrometry Conference that dealt with LC-MS applications rather than methodology.’ This transformation is largely due to the thermospray interface developed by Vestal,38 another soft ionization technique which produces ions directly from the liquid phase without prior vaporization. Originally developed for quad- rupole instruments this interface is now available for sector instruments as well,39 and in time this technique may prove more important than FAB which generally relies on pure compounds for effective operation. In biological chemistry bio- chemistry and medicinal analysis the requirement to identify and perhaps assay involatile and unstable materials in complex mixtures is commonplace.Gas chromatography often fails to provide an adequate separative technique even with derivatization and high performance liquid chromatography is frequently the method of choice. Most separations of polar materials use reverse-phase conditions with high water content and buffers are often employed. Thermospray is the first technique that actually works best under these conditions and the optimum flow rate of approximately 1 cm3 min-’ is ideal for standard bore LC columns. If the ideal chromatographic conditions do not lend themselves to thermospray as with normal phase separations micro-bore columns can be used at low flow rates with post-column addition of water/buff er etc.The ability of thermospray to handle high flow rates contributes to its greater sensitivity compared with earlier direct liquid introduction (DLI) techniques which require eluent splitting if used with conventional flow rates and may handle as little as 0.01 cm3 min-’ of liquid. The limit of detection for some antimalarials using selected ion monitoring was 30 ng by DLI with a 1/ 100 split but less than 1 ng by thermo~pray.~’ Thermospray is particularly suited to the analysis of polar materials as it generally relies on the presence of preformed ions in solution although 35 B. Sundqvist I. Kamensky H. Hakansson J. Kjellberg M. Salehpour S. Widdiyasekera J. Fohlman P. A.Peterson and P. RoepstorfT Biomed. Mass Spectrorn. 1984 11 242. 36 H. M. Fales C. J. McNeal R. D. MacFarlane and Y. Shimohigashi Anal. Chem. 1985 57 1616. 37 J. Fohlman P. A. Peterson P. RoepstorfT P. Hojrup I. Kamensky G. Sawe P. Hakansson and B. Sundqvist Biomed. Mass Spectrom. 1985 12 380. 38 D. A. Garteiz and M. L. Vestal L. C. Mag. 1985 3 334. 39 M. L. Vestal Anal. Chem. 1984 56 2590. 40 R. D. Voyksner J. T. Bursey J. W. Hines and D. E. Pellizzari Biomed. Mass Spectrom. 1984 11 616. 20 M. A. Baldwin ionization can occur in the gas phase.41 The presence of a buffer such as ammonium acetate encourages the formation of quasi-molecular ions such as (M + H)+ and (M + NH4)+.The LC eluent passes through a heated capillary tube into a pumped chamber where the ions are desolvated and extracted into the mass ~pectrometer.~~ Most systems also have a filament that can be used to enhance ionization.Some recently reported applications of thermospray include analysis of drugs used illicitly in horse racing,43 acyl carnitines in urine,& anticancer and amino-acids both free and derivatized?6 Improvements to DLI techniques including thermospray have not eliminated the use of the moving belt interface which has been adapted to provide FAB;' SIMS and LD4* directly off the belt. Future trends in LC-MS will almost certainly be determined by the dramatic improvements being brought about in LC technique^.^^ Open tubular capillary columns give very low flow rates,50 and micro-packed columns have been shown to give sufficiently low ion chamber pressures for electron impact i~nization.~' The advantages of micro-column LC-MS for trace detection have been reviewed emphasizing the benefits of the use of very low flow rates at higher concentration than can be obtained with conventional technique^.^^ Supercritical fluid chromatography has also been interfaced with mass spectrometry (SFC-MS) the two techniques enjoying much greater compatability than the LC-MS combina- tion.Low temperature separations of polar materials not amenable to gas chromatography are achieved rapidly and efficiently with a mobile phase such as carbon dioxide or nitrous oxide the entire column eluent feeding directly into a chemical ionization source.53 Henion who is a leading exponent of DLI techniques has shown that SFC-MS analysis of polar drugs is more efficient than DLI-MS.54 5 Tandem Mass Spectrometry The opening remarks concerning the development of analytical techniques relying on fundamental research apply particularly to tandem mass spectrometry.Studies on metastable ions to investigate ion structure were followed by the development of collisionally activated decomposition and now most major instrument companies that manufacture mass spectrometers offer multi-analyser instruments for tandem studies. The phrase tandem mass spectrometry refers to the study of sequential unimolecular and or bimolecular ionic processes in which both the precurser and product ions are mass selected hence the alternative name mass spectrometry-mass 41 M.M. Bursey C. E. Parker R. W. Smith and S. J. Gaskell Anal. Chem. 1985 57 2597. 42 M. L. Vestal and G. J. Fergusson Anal. Chem. 1985 57 2373. 43 T. Covey J. Crowther E. A. Dewey and J. D. Henion Anal. Chem. 1985 57 474. 44 D. S. Millington T. P. Bohan C. R. Roe A. L. Yergey and D. J. Liberato Clin. Chim. Acta 1985 145 69. 45 R. D. Voyksner J. T. Bursey and J. W. Hines J. Chromatogr. 1985 323 383. 46 D. E. Games and D. E. Ramsey J. Chromatogr. 1985 323 67. 47 J. G. Stroh J. C. Cook R. M. Milberg L. Brayton T. Kihara Z. Huang K.L. Rhinehart Jnr. and I. A. S. Lewis Anal. Chem. 1985 57 985. 48 T. P. Fan E. D. Hardin and M. L. Vestal Anal. Chem. 1984 56 1870. 49 B. L. Karger and P. Vouros J. Chromatogr.1985 323 13. 50 W. M. A. Niessen and H. Poppe J. Chromatogr. 1985 323 37. 51 T. Tsuda G. Keller and H.-J. Stan Anal. Chem. 1985 57 2280. 52 E. D. Lee and J. D. Henion J. Chromatogr. Sci. 1985 23 253. 53 R. D. Smith and H. R. Udseth Anal. Chem. 1983 55 2266. 54 J. B. Crowther and J. D. Henion Anal. Chem. 1985 57 2711. Physical Methods and Techniques -Mass Spectrometry 21 spectrometry (MS-MS). Ionization and perhaps fragmentation in the ion source ion extraction and acceleration into the flight tube and selection of ions of a particular mass in MS1 is followed by energization and fragmentation of the selected ions and the subsequent mass analysis of the ionic products in MS2. ‘Tandem Mass Spectrometry’ edited by McLafferty is recommended for a detailed study of the subject.55 Tandem mass spectrometry provides a major benefit in analyses and assays that employ selected ion monitoring.A selected ion (precurser or parent ion) and a unimolecular or collisionally induced fragment (product or daughter ion) can be monitored simultaneously in a chromatography-mass spectrometry experiment. The second mass analyser acts as a filter and only transmits ions of the daughter mass that were formed by fragmentation of ions of the parent mass thereby greatly increasing the selectivity of the analysis. This has been referred to as metastable ion monitoring or selected reaction monitoring and despite a reduction in the observed ion current has been shown to be more sensitive than high resolution single or multiple ion monitoring due to the highly specific nature of the analysis and the reduction in chemical noise.56 Ergotamine has been assayed in plasma at levels down to 2 pg cm-3 using negative ion chemical ionization.A characteristic fragment ion at m/z 314 gave the parent ion for the MS-MS analysis and this was selected by the first analyser. Collisional activation of this caused fragmentation to give a daughter ion of m/z243 which was selected in the second analyser. Dihydroergo- cryptine which gives corresponding ions at 308 and 209 was used as internal ~tandard.~’ Trace analysis by tandem mass spectrometry has been re~iewed.~’ The selectivity of tandem mass spectrometry allows rapid analyses to be carried out on complex mixtures with little or no extraction and this has proved to be highly effective in the screening for drugs in and in screening for medical conditions.Urinary acids such as methylmalonic acid indicative of inherited meta- bolic disease have been successfully screened for in crude urine extracts.60 Structural information is also obtained and can be used to characterize novel compounds in complex mixtures. Several new alkaloids were identified by tandem mass spec- trometry on extracts from the cactus Pachycereus weberi61 Tandem mass spectrometers fall into two broad classes sector instruments that transmit ions of high kinetic energy (several keV) and quadrupole instruments that transmit ions of low kinetic energy (< 100 eV) although there are hybrid instruments that combine both types of analyser.62 Both classes incorporate one or more collision cell in which the ions are energized and caused to fragment.The energization process is essentially electronic for ions of high kinetic energy and vibrational for ions of low kinetic energy.55 However statistical theories of mass spectra such as the quasi-equilibrium theory predict that this energy will be redistributed before frag- mentation and that the spectra will be relatively independent of the mode of 55 ‘Tandem Mass Spectrometry’ ed. F. W. McLafferty Wiley New York 1983. 56 G. C. Thorne and S. J. Gaskell Biomed. Mass Spectrom. 1985 12 19. 57 N. Haering J. A. Settlage S. W. Sanders and R. Schuberth Biomed. Mass Spectrom. 1985 12 197. 58 J. V. Johnson and R.A. Yost Anal. Chem. 1985,57 758A. 59 H. 0. Brotherton and R. A. Yost Am. J. Vet. Res. 1984 45 2436. 60 P. Rinaldo L. Chiandetti F. Zacchello S. Daolio and P. Traldi Biomed. Mass Spectrom. 1984 11,643. 61 R. A. Roush R. G. Cooks S. A. Sweetana and J. L. McLaughlin Anal. Chem. 1985 57 109. 62 J. N. Louris L. G. Wright R. G. Cooks and A. E. Schoen Anal. Chem. 1985 57 2918. 22 M. A. Baldwin excitation and this indeed proves to be the case. Multi-sector instruments offer the advantage of high mass resolution for both the precurser and daughter ions whereas quadrupole instruments such as the triple quadrupole have the advantage of flexible operation with high sensitivity for the detection of collision products. Hybrid instruments combine the advantages of high resolution and sensitivity a GC-MS- MS analysis of trace quantities of estradiol bis-t-butyldimethylsilyl ether in blood plasma was achieved with high sensitivity and specificity by monitoring the reaction M+'+ (M-C4H9)+ with a parent ion mass resolution of 5000 thereby reducing chemical noise and achieving a detection limit of 10 pg.63 Soft ionization techniques involve little energy transfer and they usually effect the production of relatively stable even-electron quasi-molecular ions rather than the less stable radical cations formed by electron impact ionization.Consequently there is little fragmentation and the spectral information is limited. Restricted fragmentation is advantageous for assays of trace materials in complex mixtures as the ion current is concentrated in one or two peaks and the chance of overlaps is reduced.However for fingerprinting or structural analysis the small number of peaks is a disadvantage and it may be desirable to induce fragmentation usually following energization of the ions by collision with a neutral gas. The combination of soft ionization and tandem mass spectrometry has been used to enhance the structure information from FAB ionization of oligosaccharides sequence informa- tion being obtained for complex mixtures in a high resolution four-sector tandem ir~strument.~~ Unambiguous sequencing of peptides can be achieved although this requires collisional studies on fragment as well as molecular ions.65 Ion Structures Studies by Tandem Mass Spectrometry.-In studies of gas-phase ion chemistry tandem mass spectrometry has become the major technique for charac- terizing ion structures usually by comparing collisional spectra for known and unknown structures.It is generally accepted that as long as any contribution from unimolecular processes is discounted such spectra are largely independent of the mode of preparation of the ions and provide a finger-print technique for structure recognition. For example the vinylidene cation H,C=C+' can be formed by col- lisional charge reversal of the corresponding anion and distinguished from the acetylene radical cation by its collisionally activated decomposition spectrum.66 However on occasion the spectra of isomeric structures prove indistinguishable.The dependence of collisional excitation on the collision energy and the scatteiing angle can be studied by energy resolved mass spectrometry (ERMS) and angle resolved mass spectrometry (ARMS) and may differentiate between ion structures. ERMS is best suited to low energy studies in quadrupole instruments for which the energy differences are relatively large whereas ARMS is best suited to high energy studies in sector instruments which are insensitive to relatively small energy changes but are very sensitive to directional changes due to the small acceptance angles. Hybrid instruments allow both types of study and confirm that the information given by the two techniques is essentially the same large scattering angles being 63 S. J. Gaskell C. J. Porter and B.N. Green Biomed. Muss Spectrom. 1985 12 139. 64 S. A. Carr V. N. Reinhold B. N. Green and J. R. Hass Biomed. Muss Spectrom. 1985 12 288. 65 K. Eckart H. Schwarz K. B. Tomer and M. L. Gross 1.Am. Chem. Soc. 1985 107 6765. 66 J. L. Holmes and J. E. Szulejko Chem. fhys. Lett. 1984 107 301. Physical Methods and Techniques -Mass Spectrometry associated with large losses of kinetic energy as was shown in a study of isomers of (C~H~O)+*:~ Photoexcitation is an alternative to collisional techniques. Of the C4H5N+' ions formed by electron impact on compounds (1)-(5) ionized pyrrole does not give any photoinduced decomposition and so stands out from the other four isomers all of which give photodissociation spectra that are virtually identical at any one photon wavelength.However the cross-sections for fragmentation following photo- excitation are substantially different for all except (4) and (5) which probably form ions of common structure.68 Neutral Species Studied by Tandem Mass Spectrometry.-A recent development is the study in tandem experiments of neutral species either formed by neutralization of ions by charge exchange or formed as the neutral products of the breakdown of larger ions. In both cases sector mass spectrometers are used to produce primary ions of high kinetic energy. The kinetic energy is retained on neutralization by charge exchange or partitioned between ions and neutrals on fragmentation. Any remaining ions in the beam are deflected out electrically and the neutrals are then re-ionized by collision.Non-classical ions can be neutralized to give neutral struc- tures not readily obtained by other means. In an experiment in which neutralization was followed by re-ionization within approximately 1 ps the neutralized radical ion dipole complex CH2HC1 proved to be significantly less stable than its isomer methyl chloride HCl+' being a major peak in the re-ionization spectrum of CH,HC1.69 The neutrals corresponding to the loss of 27 mass units from ionized pyridine and aniline have been shown to be HCN and HNC respectively each of which gives a characteristic spectrum in the region m/z 12-15.69*70 Fourier Transform Instruments in Tandem Mass Spectrometry.-Fourier transform mass spectrometry (FTMS) was briefly referred to in the previous review in this ~eries,~ and since then Nibbering has reviewed FTMS development and its use in studies of ion-molecule reactions and the analytical applications,'* and its analytical .potential has also been discussed by McCrery et ~1 In an ~FT~mass spectrometer the ions spend a relatively long time in the cell and unless the pressure is kept low they are likely to suffer collisionally activated decompositions. The majority of ionization techniques require higher pressures than are desirable in the cell so recent developments have aimed at separating the ionization and analysis regions.'* 67 S. Verma J. D. Ciupek and R. G. Cooks inr. J. Mass Spectrom. Ion Processes 1984 62 219. 68 E. Weger W. A. Brand and K. Levsen Org.Mass Spectrom. 1983 18 534. 69 P. 0. Danis C. Wesdemiotis and F. W. McLafferty J. Am. Chem. Soc. 1983 105 7454. 'O P. C. Burgers J. L. Holmes A. A. Mommers and J. K. Terlouw Chem. Phys. Lett. 1983 102 1. 71 N.M.M. Nibbering in 'Mass Spectrometry' ed. M. E. Rose A Specialist Periodical Report The Royal Society of Chemistry London 1985 Vol. 8 p. 141. 72 D. A. McCrery T. M. Sack and M. L. Gross Specrrosc. Int. J. 1984 3 57. M. A. Baldwin Instrument manufacturers have adopted different approaches to this a separate ionization cell adjacent to the analyser within the magnetic field allows a degree of independence in ion preparation and efficient injection of ions into the analyser (Nicolet) whereas ion preparation remote from the analyser allows complete flexibil- ity in ion preparation but perhaps less efficient transfer into the analyser (Bruker).LD ionization is a technique that does not produce high source pressures and it has been refined particularly for use in FTMS. A comparison of LD-FTMS and FAB ionization with a double focusing sector instrument has been made for some drugs of low volatility more abundant molecular ions being observed with LD- FTMS with reduced fragmentati~n.~~ FTMS can contribute to tandem studies in two different ways. An RF pulse can eject all ions from the cell except those of a selected mass; these will follow circular orbits in the analyser cell with kinetic energies of a few hundred eV and as stated above may collide with residual gas molecules and undergo collisionally activated decomposition.The collision gas may also be introduced with a pulsed valve. The ionic products of the collisions may then be detected and sequential reactions may also be observed. Nibbering has described a series of four consecutive reactions from the molecular ion of acetophenone giving the sequence:71 -CH; -co -C2H2 -H' PhCOCH;' -PhCO+-Ph+ -C4H; -C4H;' The alternative approach to tandem studies is to prepare the ions remotely mass select a precurser in a separate mass analyser such as a quadrupole collisionally fragment the precurser ions in a collision cell or an RF-only quadrupole as used in the triple quadrupole instruments and analyse the fragment ions in the FT mass spectrometer. The advantage of such a QQFT system is the combination of the flexibility and high sensitivity of the quadrupole analyser for the production of the daughter ions and the high resolution of the FT instrument for their analysis.74 The power of such a system has yet to be fulfilled but the potential has been demonstrated with a QQFT combination (using two RF-only quadrupoles) for the analysis of peptides including melittin of molecular mass 2849 dalt~n.~' 73 R.E. Shomo 11 A. G. Marshall and C. R. Weisenberger Anal. Chem. 1985 57 2940. 74 R. T. McIver Jnr. R. L. Hunter and W. D. Bowers Znt. 1. Mass Spectrom. Zon Processes 1985 64 67. 75 D. F. Hunt J. Shabanowitz J. R. Yates 111 R. T. McIver Jnr. R. L. Hunter J. E. P. Syka and J. Amy Anal. Chem. 1985 57 2728.

ISSN:0069-3030    

DOI:10.1039/OC9858200015

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

3 Theoretical Chemistry By M. GODFREY Department of Chemistry The University Southampton SO9 5NH 1 Introduction As last year in compiling the report on theoretical chemistry I have considered material concerning the nature and the application of all types of theoretical models designed for the description of chemical properties in terms of the behaviour of nuclei and electrons in molecules. The main criterion for selection from many hundreds of relevant references is the perceived general interest to organic chemists. Hence advances in computational methods are not usually reported unless they are exemplified by application to some important problem in organic chemistry. 2 Models Concepts and Rules In this section the material considered concerns innovations in and criticisms of theoretical models the concepts used in them and rules generated from them.Hehre Radom Schleyer and Pople’ have written a book on ab initio MO theory directed at the experimentalist. Their goals are to inform the practising chemist of the capabilities and the deficiencies of existing theoretical models and also to assist him or her in actually doing and interpreting theoretical calculations. The final issue of Furuduy Symposia of the R.S.C.* reviews the current state of molecular structure calculations providing valuable information on recent methods and their applica- tions. It includes the Lennard-Jones lecture by Handy on the value of calculations of very high accuracy in quantum chemistry. Among several interesting papers given at the Fifth American Conference on Theoretical Chemistry3 is one by Dewar4 on the current status of quantum-mechanical models with reference to their use in elucidating the mechanisms of chemical reactions.Clement? has described a global approach to simulations of complex chemical systems on digital computers that involves quantum mechanics statistical mechanics and fluid dynamics. He has also described6 an experimental supercomputer system designed for such computations. W. J. Hehre L. Radom P. von R. Schleyer and J. A. Pople ‘Ab initio MO Theory’ Wiley-Interscience New York 1985. Faraday Symp. Chem. SOC.,1985 19. J. Phys. Chem. 1985,89 2121-2235. M. J. S. Dewar J. Phys. Chem. 1985 89 2145. E. Clementi J. Phys. Chem. 1985,89 4426. H.L. Nguyen H. Khanmohammadbaigi and E. Clementi J. Comput. Chem. 1985,6 634. 25 26 M. Godfrey Fox and Matsen7 have presented a new view of the electronic structure of rr-systems which they claim combines the best features of Huckel MO theory and VB theory. Dewar and his co-workers' have described a new semiempirical model AM1 (Austin Model 1) based on the NDDO approximation. In it the major weaknesses of MNDO in particular the failure to reproduce the properties of hydrogen bonds (to which further attention has been drawn this year') have been overcome without any increase in computing time. The isodesmic reaction method of Pople" and the group equivalent method of Wiberg," for estimating heats of formation from ab initio total energies have been extended by Ibrahim and Schleyer12 in an atom equivalents method.The common objections to the Mulliken method of population analysis have been re~iewed.'~ An alternative method that overcomes these objections is proposed and applied to compounds of the fomula MeX. A solution to the problem of representing in a 2D picture all the information contained in a 3D electron distribution has been pr~posed.'~ It involves a perspective view of contour diagrams in a set of parallel planes. Molecular electron density distributions in momentum space as opposed to position space have been disc~ssed.'~ Zhixing and Siqun16 have proved that several of Dewar's theorems concerning the Huckel MO behaviour of alternant hydrocarbon^'^ are false and they have presented alternative theorems.In a review of the structure and valence isomerization of antiaromatic compounds by Glukhovtsev Simkin and Minkin" various criteria of aromaticity and their relationship with molecular structure are discussed and the characteristics of quan- tum-mechanical calculations of the structures of antiaromatic molecules are ana- lysed. A new index of aromatic character based upon a statistical evaluation of the deviations in peripheral bond orders has been devised by Bird." The utility of this index is exemplified by its application to five-membered ring heterocycles and their mesoionic derivatives. Y-Aromaticity as in the trimethylenemethane dianion (1 ) appears to be associated with delocalization through the centre of the molecule rather than through the periphery.20 -A- M.A. Fox and F. A. Matsen J. Chem. Educ. 1985 62 367 477 551. M. J. S. Dewar E. G. Zoebisch E. F. Healy and J. J. P. Stewart J. Am. Chem. Soc. 1985 107 3902; M. J. S. Dewar and D. M. Storch J. Am. Chem. Soc. 1985 107 3898. J. Koller V. Harb M. Hodoscek and D. Hadzi THEOCHEM 1985 23 343. 10 W. J. Hehre R. Ditchfield L. Radom and J. A. Pople J. Am. Chem. Soc. 1970 92 4796. K. B. Wiberg J. Comput. Chem. 1984 5 197. 12 M. R. Ibrahim and P. von R. Schleyer J. Comput. Chem. 1985 6 157. l3 A. E. Reed R. B. Weinstock and F. Weinhold J. Chem. Phys. 1985 83 735. 14 M. M. Gilbert J. J. Donn M. Peirce K. R. Sundberg and K. Ruedenberg J. Comput. Chem. 1985,6 209. IS D. C. Rawlings and E. R. Davidson J.Phys. Chem. 1985,89 969. 16 C. Zhixing and H. Siqun Theor. Chim. Acta 1985 67 409. 17 M. J. S. Dewar 'The Molecular Orbital Theory of Organic Chemistry' McGraw-Hill New York 1969. 18 M. N. Glukhovtsev B. Ya. Simkin and V. I. Minkin Russ. Chem. Rev. (Engl. Trans/.),1985 54 54. l9 C. W. Bird Tetrahedron 1985 41 1409. 20 I. Agranat and A. Skancke J. Am. Chem. Soc. 1985 107 867. Theoretical Chemistry 27 The concept of the captodative effect i.e. the enhanced stabilization due to the combined action of an electron-withdrawing substituent and an electron-releasing substituent on a radical centre has been discussed.21 The importance of the field- induced resonance effect has been studiedz2 by calculating the effects of HF and NH4+ on the extent of charge transfer in substituted ethylenes it was found to be very small.The use of the isolated-molecule approach in theoretical studies of the polar effect has been discussed,23 and there has been a 4-31G investigationz4 of the field effect in aliphatic systems using the following isodesmic reaction in which R = H methyl or bicyclo[2.2.2]octyl X-R+ H-R***(*) H-R+ X-R**.(*) Fran~l~~ has presented a method for the rapid calculation of polarization effects on electrostatic interaction energies from Hartree-Fock wavefunctions. It appears that polarization effects are significantly larger for electrophilic sites than for nucleophilic sites. Anomeric effects ie. the effects of interactions of two geminal substituents at a saturated hydrocarbon are greatly attenuated with second-row (Cl SH PH2) com- pared with first-row substituents.26 Hyperconjugation not induction has been shown27 to be the dominant mode of stabilization in anion systems in which an electronegative P-substituent is trans to the lone pair.Laticyclic hyperconjugative interactions involving a relay of CH or CH2CH2 units appear to be an important mechanism for transmitting interactions over large distances.28 It has been claimed that the a-eff ect in nucleophilic reactivity is thermodynamic in origin.29 Last year we reported Dewar's proposal3' that o-conjugation of C-C bonds causes pyramidalization of alkyl radicals. However ab initio MO calculation^^^ reveal that pyramidalization is strongly dependent on conformational effects.Else- where32 computational evidence is provided that the symmetric hexagonal structure of benzene is caused by the a-framework alone. The wsystem is found to favour a distorted and localized structure. Thus 7r-delocalization is forced by the u-framework. M~llay~~ has described a simple modification of his method for calculating atomic and group electronegativities that overcomes deficiencies such as failure to diff erenti- ate between isomeric groups. The relationship of Parr and pear son'^^^ concepts of absolute electronegativity and absolute hardness to chemical bonding in Lewis acid-base complexes has been examined by Pear~on.~~ Density functional theory 21 H. G. Viehe Z. Janousek R. Merenyi and L. Stella Acc. Chem. Res. 1985 18 148.22 S. Mamott and R. D. Topsom J. Chem. SOC,Perkin Trans. 2 1985 697. 23 S. Mamott and R. D. Topsom J. Am. Chem. Soc. 1985 107 2253. 24 N. Inamoto S. Masuda and J. Niwa Bull Chem. SOC.Jpn. 1985 SS 158. 25 M. M. Francl J. Phys. Chem. 1985,89 428. 26 P. von R. Schleyer E. D. Jemmis and G. W. Spitznagel J. Am. Chem. SOC.,1985 107 6393. 27 D. S. Friedman M. M. Francl and L. C. Allen Tetrahedron 1985 41 499. 28 M. N. Paddon-Row J. Chem. Soc. Perkin Trans. 2 1985 257. 29 R. F. Hudson D. P. Hansell S. Wolfe and D. J. Mitchell J. Chem. SOC.,Chem. Commun. 1985 1406. 30 M. J. S. Dewar J. Am. Chem Soc. 1984 106 669. 31 M. N. Paddon-Row and K. N. Houk J. Phys. Chem. 1985,89 3771. 32 P. C. Hiberty S. S. Shaik J. M. Lefour and G. Ohanessian J.Org. Chem. 1985 50 4657. 33 J. Mullay J. Am. Chem. Soc. 1985 107 7271; 1984 106 5842. 34 R. G. Parr and R. G. Pearson J. Am. Chem. Soc. 1983 105 7512. 35 R. G. Pearson J. Am. Chem. Soc. 1985 107 6801. 28 M. Godfrey has been shown by Parr and his co-~orkers~~ to provide a natural definition for a local molecular property called the local hardness it is shown that local hardness constitutes a generalization of the classical electrostatic potential due to an electron distribution. Leroy37 has reviewed some applications of his concept of stabilization energy to various chemical problems. Further work on free radicals ionic intermediates carbocations and carbanions has also been published.38 There are two review^^^.^' on the VBCM model for chemical reactions developed by Pross and Shaik,41 one by each worker.argues that the model presents a simple qualitative framework for understanding the factors that go into the creation of a reaction profile. It gives answers to important fundamental questions concerning the correlation of rates and equilibria in organic chemistry the relationship between charge and geometric progression in a reaction transition state and the factors which govern heterolytic versus homolytic dissociation of a bond. Shaik4O discusses the application to sN2 reactions. In a separate paper4* the variation in intrinsic barriers in several sN2 identity reactions is accounted for. P~oss~~ has also attempted to demonstrate that all two-electron pathways in organic reactions involve the shift of a single electron.Pericyclic reactions of organic radical cations have been discussedu in terms of a simple qualitative theory based on orbital symmetry conservation or frontier orbital interactions. In conrotatory electrocyclic reactions of substituted cyclobutenes there is a larger preference for outward rotation of donor substituents than expected from conventional steric effects a theoretical rationale is pr0vided.4~ Bader and Ma~Dougall~~ have presented a theory of chemical reactivity based upon the properties of the electronic charge distribution and the changes in this distribution as induced by vibrational motions. The initial approach of the reactants is determined by aligning local charge concentrations with regions of charge deple- tion as determined by the Laplacian of their charge distributions.In many examples the regions of space where HOMO and LUMO are most concentrated coincide respectively with the regions of charge concentration and depletion in the Laplacian distribution. Menger47 has reviewed work on the source of extremely large values of kin,,,/kin,, for corresponding intramolecular and intermolecular reactions operating under identical mechanisms. In particular he has considered the hypothesis that the rate of reaction between functionalities A and B is proportional to the time that A and B reside within a critical distance. 36 M. Berkowitz S. K. Ghosh and R. G. Parr J. Am. Chem. Soc. 1985 107 6811. 37 G. Leroy Adv. Quantum Chem. 1985 17 1.38 G. Leroy THEOCHEM 1985,21,91; G. Leroy C. Wilante D. Peeters and M. M. Uyewa THEOCHEM 1985 25 107. 39 A. Pross Adv. Phys. Org. Chem. 1985 21,99. 40 S. S. Shaik hog. Phys. Org. Chem 1985 15 197. 41 A. Ross and S. S. Shaik Acc. Chem. Res. 1983 16 363. 42 D. J. Mitchell H. B. Schlegel S. S. Shaik and S. Wolfe Can. J. Chem. 1985 63 1642. 43 A. Pross Acc. Chem Res. 1985 18 212. 44 I. R. Dunkin and L. Andrews Tetrahedron 1985 41 145. 4s N. G. Rondan and K. N. Houk J. Am Chem. Soc. 1985 107 2099. 46 R. F. W. Bader and P. J. MacDougall J. Am. Chem. Soc. 1985 107,6788. 47 F. M. Menger Acc. Chem. Rex 1985 18 128. Theoretical Chemistry 29 The treatment of molecular strain and of steric effects has featured prominently. Stirling48 has reported on the evaluation of strain upon reactivity.The consequences of strain for the structure of aliphatic molecules has been reviewed by Riichardt and Beckhau~.~~ Steric energies as calculated by molecular mechanics are force-field dependent and cannot serve as unbiased measures of steric effects. Moreover steric energies are highly sensitive to even minor variations in the force field and in the details of its application. These problems are overcome by DeTar and his co- workers’’ through defining a property of a given conformer called formal steric enthalpy. This property is an unbiased and transferable measure of steric properties independent of the method of estimation. Meyer” has written a computer program to calculate and display graphically the van der Waals volume and surface area of molecules using castaway material of molecular-mechanics calculations.He has also looked beyond van der Waals descrip- tors of molecular shapes2 and has noticed that inclusion of an electrostatic term in the molecular-mechanical treatment of hydrocarbons would compel the non-bonding parameters of different force fields to become more alike than they are at pre~ent.’~ Elsewheres4 nine empirical force fields in molecular-mechanics calculations have been tested for their abilities to reproduce experimental geometric and energy data on a test hydrocarbon. Trajectory calculations across a fourfold symmetric potential-energy surface with a central depression corresponding to two reactants A and A’ and two products B and B’ linked by a common intermediate I as in the Scheme show that the product distribution need not always be that predicted by transition-state theory according to Carpenter.” In particular conservation of momentum tends to take trajectories from a reactant through the intermediate and on to the product that is closest to the straight-line path.Thus for example where A and A’ and B and B‘ are pairs of enantiomers the formation of unequal amounts of B and B’ from unequal amounts of A and A is not sufficient evidence for a more complex mechanism than the one shown in the Scheme. A B’ \fl I &\ A’ B Scheme Koga and MorokumaS6 have presented a method for finding the energy-minimum crossing point between two potential-energy surfaces and have applied it to two low-lying triplet excited states of chlorobenzene.48 C. J. M. Stirling Tetrahedron 1985 41 1613. 49 C. Ruchardt and H.-D. Beckhaus Angew. Chem. Znt. Ed. Engl. 1985 24 529. 50 D. F. DeTar S. Binzet and P. Darba 1 Org. Chem. 1985,50,2826. 51 A. Y. Meyer J. Chem. SOC.,Perkin Trans. 2 1985 1161. 52 A. Y. Meyer THEOCHEM 1985 25 93. 53 A. Y. Meyer and F. R. F. Meyer J. Comput. Chem. 1985 6 1. 54 F. A. L. Anet and R. Anet Tetrahedron Lett. 1985 26 5355. 55 B. K. Carpenter J. Am. Chem. SOC.,1985 107 5730. 56 N. Koga and K. Morokuma Chem. Phys. Lett. 1985 119 371. 30 M. Godfrey Heavy-atom tunnelling has been studied by Dewar and Balabad8 has reviewed some contributions of graph theory to theoretical chemistry and Bala~ubramanian~~ haS reviewed the applications of combinatorics and graph theory to spectroscopy and quantum chemistry.A graph-theoretical approach to structure-property relationships has been described.60 Sinanoglu61 has proposed a pictorial method for obtaining MO level patterns i.e. the numbers of non-bonding bonding and anti-bonding orbitals from the actual or tentative structural formulae of saturated and unsaturated molecules or intermediates regard- less of symmetry. The rules are illustrated. 3 Simple Quantitative Relationships The material considered in this section is that which contributes to the understanding of the bases of simple quantitative free-energy relationships. Marcus’ rate-equilibrium theory6* has the major limitation that the reaction co-ordinate is assumed to depend on just one variable.While it is always possible to define a single variable that measures progress of reaction in a single reaction it may take two or more independent variables to define progress of reaction for an entire reaction series. Grun~ald~~ has shown that disparity of progress of concerted reaction events at the transition state and variation of that disparity within a reaction series are important effects in determining rate-equilibrium relationships. The VBCM model mentioned in the previous section also has implication^^^ for rate-equilibrium relationships. Jen~ks~~ has reviewed the Bell-Marcus-Hammond-Polanyi-Thornton-Leffler effect on reactivity-selectivity relationships.Among practitioners in the field this effect is called ‘Bema Hapothle’ a name constructed from the first two letters of the name of each of the contributors to the description of the effect. Kalinowski and Kryg~vrtski~~ have given an overview of the application of the concept of linear free-energy relationships to investigations of reversible organic electrochemical reactions in aprotic solvents. Mamott and Topsom66 have constructed a theoretical scale of substituent reson- ance parameters from the results of ab initio MO calculations on monosubstituted ethylenes. These workers together with Reynolds67 have also shown that charged substituents cannot be included with dipolar groups in one general scale of sub- stituent electronic effects.Substituent effects on the gas-phase acidity of benzoic acids linearly correlate with substituent effects on the HOMO energies of the corresponding anions.68 The ratio of field and electronegativity parameters correlates 51 M. J. S. Dewar and K. M. Men J. Phys. Chem. 1985,89,4739; THEOCHEM 1985 23 59. 58 A. T. Balaban THEOCHEM 1985,21 117. 59 K. Balasubramanian Chem. Rev. 1985 85 599. 60 S. C. Grossman Znt. J. Quantum Chern 1985 28 1. 61 0. Sinanoglu 7heor. Chim. Acta 1985 68 251. 62 R. A. Marcus J. Chem. Phys. 1956 24 966. 63 E. Grunwald J. Am. Chem. SOC.,1985 107 125 4710 4715. 64 W. P. Jencks Chem. Rev. 1985,85 511. 65 M. K. Kalinowski and T. M. Krygowski Croat. Chem. Acta 1985,58 107. 66 S. Mamott and R. D. Topsom J.Chem. SOC.,Perkin Trans. 2 1985 1045. 61 S. Mamott W. F. Reynolds and R. D. Topsom J. 0%.Chem. 1985 50 741. 68 G. La Manna V.Tschinke and L. Paoloni J. Chem. SOC.,Perkin Trans. 2 1985 1393. Theoretical Chemistry 31 well with the charge separation between the positive and negative poles in H-X molecules.69 A test of single and dual substituent parameter equations in the correlation of 13 C shifts in substituted styrenes indicates that the use of multiple-resonance scales in dual substituent parameter treatments is ~njustified.~' Principal-component and partial least-squares analyses of data in para-substituted benzenes and a-substituted thiophenes indicate that a unique reaction constant is not ~arranted.~' Principal-component analysis has also been applied72 to 13C chemical-shift data on P-naph- thalenes.It has been argued73 that in contrast to the traditional view the temperature dependence of the Hammett equation is both physically and experimentally better described by means of a temperature-dependent uand a temperature-independent p. Ab initio MO methods have been to simulate a typical experimental structure-reactivity study viz the effects of substituents in both nucleophilic and electrophilic partners in carbonyl addition reactions. The part played by the solvent in nucleophile-electrophile combination reactions may be the key to interpreting experimental results that contradict the reactivity- selectivity principle. MIND0/3 st~dies~'-'~on model systems have been carried out in order to test the hypothesis of partial desolvation of the electrophile at the transition state.Movements both of molecules of solvent linked to the electrophile and of those of the second layer form part of the reaction ~o-ordinate.~' Also desolvation depends at the same time on the nucleophile the electrophile and the so~vent.~~.~~ Kamlet and Taft7' have argued that linear solvation-energy relationships (LSERs) are consequences of physically significant effects rather than merely empirical rules. They have expanded the effects of the basicity of the solvent in their own LSER from a one-parameter term into a two-parameter term. Three-mode factor analysis is a good mathematical-statistical model for the simultaneous description of the influence of solvent reaction type and substituents on equilibrium constants." The residual standard deviation of the observations is of the same magnitude as that obtained by the Kamlet- Abboud-Taft" regression analysis model.However the number of parameters in the factor analysis model is far smaller and the latter model is better suited to the prediction of missing data. 69 S. Masuda N. Inamoto and J. Niwa Tetrahedron Lett. 1985 26 6469. 70 C. D. Slater C. N. Robinson R. Bies D. W. Bryan K. Chang A. W. Hill W. H. Moore T. G. Otey M. L. Poppelreiter J. R. Reisser G. E. Stablein V. P. Waddy W. 0.Wilkinson and W. A. Wray J. Org. Chem. 1985,50,4125. 71 S. Alunni S. Clementi C. Ebert P. Linda G. Musumarra M. Sjostrom and S. Wold J. Chem. Soc. Perkin Trans.2 1985 485. 72 D. Johnels U. Edlund and S. Wold J. Chem. Soc. Perkin Trans. 2 1985 1339. 73 W. Linert R. Schmid and A. B. Kudrjawtsev Aust. J. Chem. 1985 38 677. 74 I. H. Williams D. Spangler G. M. Maggiora and R. L. Schowen J. Am. Chem Soc. 1985 107 7717. 75 J. Anguiano and J. Bertran J. Chem Soc. Perkin Trans. 2 1985 1649. 76 J. Bertran and J. Anguiano THEOCHEM 1985,21 107. 77 J. A. Cristobal and J. B. Rusca J. Chem. Soc. Perkin Trans. 2 1985 1237. 78 M. J. Kamlet and R. W. Taft Acta Chem. Scand. Ser. B 1985 39 611. 79 M. J. Kamlet J.-F. Gal P.-C. Maria and R. W. Taft J. Chem. Soc. Perkin Trans. 2 1985 1583. 80 M. C. Spanjer C. L. de Ligny H. C. van Houwelingen and J. M. Weesie J. Chem. Soc. Perkin Trans. 2 1985 1401. 81 M. J. Kamlet J.-L.M. Abboud and R. W. Taft Rog. Phys. Org. Chem. 1981 13 1080. 32 M. Godfrey Chastrette and Chanon and their co-workers82 have reported a new approach to a general classification of solvents using a multi-variate statistical treatment of quantitative solvent parameters. Eighty-three solvents are grouped into nine classes. The basis set for the analysis includes eight physicochemical variables of a solvent uiz the Kirkwood function the molecular refraction the molecular dipole moment the Hildebrand parameter the index of refraction the boiling point and the energies of the HOMO and the LUMO. Ohmae83 has concluded that solvents with large dielectric constants weaken the directive power in substituent groups in aromatic substitution reactions.A simple procedure has been reported84 for calculating octanol/ water partition coefficients of about two hundred organic molecules of diverse structure and func- tionalities by using descriptors such as the number and type of their constituent atoms and the presence or absence of a few functionalities. 4 Studies of Molecular Structures and Reaction Paths The material included in this section is chosen to illustrate the methods in common use the types of system to which they are applied and the kind of information that can be obtained. A practical guide to chemical structure and energy calculations by the three most commonly used computer programs MM2 MOPAC and GAUSSIAN 82 has been prepared by Clark.85 Information and strategies for using the latest in computer technology for the study of molecular electronic structure are presented in a volume edited by Dykstra.86 A computer program has been outlined8’ for extracting from calculated potential-energy surfaces spectroscopic information including equilibrium geometries rotational constants harmonic frequencies anharmonicity constants Coriolis couplings and vibrationally averaged properties.A bibliography of ab initio calculations published in 1984 is available.88 Comparisons of semiempirical and ab initio MO calculations continue to be made. Work of Dewar and Storch’ on the calculation of heats of formation has already been referred to. Schroder and hi el^^ have compared MNDO and MNDOC (a correlated version of MND09’) with ab initio transition states for twenty-four reactions of simple organic molecules.They conclude that the overall agreement supports the use of the semiempirical methods. A comparison of MNDO and ab initio calculations on heteroatomic molecules indicates that the lone-pair electronic repulsions between neighbouring nitrogens are systematically underestimated by MND0.91 Nevertheless when corrections are made the relative stabilities of quite complex heterocyclic systems are predicted with reasonable accuracy. 82 M. Chastrette M. Rajzmann M. Chanon and K. F. Purcell J. Am. Chem. SOC. 1985 107 1. 83 T. Ohmae Bull. Chem. Soc. Jpn. 1985 58 47. 84 G. Klopman K. Namboodiri and M. Schochet J. Comput. Chem. 1985 6,28. 85 T. Clark ‘A Handbook of Computational Chemistry’ Wiley-Interscience New York 1985.86 ‘Advanced Theories and Computational Approaches to the Electronic Structure of Molecules’ ed. C. E. Dykstra Reidel Dordrecht 1984. 87 L. B. Harding and W. C. Ermler J. Compur. Chem. 1985 6 13. 88 THEOCHEM 1985 27 1. 89 S. Schroder and W. Thiel J. Am. Chem. Soc. 1985 107 4422. 90 W. Thiel J. Am. Chem. Soc. 1981 103 1413. 91 E. Fos J. Vilarrasa and J. Fernandez J. Org. Chem.. 1985. 50 4894. Theoretical Chemistry 33 Ab initio calculations on molecules containing second-row atoms are becoming common. In a-substituted carbanions XCH,- the 3d orbitals of Cl and SH play a negligible role in determining the stabilization energies but have a significant effect on some structural proper tie^.^^ The relative stabilities of the trans and gauche forms of ethyl methyl sulphide are correctly produced in calculations with extended basis sets and electron ~orrelation.~~ Calculations on model systems suggest that the thiol-disulphide exchange in proteins follows the SN2 mechanism.94 Other studies include the structures and properties of allene derivatives H,C=C= PH HP=C=NH and HP=C=PH:5 the electron demand of dienophiles containing Si and P,96the stability of the reaction co-ordinate in the unimolecular photodissoci- ation reaction of thioformaldehydey and the intramolecular rearrangement of allene episulphide to cyclopropanethione via thi~xyallyl.~~ In addition to these ab initio studies several theoretical tools have been used in a complementary manner on organosulphur compounds with S bonded to sp2 C,99 and MM2 has been extended to accommodate conjugated systems with S heteroatoms.'OO Theoretical and experimental attempts to determine the singlet-triplet energy gap in methylene have been critically reviewed by Shavitt."' A quantum-mechanical Monte Carlo method has been usedlo2 to obtain a value of 8.9 f2.2 kcal mol-1 for this energy gap a similar value to those obtained by recent ab initio MO methods.There have been several MO studies of reactions of carbene~.*~~-'~~ The location of the transition states for the addition of singlet methylene to substituted ethylenes has been e~plored."~ The barrier to addition of very nucleophilic carbenes to ethylene may be lower than expected from the extrapolation of experimental results on other carbenes.lo4 Azacyclopentadiene carbenes (2) spontaneously ring open at N-N the N=N bond."' Hydroxymethylene adds to formaldehyde via a five-centre transition state in preference to inserting into a C-H bond.lo6 The results of calculations on cyclopropenylidene should assist in the identification through matrix- isolation infrared spectros~opy.'~~ Detailed mechanisms for the isomerization of 92 F.Bernardi A. Mangini G. Tonachini and P. Vivarelli J. Chem. SOC.,Perkin Trans. 2 1985 111. 93 A. Ohsaku and A. Imamura MoZ. Phys. 1985 55 331. 94 M. Aida and C. Nagata Chem. Phys. Lett. 1984 112 129. 95 M. T. Nguyen and A. F. Hegarty J. Chem. SOC.,Perkin Trans. 2 1985 1999 2005. 96 W. W. Schoeller J. Chem.SOC.,Chem. Commun. 1985 334. 97 A. Tachibana 1. Okazaki M. Koizumi K. Hori and T. Yamabe J. Am. Chem. SOC.,1985 107 1190. 98 0. Kikuchi H. Nagata and K. Morihashi THEOCHEM 1985 25 261. 99 J. Kao C. Eyermann E. Southwick and D. Leister J. Am. Chem. SOC.,1985 107 5323. LOO J. Kao D. Leister and M. Sito Tetrahedron Lett. 1985 26 2403. 101 I. Shavitt Tetrahedron 1985 41 1531. 102 P. J. Reynolds M. Dupuis and W. A. Lester J. Chem. Phys. 1985 82 1983. 103 M. Moreno J. M. Lluch A. Oliva and J. Bertran J. Chem. Soc. Perkin Trans. 2 1985 131. 104 M. Moreno J. M. Lluch A. Oliva and J. Bertran Chem. Phys. 1985 100 33. 105 D. J. Pasto and J. P. Freeman J. Am. Chem. SOC.,1985 107 4090. 106 S. N. Ahmed M. L. McKee and P. B. Shevlin J. Am.Chem. SOC.,1985 107 1320. 107 T. J. Lee A. Bunge and H. F. Schaefer J. Am. Chem. Soc. 1985 107 137. M. Godfrey cyclopropylidene to allene on both the singlet and triplet potential-energy surfaces have been deterrnined.lo8 The barriers to the 1,2 shifts of fluorine and methyl that connect methylfluorovinylidene to methylfluoroacetylene are predicted'" to be about 30 and 18 kcal mol-' respectively. Large basis sets including polarization functions are necessary to predict the stabilities of substituted acetylenes.' lo The Al acetylene potential-energy surface has been explored"' by ab initio MO and the effect of bending on the reactivity of alkynes has been studied112 by semiempirical methods. The addition of methyl radical to acetylene is faster than to ethylene in spite of a higher activation energy because of favourable pre-exponential factors.' l3 Hydrogen bonding between F-and sp and sp2 C-H bonds is imp~rtant."~ Ab initio studies of interconversions on the methylacetylene cyclopropene allene potential-energy surface' '' and of acetylene formation from atomic C and CH on the C2H4 potential-energy surface'16 have been reported.HOMO-HOMO interactions dominate the barrier to the cyclic trimerization of acetylene preventing aromatic stabilization in the transition state.' '' Transition-state structures have been calculated for additions of LiH and MeLi to acetylene ethylene,' " and f~rmaldehyde."~ There have been several MO studies of regioselectivity in radical additions to substituted alkenes.12L'22 The anomalous behaviour of the methyl radical in attack- ing fluoro-substituted olefins sometimes at the less fluorinated carbon and sometimes at the more fluorinated carbon is attributed to a delicate balance between two opposing effects.'20 Benzene and its derivatives have also been the subject of several MO st~dies,'~~-'~~ especially with respect to ring geornetrie~.'~~-'~~ Bicyclo[ 6.2.0ldecapentaene (3) is A.Rauk W. J. Bouma and L. Radom J. Am. Chem. Soc. 1985 107 3780. lo9 J. D. Goddard THEOCHEM 1985 26 59. 110 P. Furet G. Hallak R. L. Matcha and R. Fuchs Can. J. Chem. 1985 63 2990. 111 A. C. Scheiner and H. F. Schaefer J. Am. Chem. Soc. 1985 107 4451. 112 W. F. Maier G. C. Lau and A. B. McEwen J. Am. Chem. SOC.,1985 107 4724.113 R. Amaud V. Barone S. Olivella and A. Sole Chem. Phys. Lett. 1985 118 573. 114 M. Roy and T. B. McMahon Can. J. Chem. 1985,63 708. 115 N. Honjou J. Pacansky and M. Yoshimine J. Am. Chem. SOC.,1985 107 5332. 116 M. L. McKee and P. B. Shevlin J. Am. Chem. SOC.,1985 107 5191. 117 R. D. Bach G. J. Wolber and H. B. Schlegel J. Am. Chem. Soc. 1985 107 2837. 118 K. N. Houk N. G. Rondan P. von R. Schleyer E. Kaufmann and T. Clark J. Am. Chem. SOC.,1985 107 2821. 119 E. Kaufmann P. von R. Schleyer K. N. Houk and Y.-D. Wu J. Am. Chem. SOC.,1985 107 5560. 120 R. Arnaud V. Barone S. Olivella N. Russo and A. Soie J. Chem. SOC.,Chem. Commun. 1985 1331. 121 E. Canadell 0.Eisenstein G. Ohanessian and J. M. Poblet J. Phys. Chem.1985 89 4856. 122 F. Delbecq D. Ilavsky N. T. Anh and J. M. Lefour J. Am. Chem. SOC.,1985 107 1623. 123 C. W. Bock M. Trachtman and P. George J. Comput. Chem. 1985,6 592; Chem. Phys. 1985,93,431. 124 S. S. Shaik and P. C. Hiberty J. Am. Chem. SOC.,1985 107 3089. 12' V. Melissas K. Faegri and J. Almlof J. Am. Chem. Soc. 1985 107 4640. 126 P. George C. W. Bock and M. Trachtman Tetrahedron Lett. 1985 26 5667. 127 J. M. Schulman and R. L. Disch J. Am. Chem. SOC.,1985 107 5059. 128 H. Agren and P. S. Bagus J. Am. Chem. SOC.,1985 107 134. Theoretical Chemistry 35 weakly aromatic,'29 but the cyclobutadiene dianion and dication are both confirmed as non-aroma ti^.'^' The Woodward-Hoff mann rules for 1,n sigmatropic rearrangements were confirmed in ~tudies'~' of hydrogen transfer in methyl-substituted conjugated poly- enes using ab initio SCF and correlated wavefunctions with several basis sets.The transition states for 1,5 migrations show variation in charge distribution between the migrating group and the rest of the molecule the migratory aptitude of a group should depend on the nature of the rest of the Searches for the synchronous and asynchronous transition-state structures for the butadiene-ethylene cycloaddition using the 4-31G basis set and including electron correlation give support to the synchronous pathway being the preferred However whether or not Diels- Alder reactions are synchronous appears to depend on the geometry of the cyclic There has been an MM2 e~amination'~~ of the influence of substituent-induced asynchronicity on the stereochemistries of intramolecular Diels-Alder reactions.The favoured pathway in the thermal cycloaddition of two ethylenes involves a diradical intermediate,'36 and the thermal cycloaddition of ketene to ethylene pro- ceeds via a suprafacial-antarafacial mode.137 A cyclic intermediate is involved in the conversion of silene and formaldehyde into silanone and eth~1ene.l~~ MIND0/3 calculations suggest that Lewis acid catalysts tend to increase the two-step character in Diels- Alder rea~ti0ns.l~~ S~heiner'~'has summarized theoretical studies of proton transfer carried out in his laboratory in recent years. He has also rep~rted'~' an ab initio study of proton transfer between the carbonyl and hydroxyl groups of H2C0 .-H -OH2+. Eisen- stein and Jean'42 have analysed the factors favouring an M --H-C interaction in metal-methyl complexes. In developing a force field the torsional parameters are the most difficult to determine. Allinger and his co-w~rkers'~~ have investigated how the molecular structures of selected mono- and di-substituted derivatives of ethane change as a function of the torsional angle about the C-C bond. The torsional potential function of n-butane has been calculated'u to determine the extent to which internal angles and bond lengths depend on steric interactions. 129 D. Cremer T. Schmidt and C. W. Bock L Org. Chem. 1985 50 2684. 130 B. A. Hess C. S. Ewig and L. J. Schaad J. Org. Chem. 1985 50 5869.131 B. A. Hess L. J. Schaad and J. Pancir J. Am. Chem. SOC., 1985 107 149. 132 S. D. Kahn W. J. Hehre N. G. Rondan and K. N. Houk J. Am. Chem. Soc. 1985,107 8291. 133 F. Bernardi A. Bottoni M. A. Robb M. J. Field I. H. Hillier and M. F. Guest J. Chem. SOC., Chem. Commun. 1985 1051. 134 L. A. Burke Theor. Chim. Acta 1985 68 101. 13' F. K. Brown and K. N. Houk Tetrahedron Lett. 1985 26 2297. 136 F. Bernardi A. Bottoni M. A. Robb H. B. Schlegel and G. Tonachini J. Am. Chem. Soc, 1985 107 2260. 137 L. A. Burke J. Org. Chem. 1985 50 3149. 138 S. M. Bachrach and A. Streitwieser J. Am. Chem. SOC., 1985 107 1186. 139 V. Branchadell A. Oliva and J. Bertran Chem. Phys. Lett. 1985 113 197; THEOCHEM 1985,21 85. S. Scheiner Acc.Chem. Res. 1985 18 1174. 141 S. Scheiner and E. A. Hillenbrand J. Phys. Chem. 1985,89 3053. 142 0. Eisenstein and Y. Jean J. Am. Chem. SOC., 1985 107 1177. 143 N. L. Allinger L. Schafer K. Siam V. J. Klimkowski and C. van Alsenoy J. Comput. Chem. 1985,6 331. I44 D. Steele J. Chem. SOC.,Faraday Trans. 2 1985. 81 1077. M. Godfrey Molecular-mechanical calculations have been performed on a series of alkylphenols in order to assess the effects of substituents on bond angle^.'^' Three different force fields have been used in determining the conformational properties of permethylcyclohexane. 146 Other interesting species studied by molecular-mechanical methods are beltenes i.e. molecular belts built from cyclohexa- 1,4-diene,I4' and [N] pericyclynes ie.(C=C-CH2)N.148 Be~kwith'~~ has undertaken a force-field study of the regio- and stereo-selectivity of alkenyl radical ring closures. The results are in accord with his previously p~blished'~' guidelines based on stereochemical considerations. A combination of quantum-mechanical calculations and statistical-mechanical simulation of the dielectric medium is necessary to reproduce experimental results concerning the conformational structure of 1,2-dimethoxyethane in water and other dipolar solvent^.'^' Monte Carlo simulations of solvent effects on reactants and transition states in organic reactions have been reported by several sets of worker^.'^^-''^ 14' C.Decoret B. Tinland and G. Bertholon THEOCHEM 1985 25 269. 146 0. Ermer P.M. Ivanov and E. Osawa J. Comput. Chem. 1985. 6. 401. 147 R. W. Alder and R. B. Sessions J. Chem Soc. Perkin Trans. 2 1985 1849. 148 K. N. Houk L. T. Scott N. G. Rondan D. C. Spellmeyer G. Reinhardt J. L. Hyun G. J. DeCicco R. Weiss M. H. M. Chen L. S. Bass J. Clardy F. S. Jorgensen T. A. Eaton V. Sarkozi C. M. Petit L. Ng and K. D. Jordan J. Am. Chem. SOC.,1985 107 6556. 149 A. L. J. Beckwith and C. H. Schiesser Tetrahedron 1985 41 3925; Tetrahedron Lett. 1985 26 373. 150 A. L. J. Beckwith C. J. Easton and A. K. Serelis J. Chem. Soc. Chem. Commun. 1980 482. '" M. Andersson and G. Karlstrom J. Phys. Chem. 1985,89 4957. 0.Tapia and J. M. Lluch J. Chem. Phys. 1985 83 3970. 153 . J. Chandrasekhar S. F. Smith and W. L. Jorgensen J. Am. Chem.SOC.,1985 107 154. 154 S. J. Weiner U. C. Singh and P. A. Kollman J. Am. Chem. Soc. 1985 107 2219 2229. 155 P. P. Schmidt J. Chem Soc. Faraday Trans. 2 1985 81 341.

ISSN:0069-3030    

DOI:10.1039/OC9858200025

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (i) Pericyclic Reactions By R. S. ATKINSON Department of Chemistry University of Leicester Leicester LE1 7RH 1 General Orbital symmetry conservation and frontier orbital control in the reactions of organic radical cations have been discussed in terms of simple qualitative theory.' A review has appeared on the applications of high pressure in synthesis using pericyclic reactions.* 2 Electrocyclic Reactions Since 3-substituted cyclobutenes generally give trans-substituted butadienes on thermal conrotatory ring-opening it is normally assumed that outward rotation of the 3-substituent is preferred for steric reasons. Stereoselection in conrotatory ring-opening of 3,4- trans-disubstituted cyclobutenes has been examined theoretically by Houk and R~ndan.~ Their conclusions are that there is an increasing preference for outward rotation of groups as the donor character of the substituent increases but that powerful o-electron acceptors rotate inward; steric effects by themselves are too small to explain the observed effects.For 3,4-cis-disubstituted (1) or 3,3-disubstituted cyclobutenes the model predicts that the stronger electron donor will preferentially rotate outwards. R' R' R' rotates outward H H (1) Swern oxidation of the cis-cyclobutene (2) gave the (22),(4E)-dienal (3) with at least 95% stereo~pecificity.~ This useful transformation was shown to be proceeding under kinetic control since the more stable isomer (4) is produced on standing. The cyclobutene-aldehyde (5) was shown to be an intermediate in the conversion of (2) into (3).(Powerful .rr-acceptors according to Houk and Rondan's theory above are ' I. R.Dunkin and L. Andrews Tetrahedron 1985 41 145. K. Matsumoto and A. Sera Synthesis 1985 999. N. G. Rondan and K. N. Houk,J. Am. Chem Soc. 1985 107 2099. S. Ingham R. W. Turner and T. W. Wallace J. Chem. Soc. Chem. Commun. 1985 1664. 37 R. S. Atkinson predicted to show little stereochemical preference for rotation so the outward rotation of the alkoxymethyl could be dominant here.) A clever tropolone synthesis uses double Swern oxidation of readily obtainable diols e.g. (6).Enolization of the 1,2-dione electrocyclic ring-opening of the cyclo- hexadiene and loss of hydrogen chloride leads directly without isolation of inter- mediates to the chlorotropolone (7) in good yield.The reaction is independent of the relative configuration of the di~l.~ c1 c1 c1 I HO c1 0 (7) 79% Conversion of the azido-bis( dimethylamino)-2-azabutenyliumsalt (8) with base into the stable triazinium 1-imide (9) is presumed to take place uia an unprecedented 6~-electrocyclization of (lo). An X-ray crystal structure determination suggests (9) as the best representation of this unusual product.6 3 Cycloadditions This is the era of the intramolecular cycloaddition (see later) and it is not surprising that the intramokcular ketene-alkene cycloaddition should continue to be exploited by a number of workers. For efficient cycloaddition with an alkyl-substituted alkene the reactivity of the ketene needs to be boosted -in the present case by a-methylene substitution.Thus the acid chloride (1l) derived from geranic acid was converted into the bicyclo[3.l.l]heptan-6-one(12) uia the ketene (13),7 and a similar procedure has been used to convert (14)into (+)-(P)-trans-bergamotene(19.' M. G. Banwell and R. Onrust Tetrahedron Lett. 1985 26 4543. G. V. Boyd P. F. Lindley J. C. Mitchell and G. A. Nicholaou J. Chem. Soc. Chem. Commun. 1985,1522. Y. S. Kulkarni and B. B. Snider J. Org. Chem. 1985,50 2809 see also Y. S. Kulkarni B. W. Burbaum and B. B. Snider Tetrahedron Lett. 1985 26 5619. * E. J. Corey and M. C. Desai Tetrahedron Lett. 1985 26 3535. Reaction Mechanisms -Part (i) Pericyclic Reactions 39 NMe NMe NMe2 ArCH =/ ArCH2< ArCH24 \ N \\ N --N SN4 NaN N3AN OH p4e2 NMe2 (10) (8) 1 Ar NMe HN= N 'N c-N, N="'RMe2 "2 NMe2 NMe2 NEt, i..-"""' toluene 0.03M COCl -&-& 0 (14) 43yo (15) 70% Alkoxyketenes are also reactive enough to give good yields of cyclobutanones by intramolecular addition to alkenes (Scheme l);9the electronic effects of substituents on the alkene appear to control the regiochemistry of the cycloaddition." An alternative to increasing the electrophilicity of the ketene is to use keteniminium salts which have the advantage over ketenes of not dimerizing.Intramolecular cycloaddition is successful here also e.g. (16) -,(17)." It has been suggested' that these intramolecular ketene-alkene cycloadditions are asynchronous'* and are not best regarded as concerted ,2 + ,2 reactions.A similar conclusion has been drawn for the intermolecular cycloaddition of cyanoketene (18) with the silyl enolether (19) in which there is experimental evidence for a dipolar intermediate (20) in spite of the fact that the three criteria which are usually R R. Snider R. A. H F Hui. and Y. S. Kulkarni. J Am Chem. Snc.. 1985 107 2194. 10 B. B. Snider and R. A. H. F. Hui J. Org. Chem. 1985,50 5167; see also W. T. Brady and Y. F. Giang ibid. 1985 50 5177. I. Marko B. Ronsmans A. M. Hesbain-Frisque S. Dumas L. Ghosez B. Emst and H. Greuter J. Am. Chem. SOC 1985 107 2192. 12 L. A. Burke J. Org. Chem. 1985 50 3149. R.S. Atkinson R = Me (72%) 1 I ol 0 52% Me (CF,SO,),O collidine (17) (87%) .--"..:I (16) Scheme 1 adduced to support a concerted ,2 + ,2 mechanism are satisfied in this case uiz. stereospecific cycloaddition cis-alkenes reacting faster than trans-alkenes and for- mation of kinetic rather than thermodynamic prod~cts.'~ The commonly accepted mechanism for cycloaddition of fluoro-olefins to alkenes to give cyclobutanes is that the reaction proceeds via a biradical intermediate,14 but a provocative paper has re-interpreted the evidence as supporting a ,2 + ,2 cycloaddition.* A review on new synthetic developments of the 41r + 27r cycloreversion has appeared.I6 In the Diels-Alder reaction the search for new dienes and dienophiles (or better routes to old ones) continues; particularly sought after are those which combine high regioselectivity and stereospecificity (exo/ endo).Site selectivity (e.g.the prefer- ence of a diene for one double bond over another in a q~inone'~) may be necessary l3 A.H. Al-Husaini and H. W. Moore J. Org. Chem. 1985,50 2595. 14 F. Bemardi,A. Bottoni M. A. Robb H. B. Schlegel and G.Tonachini,J. Am. Chem. SOC.,1985,107,2260. D. W. Roberts Tetrahedron 1985 41 5529. 16 M. C. Lame and J.-C. Ripoll Synthesis 1985 121. R. P.Potman F. J. van Kleef and K. W. Scheeren J. Org. Chem. 1985 50 1955. Reaction Mechanisms -Part (i) Pericyclic Reactions or design may be primarily directed at enantiospecific synthesis. The response of this remarkable reaction in particular cases to variations in solvent (including water and microemulsions’*) pressure and catalysis (including conditions which clearly bring about a change in mechanism) is known in broad outline although little systematic work has been done.Heterodienes and heterodienophiles have attracted much attention recently and rare earth complexes have been used as mild Lewis acids which are particularly suitable for catalysing reactions involving acid-sensitive substrates. It has now been found” that Yb(fod)3 can be used to accelerate the reactions of acid-sensitive all-carbon dienes (e.g. furan 1-methoxybutadiene) and those Diels-Alder reactions which fail with the usual Lewis acids. There may be confusion (out of context) in the use of the term ‘homo Diels-Alder’ as in this paper to mean the opposite of a hetero Diels-Alder when it has previously been used in an alternative sense.2o Over the past twenty years the intramolecular Diels- Alder (IMDA) has had an increasingly powerful impact on organic synthesis.This is particularly so since all the factors influencing the intermolecular reaction can invariably be applied with advantage to the IMDA. The syntheses of brexane-2-one (21)’’ and functionalized spiro[4S]decanes (22)22 make clever use of the rapid [1,5]sigmatropic rearrangement of hydrogen in monosubstituted cyclopentadienes; this allows the cycloadditions to proceed to completion even though the required diene isomer may be only a minor component of the equilibrating mixture. ,CO,Et The substrates e.g.(23) designed for IMDA are conveniently obtained by assembling the corresponding furan and then chemoselectively oxidizing with per- acid. Diactivation of the dienophile has a favourable effect upon the rate of cycliz- ation relative to monoactivated systems and cyclization takes place at room tem- perature to give a mixture of cis- and trans-fused hydrindenones (24) and (25).23 ‘*A. A.-Z. Samii A. de Savignac I. Rico and A. Lattes Tetrahedron 1985 41 3683. 19 S. Danishefsky and M. Bednarski Tetrahedron Lett. 1985 26 2507; see also J. Jurczak A. Golebiowski and T. Bauer Synthesis 1985 928. 2o See for example T. L. Gilchrist and R. C. Storr ‘Orbital Symmetry’ Cambridge University Press Cambridge 1972. 21 A. Nickon and A.G. Stem Tetrahedron Lett. 1985 26 5915. 22 J. E. Nystrom T. D. McCanna P. Helquist and R. S. Iyer Tetrahedron Lett. 1985 26 5393. 23 P. D. Williams and E. LeGoff Tetrahedron Lett. 1985 26 1367. R. S. Atkinson The cis-trans conversion of the ene-dione unit in (23) was brought about by treatment with pyridine at room temperature and IMDA was also accomplished here although a higher temperature was required. The ratio of cis-versus trans-hydrindenone formation by cyclization of 1,3,8-nonatriene (26) and its response to changes in substitution has been rationalized by Houk et aI. Activation parameters for the cycloadditions together with force-field calculations suggest that product stabilities of (27) and (28) do not determine product ratios.24 Donors at C-1 and acceptors at C-9 in (26) promote trans-selectivity.It is suggested that in this system there is a torque applied to the dienophile by the limited chain length. When an acceptor is substituted at C-9 or a donor at C-1 these substituents can accommodate the ‘twist asynchronous’ transition state with bonding more advanced internally than peripherally; MM2 model calculations show the twisting to be more favourable in the trans (29) than the cis (30) transition state.25 A solution to this problem of lack of stereospecificity in the (substituted) nona- triene26or decatriene IMDA is the inclusion of a trimethylsilyl group as a removable stereocontrol element.27 Thus whereab cyclization of (31) gave a 1 :4 ratio of cis-and trans- hydrindenes the trimethylsilyl-substituted analogue (32) gave the single stereoisomer (33).Removal of the trimethylsilyl unit is easily accomplished. 24 Y.-T. Liu and K. N. Houk Tetrahedron Lett. 1985 26,2269. 25 F. K. Brown and K. N. Houk Tetrahedron Lett. 1985 26 2297; see also T. C. Wu and K. N. Houk ibid. 1985 26 2293 and 2517. 26 A. Guy M. Lemaire M. Negre and J. P. Guette Tetrahedron Lett. 1985 26,3575. 27 R. K.Boeckrnan and J. E. Barta J. Org. Cfiern. 1985 50 3421. Reaction Mechanisms -Part (i) Pericyclic Reactions H' 'CO B u H CO,Et (33) R = SiMe (85%) Kinetically preferred but less stable to reduced pressure Simple furans are shy partners in IMDA (as they are in intermolecular Diels-Alder reactions) but respond favourably to the greater intimacy brought about by 14 kbar pressure (34) -* (35) and (36).28 The activity of allenyl ethers as dienophiles in IMDA reactions with furan has been ascribed to a reduction of steric impediment in the transition state.It is likely that the cycloaddition is reversible but even if the equilibrium (37) G= (38) lies on the left the reaction can still go to completion in the presence of base.29 The reactivity of thio- sulphoxide- and sulphone-substituted triazines (39) (40) and (41) in their IMDA reactions to give (42) (43) and (44) respectively might 28 S. J. Burrell A. E. Jerome M. S. Edenborough L. M. Harwood S. A. Leeming and N. S. Isaacs Tetrahedron Lett. 1985 26 2229; see also J. Jurczak A. L. Kawczynski and T. Koiluk J. Org.Chern. 1985 50 1106. 29 K. Hayakawa Y. Yamaguchi and K. Kanematsu Tetrahedron Lett. 1985 26 2689. R. S. Atkinson (39) n = 0 101 "C 21h 69% (42) n = 0 (40) n = 1 r.t. 27h 69% (43) n = 1 (41) n = 2 67°C 27h 75% ' (44) n =2 be expected to increase (or decrease) along the series. This is not so as shown by the conditions required. The best overlap between the HOMO(acety1ene) and LUMO(azadiene) may by coincidence be at the sulphoxide oxidation level.30 An IMDA with a difference is that occurring between a phosphole and a vinylphos- phine when both are co-ordinated to palladium. Thus mixing of (45) and (46) at room temperature results in the adduct (47) a new class of diphosphine which is clearly of potential value for asymmetric catalyst design.31 (45) PdCl2 PhP 't New dienes which have been used in the intermolecular reaction include (48)32 (whose terminal hydroxy-group is also convenient for attachment to dienophiles followed by IMDA (Scheme 2); dicyanocyclopentadiene for the synthesis of useful 1,5-disubstituted cyclohexa- 1,3-dienes (Scheme 3);33(49) (prepared on a multigram scale as shown in Scheme 4) which is the equivalent of isoprene after removal of 0 11 PhCO ,C02H CHCI A (-& H 000 (72%) Scheme 2 30 E.C. Taylor and J. E. Macor Tetrahedron Lett. 1985 26,2419. 31 M.S. Holt J. H. Nelsen P. Savignac and N. W. Alcock J. Am. Chem. Soc. 1985 107 6396. 32 . A. Ingendoh J. Becher H. Clausen and H.C. Nielsen Tetrahedron Lett.1985 26 1249. 33 G. I. Dmitrienko M. E. Savard R. W. Friesen and M. S. Thandi Tetrahedron Lett. 1985 26 1691. Reaction Mechanisms -Part (i) Pericyclic Reactions NC CN Y = C02Me;80% HC (C N)z Y = CO,Me;63'/0 Scheme 3 52% overall Scheme 4 (49) the SPh group but is much more regioselective than the latter;34 conjugated exocyclic 1,2-dienes of the general formulae (50) which are the result of the availability of 2,3-bis( chloromethy1)butadienes by palladium-catalysed reaction from allene (Scheme 5);35and (51),36 (52),37(53),38(54),39and (55)40 which show high regioselec- tivity with the second diene function of (55) reacting slower than the first and allowing attachment of two different dienophiles. (crystallized) Scheme 5 R',R2 R3 = H Me 34 P.J. Proteau and P. B. Hopkins 1. Org. Chem. 1985 50 141; see also C. L. Liotta and J. W. Verbicky Tetrahedron Lett. 1985 26 1395. 35 L. S. Hegedus N. Kambe Y. Ishii and A. Mori J. Org. Chem. 1985 50 2240. 36 A. Hosomi Y. Sakata and H. Sakurai Tetrahedron Lett. 1985 26 5175. 37 G. A. Kraus S. Yue and J. Sy J. Org. Chern. 1985 50 283. 38 D. Djahanbini B. Cazes J. Gore and F. Gobert Terrahedron 1985 41 867. 39 I. Fleming and M. Taddei Synthesis 1985 899. 40 J.-L. Metral and P. Vogel Helu. Chirn. Acta 1985 68 334. R. S. Atkinson Br Br (58) (56) (78%) (57) The unconjugated cyclohexadiene ester (56) has been prepared in good yield by debromination of (57) using the ditelluride (58).41 The chiral water soluble glucose-bound butadienyl ether (59) reacted efficiently at room temperature with methacrolein; removal of the sugar from the adduct was carried out en~ymically.~~ New dienophiles include iminium salts generated under Mannich conditions (Scheme 6);43(phenylsulphony1)propadiene(60)which adds highly regioselectively + CHzOH 60 :40 (goo/,:after acetylation) L/ (SOYO) 4 1 Scheme 6 41 L.Engman and S. E. Bystrom J. Org. Chem. 1985 50 3170. 42 A. Lubineau and Y. Queneau Tetrahedron Lett. 1985 26 2653. 43 S. D. Larsen and P. A. Grieco J. Am. Chem. Soc. 1985 107 1768. Reaction Mechanisms -Part (i) Pericyclic Reactions 47 to dienes and yields methylene-cyclohexenes after desulphonylation (Scheme 7);@ and alkenylammonium tetrafluoroborate salts e.g.(61) which are surrogates for the enamine double bond (which is unreactive in Diels- Alder reactions with ordinary dienes). The dimethylamino-group is produced by reduction with sodium borohy- dride (Scheme 8).45 OMe SOzPh (54% ) Scheme 7 Me02C &co2R g:; hC0zR "Me3 NMe2 BF (61) 60% Scheme 8 A mild method for producing sulphines in situ is by treatment of silylmethane sulphinyl chlorides with fluoride ion (Scheme 9).46 These sulphines are excellent dienophiles and the endo-sulphoxide obtained with cyclopentadiene readily under- goes [2,3] sigmatropic rearrangement and the resulting sultenes (62) can be put to good synthetic use.47 1 900 '/o-Scheme 9 An intriguing transformation occurs when (63) is treated with dienes in the presence of aluminium chloride (Scheme Diels- Alder addition to an intermedi- ate thienium ion is presumed to be involved.Overall the diene is regiospecifically 1,4-functionalized with the residual 2,3-double bond cis. 2-p-Tolylsulphinylacrylate(64) has a higher reactivity than the corresponding 3-isomer and reacts in the presence of zinc chloride with high diastereoselectivity probably uia the ~helate(65).~~ 44 K. Hayakawa N. Nishiyama and K. Kanematsu J. Org. Chem. 1985 50 512. 45 M. E. Jung and K. R. Buszek J. Org. Chem. 1985 50 5440. 46 E. Block and A. Wall Tetrahedron Lett. 1985 26 1425. 47 E. Block A. Wall and J. Zubieta J. Am. Chem. SOC.,1985 107 1783; see also R. W. Saalfrank and W.Rost Angew. Chem. Znt. Ed. Engl. 1985 24 855. 48 K. Fuji S. P. Khanapure and M. Node Tetrahedron Lett. 1985 26 779. 49 Y. Arai S. Kuwayama Y. Takeuchi and T. Koizumi Tetrahedron Lett. 1985 26 6205. 48 R. S. Atkinson OAlC13 0AlCl3 +I +I 0-Tol--S -+d'C-CH2 + a *I / COzR (64) CO,Me 99% one diastereoisomer (65) V Other specially designed dienophiles which have been shown to react with impress- ively high enantioselectivity in the Diels- Alder include (66),50(67),5' (68),52and (69).53 50 J. K. Whitesell D. James and J. F. Carpenter J. Chem. Soc. Chem. Commun. 1985 1449. " 0. DeLucchi C. Marchioro G. Valle and G. Modena J. Chem. Soc. Cbem. Commun. 1985 878. 52 T. Poll A. Sobezak H. Hartmann and G.Helmchen Tetrahedron Lett. 1985.26 3095. 53 J. Mulzer M. Kappert G. Huttner and I. Jibril Tetruhedron Lett. 1985 26 1631. Reaction Mechanisms -Part (i) Pericyclic Reactions Dimerization of tri-t-butylcyclobutadiene (70) has been shown by X-ray crystal- lography to lead not to the syn-dimer (71) as was previously thought but to (72) presumably by a two-step process via (73) (or the corresponding diradical) and not via concerted 477 + 277 cy~loaddition.~~ A remarkable tandem Diels-Alder/retro-Diels- Alder occurs when ergosterol ace- tate (74) is treated with propargylaldehyde giving the 14-membered ansa-compound (75).55 + t (73) (74) (75) 85% Reaction of the pyran-2-thione with nitrosobenzene gave (76) in 92% yield; the mechanism in Scheme 11 has been ~uggested.~~ A new type of electron acceptor for Diels- Alder reactions possibly proceeding via radical cations of both diene and dienophile uses mixtures of ketone and lithium perchlorate where the polar solvent and special salt effect together increase the yield 47r + 257 $o 0'+ PhN=O ___ 4 NPh \ Ph Scheme 11 54 G.Maier K. Euler H. Imgartinger and M. Nixdorf Chem. Ber. 1985 118,409. 55 D. Schomburg M. Thielmann and E. Winterfeldt Tetrahedron Lett. 1985 26 1705. 56 A. Defoin G. Augelmann H. Fritz G. Geffron C. Schmidlin and J. Streith Helu. Chim. Acta 1985 68 1998. R. S. Atkinson R,CO + Donor (D) 3 (R2CO"D"+) c __* [R,COLi+] + D+ fluorenone 1' (77) -% + (79 1 :1(60°/0) Scheme 12 and lifetime of the radical ion (Scheme 12).This type of electron acceptor system catalyses Diels-Alder additions [e.g. (77) +(78) + (79)] and the efficiency is com- parable to other known electron acceptors which also catalyse this cycloaddition. However the endo-em ratios (78) :(79) differ which indicates that the same chain mechanism is not involved in all cases.57 Charge-transfer bands are frequently observed on mixing dienes and dienophiles. For the reaction below (Scheme 13) it is suggested that the cycloaddition proceeds via a radical-anion-radical-cation; e.s.r. evidence confirms the presence of both these species in the reaction mixture.'* NMe NMe, qNC(CN)2 C(CN)2\I __*THF Me2+@::(cN)2 ~ *. C(CN)2 @"N)2 (CN)2 NMez NMe NMe 1000/0 Scheme 13 Calculations on the 47r + 27r cycloaddition of double bond systems containing the heavier elements (P Si) have been reported.59 A further study (split valence 4-31G basis set including electron correlation) of the butadiene-ethylene reaction support a synchronous mechanism6' but a theoretical study on the reaction of benzocyclobutene with ethylene concluded that the reaction involves a biradical intermediate followed by a stepwise cycloaddition.61 Turning to other cycloadditions; a symposium-in-print has appeared on a number of synthetic applications of dipolar cycloaddition reactions.62 Most nitrile oxides are unstable dimerizing rapidly to form furoxans in the absence of a? efficient trap and yields of A*-isoxazolines from trapping of the nitrile oxide wit some cis-or trans-disubstituted or trisubstituted alkenes are low for this reason.57 J. Mattay J. Gersdorf and J. Mertes J. Chem. SOC.,Chem. Commun. 1985 1088. 58 M. Dern H.4. Korth G. Kopp and R. Sustmann Angew. Chem. Znt. Ed. Engl. 1985,24 337. 59 W. W. Schoeller J. Chem. SOC.,Chem. Commun. 1985 334. 60 M. Bernardi A. Bottoni M. A. Robb M. J. Field I. H. Hillier and M. F. Guest J. Chem. Soc. Chem. Commun. 1985 1051. 61 T.Kametani T.Honda Y. Ebisawa and H. Ichikawa Tetrahedron 1985,41 3643. 62 W. Oppolzer (ed.) Tetrahedron 1985,41 3447-3559. Reaction Mechanisms -Part (i) Pericyclic Reactions A solution to this problem has been devised which uses the furoxan (80) from dimerization of nitrile oxide (81).At 135-165 "C this dimer is in equilibrium with a small (undetectable by n.m.r.) quantity of the monomer (81) and in the presence of alkenes good yields of cycloaddition products are obtained even with alkenes which are unreactive to the monomer when the latter is generated by the usual means.63 Thermal elimination of trimethylsilyl bromide from (82) generates the thiocarbonyl ylide (83) which adds to electron-deficient alkenes in excellent yield." 100 "C [CH2-8=CHSiMe3] DMF (83) Me,Si' (95%) C02Me (CH20) + HNCHZC02H + [CH,=&-CHJI E L N 5 Mew) 20zMeMeOK C02Me (84) 75% (Me) 85% (H) Reaction of paraformaldehyde with a-amino-acid derivatives generates methyl- eneazomethine ylides (84) by decarboxylative dehydrati~n.~~ In the reaction of the sulphonylazide (85) with 2-nitroso-2-methylpropane (86) the products are the spin-trapped nitroxides (87) and (88) identified by e.s.r.and g.c.-m.s. analysis. The authors speculate that the azosulphone (89) formed by nitrous oxide elimination from the initial 1,3-dipolar addition product (90) will be generated in its cis-form; this might account for its ready decomposition by comparison with the trans-form which is known to be significantly more stable under these condi- tions.66 D. P. Curran and C. J. Fenk J. Am. Chem. SOC.,1985 107 6023. 64 Y. Terao M. Tanaka N. Imai and K. Achiwa Tetrahedron Lett. 1985 26 3011. '' M. Joucia and J. Mortier J. Chem. SOC.,Chem. Commun. 1985 1566. 66 N. Kamigata 0. Kawakita A. Izuoka and M.Kobayashi J. Org. Chem. 1985 50 398. R. S. Atkinson Bu' N CF3S02N + Bu'N=O \ NO,,? -P But. + N2 -BU'N=N. Bu'N=O CF,. + SO2 + CE3S02. But NC F3/ I The stereospecificity of 1,3-dipolar cycloadditions of p-nitrobenzonitrile oxide with cis-and trans-dideuterioethylene has been interpreted as evidence against any involvement of a biradical intermediate in these reactions and hence in 1,3-dipolar cycloadditions in general.67 A previously claimed non-stereospecific 1,3-dipolar cycloaddition of the 1-benzylidenepyrazolid-3-onebetaine (91) and (E)-&nitro-styrene has been found to be up to 99.92% stereospecific in a further study.68 4 Sigmatropic Rearrangements The thio-Claisen rearrangement has not enjoyed widespread use because of the elevated temperatures required and the need to conduct the rearrangement in the presence of mercuric salts to trap and desulphurize the thiocarbonyl product.Oxidation of e.g. the ally1 vinylsulphide (92) to the corresponding sulphoxide (93) leads to isolable sulphines (94) at 0°C with a remarkable rate acceleration of the [3,3] sigmatropic rearrangement. Yields of the derived carbonyl compounds (95) are superior to those obtained using the thio-Claisen route [(92) + (95)].The authors speculate that the sulphoxide oxygen may have the same accelerating effect on the reaction rate as the alkxide in an anion-facilitated Cope or Claisen rearrangement. 0- I -+ (931 (94) (95) (90%) (Z)(E)95:5 61 K. N. Houk R. A. Firestone L. L. Munchhausen P.H. Mueller B. H. Arison and L. A. Garcia J. Am. Gem. SOC.,1985 107 7227. 68 R. Huisgen and R. Weinberger Terruhedron Lett. 1985 26 5119; see also H. Dorn ibid. 1985 26 5123. Reaction Mechanisms -Part (i) Pericyclic Reactions 53 A preferred (2)-configuration for the sulphine (94) is ascribed to the preference of the oxygen for an axial orientatiqn in the chair transition-state in the absence of substituents particularly at C-1 in (93).69 Thermodynamic control in the Claisen rearrangement invariably favours the y,S-unsaturated ketone [(96) (97)] and special factors must be incorporated into the system if the ally1 vinyl ether is to become thermodynamically preferred. Examples of this retro-Claisen include (98) + (99) in which conjugation of the vinyl ether with the ester and relief of ring-strain conspire to make the product more stable than the starting aldehyde.This retro-Claisen is greatly acceler3ted when conducted in the presence of a catalytic amount (0.1 equiv.) of boron trifluoride etherate e.g. the reaction of (98) +. (99) is complete in 1 h at 0 0C.70 HOAc(cat) 98% (n.m.r.1 toluene a _____, 4h 110°C 72% (isolated) I C02Me H High asymmetric induction in the aza-Claisen rearrangement of N-allylketene- N,O-acetals (100) will depend on (a) high re/si face selectivity in reaction of the C=C bond (b) a defined acetal double bond configuration and (c) absence of epimerization at C in the oxazoline product (101). With R = But in (loo) levels of diastereoisomer excess in (101) are 98'/0.~l Two similar and elegant syntheses of cis-chrysanthemic acid (102) use the Claisen rearrangement of the silyl ether of lactone (103) which is constrained to proceed via a boat transition-state.72 The enolates of a-allyloxyketones are in principle capable of undergoing [2,3] sigmatropic rearrangement (Scheme 14).In practice the 'anionic oxy-Claisen' is favoured but the rate of rearrangement is greatly affected by the nature of the counter 69 E. Block and S. Ahmad J. Am. Chem. SOC.,1985 107 6731. 70 R. K. Boeckman C. J. Flann and K. M. Poss J. Am. Chem. SOC.,1985 107 4359. 71 M. J. Kurth 0.H. W. Decker H. Hope and M. D. Yanuck J. Am. Chem. SOC.,1985 107 443. 72 A. G. Cameron and D. W. Knight Tetrahedron Lett. 1985 26 3503; R.L. Funk and J. D. Munger J. Org. Chem. 1985 50 707. R. S. Atkinson ion and is fastest with K+. It is suggested that the transition state (104) may derive some stabilization from the semidione-type stability of one of the components in a radicaloid cleavage of the C-0 bond.73 Kinetic and thermodynamic studies of the Cope rearrangement of 1,4-bis(dideuteriomethy1ene)cyclohexane (105) to ( 106) via the enforced boat-like transition-state (107) has indi~ated'~ that pyramidalization of the carbon atoms 2 and 5 occurs confirming an earlier prediction of Dewar et al. c 7 D20 D2 CD2 DD Addition of the dienolate of 2-butenoic acid (108) to the enone (109) at 66 "C leads to (110). That this is not a simple Michael addition but in fact proceeds via the oxy-Cope rearrangement shown (Scheme 15) is supported by isolation of (111) when the reaction was carried out at -95 "C and conversion of the latter into (1 10) by deprotonation at low temperature with two equivalents of base and then warming to 25 "C for 2 h.75 Macroexpansion of (112) into (113) in the presence of potassium hydride was previously interpreted as either a tandem (3,3) (3,3) (oxy-Cope then enolate-Cope) or an oxy-[5.5]sigmatropic rearrangement.Further work has indicated that both 73 M. Koreeda and J. I. Luengo J. Am. Chem. SOC.,1985 107 5572. 74 W. von E. Doering and C. A. Troise J. Am. Chem. SOC.,1985 107 5739. 75 P. Ballester A. Garcia-Raso A. Gomez-Solivellas and R. Mestres Tetrahedron Len. 1985 26 2485.Reaction Mechanisms -Part (i) Pericyclic Reactions 55 1.66"C '2. H,O-H+ H02kph Ph H 0 (110) 81% Scheme 15 these processes are contributing to the formation of (1 13).76 This macroexpansion has been used as the basis of an eight-step synthesis of (-)-(32)-cembrene A.77 Kinetic studies on the thermal rearrangement of (substituted) homopentaful- valenes (114) to (115) did not distinguish between a wholly biradical pathway for this stereospecific transformation and a possible contribution from a [5.5] sig- matropic rearrangement.78 It seems to this author that (concerted) [5.51 sigmatropic rearrangement would be more likely to lead to (115) having a syn-disposition of the two C-H bonds indicated. o^o I -. CUCI I, _-..THFJ-70"C 2Na' (114) HH Chirality transfer in the (2.3) is as efficient as in the [3.3] sigmatropic rearrangement when proper regard is paid to the likely transition-state geometry of the former. Thus Wittig rearrangement of the anion derived from optically active (2)-allylstan- nane (116) gives only the (E)-homoallylic alcohol (117) with 100% transfer of 76 P. A. Wender R. J. Ternansky and S. McN. Sieburth Tetrahedron Lett. 1985 26 4319. 77 P. A. Wender and D. A. Holt J. Am. Chem. Soc. 1985 107 7771. 78 K. Hafner and G. F. Thiele J. Am. Chem. SOC.,1985 107 5526. R. S. Atkinson Me Me -BuLi '+Me -78 "C Me CH20H H' (1 19) chirality. Using the (E)-allylstannane a mixture of (S),(E) and (R)(Z)-homoallylic alcohols was ~btained.'~ It is clear that the isopropyl group will be of importance in raising the transition-state energy of (1 18) relative to (1 19).This stereospecificity has been applied to a synthesis of (+) Prelog-Djerassi lactone.'' A number of studies involving [1,3] sigmatropic rearrangements have been reported.81982 Although the stereospecificity which obtains may be consistent with Woodward and Hoffman's predictions there is a tendency to interpret these rear- rangements as non-concerted -usually involving radical pairs. Theoretical studies of [1,n] sigmatropic rearrangements involving hydrogen transfer in simple methyl-substituted conjugated polyenes have been reported.83 5 Other Pericyclic Reactions A number of new carbenes have been generated by pyrolysis of quadricyclanes functionalized at the bridging carbon.Thus vapour phase pyrolysis of (120) brings about conversion into the norbornadiene followed by cheletropic elimination of the carbene which undergoes intramolecular cycloaddition to the double bond via its 1,3-dipolar resonance structure (Scheme 16).84 NC-g-N c-.* NC-C=N H J H CN Scheme 16 49'/o 79 M. M. Midland and Y.C. Kwon Tetrahedron Lett. 1985 26 5013. 80 D. J.-S. Tsai and M. M. Midland J. Am. Chem. SOC.,1985 107 3915. V. Clock M. Wette and F. G. Klarner Tetrahedron Left. 1985,26 1441. 82 C. Bleasdale and D. W. Jones J. Chem. Soc. Chem. Commun. 1985 1026. 83 B. A. Hess L. J. Schaad and J. Pancir J. Am. Chem. SOC.,1985 107 149. 84 R.W.Hoffmann and W. Barth Chem. Ber. 1985 118 634. Reaction Mechanisms -Part (i) Pericyclic Reactions The ene reaction of the diene (121) with enophile (122) is remarkably stereo- specific; only the exo-face of the diene one face of the aldehyde and one of the two enantiotopically related rings of the diene underwent reaction8' J. K. Whitesell and D. E. Allen 1. Org. Chem. 1985 50 3025.

ISSN:0069-3030    

DOI:10.1039/OC9858200037

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (ii) Polar Reactions By D. J. McLENNAN Department of Chemistry University of Auckland Auckland New Zealand 1 Introduction Despite the doubts expressed in last year’s Report only a few 1984 papers missed the deadline. These are cited in the appropriate sections. In a late 1984 review Williams has discussed his work on the evaluation of effective charge on reacting atoms in transition states for acyl and alkyl transfers.’ A review on solvation effects and the mechanism of heterolysis of t-butyl halides has appeared.2 What is a polar reaction? Pross addresses this point and observes that within the framework of the configuration mixing model developed by himself and Shaik the distinction between conventional ‘polar’ two-electron transfer and radical-producing single electron transfer (SET) is ill~sory.~ Polar processes are single electron shifts which are synchronized with bond formation so that radical intermediates are not necessarily formed.A formal SET process involves the occurrence of a one-electron shift before bonding interactions set in. Thus a mechanistic spectrum may exist. A 1,5-sigmatropic hydrogen shift is not normally considered to belong in either of the above categories but calculations suggest that the transferring hydrogen can have protonic or hydridic character depending on the carbanion- or carbocation- stabilizing properties of the carbon frame~ork.~ Some polar character may therefore be evident. Several important reviews and monographs are available.Stirling has reviewed the effects of strain upon organic reactivity and opens his case with a veterinary recipe which depends on the opening of a strained ring.5 A comprehensive treatise on superacids has been published,6 and a review on a-keto-carbocations has a~peared.~ Heterolysis of a C-C bond produces a carbanion and a carbocation and hence must be mentioned in a general section. Arnett and Molter discuss their work on the kinetics and thermodynamics of such processes.8a A simple master equation ’ A. Williams Ace. Chem. Res. 1984 17 425. G. F. Dvorko E. A. Ponomareva and N. I. Kuklik Russ. Chem. Rev. (Engl. Trans[.),1984 53 547. A. Pross Ace. Chem. Res. 1985 18 212. S. D. Kahn W. J. Hehre N. G. Rondan and K. N. Houk J. Am. Chem. SOC.,1985 107 8291.C. J. M. Stirling Tetrahedron 1985 41 1613. G. A. Olah G. K. Surya Prakash and J. Sommer ‘Superacids’ Wiley New York 1985. ’X. Creary Ace. Chem. Rex 1985 18 3. (a) E. M. Arnett and K. E. Molter Acc. Chem. Rex 1985 18 339; (b) E. M. Amett B. Chawla K. Armanath M. Healy and K. E. Molter J. Am. Chem. Soc. 1985 107 5288. 59 60 D.J. McLennan based on pK of the carbanion portion and pK,+ of the carbocationic portion allows prediction of heats of ionization of C-C bonds.8b An amazing hydrocarbon salt has been prepared by Okamoto and his co-workers C48H51+C67H39-. This is stable under argon for six months. Another hydrocarbon partially dissociates in Me,SO to yield a salt of Kuhn's carbanion plus the tropylium cation.' Menger advocates a spatiotemporal postulate to explain aspects of organic and enzymatic reactivity." Molecules or reactive centres must not only be in each other's proximity to ensure reaction; they must also stay close to each other for a sufficient time to consummate the chemical change.A rare case of an equilibration overshooting its equilibrium point and having to sneak back is reported. The second law of thermodynamics however survives this assault; an unexpected isotope effect is the culprit." If you don't know what a Bema Hapothle is you should read Jencks' primer on the subject.'* Even if you do know you should consult this article whether or not you believe in the existence of the Bema Hapothle. Debate on the subject will be reported later.In the meantime the Reporter would appreciate guidelines as to the accepted pronunciation. 2 Solvolysis and Carbocations All is not well with the IN + mY method of correlating solvolytic reactivity as originally proposed. Different Y-scales are needed for different leaving groups emphasizing that Y is a solvent electrophilicity parameter as well as a measure of general p01arity.l~ Additionally the spectre of dispersion amongst various solvent types which bedevilled the original Winstein-Grunwald mY correlations emer- ge~.'~" An earlier proposal that the solvolysis of t-butyl halides in nucleophilic solvents is nucleophilically solvent-assisted has been ~hal1enged.I~ Solvents that can donate strong H-bonds (HTIP TFE etc.) are proposed to provide electrophilic assistance to ionization.Investigations of bridgehead and t-butyl heptafluorobutyr- ates reveal that solvolysis rates in 80% ethanol-water are a function of the increase in strain energy as is the case for chlorides and it is suggested that the reactive OCOC3F7 substrates share a common mechanism with the chlorides. A corollary of the proposals in this work is that adamantyl substrates are more responsive to electrophilic assistance than are t-butyl compounds. It is not yet clear why this is so. Earlier IN + m Y correlations are critically examined and anomalies are revealed. One reason for the developing confusion and debate might be that one of the anchor compounds 2-adamantyl tosylate suffers variable amounts of internal ion pair return in the solvent systems of interest.Bunnett and Paradisi reported in 1981 that the benzenesulphonate exhibited extensive oxygen scrambling during solvolysis in 80% EtOH HOAc and TFA. This contradicted the common assumption that K. Okamoto T. Kitagawa K. Takeuchi K. Komatsu and K. Takahashi J. Chem. Soc. Chem. Commun. 1985 173. lo F. M. Menger Acc. Chem. Rex 1985 18 128; F. M. Menger and U. V. Venkataram J. Am. Chem. Soc. 1985 107 4706. " D. R. Boyd S. Al-Showiman W. B. Jennings and V. E. Wilson J. Chem. SOC.,Chem. Commun. 1985 443. 12 W. P. Jencks Chem. Reu. 1985 85 511. l3 (a) T. W. Bentley and K. Roberts J. Org. Chern 1985,50 4821; (b)D. N. Kevill and T. J. Rissmann ibid. 3063; (c) D. N. Kevill and S. W. Anderson ibid. 3330. 14 D. Farcasiu J.Jahme and C.Riichardt J. Am. Chem. Soc. 1985 107 5717. Reaction Mechanisms -Part (ii) Polar Reactions 61 the solvolyses of 2-adamantyl substrates are k processes (rate-limiting ionization) but the implications of this communication have been largely overlooked. The full paper now firmly restates their case that the extensive scrambling observed indicates extensive internal return even in a nucleophilic solvent such as 80% EtOH (253% return).I5 Bunnett and Paradisi do point out that while the underlying premise of the YoTsscale is damaged by their findings it is nevertheless premature to discard all conclusions based on such correlations. So long as solvent does not participate in the rate-limiting step (presumably the conversion of tight into loose ion pairs) a degree of validity remains.The same authors report also that unencumbered secondary benzenesulphonates such as 2-propyl and cyclopentyl solvolyse with measurable internal return whereas pinacolyl benzenesulphonate Me3CCH(Me)OS02Ph solvolyses without oxygen scrambling. This supports the Shiner contention that rapid methyl migration prevents internal return. Solvent participation in the solvolyses of 1-arylethyl tosylates is discounted by kinetic and stereochemical probes. Ionization to tight ion pairs or solvent attack thereon appears to be rate-limiting depending on the solvent nucleophilicity. l6 This supports the conclusion reached by the Jencks group last year. Meanwhile Jencks and his co-workers report on alcohol-ether equilibrations in the 1-arylethyl system equation 1.Only part of the combined Ar and R substituent effect can be attributed to bonding interactions. A significant part of the substituent effect appears to arise from electrostatic interactions. l7 These are now routinely accepted as structure- reactivity perturbations where transition states are concerned; the present work provides the first example in an equilibrium process. Mention was made above of the possibility of rate-limiting ionization in pinacolyl solvolyses preceding rapid methyl migration. Shiner and Imhoff now report the first apparent case where ionization is reversible and migration is rate-limiting.18 Secon- dary a-and /I-deuterium KIEs are used for diagnosis and are virtually solvent- independent ruling out any solvent-assistance component.ArCH(Me)OH + ROH ArCH(Me)OR + H,O (1) As reckoned from gas-phase chloride transfer equilibria equation 2 the norbornyl cation is unusually stable,” and the relevance of this to solvolysis is perceptively discussed. Comparison of relative R+stabilities in gas and solution phases suggests that both differential nucleophilic and non-specific solvation factors are important. The general idea that the stabilization of carbocations by solvation is inversely proportional to the stability of the ion is not wholly supported by the data. H. C. Brown’s group has reached the half-century in their series on Structural Effects in Solvolytic Reactions. Although the three papers” are the complete accounts l5 C. Paradisi and J.F. Bunnett J. Am. Chem. Soc. 1985 107 8223. 16 A. D. Allen V. M. Kanagasabapathy and T. T. Tidwell J. Am. Chem. Soc. 1985 107 4513. 17 M. E. Rothenberg J. P. Richard and W. P. Jencks J. Am. Chem. SOC.,1985 107 1340. 18 V. J. Shiner and M. A. Imhoff J. Am. Chem. SOC.,1985 107 2121. 19 R. B. Sharma D. K. Sen Sharma K. Hiraoka and P. Kebarle J. Am. Chem. SOC.,1985 107 3747. 20 (a) H. C. Brown F. J. Chloupek and K. Takeuchi J. Org. Chem. 1985 50 826; (6) H. C. Brown S. Ikegami and D. L. Vander Jagt ibid. 1165; (c) H. C. Brown D. L. Vander Jagt I. Rothberg W. J. Hammar and J. H. Kawakami &id. 2179. D. J. McLennan of work published in communication form in the 1960s they repay careful reading. In one pape?'" Brown promises that a forthcoming paper will bring his efforts in the norbornyl area to a close.In many ways this will be disappointing. Whatever one's position on the classical us. the non-classical norbornyl cation and whether or not one regards the research effort expended in this area as being worthwhile and productive it is surely agreed that the debate delineates a fascinating era of mechanistic organic chemistry. This does not mean the end of norbornyl cation chemistry. Paquette and co-workers report that ester (1) is the most solvolytically reactive tertiary system yet found and that the resultant norbornyl-fused norbornyl cation (2) is not stabilized by bridging.21 The high reactivity is attributed to severe strain in (1) resulting from repulsive interactions between inner hydrogens of the two ethano bridges and the framework interior.Additionally a world record for the exo-endo solvolytic rate ratio (1250) f0r.a pair of related compounds is claimed. Hetero analogues and their reactions claim attention. Solvolyses and alumina-catalysed reactions of norbornyl-like and [2.2.2]bicyclooctyl-like N-chloroamines are reported and .rr-participation in the latter heterolyses is proposed.22 Participation by a 7-OX0 bridge can be induced by increased electron demand.23 Destabilization of the norbornyl cation by introduction of electron-withdrawing groups on C5 and c6 apparently allows the formation of classical secondary cations which do not suffer Wagner-Meerwein rearrangement^.^^ Such substitution works to reduce the nucleophilicity of the a-electrons which would otherwise participate.Electrophilic cleavage by HOAc of bicyclic cyclopropane derivatives has been extensively in~estigated.~~ Surprisingly strain energy relief is not the dominant factor governing rates and products. This is consistent with protonation being at least partially rate-limiting. Aryl cations have long eluded direct solvolytic generation. Theory suggests that p-silyl hyperconjugative stabilization should permit their formation.26 Experiment confirms this 2,6-bis(trimethylsilyl)phenyltriflate solvolyses by an SN1 route in TFE.*' Relief of steric strain also provides a pathway since the di-t-butyl derivative behaves similarly. The Hanack cyclization route to aryl cations has undergone further 2' L.A. Paquette D. De Lucca K. Ohkata and J. C. Gallucci J. Am. Chem. SOC. 1985. 107 1015. 22 J. W. Davies J. R. Malpass and M. P. Walker J. Chem. SOC.,Chem. Commun. 1985 686; M. L. Durrant J. R. Malpass and M. P. Walker ibid. 687. 23 J. B. Lambert and E. G. Larsen J. Am. Chern. SOC.,1985 107 7547. 24 W. Kirmse U. Mrotzeck and R. Siegfried Angew. Chem. Znt. Ed. Engl 1985 24 55. 25 K. B. Wiberg and S. R. Kass J. Am. Chem. SOC.,1985 107 988; K. B. Wiberg S. R. Kass and K. C. Bishop ibid. 997 K. B. Wiberg S. R. Kass A. de Meijere and K. C. Bishop ibid. 1003. 26 S. G. Wierschke J. Chandrasekhar and W. L. Jorgensen J. Am. Chem. Soc. 1985,107 1496; Y. Apeloig and D. Arad ibid. 5285. 27 Y. Himeshima H. Kobayashi and T.Sonoda J. Am. Chem. SOC.,1985 107 5286. Reaction Mechanisms -Part (ii) Polar Reactions 63 developments." Whilst on the subject of SiMe stabilization of cations it is noteworthy that a-SiMe destabilizes the 2-adamantyl cation by 6-8 kcal mol-' relative to CH but is some 12-14 kcal mol-' more stabilizing than hydrogen.29 Turning from unstable to stable carbocations we note that Gandler has provided further examples of general base catalysis in the reactions of triarylmethyl cations with water.30 More importantly he shows why catalysis eluded detection for so long-unusual deviations on OH-and water-catalysed rates mean that catalysis will be detected only in a specific pH window. 3 Other Nucleophilic Substitutions The story of the unravelling of the Walden inversion and proof of its identity with sN2 reactions by Hughes Ingold and co-workers in the 1930s is well known.Traynham now shows that they used the wrong data insofar as the alcoholysis of 2-bromooctane is concerned.,' Happily the right answer also emerges from the correct data so textbooks need not be rewritten. Shaik has reviewed the use of state correlation diagrams in qualitatively accounting for the often confusing collage of SN2reactivity patterns.32 He too emphasizes the blurring of the distinction between one-electron and two-electron shifts. The so-called a-effect is considered from a thermodynamic rather than the usual kinetic viewpoint and a-nucleophiles are seen to have a high affinity for C-electrophiles relative to their proton affinities., Ab initio calculations suggest that their bond polarities and charge densities are low in comparison with normal nucleophiles.Nevertheless solvational factors are important and the a-eff ect can be turned on or off depending on the composition of Me2SO-H20 mixtures.34 Qualitative predictions published last year by Pross and the Reporter on the effect of a-carbonyl on sN2 reactivity have been tested by quantitative ab initio calculation^.^^ Needless to say the aforesaid predictions are borne out in all respects. Full condensed-phase sN2 reaction profiles have been calculated for the sN2 chloride exchange of MeCl in water and HCONMe2.36 Significant differences emerge -the gas-phase ion-dipole complexes exist in the aprotic solvent but disappear in water.In the gas phase naked OH- can either nucleophilically substitute or deprotonate MeCl depending on the transla- tional energy.37 Proton transfer is however suppressed when OH-.(H,O) (n = 1 or 2) is used. Last year the solution chemists concluded that the metaphosphate anion PO3- was too unstable to exist as a discrete intermediate in aqueous phosphoryl transfers. But in the gas phase it is an eminently stable and unreactive ion even 28 M. Hanack and R. Rieth J. Chem. SOC. Chem. Commun. 1985 1487. See also W. Holweger and M. Hanack Chem. Ber. 1984 117 3004. 29 Y. Apeloig and A. Stanger J. Am. Chem. SOC.,1985 107 2806. 30 J. R. Gandler J. Am. Chem. SOC.,1985 107 8218. 31 J. G. Traynham Chem. Tech. 1985 15 126. 32 S. S. Shaik Prog.Phys. Org. Chem. 1985 15 197. 33 R. F. Hudson D. P. Hansell S. Wolfe and D. J. Mitchell J. Chem. SOC.,Chem. Cornmun. 1985 1406. 34 M. Laloi-David and C. Minot Nouu. J. Chim. 1985 9 569. 35 A. Pross K. Aviram R. C. Mix D. Kost and R. D. Bach Now. J. Chim. 1984 8 711. 36 J. Chandrasekhar S. F. Smith and W. L. Jorgensen J. Am. Chem. SOC.,1985,107,154; J. Chandrasekhar and W. L. Jorgensen ibid. 2947. 37 M. Henchman P. M. Hierl and J. F. Paulson 1. Am. Chem. SOC.,1985 107 2812. 64 D. J. McLennan more so than N03-.38The reactivity in water is thus more a function of the environment than of the ion itself. Theory applied to stereochemistry at the MNDO level suggests that a nitrogen nucleophile which approaches an electrophilic centre with the lone pair pointing the wrong way is suddenly wrenched through an inversion and then reacts in a normal SN2fashion.A reaction of this type is involved in a beautiful example of kinetic vs. thermodynamic control in intramolecular SN2 reactions involving nucleophilic nitrogen.39 The mechanism of formation of the first C-C bond in the methanol to gasoline process remains under scrutiny. The intermediacy of trimethyloxonium ion and its ylide receives further support from studies which shows that thermolysis of Me,0+BF4- in the absence of added base produces C2 and higher species.40 On the other hand Hunter and Hutchings employ LiAl(OPr’) as a weak base model for the zeolite catalyst H-ZSM-5 and report that it demethylates rather than deprotonates Me30+.41a With H-ZSM-5 itself MeOH forms hydrocarbons more readily than Me2S04 but the reactivity order is reversed when the catalyst conjugate base is employed.41b The authors claim that this is evidence for 0-methylation of the catalyst surface followed by further methylation via a surface-incorporated ylide or carbene.This may well be so but there appears to be no evidence that all potential methylating agents produce hydrocarbons over ZSM-5 by identical m5chanisms. Olah has now introduced studies on alkylhalonium ylides e.g. CH3CH,XCH; from the reaction of singlet methylene with EtX.42 The cyclohexanone enolate anion is exclusively 0-methylated by MeBr in the gas phase.43 This contrasts with solution behaviour. Arnett and his collaborators continue their systematic study on the reactions of alkali metal enolates.44 This year they introduce a ‘method of isomeric pathways’ whereby the ethylation of 3-methylacetylacetonate and the methylation of 3-ethylacetylacetonate are compared.Since a common product is involved it serves as a convenient reference point for a complete thermodynamic and kinetic enthalpy analysis of the reactions. The complexity of the analysis reinforces the authors’ refreshingly candid warnings against using glib generalizations to rationalize small rate differences. Alkylation of metallated hydrazones are usually far more stereospecific than alkylations of the corresponding enolates. Wanat and Collum have enquired into the origin of this difference and propose a model involving subtle preferences between stereoisomeric solvated monomer anions working in concert with a modest stereoelectronic factor to rationalize the ~tereoselectivity.~~ The model predicts eroded stereoselectivity towards carbonyl carbon as electrophile and this is observed.A stereoelectronic factor also controls SN2substitution at benzylic carbon. Con- sideration of the rates of thiourea attack on the benzylic sulphonium ions (3) (4) M. Henchman A. A. Viggians J. F. Paulson A. Freedman and J. Wormhoudt J. Am. Chem. SOC. 1985 107 1453. 39 C. H. Heathcock T. W. von Geldern C. B. Lebrilla and W. F. Maier J. Org. Chem. 1985 50 968. 40 C. Engelen J. Wolthuizen and J. van Hooff J. Chem. SOC.,Chem. Commun. 1985 301. 41 (a) R. Hunter and G. J. Hutchings J.Chem. SOC.,Chem. Commun. 1985 886; (b) idem ibid. 1643. G. A. Olah H. Doggweiler and J. D. Felberg J. Am. Chem. SOC.,1985 107 4975. M. E. Jones S. R. Kass J. Filley R. M. Barkley and G. B. Ellison J. Am. Chem. SOC.,1985 107 109. E. M. Arnett S. G. Maroldo G. W. Shriver S. L. Chilling and E. B. Troughtm J. Am. Chem. Soc. 42 43 44 1985 107 2091. 45 R. A. Wanat and D. B. Collum J. Am. Chem. SOC.,1985 107 2078. Reaction Mechanisms -Part (ii) Polar Reactions 65 and (5) leads to the conclusion that the S.-C bonds being made and broken at the transition state must be as nearly orthogonal to the plane of the benzene ring as possible.46 Thus (5) is more reactive than (3) or (4). The orbital overlap factor proposed 36 years ago by Dewar to account for the greater SN2reactivity of PhCH2C1 over EtCl has finally been experimentally demonstrated.Reactions of small ring systems claim attention. Both (6) and (7) (R = But) react with phenoxides in MeCN to produce (8) thus the reaction of (6) is a retentive process.47 The reactions are apparently under kinetic control. The authors are Arc-Aro-RABrRJLOAr-RABr cautious about claiming SN2with retention and it remains to be demonstrated that the substitution of (6) is a clean second-order reaction and that the But group does not participate. Hine reports that 1,8-biphenylene diol is a true hydrogen-bonding catalyst in epoxide ring-opening. One OH donates a proton to provide acid catalysis whilst the other donates a hydrogen bond to the developing negative charge.48 The rates of ring-opening of 1,l-dimethylaziridinium ions by OMe-/ MeOH are not governed wholly by relief of ring strain and pronounced deviations are discerned for 3- 4- and 5-membered The same applies to eliminative ring fission of cyclopropanols under basic conditions their enhanced reactivity over the corre- sponding cyclobutanols is not accounted for on strain relief grounds alone.49b The search for free metaphosphate in solution continues.Phenyl phosphate dianion transfers its phospho-group to the hindered acceptor Bu'OH in MeCN with racemization at phosphor~s.~~ This could be regarded as the first definitive item of evidence for formation of free monomeric metaphosphate. While Friedman and Knowles also advance other possibilities including solvent-mediated transfer they do claim that metaphosphate in some form has at last been reliably detected.Further evidence for the lack of intermediates in sulphuryl and other phosphoryl group transfers is presented51 and the view that exploded SN2-like transition states are involved is confirmed. An earlier claim of a stereoelectronic effect controlling the orientation of cleavage of cyclic phosphates has been ~ontested.~~ 46 J. F. King G. T. Y. Tsang M. M. Abdul-Malik and N. C. Payne J. Am. Chem. Soc. 1985 107,3224. 47 J. Gasteiger K. Kaufman C. Herzig and T. W. Bentley Tetrahedron Lett. 1985 26 4337. 48 J. Hine S.-M. Linden and V. M. Kanagasabapathy J. Am. Chem. Soc. 1985 107 1082. 49 (a) M.L. D. Vona G. Illuminati and C. Lilloci J. Chem. SOC.,Chem. Commun. 1985 380; (b) A. Bury H. A. Earl and C. J. M. Stirling ibid. 393. so J. M. Friedman and J. R. Knowles J. Am. Chem. Soc. 1985 107 6126. 51 N. Bourne A. Hopkins and A. Williams J. Am. Chem. Soc. 1985 107 4327; A. Williams ibid.,6335. 52 R. Kluger and G. R. J. Thatcher J. Am. Chem. SOC.,1985 107 6006. 66 D. J. McLennan The intermediacy of a-complexes in nucleophilic aromatic substitution is not in question. It is nice to know that MNDO and other semi-empirical theoretical methods predict their existence.53 The reactions of aryl arenesulphonates with molten dodecyltributyl-phosphonium halides do not fit reactivity patterns expected for conventional 2-step SNAr mechanisms.A low aryl and a significant leaving group substituent effect suggest some SN2character but the authors do not dismiss the possibility of an SN2-like transition state lying on the route to a salt-stabilized a-co m p 1ex.54 So many papers have appeared dealing with assignment of SET mechanisms to substitutions previously thought to be nucleophilic polar processes that the area now lacks novelty. We content ourselves with citing an important paper by Eberson wherein the feasibility or otherwise of proposed redox steps is assessed by using Marcus theory (the electron transfer ~ersion).~’ It transpires that favourable electron transfer in some suspected SET processes is ‘forbidden’; these include reactions where alkoxides and thiolates have been recently proposed as one-electron reductants rather than nucleophiles.4 Elimination Reactions A further claim that a trigonal bipyramid carbon intermediate is involved in halide- induced elimination has appeared.56 The reactions of F- and Br- with stereo- specifically deuteriated diastereomers of 1-phenyl-1-propyl-p-nitrobenzoatein MeCN yield products indicative of a common intermediate for the two diastereomeri- cally distinct reactions. However second-order kinetics have not been established and E 1 elimination through hydrogen-bridged carbocations is not yet discounted. Furthermore no account is taken of the possibility of inverting sN2 bromide attack preceding dehydrobromination in the bromide-induced eliminations. Additionally a temperature-independent KIE is held to exemplify a bent B-..H...C moiety this criterion of transition-state geometry is now discredited (see later).Less controversially but equally unexpectedly a substantial primary deuterium isotope effect attends gas-phase based-induced elimination of EtOH from Et20.” Model calculations suggest there is a barrier in these essentially collision-controlled reactions and that the reaction coordinate involves only C-H stretching. This appears to be the first example of a gas-phase ElcB reaction. Ab initio calculations on the fluoride-induced dehydrofluorination of EtF show that a concerted E 2 mechanism prevailss8 since the FCH2CH2- carbanion is not bound with respect to CH2=CH2 + F-.59 The secondary a-deuterium KIE for E2 dehydrohalogenation of PhCH,CH,X by Bu‘O-/Bu‘OH is disturbingly concentration-dependent for X = F and C1.60 It is inverse at low [KOBu’] and normal at higher concentrations.For X = Br and I 53 N. S. Nudelrnan and P. MacCormack Tetrahedron 1984,40,4227. 54 S. E. Fry and N. J. Pienta J. Am. Chem. SOC.,1985 107 6399. 55 L. Eberson Acta Chem. Scad. Ser. B,1984 38,439. 56 H. Kwart and K. A. Wilk J. Org. Chem. 1985 50 3038. 57 V. M. Bierbaurn J. Filley C. H. De Puy M. F. Jarrold and M. T. Bowers J. Am. Chem. SOC.,1985 107 2818. 58 T. Minato and S. Yarnabe J. Am. Chem. SOC. 1985 107 4621. 59 M. Roy and T. B. McMahon Can. J. Chem. 1985 63,708. 60 P. J. Smith K. S. Rangappa and K. C. Westaway Can. J. Chem. 1985 63.100. Reaction Mechanisms -Part (ii) Polar Reactions 67 the KIE is concentration-independent and normal.The anomalous results are considered to arise from competition between syn-and anti-pathways promoted by various associated and dissociated bases. The addition of 18-crown-6 restores normality and the authors suggest the anomalous KIEs can be put to good use as criteria of E2 stereochemistry. Several novel aspects of E 1cB elimination have been reported. The question of why poor SN2 leaving groups (in cr-electron displacements) are good leaving groups from carbanions (7r-electron displacements) has been addressed by Hoz and his co-workers.61 They suggest that the nature of the P-bound carbanion-stabilizing group determines the .rr-nucleophilicity of the negative P-carbon and therefore its ability to expel an otherwise poor leaving group.Full details are now available on the high reactivity of aryl 4-hydroxybenzoate esters towards alkaline hydrolysis. Kinetic evidence is consistent with a 1,6-E1cb elimination involving an 0x0-ketene intermediate equation 3.62 Thioketone-forming eliminations from diarylmethyl -0oCOOh -OoC=O + OAr (3) thiosulphonates Ar,CHSSO,Ar' involves the complete spectrum of E 1cB mechan-ism~.~~ The identity and concentration of the base determines which variant operates. The alkaline hydrolyses of carbamates ArNHC0,R (Ar = p-NO&H4) which pro- ceed via the normal BA,2 mechanism are little affected by the identity of micellar additives. But when the mechanism is ElcB with the isocyanate Ar-N=C=O as an intermediate hydroxy-functionalized micelles are e~ceptional.~~ If the isocyanate is formed within the micelle it can be trapped as a new micellar carbamate which then decomposes by a BA,2 pathway.An E 1cB elimination involving a good leaving group (CI) departing from a propitious carbon (tertiary) is reported.65 It is suggested that a parallel E2 reaction may also operate. 5 Addition Reactions The third-order bromination of cyclohexene by Br in low-polarity solvents differs from the second-order bromination by Br3-. The former reagent attacks a pre-formed Br,-alkene charge transfer complex to form a bromonium ion-Br,- ion pair in the rate-limiting step. Addition of Br3- involves formation of the charge transfer complex followed by nucleophilic attack of Br-.66" Direct evidence for charge transfer com- plexes as essential intermediates has been aff orded.66b The reversibly formed bromonium tribromide from BrZ and adamantylideneadamantane has been shown by X-ray analysis to be a cyclic bromonium ion rather than a ~r-cornplex.~' Impeded access of nucleophiles to the bromonium ion accounts for its stability.61 S. Hoz Z. Gross and D. Cohen J. Org. Chem. 1985 50 832. 62 G. Cevasco G. Guanti A. R. Hopkins S. Thea and A. Williams J. Org. Chem. 1985 50,479; S. Thea G. Cevasco G. Guanti N. Kashafi-Naini and A. Williams ibid. 1867. 63 J. L. Kice and L. Weclas J. Org. Chem. 1985 50 32. 64 T. J,Broxton Aust. J. Chem. 1985 38 77. 65 M. OlwegHrd I. McEwan A. Thibblin and P. Ahlberg J. Am. Chem. Soc.1985 107 7494. 66 (a) G. Bellucci R. Bianchini R. Ambrosetti and G. Ingrosso J. Am. Chem. SOC. 1985 SO 3313; (6) G. Bellucci R. Bianchini and R. Ambrosetti ibid. 2464. H. Slebocka-Tilk R. G. Ball and R. S. Brown J. Am. Chem. Soc. 1985 107 4504. 67 68 D. J. McLennan Addition of hydrogen halides to cyclopropanes bearing electron-withdrawing groups is not the usual electrophilic ring-opening. Instead when EWG = COMe HX + ~EW -+G XCH,CH,CH,-EWG (4) COPh C02H or CN the group itself is protonated and the reaction is therefore a 1,5-homoconjugate addition.68 The hydration of simple alkenes such as cis-and trans-cyclooctenes would seem to be well-understood processes. However analyses in modern terms have been presented.Carbocation lifetimes have been estimated and an interesting point arises regarding the lifetime of 5 x s suggested for the cyclooctyl cation arising from reaction of the trans-alkene with dilute acid. Ordinarily such a short-lived intermedi- ate would have to form by a pre-association pathway but in this case the authors argue that return to reactants may be slow thus the mechanism assigned involves rate-determining production of a carbocation that is not solvationally equilibrated followed by solvent re~rganization.~~ The acid-catalysed hydration of 5-substituted norbornenes has been re~iewed.~' Comparison with solvolysis studies suggests that unsymmetrically bridged cations are involved. 6 Aromatic Substitution and Rearrangements The absence of a Mills-Nixon effect in cyclobutene-annelated dihydropyrenes discussed last year appears not to be a general result.Ab initio VB calculations suggest that benzocyclo-propene and -butene exhibit bond fixation.71 Marcus theory calculations are inconsistent with SET to NO2+ from normal or poorly oxidizable aromatic substrate^.^^ The observed cases of SET in nitration are suggested to arise from electrophilic formation of the Wheland intermediate followed by homolytic cleavage to yield ArH' and NO2. Nitrosonium ion is predicted to be an effective SET acceptor. Thus direct SET is inoperative in the nitrations of polycyclic aromatics by N204 in CH2C12.72" These reactions are catalysed by NO+ and a novel electrophile nitrosated N204 is proposed. The o-complex formed from this then homolyses to form a radical pair which accounts for the observed CIDNP Direct evidence for the non-SET nature of the first step is also advanced perylene radical cation does not react cleanly with NO2 whereas the normal nitration of perylene yields mononitroperylenes.72c Studies on the ipso-nitration of aryl aFines concur.I5N Nuclear polarization experiments implicate the radical pair [ArNMe2 NO2'] in the HN02-catalysed reac- tion but it is still not clear whether the subsequent rearrangement of the ipso-intermediate to the 2-nitrodimethylaniline involves further radical pairs.73 A sug-gested mechanism is shown in Scheme 1. Similar results are reported for the 68 J. B. Lambert J. J. Napoli K. K. Johnson K. N. Taba and B. S.Packard J. Org. Chem. 1985,50,1291. 69 Y. Chiang and A. J. Kresge J. Am. Chem. Soc. 1985 107,6363. 70 M. Lajunen Acc. Chem. Res. 1985 18 254. 71 P. C. Hibberty G. Ohanessian and F. Delbecq J. Am. Chem. Soc. 1985 107 3095. 72 (a)L. Eberson and F. Radner Acta Chem. Scand. Ser. B. 1984,38 861; (b) idem ibid. 1985,39 343; idem ibid. 357. 73 A. H. Clemens P. Helsby J. H. Ridd F. Al-Omran and J. P. B. Sandall J. Chem. Soc. Perkin Truns. 2 1985 1217. Reaction Mechanisms -Part (ii) Polar Reactions ArkMe,H + NO+ + ArhMe + NO’ + H+ NO’ + NO2+ -+ NO+ + NO; ArhMe + NO,’ -+ [ArhMe,NO,.] [Ar&Me,NO,.] -+ ipso-intermediate Scheme 1 HN0,-catalysed nitration of d~rene.~~ Nuclear polarization is however also found when durene is nitrated by NO,+.This can of course be understood in terms of partition of the radical pair [ ArH’ NO2’] between recombination and dissociation but the radical pair does not arise from direct SET from durene to NO2+. It is suggested instead that a normal Wheland intermediate formed in a polar elec- trophilic process homolyses to produce the radical pair. ipso-Aromatic alkylation of hexamethylbenzene in the gas phase involves ben- zenium ions the structure of which is consistent with a normal a-complex as a stable gas phase species.75 The o,o’-benzidine rearrangement of 2,2’-hydrazonaphthalene is a concerted [3,3]- sigmatropic rearrangement under both thermal and acid-catalysed condition^.^^" However differences in carbon and nitrogen KIEs suggest that C-C formation and N-N cleavage have progressed to unequal extents.This may well explain why o,o‘-combination is preferred over other possible pathways. A similar result is obtained for the rearrangement of N-2-naphthyl- N’-phenylhydrazine to 1-(o-amin0phenyl)-2-naphthylarnine.~~~ 7 Carbanions and Proton Transfer Although Schleyer and Kos claimed to have said the final word on anionic (negative) hyperconjugation in carbanions in 1983 further words were said in 1985. Ab initio calculations leading to molecular orbital maps fully support the concept of a r-component in anions such as CF3CH2- and reveal a hitherto unrecognized a-enhan~ement.’~ Negative hyperconjugation may now be reasonably taken to be as well established as positive hyperconjugation in carbocations.Also reported are calculations on a-substituted carbanions XCH2-.78 The stabilization energies run in the order C1 > SH > F > OH and while 3d orbitals play a negligible role in determining stabilization energies for second-row substituents they have a significant effect as far as geometries are concerned. A similar situation was reported last year for organometallic species. Anomalies attending the ring closure of carbanions have been investigated. For small rings AH’ values for odd-membered rings are consistently lower than those for the next higher even-membered ring despite less strain in the latter. It is contended that a-assistance (odd) and a-resistance (even) rationalize the phenomenon the a-effects being the a-electron counterparts of the symmetry rules 74 A.H. Clemens J. H. Ridd and J. P. B. Sandall J. Chem. SOC.,Perkin Trans. 2 1985 1227. 75 M. Attina F. Cacace G. de Petris S. Fornarini and P. Giacomello J. Am. Chem. SOC.,1985 107,2297. 76 (a) H. J. Shine E. Gruszecka W. Subotkowski M. Brownawell and J. San Filippo J. Am. Chem. SOC. 1985 107 3218; (b)H. J. Shine L. Kupczyk-Subotkowska and W. Subotkowski ibid. 6674. 77 D. S. Friedman M. M. Francl and L. C. Allen Tetrahedron 1985 41 499. 78 F. Bernardi A. Mangini G. Tonachini and P. Vivarelli J. Chem. SOC.,Perkin Trans. 2 1985 111. 70 D. J. McLennan for r-systems. These ideas have now been tested by MNDO calculations and AH' differences are reproduced reasonably well.79 Phase relationships in HOMOS are as earlier predicted.Nucleophilic attack of OH-and CN-on electrophilic alkenes of the 9-nitromethylene-fluorene type are strangely zero-order in substrate and zero-order with respect to nucleophile within a kinetic rum8' The authors suggest and cite ultracentrifuge results in support that in water the substrate molecules are heavily aggregated in molecular stacks and that the reactive monomer is present at a constant saturation concentration. More normal behaviour is observed in the deprotonation of cyclopentadiene- indene- and fluorene-type hydrocarbons by OMe-/ MeOH.81 The Bronsted plot is now extended to cover lOpK units and is despite the Bema Hapothle linear. Hydrogen KIEs are constant and independent of pK,. This is rationalized in terms of Marcus proton transfer theory the results are consistent with a large intrinsic AG; value and indeed if the Bronsted plot is linearly extrapolated to ApK = 0 a large intrinsic barrier of 17 kcal mol-' is calculated.But if a linear extrapolation of a Bronsted plot is needed to explain why the plot is linear in the first place are not the elements of a circular argument present? Rate constants at or beyond ApK = 0 would be welcome so as to confirm what is otherwise a sensible explanation. Bednar and Jencks report that in the Eigen sense HCN is the most normal carbon acid known.82 Proton exchange with oxygen and nitrogen bases occurs without solvent mediation and rates are diffusion-controlled in the thermodynami- cally favoured direction. Diamine monocations are however an exception and proton transfers to these bases occur through intermediate solvent 8 Carbonyl Derivatives and Tetrahedral Intermediates Ab initio calculations have been used to do what laboratory physical organic chemists have been doing for decades-probing the effects of substituents on rates and equilibria.Calculations however 'reveal' the structure of the transition state rather than leaving it to be inferred. Several surprising findings emerge from a theoretical study of nucleophilic attack on simple carbonyl compounds.83 Firstiy all reactions utilize cyclic transition states wherein heavy atom reorganization has run ahead of proton transfer from the nucleophile to the carbonyl oxygen. Secondly the transition state structures are almost insensitive to structural variation.No systematic rate- equilibrium relationship of the type predicted by the Bema Hapothle are found which is perhaps not surprising since the structural variation formal-dehyde -+acetaldehyde -* formyl fluoride is scarcely subtle. These are however gas phase calculations and the real situation in solution may well be different. KIEs in ester aminolysis are in fact sensitive to the structure of the nucleophile but this is occasioned by changes in rate-limiting steps.84 79 S. M. van der Kerk J. W. Verhoeven and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1985 1355. 80 S. Hoz S. Gross and D. Speizman J. Chem. SOC.,Perkin Trans. 2 1985 1143. 81 A. Streitwieser M. J. Kaufman D. A. Bors J. R. Murdoch C.A. MacArthur J. T. Murphy and C. C. Shen J. Am. Chem. Soc. 1985 107 6983. 82 (a) R. A. Bednar and W. P. Jencks J. Am. Chem. SOC.,1985 107 7117; (b) ibid. 7126; (c) ibid.,7135. 83 I. H. Williams D. Spangler G. M. Maggiora and R. L. Schowen J. Am. Chem. SOC.,1985 107 7717. 84 1. Kovach M. Belz M. Larson S. Rousy and R. L. Schowen J. Am. Chem. SOC.,1985 107 7360. Reaction Mechanisms -Part (ii) Polar Reactions 71 Ashby showed three years ago that radical anions are present in alkaline solutions of aldehydes undergoing the Cannizzaro reaction. An MNDO study suggests however that the conventional hydride-transfer route is preferred for simple aliphatic aldehydes with a radical chain process involving H-atom transfer as rate-limiting step being a reasonable alternati~e.’~ A simple SET process is not sustained but may be competitive with aromatic aldehydes.The spontaneous dehydration of HC03- to form C02 and H20 is a stepwise process as judged from carbon isotope effects.86 Qotonation of the hydroxyl oxygen appears to yield the zwitterionic intermediate H20-C02- which gives the product in the rate-limiting step. This is supported by the results of model KIE calculations. A detailed mechanism for the acid-catalysed aldol condensation of acetaldehyde has been pre~ented.’~ Production of the equilibrium mixture of aldol and crotonal- dehyde equation 5 is second-order in [MeCHO] contrary to earlier reports. The 2MeCHO MeCH(OH)CH2CH0 +MeCH=CHCHO +H,O (5) excess acidity method88 suggests that a water molecule is involved in the rate-limiting step which is depicted as the base-assisted addition of vinyl alcohol (from enoliz- ation) to protonated acetaldehyde.Excess acidity methods have also been used to study the reactions of substituted acetamides MeCONHR in aqueous H2S04.89 Depending on R and the acidity any one of three mechanistic pathways can prevail N-acyl cleavage with variable transition state hydration N-alkyl fission or sulphon-ation if R is aromatic. Tetrahedral intermediates continue to be of interest. The products of acid hydroly- sis of isomeric methoxy bizyclic and tricyclic orthoesters can be accounted for by the stereoelectronic theory pertaining to breakdown of intermediates.” Some of the intermediates postulated are however incapable of cleaving with stereoelectronic control when in a chair form and the unexpected products arising therefrom result from prior inversion to a boat form.Under stopped-flow conditions bromine reacts instantaneously with a-methoxystyrene PhC(OMe)=CH, to produce (after hydra- tion) the hemiacetal PhC(OH)(OMe)CH,Br. This then breaks down to the observed products PhCOCH2Br and MeOH in the rate-limiting step.” Complex kinetics are observed for the reversible base-catalysed cyclization of cis-chalcone (9) to its cyclic hemiacetal form (10). It is proposed that in dilute buffers proton transfer from (9) is rate-limiting (most unusual) whilst at higher concentrations protonation of the mAr // (9) H. S. Rzepa and J. Miller J. Chem. Soc. Perkin Trans.2 1985 717. 86 P. Paneth and M. H. O’Leary J. Am. Chem. Soc. 1985 107 7381. 87 L. M. Baigrie R. A. Cox H. Slebocka-Tilk M. Tencer and T. T. Tidwell J. Am. Chem. Soc. 1985 107 3640. 88 R. A. Cox and K. Yates Can. J. Chem. 1984 62 2155. 89 L. M. Druet and K. Yates Can. J. Chem. 1984 62 2401. 90 P. Deslongchamps D. Guay and R. Chhevert Can. J. Chem. 1985 63 2493. 91 V. M. Kanagasabapathy and R. A. McClelland J. Chem. SOC.,Chem. Commun. 1985 691. 72 D. J. McLennan anion of ( 10) becomes rate-limiting. In even more concentrated buffers equilibration of the anions is rate-limiting. This unusual behaviour whereby proton transfers are uncoupled from C-0 formation or cleavage appears to result from the stability of the phenoxide as both a nucleophile and leaving group.92 In this context it is pertinent to cite the cyclization of 2'-hydroxychalcones to fla~anones.~~ A conforma- tional step is an important component of the mechanism.The acid-catalysed hydrolysis of an a-arabinofuranoside can occur uia one of two pathways protonation of the exocyclic oxygen expulsion of ROH to yield a cyclic oxonium ion followed by hydrolysis to give the aldose; or protonation of the ring oxygen with rate-limiting ring opening to follow. Depending on the electronegativity of the R group in the departing ROH moiety either pathway can prevail as demonstrated by an l8OKIE The heavy-atom KIEs were evaluated using a novel and sensitive quasi-racemate method. An equimolar mixture of a substrate and its optical antipode (100% "0 labelled) is allowed to react.Any departure of the optical rotation from 0" during the reaction is caused by the KIE which can be numerically evaluated from the rotation versus time curve. An n.m.r. kinetic study (31P,13C 'H) has provided new insight into the stereochemistry of the Wittig reaction. The E/Z ratios of product alkenes are time-dependent as a result of competing kinetic and thermodynamic control and stereochemical drift arises from oxaphosphetane equilibration through the inter- mediacy of reactants. Thus the final alkene stereochemistry cannot be rationalized simply in terms of the comparative rates of formation and destruction of the intermediate^.^^ 9 Some Probes of Polar Mechanisms Last year Taft and Kamlet questioned the validity of Swain's dual-parameter solvent effect equation.This year they take on the Chemometricians of Umei. They argue in a lively and amusing fashion that linear free (and solvation) energy relationships contribute to chemical understanding at the molecular level and may therefore approach the status of scientific laws.96 On the other hand the Chemometricians aver that such relationships are merely local empirical rules of limited predictive value. Taft and Kamlet draw on a vast array of data relating to solvent effects including the fate of the fathead minnow in a variety of solvents in illustrating their case that the correlations with fundamental physical and spectral properties of the solvents do have chemical rather than statistical meaning.One hopes that the Chemometricians will reply to this challenge in an equally spirited fashion and so fulfil the wish of Taft and Kamlet that the heat generated may also shed light. One of the cornerstones of the Swain F-R scale of substituent parameters (for mainly dipolar groups) is the NMe3+ pole. Ab initio calculations reveal that a constant F value for a polar substituent is not possible within the context of a scale based on dipolar groups. Geometric factors are more important for charged sub- 92 R. A. McClelland D. B. Devine and P. E. Sorensen J. Am. Chem. SOC.,1985 107 5459. 93 J. J. P. Furlong and N. S. Nudelman J. Chem. Soc. Perkin Trans. 2 1985 633. 94 A. J. Bennet M. L. Sinnott and W. S. Sulochana Wijesundera J.Chem. SOC.,Perkin Trans. 2,1985 1223. 95 B. E. Maryanoff A. B. Reitz M. S. Mutter R. R. Inners and H. R. Almond J. Am. Gem. SOC.,1985 107 1068. 96 M. J. Kamlet and R. W. Taft Acfa Chem. Scund. Ser. B. 1985 39 611. Reaction Mechanisms -Part (ii) Polar Reactions 73 ~tituents.~' Similarly calculations provide a theoretical scale of substituent resonance parameters a for some 40 substituents some of which lacked well-established values.98 Interestingly NMe,+ is calculated to have an insignificant resonance effect. Swain and the multi-resonance-scale-DP advocates at last agree on something. Theoretical work on isotope effects continues to be useful in aiding the interpreta- tion of experimental studies. Secondary deuterium isotope effects have been calcu- lated for equilibrium heterolyses of 2-propyl substrates by ab initio methods; these correspond to KIE maxima for product-like transition states.99 The Reporter is gratified that maximal a-deuterium KIEs calculated by him using an empirical valence force field model in 1981 are confirmed by the present higher level study.A surprising result is however obtained for P-deuterium isotope effects. Both the conformationally-dependent (hyperconjugative) and -independent (inductive?) components of the isotope effect are influenced by the identity of X a factor which is not usually taken into account when interpreting the results of say solvolysis studies. Thus the carbocationic character of the 2-propyl group in the substrate itself is of crucial importance.Since the transition state in a [1,5]-sigmatropic rearrangement has polar charac- ter4'lo0 we can discuss the H-shifts in this section with a clear conscience. The earlier proposal of Kwart that temperature-dependent hydrogen KIEs signify a linear hydrogen (or proton or hydride) transfer whilst temperature-independent KIEs can be associated with a bent transition state is not supported by simple model KIE calculations on the H-shift in 1,3-pentadiene.lo1 Bent transition state models are capable of yielding strongly temperature-dependent KIEs. Direct MO calculations based on the optimized transition state structure concur; both MND010','02" and ab initio"*' methods were used. All calculations however yielded KIEs significantly lower than the experimental values and vibrationally assisted tunnelling (VAT) has been proposed as the cause of this.lo2" Saunders has published a full account of his calculations on tunnel-related phenomena associated with anomalous secondary KIEs.lo3 The fact that several spectacular examples of a secondary KIE exceeding the equilibrium isotope effect with the KIE being larger for a H-transfer than a D-transfer means that the motions of reacting and non-reacting atoms are coupled in the reaction coordinate vibrational mode and that tunnelling must be of importance.Secondary a-deuterium isotope effects in SN2104 and E2607'04 reactions involving anionic nucleophiles are concentration-dependent. This unexpected finding does little to inspire confidence in mechanistic interpretation but it does serve as a worthwhile caution.We conclude with a report on matters related to the Bema Hapothle. Grunwald has merged Marcus theory and the More O'Ferrall-Jencks energy surface concepts 97 S. Marriott W. F. Reynolds and R. D. Topson J. Org. Chem. 1985 50 741. 98 S. Marriott and R. D. Topsom J. Cfiem. SOC.,Perkin Trans. 2 1985 1045. 99 I. H. Williams J. Chem. SOC.,Chem. Commun. 1985 510. 100 K. S. Replogle and B. K. Carpenter J. Am. Chem. SOC.,1984 106 5751. 101 D. J. McLennan and P. M. W. Gill J. Am. Chem. SOC.,1985 107 2971. 102 (a) M. J. S. Dewar K. M. Merz and J. J. P. Stewart J. Chem. SOC.,Chem. Commun. 1985 166; (b) B. A. Hess L. J. Schaad and J. Pancir 1. Am. Chem. SOC., 1985 107 149. 103 W. H.Saunders J. Am. Chern. SOC.,1985 107 164. 104 K. C. Westaway Z. Waszczylo P. J. Smith and K. S. Rangappa Tetrahedron Leu. 1985 26 25. D. J. McLennan in constructing quantitative potential energy surfaces for processes in which two progress variables a mean progress variable in the reactant-product frame (the Thornton parallel effect) and a disparity progress variable linking hypothetical intermediates (the Thornton perpendicular effect) are imp~rtant."~" Theory has been applied to base- and acid-catalysed addition of alcohols to f~rmaldehyde,"~' and concerted mechanisms are confirmed. The curvature of 'linear' free energy relationships is discussed in detail and it is considered that disparity factors where for instance bond-making runs ahead of electronic reorganization are of consider- able importance.The principle of imperfect synchronization enunciated by Bernas- coni'06 is a formal statement of this fact and an experimental example can be cited.lo7 Despite this linear and parallel Bronsted plots continue to be found and whether their existence results from careful choice of reaction families,"' the failure of the Bema Hapothle,"' or the involvement of high Marcus intrinsic remains a matter for debate. Many apparent anomalies in free energy relationships have in recent years been ascribed to interactions in the transition state which are not present in either reactants or products i.e. to imperfect synchronization. Lewis and co- workers have deliberately attempted to engineer such a situation by employing soft nucleophiles in SN2methyl transfers.* lo Even though soft-soft or hard-hard interac- tions are absent from the identity exchanges the linear Marcus equation holds extremely well over a lo8 rate range.Much remains to be understood. 105 (a) E. Grunwald J. Am. Chem. Soc. 1985 107 125; (b) idem ibid. 4710; 4715. 106 C. F. Bernasconi Tetrahedron 1985 41 3219. 107 F. Terrier J. Lelievre A.-P. Chatrousse and P. Farrell J. Chem. SOC.,Perkin Trans. 2 1985 1478. I08 F. G. Bordwell and D. L. Hughes J. Am. Chem SOC.,1985 107 4737. 109 F. G. Terrier F. L. Debleds J. F. Verchere and A.-P. Chatrousse J. Am. Chem. SOC.,1985 107 307. 110 E. S. Lewis M. L. McLaughlin and T. A. Douglas J. Am. Chem. Soc. 1985 107 6668.

ISSN:0069-3030    

DOI:10.1039/OC9858200059

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Free-radical Reactions By D. GRILLER Division of Chemistry National Research Council of Canada. Ottawa Ontario Canada KIA OR6 1 Synthesis Synthetic methods involving free radicals attained a new maturity in 1985 as investigators moved away from ring closure reactions to more generalized themes. Barton and his colleagues continued their development of syntheses involving thiohydroxamic esters.'-3 These compounds participate in radical chain processes and function as sources of alkyl or aryl radicals which in turn can be trapped by a variety of substrates. For example bromotrichloromethane was used to convert aryl radicals into their corresponding bromides.2 Overall the reaction represented a decarboxylative bromination of aromatic acids which gave far better yields than any of the previously reported procedures (Scheme 1).In similar vein a mixture of oxygen tris(phenylthio)antimony and water led to a sequence of reactions which effectively converted the acid used in the preparation Qs OH 't ArCOzH -ArCOCl -ArCO-N 9 S 0 II ArCO-N + CCls -ArCO; + N 2. 2 CI3CS 'T I CClgBr ArBr + CC13 -Ar-+ CO Scheme 1 D. H. R. Barton and D. Crich Tetrahedron Lett. 1985 26 757; D. H. R. Barton H. Togo and S. 2. Zard Tetrahedron Lett. 1985 26 6349. D. H. R. Barton B. Lacher and S. Z. Zard Tetrehedron Lett. 1985 26 5939. 75 D. Griller of the thiohydroxamic ester into its nor-alcohol (Scheme 2).3Again isolated yields were high >80%.Angoh and Clive developed an interesting method for ann~lation.~ The starting material was an epoxide which was converted by standard routes into a bromoacety- lene. Annulation was achieved by the free radical route described in Scheme 3. 0 II RC-0-N + PhS + R. + COZ + N9 S PhSS R-+ (PhS),Sb -+ RSSb(SPh)2 + PhS. 1 OJH*O ROH + Sb203 Scheme 2 1 Ph,SnH q-+ Ph,Sn Y = CO Me CN SO2 Ph Scheme 3 Yields for the radical process were modest (30-50%) and there was no control of stereochemistry. However previous experience has shown that radical routes of this kind can be developed into general synthetic methods if the reaction conditions are adjusted to suit the kinetic requirements of the individual steps. Similar chemistry was employed to create quaternary carbon centres from tertiary nitro-compounds D.H. R. Barton D. Bridon and S. Z. Zard J. Chem. Soc. Chem. Cornmun. 1985 1066. A. G. Angoh and D. L. J. Clive J. Chem. Soc. Chem. Commun. 1985 980. Reaction Mechanisms -Part (iii) Free-radical Reactions with yields of ca. 50% (Scheme 4).' When the double bond was included in the starting nitro compound cyclizations were readily achieved.' An important charac- teristic of these methods is that there is no overall loss of functionality which was an unattractive feature of the more traditional uses of tin hydrides as reagents. gem-Halogeno-nitro compounds were used in an &2' reaction to produce aliphatic nitro-compounds (Scheme 5).6 This theme was elaborated by Russell and Herold who used a similar SH2' process to synthesize olefins containing groups such as PhS CCl, and PhS02.7 I -C-NO,I + CH2=CH-Y Bu SnH I 3-C-CH2-CH2-Y I Y = CN,C02Me Scheme 4 R'R'C-X + Bu,Sn-+ R'R'C-+ Bu,SnX I I NO2 NO2 T I Bu,SnCH,CH=CH CH2=CHCH2CR'RZ + Bu,Sn.t Bu,SnCH,CH-CH2CR'R2 I I NO2 NO2 X = halogen Scheme 5 In an interesting and efficient synthesis Crozet and Kassar started with aniline and produced tricyclic thiazolidines in four steps the last of which involved a free radical cyclization (Scheme 6).*The method is particularly useful since compounds of this kind are difficult to obtain by other routes. Intramolecular SH2 reactions were used in the synthesis of fused p-lactams (Scheme 7).9 For R = But a 42% yield of the tricyclic product (1) was obtained together with 16% of (2) which was formed by direct reduction.The latter became the dominant product when R = Me. An attempt was made to form a 5-membered ring by a similar reaction." However the major product was the thiol (3) which arose by an interesting abstraction-elimination sequence (Scheme 8). Further examples of free radical methodology for ring closures were reported" and Giese provided a sound overview of the use of free radicals in synthesis.12 N. Ono H. Miyake and A. Kaji Chem. Lett. 1985 635. N. Ono K. Zinsmeister and A. Kaji Bull. Chem. SOC.Jpn. 1985 58 1069. G. A. Russell and L. L. Herold J. Org. Chem. 1985,50. 1037; See also G. A. Russell and P. Ngoviwatchai Tetrahedron Lett. 1985 26 4975.M. P. Crozet and W. Kassar CR. Hebd. Seances Acad. Sci. Ser. 2 1985 300,99. A. L. J. Beckwith and D. R. Boate Tetrahedron Lett. 1985 26 1761. 10 A. L. J. Beckwith and D. R. Boate J. Chem. SOC. Chem. Commun. 1985 797. " C. S. Wilcox and L. M. Thomasco J. Org. Chem. 1985 50 546. G. Stork and N. H. Baine Tetrahedron Lett. 1985 26 5927. K. Shankaran C. P. Sloan and V. Snieckus Tetrahedron Lett. 1985 26 6001. B. B. Snider R. Mohan and S. A. Kates J. Org. Chern. 1985,50,3659. T. A. K. Smith and G. H. Whitham J. Chem. SOC. Chem. Commun. 1985 897; G. Stork and M. Kahn J. Am. Chem. SOC. 1985 107 500; A. L. J. Beckwith D. H. Roberts C. H. Schiesser and A. Wallner Tetrahedron Lett. 1985 26 3349. 12 B. Giese Angew. Chem. Int. Ed. Engl. 1985 24 553. D.Griller R Bu'OOBu' \ R Scheme 6 Br / I Bu,SnH -R. Scheme 7 A simple synthesis of Fremy's salt was developed which will be of great interest to e.s.r. spectroscopists who often use it as a field marker and to those whose synthetic ability is limited.I3 The salt was made in situ by bubbling oxygen through an aqueous solution of sodium nitrite and sodium hydrogen sulphite (Scheme 9)! l3 T. Ozawa and T. Kwan J. Chem. SOC.,Chem. Commun. 1985 54. Reaction Mechanisms -Part (iii) Free-radical Reactions I Me Scheme 8 NO,-+ 2HS03-+ HON(SO3-)2 + OH-HON(SO,-) + O2 -ON(SO,-) + H02-Scheme 9 2 Mechanism Several paper^'^.'^ were published in an attempt to disprove the proposal that the (+ and T states of the succinimidyl radical are thermally accessible at room tem- perature and that they react in different ways.The original hypothesis was based on the observation that P-bromopropionyl isocyanate which is formed by ring opening of succinimidyl was absent under certain experimental condition^.'^ Many of the criticisms expressed in last year's report proved to be well founded and the antagonists finally showed that if the experiments were carried out carefully enough the readily hydrolysed isocyanate was present under all of the experimental condi- tion~.'~ This was sufficient to disprove the u-T hypothesis. However its detractors continued the argument with such zeal that they investigated kinetics under heterogeneous conditions and committed an interesting abuse of statistic^.'^ They achieved a correlation coefficient of 0.97 in one of their plots by dropping 11 out 14 D.D. Tanner C. P. Meintzer and S. L. Tan J. Org. Chem. 1985 50 1543; D. D. Tanner and C. P. Meintzer J. Am. Chem. Soc. 1985 107 6584. 15 D. D. Tanner D. W. Reed S. L. Tan C. P. Meintzer C. Walling and A. Sopchik J. Am. Chem. Soc. 1985 107 6576. D. Griller of 44 data points! It is noteworthy that two theoretical studies were published which were quite consistent with the original u-T propo~al.'~,'' Skell and Baxter" observed an interesting cage effect during the radical chain chlorination of cyclohexane. They found that the reaction of chlorine (10 mol YO) with neat cyclohexane at 20 "C gave 6% of polychlorinated product.However the yield of polychlorinated material went up to CQ. 50% when the experiment was repeated at the same cyclohexane :chlorine ratio in carbon tetrachloride or freon as solvent. The results were rationalized in terms of the reactions described in Scheme 10. The essential feature of this mechanism is that the chlorine atom formed via the reaction of cyclohexyl with molecular chlorine was so reactive that it tended to attack the first hydrogen donor which it encountered. When carbon tetrachloride was the solvent an in-cage reaction dominated which ultimately gave rise to dichloride. However in neat cyclohexane the molecules forming the cage were good hydrogen donors themselves and scavenged the chlorine atoms so that mono- chlorination was dominant.Does a 1,Chydrogen shift occur in p-( alky1thio)ethyl radicals? This question was addressed by Grossi et aLi9 in an e.s.r. study. It was found that that photolysis of dimethyl disulphide in the presence of ethylene at -140°C gave spectra due to CH3SCH2CH2 and CH2SCH2CH3. The same radicals were observed when trimethyl- stannyl radicals were used to abstract bromine from CH3SCH2CH2Br. The CH2SCH2CH3 radical was thought to have been formed by the intramolecular rearrangement described in Scheme 11. An intramolecular process was thought to have been likely since the ratio of radical concentrations seemed to be independent CH3 SCH2CH2 4CH2 SCH2CH3 Scheme 11 16 M. J. Field I. H. Hillier S. A. Pope and M. F. Guest J. Chem. SOC.,Chem. Commun. 1985 219.l7 M. J. S. Dewar and S. Olivella J. Chem. SOC.,Chem. Commun. 1985 301. 18 P. S. Skell and H. N. Baxter 111 J. Am. Chem. Soc. 1985 107 2823. 19 D. Casarini L. Grossi L. Lunazzi and G. Placucci J. Org. Chem. 1985 50 703. Reaction Mechanisms -Part (iii) Free-radical Reactions of the concentrations of the starting materials. This is an unusual rearrangement and its Arrhenius parameters would certainly be of interest. The photodissociation of azomethane was studied in a remarkable experiment in which the evolution of the methyl radical and of nitrogen were monitored by coherent anti-Stokes Raman spectroscopy.'' It was found that both products were formed in <2 ns. However the population of the nitrogen vibrational levels suggested that it was derived from a diazenyl radical.Thus the photodecomposition although rapid led to single bond rather than two bond cleavage (Scheme 12). hv R-N=N-R +R-N=N* + R. + Re + N2 + R. Scheme 12 Sakurai et al. photolysed [(acyIoxyI)methyI]benzyIsilanesin an attempt to prove that the benzyl-silicon bond is easily cleaved by this method.21 The acyloxy group served as an intramolecular trap for the silyl radical and led to the products shown in Scheme 13. Product (6) was of particular interest since it must have been derived from radical (5) an intermediate in the rearrangement. By contrast all of the evidence on the rearrangement of simple acyloxy radicals suggests that cyclic Me /I + ~CH2~iCH20CR O t H , [ Me2ryR] Me 0 '2'-0 cage Scheme 13 20 P.L. Holt K. E. McDurdy J. S. Adams K. A. Burton R. B. Weisman and P. S. Engel 3. Am. Chem. Soc. 1985 107 2180. 21 M. Kira H. Yoshida and H. Sakurai 1.Am. Chem. Soc. 1985 107 7767. D. Griller structures analagous to (5) are at best transition states in the rearrangement.22 The authors extended their investigation of the silicon rearrangement using deuterium labelling and e.s.r. studies. They found that (6) must have been formed uia an in-cage reaction between the benzyl radical and (5) whereas cage escape led to product (8). It was also shown that (5) must have had a rather short lifetime since only (4)and (7) were detected by e.s.r. spectroscopy when (4)was generated independently. In a similar search for radical intermediates in a rearrangement process Porter and Zuraw demonstrated that radical (9) was not formed in the allylic rearrangement of hydroperoxides (Scheme 14).23 Their proof came from a study of the reaction between (10) and sodium borohydride in air at 0 "C where they found substantial yields of (11)-( 13).The presence of (13) proved that (9) is easily trapped by oxygen (Scheme 15). However (13) is not formed in the hydroperoxide rearrangement. It therefore follows that (9) is not an intermediate in that process. It was suggested OOH 00. I I OOH Scheme 14 0-0 0 0-0 NaBH UR2 I R1 R' . I HgBr I (10) OOH (13) Scheme 15 22 L. R. C. Barclay J. Lusztyk and K. U. Ingold J. Am. Chem. SOC.,1984 106 1793 and references cited therein.23 N. Porter and P. Zuraw J. Chem. SOC.,Chem. Commun. 1985 1472. Reaction Mechanisms -Part (iii) Free-radical Reactions that structures akin to (9) must be transition states in the hydroperoxide rearrange- ment. However oxygen elimination from the starting peroxyl radical followed by readdition would also explain the observations. Sustmann and his colleagues carried out a comprehensive e.s.r. study of rearrange-ments involving radicals of the general structure C7H7(Scheme 16),24 and developed many imaginative methods for their generation. They found that (14) when isolated in an adamantane matrix undergoes a slow rearrangement to (15). Radical (16) could not be detected in solution even below -146 "C since it rearranged rapidly to (14).The structurally related radical (17) showed no sign of rearrangement to (14) during the millisecond timescale of the solution experiment. However when attempts were made to generate (17) at low temperatures in matrices this radical was not observed and only the spectrum of (15) was detected. This surprising result was thought to be due to a photochemically induced rearrangement of (17) since a photolytic route was used for radical generation. 3 Structure A variety of persistent radicals were discovered in 1985. Scherer and his colleagues25 added fluorine to F-3-isopropyl-4-methyl-2-pentene and obtained the free radical F-2,4-dimethyl-3-ethyl-3-pentyl in concentrations as high as 3M! At room tem- perature the radical was quite persistent and did not react with 02,C12 Br2 12 acid or base.It had a half-life of 1 hour at 100 "C and decomposed cleanly to give trifluoromethyl. Its remarkable persistence and inertness was acribed to steric protec- tion of the radical centre. The e.s.r. spectrum showed that the central ethyl group was locked in a conformation which minimized steric interactions thus supporting this conclusion. Similar properties were discovered for F-di-isopropylmethy126 which was obtained by addition of CF3 to F-4-methylpent-2-ene. This radical showed a large hyperfine splittings of 6.2 mT and 1.5 mT from the (Y and p fluorines respectively. 24 R. Sustmann D. Brandes F. Lange and U. Nuchter Chem. Ber. 1985 118 3500. 2s K. V. Scherer Jr. T. Ono K. Yamanouchi R. Fernandez and P.Henderson J. Am. Chem. SOC.,1985 107 718. 26 S. R. Allayarov A 1. Mikhailov and I. M. Markalov Izv. Akad Nauk SSSR Ser. Khim. 1985 1667. 84 D. Griller Neugebauer and Siege127 generated 1,2,4,5-tetrazin- 1 (2H) -yl radicals (18) by hydrogen abstraction from the corresponding tetrazines. The radicals were par- ticularly long lived and their e.s.r. spectra pointed to a fairly even distribution of spin density on the 1 2 4 and 5 positions of the ring. R / N-N’ ---ArS-N-C-N-SAr R< N-N /bR I Ar N,N’-Bis(ary1thio)arenecarboximidamidylradicals (19) were generated by a variety of routes including oxidation of the parent amines by lead dioxide.28 Theoreti- cal calculations and the e.s.r. hyperfine splittings suggested that most of the spin density was concentrated on the nitrogen and sulphur atoms and that very little delocalization was afforded by the aryl groups.The radicals formed nitrogen bonded dimers which had a dissociation enthalpy of 20-25 kJ mol-’ and which were isolable as dark green or brown crystalline solids. Several theoretical calculations on alkyl radicals appeared but were not always particularly informative. An attempt was made to discover why ab initio calculations did not predict radical hyperfine splittings particularly well.29 However a number of minor effects were cited for each case investigated and no particularly firm conclusions were reached. In a lengthy pole mi^,^' the effect of alkyl group conforma- tion on pyramidalizing a radical centre was discussed and it was concluded that ‘a planar tricoordinate atom placed in an unsymmetrical environment will pyramidalize towards a staggered conformation’.This fairly obvious deduction hardly needed the benefit of theory and did little to advance the subject beyond the point where Packansky had left it with his outstanding experimental and theoretical work.31 However an interesting calculation appeared on the t-butyl radical32 which suppor- ted earlier conclusions based on e.s.r. data that the rotation of the methyl groups and the inversion of the radical centre were strongly coupled. Illustrations of the potential energy surface made the treatment particularly easy to follow. A 1,3-biradical (20) was detected by flash photolysis methods upon irradiation of its cyclopropane precursor.33 Its lifetime was a few nanoseconds in solution at room temperature.While the ‘1,3-’ description is formally correct the aryl groups would almost certainly have delocalized the unpaired electrons to a significant ’’F. A. Neugebauer and R. Siegel Chem. Ber. 1985 118 2157. 2a Y. Miura T. Kunishi M. Isogai and M. Kinoshita J. Org. Chem. 1985 50 1627. 29 D. Feller and E. R. Davidson Theor. Chim. Acta 1985 68 57. 30 M. N. Paddon-Row and K. N. Houk J. Phys. Chem. 1985 89 3771. 31 J. Pacansky and J. S. Chang J. Chem. Phys. 1981 74 5539 and references cited therein. 32 I. Carmichael 1. Phys. Chem. 1985 89 4727. 33 K. Mizuno N. Ichinose and Y. Oksuji J. Am. Chem. SOC.,1985 107 5797. Reaction Mechanisms -Part (iii) Free-radical Reactions extent.In a more elegant approach Snyder and D~ugherty~~ made 2,4-dimethylene- 1,3-cyclobutadiyl (21) by photolysis of its parent azo compound. The rationale behind this experiment was that the biradical would not be able to close readily to its covalent isomer (22) since the latter would be a highly strained compound. This expectation was well justified and an excellent e.s.r. spectrum of the triplet biradical was detected. Symons and his colleagues made an important contribution to the interpretation of e.s.r. spectra in matrices.35 They showed that y-radiolysis of methyl or t-butyl chloride at 77.K in rigid matrices of tetramethylsilane or adamantane gave spectra of alkyl radicals which were perturbed by the presence of the halide anion.The spectra underwent an irreversible change to give the pure radical spectra when the matrices were annealed. Thus the annealing process allowed the radical and its neighbouring anion to separate. The radical-anion interaction was therefore thought to be very weak and was viewed as a collision or charge transfer complex. It was concluded that true radical anions of alkyl halides were unlikely to be formed in condensed phases. Muonium is the light isotope of hydrogen in which the proton nucleus is replaced by a positive muon. The technique of muon spin rotation p.s.r. was used to investigate the reaction between muons and 2-propanone. The resulting radical was identified as (CH3)2COMu and comparison with (CH3)2COH provided a great deal of information on subtle conformational effects and solvent interactions involving -0Mu and its equivalent OH group.36 Muons reacted readily with phenylacetylene to give the vinyl radical PhC=CHMu which was again detected by p.~.r.~' The spectral parameters were consistent with a linear structure which was not an artefact of rapid vibrational averaging on the timescale of the experiment.Several cyclohexadienyl radicals were detected in the same experiment and these resulted from muon addition to the aromatic ring. Generation of t-butylperthiyl by a number of routes allowed conclusive iden- tification of its e.s.r. and optical absorption spectra.38 The methods included photoly- sis of Bu'S4Bu' and of Bu'SSCl as well as triplet sensitized photolysis of Bu'SSBu'.The radical showed a broad line in its e.s.r. spectrum at g = 2.002 and a strong optical absorption band at 400 nm. It was demonstrated that perthiyl radicals have frequently been misassigned as thiyl radicals in experiments on the radiolysis and photolysis of disulphides. An inorganic analogue H3N-+BH2 of the ethyl radical was detected by e.s.r. spectroscopy on photolysis of a t-butyl alcohol-dimethyl ether solution containing 34 G. J. Snyder and D..A. Dougherty J. Am. Chem. SOC.,1985 107 1774. 35 M. C. R. Symons and I. G. Smith J. Chem. SOC.,Faraday Trans I 1985 81 1095. 36 A. Hill M. C. R. Symons S. F. J. Cox R. de Renzi C. A. Scott C. Bucci and A. Vecli J. Chem. SOC. Faraday Trans. 1 1985 81 433. 37 D. A.Geeson M. C. R. Symons E. Roduner H. Fischer and S. F. J. Cox Chem. Phys. Lett. 1985 116 186. 38 T. J. Burkey J. A. Hawari F. P. Lossing J. Lusztyk R. Sutcliffe and D. Griller J. Org. Chem. 1985 50. 4966. 86 D. Griller di-t-butyl peroxide and H N-+ BH3?9 The radical showed equal hyperfine splittings from all five hydrogens which was thought to have been fortuitous rather than a consequence of rapid hydrogen scrambling. The spin population in the boron 2s orbital (5.9'/0) was significantly higher than that in the C,s orbital of the ethyl radical (3.6%) and was thought to point to a bent radical structure although a higher amplitude of vibration at boron about a planar structure would have led to the same observation. Cyclobutadiene radical cations were generated in a most unusual way.40 Irradi- ation of but-2-yne in a solid matrix did not give rise to an e.s.r.spectrum. However on annealing to 150 K a strong spectrum of the tetramethylcyclobutadiene radical cation was detected aH = 0.87 mT (12H); g = 2.0030. It was thought that the initial radiolysis produced the radical cation of the butyne which went undetected because of its broad spectrum. On annealing the radical cation migrated through the matrix and reacted with a molecule of the alkyne to give the cyclobutadiene radical cation which was detected by e.s.r. spectroscopy. A similar effect was achieved in fluid solution when deca-2,8-diyne closed intramolecularly (Scheme 17). It is interesting to note that these reactions are formally symmetry forbidden.Scheme 17 4 Kinetics Reactions of carbon-centred radicals with a variety of molecules that are frequently used as traps or chain carriers were the subject of several investigations. Rate constants for the reactions of alkyl radicals with carbon tetrachloride were ca. lo4 M-' s-l at 300 K with Arrhenius A-factors and activation energies of lo8M-' s-' and 20 kJ mol-' re~pectively.~' Rate constants for hydrogen abstraction by carbon-centred radicals from cyclo- hexadiene were very sensitive to the exothermicity of the reaction.42 Thus for methyl the rate constant at 300 K was 1.3 x lo5M-' s-' (AH = -142 kJ mol-') whereas for ally1 and benzyl the rate constant was <lo2 M-' s-' (AH = -59 kJ mol-'). Similar effects were seen when tributylgermane was used as the substrate.43 The rate constant for hydrogen abstraction by phenyl (2.6 x 10' M-' s-' at 300 K) was some three orders of magnitude greater than that for n-alkyls (1.0 x lo5M-' s-').In an elegant kinetic e.s.r. experiment Munger and Fischer measured rate con- stants for the reaction of t-butyl with a variety of olefins.44 In essence they monitored perturbations of the bimolecular decay of the t-butyl radical as a function of olefin concentration. The range of rate constants which was accessible was surprisingly 39 J. A. Baban V. P. J. Marti and B. P. Roberts J. Chem. Res. (S) 1985 90 40 J. L. Courtneidge A. G. Davies S. M. Tollerfield J. Rideout and M. C. R. Symons J. Chem. SOC. Chem. Commun. 1985 1092. 41 J.A. Hawari S. Davis P. S. Engel B. C. Gilbert and D. Griller J. Am. Chem. SOC.,1985 107 4721. 42 J. A. Hawari P. S. Engel and D. Griller fnt. Chem. Kinet. 1985 17 1215. 43 L. J. Johnston J. Lusztyk D. D. M. Wayner A. N. Abeywickreyma A. L. J. Beckwith J. C. Scaiano and K. U. Ingold J. Am. Chem. Soc. 1985 107 4594. 44 K. Munger and H. Fischer Int. J. Chem. Kinet. 1985 17 809. Reaction Mechanisms -Part (iii) Free-radical Reactions 87 large 60 M-' s-l (1,2-dimethylethylene) to 4.6 x lo5 (2-vinylpyridine). In simple series e.g. mono- and 1,l -disubstituted ethylenes rate constants increased and activation energies decreased with increasing electron affinity of the olefins. Two papers provided concrete data on biologically important phenolic antioxi- dants.Barclay and his c011eagues~~ studied the oxidation of linoleic acid in sodium dodecyl sulphate micelles. They found that micelle-soluble phenol vitamin E functioned as an efficient oxidation inhibitor whereas water soluble vitamin C was far less effective. However when the two were combined vitamin C was capable of reducing oxidized vitamin E with high efficiency so that the latter continued effective inhibition of the oxidation. The conformational and electronic factors which regulate the antioxidant activity of phenols were also explored in great The quantitative work contrasts sharply with the speculative and sometimes bizarre perceptions about the role of free radicals in v~vo.~~ The photochemistry of excited states of arylmethyl radicals was investigated by flash photolysis techniques in which a laser pulse is used to produce the groundstate of the radical of interest and a second pulse is used to generate the excited ~tate.~**~~ Relaxation to the groundstate was generally rapid so that possibilities for observing chemical reactions of the excited state were limited.The excited state of the 1 -napthylmethyl radical was converted back to the groundstate by oxygen with a rate constant of 4 x lo9 M-' s-' and there was no evidence that the excited state formed a peroxy radical.49 In general reactions of the excited states of free radicals seemed to involve relaxation uia charge transfer complexes with the substrates. The lifetimes of triplet biradicals were investigated by two quite different tech- niques.Closs and Redwine" used nanosecond flash photolysis for biradical gener- ation. Lifetimes of ca. 100ns were measured by looking at product formation at different time intervals using pulsed n.m.r. detection. This technique took advantage of CIDNP enhancement in the spectra. Most were 1,7- or 1,s-biradicals with unpaired electrons localized on CH2 and CO centres. It was concluded that the lifetimes were controlled by intersystem crossing and that they were relatively long because of a poor match of singlet and triplet levels rather than a lack of mixing interactions. Doubleday et aL5' used laser flash photolysis in a related study and reached somewhat different conclusions. They compared lifetimes for biradicals centered on two benzylic carbons with those located on a benzylic and an acyl centre.The latter had much shorter lifetimes which was thought to be due to enhanced spin-orbit coupling brought about by the presence of the acyl group. These authors also systematically varied the distance between the radicals and found that lifetimes were longest when 8-10 membered rings were being formed as products. By drawing an analogy with other cyclization reactions they concluded that the radical centres must come close together before intersystem crossing can take place. 45 L. R. C. Barclay S. J. Locke and J. M. MacNeil Can. J. Chem. 1985 63 366. 46 G. W. Burton T. Doba E. J. Gabe L. Hughes F. L. Lee L. Prasad and K. U. Ingold J. Am. Chem. SOC.,1985 107 7053. 47 See for example P.Henriksson K. Bergstrom and 0. Edhag Thrombosis Rex 1985 38 195. 48 J. C. Scaiano M. Tanner and D. Weir J. Am. Chem. SOC., 1985,107,4396; A. Bromberg K. H. Schmidt and D. Meisel J. Am. Chem. SOC.,1985 107 83. 49 L. J. Johnston and J. C. Scaiano J. Am. Chem. SOC., 1985 107 6368. 50 G. L. Closs and 0. D. Redwine 1. Am. Chem. SOC 1985 107 4543. 51 M. B. Zimmt C. Doubleday Jr. 1. R Could end N 'J Turro J. Am. Chem. SOC.,1985 107 6724. 88 D. Griller Chen and Paul" extended the technique of optical modulation spectroscopy in which transients are generated by modulated photolysis and are detected optically by phase sensitive means. They developed a method for measuring bimolecular decay kinetics and extinction coefficients for radicals that did not require measure- ment of the rate of radical generation.This 'actinometry free' method relied upon detecting the kinetic behaviour of the radical at a point where its optical absorption spectrum overlapped with that of the starting materials and/or reaction products. In essence the extinction coefficient of the radical was related to the known coefficients for the persistent molecules. As a test of the method they determined ~ ~~~ extinction coefficients for t-butyl (E = 230 f30~ M-' cm-' and &230nm = 910 f 100 M-' cm-') and found 2k = (9.4 f 1.4) x lo9 M-'s-' for the termination rate constant. These results were in excellent agreement with the data obtained by other methods. Radical rearrangments were again the focus of several investigation^,^^*^^ in part because of their usefulness as 'radical clocks'.In what was technically the most unusual of these,54 Fischer and his colleagues synthesized radicals by muon addition to double bonds and obtained their lifetimes from the decay of the resulting p.s.r. signals. The timescale of the technique is very restricted (0.5-1.0~~) and while Arrhenius parameters were reported they seem unlikely to be very accurate in view of the limited range for rate constant measurements. 5 Thermochemistry Heats of formation of simple radicals were again the subject of controversy. A shock tube study of 1,3-butadiene pyrolysis55 led to AHf,298(CH,=CH) = 265 f8 kJ mol-' whereas studies of the ion molecule reaction56 between CHZ and C2H2 giving CH; and vinyl led to a value of 301 f8 kJ mol-' and hence to BDE(CH2=CH-H) = 464 f8 kJ mol-'.It was noted that literature values for the heats of formation of vinyl cluster around the two values given above and it was suggested that a low lying excited state of the radical or of the cation might be implicated in one of the sets of experiment^.^^ Tsang reviewed a great deal of data on the thermal decomposition of alkyl radicalss7 and reiterated earlier arguments in favour of higher values for C-H bond strengths than those which are normally accepted." His argument is strongly suppor- ted by data accumulated over the last four years with the exception that the recommended value of BDE(Bu'-H) = 404.6 kJ mol-' is ca. 10 kJ mol-' higher than more recent values.What is perhaps most significant is that the original data were dismissed by subsequent reviewers. Straightforward prejudice by reviewers in favour of certain sets of data (normally their own) is a common feature of modem radical thermochemistry. This is harmful since unbalanced reviews cause a great deal of confusion amongst end users who are often not specialists in the field. 52 T. Chen and H. Paul J. Phys. Chem. 1985 89 2765. 53 M. Newcomb and W. G. Williams Tetrahedron Lett. 1985 26 1179; B. Maillard and J. C. Walton J. Chem. SOC.,Perkin Trans. 2 1985 443. 54 P. Burkhard E. Roduner and H. Fischer Znt. J. Chem. Kinet. 1985 17 83. 55 J. H. Kiefer H. C. Wei R. C. Kern and C. H. Wu Int. J. Chem. Kinet. 1985 17 225. 56 R. B. Sharma N.M. Semo and W. S. Koski Znt. J. Chem. Kinet. 1985 17 831. 57 W. Tsang J. Am. Chem. SOC.,1985 107 2872. 58 D. M. McMillen and D. M. Golden Ann. Rev. Phys. Chem. 1982 493. Reaction Mechanisms -Part (iii) Free-radical Reactions The thermolysis of 2,3-di- l-adamantyl-2,3-dimethylbutane to 2-( 1-adamanty1)pro-pyl radicals was the subject of a careful in~estigation.’~ Steric congestion in the parent hydrocarbon was quite acute as evidenced by long bond lengths (163.9 pm for the central C-C bond). As a consequence thermal cleavage at 180 “Cwas facile and required an activation energy of only 182.7 f 0.4 kJ mol-‘. The reduction and oxidation potentials of several transient carbon-centred radicals were measured by a new technique.60 The radicals were generated by modulated photolysis of appropriate precursors in acetonitrile solution.Their electrochemical properties were measured using phase sensitive detection such that the output of the instrument was a polarogram of the free radical. Traces with excellent signal to noise ratios were detected when radical concentrations were ca. M and lifetimes were ca. s. As an example the reduction and oxidation potentials of the benzyl radical were found to be -1.78 and 0.40 V with respect to the silver-silver nitrate electrode. The capto-dative effect was again persued with vigour. Sustmann and his col- leagues61 measured the rotational barrier in the ‘capto-dative’ a-cyano-a-methoxy- benzyl radical (41 f4 kJ mol-’). However comparison with rotational barriers in a-monosubstituted benzyl radicals revealed no special stabilization which exceeded the additivity of the substituent effects.Rotational barriers about the C-N bonds in aminoalkyl radicals:’ H2NCHR were found to be greater when R was an acceptor group than a donor. Again there was no evidence that the combined effect of the two groups (H2N and R) actually exceeded the sum of the effects due to the individual groups. Some evidence in favour of the capto-dative effect was obtained in an e.s.r. study of a,a-disubstituted benzyl radicals containing a p-methyl group.63 The hyperfine splitting due to the latter functioned as a device for measuring changes in spin density at the a-position. A very small synergistic effect was finally demonstrated when the combined effects of an a-cyano and an a-methoxy outweighed the sum of the effects due to the individual groups.It seems that the capto-dative effect in simple organic systems is likely to be so small as to be beyond the range of true thermochemical measurements. 59 M. A. Flamm-ter Meer H.-D. Beckhaus K. Peters H.-G. von Schnering and C. Ruchardt Chem. Ber. 1935 118,4665. 60 D. D. M. Wayner and D. Griller J. Am. Chem. Soc. 1985 107 7764. 61 H.-G. Korth P. Lommes W. Sicking and R. Sustmann Chem. Ber. 1985 118 4627. 62 I. MacInnes J. C. Walton and D. C. Nonhebel J. Chem. Soc. Chem. Cornmun. 1985 712. 63 L. Sylvander and L. Stellar Tefrahedron Lett. 1985 226 749.

ISSN:0069-3030    

DOI:10.1039/OC9858200075

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (i) Hydrocarbons By B. V. SMITH Department of Chemistry King‘s College London (KQC) Kensington Campus Campden Hill Road London W8 7AH 1 Alkanes Efficient photochemically induced reduction of alkenes or alkynes relies on Pt-Ti02 powder suspended in ethanol. Some isomerization was noted for alkenes and more highly substituted compounds e.g. Me2C=CMe2 gave notably lower yields. Inter- estingly oct-2-yne furnished principally the cis-2-ene after 24 h without any measur- able quantity of the trans-isomer.’ Photosensitized reductive cleavage of an alkyne R-CECH mediated by [Ru(bipyr),12+ triethanolamine and [RuL,( H20)]’+ as respectively sensitizer electron donor and electron acceptor/ catalyst afforded methane and RCH3. This process was compared to nitrogen fixation and the stoicheiometric expression in Scheme 1 expresses this.Evidence was secured that the complex (1) was formed as the primary intermediate followed by rearrangement to (2) and cleavage.2 H-CGC-H + 6H+ + 6e + 2CH Scheme 1 H Methylating agents e.g. Me2S04 were transformed into hydrocarbons over zeolite H-ZSM-5; evidence was obtained that a trimethyloxonium ylide was not in~olved.~ Homocoupling of benzylic halides via NiBr2(PPh3)’-Zn-Et,NI proceeded ~moothly;~ in a few cases there was an accompanying dehalogenation. Three studies on alkane hydroxylation have been rep~rted;~ photolytic reaction of H202 with a H. Yamataka N. Seto J. Ichihara T. Hanafusa and S. Teratani J. Chem. SOC.,Chem. Commun. 1985 788.Y. Degani and I. Willner J. Chem. SOC.,Chem. Commun. 1985 648. R. Hunter and G. J. Hutchings J. Chem. Soc. Chem. Commun. 1985 1643. M. lyoda M. Sakaitani H. Otsuka and M. Oda Chem. Lett. 1985 127. S. N. Sharma H. R. Sonawane and S. Dev Tetrahedron 1985,41,2483; H.-J. Schneider and W. Muller J. Org. Chem. 1985 50 4609; K. Suslick B. Cook and M. Fox J. Chem. SOC.,Chem. Commun. 1985 580. 91 B. V. Smith range of hydrocarbons has been explored and with for example n-octane a mixture of isomeric octanols (and unidentified products) was obtained. A thorough analysis of the peracid-mediated reaction has been published which examines stereochemistry steric effects substituent and solvent effects. 'Shape-selective hydroxylation' has been examined in the PhIO-porphyrin system where it was found that increasingly hindered porphyrins led to enhanced positional selectivity with increasing chain length in the alkane.A vigorous defence of the mechanism for photochemical chlorination of alkanes6= has been given by Ingold and co-workers6' in which the proposal of Skel16" has been rejected. Five potential sources of chlorine atoms were used in an exhaustive kinetic spectroscopic and product study of the chlorination of dimethylbutane in the presence of benzene. Although the earlier proposal6" lacked kinetic data these have now been fully supplied and the conclusions reinforce the earlier view that only two species are involved -c1' and C6H6Cl'. The senior author combines a blend of humour and acerbity in this paper and doffs his hat to G.Russell. The rates of reaction of trichloromethyl radicals and alkanes have been compared to those of alkyl radicals and CC1,; the origin of rate enhancement in solution for the second process (compared to the gas phase) is not entirely clear.7 The organometallic chemistry of alkanes has been reviewed.* 2 Alkenes Synthesis.-Reduction of alkynes with Me3Al-C12-ZrCp2 proceeds in a stereo- and regio-defined sense to give alkenes. As shown in Scheme 2 the product ratio of (5) :(6) was 96 :4; (3) was judged to represent the favoured geometry of the intermedi- ate organo-aluminium compound since quenching with D20 gave 96% E-(7).9A useful variation was formation of iodoalkene by iodination of the intermediate.This process of metallation was catalytic in Zr and probably proceeds via Zr-assisted A1-C bond formation; in the absence of Zr no reaction took place. Alkynes containing a B-H bond gave lower selectivity because of hydrometallation which can be overcome by using a chlorodialkylalane instead of Me3Al. Ph H PhCECH -\/" + phH Me (3) AlMe2 MezAl Me ii H ph)+H Me D Me H (7) Reagents i Me,Al/Cl,ZrCp,; ii 3M-HCI Scheme 2 (a) G. A. Russell J. Am. Chem. SOC.,1958 80 4997; (b) N. J. Bunce K. U. Ingold J. P. Landers J. Lusztyk and J. C. Scaiano ibid. 1985 107 5464; (c) P. S. Skell ibid. 1983 105 120. J. A. Hawari S. Davis P. S. Engel B. C. Gilbert and D. Griller J. Am. Chem. SOC.,1985 107 4721. R. H. Crabtree Chem. Rev. 1985 85 245.E. Negishi D. E. Van Horn and T. Yoshida J. Am. Chem. SOC.,1985 107 6639. Aliphatic Compounds -Part (i) Hydrocarbons 93 The system NaBH,-PdC1,-polyethylene glycol-CH,Cl represents the first use of NaBH to reduce an acetylenic function." The preference is for cis-product although examples were recorded of trans-alkene formed in significant quantity. Reduction to alkane also occurs notably with Me02CCECC02Me (44%); the remainder of the product was MeO,CCH=CHCO,Me (27% ;trans) and the cis-diester (10%). The method is quick (30 min) convenient (10 "C) and given efficient separation of products seems certain to be exploited. Replacement of PEG by EtOH gave a less satisfactory system. Secondary alkylphenylselenides gave with various oxidants trans-alkene independently of the amount of oxidant; with the analogous tellurides product geometry was a function of the reactant :oxidant ratio." Brief mention will now be made of some routes to functionalized alkenes.The adduct RCH(OLi)CH( SPh)OMe [from RCHO-LiCH2( SPh)OMe] was transformed into the xanthate which on alkylation followed by reduction (Bu,SnH) gave RCH=CHOMe. Selectivity was low; for R = PhCH, the ether was a 42 :58 2 :E-mixture.' An efficient route to E-vinyl sulphides as shown in Scheme 3 gave almost complete isomeric p~rity;'~" an alternative process is compared in the same Scheme.l3 H ii R3S IC=CR* -R:B +(-HH I R' R:B R' I iii Reagents i R:B; ii R3SMgBr; iii BuLi then aq. NaOH R3S H R' R OSiMe3 \ i\ / CHCHO -R CHCH, / R'/ R' SH I ii ">=<" R' SR2 Reagents i HIS Me,SiCI C,H,N 25 "C; ii NaH-DMF 0 "C then R2X 0 -P 25 "C Scheme 3 An efficient stereoselective (>%YO isomeric purity) preparation of 2-1,2-dihalogenoalkenes relies on bromoboration of alkynes affording RC( Br)=CHBBr which with XCl (X = Br or I) gives RC(Br)=CHX.14 Alkenyl io$onium compounds e.g.(8) obtained from precursors (9)by reaction with PhIO-Et,OBk show enhanced 10 N. Suzuki Y. Kaneko T. Tsukanaka T. Nomoto Y. Ayaguchi and Y. Izawa Tetrahedron 1985,41,2387. I' S. Uemura Y. Hirai K. Ohe and N. Sugita J. Chem. SOC.,Chem. Commun. 1985 1037. 'I J.-M. Vatele Tetrahedron Lett. 1984 25 5997. l3 (a) M. Hoshi Y. Masuda and A. Arase 1.Chem. SOC.,Chem. Commun. 1985 1068; (b)D.N. Harpp T. Aida and T. H. Chan Tetrahedron Lett. 1985 26 1795. 14 S. Hara T. Kato H. Shimizu and A. Suzuki Tetrahedron Lerr. 1985 26 1065. B. V. Smith + Ph,+pSiMe3.BF3 C8HI7 SiMe3 R rl R2 RxiMe3 R=<' R3-hBF4 R2 R3 H >=(H 14*M H (8) (9) (10) (11) reactivity in replacement behaving like activated vinyl halides; a range of displace- ment reactions with R,CuLi KCu(CN), CuS0,-NaNO, PhSNa and CUX-KX (X = C1 Br or I) was listed and the appropriate products obtained in high yield.15 The reaction of (10) (E or 2)with PhIO-BF,-Et,O gave via elimination from (ll) an alkyne in good/excellent yield.16 Other miscellaneous processes include generation of vinyl triflates (from enones) and preparation of the interesting compounds (12) which are potential precursors of carbonyl compounds via base-catalysed deprotonation and cleavage." R' CH=C( SO Ar)C( OH)R* R3 (12) Reactions.-A report has appeared of the regioselectivity of radical addition to alkenes.'* Hydroboration still attracts attention and a reinvestigation of the kinetics of addition of disiamylborane (dimer) in THF at 0 "C showed 3/2 order kinetics which was interpreted as arising from dissociation of dimer prior to addition to the alkene.Extension of borane addition to acylic or cyclic trienes has showed that it is possible to isolate mixtures of cyclic alcohols after a sequence of heating the primary product with CO under pressure followed by oxidation with alkaline H2O2.I9 Asymmetric hydroboration in the hands of Masamune and co-workers has been improved by preparation of a new class of borolane e.g.(13) and (14) of R,R-and S,S-configuration.*' Although the preparation is more costly and elaborate than with other chiral boranes it has the advantages of (i) stability to air and water (ii) high enantiomeric excesses from di- and tri- substituted alkenes and (iii) predictable configuration in the derived alcohols. Even these reagents give low e.e. with 1,l-dialkylethylenes and no truly general asymmetric hydroboration is yet possible with this class. A general account of asymmetric transformations of alkenes has appeared.2' Other reactions of boration included here for convenience are the preparation of (19 a precursor for a halogeno-substituted unsaturated ketone (16) formed in high isomeric purity and formation of (17) which afforded (18) with R3SMgBr oxidized by H202-OH-to R'CH2COSR3.22 l5 M.Ochiai K. Sumi Y. Nagao and E. Fujita Tetrahedron Lett. 1985 26 2351. I6 M. Ochiai K. Sumi Y. Nagao E. Fujita M. Arimoto and H. Yamaguchi J. Chem. SOC.,Chem. Commun. 1985 697. 17 G. J. Crisp and W. J. Scott Synthesis 1985,335; J. L. Kice and Y.-H. Kang Tetrahedron 1985,41,4739. F. Delbecq D. Ilavsky N. T. Anh and J. M. Lefour J. Am. Chem. SOC.,1985 107 1623. 18 19 J. Chandrasekharan and H. C. Brown J. Org. Chem. 1985 50 518. 20 S. Masamune B.-M. Kim J. S. Petersen T. Sato S. J. Veenstra and T. Imai J. Am. Chem. Soc. 1985 107,4549; Science Report in Chem. Eng. News 1985 August 5 p. 22.21 'Asymmetric Synthesis Vol. 5 Chiral Catalysis' ed. J. D. Morrison Academic Press Orlando U.S.A. 1985. 22 Y. Satoh H. Serizawa S. Hara and A. Suzuki J. Am. Chem. Soc. 1985 107+ 5225; M. Hoshi Y. Masuda and A. Arase J. Chem. Soc. Chem. Commun. 1985 714. Aliphatic Compounds -Part (i) Hydrocarbons I I (13) (14) R' H X CH( R3)CH( R4)CORS RWH (15) (16) [X = Br or I] R' BR; H BR H SR3 Solvomercuration-demercuration of olefins by Hg( OCOCF3)2 in a range of sol- vents forms the basis of an ether synthesis of wide general it^.^^ A study of the stereochemistry of tetra-alkyl ethylenes using 'H d.n.m.r. X-ray and molecular mechanics calculations has been combined with a study of the relative rates of reaction toward PhC03H as a measure of steric effects.24 The high temperature-dilute acid exchange of a range of alkenes shows high exchange and in some cases isomerization.Mechanisms for these processes have been discussed.25 Substituted alkenes e.g. Ph2C=CH2 adsorbed on a silica matrix undergo photo- chemical oxidation/cleavage to carbonyl compounds.26 A mixture of glycol monoacetates with other products was found in addition of acetic acid catalysed by bis(acetonitri1e)chloronitro Pd11.27 A biomimetic model of methyl transfer to olefins has employed Ar2SMeBF4 in 2,6-di-butylpyridine; this compared favourably with methyl transfer from Meerwein's salt or MeOTf.28 A long chain alkyl group in one aryl ring enhanced yields. Five products were identified from 2-methyloct-2- ene the principal product being 2,3-dimethyloct-2-ene (47%) and an ionic mechan- ism was invoked to rationalize the formed products.Boron trichloride acts as catalyst for addition of electron-deficient nitriles to mono- di- and tri-substituted alkenes and hence to p,y-unsaturated ketones.29 Examples of carbon-carbon bond formation include addition of isocyanates catalysed by Nio complexes addition of ketenes and addition of CI,C=C=O as a route to vicinal dicarboxylic acids.30 Arylation of alkenes via Pdo-mediated attack of aryl radicals from ArN(N0)COMe is easily effected. The intermediacy of aryl palladium acetate was suggested. For oct-1-ene a mixture of products was formed (see Scheme 4); ethyl acrylate gave ethyl cinnamate in modest yield (56%; E-i~omer).~' 23 H.C. Brown J. T. Kurek M.-H. Rei and K. L. Thompson J. Org. Chem. 1985 50 1171. 24 L. Andersen U. Berg and I. Pettersson J. Org. Chem. 1985 50 493. 25 N. H. Werstiuk and G. Timmins Can. J. Chem. 1985 63 530. 26 C. Aronovitch and Y. Mazur J. Org. Chem. 1985 50 149. 27 F. Mares S. E. Diamond F. J. Regina and J. P. Solar J. Am. Chem. SOC.,1985 107 3545. 28 M. Julia and C. Marazano Tetrahedron 1985 41 3717. 29 H. Hamana and T. Sugasawa Chem. Lett. 1985 571 and 575. 30 H. Hoberg K. Summermann and A. Milchereit Angew. Chem. In(. Edn. Engf. 1985,24,325; I. Marko B. Ronsmans A.-M. Hesbain-Frisque S. Dumas L. Ghosez B. Ernst and H.Greuter J. Am. Chem. Soc. 1985 107 2192; J.-P. DeprCs F. Coelho and A. E. Greene J. Org. Chem. 1985 50 1972.3' K. Kikukawa M. Naritomi G.-X. He F. Wada and T. Matsuda 1.Org. Chem. 1985 50 299. 96 B. V; Smith -. Ph Ph (23%) (5%) \-Ph-Ph-(44%) (28%) Reagents i ArN(N0)COMe-Pd(dba),-MeCN Scheme 4 Addition of azide to alkene has been brought about by AlC13 or Mn”’ catalysis. In the latter case vicinal diazides were formed in good yield and in the former aziridines products of ring opening were found.32 Cyanamide with NBS gave vicinal diarnine~,~ and N-halogenoadducts were formed from an alkene R2N-X and F3B OEt2.34 Thiirane formation was noted for t,he system R3N-0-CS2-alkene3’ and BF,-catalysed addition of disulphide ( Me2SSMe or MeSSMe-F3B OEt in CH,Cl,-MeNO,) showed stereospecificity in anti-addition of MeS addends.36 PhCECS0,Ar was found to add by a thermal or photochemical process to a double bond affording uia trans-addition a product formed from fragments derived by C-S bond cleavage.37 The preparation and versatility of 3-bromo-2-(t-butylsul- phony1)prop- 1 -ene ( 19) has been rep~rted.~’ It allows functionalization with car- banions or electrophiles sequentially and conversion of the products into enones or dienones.Tungstate-catalysed epoxidation of a,P-unsaturated acids has been reported.39 The response of the asymmetric epoxidation to steric bulk was tesied by the synthesis and reaction of t-butyl-substituted allylic alcohols.40 The reaction time for Sharpless asymmetric epoxidation was found to be greatly reduced when a catalytic amount of metal hydride and silica gel was added; e.g.2-tridec-2-en-1-01 gave 76-80% of epoxide (95% e.e.) in 96 h but in the presence of CaH2 and silica gel (5 and 10 mol% respectively) reaction was twelve times faster without any loss in yield or e.e.41 Direct chlorohydroxylation of alkenes (Bu‘OOH-TiC1,) gave some 32 H. Takeuchi Y. Shiobara M. Mitani and K. Koyama J. Chem. SOC.,Chem. Cornmun. 1985 1251; W. E. Fristad T. A. Brandvold J. R. Peterson and S. R. Thompson 1985 50 3647. 33 S. H. Jung and H. Kohn J. Am. Chem. SOC.,1985 107 2931. 34 G. E. Heasley J. M. James S. R. Stark B. L. Robinson V. L. Heasley and D. F. Shellhammer Tetrahedron Lett. 1985 26 1811. 35 M.F. Zipplies M. J. De Vos and T. C. Bruice J. Org. Chem. 1985 50 3228. 36 M. C. Caserio C.L. Fisher and J. K. Kim J. Org. Chem. 1985 50 4390. 37 0. De Lucchi G. Licini L. Pasquato and M. Senta J. Chem. SOC.,Chem. Commun. 1985 1597. 38 P. Knochel and J. F. Normant Tetrahedron Lett. 1985 26 425; P. Auvray P. Knochel and J. F. Normant ibid. 1985 26,2329. 39 K. S. Kirsenbaum and K. B. Sharpless J. Org. Chem. 1985,50 1979. 40 M. J. Schweitzer and K. B. Sharpless Tetrahedron Lett. 1985 26,2543. 41 W. Zhi-min Z. Wei-shan and L. Guo-qiang Tetrahedron Lett. 1985 26,6221. 97 Aliphatic Compounds -Part (i) Hydrocarbons diastereoselectivity for chiral substrates carrying allylic or homoallylic substituents; the products of primary reaction with base gave epoxides with selectivities sig- nificantly different from those found with pera~id.~~ A convenient and efficient synthesis of cyclopropanes has been published; a 1,l-di-iodoalkane and a trialkyl aluminium with an alkene in CH2C12 at room temperature react smoothly to form the product in good/excellent yield.If such a method can be extended to a range of substituted alkenes then it promises consider- able synthetic 3 Polyenes Synthesis.-Controlled lithiation of allenes generates a propargylic anion equivalent; at low temperature in THF coupling with an alkyl halide afforded an allene as principal product. Product switching was noted however under different conditions and an alkyne was then isolated.& An allene and a carbonyl compound were formed in the thermolysis (680 "C) of but-3-yn-1-01s; e.g. (20) formed MeCH=C=CH (98%).In some cases allenic carbonyl compounds were formed as by-pr0ducts.4~ A route to substituted allenes (70+% ) relies on elimination from P-phenylsulphinyl- P,y-unsaturated ethers brought about by Bu3SnLi in THF.46 Unsaturated chlorohy- drins derived from crotonaldehyde were converted by a methylation-lithiation sequence into alka-2,3-diene~.~' Bu~' But H. H +.=( H Me R' RZ (a) R' = Hal R2 = Me (b) R' = Hal R2= But (c) R' = R2= But The reaction of allenic bromides with metal alkyls in the presence of Ni complexes gave substituted allene~.~~ It was claimed that inversion of configuration in the allenyl moiety was the general rule; the stereoselectivity was dependent on the organometallic used however. For (S)-(+)-1-bromo-3-methylpenta-l,2-diene the order of effectiveness in BuLM was A1 > Mg >> Zn.For the reaction (21) + (Z!)49n 42 J. M. Klunder M. Caron M. Uchiyarna and K. B. Sharpless J. Org. Chem. 1985 50 912. 43 K. Maruoko Y. Fukutani and H. Yamarnoto J. Org. Chem. 1985 50,4412. 44 J. Hooz J. G. Calzada and D. McMaster Tetrahedron Lett. 1985 26 271. 45 H. Hopf and R. Kirsch Angew. Chem. Int. Edn. Engl. 1985 24 783. 46 T. Takeda K. Suzuki H. Ohshima and T. Fujiwara Chem. Lett. 1985 1249. 47 J. Barluenga J. R. Fernindez and M. Yus J. Chem. SOC.,Chem. Commun. 1985 203. 48 A. M. Caporusso F. Da Settirno and L. Lardicci Tetrahedron Lett. 1985 26,5101. 49 (a) E.J. Corey and N. W. Boaz Tetrahedron Lett. 1984,25 3059; (b) H. N. Mooiweer C.J. Elsevier P. Wykens and P. Vermeer ibid. 1985 26,65. B. V. Smith the assignment of (S)-configuration to (22) based on the Lowe-Brewster rules has been challenged.49b It is claimed that these rules do not apply to a trisubstituted allene and that independent synthesis of (22) showed that (-)-(22) had the (R)-configuration. The stereoselective synthesis of compounds (23a-c) has afforded reference points in studying such replacement reaction^.^' Assignment of the (R)-configuration to (+)-l-bromo-3,4,4-trimethylpenta-1,2-dienehas caused the stereochemistry of the conversion t-propargylic alcohol +allenic halide to be amen- ded.5' The complexities of the palladium-mediated phenylation of I -halogenoallenes have been unravelled by using optically active halides.For X = C1 and Br in RCH=C=CHX inversion of configuration was observed but for X = I configur- ation was retained. The chloro- and bromo-allenes reacted faster than the iodo- compound. Two reaction pathways were proposed to accommodate the differences ob~erved.'~ gem-Dihalogenocyclopropanes with metals (Li Na Mg) and sonication are converted into cyclopropylidenes and hence into allenes thus 1,l -dibromo-2-pentyl- cyclopropane gave C5Hl,CH=C=CH2 (81% 10 min r.t.).53 Nucleophilic displacement by azide ion on 4-chloro-3-methylbuta-l,2-diene fur-nished 2-azido-3-methylbuta-1,3-diene (24) uia initial attack at C-4.54 A stereospecific carbocupration of acetylene has been used in a novel and success- ful synthesis of conjugated Z,Z-diene~.~~ Careful control over solvent and reaction temperature was necessary; it was noticed that whilst two equivalents of alkyne were readily absorbed at -50 "C it was beneficial to allow the mixture to warm to 0°C for a reasonable rate of incorporation (see Scheme 5).In this scheme E was Reagents i 4 eq. HC=CH -50 -+ 0 "C; ii E (e.g. MeI) Scheme 5 COzMe MeI C02 or HC=CCO2Me etc. The products of such reactions [e.g. (25) and (26)] were free of the isomeric compounds as judged by g.1.c. and 13C n.m.r. A short specific synthesis of the principal component of the Navel Orange worm pheromone (52-hexadeca-1 1,13-dienal) was achieved by application of this methodology. Scheme 6 summarizes a method for the synthesis of 2,3-dialkylb~ta-l,3-dienes.~~ A 50 C.J. Elsevier P. Vermeer A. Gedanken and W. Lunge J. Org. Chem. 1985 50 364. 51 A. M. Caporusso A. Zoppi F. Da Settimo and L. Lardicci Gazz. Chim. ItaL 1985 115 293. 52 C. J. Elsevier and P. Vermeer J. Org. Chem. 1985 50 3042. 53 L. Xu F. Tao and T. Yu Tetrahedron Lett. 1985 26 4231. 54 K. Bauert Angew. Chem. Int. Edn. EngL 1985 24 216. 55 M. Furber R. J. K. Taylor and S. C. Burford Tetrahedron Letf. 1985 26 3285. 56 S. Araki M. Ohmura and Y. Butsugan Synthesis 1985 963. Aliphatic Compounds -Part (i) Hydrocarbons 99 thorough examination of the rearrangement (27) -+ (28) as shown in Scheme 7 has led to the conclusion that >95'/0 chirality transfer occurs and that the preferred transition state is (29) rather than (30).57 0 0 II II HOCH,C=CCH,OH (EtO),POCH,C~CCH,OP(OEt) Reagents i CIP(=O)(OEt), CSHsN 0 "C 2 h; ii RMgX-Cu,I, THF 0 + 25 "C 12 h Scheme 6 RI 0 Me OCb MezN- C'i-F (27) \\ I-! 0 Me0 (28) RZ Reagent i Me2N €4 PhMe heat (50 "C,2 h) Scheme 7 Me H R' Me2N ;e,OCb (29) (si) [Cb = C(=O)NPr;] (30) (re) Some metal-promoted 1,3-diene syntheses include the palladium-mediated trans- formation of vinyl bromide^;^' dehalogenative coupling of vinyl halides via Ni' generated in ~itu;~~ preparation of terminal E-dienes from an aldehyde and l-bromo- 3-iodopropene with SnCl, (an unsaturated aldehyde gave a triene):60 the Ru"- assisted coupling of an aryl-substituted alkene and an E -2-arylethenylsulphonyl chloride (which can furnish symmetrical or unsymmetrical 1,4-diarylbuta-l,3- 57 D.Hoppe C. Gonsch8rrek E. Egert and D. Schmidt Angew. Chem. Int. Edn. Engl. 1985 24 700. 58 R. Grigg P. Stevenson and T. Worakun 1. Chem. SOC.,Chem. Commun. 1985 971. 59 K. Takagi H. Minura and S. Inokawa Bull. Chern. SOC.Japan 1984 57 3517. 6o J. Auge Tetrahedron Lett. 1985 26 753. 100 B. V. Smith dienes);61 and the conversion of enynes into dienes in the presence of a tungsten complex.62 The product of reaction obtained from TFA and 4-chlorophenylmethyl sulphoxide uiz. 4-chlorophenylthiomethyl trifluoroacetate (3l) was added to a terminal alkene in TFA affording (32) which by oxidation (peracid) and thermolysis led to a 1 ,3-diene.63 A one-pot synthesis of l,l-bis(methylthio)alka-1,3-dieneshas been de~eloped.~~ By choice of conditions a Wittig sequence has been developed for 1,Sdisubstituted penta-l,4-dienes; high Z-selectivity was found when HMPA was present.65 Ph Ph H >-.= 2 )=*=i ,,R' MeOzC Me02C HO/c\R2 1 iii iv Reagents i LiN(SiMe,), -78 "c; ii R1R2C=O; iii MeC6H4SOCI NEt, -78 "C; (iv) LiOR -78 + +25 "C Scheme 8 MeOzC COzMe PhQI'h Me02C Ph fi MeO,C >_.=.+ph Ph Ph Ph C02Me Me02C C02Me Me02C Ph (33) (34) (35) (36) (37) (38) N.Kamigata J. Ozaki and M. Kobayashi Chern. Lett. 1985 705. T. J. Katz and T. M. Sivarec J. Am. Chem. SOC.,1985 107 737. H. Ishibashi H. Komatsu K. Maruyama and M. Ikada Tetrahedron Lett. 1985 26 5791. Y. A.Heus-Kloos R. L. P. De Jong H. D. Ver Kruijsse L. Brandsma and S. Julia Synthesis 1985 958. G. Just and B. O'Connor Tetrahedron Lerr. 1985 26 1799. 61 62 63 64 65 Aliphatic Compounds -Part (i) Hydrocarbons 101 The first synthesis of substituted buta-l,2,3-triene carboxylic acids has been achieved.66 Possible routes via elimination reactions of several precursors were unsuccessful; the successful route is outlined in Scheme 8. The stability of these compounds shows considerable variation and the diester (33) is transformed during 5 days at 100°C to the cycloadduct (34). Surprisingly the expected product (35) was not formed. In solution the reaction of (33) was marked by a lower yield and a mixture of by-products. Thermolysis of sulpholenes results in the formation of 1,3,5-trienes; e.g.(36) gave (37) (83%) and (38) (17°h).67 Some triene diamines have been obtained from 1,9-bis-dialkylaminonona-2,7-diynes.68 Reactions.-An allene-alkyne isomerase (from hog liver) is the first recorded example of an enzyme which is not inactivated by such a substrate. The mechanism of the process was probed by using appropriately labelled derivatives of dec-3-ynoic and (+)-deca-2,3,-dienoic acids. It was suggested that protonation occurred at C-2 on the si-face of the allene.69 Selective isomerization of dienes and trienes via the use of an i.r. laser has been summarized and disc~ssed.~" Allenes undergoe combined dimerization-hydroxylation in water in the presence of C02 and Pd" species; alcohols gave ethers (39) in variable yield.71 Photolysis of a triarylchloroallene has been interpreted as generating a triarylal- lenyl cation which can be captured by attack of a nucleophile (e.g.MeOH) to form allenic and propargylic products; the latter forms nearly 50% of the product in a favourable case.72 In the presence of Pd" catalyst allene and CuCl formed 2,3- bis(chloromethyl)buta-l,3-dienein excellent yield. Not all allenes behaved in this simple way and mixtures/ polymers/ trimers were found in some cases. The diene underwent reaction with a variety of bifunctional nucleophiles to produce cyclic products containing exocyclic diene f~nctionality.~~ The thi-iranes from reaction of propadiene and buta-l,2-diene with elemental sulphur have been described.74 Two examples of cycloaddition are the reaction of nitrones with fluorallene and that of p-allenic carbonyl compounds with isocyanides RNC.75 Tetraethoxyallene with S0Cl2 was presumed to form the heteroallene (EtO,C),C=S=O since this could be trapped with 2,3-dimethylbuta-l,3-diene or dimerized to a 1 ,2-dithietane.76 Phenylsulphonyl propadiene (PhS02CH=C=CH2) undergoes efficient Diels-Alder addition to e.g.(40) affording (41) (72'/0).~~ Alkyla-tion of e.g. (41) followed by desulphonylation can thus afford an entry into functionalized methylenecyclohexanes. 66 F. W. Nader and C.-D. Wacker Angew. Chem. Int. Edn. Engl. 1985 24 851; F. W. Nader C.-D. Wacker H. Irngartinger U. Huber-Patz R. Jahn and H. Rodewald ibid. 1985 24 852. 67 R.Block C. Benecou and E. Guibe-Jampel Tetrahedron Lett. 1985 26 1301. 68 R. Epsztein and N. Le Goff Tetrahedron 1985 41 5347. 69 J. M. Schwab and D. C. T. Lin J. Am. Chem. Soc. 1985 107 6046. 70 F. D. Lewis and E. Weitz Acc. Chern. Rex 1985 18 188. 71 Y. Inoue Y. Ohtsuka and H. Hashimoto Bull. Chem. SOC.Jpn. 1984 57 3345. 72 T. Kitamura S. Miyake S. Kobayashi and H. Tamiguchi Chem. Lerr. 1985 929. 73 L. S. Hegedus N. Kambe Y.Ishii and A. Mori J. Org. Chem. 1985 50 2240. 74 M. Green B. Verkoczy E. M. Lown and 0. P. Strausz Can. J. Chem. 1985 63 667. 75 W. R. Dolbier Jr. C. R. Burkholder G. E. Wicks G. J. Palenik and M. Gawron J. Am. Chem. Soc.. 1985 107 7183; G. Gil and J.-P. Zahra Tetrahedron Lett. 1985 26 419. 76 R. W. Saalfrank and W.Rost Angew. Chem. Int. Edn. Engl. 1985 24 855. 71 K. Hayakawa H. Nishiyama and K. Kanematsu J. Org. Chem. 1985 50 512. 102 B. V. Smith c:i.). Me3Si0 'H Structure determination on propadienone ( H2C=C=C=O) has revealed sig- nificant departure from linearity in the hai in.'^ Phenylsulphonyl-mercuration of 1,3-dienes ( PhS02Na-Hg"C12- H,O- Me,SO 20 "C)proceeds smoothly to form adducts (see Scheme 9) which generate sulphonyl dienes with potential in Michael addition processes.79 1,3-Dienes add PhSCl at low temperature to form (42) rearranging on distillation or standing to (43).Although (42) was inert to LiEt3BH (43)was dehalogenated to Me2C=C(Me)CH2SPh.80 A new reagent 2-dipropylborylmethylbuta-1,3-diene(44),serves as an isoprenylating agent for carbonyl compounds and the acetylene moiety; e.g.from EtOCECH and (44) followed by deboronation 2-ethoxy-4-methylenehexa-1,5-diene was obtained (98%). This latter application marks the first isoprenylation of an alkyne.8' ClHg #/ I_ VHgCl + wSOzPh S02Ph (major) iiI (minor) ii 1 V' wSO,Ph S02Ph Reagents i PhS02Na HgCI, H,O-Me,SO 20 "C; ii base Scheme 9 1-Arylbutadienes have been hydrosilylated asymmetrically with HSiC13 in the presence of a chiral ferrocenylphosphine-palladium catalyst to yield optically active allylsilanes 2-1 -aryl- 1 -silylbut-2-enes and their regioisomers. Reduction ( H2/ Pd-C) of these primary products followed by treatment of the reduced silanes with peracid-KHF,-DMF gave chiral alcohols.82 Functionalized isoprenylsilane (and related compounds) gave smooth cycloaddition with a range of dien~philes;'~" a Cationic similar property was noted with 2-silyl- and 2-stannyl-buta- 1,3-diene~.~~ complexes of molybdenum have been used to prepare diene complexes; these react with LiCuR and by this strategy (E,,E)-undeca-1,3,5-triene was prepared stereos elective^y.84 78 R.D. Brown R. Champion P. S. Elmes and P. D. Godfrey J. Am. Chern. SOC. 1985 107 4109. 79 0. S. Andell and J. E. Backvall Tetrahedron Lett. 1985 26,4555. B. T. Golding E. Pombo-Villar and C. J. Samuel J. Chern. Soc. Chern. Cornrnun. 1985 1444. Y. N. Bubnov and M. Y. Etinger Tetrahedron Lett. 1985 26,2791. 82 T.Hayashi and K. Kabeta Tetrahedron Lett. 1985 26,3023.83(a)A. Hosomi Y. Sakata and H. Sakurai Tetrahedron Lett. 1985 26,5175; (b) I. Fleming and M. Taddei Synthesis 1985 899. 84 M. Green S. Greenfield and M. Kersting J. Chern. SOC.,Chern. Cornrnun.,1985 18. Aliphatic Compounds -Part (i) Hydrocarbons (42) [X = CI] (45) A synthesis of dicyclobutylideneethane (45) a strain activated diene has been achieved.85 Owing to steric congestion it showed only reasonable diene reactivity in cyclic addition. Reaction of each of the stereoisomers of 1,4-di-t-butoxybuta-l,3-diene with singlet oxygen gave dioxetanes as the predominant products. Very little isomerization of starting material occurred.86 The reaction of ozone and a number of dienes gave a complex mixture of ozonides and hydroperoxides; 2,3,4,5-tetramethylhexa-2,4-diene did not react in this way and some epoxide was formed.” Dienes undergo 1,2- and 1,4-addition of OAc with Te02-LiBr-AcOH;88 for butadiene the ratio of the 1,4 to 1,2 addition is 90 10 and evidence was obtained that the ratio of 1,4 to 1,2 addition (and the total yield) depended on the ratio of LiBr to TeO,.2,5-Dimethylhexa-2,4- diene with meta -chloroperoxybenzoic acid gave principally the diol monobenzoate (46)which with dilute base gave the unsaturated epoxide; excess of the peracid formed meso-and (*)-bi~-epoxide.’~ Small amounts of cyclic by-products cis-and trans-(47) were also formed presumably via intramolecular neighbouring group participation. Vinyl triflates in polar solvents react with olefins to form conjugated dienes; a Pd1’-Et3N-THF system was used.” Assorted ene reactions of conjugated dienes and EtO,CN=NCO,Et have been studied.” 4 Alkynes Synthesis.-Silyl acetylenes with a tertiary alkyl halide in the presence of a Lewis acid give substituted acetylenes.This reaction is successful with bis-silylated acety- lene and di-t-butylacetylene was obtained in good yield.92 Elimination of Ph3P0 by FVP has been used in synthesis of alkynes from e.g. (48).These reactions were run on multigram levels and the product was free of allene contaminant^.^^ Reductive 85 G. Wickham. G. J. Wells L. Waykole and L. A. Paquette J. Org. Chem. 1985 50 3485. 86 E. L. Clennan and R. P. L’Esperance J. Am. Chem. Sot. 1985 107 5178. 87 K. Griesbaum and G. Zwick Chem.Ber. 1985 118 3041. 88 S. Uemura S. Fukuzawa S. R. Patil and M. Okana J. Chem. Soc. Perkin Trans. 1 1985 499. 89 M. A. Hashen E. Manteuffel and P. Weyerstahl Chem. Ber. 1985 118 1267. 90 W. J. Scott M. R. Pefia K. Sward S. J. Stoessel and J. K. Stille J. Org. Chem. 1985 50 2302. 91 B. M. Jackson G. M. Arnavitis C. A. Eliosen and R. Mitelman i. Org. Chem. 1985 50 194. 92 G. Capozzi R. Ottana G. Romeo and F. Marcuzzi Gazz. Chim. ZtaL 1985 115 311. 93 R. A. Aitken and J. I. Atherton J. Chem. Soc. Chem. Commun. 1985 1140. 104 B. V. Smith dephosphorylation of 2-bis(diethoxyphosphiny1)stilbene gave PhCzCPh; some alkene and alkane were formed sim~ltaneously.~~ Terminal (and internal) monoalkenes were converted into alkynes by a heterogeneous system [Pd(OAc),-0,- EtOH-H,O] in acceptable yields.In dioxan-water Wacker-type ketonization occur- red9' and some hydration of alkyne also occurred as expected. Reduction of cobalt carbonyl complexes of acetylenic alcohols gave s-alkyla~etylenes.~~ Alkenynyl tri- flates have been used as precursors of unsymmetrical diacetylenes; treatment with base (ArOK or Pr'Li) in glyme led to the diynes in good/very good yield.97 The synthesis and resolution of the chiral intermediate (*)hex-5-yn-3-01 has been reported.98 Chiral synthesis of the (R)-isomer from D-glUCOSe confirmed the stereochemical assignments given to the enantiomers. Synthesis of terminal per- fluoracylacetylenes and perfluoroalkynals was reported.99 A one-pot synthesis of conjugated enynes relies on initial reaction between R'CH(C1)COR2 and R3C-CMgBr and elimination (via LiCIOHg) to give a mixture of 2-and E-enynes in modest yield."' Selective linear co-dimerization of terminal acetylenes and 1,3-dienes efficiently catalysed by dihydrotetrakis(tria1kylphos-phine)ruthenium complexes led to enynes in excellent yield.A second stereo-defined synthesis of enynes has been published; an alkenylborane undergoes cross-coupling with an alkenyl halide (furnishing a diene) or with an alkynyl halide to form conjugated E or 2-enynes."' This latter reaction is catalysed by Pd(PPh3) in the presence of a sodium alkoxide. In both the bromoalkene and alkenylborane moieties reaction proceeds with retention of configuration. Taken together these two reactions afford considerable synthetic potential for enyne chemistry.E-Enynyldialkylboranes have been prepared from successive reactions of boration of 1-iodoalk- 1 -ynes and coupling with an alk- 1 -ynyl-lithium in variable yield. Alkaline oxidation (H202-MOH) gave alkynones whereas protonolysis (AcOH) followed by cross-coupling with ally1 or hex-1 -ynyl bromide gave conjugated enynes."* (49) 94 S. C. Welch and M. C. Kabay J. Org. Chem. 1985 50 136. 95 G. Cum R. Gallo S. Ipsale and A. Spadaro J. Chem. SOC.,Chem. Commun. 1985 1571. 96 K. M. Nicholas and J. Siegal J. Am. Chem. SOC.,1985 107 4999. 97 P. J. Stang and V. Dixit Synthesis 1985 962. 98 B. L. Roy and P. Deslongchamps Can. J. Chem. 1985 63 651. 99 Y. Shen W.Cen and Y. Huang Synthesis 1985 158. loo J. Barluenga M. Yus J. M. Concellon P. Bernard and F. Alvarez J. Chern. Res. (S) 1985 128. LO1 T. Mitsuda Y. Nakagawa K. Watanabe Y. Hori H. Misawa H. Watanabe and Y. Watanabe J. Org. Chem. 1985 50 565; N. Miyaura K. Yamada H. Suginome and A. Suzuki J. Am. Chem. Soc. 1985 107 972. 102 M. Hoshi. Y. Masuda and A. Arase Bull. Chem. SOC.Jpn. 1985 58 1683. Aliphatic Compounds -Part (i) Hydrocarbons 105 A stereospecific synthesis of 2-and E-1,6-bistrimethyl silyhex-3-ene-1,Sdiyne has been ~ndertaken."~ Reactions.-Dimetallation of PhCGCH has been studied thoroughly and the reac- tion of the formed species towards a range of electrophiles has been investigated. With C02 for instance a mixture of products from 0-and terminal-site attack was formed.With other reactions of e.g. RBr Se or RC(=O)NMe2 o-substituted products were formed preferentially.'04 Stereospecific semihydrogenation of alkynes to 2-alkenes by H,-(arene)Cr(C0)3 catalysts has been de~eloped."~ The regiocontrol observed in Nio-catalysed hydrocyanation of alk- 1-ynes reflects the steric bulk of substituents on silicon in R3SiCzCR'; thus for R3=Bu'Me2 and R' = Me the ratio of (49):(50) was 92 :8. This method offers a simple route to E-2-alkyl-3-trialkylsilylalk-2-ene nitriles.'06 Acylation of acetylene (AcC1-Lewis acid) has been probed by n.m.r. and two complexes (1:l and 2:l) were detected. The isolatable product was trans-p-chlorovinylketone.'07 Chiral acetylenic acetals have been transformed into chiral alkoxyallenes via reaction with RMgX; thus (51) gave (52) with variable d.e.e.g. Bu'MgBr gave 10Oo/o but lower values were found for MeMgBr and Cur salts.'Og 1-Ethoxy-3-trimethyl- silylprop-1-yne reacts with a range of carbonyl compounds in the presence of TiC14 forming a-functionalized allylic dienes or trienyl silanes.'09 Acetylenic ketals e.g. (53) have been converted into allenic acetals (and hence the ketones) via a sequence of mesylation and reaction with RMgX-CuBr."' Alkynyl halides with Cr"C12 in DMF are presumed to form an alkynyl chromium species (not isolated) selective for addition to the aldehyde carbonyl group; no reaction occurred at the keto-group of a ketoaldehyde. This methodology allows two-carbon homologation (Stcheme 10) with the formation of an enal.":Trimethyl- silylalkynes with PhIO-Et30 BF4-CH2CI2 smoothly form [RCEC-IPh]BF4.112 Addition of HF to activated alkynes (R-CEC-A or A-CsC-A; A = CN C02R COR etc.; R =+alkyl phenyl) has been moderated by use of polymer- supported HZF3-or Bu4NHF2; fluoralkenes were formed in moderate yields.Alkynyl alcohols add iodine (and several oxides) in methanol forming p -iodo-cqp-unsatur-ated ketones. A rearrangement was disclosed by the production of (55) and (56) from (54).'13 A kinetic and mechanistic study of the oxidation of alkynes by Bu4~Mn04-CH2C12 has revealed that rates of reaction are more sensitive to electronic than steric factors.' l4 103 K. P. C. Vollhardt and L. S. Winn Tetrahedron Lett. 1985 26,709. 104 L.Brandsma H. Hommes H. D. Verkruijsse and R. L. P. de Jong J. Roy. Neth. Chem. Soc. 1985 104 226. 105 M. Sodeoka and M. Shibasaki J. Org. Chem. 1985 50 1147. 106 G. D. Fallon N. J. Fitzmaurice W. R. Jackson and P. Perlmutter 1.Chem. Soc Chem. Commun. 1985 4. 107 S. Brownstein A. Morrison and L. K. Tan J. Org. Chem. 1985 50 2796. 108 A. Alexis P. Mangeney and J. F. Normant Tetrahedron Lett. 1985 26,4197. 109 J. Pornet B. Khonz and L. Miginiac Tetrahedron Lett. 1985 26 1861. 110 D. Bernard and A. Doutheau Tetrahedron Lett. 1985 26,4923. 111 K. Takai T. Kuroda S. Nakatsukasa K. Oshima and H. Nozaki Tetrahedron Lett. 1985 26 5585. 112 M. Ochiai M. Kunishima K. Sumi Y. Nagao and E. Fujita Tetrahedron Lett. 1985 26 4501. 113 P.Albert and J. Cousseau J. Chem. Soc. Chem. Commun. 1985 26 1967. 114 D. G.Lee E. J. Lee and W. D. Chandler J. Org. Chem. 1985 50 4306. 106 B. V. Smith HO 0 I1 MeC Me0 Me-)- f-Ph Me-f -Ph Ph PhH PhI Ph (54) (55) (56) OH Reagents i PhMe,SiC_CBr CrCI,; ii KF MeOH-H20; iii (Ph,SiO),VO C,H,Me Scheme 10 A one-pot conversion of terminal acetylenic alcohols (and their 0-derivatives) into E-olefinic alcohols has been rea1i~ed.l'~ The preparation and some reactions of acetylenic tosylates has been reported; e.g. RCECOS0,Ar rapidly formed RCH,CO,Me with base in methanol.l16 Allenic ethers and amines have been realised from their acetylenic counterpart^."^ Addition of chiral t-butyl p-tolylsulphinyl acetate to propargylic aldehydes led to functionalized propargylic alcohols in high enantiomeric purity (70-90% ).' l8 Such a process is described in Scheme 11.Disilylation of acetylenes proceeds with variable stereoselectivity (via R,SiLi); thus CloH,,CrCH gave 56% (lOOo/~ 2-isomer) of disilylated product whereas for PhCECH a 50 50 E :2-mixture resul- ted.'I9 The related silylstannylation with Me,SnSiMe,Bu' has been explored with respect to regio- and stereo-selectivity of addition to RCECH.'" Addition of RLi to 3-(trimethylsilyl)prop-2-yn-l-ols gave a low yield of a functionalized vinyl silane."' Trimethylsilyl cyanide Me,SiCN adds with high regio- and stereo-selectivity to ArCECH via cis-addition. The product a p -cyano-P -arylalkenylsilane can be reduced to a saturated analogue.Silyl enol ethers of acetylenic carbonyl compounds undergo intramolecular C-vinylation in the presence of Hg".'22 115 J. W. Patterson Synthesis 1985 337. 116 P. J. Stang and B. W. Surber J. Am. Chem. SOC.,1985 107 1452. 117 F. Barbot B. Dauphin and P. Miginiac Synthesis 1985 768. 118 G. Solladit C. Frechou and G. Demailly Nouu. J. Chim. 1985 9 21. 119 J. Hibino S. Nakatsukasa K. Fugami S. Matsubara K. Oshima and H. Nozaki J. Am. Chem. Soc. 1985 107 6416. 120 B. L. Chenard E. D. Laganis F. Davidson and T. V. Rajan Babu J. Org. Chem. 1985 50 3666. 121 K. J. H. Kruithof R. F. Schmitz and G. W. Klumpp J. Roy. Neth. Chem. SOC.,1985 104 3. 12* N. Chatani and T. Hanafusa J. Chem. SOC.,Chem. Commun. 1985 838; J. Drouin M.-A. Boaventura and J.-M.Conia J. Am. Chem. SOC.,1985 107 1726. Aliphatic Compounds -Part (i) Hydrocarbons 0 0 R Reagents i Bu'MgBr(xs.) THF -78 "C; ii RC-CCOR' 4 eq. -78 "C; iii NH4CI aq.; iv AI-Hg Scheme 11 Hydrosilylation of 1,4-bis(trimethylsilyl)buta-l,3-diynewith R and Rh catalyst proceeded stepwise; initially a silylbutenyne was formed and then subsequently a bis-silylated allene. Carbometallation of the silylated allene then occurred. Car- bometallation of the silylated diyne (Me,Al-Cp,ZrCl,) afforded an alkenyl aluminium which quenched with water or electrophiles gave derivatives of but- l-ene- 3-yne.12 Some other reactions of addition include those of 2-(tri-n-butylstanny1)tetrazoles and activated alkynes forming alkenyl-tetrazoles; of alk-3-yn- 1,2-diols and ethanol- Pd to form furans; of chlorocyanoketen and alkynes (a route to cyclobutanones) and of Pd-mediated addition of Ph,C=C=O to a terminal alk~ne.'*~ Vinylacetylene with triplet sensitizers adds to alkenes dienes allenes and diynes forming cyclobutane derivatives; since the C-C- Me functionality forms COMe on hydration vinyl acetylene has been described as the photochemical equivalent of MeCOCH=CH2.125 Trost has explored the reasons behind differences in the thermal and Pd-catalysed reactions of a 1,6-enyne.As shown in Scheme 12 significant differences were found according to the conditions used and the ligands on the phosphine portion of the complex. The notion that conformational control exerted by remote binding sites directs the selectivity of the process was argued in this interesting paper.'26 Under defined conditions only the terminal triple bond of alk-3-en-1-ynes add amines via catalytic aminomercuriation to give 1-aza-l,3-dienes and 2-morpholino- 1,3-dienes.These compounds are of interest as Diels-Alder addends.',' Enyne triflates react with nucleophiles via an SN2'mechanism and form functionalized 123 T. Kusumoto and T. Hiyama Chem. Lett. 1985 1405; T. Kusumoto K. Nishide and T. Hiyama ibid. 1985 1409. I24 M. Casey C. J. Moody C. W. Rees and R. G. Young J. Chem. SOC.,Perkin Trans. 1 1985 741; Y. Wakabayashi Y. Fukuda H. Shirogami K. Ultimoto and H. Nozaki Tetrahedron 1985 41 3655; P. L. Fishbein and H. W. Moore J. Org. Chem. 1985,50,3226;T. Mitsudo M.Kadokura and Y. Watanabe Tetrahedron Lett. 1985 26 3697. 125 H. Siegel L. Eisenhuth and H. Hopf Chem. Ber. 1985 118 597. 126 B. M. Trost and M. Lautens Tetrahedron Lett. 1985 26 4887. 127 J. Barluenga F. Aznar R. Liz and M. P. Cabal J. Chem. SOC.,Chem. Commun. 1985 1375. 108 B. V. Smith i 1 /iii (73%) 83% (1.2 1) Reactions i FVP 625 "C;ii Pd" C,D, 66 "C;iii -H-,-Pd Scheme 12 enynes; the initial formation of butatrienes and 1,3-hydride shift was presumed. The triene was not isolated but some spectroscopic evidence was secured for its formation. A series of remote-deuterium isotope effects was measured for solvolysis of ethynyl- and butadiynyl-vinyl triflates in EtOH-H,O and TFE.'28 Ethyl a-propargylacrylate (57) has been synthesized for its potential as a 5-carbon synthon via addition reactions.'29 128 P.Stang and V. Dixit Tetrahedron Lett. 1985 26 2307; M. Ladika M. D. Schiavelli M. Kowalski and P. J. Stang J. Org. Chern 1985 50 4397. 129 V. T. Ravikumar S. Swarninathan and K. Rajagopalan Tetrahedron Lett. 1984 25 6045.

ISSN:0069-3030    

DOI:10.1039/OC9858200091

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By P. F. GORDON ICI Organics Division Blackley Manchester M9 3DA 1 Introduction The following discussion covers only a small proportion of the enormous number of publications which fall within the category ‘other aliphatic compounds’. Neverthe- less some of the major themes dominating work in this area and particularly that of stereocontrolled reactions are reflected in the nine sections that follow. 2 Alcohols and Ethers The synthesis and reactions of alcohols and ethers is an important and stimulating area of work. Much of this work is directed towards the stereocontrolled formation of the carbon-oxygen bond and this is reflected in many of the papers published this year as can be seen from the following discussion.An important and well known route to alcohols involves the reduction of ketones a reaction which Nature does with relative ease and frequently enantiospecifically. The use of Nature’s own reducing agents is therefore an obvious ploy which has once again received attention. For example Baker’s yeast enantioselectively reduces 1-hydroxy-3-phenylthio-propanone to optically pure (S)-3-phenylthio-1,2-propanediol; the latter has been used as a convenient precursor to both enantiomers of secondary alcohols as shown in the synthesis of both optical isomers of 5-hexadecanolide.’ Baker’s yeast also reduces ethyl 4-azido- and 4-bromo-3-oxobutyrates giving 4-azido-3( R)-hydroxybu-tyrate and 4-bromo-3( S)-hydroxybutyrate respectively in high optical yield and thence (R)-and (S)-carnitim2 One of the problems with using Baker’s yeast as a reagent is in the extraction of the products from the brew and so attempts have been made to immobilize it in or on a polymer support so as to provide a convenient work-up procedure.With this intention in mind polyurethane has been used as the support in the reduction of ketoesters (1) and as expected the work-up is fairly easy. However perhaps surprisingly the configuration and enantiomeric excess (ee) of the products are changed dramatically. For instance without the polymer support ketoester (la; R = C1 R’ = Et) is reduced to give the (+)-alcohol in 42% ee whereas with PU support the (-)-isomer is obtained in 82% ee.3 In many cases asymmetric reductions of ketones to alcohols involve the use of a chirally modified reagent or the exploitation of chirality already present in the ’ T.Fujisawa T. Itoh M. Nakai and T. Sato Tetrahedron Lett. 1985 26 771. C. Fuganti and P. Grasselli Tetrahedron Lett. 1985 26 101. K. Nakamura M. Higaki K. Ushio S. Oka and A. Ohno Tetrahedron Lett. 1985 26 4213. 109 110 P. E Gordon molecule to be reduced. In this context prochiral3-aryl-3-0x0 esters can be reduced to the 3-hydroxy ester with enantiomeric excesses of over 80% (nine examples) by lithium borohydride partly decomposed by chiral N,N'-dibenzoylcystine and t-butyl alcoh01.~ On the other hand L-selectride reduction of optically pure lactones (2) affords pure syn-diols with high diastereoselectivity a method used in the synthesis of (+)-exo-brevic~rnin.~ Sat0 and his group have utilized the same reagent in the diastereoselective reduction of the silyl ketones (3) which forms a key step in the first total synthesis of (+)-corynornycolic acid.6 Indeed the silyl-substituted aldehydes or ketones (3) are extremely versatile intermediates and as well as facilitating 1,2-asymmetric inductions by reduction as just described they are also attacked by nucleophiles at the carbonyl group e.g.(3; R2 = H) to give alcohols (5) which have the opposite stereochemistry about the C-OH bond to that found in the reduction reaction CJ (5) us. (4).'" This fact can be seen in the addition of 1-trimethylsilylvinylmagnesiumbromide to (3; R2 = H) to yield [5; R2 = -C(SiMe3)=CH2] a sequence which forms a key element in the synthesis of (+)-blastmycinone.This ability to control the relative stereochemistry about two adjacent centres by merely altering the nature of the reagents is a desirable feature of these systems and has been taken a step further since conditions have now been worked out which allow the preparation of all four stereoisomers of the vicinal di01s.~' Furthermore the alcohols (4) and (5) can be stereoselectively epoxidized thus allowing the introduction of more useful functionality; this particular strategy has been implemented in the synthesis of erythr~nolides.~" If dithiane anions are added to aldehydes (3; R2 = H) then the ketones (6)are formed after unmasking and in their turn (6) react with Grignard reagents (R4MgBr) to yield alcohols (7) in which three contiguous and stereocontrolled centres have been e~tablished.~~ In a similar vein Suzuki and his group have studied the addition of nucleophiles (crotylmetal or H-) to aldehydes (3; R2 = H) and have devised conditions whereby K.Soai T. Yamanoi H. Hikima and H. Oyamada J. Chem. SOC.,Chem. Commun. 1985 138. M. Larcheveque and J. Lalande J. Chem SOC.,Chem. Commun. 1985 83. 'Y. Kitano Y. Kobayashi and F. Sato J. Chem. SOC.,Chem. Commun. 1985 498. ' (a) H. Uchiyama Y. Kobayashi and F. Sato Chem. Lett. 1985 467; (b) F. Sato 0. Takaheshi T. Kato and Y. Kobayashi J. Chem. SOC.,Chem. Commun. 1985,1638; (c) Y. Kobayashi H. Uchiyama H. Kanbara and F. Sato J. Am. Chem. SOC.,1985 107 5541; (d) A. K. Samaddar T.Chiba Y. Kobayashi and F. Sato J. Chem. SOC.,Chem. Commun. 1985 329; (e) K. Suzuki E. Katayama K. Tomooka T. Matsumoto and G-i. Tsuchihashi Tetrahedron Lett. 1985 26 3707. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds all four stereoisomers of alcohols (8) again with three contiguous chiral centres can be ~btained.~' The theme of manipulating reaction conditions reagents etc. so as to control not just the formation of one stereoisomer but all the stereoisomers possible from a system (in a predictable fashion) has been a recurrent one. Complementary stereoselection in the addition of carbon and hydride nucleophiles to a,@-dialkoxy- carbonyl systems is possible by altering the metal cation with magnesium based reagents giving syn addition and lithium and titanium based reagents giving anti addition.8 Similarly titanium and aluminium reagents derived from carbamates (9) add to aldehydes giving anti addition products (10) and (ll),respectively with complementary stereochemistry about the double bond.' The silyl alcohols (10) and (11)can then be converted into all four stereoisomeric butadienes (>99% selectivity) by carefully choosing the conditions for the Peterson elimination.The use of titanium reagents for additions to a-chiral aldehydes and cyclohexanones is also to be recommended since over 80% diastereofacial selectivity is possible in the adducts obtained from aldehydes; strong and predictably variable axial-equatorial preferen- ces are also observed for the cyclohexanone addition products by varying the nature of the titanium reagent." \ N(Pr') (9) If the titanium reagent is complexed with a chiral auxiliary e.g.a chiral binaphthol then high enantioselectivity may be expected as observed in the addition of aryl groups to aromatic aldehydes to generate benzhydrols (ee 39-98%)." In an asym- metric variant of the Sakurai reaction a different chiral auxiliary is used i.e. l-phenylethanol as shown in Scheme 1 and s'o the reaction is claimed to be the first asymmetric synthesis of homoallylic alcohols uia open chain compounds.12 Continuing in the same vein organolithium and Grignard reagents react with the 3-acylisoxazolines (12) to produce tertiary alcohols with high but opposite stereochemistry about the carbon-oxygen bond.13 The reason for this marked difference is thought to stem from competing reaction pathways involving attack on s-trans or s-cis metal chelated conformations of the 'O=C-C=N-' fragment.K. Mead and T. L. Macdonald J. Org. Chem. 1985 50 422. E. van Hulsen and D. Hoppe Tetrahedron Lett. 1985 26 411. M. T. Reetz R. Steinbach J. Westermann R. Peter and B. Wenderoth Chem. Ber. 1985 118 1441. '' D. Seebach A. K. Beck S. Roggo and A. Wonnacott Chem. Ber. 1985 118 3673. I2 R. lmwinkelried and D. Seebach Angew. Chem. Int. Ed. Engl. 1985 24 765. l3 P. A. Wade D. T. Price J. P. McCauley and P. J. Carroll J. Org. Chem. 1985 50 2804. 112 I? E Gordon Ph H x OH 0' . 2 Ph __.+ R Reagents i 2 BuLi; ii TiCI,; iii RCHO; iv Me3SiCH2CH=CH2; v Me3SiI Scheme 1 The Grignard reagent (PhCH,MgBr) also attacks the acyloxathiane (13) specifically to yield the chiral diol (14; >95% ee) from which (R) and (S)-mevalolactones have been elaborated with high enantiomeric purity.14 A remarkable change in selectivity has been observed in additions of ethyl metallics to the acrolein dimer (15).Thus ethyl lithium in HMPA provides the erythro-alcohol whereas diethylzinc gives the threo-alcoh01.'~ The latter has been converted into exo-brevicomin and the Mus rnusculus pheromone in less than three steps. Efficient new routes to 1,2-diols are always to be welcomed and the more so if they are stereoselective. This is the case for a unique variant of the boron-Wittig reaction which leads to erythro-1,2-diols (16) in high chemical yield and with selectivities varying between 10 1 and 100 1.16 The reaction is brought about by the addition of dimesitylboron-stabilized carbanions (17) to aldehydes (RCHO) followed by an oxidation step which goes with retention of configuration.Interest- ingly no detectable quantities of alkenes are found in the reaction. Despite the extensive use of organometals in many of the reactions just discussed it is not always necessary to use them as illustrated in a stereocontrolled homologation of a-hydroxy-aldehydes to yield polyalkoxy-aldehydes with several contiguous stereodefined centres e.g. Scheme 2.'' H..jqHH Li I Ar R Mes2BCHR Several papers have appeared relating to the synthesis and reactions of 2,3-epoxy- alcohols.In one a procedure for obtaining the less commonly observed optically active syn addition products (18) involves the addition of organocopper compounds to 2,3-O-isopropylideneglyceraldehyde.18 The alcohols (18) can then be converted S. V. Frye and E. L. Eliel J. Org. Chem. 1985 50 3402. Is M. Bhupathy and T. Cohen Tetrahedron Lett. 1985 26,2619. 16 A. Pelter D. Buss and A. Pitchford Tetrahedron Lett. 1985 26,5093. 17 A.Dondoni M. Fogagnolo A. Medici and P. Pedrini Tetrahedron Lett. 1985 26,5477. 18 F.Sato Y. Kobayashi 0.Takahashi T. Chiba T. Takeda and M. Kusakabe J. Chem. Sac. Chem. Commun. 1985 1636. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds I OSiMe3 OBn Me Reagents i THF H20-F-; ii SO, Me,OBF,; iii NaBH,; iv NaH IN(Bu), BnBr; v HgCI,-MeOH-H20 Scheme 2 into 2,3-epoxy-alcohols in high yield by standard methods.1,6-Anhydroglucose is the precursor for another epoxy-alcohol derivative (19) which is in itself a precursor to optically active units (2O).I9 The route to (20) is fairly simple and proceeds from epoxy-alcohol (19) by way of two separate organometal additions to give the alcohol (21) in three steps or alternatively the alcohol (22) in four steps. By reaction with 1,3-propylenedithiol alcohols (21) and (22) can be converted readily into alcohols (20) which should be suitable for the synthesis of propionate-derived natural prod-ucts. Opening of 2,3-epoxy-alcohols (23) by isocyanate occurs exclusively by attack at the a-position yielding 2-amin0-1,3-diols,2~"whereas in the presence of titanium nucleophilic attack (amines thiols azides etc.) takes place at the /3-position.20b*' b; X = H,Y= OH (20) An alternative route to amino-alcohols to that just described starts from chiral cyanoamines e.g.(24) which can be either metallated and then reacted with ketones/ aldehydes followed by removal of the cyano-group or treated with P. J. Hodges and G. Procter Tetrahedron Lett. 1985 26 4111. 2o (a) W. R. Rousch and M. A. Adam J. 0%.Chem. 1985 50 3752; (b) M. Caron and K. B. Sharpless ibid p. 1557; (c) J. M. Chong and K. B. Sharpless ibid. p. 1560. 114 P. F. Gordon organolithiums followed by reduction and hydrolysis.21 a-c This strategy has been used in the synthesis of chiral P-amino-alcohols and in particular (+)-P-conhydrine.In contrast in a general synthesis of y-amino-alcohols (25) oxetanes (26) are opened regiospecifically with trimethylsilylcyanide-zinc iodide to yield y-hydroxyisonitriles (27) in good yield; amino-alcohols (25) are then obtained simply by hydrolysis.22 The synthesis of 1,3-diols has been described already; nevertheless Scheme 3 describes another approach this time to monoprotected diols containing a chiral centre at the 2-po~ition.~~ Particularly noteworthy is the complete chirality transfer that is observed during the [2,3]-sigmatropic rearrangement of the anion derived from the 2-stannyl ether. Reagents i BuLi; ii NaH BnCI; iii 03,NaBH. Scheme 3 Starting from racemic alcohols chiral ethers have been prepared by a phase transfer catalysed enantiomeric alk~lation.~~ The reaction which+ is claimed to be the first of its type requires the use of a chiral quaternary Et,NCH,CH(Et)Me and gives good chemical yields although the optical yields are only mediocre.A novel method for the preparation of symmetrical and unsymmetrical ethers relies upon a catalytic reduction of aldehydes and ketones with trityl perchlorate in the presence of a silane. If triethylsilane is the co-reactant then symmetrical ethers (RCH20CH2R) are formed from aldehydes (RCHO) whereas unsymmetrical ethers (RR'CHOR2) are produced when alkoxysilanes (R20SiMe3) and ketones and aldehydes (R'RCO) are reacted together.2s As usual many references have appeared relating to the protection of alcohols and selective protection of polyols.Thexyldimethylsilyl chloride falls within the first category and is a conveniently accessible reagent formed by a non-hazardous route; in this latter respect it has notable advantages over butyldimethylsilyl chloride.26 Apart from alcohols it will also act as protecting group for amines amides mercap- tans and acids. Organotin compounds allow for the selective acylation (and hence protection) of glycols. The method is simple and is demonstrated in Scheme 4.27 21 (Q) V. Ratovelomana J. Royer and H.-P. Husson Tetrahedron Lett. 1985 26 3803; (b)J. L. Marco J. Royer and H. P. Husson ibid. p. 6345; (c) ibid. p. 3567. 22 P. G. Gassman and L. M. Haberman Tetrahedron Lett. 1985 26,4971. 23 M. M. Midland and Y. C.Kwon Tetrahedron Lett. 1985 26 5013. 24 J. W.Verbicky jun. and E. A. O'Neil J. Org. Chem. 1985 50 1786. 25 J.4. Kato N. Iwasawa and T. Mukaiyama Chem. Lett. 1985 743. 26 H. Wetter and K. Oertle Tetrahedron Lett. 1985 26 5515. 27 A. Ricci S. Roelens and A. Vannucchi 1. Chem. SOC.,Chem. Commun. 1985 1457. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds R RxoHrm2-Rxocoph -ii iii OH OSiPhMe2 1 1iv iii ii -YOSiPhMe2 RYocoPh < < OCOPh OH I iv .y"" LOCOPh Reagents i Bu2SnO; ii PhCOCI; iii Me,PhSiCI; iv H,O+ Scheme 4 Primary alcohols are also preferentially acylated when 3-acyl-2-oxazolones are combined with zirconium complexes such as Zr( acac) and CP,Z~HC~.~* 3 Alkyl Halides The conversion of alcohols into alkyl halides is one of the standard synthetic routes to alkyl halides and in this context boron trifluoride etherate-halide ion is cited as a novel reagent for transforming alkyl benzyl and tertiary alcohols to the corresponding halides.29 On the other hand a more general route to iodides which allows for the preparation of primary and secondary alkyl iodides as well as activated ones is to treat the corresponding alcohol with a-chloroethyl chloroformate and sodium iodide in a one-pot rea~tion.~' In this case yields vary between 50-90% in the 11 examples attempted.Synthetically useful vinyl chlorides are obtained by a different approach i.e. direct chlorination of (E)-vinyl boronic acids,31 and have been further converted into (E,Z)-conjugated dienoates dienones and dienols with high stereospecificity by a palladium-catalysed reaction with vinylic substrates such as acrylates vinyl-ketones and a~rolein.~~ Another halogenation though this time using NCS or NBS as halogenating agent generates a-chiral halogeno-esters (28) with high enantiomeric excess.33 Thus camphor- 10-sulphonic acid derived esters give (28) after successive treatments with LDA-trimethyl chlorosilane followed by NCS or NBS; the halogeno-esters (28) so formed can then be converted into chiral halogeno-hydrins which themselves furnish chiral terminal epoxides in high enantiomeric excess.20 T. Kunieda T. Mori T. Higuchi and M. Hirobe Tetrahedron Lett. 1985 26 1977. 29 A. K. Mandal and S. W. Mahajan Tetrahedron Lett.1985 26 3863. 30 J. J. Brunet H. Laurent and P. Caubere Tetrahedron Lett. 1985 26 5445. 31 S. A. Kunda T. L. Smith M. P. Hylarides and G. W. Kabalka Tetrahedron Lett. 1985 26 279. 32 T. Jeffery Tetrahedron Lett. 1985 26 2667. 33 W. Oppolzer and P. Dudfield Tetrahedron Lett. 1985 26 5037. 116 P. F. Gordon In a preparatively useful carbon-carbon bond forming reaction alkyl bromides have been used as precursors to alkyl radicals which then add to the tri-n-butyl- stannane-substituted terminus of alkenes to produce various alkylated aliphatic compounds.34 X = C1,Br 4 Aldehydes and Ketones Over the past decade significant advances have been made in the art of controlling selectivity in the aldol reaction. This trend continues as does its exploitation in natural product synthesis.For example a key step in the synthesis of (+)-milbemycin p3is a Lewis acid [BF3(OEt),] catalysed and directed intramolecular aldol reaction used for the conversion of the bicycle (29) into the undecane (30).3' Good selectivity can also be imposed in intermolecular aldol reactions by using a metal to chelate with oxygen and/or nitrogen functionality present in the reactants as demonstrated by a chelation-controlled stereoselective synthesis of cyanohydrins (31)? In this case a a-chiral acyl cyanide (32) is combined with a silyl enol ether and titanium chloride resulting in a 1,2-asymmetric induction in high yield both chemical and optical. A similar strategy only this time starting from the a-chiral aldehyde (33) and the sulphur-substituted enol ether (34) results in the formation of syn-diols (35) with high selectivity only if magnesium cations are present.37a3b Interestingly the sulphur group which is easily removed aids in the observed selectivity.anti-Diols can also be synthesized from the same starting materials merely by omitting the magnesium salt as shown in the synthesis of (+)-blastmycinone. \ OH OHCq OSiMe3 0 I RG RI0PCN 4 O> SMe SMe 0 H Ph > (33) (34) (35) Ph 34 J. E. Baldwin and D. R. Kelly J. Chem. Soc. Chem. Commun. 1985 682. 3s S. D. A. Street C. Yeates P. Kocienski and S. F. Campbell J. Chem. Soc. Chem. Cornmun. 1985 1386. 36 M. T. Reetz K. Kesseler and A. Jung Angew. Chem. Znt. Ed. Engl. 1985 24 989.37 (a) J.4. Uenishi H. Tomozane and M. Yamato J. Chem. Soc. Chem. Cornmun. 1985 717; (b)J.4. Uenishi H. Tomozane and M. Yamamoto Tetrahedron Lett. 1985 26 3467. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds By the appropriate choice of counter-ion three of the four aldol adducts from the reaction of chiral siloxy-ketones (36) with aldehydes can be obtained. For instance the (2)-lithium enolate gives adduct (37a) the (2)-boron enolate affords adduct (37b) and the (2)-magnesium enolate provides adduct (37~).~* In the aldol reaction between siloxy-ketones (38) and aldehydes (RCHO) tin(I1) triflate is used as the chelate and again successfully provides a good yield of the aldol adduct (39) from which the epoxides (40)are obtained readily (with potassium fluoride-crown ethers).39 Since epoxides (40) can be converted easily into a,P-epoxy-esters (NaIO,) and to a$-epoxy-aldehydes (NaBH then NaIO,) the route is a convenient means of accessing cis-a,P-epoxy-esters and aldehydes with high selectivity and is therefore an attractive alternative to the Darzens reaction.The utility of this general approach has been demonstrated in the synthesis of 2-amino-2-deoxy-~-arabinitol, starting from a chiral aldehyde. Similarly a tin (aza) enolate gives high diastereo- and enantio-selectivity in the aldol reaction between aldehydes (RCHO) and chiral oxazolidine (41) derived from norephedrine and 3-pentan0ne.~' Furthermore the chiral aldol adducts that are obtained have the less accessible anti configuration.0 OSiMe3 But+OSiMe3 0 a A H BdX Me H Y OH (38) b Me H OH H c H Me OH H (37) RJ%J0 Me An interesting route to optically pure a-substituted aldehydes has been developed based upon an aluminium-induced asymmetric pinacol rearrangement. The stereodefined P-mesyloxy-alcohols (42)when treated with di-isobutylaluminium hydride-ethyl aluminium chloride rearrange highly selectively to ketones (43) assuming that X migrates in preference to Y?l The usual order of migratory aptitude found in the pinacol reaction applies here. However by using the above reagent combination adequate migratory preference is shown even between different alkyl groups provided that they exhibit a significantly different steric requirement. The same authors also report on a rather similar rearrangement of a-mesyloxy-acetals 38 C.H. Heathcock and S. Arseniyadis Tetrahedron Lett. 1985 26 6009. 39 T. Mukaiyama T. Yura and N. Iwasawa Chem. Lett. 1985 809. 40 K. Narasaka and T. Miwa Chem. Lett. 1985 1217. 41 (a) K. Suzuki K. Tomooka M. Shimazaki and G.-i. Tsuchihashi Tetrahedron Lett. 1985 26 4781; (b) K. Suzuki K. Tomooka T. Matsumoto E. Katayama and G.4. Tsuchihashi ibid. 3711; (c) Y. Honda M. Sakai and G.4. Tsuchihashi Chm. Left.,1985 1153. 118 P. E Gordon though this time involving a reductive step to give chiral a-substituted aldehyde ketals (44).41cThe above reactions have formed the basis of routes to (R)-(-)-circumene and the C-1-C-9 and C-11-C-17 fragments of protomycinolide( IV).In a recent study it has been shown that methylation of enolates (45; R4= H) and protonation of enolates (45; R4= alkyl) are diastereoselective and selective in the opposite sense to nucleophilic attack on the corresponding aldehyde and ketone respective~y.~' Several papers have appeared which are devoted to stereoselectivity in the Michael reaction. Thus silyl enol ethers derived from ketones show a general tendency for anti addition regardless of the stereochemistry of the enol-~ilane.~~ For enol-ethers derived from aliphatic ketones the selectivity increases from a rather poor 1.5 :1 to a good 10 :1 with increasing steric hindrance whereas (2)-enol-silanes derived from propiophenone and related aromatic ketones show excellent selectivity (10 1-20 1) although (E)-enol-silanes give poorer results (3 1-4 1).In complete contrast silyl-ketene acetals show high syn-selectivity in their reaction with acyclic t-butyl- unsaturated ketones although the selectivity is considerably lower with cyclo- alkenones. Like silyl enol ethers enamines will also undergo the Michael reaction with electrophilic alkenes and furthermore it has been found that in the addition of chiral organotin enamines (46) high asymmetric induction is observed.44",b The Michael adducts thus obtained can be hydrolysed to ketones (47) with enantiomeric excesses in the range 10-98°/~. The higher enantiomeric excesses (>go%) invariably arise from reactions involving acrylates as Michael acceptor whereas acrylonitriles appear to give rather poor results (10-44%).Two papers have dealt with catalysis in such Michael reactions; one recommends tritylperchl~rate~~ and the other uses potassium t-butoxide on xonotlite or potassium fluoride on alumina.46 Several new and interesting routes have been reported which involve the formation of aldehydes and ketones and in some cases their homologation. For instance 42 1. Fleming and J. Lewis J. Chern. Soc. Chem. Commun. 1985 149. 43 C. H. Heathcock M. H. Norman and D. E. Uehling J. Am. Chem. SOC.,1985 107 2797. 44 (a) C. Stetin B. de Jeso and J.-C. Pommier J. Org. Chem. 1985 50,3863; (b)B. Nebout B. de Jeso and J.-C. Pommier J. Chem. Soc. Chem. Commun. 1985 504. 4s S. Kobayashi M. Murakami and T. Mukaiyama Chem.Lett. 1985 953. 46 P. Laszlo and P. Pennetreau Tetrahedron Lett. 1985 26 2645. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 4-formyl-2-methyl-l,3,4-thiadiazolin-5-thione is a new highly reactive crystalline formylating reagent for amines and alcohols giving N-and 0-formylated products in yields generally in excess of 70Y0.~~ Scheme 5 illustrates some of these new and efficient routes to unsymmetrical ketones starting from aldehydes and acid chlorides and the homologation to a-hydroxy-ket~nes.~*-~~ RCHO + R'M RCOCl + R'I II R-C-R' 0 (ITLi Reagents i VC1,;48 ii Pd/zn-C~;~~ ;iv LiAlH,; v H30+;50 vi MCPBA; vii NaBH,;" iii viii HCGC-MgBr; ix PhI(OCOCF3)2PIFA52 Scheme 5 p-Hydroxy-ketones are obtained by coupling a-halogeno-ketones and aldehydes in the presence of cerium(111) chloride-sodium iodide; the choice of reagent is vital since cerium( 111) iodide gives the corresponding a$-unsaturated ketone.53 In con- trast a#-unsaturated aldehydes (48)are synthesized by opening of the cyclopropane (49),which can therefore be classed as a d3 reagent.54 Apart from the synthesis of ketones and hydroxy-ketones just described two useful syntheses of unsymmetrical a-diketones have been reported.In one acylating reagents are cross-coupled with acyl halides in reasonable yield with palladium catalysis,55 and in the second a-diketones can be prepared by oxidation of a-thiomethyl-ketones with CuCl,-CuO in aqueous acetone.56 OMEM (48) (49) 47 H. Yazewa and S.Goto Tetrahedron Lett. 1985 26 3703. 48 T. Hirao D. Misu and T. Agawa J. Am. Chem. Soc. 1985 107 7179. 49 Y. Tamaru H. Ochiai F. Sanda and Z.-i. Yoshida Tetrahedron Lett. 1985 26 5529. 50 M. Fetizon I. Hanna and J. Rens. Tetrahedron Lett. 1985 26 3453. 51 M. Fetizon P. Goulaouic and I. Hanna Tetrahedron Lett. 1985 26 4925. 52 Y. Tamura T. Yakura J.-i. Haruta and Y. Kita Tetrahedron Lett. 1985 26 3837. 53 S.-i. Fukuzawa T. Fujinami and S. Sakai J. Chem. Soc. Chem. Commun. 1985 777. 54 M. Pohmakotr and S. Pisutjaroenpong Tetrahedron Lett. 1985 26 3613. 55 J.-B. Verlhac E. Chanson B. Jousseaume and J.-P. Quintaro Tetrahedron Lett. 1985 26 6075. 56 M. C. Carre and P. Caubere Tetrahedron Lett. 1985 26 3103. 120 P. F.Gordon Finally in this section Kauffmann and his group have reported on the selectivity of hafnium reagents in their reaction with carbonyl group^.^^‘'*^ Trichlorohafnium methyl is not able to attack an ester or a nitrile and fails to discriminate in competition experiments between aldehydes and ketones. On the contrary trichlorohafnium butyl and triethoxyhafnium methyl are both aldehyde selective and likewise the complexes (hal),M-Me show high aldehyde selectivity where M is scandium yttrium or lanthanum. However no selectivity is observed where the metal is praseodymium cerium neodymium samarium or gadolinium. 5 Carboxylic Acids and Derivatives In common with ketones esters will also form enolates (and the corresponding silyl enol ethers) readily and so many of the methods used for achieving stereospecificity in ketone enolate reactions can be applied to reactions involving ester enolates.Over the last few years a very popular strategy for controlling the stereochemistry in such reactions has been to employ metals capable of chelating with the ester enolate anion and other functionality within the reacting species. In many cases titanium has been found to be the metal of choice and this is so in the synthesis of the thioester (50). In fact two separate highly enantiospecific aldol reactions are used to generate (50); in the first the ephedrine silyl acetal (51) is reacted with trimethyl acetal in the presence of titanium tetrachloride to give (52) after further transformations.s8n The latter is then converted into aldehyde (53) which reacts with the thioestersilylketene acetal from acetic acid giving product (50) once again in the presence of titanium tetrachloride.These reactions have been extended so that various anti-a-methyl-@ hydroxy-esters (54) can be synthesized in high optical yield by reaction of the ephedrine silylacetal (51) with aldehydes again with titanium tetrachloride present.58b Further examples of thioester silylketene acetal additions to a-alkoxy-aldehydes have also been recorded and give good yields of the syn-addition products (55) (SnC1 catalyst).58c In the presence of another Lewis acid BF,OEt, thioester silylketene acetals add to aldehydes with good yield and selec- Me Me0 OMe ,+OH 57 (a) T. Kauffmann C. Pahde and D.Wingbermuhle Tetrahedron Lett. 1985,26,4059;(6)T. Kauffmann C. Pahde A. Tannert and D. Wingbermuhle ibid. p. 4063. 58 (a) C. Gennari A. Bernardi C. Scolastico and D. Potenza Tetrahedron Left. 1985 26 4129; (b) C. Gennari A. Bernardi L. Colombo and C. Scolastico J. Am. Chem. SOC.,1985,107,5812;(c) C. Gennari A. Bernardi G. Poli and C. Scolastico Tetrahedron Lett. 1985 26 2373; (d) C. Gennari A. Bernardi S. Cardarni and C. Scolastico ibid. p. 797. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 121 tivity giving anti-addition products (56).58dIt can therefore be seen that by varying the nature of the ester enolate the substrate and the catalyst various stereochemis- tries can be obtained predictably at the a,p and y positions to the ester group.An alternative and very effective chiral auxiliary to the N-methylephedrine just described is the camphor derivative (57) which promotes high asymmetric inductions in aldol reactions of 0-silylketene acetals generated from (57) with aldehyde^;'^" this reaction forms the key step in the synthesis of dictyopterene (h~rmosirene).~~’ Exceptionally high diastereofacial selectivity is observed in aldol reactions between sulphur-substituted ester enolates (58) and a-chiral aldehydes6’ The syn 2,2-dithioaldol adducts so obtained can be desulphurized under very mild conditions with nickel boride-hydrogen to yield the more usual aldol products. Sulphur has figured in several of the reactions discussed already either as thioesters or thioketals.Its use in the chiral 1,3-oxazolidine-2-thiones(59) is a further illustration of its versatility. Amides derived from the above thiones are easily transformed to their tin and boron enolates which then add to aldehydes to give good yields of the corresponding aldol adducts with diastereoselectivities varying between 4 :1 and 9 1.61apbFrom these aldol adducts the same authors have prepared chiral azetidinones and p-lactams. Continuing with the chemistry of ester enolates Fleming has published results of his studies showing that P-silylenolates (60) react with electrophiles to give silyl esters (61). Apparently the observed diastereoselectivity is substantially electronic in origin. Silyl esters (61) can then be oxidized (MCPBA) to the corresponding p-hydroxy-esters and the overall reaction is therefore an alternative to the aldol V I BY A B X Y H H E t H H Ph H Me (59) 59 (a) G.Helmchen U. Leikauf and I. Taufer-Knopfel Angew. Chem. Int. Ed. Engl. 1985 24 874; (6) D. Dorsch E. Kunz and G. Helmchen Tetrahedron Lett. 1985 26 3319. 60 L. A. Flippin and M. A. Dombroski Tetrahedron Lett. 1985 26 2977. 61 (n)Y. Nagao S. Yamada T. Kumagai M. Ochiai and E. Fujita J. Chem. SOC.,Chem. Commun. 1985 1418; (b) C.-N. Hsiao S. P. Ashburn and M. J. Miller Tetrahedron Lett. 1985 26 4855. 62 (a) I. Fleming J. H. M. Hill D. Parker and D. Waterson J. Chem. SOC.,Chem. Commun. 1985 318; (6)H.-F. Chow and I. Fleming Tetrahedron Lett. 1985 26 397. 122 P. E Gordon Davies and his group have published a number of papers concerned with the use of chiral iron compounds in asymmetric aldol and Michael reactions.In a series of papers they have dealt with the synthesis and stereoselective reactions of chiral iron acyls (62) and (63).63a-eFor example a,P-unsaturated acyl complexes (62) can be prepared by Peterson olefination and undergo highly stereoselective conjugate additions and conjugate addition-alkylations giving the Michael adducts (64) with almost complete control of the regiochemistry i.e. diastereoisomeric ratios 10 1-30 1. On the other hand copper enolates of complexes (63) react with symmetrical ketones to generate (R&SS)-a-methyl-P-hydroxy acyl complexes and with aldehydes to provide erythro-aldol adducts in good yield.If the cation in this latter case is changed from copper to aluminium threo products are obtained with equally high selectivity. A further illustration of the synthetic utility of these complexes is given by their reaction with butene oxides in which lithium enolates of (63; BF,OEt, catalyst) preferentially open the epoxide where the enolate configuration at iron matches that at the epoxide carbon being attacked. Another author has reported on a high yield preparation of iron complexes (62) from (63) by aldol reaction and dehydrati~n.~~ In all the foregoing examples the iron can be removed at the end of the reaction to leave the corresponding acid. It therefore appears that these reagents are extremely useful ‘chiral carboxylic acid equivalents’ and should prove most valuable to the synthetic chemist; it is unlikely that the last has been heard of their use.OC-Fe I \O The synthesis of several different hydroxy-acids has been discussed already. These methods have generally relied upon the aldol reaction to generate the hydroxy-group. However it is possible to insert a hydroxy-group (Y to a carboxylic group by an oxidation reaction (see also reference 62) in a stereocontrolled fashion. The oxaziridine (65) seems to be a particularly efficient oxidizing reagent for converting carboxylic acid enolates into a-hydroxy-acids and high asymmetric induction can be observed if the carboxylic acid is converted first into a chiral amide derivative e.g. with prolinol or oxazolidinone before making the en~late.~~~’~ Using a different combination of chiral auxiliary e.g.(66) and oxidizing agent (molybdenum peroxide) 63 (a) L. S. Liebeskind and M. E. Welker Tetrahedron Lett. 1985 26 3079; (b) S. G. Davies and J. C. Walker J. Chem. Soc. Chem. Commun. 1985 209; (c) P. W. Ambler and S. G. Davies Tetrahedron Lett 1985 26 2129; (d) S. G. Davies I. M. Dordor-Hedgecock and P. Warner ibid. p. 2125; (e) S. G. Davies and P. Warner ibid. p. 4815. 64 L. S. Liebeskind R. W. Fengi and M. E. Welker Tetrahedron Left. 1985 26 3075. 65 (a) F. A. Davies and L. C. Vishwakarma Tetrahedron Lett. 1985 26 3539; (b) D. A. Evans M. M. Momssey and R. L. Dorow J. Am. Chem. Soc. 1985 107 4346. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 123 a similar high level of asymmetric inductions can be attained via the ester enolate.66 In contrast chiral a-hydroxycarboxylic acids can be produced starting from achiral 1,2-diols by oxidizing the primary alcohol selectively with co-immobilized alcohol and aldehyde dehydrogenases as catalysts.67 The reaction is claimed to offer several advantages over enzymic reductions of a-keto-acids not least being the greater stability of the starting material.This oxidation is in fact not just limited to hydroxy- acids since a very similar process allows the preparation of chiral P-hydroxy-a- amino-acids from 2-amino- 1,3-diols. Similar amino-acids have been synthesized in optically pure form by utilizing a different route as described in Scheme 6.6* The route depends on a novel epoxide ring opening by in situ generated hydrazoic acid followed by a selective reduction of the ester.> L-Tartaric - -C02Et -D-Tartaric acid Et02C-~C02Et EtO2C acid Ii Ii ?H ?H ?H \ OH OH I I EtOzC~Co2Et C0,Et Eto2Cp o*02Et NHBoc NHBoc NH2 Reagents i HN,-DMF; ii BH,.Me,S cat. NaBH,; iii Me2C(OMe)z H+,Me2CO; iv H2 Pd (t-BOC),O Scheme 6 In the last sequence the selective opening of a glycidic ester constitutes a key step in the synthesis of P-hydroxy-acids. In a further synthesis of hydroxy-acids the acid itself is used rather than the ester deri~ative.~~ The stereochemistry at the epoxide ring ultimately determines the regiochemistry of the products such that trans-epoxides are attacked at the 2-position as are the corresponding esters giving 66 R.Gamboni P. Mohr N. Waespe-Sarcevic and C. Tamm Tetrahedron Lett. 1985 26 203. 67 C.-H. Wong and J. R. Matos J. Org. Chern. 1985 50 1992. 68 S. Saito N. Bunya M. Inaba T. Moriwake and S. Torii Tetrahedron Lett. 1985 26 5309. 69 J. M. Chong and K. B. Sharpless Tetrahedron Len 1985 26 4683. 124 P.F. Gordon P-hydroxy-a-substituted acids whereas cis-epoxides yield a-hydroxy-P-substituted acids arising from attack at the 3-position in contrast to the corresponding esters. This report therefore appears to be the first published on organocuprate additions to glycidic acids. One aspect of asymmetric Michael addition reactions has already been covered in the context of chiral iron complexes. However there are several more reports of asymmetric Michael reactions involving more conventional chiral auxiliaries.For example 1,4-addition of Grignard reagents to chiral amides (67) occurs with high diastereoselectivity to yield 3-substituted carboxylic acids after hydrolysis in enan- tiomeric excesses up to 89?40.~' Interestingly the presence of tertiary amines e.g. DBU significantly increases both the chemical and optical yields of the 1,4-addition. In the highly diastereoselective tandem alkylation of prochiral a,P-unsaturated esters novel use is made of lithiated dithioacetals as stereocontrolling agents.71" Almost complete anti addition is observed giving products (68) from the esters (69; R = H); the other isomers (70) are also available simply by starting with esters (69) and using acetic acid to quench the enolate anion.If chiral amines are used then asymmetric induction is observed although enantiomeric excesses are at best only mediocre.71b Most impressive yields both chemical and optical are seen in 1,4-additions of organocopper reagents to a,P-unsaturated esters derived from chiral sulphonamide-shielded alcohols (57).724b By appropriate choice of solvent e.g. THF and the method by which the organocopper reagent is generated (best from Grignard reagents) it is possible to obtain diastereoselectivities of 99 :1accompanied by chemical yields of greater than 80%. ,OR' Another powerful strategy for elaborating new stereodefined centres relies upon the high level of stereocontrol possible in rearrangement reactions such as the Claisen rearrangement.A good example of this approach can be seen in the rearrangement of ally1 vinyl ether (71) to the P-ketoester (72) which has the correct relative stereochemistry at C8 C9,and C,4 of the quas~inoids.~~ In particular this route has been used in the synthesis of (-)-bruceantin. High asymmetric induction is also observed in the Claisen rearrangement of N-allylketene- N,0-acetals as shown by the rearrangement of (73) which occurs with 84-96% diastereoselection leading eventually to the chiral acids (74) after deprotection and recovery of the chiral amino-al~ohol.~~ The Claisen rearrangement figures again in the synthesis of bistetrahydrofuran (75) which is a useful precursor in the synthesis of polyether 70 K.Soai H. Machida and A. Ookawa J. Chem. SOC.,Chem. Commun. 1985 469. 71 (a) H. Kawasaki K. Tomioka and K. Koga Tetrahedron Lett. 1985 26 3031; (b) K. Tomioka M. Sudani Y. Shinmi and K. Koga Chem. Lett. 1985 329. 72 (a) G. Helmchen and G. Wegner Tetrahedron Lett. 1985,26 6051; (6) ibid. p. 6047. 73 F. E. Ziegler S. I. Klein U. K. Pati and T.-F. Wang J. Am. Chem. SOC 1985 107 2730. 74 M. J. Kurth 0. H. W. Decker H. Hope and M. D. Yanuck. 1.Am. Chem. Soc. 1985 107 443. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds ionophores.’’ The key step is thought to be the rearrangement of the ‘in situ’ formed ester (76) via its ester enolate anion and occurs with high stereocontrol. A different type of rearrangement namely the ene reaction is responsible for the efficient generation of chiral a-hydroxy-acids and relies heavily upon the chiral auxiliary (77; R = H) for the high asymmetric induction ~bserved.~~*~~~ In the first step of the reaction the auxiliary (77) is converted into the glyoxylate ester which in the presence of tin( IV) chloride undergoes the ene reaction.In one example illustrating the usefulness of this approach bicyclo [3.3.0]octadiene (78) and the glyoxylate (77; R = COCHO) are reacted to give the acid (79) thus providing for selection between the enantiotopically related rings of (78). X uc0r (74) (75) (76) doR H H A different approach to asymmetric induction does not rely upon metal chelation or rearrangements but uses the symmetry of the molecule.For instance derivative (80) is formed from 3-methyl glutaric acid and can be aminolysed to amide (81) with high ~electivity.’~ If (81) is in turn treated with a nucleophile then a series of synthetically useful optically pure bifunctional synthons become available for further exploitation. The selectivity observed is thought to originate from dipole-dipole repulsions between the carbonyl groups and the pro-R and pro-S groups such that the molecule adopts a W-Shape. In this W-conformation nucleophiles would be 75 R. E. Ireland and D. W. Norbeck J. Am. Chem. Soc. 1985 107 3279. 76 (a) J. K. Whitesell and D. E. Allen J. Org. Chem. 1985,50 3025; (b)J. K. Whitesell H.-H. Chen and R. M. Lawrence J. Org. Chem. 1985 50 4663. Y.Nagao T. Ikeda T. Inoue M. Yagi M. Shiro and E. Fujita J. Org. Chem. 1985 50 4072. 77 126 P. F. Gordon pro-S pro-R COzMe CH 1. CpTi AlMe, \/ c1 expected to attack predominantly at the pru-S ligand from the least hindered face in the transition state. Finally in this section porcine liver esterase has been immobilized on acrylic beads to give a reagent which can be conveniently used for asymmetric hydrolyses of esters and yet retains 70% of the activity of untreated e~terase.~~ In complete contrast the titanium complex (82) methylenates carbonyl corn pound^.^^ A unique feature of this reagent is that it converts carboxylic acid esters into vinyl ethers and amides into enamines. 6 Lactones Some recent advances in the use of chiral sulphur groups are discussed more generally in the section on sulphur.However several reports of their use specific to the synthesis of lactones will be dealt with here. For instance optically pure (+)-R-p-tolyl sulphoxides have been lithiated and alkylated with lithium a-bromoacrylate with medium to high stereoselectivity to yield an adduct which can be converted into optically active y-lactones (83) in three straightforward steps." An alternative route to y-lactones Le. (84) utilizes another chiral sulphoxide (R3R2C=CR2SOTol) to direct the lactonization reaction with dichloroketene.81 In this way almost complete enantiospecificity is observed during the lactonization with (E)-3(R)-p-tolylsulphinylocteneto give a precursor for the synthesis of opti- cally pure oak lactones.SiMeq +-R H R2__ R3C1 78 K. Laumen E. H. Reimerdes M. Schneider and H. Gorisch Tetrahedron Lett. 1985 26 407. 79 S. H. Pine R. J.Pettit G. D. Geib S. G. Craz C. H. Gallego T. Tijerina and R. D. Pine J. Org. Chem. 1985 50 1212. 80 P. Bravo G. Resnati and F. Viani Tetrahedron Lett. 1985 26 2913. J. P. Marino and R. F. de la Pradilla. Tetrahedron Lett. 1985. 26 5381. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Several papers have been released relating the use of chiral lactones as templates for asymmetric induction reactions. In this context the silyl-substituted ketones (85) react with aldehydes (RCHMeCHO) giving lactones (86) with extremely high diastereoselectivity (Cram).** On the other hand chiral a-alkylidene- y-butyrolac- tones (87) act as Michael acceptors in the construction of contiguous tertiary and quaternary carbon centres by tandem alkylati01-1.~~ Nucleophilic attack takes place almost exclusively from the face opposite to the bulky oxy-substituent in (87); however the selectivity of the electrophilic attack depends critically on R and R'.For (87; R = Me R' = H) high diastereoselectivity is observed whereas for (87; R = H R' = Me) rather poor diastereoselectivity is found. These effects can be rationalized by studying transition-state geometries. Hanessian also uses chiral butyrolactones as chiral templates to control elegantly the stereochemistry of both nucleophilic and electrophilic additions.84"-" The butyrolactones are prepared from simple readily available chiral precursors such as (S)-glutamic acid and acyclic carbon skeletons can be constructed with a stereochemically predictable substitution pattern at the 1,3- 1,4- and 1,5-positions.A notable feature is the repeated use of the butyrolactone template to control the stereochemistry of further chiral centres. It thus seems that the overall strategy is quite versatile in allowing the efficient generation of multiply defined stereocentres in compounds of relevance to natural product synthesis. R' OSiMe3 OPSiM" In the synthesis of tricyclic lactones a highly enantioselective intramolecular hetero-Diels- Alder reaction allows for stereospecific construction of two of the three rings.85 In this case ephedrine is incorporated into the precursor (88) to act as the chiral auxiliary.A general route for the construction of the cis-fused bicyclic lactones (89) also relies upon a selective ring-forming reaction and is catalysed by palladium; R3*o I Ph R x2 Y. Tomo and K. Yamamoto Tetrahedron Lett. 1985 26 1061. 83 K. Tomioka H. Kawasaki and K. Koga Tetrahedron Lett. 1985 26 3027. 84 (a) S. Hanessian P. J. Murray and S. P. Sahoo Tetrahedron Lerr. 1985 26 5623; (b) ibid. p. 5627 (c) ibid. p. 5631. L. F. Tietze S. Brand and T. Pfeiffer Angew. Chem. Int. Ed. Engl. 1985 24 784. 85 128 P. F. Gordon furthermore only mild conditions are required in the oxycarbonylation step and yields can be as high as 80Y0.’~ There are many procedures that exist for the synthesis of a-methylene-y-butyrolac-tones however there are relatively few for the isomeric P-methylene- y-lactones.Hence a report concerned with a general synthesis of the latter is to be welcomed. Acrylates (90) are first dialkylated in two separate stages and hydrofluoric acid is then used to deprotect the oxygen and promote cyclization to the lactone (91).” Turning to larger rings two papers have been published dealing with the formation of medium-ring lactones; in the first catacondensed lactols (92) undergo radical induced p-scission to give lactones (93),’* whereas in the second ethylaluminium dichloride effects ring closure of the allylsilane (94).89 7 Amines Imines and other Nitrogen Compounds The synthesis and reaction of amides and nitriles is covered in Section 5.There are surprisingly few clean efficient methods for the reduction of aliphatic nitro-compounds to the corresponding amines despite the continued increase in the number of methods to generate such nitro-compounds. The reagent combination sodium borohydride-nickel chloride is now claimed to carry out this conversion rapidly and efficiently.” The active agent is thought to be nickel boride and is catalytic in nickel; furthermore several other reducible groups are tolerated e.g. esters acids -but not conjugated alkenes. Organic azides are also converted efficiently into amines by a reductive amination process using tetracarbonylhy- dridoferrate(0) under carbon monoxide and yields are usually excellent.’l A useful route to tertiary N-methylated amines also involves a reduction step and starts from the corresponding secondary amine.92 Two steps are required for the conversion which can be carried out as a ‘one-pot’ reaction; the first is the conversion of the amine into its carbonate ester and the second is a reduction by lithium aluminium 86 Y.Tamaru T. Kobayashi S.-i. Kawamura H. Ochiai M. Hojo and Z.4. Yoshida Tetrahedron Lett. 1985 26,3207. 87 A. E.Greene F. Coelho and J.-P.Depres J. Org. Chem. 1985 50 1973. 88 H. Suginome and S. Yamada Tetrahedron Lett. 1985 26,3715. 89 M.Wada T. Shigehisa and K.-y. Akiba Tetrahedron Lett. 1985 26,5191. 90 J. 0.Osby and B. Ganem Tetrahedron Lett. 1985 26,6413. 91 S. C. Shim and K.N. Choi Tetrahedron Lett. 1985 26,3277. 92 S. Ram and R. E. Ehtenkaufer Tetrahedron Lett. 1985 26,5367. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds hydride. In contrast amines bearing an a-cyano-substituent are prepared by an oxidative route from secondary amines; phenylseleninic anhydride (or acid) combined with sodium cyanide (or trimethylsilylcyanide) effects the desired trans- formation.93 In the synthesis of enantiomerically pure enamines a chiral rhodium reagent {bis[(R)-(+) -binap]rhodium(I) perchlorate} catalyses the isomerization of the corre- sponding allylamines with enantiomeric excesses exceeding 96%.94 In their turn the practically unknown allylamines e.g. (99 have been synthesized via the Bruylants reaction in which allylaminonitriles are reacted with Grignard reagents (R4MgBr).95 A variety of different groups (R' R2 R3 R4) can thus be incorporated into (95) as illustrated by the eighteen examples which have been successfully attempted.Protec- ted allylamines can be prepared by palladium-catalysed attack of sulphonamides upon allylic substrate^.^^ The displacement goes with retention of configuration and since allylic chlorides are displaced before allylic acetates a degree of regioselectivity is possible. On the other hand protected amino-alcohols can be obtained directly from amino-alcohols by benzoylation with benzoyl cyanides generated by a ruthenium-catalysed oxidation of ~yanohydrins.~~ But Tertiary butyl formamidines (96) have been shown to be good a-amino-carbanion precursors since after metallation they can be alkylated with a,@-dihalogeno-alkanes providing access to various nitrogen-based heterocycles such as 2-arylpyridines pyrrolidines and nicotine analogue^.^^ Obviously they have considerable potential in natural product synthesis.Similarly a,P-alkoxyamines can be metallated and by varying the metal and employing double stereodiff erentiation enantiodivergent 1,2- and 1,3-asymmetric inductions are fa~ilitated.~~ For instance chelation control with metals such as magnesium aluminium and zinc gives alkoxyamines (97) and (98) from imines (99) and (loo) whereas non-chelation products having the opposite configuration about the carbon-nitrogen bond result when using boron reagents. Double stereodiff erentiation is possible if a chiral substituent is incorporated at the nitrogen in imines (99) and (100) giving a further level of stereocontrol.Thus 1,2-asymmetric inductions [for (97)] are controlled primarily by the chirality at the alkoxy-carbon whereas 1,2-asymrnetric inductions [for (98)] are controlled by the chirality at nitrogen. 92 S. Ram and R. E. Ehrenkaufer Tetrahedron Lett. 1985 26 5367. 93 D. H. R. Barton A. Billion and J. Boivin Tetrahedron Lett. 1985 26 1229. 94 K. Tani T. Yamagata Y. Tatsuno Y. Yamagata K.4. Tomita S. Akutagawa H. Kumobayashi and S. Otsuka Angew. Chem. Int. Ed. Engl 1985 24 217. 95 H. Ahlbrecht and H. Dollinger Synthesis 1985 743. 96 S. E. Byrstrom R. Aslanian and J.-E. Backvall Tetrahedron Lett.1985 26 1749. 97 S.4. Murahashi T. Naota and N. Nakojima Tetrahedron Lett. 1985 26 925. 98 A. I. Meyers and J. M. Marra Tetrahedron Lett. 1985 26 5863. 99 Y. Yarnamoto T. Komatsu and K. Maruyama J. Chem. Soc. Chem. Commun. 1985 814. 130 I? E Gordon Nitrones are formed in high yield by alkylation of aldoximes and ketoxime o-trimethylsilyl ethers with trialkyloxonium tetrafluoroborate and alkyl triflates at or below room temperature; loo nitrones in their turn have been photoisomerized in a chiral solvent to oxaziridines albeit in mediocre optical yields."' 8 Sulphur A recent trend in the area of sulphur-based reagents has been towards asymmetric induction reactions involving chiral sulphur groups. This trend continues as shown by the preparation of optically active allylic sulphoxides (101) in only three steps.lo2 If desired the other epimer can be obtained simply by heating (101).After metallation the anions of both epimers undergo highly stereospecific conjugate additions to cyclopent-2-en- 1 -one; presumably this reaction has wider scope. As the last reaction demonstrates chiral sulphoxides are not only easily accessible but are also capable of controlling the stereochemistry during addition reactions. This behaviour is further illustrated by the highly enantioselective synthesis of both enantiomers of allylic alcohols (102).'03" The anion from chiral p-tolyl methyl sulphoxide adds 1,2 to the imidazole (103) to yield the corresponding ketone which after reduction by lithium aluminium hydride is desulphurized to give the (R)-isomer of (102).In contrast di-isobutylaluminium hydride (ZnCl,) gives the (S)-isomer. The same authors have used a very similar method to prepare chiral epoxides (104) except that in this case the sulphur is removed concomitant with ring closure to give the ep~xide."~~ An almost identical approach has been used to generate rather similar epoxides which can then be converted into chiral lactones (105).'03' LOO N. A. Lebel and N. Balasubramanian Tetrahedron Lett. 1985 26 4331. 101 D. R. Boyd R. M. Campbell P. B. Coulter J. Grimshaw D. C. Neill and W. B. Jennings J. Chem. Soc. Perkin Trans. 1 1985 849. 102 M. S. Binns R. J. Goodridge R. K. Haynes and D. D. Ridley Tetrahedron Lett. 1985,26 6381.103 (a) G. Solladie G. Demailly and C. Greck J. Org. Chem. 1985 50 1552; (6) ibid. Tetrahedron Lett 1985,26,435; (c) H. Kosugi H. Konta and H. Uda J. Chem. SOC.,Chem. Commun. 1985 211. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Optically active sulphinates (106) and thiosulphinates (107) are also prepared readily and might be useful reagents in the fut~re."~",~ The sulphinates are prepared from symmetrical sulphites and t-butylmagnesium chloride in the presence of chiral amino-alcohols whereas the thiosulphinates are obtained by treatment of optically active p-toluenesulphinamides with thiols; enantiomeric excesses for both reactions are in the range 30-80°/0. A reaction which enhances the utility of chiral sulphur compounds has been published and is claimed to be the first general method for direct displacement of sulphur from chiral carbon centres.lo5 Thus chiral thiols are treated with tertiary butyl hypochlorite hexamethylphosphorous triamide and ammonium hexafluorophosphate to provide an intermediate which is readily attacked by various nucleophiles to give products with complete inversion at the chiral carbon centre.Yields tend to be high and examples of carbon halogen and nitrogen nucleophiles are given. .. Sulphur reagents have a wider role in organic synthesis and their usefulness is not just limited to asymmetric induction reactions as the following demonstrates. Sulphone (108) acts as a multi-coupling reagent since it can be reacted with two nucleophiles in a stepwise fashion to yield sulphones (109a) or alternatively reacted with an electrophile followed by a nucleophile to provide sulphones ( 109b).'06"*h The sulphones (109) are of obvious synthetic utility.In many cases after a sulphur reagent has been used a convenient desulphurization process is required to generate the target compound. Hence a report that nickelocene-lithium aluminium hydride is a new and effective desulphurization agent will be of intere~t."~ This reagent combination cleaves carbon-sulphur bonds in thiols sulphides and dithioacetals in fair-to-good yields and will even leave other reducible functionality untouched e.g. carbonyl groups double bonds. 9 Phosphorus As might be expected the Wittig reaction and its modifications dominate the area of phosphorus reagents and their role in organic synthesis.In the last few years Warren and his group have published a series of papers dealing with directing effects and stereocontrol in such reactions. Scheme 7 describes some of the more recent developments in this field. Route A depends upon the efficient acyl rearrangement which occurs in over 70% yield and the stereospecific reduction which favours the 104 (a) J. Drabowicz S. Legedz and M. Mikolajczyk J. Chem. Soc. Chem. Commun. 1985 1670; (b) J. Drabowicz and M. Mikolajczyk Tetrahedron Lett. 1985 26,5703. 10s G. A. KrafTt and T. L. Siddall Tetrahedron Lett. 1985 26,4867. 106 (a) P.Knochel and J. F. Normant Tetrahedron Lett. 1985 26,425; (b) P. Auvrey P. Knochel and J.F. Normant ibid. p. 2329. 107 M.-C. Chan K.-M. Cheng M. K. Li and T.-Y. Luh J. Chem. SOC.,Chem. Commun. 1985 1610. 132 P. F. Gordon i-iii 1 0 II ph2p> R' i vii R' 1viii 0 vR2 OAc R2 OH P$&Rh a R'& R3 R' (111) xii 1a R' (110) ix i x SR Ph)+ R3 R' OH 4 Reagents i. RuLi ii. R2 ; iii BuLi R'COCI; iv LDA; v NaBH,; vi NaH; vii R'COCHCHR'; viii Ac,O,PTSA; ix K2C03; x R4R5CO; xi MCPBA; xii RSH Scheme 7 threo-isomer.'08a A different rearrangement is used (in Route B) to generate stereo- specifically 8-hydroxyallylic phosphine oxides (110) from single isomers of the Homer-Wittig adducts.lo8' Phosphine oxides (110) have then been converted into hydroxydienes (Route C)'08cand also into all four isomers of epoxides (111) in a highly stereocontrolled fashion and thence to P-hydroxyallylic suiphides with the stereochemistry at the two chiral centres defined (Route D).108d*e 2-Triphenylphosphonium salts and 2-diphenylphosphine oxides of tetrahydro-furan and tetrahydropyran react with aldehydes and lactols to afford good yields of the corresponding enol ethers some of which have been converted into spiroketals (a)P.Wallace and S. Warren Tetrahedron Left 1985 26 5713; (b) A. B. McElroy and S. Warren ibid. p. 1677; (c) P. S. Brown A. B. McElroy and S. Warren ibid. p. 249 (d) A. B. McElroy and S. Warren ibid. p. 5709; (e) ibid. p. 2119. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 133 related to natural pheromones from such as Dacus oleae and Parauespula uulg~ris.'~' In contrast an intramolecular variation of the Horner-Wittig reaction allows for a simple and regiospecific conversion of y or S ketones to the corresponding cyclopen- tenones or cyclohexenones respectively.' lo The transformation is effected simply by adding the lithium phosphonate salt LiCHR*PO(OEt) to the lactones (112) and then by treatment of the ring-opened phosphonate with oxalyl chloride the ring closure is accomplished to provide the cycloalkenones (113).Finally in this section an unusual reaction of the phosphorane Ar,P=CHCH2TMS with a-methylal- dehydes allows for a novel method for a highly Cram-diastereoselective introduction of a vinyl group."' By careful choice of the substituent in the phosphorus reagent i.e.a 4-methoxy-group almost exclusive formation of the vinyl addition product (114) can be accomplished with virtually none of the product from the normal Wittig reaction being formed. Interestingly in the formation of (114) a strong preference for the formation of the syn-addition product is shown. OSiMe3 10 Reviews The following tables lists some of the more relevant reviews published in 1985. Title Reference Regioselective manipulation of hydroxyl groups via organotins 112 Use of organosilicon reagents as protective groups in organic synthesis 113 Oxoalkylation of carbonyl compounds with conjugated nitro-olefins 114 Reactive enolates from enol silyl ethers 115 Carbocationic and related processes in reactions of a-ketomesylates and triflates 116 Malonaldehyde succinaldehyde glutaraldehyde monocetals.Syn- thesis and applications 117 Thionation reactions 118 Synthesis and biological activity of a-methylene y-butyrolactones 119 Organothiophosphorus reagents in organic synthesis 120 Synthetic applications of tellurium 121 I09 S. V. Ley B. Lygo H. M. Organ and A. Wonnacott Tetrahedron 1985,41 3825. 110 H.-J. Altenbach W. Holzapfel G. Smerat and S. H. Finkler Tetrahedron Left. 1985 26 6329. 111 M. Tsukamoto H. Iio and T. Tokoroyarna Tetrahedron Lett. 1985 26 4471. 112 S. David and S. Hannessian Tetrahedron 1985 4 643. I13 M. Lalonde and T. H. Chan Synthesis 1985 817. 114 A. Yoshikoshi and M. Miyashita Acc. Chem. Res. 1985 18 284. 115 I.Kuwajirna and E. Nakumura Acc. Chem. Res. 1985 18 181. 116 X. Creary Acc. Chem. Res. 1985 18 3. 117 C. Botteghi and F. Soccolini Synthesis 1985 592. 118 M. P. Cava and M. I. Levinson Tetrahedron 1985,41 5061. 119 H. M. R. Hoffrnann and J. Rabe Angew. Chem. Int. Ed. Engl. 1985 24 94. IL0 R. A. Cherkasov G. A. Kutyrev and A. N. Pudovik Tetrahedron 1985 41 2567. L. Engman Acc. Chem. Res. 1985 18 274.

ISSN:0069-3030    

DOI:10.1039/OC9858200109

出版商:RSC    

年代:1985

数据来源: RSC

摘要:

6 Alicyclic Chemistry By S. A. MATLIN Chemistry Department The City University Northampton Square London EC 1 VO HB 1 General The effects of strain on reactivity have been reviewed.’ A number of reports have dealt with the properties of unsaturated bonds in alicyclic rings. Enthalpies of hydration of cyclic olefins have been measured leading to new and more reliable calculations of enthalpies of reaction of cycloalkanols.2 Large rate differences have been observed in the acid-catalysed hydration of cis-and trans-cyclooctenes suggesting that the former reacts by a conventional mechan- ism in which a solvationally equilibrated carbocation is formed reversibly but that the latter reacts by a rate-determining irreversible protonation step followed by solvent-reorganization-controlled reaction of the carbocation with water.3 Theoretical arguments have been presented in favour of the existence of singlet cyclopentyne as an intermediate with a true energy minimum in contrast to a recent MINDO/3 predi~tion.~ Deuterium exchange reactions show that on treatment with the lithium salt of 1,3-diaminopropane the triple bond in cycloalkynes (12-15 membered) circumnavigates the ring and this provides a simple method for per- deuteration.’ Cyclodeca-l,6-diyne has been prepared and photoelectron spectros- copy shows a strong interaction between its in-plane T-orbitak6 An extensive examination of the four isomeric cyclooctadienynes has been reported including their syntheses conformations stabilities and isomerizations.’ MNDO studies of didehydrocyclooctatetraene isomers predict that ( l) the cyclized form of the biradi- cal (2) should be as stable as the 1,2-didehydro isomer (3) and the latter is known to exist.8 ’ C.J. M. Stirling Tetrahedron 1985 41 1613; see also A. Bury H. A. Earl and C. J. M. Stirling J. Chem. SOC.,Chem. Commun. 1985 393. ’ K. B. Wiberg D. J. Wasserman E. J. Martin and M. A. Murcko J. Am. Chem. Soc. 1985 107 6019. Y. Chiang and A. J. Kresge J. Am. Chem. SOC.,1985 107 6363. S. Olivella M. A. Pericas A. Riera and A. Sole J. Chem. Res. (S) 1985 328. S. Abrams and A. Shaw Tetrahedron Lett. 1985 26 3431. R. Gleiter M. Karcher and W. Schafer Tetrahedron Lett. 1985 26 1635. ’ H. Kolshorn and H. Meier Chem. Ber. 1985 118 176; T. Echter and H. Meier ibid.p. 182; N. Hanold and H. Meier ibid. p. 198; H. Meier P. Konig T. Molz R. Gleiter and W. Schafer ibid. p. 210. M. J. S. Dewar and K. M. Merz jun. J. Am. Chem. SOC.,1985 107 6175. 135 136 S. A. Math The first members of a series of cyclic polyacetylenes termed the [nlpericyclynes containing rings composed of n ethynyl units alternating with n saturated C atoms have been reported. The permethyiated [5]-[8]pericyclynes were synthesized as colourless air-stable solids from linear polyacetylenes e.g. the [Slpericyclyne (Scheme l) but the method failed for smaller ring sizes.' / SiMe3 Scheme 1 Interest in cyclic allenes continues with reports of further details of theoretical studies on their structures and barriers to inversion," methods for convenient syntheses" of the cyclonoadienones (5) and (5a) via the dibroniocyclopropanes (4) and (6) and studies of the thermal12 (via retro-ene) and phot~chemical'~ (via cyclopropylidenes) fragmentations of cycloalka- lY2-dienes.Br Br Sugar molecules continue to provide a rich source of asymmetric carbon atoms for the construction of chiral alicyclic compound^.'^ Additions of butadiene and 2-diazopropane to the butenolide (7; R = Ph3Cor Bu'Ph,Si) derived from ribonolac- L. T. Scott G. J. DeCicco J. L. Hyun and G. Reinhardt J. Am. Chem. SOC.,1985 107 6546; K. N. Houk L. T. Scott N. G. Rondan D. C. Spellmeyer G. Reinhardt J. L. Hyun G. J. DeCicco R. Weiss M. H. M.Chen L. S. Bass J. Clardy F. S. Jorgensen T. A. Eaton V. Sarkozi C. M. Petit L.Ng and K. D. Jordan ibid. p. 6556. 10 R.0. Angus jun. M. W. Schmidt and R. P. Johnson J. Am. Chem. SOC.,1985 107 532. G. H. Perez and P. Weyerstahl Synthesis 1985 174. 12 J. D. Price and R. P. Johnson Tetrahedron Lett. 1985 26 2499. 13 J. D. Price and R. P. Johnson J. Am. Chem. SOC.,1985 107 2187. 14 C. S. Wilcox and L. M. Thomasco J. Org. Chem. 1985 50 546; H.-J. Altenbach W. Holzapfel G. Smerat and S. H. Finkler Tetrahedron Lett. 1985 26 6329. Alicyclic Chemistry tone afforded enantiomerically pure products with 6-and 3-membered rings respec- ti~e1y.I~ The diacetone glucose-derived dienes (8; R = H CH20H) also show stereospecificity in their Diels-Alder reactions with maleic anhydride.16 Cyclic a-amino esters with 4-6 membered rings can be prepared in high yields from ethyl isocyanoacetate and aliphatic dibromides.” Synthetic applications of [4 + 21 cycloreversion reactions have been reviewed.18 Free radical methods of initiating cyclization reactions are coming increasingly into vogue.The allylic sulphones (9; R’ R2 = H Me) cyclize on initiation with benzoyl peroxide to give cycl~pentanes.’~ Radical annulations of acetylenes ( 10; X = Br SePh) and (11) have been reported2’ and the photoreductive cyclization of 5,ti-unsaturated ketones via anion radicals has been described.” Other examples are given later in the chapter. R2 R2 CHR Y = C0,Me CN SO Ph Ph PhSe Ph,SnH R& - OH OH l5 J. Mann and A. Thomas J. Chem. SOC.,Chem.Commun. 1985 737. 16 K.-M. Sun R. M. Giuliano and B. Fraser-Reid J. Org. Chem. 1985 50 4774. D. Kalvin K. Ramalingam and R. Woodard Synth. Commun. 1985 15 267. l8 M.-C. Lasne and J.-L. Ripoll Synthesis 1985 121. 19 T. A. K. Smith and G. H. Witham J. Chem. SOC. Chem. Commun. 1985 897. 2o A. G. Angoh and D. J. Clive J. Chem. SOC.,Chem. Commun. 1985; 980; L. Set D. R. Cheshire and D. J. Clive ibid. p. 1205. 21 D. Belotti J. Cossy J. P. Pete and C. Portella Tetrahedron Lerr. 1985 26. 4591. 138 S. A. Matlin Aspects of topological sterochemistry have been reviewed22 and the problem of specification of relative stereochemistry in bridged bicyclic and spirobicyclic systems has been addressed by Whitesell and Mint~n.~~ For bridged bicyclic systems an axis passing through the bridgehead atoms is used together with the numbering system for the bicyclic skeleton to define two possible directions of rotation M (rnit) and G (gegen).This provides a simple solution to the most difficult cases where the three bridges are of identical length. Thus the relative stereochemistry of the bicyclo[2.2.2]octanediol (12) is specified as M-2,G-6 (or G-2,M-6) and its isomer (13) as M-2,M-6 (or G-2,G-6).For spirobicyclics the classical numbering system (smallest bridge numbered first) is used. Ring substituents are then specified as M if they lie on the same face of that ring as the lowest numbered atom of the other ring and as G if they lie on the opposite face. Thus (14) is named 1 -G,4-M and (15)is 1 -G,4-G.In cases where pseudosymmetry gives two alternative numbering systems it is proposed that M takes precedence over G to give a unique name.Hence (16) is named 2-M,6-M rather than 2-M,6-G.The system is commendable not only because it is easy to apply but also because stereochemical relationships are often apparent from the name even before examination of the structural drawing. a OH 2 Three-membered Rings The classical Simmons-Smith procedure for cyclopropanation utilizes diiodo- methane. It has now been shown that with the aid of ultrasonic agitation the more convenient and economical dibromomethane can be used with good yields.24 A direct approach to the synthetically useful 1-phenylsulphonylcyclopropanecar-boxylic acid and its derivatives has been e~tablished,~~ using phase transfer-catalysed alkylation of the phenylsulphonyl methyl derivatives (17; R = CO,Et CN).+ PhS02CH2R PhCH,NMe,+ OH-(Bi Br (17) 22 D. M. Walba Tetrahedron 1985 41 3161. 23 J. K. Whitesell and M. A. Minton J. Org. Chem. 1985 50 509. 24 E. C. Friedrich J. M. Domek and R. Y. Pong J. Org. Chem. 1985 50 4640. 25 M. Takahashi H. Suzuki and Y. Kata Bull. Chem. SOC.Jpn. 1985 58. 765. Alicyclic Chemistry 0 BF4- /-/o I1N-S+CH~ - 1 N Me/\Ar \ / I N Me/\Ar R (A) R r' Me \ Ar IN U Me/\Ar Ar Scheme 2 Cyclopropyl diaminooxosulphonium salts are formed in good yields by the reac- tion of diaminooxosulphonium ylides with aldehydes (Scheme 2).26 Malonate anion2' addition to a-chlorovinyl sulphones (Scheme 3; Ar = Ph 4-02NC6H4) and enamine2' addition to a -halogenoacrylonitriles (Scheme 4; n = 43; X = C1 Br; R = Et pentyl) afford substituted cyclopropanes.Another example of conjugate addition/cyclization is seen in the synthesis of chrysanthemates by attack of nitroalkane anions on a~rylates.~~ Ar C1 I Scheme 3 Attack of the anion of di-t-butyl malonate on the meso-and (*)-dibromides (18a) and (18b) takes place with Walden inversion at each bromide carbon affording cyclopropyl diesters stereospecifically. Hydrolysis methylation and semi-hydrolysis gives the mono-ester with the free acid trans to the methyl group in each case (Scheme 5). Either the free acid group can be transformed into an amino group (NaN3 then thermolysis) or the ester group can be replaced by an amino group (NH2NH2 then diazotization) providing access to a complete set of stereochemically 26 K.Okuma K. Nakanishi T. Honda H. Ohta Y. Yokomori and K. Sekido Chem. Lett. 1985 333. 27 I. Yamamoto T. Sakai K. Ohta and K. Matsuzaki J. Chem. SOC.,Perkin Trans. 1 1985 2785. 28 A. Dancso M. Kajtar-Peredy and C. Szantay Synthesis 1985 11 16. 29 A. Krief L. Hevesi G. Chaboteaux P. Mathy M. Sevrin and M. J. De Vos J. Chem. Soc. Chem. Commun. 1985 1693. 140 S. A. Math + H+ -Ht \ X kCN kCN Scheme 4 defined 2-methyl-3-deuterio-l-aminocyclopropanecarboxylic acids.30 1-Aminocyc- lopropanecarboxylic acid is the biosynthetic precursor of ethylene in plants and a number of recent studies have utilized 2,3-disubstituted analogues of the natural amino acid to elucidate the stereochemistry and mechanism of the biological oxida- tive fission process which involves a radical path~ay.~' Me i ii H-fI3; + ~e~co2Bu1iii iv COzBuf -H I I H H Me H C02Bu' H C02Me Br$H MewC02But -MewC02H H Br ii iii iv I I H H Reagents i PhCH2NEt3+ OH-; ii CF3C02H;iii CH,N,; iv 1.4 eq.KOH Scheme 5 Pdo-catalysed addition of vinyl bromide to a p-allenyl malonate anion affords the cyclopropane (19),but other bromoolefins (cycloprop-2-enyl cyclohexenyl) and iodobenzene favour formation of the cyclopentenes (20) via alternative cyclization modes of the intermediate n-ally1 complex (Scheme 6).32 1,l-Dibromocyclopropanes are versatile intermediates for the synthesis of other classes of cyclopropyl derivatives as illustrated in Schemes 7-10.The behaviour of the 1,I-dibromides on solvolysis (MeOH-AgOCOCF3) is verx substituent-dependent compounds with a 2-carbonyl substituent (21; X = 0;R = 30 J. E. Baldwin R. M. Addlington and B. J. Rawlings Tefruhedron Lett 1585 26 481. 31 J. E. Baldwin D. A. Jackson R. M. Addlington and B. J. Rawlings J. Chern. SOC.,Chem. Cornrnun. 1985 206; M. Pirmng and G. M. McGeehan Angew. Chern. Znf. Ed. Engl. 1985,24 1044. 32 M. Ahmar B. Cazes and J. Gore Tetrahedron Len. 1985 26 3795. AlicycIic Chemistry C02Me 4.dC02Me Scheme 6 R' R2y;:+ P(OR)3 R2 Et,N-H,O R'?$OR)'- + i+-Br Re$ 33 R3 R3 R3 Scheme 7 R' 1. Ni(CO),-DMFR'RvI:-t Me3SiX 2.H,O ' R V i -0x Re$ 34 1 R3 R3 Scheme 8 ReJ 35 Scheme 9 R2b:R3 R4 R' R' Ref 36 R4 R4 Scheme 10 33 T. Hirao M. Hagihara and T. Agawa Bull. Chem. SOC.Jpn. 1985 58 3104; G. F. Meijs Tetrahedron Lett. 1985 26 105. 34 T. Hirao S. Nagata Y. Yarnana and T. Agawa Tetrahedron Lett. 1985 26 5061. 35 P. Dowd C. Kaufman P. Kaufrnan and Y. H. Paik Tetrahedron Lett. 1985 26 2279. 36 R. L. Danheiser and A. C. Savoca J. Org. Chem. 1985 50 2401. 142 S. A. Matlin alkyl akoxy) are unreactive whereas olefins (21; X = CHJ undergo ring opening to dienes. Monobromocyclopropanes are generally more reactive towards solvolytic ring opening.37 In the case of 2-vinylcyclopropyl bromides capture of the intermedi- ate cation by hydrogen peroxide affords alkadienyl hydroperoxides of value in the synthesis of fatty acid metabolite^.^^ Br Me :1 :1 c1 Br Tri- and tetrahalogenocyclopropanes (22) and (23) undergo thermal ring opening at 150-220 "C in quinoline affording di- and trihalogenobuta- 1,3-diene~.~~ When pyrolysed in the presence of vinyl acetate tetrachlorocyclopropene ring opens and traps to give a tetrachlorovinylcyclopropane (24) which can be manipu- lated as a useful synthetic building Alkoxycyclopropanes undergo cycloaddi- tion reactions with tetra~yanoethylene.~~ 155°C t L ii c1x AcO c1 1 -Ethoxycyclopropyl lithium is conveniently prepared by metal-halogen exchange between 1-bromo-1 -ethoxycyclopropane and Bu'Li.Via its condensation with ketones it provides a valuable route to cyclobutanones (Scheme 1l).42 1.Bu'Li OEt H+ - ___3 2. R'R*CO %OHR' R2 R' Scheme 11 37 L. K. Sydnes and T. H. Hemmingsen Actu Chem. Scund. 1985 B39 93. 38 N. A. Porter C. B. Ziegler jun. F. F. Khouri and D. H. Roberts J. Org. Chem. 1985 50 2252. 39 M. S. Baird and H. H. Hussain J. Chem. Res (S) 1985 182. 40 S. Keyaniyan M. Apel J. P. Richmond and A. de Meijere Angew. Chem. Znt. Ed. Engl. 1985,24,770. 41 P. G. Wienng and H. Steinberg Red. Truv. Chim. Puys-Bus 1985 104,70. 42 R. C. Gadwood. M. R. Rubino S. C. Nagarajan and S. T. Michel J. Org. Chem. 1985 50 3255. Alicyclic Chemistry 143 1,l-Dilithio-2,2,3,3-tetramethylcyclopropane has now been synthesized by thermal disproportionation of 1-lithio-2,2,3,3-tetramethylcyclopropane and it should soon be known whether the di-lithiated carbon is planar as has been predicted by the0reticians.4~ A one-pot method for the hydrolysis reduction and cyclization of /3 -doxy-cyclopropanecarboxylic esters provides an efficient method for butyrolactone annu- lation (Scheme 12).@ Me3Si0 D3 R4 ,C02Me I R' R2 Scheme 12 SN2displacement of the triflate group from a cyclopropane ring by azide anion takes place with clean inversion of ~tereochemistry.~~ The methylene group adjacent to a cyclopropane ring can be converted directly into a keto group using ruthenium tetr~xide.~~ Cyclopropenes are formed by the action of lithium alkyls on cis-l-iodo-3-chloroprop-1 -enes (readily available from propargyl alcohols) providing access to substituted cyclopropanes via organometallic and hydride additions to the double bond.47 1,3-Diarylcyclopropenes,formed via dibromocarbene adducts of stilbenes are highly unstable and undergo ene dimerization to give cyclopropylcyclopropenes (Scheme 13).48 H r -v i-iii __+ Ar.Q iv Br Ar Ar H Ar Ar Reagents i BuLi THF-Et20 -100 "C; ii EtOH -100 "C;iii Bu'OK THF -30 "C;iv -30 "C to r.t.Scheme 13 Regioselective [3 + 21 cycloadditions of methylenecyclopropane with electron- deficient alkenes catalysed by R3P-Nio complexes afford methylenecy~lopentanes.~~ Allylic chlorinations of methylenecyclopropenes (25;R = CO,Et CR,OH) via methylenecyclopropyl radicals are highly regio- and stero-selective giving methyl- enecyclopropanes (26).50 43 H.Kawa B. C. Manley and R. J. Lagow J. Am. Chem. SOC.,1985 107 5313. 44 E. L. Grimrn and H.-U. Reissig J. Org. Chem. 1985 50 242; see also P. Buttinelli G. Gargaro M. A. Loreto L. Pellacani and P. A. Tardella Gazz. Chim. Ital. 1985 115 155. 45 K. Banert Chem. Eer. 1985 118 1564. 46 T. Hasegawa H. Niwa and K. Yamada Chem. Left. 1985 1385. 47 A. T. Stoll and E. Negishi Tetrahedron Lett. 1985 26 5671. 48 K. Kornatsu T. Niwa H. Akari and K. Okarnoto J. Chem. Rex (S) 1985 252; see also 1. N. Dornnin J. Kopf S. Keyaniyan and A. de Meijere Tetrahedron 1985 41 5377. 49 P. Binger and P. Wedemann Tetrahedron Lett. 1985 26 1045. 50 R. Amaud S. Choubani R. Subra M. Vidal M. Vincens and V.Barone Can. J. Chem. 1985,63 2512. 144 S. A. Matlin Cl Me (25) (26) Evidence has been presented for the ring opening of gas-phase cyclopropane radical cation to a trimethylene radical ~ation,~' and for the intermediacy of the trimethylenemethane radical cation (28) in the [3 + 21 photoreaction of methyl-enecyclopropane (27) with the carbonyl groups of quinones. The isomeric methyl-enecyclopropane (29) reacts uia a different radical cation (30).52 II H Ar H Ar (29) Modified force field calculations (MM2') of substituted cyclopropanes continue to be refined but still do not give adequate barrier heights for conformational inter conversion^.^^ The antiaromatic cyclopropenyl anion is predicted to be strongly distorted from planarity in both singlet and triplet states and even the lowest energy non-planar singlet is indicated not to be stable towards the spontaneous ejection of an electron in the gas phase.54 Calculations of one-electron density distribution p( r),provide a means of unifying the bent bond and Walsh models of cyclopropane and other 3-membered ring species and provide results of direct relevance to the chemistry of these species.Cyclopro-pane is pictured as a a-aromatic system which is stabilized by electropositive substituents and with electrophilic attack being edge-dire~ted.~' Extensive investigations of the acetolysis of cyclopropanes have been reported.56 It was concluded that protonation is at least partially rate-determining that the protonated species is highly unsymmetrical and that the degree of bond polarization 51 T.M. Sack D. L. Miller and M. L. Gross J. Am. Chem. Soc. 1985 107 6795. 52 T. Miyashi T. Takahashi and T. Mukai J. Am. Chem. Soc. 1985 107 1079. 53 P. M. Ivanov J. Chem. Rex (S) 1985 86. 54 G. Winkelhofer R. Janoschek F. Fratev G. W. Spitznagel J. Chandrasekhar and P. von R. Schleyer J. Am. Chem. Soc. 1985 107 332. 55 D. Cremer and E. Kraka J. Am. Chem. Soc. 1985 107 3800; 3811. 56 K. B. Wiberg and S. R. Kass J. Am. Chem Soc. 1985; 107 988; K. B. Wiberg S. R. Kass and K. C. Bishop ibid. p. 996; K. B. Wiberg S. R. Kass A. de Meijere and K. C. Bishop ibid. p. 1003. Alicyclic Chemistry in the presence of a proton is more important than either strain relief or incipient carbocation stability in determining reaction rates.3 Four-membered Rings The synthesis of 4-membered rings via cycloadditions and insertion reactions of isocyanides has been re~iewed.~' A general approach to substituted cyclobutanes has been described,58involving nucleophilic additions to the bridging bond in 1-(arylsulphony1)bicyclo-[l.l.O]butanes. Thermal ring opening of cyclobutanes has been used for the stereoselective synthesis of dienal intermediates for leukotriene synthesis.59Cyclobutane-1,2-dione undergoes thermal fragmentation in the gas phase to ethylene and CO probably by a concerted process.60 Much of the recent attention given to cyclobutanes has focused on their ring expansion reactions. Cyclopentene derivatives are formed by the rearrangement of 1-t-alkylcyclobutanols on contact with dry FeCl -SiOz (Scheme 14)61 and by rearrangment of 1-vinylcyclobutanols with Pdo catalysts (Scheme 15).62 2-(Pheny1thio)-1-vinylcyclobutanols as their potassium salts undergo ring expansion to cyclohexanones (Scheme 16).63 Scheme 14 PdCI,(PhCN) 0 Me w Me w Scheme 15 Scheme 16 57 D.Moderhack Synthesis 1985 1083. 58 Y. Gaoni A. Tomazic and E. Potgieter J. Org. Chern. 1985 50 2943; Y. Gaoni and A. Tomazic ibid. p. 2948. 59 S. Ingham R.W. Turner and T. W. Wallace J. Chern. SOC.,Chern. Comrnun. 1985 1664. 60 J.-R.Cao and R. A. Back Can. J. Chern. 1985,63 2945. 61 A. Fadel and J. Salaun Tetrahedron 1985 41 413 and 1267. 62 G. R.Clark and S. Thiensathit Tetrahedron Lett.1985 26 2503. 63 T. Cohen L.-C. Yu and W. M. Daniewski J. Org. Chern. 1985 50 4596. 146 S. A. Matlin Similarly 2-vinylcyclobutanones can be rearranged under acid conditions to give mixtures of cyclopentenones and acyclic die none^^^ and the inclusion of sulphur in the vinyl group encourages thermal ring expansion of the trimethylsilyl cyanohy- drins to cyclohexenones (Scheme 17).65 SBu SBu SBU Scheme 17 -Me + 60 I I Scheme 18 An oxyanionic [3,3]-sigmatropic rearrangement approach has been used for the construction of the ophiobolin ring system (Scheme 18).66 4 Five-membered Rings Lewis acid catalysed addition of isonitriles to /3 -allenic aldehydes and ketones furnishes cyclopentenones (3 1) or (32) re~pectively.~’ A synthesis of cyclopentenones with asymmetric induction has been devised using the cycloaddition of dichloroketene to chiral enol ethers followed by diazomethane ring expansion and elimination.The best chiral auxiliary (R”)for the enol ethers was found to be a camphorsulphonamide derivative (Scheme 19).68 Cyclopentadienone has been observed for the first time following isolation in an argon matrix.69 1-Alkenylcyclopropanols,which can be prepared by olefination of l-acylcyclo-propanol TMS ethers undergo acid-catalysed rearrangement to cyclopenten~nes.~~ The vinylcyclopropane-cyclopentenerearrangement is accelerated by a carbanion 64 D. A. Jackson M. Rey and A. S. Dreiding Helv. Chim. Acta 1985 68 439. 65 J. H. Byers and T. A. Spencer Tetrahedron Lett.1985 26 713. 66 L. A. Paquette J. A. Colapret and D. R. Andrews J. Org. Chem. 1985 50 201. 67 G. Gill and J.-P. Zahra Tetrahedron Lert. 1985 26 419. A. E. Greene and F. Charbonnier Tetrahedron Lett. 1985 26 5525. 69 G. Maier L. H. Franz H.-G. Hartan K. Lanz and H. P. Reisenauer Chem. Ber. 1985 118 3196. ’O J. P.Barnier B. Karkour and J. Salaun J. Chem. Soc. Chem. Commun. 1985 1270. Alicyclic Chemistry 147 R' R' Rj-vR3 Bu'NC R2 OAlX3 1 F~~~~~3-N R2 Bu' \ But R' But (31) 0 SO,N(Pr') 10:90 1. CH,N 2. Cr(ClO,) 0 Scheme 19 substituent on the cyclopropane; subsequent trapping of the cyclopentenylmethyl sulphone anion and reductive desulphonylation provides access to a wide variety of cyclopentenes (Scheme 20).71 Pd"-catalysed cyclization of 1,6-enynes can give rise to bis-methylene- or vinyl-methylenecyclopentanes (Scheme 21).'* 1.E+ OCHS02Ph 2. Reduction ' 0CH2-E IH+ @H2SO2PL Scheme 20 71 R. L. Danheiser J. J. Bronson and K. Okano J. Am. Chem. Soc. 1985 107,4579. 72 B. M. Trost and M. Lautens J. Am. Chem. Soc. 1985 107 1781; see also B. M. Trost and K. Burgess J. Chem. Soc. Chem. Commun. 1985 1084; E. Negishi S. J. Holmes J. M. Tour and J. A. Miller J. Am. Chem. Soc. 1985 107 2568; R. Epsztein and N. Le Goff Tetrahedron 1985 41 5347. 148 S. A. Matlin A R' R2 L,PdX R'1 R2 Scheme 21 5 Six-and Seven-membered Rings An efficient assembly of three 2-C components has been de~eloped:~ involving enolate condensation with 2 equivalents of vinylphosphonium bromide and has been applied to the construction of fused and spirobicyclic systems e.g.(33). PPh; Br-PPhc Br-phg IKOH 0 (33) 69% An assembly method for 7-membered rings involving [ (2 + 2) + 21 cycloaddition to homodienes has been de~eloped'~ in which homofurans and homothiophenes serve as reaction partners with TCNE or maleic anhydride (Scheme 22). z Scheme 22 73 G. H. Posner and S.-B. Lu J. Am. Chem. SOC..,1985 107 1424. 74 R. Herges and I. Ugi Angew. Chem. Int. Ed. Engl. 1985 24 594. Alicyclic Chemistry 149 The synthesis of cyclohexanols by cyclization of prochiral unsaturated aldehydes with a chiral reagent derived from dimethyl zinc and (R)-171,-bi-2-naphtho1 shows high enantioselectivity.3-Methylcitronellal (34) gave 90% enantiometrk excess of isomer (35) in 91% yield. However enal (36) gave racemic vinyl alcohol (37). The (R)-and (S)-citronellals gave exclusively the (R)-and (S)-isopulegols respectively (Scheme 23) showing that in these cases the asymmetric induction is controlled by the substrate chirality and is independent of the chirality of the zinc reagent.75 0- R’ R2 ‘.OH Me (R)-form H Me (S)-form Scheme 23 An improved synthesis of 4-carbethoxycyclohexanone has been p~blished.’~ Re-action of 2-carbethoxycyclohexanone with the propenyl selenone (38) affords a mixture of the cycloheptanones (39) and (40) the ratio depending on the configur- ations of the olefiin (38).” Q 9- COzEt CO2Et Se02Ph Se02Ph Se02Ph I (YCOZEt COzEt 75 S.Sakane K. Maruoka and H. Yamamoto Tetrahedron Lett. 1985 26 5535. 76 I. H. Sanchez A. Ortega G. Garcia M. I. Larraza and H. J. Flores Synth. Commun. 1985 15 141. 77 T. Sugawara and I. Kuwajima Tetrahedron Lett. 1985. 26 5571. 150 S. A. Matlin The conformational free energy difference of the CH2- group on a cyclohexane ring has been determined for the first time by e.p.r. spectro~copy.~~ At 300 K equatorial is preferred by 3 kJ mol-'. cis-trans-Cyclohepta-l,3-diene has been observed spectroscopically as an unstable phototransformation product of the cis-~is-isorner.~~ New studies of sub-stituent effects on the cycloheptatriene-norcaradiene equilibrium give an estimate of an enthalpy difference of 38.7 kJ mol-' between the unsubstituted isomers.80 6 Medium Rings Titanium-catalysed intramolecular aldol reaction between a trimethylsilyl enol ether and an acetal gives a cyclooctanone (41; R' = H Me).The yields are only moderate but high dilution conditions are not required.81 R'w R' R1 OSiMeJ Cyclononatetraenyl anion has been quenched with a variety of 1,l-bifunctional electrophiles in an approach to nonafulvenes.82 Cyclooligomerization of the octatetraene (42) with an Nio catalyst produces the cyclic trimer (43) q~antitatively.'~ ./A / (Ph,P),Ni c.,Y The photochemical behaviour of cyclooctene cyclodecene and cyclododecene has been studied84 and is accounted for by a combination of cis-trans isomerizations and rearrangements to the cycloalkylidenes which further react with adjacent and transannular bonds.78 K. U. Ingold and J. C. Walton J. Am. Chem. SOC.,1985 107 6315. 79 Y. Inoue S. Hagiwara Y. Daino and T. Hakushi J. Chem. SOC.,Chem. Commun. 1985 1307. J. Daub H.-D. Ludemann M. Michna and R. M. Strobl Chem. Ber. 1985 118 620. 81 G. S. Cockerill P. Kocienski and R. Treadgold J. Chem. SOC.,Perkin Trans. 1 1985 2101. 82 G. Sabbioni and M. Neuenschwander Helu. Chim. Acta 1985 68 623 and 887. 83 D. J. Pasto and N.-Z. Huang J. Org. Chem. 1985 50 4465. 84 P. J. Kropp J. D. Mason and G. F. H. Smith Can. J. Chem. 1985 63 1845. Alicyclic Chemistry The relative thermodynamic stabilities of the isomeric cis- cis-cyclooctadienes have been assessed and the AGO values (kJ mol-’ in DMSO 298.15 K) for their interconversions are shown in Scheme 24.85 -4.65 +--0 Scheme 24 cis- trans- 1,3-Cyclooctadiene has now been resolved by chromatography on swollen microcrystalline triacetylcellulose.86 MINDO/3 and MNDO calculations indicate that chair cyclooctatetraene should be an observable species at low temperature but readily isomerizing to the normal tub isomer uia bicycl0[4.2.0]0cta-2,4,7-triene.~~ 7 Large Rings cis- trans- trans-Cyclotrideca-1,5,9-trienehas been synthesized by a route involving dichlorocarbene ring expansion on the corresponding all- trans-cyclododeca- 1,5,9- triene.88 Thermal decomposition of steroidal 5a,8a-peroxide (44) provides an interesting mode of access to a functionalized 14-membered ring.89 ?Ac A AcO&-& ‘\ / 0 AcO- 0 0’ Two new syntheses of the 15-membered ring ketone muscone (45)have been reported one based on an intramolecular nitrile oxide cycloadditiongO and the other on a [ 1,3]-siloxy-Cope rearrangement (none of the [3,3]-shift was observed).’l 85 E.Taskinen and K. Nummelin Acta Chem. Scand. 1985 B39 791. 86 R. Isaksson J. Roschester J. Sandstrom and L.-G. Wistrand J. Am. Chem. SOC.,1985 107 4074. 87 M. J. S. Dewar and K. M. Men jun. J. Chem. SOC.,Chem. Commun. 1985 343. 88 H. Trauer and G. Haufe Synthesis 1985 343. 89 L. Lorenc L. Bondarenko and M. L. Mihailovic Tetrahedron Lett. 1985 26 389. 90 M. Asaoka M. Abe and H.Takei Bull. Chem. SOC.Jpn. 1985 58 2145. 91 R. W. Thies and K. P. Daruwala J. Chem. Sac. Chem. Commun. 1985 1188. 152 S. A. Matlin 0 1. H2-R0 * 2. MsCI-Et3N 8 Bicyclic Compounds The catalytic hydrogenation of bicycle[ n. 1 .O]alkanes readily available by the cyclo- propanation of cyclic olefins gives rise to cycloalkanes by internal bond cleavage for small ring sizes (n = 1,2) but external cleavage to methylcycloalkanes becomes increasingly dominant for larger ring sizes (exclusive from n = 5 upwards).92 The 3-stannyl acetal (46) reacts with silyl enol ethers in the presence of a Lewis acid to give cyclopentannulated products.93 OSiMe3 + M e Me0 O p SnMe3 -q S n M e 3 OMe OH H OMe n = 1-3 Two new annulation methods have been reported which afford bicyclo-[n.4.0]alkenones one involving addition of sodium enolates of P-ketoesters to 2-formyl-2,3-unsaturatedketones (Scheme 25)94 and the other the reaction of dieno- late anions of a,@-unsaturated carboxylic acids with cyclic ketones (Scheme 26; n = 1-8).95 92 K.J. Stahl W. Hertzsch and H. Musso Liebigs Ann. Chem. 1985 1474; W. Hertzsch and H. MUSSO ibid. p. 1485. 93 T. V. Lee and K. A. Richardson Tetrahedron Lett. 1985 26 3629. 94 W. L. Meyer M. J. Brannon C. da G. Burgos T. E. Goodwin and R. W. Howard J. Org. Chem. 1985 50 438. 95 P. Ballester A. Garcia-Raso and R. Mestres Synthesis 1985 802. Alicyclic Chemistry 153 0 R4 0 R4 I II + I -I I 1.' R' RZ COzR R' R2 Scheme 25 J CHCO2H 2.PPA 0 Scheme 26 Bicyclo[n.2.0] compounds can be assembled in one step by the intramolecular addition of in situ-generated ketenes or ketene immonium salts to olefins and as illustrated in Scheme 27 the ketene immonium salt method works well even for medium-sized rings.96 m+yN hi (CF,SOz)zO -.H=C=&3 Collidine + 0-0 0 H H Scheme 27 72% Inter- and intra-molecular allene-olefin cycloadditions have also been exploited for the construction of polycyclic framework^.^^ Intramolecular Diels- Alder reactions of the unsubstituted trans-1,3,8-nonatriene and truns-1,3,9-decatriene have been examined for the first time (Scheme 28; n = 3,4; X = Y = H). Moderate selectivity for the cis product (ca. 75%) is seen for the nonatriene cyclization but only very slight cis preference (ca.53% ) for the decatriene case.98 For the substituted series (Scheme 28; X = NEt, Y = C0,Et) I. Marko B. Ronsmans A.-M. Hesbain-Frisque S. Dumas L. Ghosez B. Emst and H. Greuter J. Am. Chem. Soc. 1985 107 2192; see also B. B. Snider R.A. H. F. Hui and Y. S. Kulkami ibid. p. 2194; Y. S. Kulkami B. W. Burbaum and B. B. Snider Tetrahedron Lett. 1985 26 5619; H. R. Sonawane B. S. Nanjundiah and M. U. Kumar ibid. p. 1097. 97 L. Skattebol and Y. Stenstrom Acta Chem. Scand. 1985 B39,291; W. G. Dauben V. P.Rocco and G. Shapiro J. Org. Chem. 1985,50 3155; W. G. Dauben and G. Shapiro Tetrahedron Lett. 1985 26 989; V.Dave R.Farwaha P.de Mayo and J. B. Stothers Can. J. Chem. 1985,63,2401; R.L.Danheiser and D.M. Fink Tetrahedron Lett. 1985 26 2513; M.Bertrand G. Gill A. Junino and R. Maurin Tetrahedron 1985 41 2759. 98 Y.-T. Lin and K. N. Houk Tetrahedron Lett. 1985; 26 2269; 2517. 154 S. A. Matlin Scheme 28 there is a dramatic shift in favour of the trans isomer (to 85% trans) for n = 3 but only a slight shift (to 55% trans) for n = 4. By contrast acceptor groups at the internal position of the olefin promote cis stereoselectivity e.g. trienone (47) affords the cis product with 95% stereo~electivity.~~ The explanation of these effects appears to lie in a 'twist-asynchronous' model of the Diels- Alder reaction. loo Several applica- tions of acceptor-substituted alkatriene cyclizations have been reported some involv- ing asymmetric syntheses in all cases the trans product being favoured,1o1 attesting to the generality of these results.The nitrone (48) undergoes cyclization to the eudesmol precursor (49) whereas the isomeric nitrone (50) gives the bicycle (51).'02 Use of a furan ring to terminate cyclization provides a valuable means of entry into simple spiro and bridged systems (Scheme 29).'03 Intramolecular Lewis acid-catalysed allylsilane conjugate addition^"^ and enol- olefin addition~''~ provide access to a variety of bicyclic systems (Scheme 30; n = l,2). 99 T.-C. Wu and K. N. Houk Tetrahedron Lett. 1985 26 2293. 100 F. K. Brown and K. N. Houk Tetrahedron Lett. 1985 26 2297. 101 A. H. Davidson C. D. Floyd A. J. Jones and P. L. Myers J. Chem. Soc. Chem. Commun.1985 1662; M. J. Kurth M. J. O'Brien H. Hope and M. Yanuck J. Org. Chem. 1985,50,2626; W. R. Roush and M. Kageyama Tetrahedron Lett. 1985 26 4327; W. Oppolzer and D. Dupuis ibid. p. 5437. 102 M. A. Schwartz and A. M. Willbrand J. Org. Chem. 1985 50 1359; see also A. E. Walts and W. R. Roush Tetrahedron 1985,41 3463; R. L. Funk G. L. Bolton J. U. Daggett M. V. Hansen and L. H. M. Horcher ibid p. 3479. S. P. Tanis and P. M. Hemnton J. Org. Chem. 1985 50 3988. 104 G. Majetich K. Hull J. Defauw and R. Desmond Tetrahedron Lett. 1985 26 2747; G. Majetich K. Hull and R. Desmond ibid p. 2751; G. Majetich K. Hull J. Defauw and T. Shawe ibid. p. 2755; G. Majetich J. Defauw K. Hull and T. Shawe ibid. p. 4711. 105 E. H. Evans A. T. Hewson and A. H. Wadsworth Synrh.Commun. 1985 15 243. Alicyclic Chemistry - HCO,H n = 2,3 HCO H 2 3 n = 1-3 0 HCO,H 8-0 Scheme 29 SiMe ( EtAICl R2 R2 I I R2 R2 Scheme 30 The vinyl stannanes (52; R = H Me; n = 1,2) cyclize cleanly under Pdocatalysis to exomethylene bicyclics.lo6 A key step in a new synthesis of sesquiterpenes with bicyclo[4.1 .O]alkane skeletons involves the photochemical rearrangement of bicyclo[3.2.2]nonadienone (53).'07 The total synthesis of the bulnesene framework has been accomplished"* by intramolecular cyclization of the pyranone (54) via trapping of the oxidopyrilium betaine (55). 106 E. Piers R.W. Friesen and B. Keay J. Chern. SOC.,Chem. Cornrnun. 1985 809. 107 T. Uyehara J.Yarnada K. Ogata and T. Kato Bull. Chem SOC.Jpn. 1985 58 211; T. Uyehara J. Yarnada T. Kato and F. Bohlmann ibid. p. 861. S. M. Bromidge P. G. Sarnmes and L. J. Street J. Chem. SOC.,ferkin Trans. 1 1985 1725. 156 S. A. Matlin CF3S020 SiMe3 I 0 XO K -0 I' ?fo- 'O' Y -OH 9- & H The sesquiterpene dactylol (56) has attracted attention from several groups. New strategies for its synthesis involve the Birch red~ction''~ of the related natural product poitediol (57) and rearrangement of the tricyclic compound (59) prepared either by total synthesis"' or by dehydration and epoxidation of africanol (58) which has previously been obtained by cyclization of humulene."' The first synthesis of precapnelladiene (60) utilizes a Claisen rearrangement to form the 8-membered ring.'12 Thermal'13 and acid-catalysed' l4 rearrangements of norbornenes have been reviewed.The synthesis of a large number of endo-substituted isocamphanes has 109 R. C. Gadwood J. Chem. SOC.,Chem. Comrnwn. 1985 123. L. A. Paquette W. H. Ham and D. S. Dime Tetrahedron Lett. 1985 26 4983. 111 K. Hayasaka T. Ohtsuka H. Shirahama and T. Matsumoto Tetrahedron Lett. 1985 26 873. 11* W. A. Kinney M. J. Coghlan and L. A. Paquette J. Am. Chem. SOC.,1985 107 7352. R. W. Hoffman Acc. Chem. Res. 1985 18 248. '14 M. Lajunen Acc. Chem. Res. 1985 18 254. AZicycZic Chemistry - 1. POCl 2. W-CIPBA BF,.Et20 ___ H2-Pt02 (56) H been de~cribed"~ and reinvestigation of the oxidation of fenchone (61) has led to the identification of two new cationic rearrangement products (62) and (63).'16 The enantioselective construction of chiral norbornenes by Diels- Alder reactions using chiral olefins continues to attract attention and excellent results with chiral vinyl sulphoxides' '' and acrylate esters of neopentyloxyborneol' l8 have been reported.9 Polycyclic Compounds Whereas cis-1,2-bis(phenylsulphonyl)ethylene adds only to the endo face of the cyclopentadiene (64) the trans isomer unexpectedly shows a 9 1 preference for em addition (for discussions of regioselectivities in such polyenes see re$ 119). 'I5 R.Vitek and G. Buchbauer Monatsh. Chem 1985 116 801. W.Cocker R. L. Gordon and P. V. R. Shannon J. Chem. Rex (S) 1985 172. 117 0.De Lucchi C. Marchioro G. Valle and G. Modena J. Chem SOC.,Chem. Commun. 1985 878; Y. Arai S. Kuwayama Y.Takeuchi and T. Koizumi Tetrahedron Lett. 1985 26 6205; M. A. Brimble and B. R. Davis Tetrahedron 1985 41 4965. 118 W. Oppolzer C. Chapius D. Dupuis and M. Guo Helu. Chim. Acta 1985 68 2100. 119 J.-L. Metral and P. Vogel Helu. Chim. Acta 1985 68 334; J.-M. Tomare P. Vogel A. A. Pinkerton and D. Schwarzenbach ibid. p. 2195; L. A. Paquette T. M. Kravetz and L.-Y. Hsu J. Am Chem SOC. 1985 107 6598. 158 S. A. Matlin PhSoFso~Ph , & Na-Hg ,&$ SOzPh SOzPh PhS02 ToZPh A SOzPh Reductions of the two isomers make syn (65) and anti (66) sesquinobornenes available for the first time with future interest likely to focus on the question of non-bonding interactions between the parallel olefinic bonds and distortion of the central one.'*' X-Ray analysis reveals that the bridgehead bond length in the tricyclo-[2.1.0.0.02.5]pentanone (67) is shorter than in the ketal(68) indicating a transannular interaction of the bridgehead bond with the carbonyl group.'21 Halogenation reac- tions of the diol obtained by hydrolysis of the diacetate (67) have been reported.'22 Attempted chlorination led to rearrangement to the furanocyclopentanone (69).(67) X,X = =O (68) X,X = -0-CH2CH2-0-(69) Treatment of the chloro-bromide (70) with Bu"Li effects ring closure to the tetracyclic hydrocarbon (71) and a similar reaction on the tetrahalide (72) provides a facile synthesis of [1.l.l]pr~pellane,'~~ whose structure has been examined in detail spectros~opically.'~~ The short-lived olefins (73) and (74) have been generated and trapped following HC1 elimination from the corresponding saturated chloro 120 0.De Lucchi G. Licini and L. Pasquato J. Chem. SOC.,Chem. Cornmun. 1985 418; L. A. Paquette H. Kunzer and K. E. Green 1. Am. Chem. SOC.,1985 107 4788. 121 H. Imgartinger A. Goldmann R. Schappert P. Gamer C. L. Go and P. Dowd J. Chem. Soc. Chem. Commun. 1985 113. lz2 P. Dowd R. Schappert P. Gamer and C. L. Go J. Org. Chem. 1985 50 44. 123 K. Semmler G. Szeimies and J. Belzner J. Am. Chem. SOC.,1985 107 6410. 124 E. Honegger H. Huber and E. Heilbronner J. Am. Chem. SOC.,1985 107 7172; K. B. Wiberg W. P. Dailey F.H. Walker S. T. Waddell L. S. Crocker and M.Newton ibid. p. 7247; L. Hedberg and K. Hedberg ibid. p. 7257. A. D. Schluter H. Harnisch J. Harnisch U.Szeimies-Seebach and G. Szeimies Chem. Ber. 1985 118 3513. Alicyclic Chemistry A simple synthesis of the polyspiroketones (76)and (77) involves dehalogenation of the bromo-acid chloride (75).'26 A comprehensive review of polyquinane synthesis has recently appeared'27 and a steady stream of publications'28 signifies the continuing variety of new approaches which are being devised for the synthesis of triquinanes such as hirs~tene,'~~ hirsutic acid,'30 triq~inacene,'~' ~apnellene,'~~ ~ilphiperfolenes,'~~ ~ilphinene,'~~ pen-talene,'35 and is~cornene.'~~ Identification of the antibiotically active cripnellins (78)-(80) as the first examples of natural tetraquinanes will no doubt stimulate further intensive synthetic efforts.137 Meanwhile the first synthesis of the tetraquinene (81) and its saturated counterpart [5.5.5.5]fenestrane have been reported.'38 126 H. M. R. Hoffmann A. Walenta U. Eggert and D. Schomburg Angew. Chem. Znt. Ed. Engl. 1985 24 607. 127 L. A. Paquette Top. Curr. Chem. 1984 119 1. 128 J. P. Marino and E. Laborde J. Am. Chem. SOC.,1985 107 734; A. B. Smith B. A. Wexler C.-Y. Tu and J. P. Konopelski ibid. p. 1308; T.-C. Wu and K. N. Houk ibid. p. 5308; P. Magnus and L. M. Principe Tetrahedron Lett. 1985 26 4851; W. R. Leonard and T. Livinghouse ibid. p. 6431; G. Pattenden and G. M. Robertson Tetrahedron 1985 41 4001.129 B. W. Disananyaka and A. C. Weedon J. Chem. Soc. Chem. Commun. 1985 1282; D. P. Curran and D. M. Rakiewicz J. Am. Chem. SOC. 1985 107 1448; Tetrahedron 1985 41 3943; D. H. Hua G. Sinai-Zingde and S. Venkataraman ibid. p. 4088; A. T. Hewson and D. T. MacPherson J. Chem. SOC. Perkin Trans. 1 1985 2625; P. Magnus and D. Quagliato J. Org. Chem. 1985 50 1621; S. V. Ley P. J. Murray and B. D. Palmer ibid. 4765; A.-M. Montana A. Moyano M. A. Pericas and F. Serratosa ibid. p. 5995. 130 A. E. Greene M.-J. Luche and A. A. Serra J. Org. Chem. 1985 50 3957. 131 E. Carceller V. Centellas A. Moyano M. A. Pericas and F. Serratosa Terrahedron Lett. 1985 26 2475; S. H. Bertz G. Lannoye and J. M. Cook ibid. p. 4695; J. M. Schulman and R. L. Disch ibid. p.5647. D. P. Curran and M.-H. Chen Tetrahedron Lett. 1985 26 4991. 132 133 D. D. Sternbach J. W. Hughes D. F. Burdi and B. A. Banks J. Am. Chem. Soc. 1985 107 2149; M. T. Crimmins S. W. Mascarella and L. D. Bredon Tetrahedron Lett. 1985 26 997; P. A. Wender and R. J. Ternansky ibid. p. 2625. 134 P. A. Wender and S. K. Singh Tetrahedron Lett. 1985 26 5987. 135 G. Mehta and K. S. Rao J. Chem. SOC.,Chem. Commun. 1985 1464. 136 Y. Tobe T. Yamashita K. Kakiuchi and Y. Odaira J. Chem. SOC.,C'hem. Commun. 1985 898. I37 T. Anke J. Heim F. Knoch U. Mocek B. Steffan and W. Steglich Angew. Chem. Int. Ed. Engl. 1985 24 709. 138 A. Pfenninger A. Roesle and R. Keese Helv. Chim. Am 1985 68 493; M. N. Deshpande M. Jawdosiuk G. Kubiak M.Venkatachalam U. Weiss and J. M. Cook J. Am. Chem. SOC.,1985 107 4786; M. Venkatachalam G. Kubiak. J. M. Cook and U. Weiss Tetrahedron Lerr. 1985; 26 4863. 160 S. A. Matlin @ 0 H-H R' 'R2 R' R2 R3 R4 (78) =O OH H (79) =O OAc H (80) H OH =O Total syntheses of marine nautral products*39 and of several classes of polycyclic ~esquiferpenes'~~ have been reviewed. Two groups have published syntheses (Scheme 31) of simularene (82).I4l -&--{ H2,Pd-C H2,Pd-C ,@::0? COzMe C02Me 1 @--{ ++O& I k Y"= A DMAP TsCl @--(Q--{ \I osi+ OH 0 I Scheme 31 A vinyl radical cyclization approach to the seychellene skeleton has been reported (Scheme 32)14* and a radical cyclization was also used to construct the P-copaene (83) and P-ylangene (84) systems (Scheme 33).'43 139 F.Pietra Guzz. Chim. IfuL 1985 115 443. 140 M. Vandewalle and P. De Clercq Tetrahedron 1985 41 1767. 141 K. Antczak J. F. Kingston and A. G. Fallis Can. J. Chem. 1985 63 993; E. Piers and G. L. Jung ibid. p. 996. 142 G. Stork and N. H. Baine Tetrahedron Lett. 1985 26 5927. 143 B. B. Snider and Y. S. Kulkami Tetrahedron Lett. 1985 26 5675. 161 AZicycZic Chemistry Scheme 32 (83) R = rH Scheme 33 (84)R= --H The P-ketoester (85) cyclizes on treatment with Mn"' to give a precursor to podocarpic acid very efficiently. This type of oxidative cyclization appears to be a very general method of ring synthesis.l4 A key step in a new chiral synthesis of the atisirane ring system involves cyclization of the dienolate salt (86).'45 OMe OMe '/ ''1 The goal of total synthesis of taxanes such as taxof (87) is being hotly and MM2 yakulations have been used to explore the strain in the bridgehead 01efin.l~~ Verticillene (88) a putative biogenetic precursor has been synthe~ized,'~~ but attempts to cyclize it to the taxane skeleton have so far failed.'49 144 B.B. Snider R. Mohan and S. A. Kates J. Org. Chem. 1985,50,3659; A. B. Ernst and W. E. Fristad Tetrahedron Lett. 1985 26 3761. 145 M. Ihara M. Toyota K. Fukurnoto and T. Kametani Tetrahedron Lett. 1985 26 1537. 146 T. Kojima Y. Inouye and H. Kakisawa Bull. Chem. SOC.Jpn. 1985 58 1738; Chem. Lett. 1985 323; W. F. Berkowitz J.Perumattam and A. Amarasekara Tetrahedron Lett. 1985 26 3665. C. S. Swindell T. F. Isaacs and K. J. Kanes Tetrahedron Lett. 1985 26 289. C. B. Jackson and G. Pattenden Tetrahedron Lett. 1985 26 3393. 149 M. J. Begley C.B. Jackson and G. Pattenden Tetrahedron Lett. 1985 26 3397. 14' 14' 162 S. A. Matlin From the photodimers (89) and (90) of 3,6-dihydrophthalic anhydride the tetraenes (91) and (92) have been synthesized,’” the latter being a potential precursor to bistetrasterane (93). Other curious hydrocarbons newly synthesized include the 2-homotwistbrendane (94)15’ and the twistadiene isomer (95).15* 0 Na-NH, Tio + G -a \ H H 0 0 0 (89) (90) 0 I 1 @ (94) (95) 150 G. Kaiser and H. Musso Chem.Ber. 1985 118 2266. 151 H.-R. Kanel and C. Ganter Helu. Chim. Acta 1985 68 1226. 152 B. Kissler and R. Gleiter Tetrahedron Lett. 1985 26 185.

ISSN:0069-3030    

DOI:10.1039/OC9858200135

出版商:RSC    

年代:1985

数据来源: RSC