ISSN:0069-3030    

DOI:10.1039/OC98784FX001

出版商:RSC    

年代:1987

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC98784BX003

出版商:RSC    

年代:1987

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (ii) Mass Spectrometry By M. A. BALDWIN Department of Pharmaceutical Chemistry School of Pharmacy University of London 29/39 Brunswick Square London WClN 1AX 1 Introduction This report will begin by updating some of the analytical techniques dealt with in the preceding review,’ in particular those relating to the rapid growth of new ionization methods. It will deal with developments in mass analysers with particular emphasis on ion trapping techniques. Finally the ability of mass spectrometry to produce and study novel chemical species will be discussed. It is not intended to update the remarks on the general mass spectrometry literature as the sources listed previously are still recommended.’ The proceedings of the 10th International Mass Spectrometry Conference held in Swansea in September 1985 have been published.2 The two-volume set contains 31 invited review papers and 528 two-page abstracts of submitted contributions.This provides an excellent snap- shot of the state of mass spectrometry at that time. A new volume has appeared in the series Specialist Periodical Reports in Mass Spe~trometry,~ and a further very comprehensive Analytical Chemistry review of the field has been published by Burlingame et aL4 2 Fast Atom Bombardrnent/Secondary Ion Mass Spectrometry Grouping these two techniques together is an acknowledgement that fast atom bombardment mass spectrometry (FABMS) and secondary ion mass spectrometry (SIMS) are essentially indistinguishable.SIMS was already long-established for inorganic and surface analysis when Barber et al. introduced FAB as a new tech- niq~e.~ At that time there was an implicit assumption that the use of inert gas atoms to bombard a sample to produce sputtered ions was significantly different to bom- bardment by ions. However the crucial innovation was in fact the use of a liquid matrix as a solvent and support for the sample in FAB allowing the successful analysis of a range of involatile and thermally labile biomolecules.6 More recently ’ M. A. Baldwin Annu. Rep. Frog. Chem. Sect. B 1986 82 15. ’‘Advances in Mass Spectrometry 1985’ ed. J. F. J. Todd Wiley Chichester 1986. ‘Mass Spectrometry’ Vol. 9 ed. M. E. Rose A Specialist Periodical Report The Royal Society of Chemistry London 1987.A. L. Burlingame T. A. Baillie and P. J. Derrick Anal. Chem. 1986 58 165R. M. Barber R. S. Bordoli R. D. Sedgewick and A. N. Tyler J. Chem. SOC. Chem. Commun. 1981 325. M. Barber R. S. Bordoli G. J. Elliot R. D. Sedgewick and A. N. Tyler Anal. Chem. 1982 54 645A. 15 16 M. A. Baldwin it has been appreciated that there are advantages in dealing with ion rather than with neutral beams i.e. higher kinetic energies can be achieved the beams are readily focused and the residual pressure of the inert gas is avoided. This has encouraged the use of caesium ion guns for the bombardment of liquid samples,' which with 35 keV primary ions has extended the molecular mass range for FAB/SIMS of proteins to about 23 OOO.* Some authors persist in describing this as FAB which in fact is a FIB i.e.fast ion bombardment or an untruth! A grammatically unacceptable alternative in current use is liquid SIMS (LSIMS) ie.SIMS of liquid rather than solid samples. This topic of nomenclature has been discussed elsewhere without any very satisfactory conclusions being reached." The role of the matrix has been identified as providing a fresh sample surface for bombardment with sample molecules diffusing to replace those damaged by the high energy impact. (10 keV particles have kinetic energies equivalent to lo6kJ mol-I.) Surface-active samples are advantageous and the choice of matrix may be critical. It has been pointed out that enhanced sensitivity may be attained by derivatizing hydrophilic samples with more hydrophobic groups to encourage surface activity e.g.esterification of carboxylic acid groups in peptides.' A number of groups have experimented with cooled sample probes that allow more volatile liquids to be analysed without added matrix. The mass spectrum of propanol was obtained at temperatures close to its melting point (-lOS0C) and at higher sub- ambient temperatures a range of terpenes and related compounds such as geraniol and terpinyl acetate gave good mass spectra." Quantitative studies in solution using FAB analysis are still problematical as suppression of certain ions is commonplace. The ions observed from gfycine/Cu'' equilibria in glycerol did not include any copper-containing species even though it was known that chelated structures were present in solution." By contrast using stable isotope dilution techniques several very successful analyses of trace metals have been carried out with dry rather than liquid samples.Calcium has been analysed in plasma with a coefficient of variation of 0.2'/0,'~ and zinc was assayed in faeces with a CV of 1% at an enrichment of 1'/o .I3 Isotope dilution minimizes the sup- pression problem as both the isotopes will be similarly affected and the use of stable rather than radioisotopes allows their use in human studies. The use of mass spectrometry for trace analysis of metals has been reviewed.I4 The experience with the copper-glycine complex is perhaps atypical in that the use of FABMS in inorganic analysis is widespread. The choice of matrix is probably more critical with inorganic samples and the nature of the material from which the probe has been constructed may also be important.The complex (PC3H7.Hg12)2 was analysed successfully from an aluminium surface but with a copper probe there was complete exchange of the mercury by ~opper.'~ Solubility in the matrix is ' G. Elliot and J. S. Cottrell Proceedings of the 34th Annual Conference on Mass Spectrometry and Allied Topics Cincinatti Ohio 1986. a M. Barber and B. N. Green Rapid Commun. Mass Spectrom. 1987 1 80. S. A. Naylor A. F. F. Findeis B. W. Gibson and D. H. Williams J. Am. Chem. Soc. 1986 108 6359. 10 K. Heckles R. A. W. Johnstone and A. H. Willby Tetrahedron Lett. 1987 28 103. I' M. J. Connolly and R. G. Orth Anal. Chem.1987 59 903. 12 X. Jiang and D. L. Smith Anal. Chem. 1987 59 2570. l3 P. L. Peirce K. M. Hambidge C. H. Goss L. V. Miller and P. V. Fennessey Anal. Chem. 1987,59,2034. 14 D. E. Pratt J. Eagles and R. Self in ref. 3 p. 407. '' P. R. Ashton and M. E. Rose Org. Mass Spectrom. 1986 21 388. Physical Methods and Techniques -Part (ii) Mass Spectrometry 17 essential for effective ionization hence the need for a DMSO-thioglycerol mixture for the analysis of cisplatin analogues which gave useful spectra in both positive and negative ion modes.16 Continuous Flow FAB.-A very interesting development is the introduction of con- tinuous flow methods. 17*18 Hitherto sample introduction has usually been effected with the sample dissolved in a relatively viscous and involatile liquid such as glycerol a small drop of the solution being inserted into the mass spectrometer via a vacuum lock.This is then bombarded by the atom beam for a period of several minutes the maximum lifetime of the experiment being determined by the time taken for the liquid matrix to evaporate. The range of satisfactory matrix materials is limited but continuous flow methods allow a much wider choice of solvents and allow the experiment to continue almost indefinitely. The solvent generally contains a small proportion of glycerol to improve the flow characteristics and to prevent too rapid evaporation but the clustering of glycerol -producing interfering ions of quite high mass -is greatly reduced. This technique provides improved signal-to-noise for trace analysis and has given spectra of peptides ranging from substance P (RMM 1347) up to insulin," and a number of 'difficult' samples have been analysed in this way.'' This technique also offers new opportunities in interfacing high performance liquid chromatography with mass spectrometry.The optimum flow rate for con- tinuous flow FAB is about 5 p1 min-' which is ideal for microbore HPLC.20 This has been used for direct analysis of peptide digests,21,22 peptides and proteins,21 and antibiotics.22 HPLC with standard packed columns at a flow rate of 1ml min-' has been used. After the column the eluent (methanol-water-trifluoroacetic acid) was mixed with a little glycerol from a second pump. It then flowed through a standard UV detector before being split to deliver approximately 1% to the con- tinuous flow FAB probe via a fused silica tube.Peptides of different masses that were not well-resolved in the UV chromatogram were readily separated by the mass spectrometer using selected ion monitoring. Alternatively the mass spectrometer could produce a mass spectrum for each component of interest in the UV Caprioli has investigated continuous flow FAB as an alternative to 'static' FAB for continuous monitoring of reactions such as tryptic digestion of peptides. One advantage is the ability to use predominantly aqueous solvent for the reactions rather than glycerol making the results more consistent with other techniques. Water provides another benefit in reduced suppression of certain peptides.There are nine peptides of masses greater than 700 produced by tryptic digestion of myoglobin and they have various hydrophilicity/ hydrophobicity indices. The five hydrophobic peptides are surface active in glycerol and they were detected strongly in standard 16 M. M. Seigel P. Bitha R. G. Child J. J. Hlavka Y.-I. Lin and T. T. Chang Biomed. Enuiron. Muss Spectrom. 1986 13 25. Y. Ito T. Takeuchi D. Ishi and M. J. Goto J. Chromutogr. 1985 346 161. '* R. M. Caprioli T. Fan and J. S. Cottrell Anal. Chem. 1986 58 2949. 19 M. Barber L. W. Tetler D. Bell A. E. Ashcroft R. S. Brown and C. Moore Org. Muss Spectrom. 1987 22 647. 2o A. E. Ashcroft J. R. Chapman and J. S. Cottrell J. Chromatogr. 1987 394 15. 21 D. W. Hutchinson A. R. Woolfitt and A.E. Ashcroft Org. Muss Spectrom. 1987 22 304. 22 A. E. Ashcroft Org. Mass Spectrom. 1987 22 754. 23 D. E. Games S. Pleasance E. D. Ramsey and M. A. McDowell Biomed. Enuiron. Mass Specworn. 1988 15 179. 18 M. A. Baldwin FAB whereas the four hydrophilic peptides gave no signals in the presence of the hydrophobics. This suppression problem was much reduced with continuous introduction of aqueous solutions only one hydrophilic peptide showing no signal at Ionization Mechanisms in Sputtering Techniques.-The development of FAB/SIMS and other desorption methods has been an outstanding success in broadening the scope of mass spectrometry in organic and biochemical analysis. Many examples of new areas of application are described in two recent books one on general applications of mass spectrometry to bio~hemistry,~~ and the other on the analysis of large molecules.26 This latter topic is not restricted to biochemistry and also embraces the analysis of polymers.The production and characterization of cluster ions is also a new area which has been reviewed independently by Derri~k,~’ Mark,28 and Sta~e.~~ All three authors address the fascinating subject of magic numbers i.e. a particular number of individual atoms or molecules that provide the cluster with enhanced stability. Examples include the caesium ion clusters CS1& which is a 3 x 3 x 3 cube and Cs231r2 which is 3 x 3 x 5. Amongst protonated water clusters H(H20)11,which forms a pentagonal dodecahedron is favoured; for carbon C60 Buckminsterfullerene shows enhanced stability both as a cation and as an anion.It has been pointed out by many authors that the spectra from FAB/SIMS are extremely similar to those from other sputtering/desorption mass spectrometry techniques including field desorption (FDMS) laser desorption (LDMS) and plasma desorption (PDMS) induced by fission fragment bombardment (252Cf fission) or particles from accelerators. For example the LDMS spectrum of bovine insulin has recently been p~blished,~’ and is very similar to that from FABMS. Desorption and ionization induced by MeV energy particles is essentially the same as that from 10 keV FAB although the higher energy particles are better at ionizing high mass compounds and they are more efficient in terms of secondary ion yield per initial bombardment which is consistent with statistical RRK-based kinetic theory.31 In practical terms the latter advantage of PDMS may be cancelled out by the more intense primary beams attainable in FAB/ SIMS.Nevertheless the ionization mechanisms are still not clearly understood. Derrick and Sundqvist have edited a special volume of International Journal of Mass Spectrometry and Ion Processes entitled ‘Gaseous ions from involatile ther- mally-sensitive materials energetics and mechanisms’. In a preface they state that ionization precedes volatilization -far more neutrals than ions are sputtered into the gas phase and the ionization process is inefficient and uncontrolled and they suggest that for more effective techniques it will be necessary to achieve volatilization before ionization.32 This is consistent with a report from Williams et al.that neutral species in solution are generally sputtered as neutrals giving weak FAB spectra 24 R. M. Caprioli W. T. Moore and T. Fan Rapid Commun. Mass Spectrom. 1987 1 15. 25 ‘Mass Spectrometry in Biomedical Research’ ed. S. J. Gaskell Wiley Chichester 1986. 26 ‘Mass Spectrometry in the Analysis of Large Molecules’ ed. C. J. McNeaI Wiley Chichester 1986. 27 P. J. Derrick in ref. 2 p. 85. 28 T. D. Mark Int. J. Mass Spectrom. Ion Processes 1987 79 1. 29 A. J. Stace in ref. 3 p. 96. 30 J. Grotemeyer and E. W. Schlag Org. Mass Spectrom. 1987 22 758. 31 I. S. T. Tsong J. W. Christiansen S. H. Lin and B.V. King in ref. 26 p.67. 32 P. J. Demck and B. Sundqvist Int. J. Mass Spectrom. Ion Processes 1987 78 ix. Physical Methods and Techniques -Part (ii) Mass Spectrometry 19 whereas preionized species such as peptides containing basic amino acids are sputtered as ions and neutrals to a comparable extent.33 It has also been shown that addition of organic bases to the matrix promotes (M-H)- formation for nucleic acids in negative ion FAB.34 However this view of the ionization mechanism is not universally held Sunner et al. have developed a phase explosion model of desorption in which most of the ionization occurs in the relatively high pressure region immedi- ately above the liquid. Here the densities are 10%-30% of those in the liquid phase and kinetic modelling can be achieved with a gas collision Ionization occurs by processes analogous to chemical ionization hence the importance of gas phase basicities in determining the protonated species observed in FAB.36 Undoubtedly the tendancy is for many more neutrals than ions to be sputtered into the vapour phase.For LDMS this has been exploited by using two lasers operating at different wavelengths one for sample evaporation and the other for ionization thereby achieving temporal and spatial separation of these two processes. In one example a C02 infra-red laser was used for evaporation and a ND:YAG UV laser at 266nm was pulsed approximately 100 ps later to cause resonance enhanced multiphoton ionization (REMPI). This instrument gave good detection of PTH-amino acids at the 1 pmole level and gave a linear response up to 1 nm01e.~’ However it should be emphasized that the PTH-amino acids are by no means as demanding to vaporize and ionize as the proteins that are now being observed in FAB/SIMS and PDMS experiments.The insulin molecule has 2358 normal modes of vibration about 450 of which must be excited for the intact molecule to be desorbed with an average energy deposition of about 800 ev/m~lecule.~’ Multiphoton ionization (MUPI) LDMS from the solid phase with an excimer laser operating at different wavelengths in the UV shows that spectral characteristics change with the photon energy and this has been related to competitive photoioniz- ation and energy transfer processes in the solid.38 Ionization mechanisms in MUPI have been reviewed by Neusser and he also discusses the production of state-selected and energy-selected ions and their role in studying unimolecular ion reaction kinetics.39 Mass Analysers for Sputtering Techniques.-The majority of mass spectrometers in widespread use employ either magnetic sectors (and perhaps electric sectors) or quadrupole analysers for the separation of ions.Both of these are ‘continuous mode’ techniques in that a continuous beam of ions is produced in the ion source and passed through the instrument. The flux of ions is usually great enough for this to be treated as an electrical current which is amplified as an analogue signal. Weak signals will result in statistical ‘noise’ but commercial mass spectrometers are rarely equipped for the ion counting that very weak signals might require.This approach is compatible with FABISIMS as continuous high intensity beams of primary atoms or ions are readily produced in turn giving secondary ion beams of reasonable 33 D. H. Williams A. F. F. Findeis S. Naylor and B. W. Gibson J. Am. Chem. SOC.,1987 109 1980. 34 A. Sandstroem and J. Chattopadhyaya J. Chem. SOC. Chem. Commun. 1987 862. 3s J. Sunner A. Morales and P. Kebarle Anal. Chem. 1988 60,98. 36 J. Sunner A. Morales and P. Kebarle Anal. Chem. 1987 59 1378. 31 F. Engelke J. H. Hahn W. Henke and R. N. Zare Anal. Chem. 1987 59 909. 38 B. Spengler M. Karas U. Bahr and F. Hillenkamp J. Phys. Chem. 1987 91 6502. H. J. Neusser Inf. 1.Mass Spectrom.Ion Processes 1987 79 141. 20 M. A. Baldwin intensity. However LDMS and PDMS are both pulsed techniques neither of which is ideally suited to the production of continuous signals. For LDMS this is determined by the duty cycle of the laser whereas for 252Cf fission fragment PDMS the flux of high energy particles is low and the resulting ion current is intermittent. The advent of LDMS and PDMS has led to the renascence of a pulsed mass analysis technique namely time-of-flight (TOF). For LDMS the TOF analysis can be readily synchron- ized with the firing of the laser and for fission-fragment PDMS the detection of a second fission fragment is used to gate the mass analyser. There is no theoretical upper mass limit for TOFMS which is obviously advantageous for high mass analysis.However TOF instruments have tended to have low resolving power due to a spread of ion velocities. This disadvantage can be remedied by an ion optical device known as a reflectron and a REMPI TOFMS instrument has been described having a mass resolution of 10OO0.40 An alternative is to form the ions in a burst and then to trap them allowing the build-up of sufficient ions in the trap before analysing them. This topic will be covered in the following section. 3 Ion Trapping Ion traps have recently been re~iewed.~' A very simple ion trap has been marketed in recent years as a GC detector.42 This is based on the two-dimensional quadrupole trap consisting of a circular electrode with two end caps but this has not been employed in studies of high mass or involatile species.However the Fourier transform ion cyclotron resonance instrument (FTICR or FTMS) has been used in this area. Very low kinetic energy ions can be stored in the cell and built up over a period of time. These are then excited into circular orbits by a pulse of radiation and their cyclotron frequencies specify their masses with high precision. Unlike a scanning sector instrument this technique allows all masses to be monitored simul- taneously and thus enjoys the Fellget advantage. (Early sector instruments used photographic detection at a focal plane and thereby allowed simultaneous detection of a range of masses. This has been up-graded by one manufacturer of double focusing instruments with a multichannel electro-optical detector allowing all masses within a 4% spread to be monitored.Recording a 200 amu wide spectrum in region of the molecular ion of bovine insulin with this detector gave an eightfold improve- ment in signal-to-noise compared with conventional scanning.43) LD is the most frequently used ionization method for high mass FTMS. Shomo et al. obtained comparable or better sensitivity with LDFTMS compared with FD and FABMS using sector instruments for a number of drugs of low volatility in the mass range 404-819 and they obtained mass measurements accurate to *0.003 am^.^^ Tabet et al. obtained the spectrum of Leu-enkephalin by 252Cf PDFTMS,45 and McLafferty et al. have experimented with the use of both caesiurn 4" K. Waiter U. Boesl and E.W. Schlagg Int. J. Mass Specrrom. fon Processes 1986 71 309. 41 J. Allison and R.M. Stepnowski Anal. Chem. 1987 59 1072A. 42 Finnigan MAT San Jose California. 43 J. S. Cottrell and S. Evans Anal. Chem. 1987 59 1990. 44 R. E. Shomo A. G. Marshall and R. P. Lattimer fnt. J. Mass Spectrom. fon Processes 1986 72 209. 45 J. C.Tabet J. Rapin M. Poreti and T. Gaumann Chimia 1986 40 169. Phvsical Methods and Techniques -Part (ii) Mass Spectrometry 21 ion SIMS,4h and 252Cf PDMS with FTMS.47 It is desirable to use dry samples with FTMS as the vapour pressure of the liquid matrix gives an unacceptably high pressure in the cell. With Cs' SIMS from dry samples they showed that addition of the tripeptide glutathione enhanced the spectra.36 With 52Cf PDMS they were able to produce spectra for compounds of masses up to 2000 by desorption from mylar or nitrocellulose but the trapping efficiency was very low and was estimated to be only 0.1% giving poor sensitivity compared with PDMS using TOF analysis.47 The use of glutathione or nitrocellulose was already established in PDTOFMS and it has been shown for peptides up to RMM 14 000 that ions desorbed from nitrocel- lulose have lower internal energies and they are less susceptible to unimolecular decay.48 Hunt et al.have shown that with FTMS it is possible to detect protonated molecular ions of cytochrome c (RMM 12384) formed externally to the analyser cell by FAB i~nization.~~ LDFTMS has been compared favourably with FAB/SIMS for the analysis of polymers more regular polymer distributions being obtained with less fragmentation and less mass dis~rimination.~~ Ion traps are also used with the more traditional ionization techniques of EI and CI and the quadrupole ion trap has shown itself to be a very versatile device for studies in ion chemistry as well as for conventional mass spectrometry.It is possible to select and trap ions of a specific mass. Trapping the ions for long periods of time can allow low energy collisions with background gases to bring about collisional dissociation with high efficiency. Approximately 2 ev is deposited in the ions on collision and sequential reactions can be studied." In a similar way it is possible to carry out low pressure chemical ionization extended trapping times leading to the elimination of peaks due to electron impact.The use of a range of reagent gases with selective ion trapping allows versatile ion/molecule studies.52 Another advantage of ion trapping may prpve to be important in tandem mass spectrometry of high mass ions. Analysis of high mass compounds by techniques such as FAB provide protonated molecular ions that show little tendency to fragment. Small groups may be lost from these ions to give some peaks in the upper part of the spectrum but there are usually very few structurally diagnostic peaks. This is a particular problem for compounds of RMM greater than 2000 but even below 1000 the fragmentation of these even-electron ions is unpredictable. Tandem mass spectrometry allows ions of a particular mass to be selected the ions to be energized by collisions with an inert gas and the resulting fragments to be analysed.Biemann et al. have used this technique for the analysis of several unknown peptides up to RMM 3000 and have reported that the fragmentation obtained in this way is far more predictable and comprehensive often allowing unambiguous structure determi- nation.53 They have demonstrated superior performance for FAB/tandem mass 46 I. J. Amster J. A. Loo J. J. P. Furlong and F. W. McLafferty Anal. Chem. 1987 59 313. 47 J. A. Loo E. R. Williams 1. J. Amster J. J. P. Furlong B. H. Wang F. W. McLaffertl B. T. Chait and F. H. Field And. Chem. 1987 59 1880. 4n B. T. Chait Int. J. MASSSpectrom. Ion Processes 1987 78 237.49 D. F. Hunt J. Shabanowitz J. R. Yates 111 N.-Z. Zhu D. H. Russell and M. E. Castro Proc. Narl. Acad. Sci.,1987 84 620. 50 L. M. Nuwaysir and C. L. Wilkins Anal. Chem. 1988 60 279. J. N. Louris R. G. Cooks J. E. P. Syka. P. E. Kelley G. C. Stafford Jun. and J. F. J. Todd AnalChem.. 1987 59 1677 52 J. S. Brodbelt J. N Louris and R. G. Cooks Anal. Chem. 1987 59 1278. 53 S. A. Martin and K. Biemann Inr. .I. Mass Spectrom. Ion Processes 1987 78 213. 22 M. A. Baldwin spectrometry over acid hydrolysis/FABMS for the analysis of substance P,54 and they have described a computer aided graphics-based interactive interpretation system that rapidly calculates all possible amino acid sequences corresponding to observed mass differences in the collision ~pectra.~' However as the mass of ions increases there are more and more vibrational modes available.Consequently there is increasing difficulty in introducing sufficient energy in a collision to induce fragmentation within the lifetime of the experiment so as to obtain coherent structural information. Ion trapping has been recommended as a means of extending the time available for the fragmentation of large molecules thereby increasing the chance of obtaining structural inf~rmation.'~ 4 Chromatography/Mass Spectrometry The combination of chromatography and mass spectrometry continues to be an important growth area. Despite the increasing importance of HPLC/MS GC/MS is still widely used; in reviewing GC/MS over a two-year period Evershed has listed nearly 500 papers that contain novel development^.'^ GC/MS is generally more sensitive than LC/MS e.g.for the determination of cortisol in blood serum at physiological levels GC/ MS gave better precision and better sensitivity. However after an initial extraction the GC assay involved HPLC fractionation and then derivatization to form the bis(methy1)-oxime tris(trimethylsily1)-ether derivative whereas thermospray HPLC was carried out on the crude extract." This is a common situation in that GC/MS gives greater accuracy and precision whereas LCMS gives a quicker analysis. The obvious target for improvement in LC/MS is sensitivity. GC/MS has been compared favourably with radioimmunoassay in terms of sensitiv- ity and linearity of response for the assay of leukotriene B4 in human neutrophil samples.59 Several interface techniques are available for LC/ MS including the continuous flow FAB described earlier.Thermospray which was described in the last review in this series,' has become established as the most widely used method. This relies on desolvation of preionized species and favours polar materials and reversed-phase chromatography although additional ionization can be achieved in the gas phase by corona discharge or electron bombardment from a heated filament. An alternative ionization method is atmospheric pressure ionization (API) with an ion spray interface which reportedly can give high sensitivity. Widely varying flow rates can be accommodated and the limits of detection have been reported as 10 ng for full scans and 1Opg with single ion monitoring.60 This technique has been compared with thermospray/API.6' Chromatography/mass spectrometry is widely used in biochemistry phar- macology drug metabolism etc.and it is commonplace to use heavy isotope-labelled 54 H. A. Scoble S. A. Martin and K. Biemann Biochem. J. 1987 245 621. 55 H. A. Scoble J. E. Biller and K. Biemann Fresenius' Z. Anal. Chem. 1987 327 239. 56 P. Demirev J. K. Olthoff C. Fenselau and R. J. Cotter Anal. Chem.. 1987 59 1951. 57 R. P. Evershed in ref. 3 p. 196. 58 S. J. Gaskell K. Rollins R. W. Smith and C. E. Parker Biomed. Enuiron. Mass Spectrom. 1987 14,717. 59 W. R. Mathews G. L. Bundy M. A. Wynalda D. M. Guido W. P. Schneider and F. A. Fitzpatnck Anal.Chem. 1988 60,349. 60 A. P. Bruins T. R. Covey and J. D. Henion Anal. Chem. 1987 59 2642. 61 T. R. Covey A. P. Bruins and J. D. Henion Org. Mass Spectrom. 1988 23 178. Physical Methods and Techniques -Part (ii) Mass Spectrometry 23 standards as these are readily identified by mass spectrometry e.g. isotope dilution can be used to monitor the kinetics of metabolism of endogenous compounds and thermospray LC/MS has been used for quantitative analysis in a number of such studies.62 The binding of caffeine to human serum albumin showed a significant isotope effect when deuterated standards were employed. This points to ways in which the biochemical mechanisms can be detected but it also provides a warning against the ubiquitous use of labelled compounds as standards which are assumed to differ from the compounds of interest only in terms of mass.63 The powerful combination of GC/FTIR/MS has been and has been described using an ion trap as the mass analy~er.~~ The much greater sensitivity of mass spectrometry over Fourier transform infra-red spectroscopy means that a sample split of the GC eluent of perhaps 50:l is required in favour of the FTIR.Chromatographic resolution is retained in the mass spectrum by splitting rather than having a flow-through IR cell preceding mass spectrometry. The techniques of IR and MS provide highly complementary information and the greatest advantage is obtained through searching separate IR and MS databases.64 ITMS has also been interfaced with chromatography including supercritical fluid chromatography (SFC).As explained above it is desirable to maintain high vacuum in the FTMS analyser cell and this was achieved through the use of a differentially pumped dual-cell instrument which gave a one hundred-fold pressure differential in the ionization and analysis regions.66 The analysis of caffeine has been described using SFC/FTMS with ‘self CI’ i.e. chemical ionization in which the primary ions collide with un-ionized sample molecules to produce new ionic species.67 SFC/MS is a technique of great promise that has yet to become firmly established. A recent review lists more than 100 literature references although the authors concede that early hopes that LC/ MS would be replaced by SFC/ MS were ‘naive’.68 5 Novel Neutral Species Mass spectrometry is well established as a means of studying the unimolecular and bimolecular chemistry of ions free of the solvent effects associated with ~olutions.~~ Tandem mass spectrometry allows oxidation and reduction reactions to be studied through collisional charge exchange (CE) reactions ‘charge permutation reac-tion~’,’~ although it is normally necessary for both the reactants and the products to be ions.More recently it has become possible to study neutral species which have been produced from an ion beam in a mass spectrometer in one of a number of ways (i) by unimolecular fragmentation of an ion giving a neutral fragment (ii) by a similar collision-induced reaction with an atom such as He or (iii) by collisional CE with an atom such as Hg or Xe which neutralizes an ion.The neutrals thus 62 A. L. Yergey N. V. Esteban and D. J. Liberato Biomed. Environ. Mass Spectrom. 1987 14 623. 63 Y. Cherrah J. B. Falconnet M. Dessage J. L. Brazier R. Zini and J. P. Tillement Biomed. Environ. Mass Spectrom. 1987 14 653. 64 C. L. Wilkins Anal. Chem. 1987 59 571A. 65 E. S. Olson and J. W. Diehl Anal. Chem. 1987 59 443. 66 D. A. Laude Jun. S. L. Pentony Jun. P. R. Griffiths and C. L. Wilkins Anal. Chem. 1987 59 2283. 67 E. D. Lee J. D. Henion R. B. Cody and J. A. Kinsinger Anal. Chem. 1987 59 1309. 68 R. D. Smith H. T. Kalinoski and H. R. Udseth Mass Spectrom. Rev. 1987 6 445. 69 M. A. Baldwin in ref. 3 p. 59. 70 J. H. Beynon R. K. Boyd and A.G. Brenton in ref. 2 p. 437. 24 M. A. Baldwin produced are then ionized by CE with a molecule such as O2and analysed by mass spectrometry. If the neutrals are formed by process (iii) and then reionized this can properly be termed neutralization/reionization mass spectrometry (NRMS). However if He is used for the ionization step this brings about fragmentation as well as ionization and this may be called collision-induced dissociative ionization (CIDI). Yet another term that has been used to describe such experiments is neutralized ion beam spectroscopy (NIBS). Thus it can be seen there is anarchy amongst the acronyms and the suggestion that all such experiments should be described by the terms NRMS71 is perhaps as welcome as it is inaccurate.There have been two recent reviews of this which highlight the very interesting chemistry that can be studied. A number of compounds not obtainable by conventional chemical means can be formed in the gas phase by neutralization of the corresponding radical cations. Vinyl alcohol CH2=CHOH hydroxymethylcarbene CH,COH and methoxycarbene HCOCH3 which are isomers of acetaldehyde can be formed in this way e.g. the elimination of ethene from ionized cyclobutanol gives the radical cation of vinyl alcohol which is then subjected to CE. There are high energy barriers to the unimolecular isomerization of the various neutrals and these have been identified and characterized by NRMS7’ Many ions formed by indirect processes such as rearrangement do not conform to normal valency rules and when neutralized they can provide hypervalent species.The interpretation of the observed data is not without controversy for a number of these species. The CH; radical has been reported to exist with a lifetime > 3.9 x s although this conflicts with earlier results.73 Hi can exist in metastable and electronically excited dissociative states.74 Isotope effects can play a significant role in increasing the lifetimes of such species e.g. D,O’ is substantially more stable than H30’.75 Reference was made in the preceding review’ to the species CH2ClH. That this exists as a stable radical cation is undisputed and new MS/MS/MS experiments from Wesdemiotis et al. reinforce the claim that neutralization with Hg gives a neutral of the same structure that is stable for at least 1 ps.76This stability is disputed by Hop et al.who have neutralized the ions with Xe and claim isomerization occurs to give CH3C1.77 A6 initio molecular orbital calculations predict that the ground-state neutral exists only in a shallow well and therefore can readily is~merize.’~ If neutral species such as this do exist they may be regarded as ylides i.e.-CH,-ClH+. NRMS spectra have been obtained for species that could possibly exist as betaines -CH2CH20Hl and -CH2CH2NHl or as dipole-alkene c~mplexes.’~ 71 C. Wesdemiotis and F. W. McLafferty Chem. Rev. 1987 87 485. 72 J. K. Terlouw and H. Schwarz Angew. Chem. Int. Ed. Engl. 1987 26 805. 73 W. J. Griffiths F. M. Harris A. G. Brenton and J. H. Beynon Inr.J. Mass Spectrorn. Ion Processes 1986 74 317. 74 G. I. Gellene and R. F. Porter Int. J. Mass Spectrom. Ion Processes 1985 64 55. 75 G. I. Gellene and R. F. Porter J. Chem. Phys. 1984 81 5570. 76 C. Wesdemiotis R. Feng M. A. Baldwin and F. W. McLafferty Org. Mass Spectrom. 1988 23 166. 77 C. E. C. A. Hop J. Bordas-Nagy J. L. Holmes. and J. K. Terlouw Org. Mass Spectrom. 1988 23 155. 78 B. F. Yates W. J. Bouma and L. Radom J. Am. Chem. Soc. 1987 109 2250. 79 C.Wesdemiotis P. 0. Danis R. Feng J. Tso and F. W. McLafferty J. Am. Chem. SOC.,1985 107 8059.

ISSN:0069-3030    

DOI:10.1039/OC9878400015

出版商:RSC    

年代:1987

数据来源: RSC

摘要:

3 Theoretical Chemistry By I. H. WILLIAMS School of Chemistry University of Bristol Bristol BS8 1 TS 1 Introduction What has theoretical chemistry had to say to organic chemistry during 1987? If judged by the sheer volume of published literature the answer is plenty. Increasingly theoretical methods are being used by organic chemists as tools for the investigation of structure and reactivity; such applications should be guided by awareness of the scope and limitations of the available methods. Ab initio calculations for individual molecular species are catalogued annually in a bibliography (the supplement for 1986 contains 1667 references') but a classification of theoretical studies of reactions is lacking. Theoretical organic chemistry is not merely the business of cranking ever-more-accurate numbers from a computer its primary role is the establishment and refinement of concepts and models for the interpretation and prediction of organic molecular behaviour.2 Computational Methods Two volumes (67 and 69) of the series Advances in Chemical Physics were devoted to ab initio methods in quantum chemistry and contain authoritative reviews of numerous topics including the use of analytical derivative methods2 Handy and co-workers have described the accurate prediction of molecular geometries and spectroscopic constants using SCF and MP2 energy derivative^;^ the use of large basis sets (triple zeta in the valence region with multiple sets of polarization functions) leads to errors of only k0.002 8 in single bond lengths kO.01 8 for multiple-bond lengths k0.2" for angles and a mean error of only 1.5% in harmonic vibrational frequencies at the MP2 level.4 Analytical energy gradients have been implemented at the MP3 and MP4 level^,^ but the resulting geometries and frequen- cies do not seem to be better than those at the MP2 level.Schlegel has reviewed methods for optimization of equilibrium geometries and transition structures6 and Baker has described a numerical version of his efficient saddle-point searching ' Quantum chemistry literature database. Supplement 6. Bibliography of a6 inirio calculations for 1986 ed. K. Ohno and K. Morokuma THEOCHEM 1987 39 1. * P. Pulay Adu. Chem. Phys. 1987 69 241. N. C. Handy J. F. Gaw and E. D. Simandiras J. Chem. SOC.,Faraday Trans.2 1987 83 1577. 'E. D. Simandiras N. C. Handy and R. D. Amos Chem. Phys. Lett. 1987 133 324. J. Gauss and D. Cremer Chem. Phys. Lett. 1987 138 131. H. B. Schlegel Adv. Chem. Phys. 1987 67,249. 25 26 I. H. Williams algorithm which may be used without analytical gradients.’ Transition-structure computations and their analysis was the subject of a review by Bernardi and Robb,’ emphasizing the use of multiconfigurational wavefunctions; the formalism of their diabatic-surface approach to reactivity has been presented in a unified fa~hion.~ The CASSCF method has been reviewed,“ and both gentle” and thoroughL2 dis- cussions of modern valence bond theory have been given. Errors in heats of formation calculated with the AM1 semi-empirical method are comparable with those at the 3-21G level of ab inztio SCF theory but are larger than those calculated at the 6-31G* 1e~el.l~ There is a tendency in this year’s literature for the latter basis to be referred to as 6-31G(d).The nomenclature for other bases of the same ilk is undergoing similar revision supposedly to clarify the nature of the polarization functions added to more extended bases [e.g.6-31G(2dLp) indicates a basis augmented by two sets of d and f functions on heavy atoms and a single set of p functions on hydrogens] but differing examples of usage betray a lack of consistency. Are the functions in parentheses to be understood as being in addition to or instead of those implied by the conventional asterisk notation? (Caveat lector!) An economical polarized basis set 3-21G( N*) for nitrogen-containing molecule^,'^ and diff use-function augmented bases for second-row elements (Na to C1) have been evaluated l5 the 3-21 +G* basis is recommended particularly for anions containing these atoms.Extended (3-21G-like) bases for first- and second-row transition metals have been reported.I6 A stochastic method for locating the global minimum on an energy surface has been reported,” and a program WIZARD which applies artificial-intelligence methods to conformational analysis has been described.” Intrinsic reaction coordin- ates and dynamic reaction coordinates may be obtained from semi-empirical calcula- tions of molecular trajectories.” The semi-empirical SINDO 1 method has been parameterized” for second-row atoms (Na to C1) and may include d orbitals (not present in MNDO) which are necessary for the description of hypervalent molecules.21,22 Jug’s SINDO 1 differs philosophically from Dewar’s MNDO (and AM1) in an important respect.The parameters of Dewar’s methods are adjusted directly to experimental heats of formation at room temperature; computation of zero-point and thermal energy corrections to enthalpies of reaction and activation enthalpies using the calculated vibrational frequencies in effect includes these quantities twice over. SINDOl is ’ J. Baker J. Comput. Chem. 1987 8 563. * F. Bernardi and M. A. Robb Adu. Chem. Phys. 1987 67 155. F. Bernardi J. J. W. McDouall and M. A. Robb J. Compur. Chem. 1987 8 296.10 B. 0. Roos Ado. Chem. Phys. 1987 69 399. J. Gerratt Chem. Brit. 1987 23 327. D. L. Cooper J. Gerratt and M. Raimondi Adu. Chem. Phys. 1987 69 319. l3 M. J. S. Dewar and B. M. O’Connor Chem. Phys. Lett. 1987 138 141. 14 N. V. Riggs and L. Radom In?. J. Quuntum Chem. 1987 31 393. Is G. W. Spitznagel T. Clark P. v. R. Schleyer and W. J. Hehre J. Cornput. Chem. 1987 8 1109. l6 K. D. Dobbs and W. J. Hehre J. Compur. Chem. 1987 8 861 880. M. Saunders J. Am. Chem. SOC.,1987 109 3150. 18 D. P. Dolata J. Computer-Aided Mol. Design 1987 1 73. 19 J. J. P. Stewart L. P. Davis and L. W. Burggraf J. Compur. Chem. 1987 8 1117. 20 K. Jug R. Iffert and J. Schulz In?.J. Quantum Chem. 1987 32 265. 2’ K. Jug and R. Iffert J. Comput. Chem. 1987 8 1004; K.Jug and J. Schulz ibid. p. 1040. 22 J. T. Sprague J. C. Tai Y. Yuh and N. L. Allinger J. Comput. Chem. 1987 8 581. Theoretical Chemistry 27 parameterized so as to reproduce experimental heats of formation extrapolated to 0 K and from which the zero-point energy has been subtracted; consequently the consideration of vibrational properties of molecules by this method does not involve any logical inconsistency. The MMP2 program and procedures for the treatment of conjugated hydrocarbons have been properly documented,22 and the deficiencies of this method and MM2 in regard to out-of-plane deformations of aromatic rings have been corrected;23 the revised MM2(85) program (available from QCPE) contains MMP2. However partly in response to the further inadequacy of these methods for the description of phenyl-phenyl interaction^,^^ Allinger has also announced25 an entirely new molecular mechanics method MM3.Not only does this new force field incorporate C,,-H and Crp2-Csp3 dipoles for correct descriptions of electrostatic interactions (such as the 'T' structure for benzene dimer) but it also breaks the mould of 'empirical force fields' by virtue of the explicit use of ab initio theoretical results along with experimental data in the determination of its parameters for non-bonded interactions. Ab initio results have also been used by Houk as a source of MM2 parameters to describe transition structures for intramolecular radical additions26 and Diels- Alder cycl~additions.~~ MM2 parameters are reported for the anomeric effect in t-butoxy and trimethyl silyloxy derivatives of 1,4-di0xane,~' for enolate equilibria29 and boron en~lates,~'for ketones and aldehyde^,^' cyclic ketones,32 and p-heteroatom-substituted cyclohe~anones,~~ allenes and and for organoph~sphines,~~ non-linear acety~enes.~' Ab initio theoretical treatments of weakly-bonded systems have been reviewed36 and the energetics of hydrogen-bonding have been discussed in regard to basis counterpoise procedure^,^^ and the effects of ~orrelation.~~ A plethora of modifications to MIND0/340 and MND04' semi-empirical procedures for hydrogen bonds have been described.The AM 1 method underestimates hydrogen-bond strengths for charged systems and prefers bifurcated geometries for neutral systems.42 23 T.Liljefors J. C. Tai S. Li and N. L. Allinger J. Compur. Chem. 1987 8 1051. 24 I. Petterson and T. Liljefors J. Comput. Chem. 1987 8 1139. 25 N. L. Allinger and J.-H. Lii J. Comput. Chem. 1987 8 1146. 26 D. C. Spellmeyer and K. N. Houk J. Org. Chem. 1987 52 959. 27 F. K. Brown K. N. Houk D. J. Burnell and Z. Valenta J. Org. Chem. 1987 52 3050. 28 P. Aped Y. Apeloig A. Ellencweig B. Fuchs I. Goldberg M. Karai and E. Tartakovsky J. Am. Chem. Soc. $987 109 1486. 29 G. W. Spears C. E. Caufield and W. C. Still J. Org. Chem. 1987 52 1226. 30 J. M. Goodman I. Paterson and S. D. Kahn Tetrahedron Lett. 1987 28 5209. 31 J. P. Bowen A. Pathiaseril S. Profeta and N. L. Allinger J. Org. Chem. 1987 52 5162.32 D. J. Goldsmith J. P. Bowen E. Qamhiyeh and W. C. Still J. Org. Chem. 1987 52 951. 33 J. P. Bowen and N. L. Allinger J. Org. Chem. 1987 52 1830. 34 J. P. Bowen and N. L. Allinger J. Org. Chem. 1987 52 2937. 35 N. L. Allinger and A. Pathiaseril J. Comput. Chem. 1987 8 1225. 36 J. H. van Lenthe J. G. C. M. van Duijneveldt-van de Rijdt and F. B. van Duijneveldt Ado. Chem. Phys. 1987 69 521. 37 Z. Latajka and S. Scheiner J. Compur. Chem. 1987 8 663 674. 38 G. Alagona C. Ghio R. Cammi and J. Tomasi Inr. J. Quantum Chem. 1987 32 207. 39 J. E. Del Bene J. Comput. Chqn. 1987 8 810; J. Chem. Phys. 1987 86 2110. 40 N. U. Zhanpeisov A. G. Pel'menshchikov and G. M. Zhidomirov Zh. Strukt. Khim 1987 28 3. 41 A. Goldblum J. Compuf. Chem.1987 8 835; A. A. Voityuk and A. A. Bliznyuk Theor. Chim.Acta 1987 71 327; 1987 72,223. 42 I. H. Williams 1.Am. Chem. SOC.,1987 109 6299. I. H. Williams 3 Electronic Structure Bonding and Properties Charge Distributions and Chemical Bonds.-Molecular structures can be assigned and their relative stabilities and reactivites understood in terms of global and local properties of the electronic charge density such as bond orders and ellipticities (the tendency for charge density to accumulate in a particular plane) and the Laplacian of the charge distribution (measuring local concentration or depletion of charge).43 A theory of atoms in molecules yields average atomic electron populations and energies.44 In unstrained hydrocarbons H is more electronegative than C thus the order of electron-withdrawing abilities is H > CH3 > CH2 > CH > C.Geometrical strain increases the electronegativity of C and decreases the atomic energy of C but increases the energy of H to a greater extent; this provides an explanation for the origin of strain energy. Methyl and methylene groups may often be regarded as transferable units and group properties are often additive.@ ‘Bonds are a fundamental construct of chemistry’ wrote Ritchie and Ba~hrach,~’ who continued ‘nevertheless many chemists are hard pressed to define exactly what a bond is and instead rely upon intuition to identify bonds in unusual structures . . .’ However they have claimed (optimistically?) that electron density distribution analysis46 provides rigorous definitions of bonds rings and cages in molecules; an examination of bond paths (paths of maximum electron density joining pairs of bonded nuclei) for some organolithium compounds yielded surprising result^.^' Feller and Da~idson~~ described [1,1,1] propellane (1) as just a strained cage with little intra-bridgehead covalent bonding and commented (pessimistically?) that ‘it is not possible to translate the concept of a bond into something which can be universally extracted from theoretical calculations.’ Meanwhile Wiberg et ’ obtained a bond order of 0.73 for this bond which they described as arising from in-phase overlap of the tails of outwardly directed sp3 hybrids on the bridgehead carbon atoms.In contrast the bridgehead carbons of [2,2,2] propellane (2) are sp2-hybridized and the intra-bridgehead bond arising from overlap of pure p orbitals has a bond order of 1.26.43 The fact that standard deformation densities sometimes give rise to (counter- intuitive) charge deficits in regions associated with covalent bonds has been shown to be due to the assumption of spherical atomic charge densities;“8 consideration of bond formation between (non-spherical) valence-state atoms restores the intuitive 43 K.B. Wiberg R. F. W. Bader and C. D. H. Lau J. Am. Chem. SOC.,1987 109 985. 44 K. B. Wiberg. R. F. W. Bader and C. D. H. Lau J. Am. Chem. Soc, 1987 109 1001. 45 J. P. Ritchie and S. M. Bachrach J. Am. Chem. SOC.,1987 109 5909. 46 J. P. Ritchie and S. M. Bachrach J.Comput. Chem. 1987 8 499. 47 D. Feller and E. R. Davidson J. Am. Chem. SOC.,1987 109 4133. 48 K. L. Kunze and M. B. Hall J. Am. Chem. SOC.,1987 109 7617. Theoretical Chemistry 29 picture. Various alternative definitions of bond orders49 and atomic charges" have been proposed. Molecular electrostatic potentials have been used to investigate the intra-bridgehead bond in bicy~lobutane,~' and the properties of nitroso- and nitro- aromatic^^^'^^ anii acetylene^;^^ there is only a minor degree of conjugation between the nitro-group and the phenyl ring in nitr~benzene.~~ The P-0 and P-C bonds of phosphine oxide hypophosphite and methylene phosphoranes metaphosphate and tris(methy1ene)metaphosphate anions are semi- polar and have little double-bond ~haracter.~' However phosphorothiolate anions have appreciable P=O double-bond character and a corresponding absence of P=S double-bond character although these results depend upon the overall charge on the anion.56 Delocalization and Aromaticity.-The spin-coupled VB description of benzene" (involving six equivalent essentially localized spin orbitals) has provoked some interesting exchanges in the pages of Schaefer and co-workers quoted Streitwieser ('There is no operational definition of aromaticity') in their ab initio study of [5]paracyclophane5* (3) some of the properties of which are indicative of aromatic character and others not bond alternation is modest but the ring is substantially bent with a consequent loss of thermochemical stability.MNDO calculations on [ nlmetacyclophane~~~ showed that localization of the bonds of the aromatic ring was unfavourable even for highly bent systems. Delocalized structures for [14] and [18] annulene are more stable than localized ones only if interpair electron correlation is included and the Davidson correction added.60 Correlation is responsible for higher ring currents in charged annulenes than neutral ones;6' large neutral 4n-electron systems become weakly aromatic but charged systems are all anti-aromatic. Aromatic stabilization may be explained in terms of highly corre- (CW5 L? (3) (4) 49 H. 0. Villar and M. Dupuis Chem. fhys. Left. 1987 142 59. C. M. Smith and G. G. Hall Int. J. Quantum Chem. 1987 31 685; L. E. Chirlian and M.M. Franc] J. Compuf. Chem. 1987 8 894; K. E. Edgecombe and R. J. Boyd J. Chem. SOC. Faraday Trans. 2 1987,83 1307. " P. Politzer G. P. Kirschenheuter and J. Alster J. Am. Chem. SOC.,1987 109 1033. 52 P. Politzer P. Lane K. Jayasuriya and L. N. Domelsmith J. Am. Chem. Soc. 1987 109 1899. 53 P.Politzer and R. Bar-Adon J. fhys. Chem. 1987,91 2069. 54 P. Politzer and R. Bar-Adon J. Am. Chem. SOC.,1987 109 3529. 55 A. Streitwieser R. S. McDowell and R. Glaser J. Compur. Chem. 1987 8 788; A. Streitwieser A. Rajca R. S. McDowell and R. Glaser 1.Am. Chem. Soc. 1987 109 4184; A. Rajca J. E. Rice A. Streitwieser and H. F. Schaefer ibid. p. 4189. C. Liang and L. C. Allen J. Am. Chem. SOC.,1987 109 6449. 57 L. Pauling Nature (London) 1987 325 396; J.Maddox ihid. 1987 327 551; R. D. Harcourt ibid. 1987 329 491; R. P. Messmer and P. A. Schultz ibid. 1987 329 492; J. Gerratt M. Raimondi and D. L. Cooper 1987 329 492. 58 J. E. Rice T. J. Lee R. B. Remington W. D. Allen D. A. Clabo and H. F. Schaefer J. Am. Chem. SOC.,1987 109 2902. 59 L. W. Jenneskens F. J. J. de Kanter W. H. de Wolf and F. Bickelhaupt J. Compur. Chem. 1987,8 1154. 60 K. Jug and E. Fasold J. Am. Chem. Soc. 1987 109 2263. 61 S. Kuwajima and Z. G. Soos J. Am. Chem. Soc. 1987 109 107. I. H. Williams lated Cooper pairs and a limit of n = 6 or 7 for aromaticity in 4n + 2 electron systems is predicted.62 Correlation decreases the amount of bond alternation in linear polyene~.~’ The electronic properties of a new class of (4n+ 2) alternant hydrocarbons the dimethylene polycyclobutadienes (4), have been examined by a variety of theoretical methods.64 Whereas the properties of classical (Kekult) acenes change progressively with n a parity rule is predicted for these non-Kekult acenes which should have fascinating optical electronic and magnetic properties for even n,the ground state is a singlet with n disjoint non-bonding MOs; for odd n the ground state is a triplet with (n + 1) not-fully-disjoint non-bonding MOs.Electronic properties of poly- acenes and other hydrocarbon polymers have been studied6’ by a new molecular- orbital based molecular mechanics method.66 The topic of v-u interactions has been reviewed,67 and a v-orbital axis vec- tor/three-dimensional Huckel MO (POAVI3D-HMO) theory which provides a unified treatment of both planar and non-planar conjugated organic molecules has been proposed.68 Deviations of such systems from planarity are aptly described in terms of geometrical pyramidali~ation.~~ There emerges a natural definition of a homoconjugate bond as one between conjugated atoms whose overlap integral is not dominated by the pT pT contribution.68 Four-centre two-electron bonding in a tetrahedral topology has been calculated for the cation (5) -an example of 3D-homoaromati~ity.~~ Two types of 1,3-dipole may be distinguished at the UHF/6-31G* Molecules such as diazomethane (22 electrons) are hypervalent closed-shell species involving full double and triple bonds to the central nitrogen (6); 24-electron (allyl-type) 1,3-dipoles such as nitrone (7) each have two bonds midway between single and double and may be described by resonance structures in which the central atom has normal ~alency.~~ Spin-coupled valence-bond calculations for these molecules are illuminating the two electrons on the central nitrogen of diazomethane occupy orbitals which overlap very substantially and are coupled not to each other but to the terminal atoms respectively confirming the double bond f triple bond 62 R.H. Squire J. Phys. Chem. 1987 91 5149. 63 P. G. Szalay A. Karpfen and H. Lischka J. Chem. Phys. 1987 87 3530. 64 J. Pranata and D. A. Dougherty J. Am. Chem. Soc. 1987 109 1621. 65 J. Kao and A. C. Lilly J. Am. Chem. Soc. 1987 109 4149.66 J. Kao J. Am. Chem. Soc. 1987 109 3817. 67 R. Gleiter Pure Appl. Chem. 1987 59 1585. 68 R.C. Haddon J. Am. Chem. SOC.,1987 109 1676. 69 R. C. Haddon J. Phys. Chem. 1987 91 3719. 70 M. Bremer P. v. R. Schleyer K. Schotz M. Kausch and M. Schindler Angew. Chem. Inr. Ed. Engl. 1987 26 761. 71 S. D. Kahn W. J. Hehre and J. A. Pople J. Am. Chem. Soc. 1987 109 1871. Theoretical Chemistry 31 structure (6).72Nitrone (7) with a C=N double bond and a polar N-0 bond of order -1.5 does not possess singlet diradical character.72 A CASSCF wavefunction for nitrone may be transformed to a valence-bond space to yield results in agreement with the spin-coupled de~cription.~~ MCSCF calculations on carbonyl ylides have suggested that the allylic resonance is unstable with respect to out-of-plane vibration.74 Shaik et uZ.~~ have questioned whether delocalization is a driving force in chemistry and have argued that the .rr-electron delocalization of the ally1 radical and of benzene is in each case a by-product of the geometric constraint imposed by the a-bonded framework which prefers a symmetrical structure.Furthermore they have argued that the stabilization conferred by delocalization of a 7r system at a given geometry is not contradictory with the distortive propensity of the .rr-system towards a lower-symmetry structure. Radicals Carbenes and Diradicak-Accurate calculations (MCSCF/6-31G* + large CI) on succinimidyl radical have predicted the singlet .rr state to be 21.5 kJ mol-' lower than the singlet aNstate responsible for most of the known imidyl chemistry; the authors have commented that their calculations 'emphasise the care that is required in applying ab initio techniques to many molecular species to produce meaningful results and illustrate the great attention to detail and awareness of the limitations of the techniques used which are needed to obtain a minimum qualitative description of a potential-energy surface.'76 The spin-coupled orbitals of methylene are highly localized the singly occupied orbitals of the 3B1ground state correspond to the usual sp'( a) and pT description but those of the 'A excited state are equivalent sp3 hybrids.77 The spin-coupled VB method77 and the simple GVB method78 both give essentially the same (slightly too high) value for the methylene singlet-triplet separation as does full CI using a DZP basis but each method is capable of reproducing the experimental value using more extended Singlet-triplet separations for substituted carbenes may be reliably estimated by a GVB + CI procedure.80 It has been argued that the experi- mental observation of an e.p.r.signal for cycloheptatrienylidene is not inconsistent with the theoretical prediction of a singlet ground state since at the optimum triplet geometry the singlet is higher in energy." A singlet ground state has also been predicted8* for tetramethyleneethane (8) the simplest non-KekulC hydrocarbon '* D. L. Cooper J. Gerratt M. Raimondi and S. C. Wright Chem. Phys. Let?.,1987 138 296.73 J. J. W. McDouall and M. A. Robb Chem. Phys. Lett. 1987 142 131. 74 A. Tachibana M. Koizumi I. Okazaki H. Teramae and T. Yamabe Theor. Chim. Acta 1987 71 7. 75 S. S. Shaik P. C. Hiberty J.-M. Lefour and G. Ohanessian J. Am. Chem. Soc. 1987 109 363. 76 M. J. Field I. H. Hillier and M. F. Guest J. Chem. Soc. Perkin Trans. 2 1987 1311. 77 M. Sironi M. Raimondi D. L. Cooper and J. Gerratt J. Chem. Soc. Furuday Trans. 2 1987,83 1651. 78 E. A. Carter and W. A. Goddard J. Chem. Phys. 1987 86 862. 79 C. W. Bauschlicher S. R. Langhoff and P. R. Taylor J. Chem. Phys. 1987 87 387. 8J E. A. Carter and W. A. Goddard J. Phys. Chem. 1987,91 4651. C. L. Janssen and H. F. Schaefer J. Am. Chem. Soc. 1987 109 5030. 82 P. Du and W. T. Borden J.Am. Chem. Soc. 1987 109. 930. 32 I. H. Williams whose non-bondings MOs are disjoint (i.e. can be localized to different regions of space); this finding contradicts previous theoretical results and also is in apparent conflict with e~periment.~~ The problem of spin-orbit coupling and intersystem crossing between singlet and triplet states of diradicals and radical pairs has been addressed by MCSCF calculations for trimethylene and the methyl-methyl pair.84 4 Molecular Structure and Energetics Geometry optimization of indkidual equilibrium structures at low levels of theoreti- cal sophistication remains a popular pastime but increasingly there is a trend towards more complete characterization of a potential energy surface corresponding to a particular molecular formula these studies involve consideration not only of the various energetic minima but also of the saddle points for their interconversion and hence defy neat categorization into the pigeon-holes of structure and reactivity.Nonetheless conformational and configurational isomerizations may be distin- guished. The structure of fluorine peroxide (FOOF) provides a problem for normally reliable theoretical methods CI methods including all single and double excitations fail to predict the bond lengths correctly even when high-quality bases are empl~yed.~’ However the use of externally contracted CI from a large complete- active-space reference does yield reasonable agreement with the experimental geometry.86 EpiotisS7 has expounded the thesis that molecular stereoelectronics cannot be understood on the basis of orbital symmetry considerations alone but requires consideration of what he calls ‘colour’ -the intrinsic ability of an atom to form bonds by overlap.A valence-bond approach has been employed to explain the occurrence and extent of non-classical distortion from planarity of double bonds or from linearity for triple bonds and cumulenones as related by the singlet-triplet energy separation of the interacting fragments forming the multiple bond.88 Neutral Molecules.-Bicyclobutene (9) is predicted89 to have a singlet ground state with a non-planar skeleton and an inversion barrier of -50 kJ mol-’; the dimethyl- ene-bridged species (lo) which has been trapped experimentally is a minimum on the MP2/6-31G* surface (but not the HF/6-31G* surface) and is less stable than the as yet unobserved parent (9).90 A (9) (10) 83 P.Dowd W. Chong and Y. Paik J. Am. Chem. SOC.,1987 109 5284. 84 L. Carlacci C. Doubleday T. R.Furlani H. F. King and J. W. McIver J. Am. Chem. SOC.,1987 109 5323. 85 D. A. Clabo and H. F. Schaefer Int. J. Quantum Chem. 1987 31 429. 86 C. M. Rohlfing and P. J. Hay J. Chem. Phys. 1987 86 4518. 87 N. D. Epiotis THEOCHEM. 1987 38 1. G. Trinquier and J.-P. Malrieu J. Am. Chem. SOC.,1987 109 5303. 89 B. A. Hess W. D. Allen D. Michalska L. J. Schaad and H. F. Schaefer J. Am. Chem. SOC.,1987 109 1615. 90 B. A. Hess D. Michalska and L. J. Schaad J. Am. Chem. SOC.,1987 109 7546. Theoretical Chemistry 33 The ring puckering potential of oxetane is primarily due to intramolecular disper- sion interactions involving oxygen lone pairs which are very difficult to calculate accurately." The inversion barrier for azetidine is comparable with that of ammonia and much lower than that of a~iridine.'~ Dioxetenes and diazetines tend to be unstable towards ring ~pening.'~ Dimethyldi~xirane'~is more stable than dioxirane the peroxide bond of which is strained and weaker than those in hydrogen peroxide and peroxytrifluoroacetic acid.95 The concept of strain has been explored by theoretical studies on cyclopoly-~ilanes:'~ cyclotrisilane is -40 kJ mol-' more strained than cyclopropane whereas cyclotetrasilane is -40 kJ mol-' less strained than cyclobutane.Silicon analogues bicy~lobutane,~~ of ethene,97 cycl~butadiene,'~ benzene,"' tetrahedrane prismane and cubane"' have been considered and theoretical studies of silicon chemistry have been reviewed.'02 Cations and Radical Cations.-The non-classical bridged structure (1 1) for vinyl cation is more stable than the classical structure (12) by 21 kJ mol-' at the MP4SDTQ/6-31 lG**(2df)//MP2(ful1)/6-31G* level;'03 a multi-reference CASSCF-CI studylo4 concurs except that (12) is found to be in a shallow minimum rather than at a saddle point. Unsubstituted vinylacetylene ( 13) is predictedlo5 to be less stable than its bridged isomer (14). Corner-protonated cyclopropane prefers an unsymmetrical bridged structure (15) in which the ratio of charges on the basal C atoms is 3:2; the symmetrical structure is at a saddle point.lo6 There is no F-bridging in CF3CH2+ and its isomer^,'^' and the ethyl dication CH3CH2'2+ has an open structure.'08 H+ H HCEC \+ \+ HC\ + /C=CH /C=CH 1 I HC-CH H H HC 91 H.Sellers J. Almlof S. Saebo and P. hlay J. Phys. Chem. 1987 91 4216. R. Dutler A. Rauk and T. S. Sorensen J. Am. Chem. SOC., 92 1987 109 3224. 93 P. H. M. Budzelaar D. Cremer M. Wallasch E.-U. Wiirthwein and P. v. R. Schleyer J. Am. Chem. SOC.,1987 109 6290. 94 W. Adam Y.-Y. Chan D. Cremer J. Gauss D. Scheutzow and M. Schindler J. Org. Chem. 1987 52 2800; D. Cremer and M. Schindler Chem. Phys. Left.,1987 133 293. 95 P. Politzer R. Bar-Adon and R. S. Miller J. Phys. Chem. 1987 91 3191.96 R. S. Grev and H. F. Schaefer J. Am. Chem. Soc. 1987 109 6569. 97 H. Teramae J. Am. Chem. SOC.,1987 109 4140. 98 A. F. Sax and J. Kalcher J. Chem. SOC.,Chem. Commun. 1987 809. 99 S. Collins R. Dutler and A. Rauk J. Am. Chem. SOC.,1987 109 2564; P. v. R. Schleyer A. F. Sax J. Kalcher and R. Janoschek Angew. Chem. Int. Ed. Engl. 1987 26 364. 100 S. Nagase H. Teramae and T. Kudo J. Chem. Phys. 1987 86 4513. 101 S. Nagase M. Nakano and T. Kudo J. Chem. SOC., Chem. Commun. 1987 60. 102 K. K. Baldridge J. A. Boatz S. Koseki and M. S. Gordon Ann. Rev. Phys. Chem. 1987 38 211. I03 J. A. Pople Chem. Phys. Lett. 1987 137 10. 104 R. Lindh B. 0. Roos and W. P. Kraemer Chem. Phys. Lett. 1987 139 407. I05 K. Hori T. Yamabe A.Tachibana Y. Asai K. Fukui S. Kobayashi and H. Taniguchi THEOCHEM 1987 38 295. I06 M. J. S. Dewar E. F. Healy and J. M. Ruiz J. Chem. SOC., Chem. Commun. 1987 943. 107 M. Charpentier J. Fossey T. T. Tidwell. and S. Wolfe Can. J. Chem. 1987 65 473. 108 M. W. Wong J. Baker R. H. Nobes and L. Radom J. Am. Chem. SOC. 1987 109 2245. 34 I. H. Williams Ylidions are radical cations with unusual structures whose neutral (ylide) counterparts are unknown or extremely reactive; theoretical structures and stabilities of ylidions CH2X+H and their corresponding ylides CH2XH have been ~urveyed.'~' Structures such as (CH2CH2CO)'+ (CH2CH2 -' -OC)'+ and (CHCHCHOH)'+ have remarkable stability on the C&O'+ surface as compared with ionized methylketene and propenal.l'o An ab initio theoretical analysis has provided a coherent description of the gas-phase ion chemistry of metastable ionized methyl acetate."' Ionized ethane- 1,2-diol undergoes spontaneous intramolecular 1,4-H migration l2 and gives stable hydrogen-bridged radical cation i~orners."~ Conformational Isomerism.-Amide 'resonance' involves charge transfer from C to N not from N to 0 since in the planar conformation N is more electronegative (has more s character) than C.I14 Similarly the 2 conformers of formic acid methyl formate acetic acid and methyl acetate are stabilized by virtue of the singly-bonded oxygen possessing more s character (leading to lower energy) in the 2 than in the E conformers.' l4 Comparative studies of the conformational energetics of the monothio115 and dithio1I6 analogues of these species have been performed.The effect of electron correlation on the conformational energy difference in glyoxal is significant;"' trans-dithioglyoxal is more stable than the not-rigidly-planar cis con- former whose energy is close to that of the cyclic structure 1,2-dithiete.l'* The observation of an eclipsed C,3-CH3 in the crystal structure of a tricyclic orthoamide thought to arise from hydrogen bonding to the methyl group by three water molecules has prompted a theoretical study of C- H .-.0 hydrogen bond- ing:"' the interaction between methane and water is worth -7.2 kJ mol-' at the MP4/6-311G(2d,p) level. 5 Reactivity and Mechanism Theory of Reactivity.-Diabatic surfaces and the resonance interactions between them have been computed for two-bond cycloaddition reactions.12' The intersection of the reactant-like and product-like diabatic surfaces determines the topology of the adiabatic surface; these intersections occur at roughly the same energies for different mechanistic possibilities such as concerted synchronous concerted asyn- chronous and stepwise processes.Mechanistic preferences are controlled by the resonance interactions which tend to favour concerted synchronous paths for allowed reactions in contrast to the dictum that 'synchronous multibond mechanisms are normally prohibited.' 1UY B. F. Yates W. J. Bouma and L. Radom J. Am. Chem. SOC.,1987 109 2250. G. Bouchoux THEOCHEM 1987 36 107. 111 N. Heinrich J.Schmidt H. Schwarz and Y. Apeloig J. Am. Chem. SOC.,1987 109 1317. 112 B. F. Yates W. J. Bouma J. K. Macleod and R. Radom J. Chem. SOC., Chem. Commun. 1987 204. 113 P. C. Burgers J. L. Holmes C. E. C. A. Hop R. Postma P. J. A. Ruttink and J. K. Terlouw J. Am. Chem. SOC.,1987 109 7315. 114 K. B. Wiberg and K. E. Laidig J. Am. Chem. SOC.,1987 109 5935. 'I5 R. Fausto and J. J. C. Teixeira-Dias THEOCHEM 1987 35 381; S. P. So ibid. 1987 36 141; A. Toro-Labbe and C. Cardenas In?. J. Quantum Chem. 1987 32 685. 116 R. Fausto J. J. C. Teixeira-Dias and P. R. Carey THEOCHEM 1987 37 119. 11' S. Saebo Chem. Phys. 1987 113 383. 118 J. D. Goddard J. Compur. Chem. 1987 8 389. I19 P. Seiler G. R. Weisman E. D. Glendening F. Weinhold V. B. Johnson and J.D. Dunitz Angew. Chem. Int. Ed. EngL 1987 26 1175. 120 F. Bernardi M. Olivucci J. J. W. McDouall and M. A. Robb J. Am. Chem. SOC.,1987 109 544. Theoretical Chemistry 35 A practical formulation of symmetry selection rules for reaction mechanisms has been applied to some electrocyclic processes,'21 and these rules have been re-expressed in terms of permutation-inversion group symmetries.'22 A way of looking at chemical interactions in terms of pairs of interacting localized orbitals has been reviewed123 and a Riemann geometrical formulation of the principle of least elec- tronic motion has also been applied to electrocyclic reaction^.'^^ Topological aspects of chemical reactivity have been discussed.'2s Energy profiles and reaction surfaces have been considered in regard to perpen- dicular effects on transition states;'26 reaction-surface and curve-crossing approaches lead to similar mathematical descriptions of reactivity.The curve-crossing model has been used to correlate nucleophilicity with vertical ionization potentials in cation-anion recombinations and to gain insight into the physical significance of the N+scale.'27 The roles of transition-state bond order and reaction energy in methyl nucleophilic substitutions'** and Bronsted relationships in proton-transfer reactions'29 have been studied using an intersecting parabolae model. Extremely loose SN2transition states give rise to unexpected bond-order relationships in that they are dominated by anti-Hammond eff ect~.'~' A simple modification of the Morse equation yields several relationships among bond lengths energies and stretching force constants with interesting consequence^.'^' A general definition of formal steric enthalpies and their differences has been given which provides the basis for the use of molecular mechanics for calculations of equilibrium and rate constant^;'^^ the effects of steric hindrance on rates of esterification and acid-catalysed hydrolysis have been studied by molecular mechanics using this f~rrnalism.'~~ A modified MM2 model for the rates of acid- catalysed lactonizations of hydroxy acids based upon ab initio calculations for H20 + HC(OH)2+ has reproduced experimental relative activation energies over ten orders of magnit~de:'~~ no relationship has been found between reactivity and either the angle of nucleophilic attack or the distance between the reacting atoms; hence there is no support for either the concept of 'angularity' (orbital steering) or the 'spatiotemporal hypothesis'.Rearrangements.-The degenerate Cope rearrangement of hexa- 1,Sdiene is pre- dicted by AM1 135,136 and MP4SDQ/6-31G*'37 calculations to involve a biradicaloid intermediate with chair geometry; an alternative pathway via an aromatic transition 121 A. Rodger and P. E. Schipper J. Phys. Chern. 1987 91 189. 122 A. Metropoulos J. Phys. Chern. 1987 91 2233. 123 H. Fujimoto Acc. Chern. Res. 1987 20 448. 124 A. Igawa and H. Fukutome Chem. Phys. Lett. 1987 133 399. 125 R. Ponec Collect. Czech. Chern.Cornrnun. 1987 52 555 1375 2603. 126 N. Agmon J. Org. Chern. 1987 52 2192. 127 S. S. Shaik J. Org. Chem. 1987 52 1563. 128 S. J. Formosinho Tetrahedron 1987 43 1109. I29 S. J. Formosinho J. Chern. SOC.,ferkin Trans. 2 1987 61. 130 G. P. Ford and C. T. Smith J. Chern. SOC. Chern. Cornrnun. 1987 44. 131 H.-B. Biirgi and J. D. Dunitz J. Am. Chem. SOC.,1987 109 2924. 132 D. F. DeTar J. Org. Chern. 1987 52 1851. 133 D. F. DeTar S. Binzet and P. Darba J. Org. Chern. 1987 52 2074. 134 A. D. Dorigo and K. N. Houk J. Am. Chern. SOC.,1987 109 3698. I35 M. J. S. Dewar and C. Jie 1. Am. Chem. SOC. 1987 109 5893. 136 M. J. S. Dewar and C. Jie J. Chem. SOC. Chern. Cornrnun. 1987 1451. 137 M. J. S. Dewar and E. F. Healy Chem. Phvs.Lett. 1987 141 521. I. H. Williams structure of boat geometry has a different activation entr0~y.l~~ Rearrangements of 2-phenyl and 2,Sdiphenyl hexa-l,Sdienes are also predicted to involve biradicaloid intermediates in very shallow wells whereas other derivatives rearrange by concerted (but not synchronous) mechani~rns.'~~ According to Dewar 'unambiguous [mechanistic] conclusions cannot.. .be drawn from calculations [for a single reac-tion] by any current procedure because the errors in energies given by even the best of them are too large. A better approach is to calculate a number of examples of the reaction for which activation parameters are available. . . Even if the errors in the calculated activation parameters for the individual reactions are too large for definite conclusions to be drawn from them the relative values for a number of related reactions are likely to be reproduced at least qualitatively.Comparison of the predicted pattern of rates with experiment should then provide a more reliable test of the predicted mechanism than any calculation for a single case.'135 Q A CASSCF and MP4/6-3lG* study'38 of thermal reactions of bicyclopentene (16) has suggested that the degenerate walk rearrangement is probably a stepwise process involving a diradical intermediate since the activation energy for this symmetry-allowed reaction is -40 kJ mol-' higher than that for the symmetry- forbidden disrotating ring opening to cyclopentadiene. Rearrangement of cyclo- he~yne,'~~ isomerization of allene to pr~pyne,'~' and of acetylene to vinylidene (catalysed by a metal atom),I4' ring opening of cyclopropane (catalysed by pal- ladium),14* methylenecyclopropane radical cation,143 three-membered ring car-banions,la and ethene episulphoxide anion,'45 have been studied at various theoreti- cal levels.The acyl carbene intermediate involved in the Wolff rearrangement has a singlet ground state which is a pure diradical; the triplet state is important too and there is almost no barrier to cyclization of either state to ~xirene.'~~ Rearrange-ments of H3PX to H2PXH have been studied for X=0147,148and X=NH and CH2.'47 The importance of using a uniform level of theory to study reaction paths has been illustrated by CASSCF calculations of the ground-state potential energy surface of diazene its conformational and configurational isomers and the transition structures for their intercon~ersion.'~~ 138 P.N. Skancke K. Yamashita and K. Morokuma J. Am. Chem. SOC.,1987 109 4157. 139 J. Tseng M. L. McKee and P. B. Shevlin J. Am. Chem. SOC.,1987 109 5474. I40 T. Kakumoto T. Ushirogouchi K. Saito and A. Imamura J. Phys. Chem. 1987 91 183. 141 S. Sakai and K. Morokuma J. Phys. Chem. 1987,91 3661. 142 M. R. A. Blomberg P. E. M. Siegbahn and J.-E. Backvall J. Am. Chem. SOC. 1987 109 4450. 143 P. Du and W. T. Borden J. Am. Chem. SOC.,1987 109 5330. 144 I. Rajyaguru and H. S. Rzepa J. Chem. Soc. Perkin Truns. 2 1987 359. 145 G. Maccagnani H. B. Schlegel and G. Tonachini J. Org. Chem.1987 52 4961. 146 J. J. Novoa J. J. W. McDouall and M. A. Robb J. Gem. SOC.,Farday Truns. 2 1987 83 1629. 147 M. T. Nguyen and A. F. Hegarty J. Chem. Soc. Perkin Trans. 2 1987 47. 148 C. J. Cramer C. E. Dykstra and S. E. Denmark Chem. Phys. Lett. 1987 136 17; J. A. Boatz M. W. Schmidt and M. S. Gordon J. Phys. Chem. 1987 91 1743. 149 H. J. Aa. Jensen P. Jorgensen and T. Helgaker J. Am. Chem. SOC.,1987 109 2895. Theoretical Chemistry 37 Hydron Transfer.-The facile suprafacial 1,3-H shift predicted for the radical cation of propene (in contrast to the symmetry-forbidden nature of the process for propene itself) has hinted at the general willingness of radical cations to undergo sigmatropic rearrangements which would be difficult for the neutral parent molecule^.'^^ Barriers for intermolecular H migrations of ionized amines CH3(CH2) NH;+ to 6H,(CH2) NH3+ (gas-phase analogues of the Hofmann-Loiller and related re-arrangements) decrease with increasing n as the angle about the transferring H increases in the respective transition struct~res.'~' Similarly the activation enthalpy for intramolecular H migration in alkoxy radicals CH3(CH2),0 is lower for n = 4 F-H abstraction involving a seven-membered cyclic transition structure) than for n = 3; the experimental observation of 8-H abstraction (viu a six-membered cyclic transition structure) is due to entropic fa~t0rs.l~~ The suggestion of a planar C, transition structure for the 1,5-H shift of 1,3-pentadiene has been shown to be incorrect owing to the failure to use a uniform level of theory for the alternative pathways; a non-planar C,transition structure is preferred for the suprafacial migration at the MP2 Hydride transfer from methoxide anion to formaldehyde proceeds uia an unsym- metrical transition structure (17) on a very flat potential energy surface;'54 the 'w'-shaped C2,structure (18) has two imaginary frequencies.The primary deuterium kinetic isotope effect calculated for the transition structure (19) is in fair agreement with e~periment.'~~ The hydroxide-anion promoted intramolecular hydride transfer of glyoxal is predicted to have a larger primary deuterium kinetic isotope effect than the intermolecular Cannizzaro reaction of formaldehyde; 15' the mechanisms of the benzilic acid and related rearrangements have also been ~tudied.'~' Hydride transfer to methyleniminium cation from methylamine and 1,4-dihydropyridine prefers a syn transition structure with a 150-160" angle at the transferring H; the bent syn geometry is favoured with respect to the essentially linear anti geometry by virtue of stabilizing orbital interaction^."^ The initial step of the ene reaction between the alkoxide anion of propenol and ethene is H-atom transfer whereas with propenal as the enophile it is hydride transfer.'59 150 T.Clark J. Am. Chem. SOC.,1987 109 6838. 151 8. F. Yates and L. Radom J. Am. Chem. Soc. 1987 109 2910. A. E. Dorigo and K. N. Houk J. Am. Chem. Soc. 1987 109 2195. IS3 F. Jensen and K.N. Houk J. Am. Chem. Soc. 1987 109 3139. 154 Y.-D. Wu and K. N. Houk J. Am. Chem. SOC.,1987 109 906. 155 M. J. Field I. H. Hillier S. Smith M. A. Vincent S. C. Mason S. N. Whittleton C. 1. F. Watt and hl. F. Guest J. Chem. Soc. Chem. Commun. 1987 84. 156 I. Rajyaguru and H. S. Rzepa J. Chem. SOC.,Chem. Commun. 1987 998. 157 I. Rajyaguru and H. S. Rzepa J. Chem. SOC.,Perkin Trans. 2 1987 1819. 158 Y.-D. Wu and K. N. Houk J. Am. Chem. SOC.,1987 109 2226. 15'9 I. A. Gad El Karim and H. S. Rzepa J. Chem. Soc. Chem. Comrnun. 1987 193. 38 I. H. Williams Additions to Double Bonds.-The stereochemistry of electrophilic addition to allylic double bonds has been explored by the use of a proton as an electrophilic probe.’60 Electrostatic’61 and steric’62 interactions are important in determining the facial selectivity of Diels- Alder cycloadditions between chiral dienes and/or dienophiles; the frontier molecular orbital (FMO) approach is deficient.161 While FMO considera- tions explain the nature of Lewis-acid catalysis on Diels- Alder reactions of propenal it is secondary orbital interactions which establish their regio- and stereo-selectivities according to Guner et ay3but Fox et have maintained that steric effects are at least as important and Sustmann’s perturbation MO analyses of cycloadditions have concurred with MCSCF calculations for 1,3-dipolar cycloadditions have indicated a preference for concerted mechanisms; 166 pericyclic dihydrogen transfers from HXYH species also prefer concerted whereas 2 +2 cycloadditions of dialkoxyethynes with heterocumulenes may be borderline between non-synchronous concerted and stepwise.’68 The barrier for the concerted ene reaction of propene with formaldehyde is -21 kJ mol-’ lower than that with ethene although the transition structures are remarkably ~imi1ar.l~~ The spin-coupled VB description of carbene addition to ethene has provided a straightforward explanation for the stereospecificity of singlet addition and the lack of it for triplet additi~n.~’ Concerted addition of hydrogen halides HX to olefins may be catalysed by a second HX molecule in a cyclic transition stru~ture.”~ Hydrogenation of ethene may be similarly catalysed by HF but catalysis by H,O+ involves a cationic interrnediate.l7‘ Barrier heights for addition of OH to ethyne and ethene are overesti- mated by unrestricted Moller-Plesset perturbation theory calculations but annihila- tion of the largest spin component at the PMP4 level provides good agreement with experimental estimate^."^ The importance of steric effects and the role of the Felkin torsional model in determining the facial stereoselectivity of nucleophilic additions to carbonyl com- pounds has been noted.’73 A concerted mechanism for enamine addition to carbonyl compounds involving proton transfer in a cyclic transition structure avoids the unfavourable charge-separation required by the alternative stepwise mechanism via a zwitterionic ir~termediate.”~ Bifunctional catalysis by water of ammonia addition to formaldehyde is effective owing to strong transition-state hydrogen bonding 160 S.D. Kahn C. F. Pau A. R. Chamberlin and W. J. Hehre J. Am. Chem. SOC.,1987 109 650; S. D. Kahn and W. J. Hehre ibid. p. 666; A. R. Chamberlin R. L. Mulholland S. D. Kahn and W. J. Hehre ibid. p. 672. S. D. Kahn and W. J. Hehre J. Am. Chem. SOC. 1987 109 663. 162 F. K. Brown K. N. Houk D. J. Burnell and Z. Valenta J. Org. Chem. 1987 52 3050. 163 0.F. Guner R. M. Ollenbrite D. D. Shillady and P. V. Alston J. Org. Chem. 1987 52 391. 164 M. A. Fox R. Cardona and N. J. Kiwiet J. Org. Chem. 1987,52 1469. 16’ R. Sustmann and W. Sicking Chem. Ber. 1987 120 1323 1471 1653. 166 J. J. W. McDouall M. A. Robb U. Niazi F. Bernardi and H. B. Schlegel J. Am. Chem. SOC.,1987 109 4642.167 D. K. Agrafiotis and H. S. Rzepa J. Chem. SOC.,Chem. Commun. 1987 902. M. A. Pericas F. Sarratosa and E. Valenti J. Chem. SOC.,Perkin Trans. 2 1987 151. 169 R. J. Loncharich and K. N. Houk J. Am. Chem. SOC., 1987 109 6947. 170 C. Clavero M. Duran A. Lledos 0. N. Ventura and J. Bertran J. Cornput. Chem. 1987 8 481. 17’ J. C.Siria M. Duran A. Lledos and J. Bertran J. Am. Chem. SOC. 1987 109 7623. ”* C. Sosa and H. B. Schlegel J. Am. Chem. Soc, 1987 109 4193. 173 Y.-D. Wu and K. N. Houk J. Am. Chem. SOC.,1987 109,908; Y.-D. Wu K. N. Houk and B. M. Trost ibid. p. 5560; E. P. Lodge and C. H. Heathcock ibid. p. 2819. Theoretical Chemistry 39 involving these partial positive and negative charges4 Acid hydrolysis of methyl carbamate involves rate determining attack of water upon the N-protonated arba am ate.'^^ Stereoelectronic effects upon nucleophilic addition of phosphite to formaldehyde have been discussed.176 A study of the displacement reaction of chloride ion with formyl chloride at the MP3/6-31+ G*//3-21+ G has revealed the tetrahedral C,symmetrical species (20) to be a transition structure between the reagent and product ion-dipole com- plexes (21) on a double-well energy surface; 3-21 +G calculations for the reaction with acetyl chloride have suggested that the transition structure is planar with C, symmetry -the 'tetrahedral intermediate' is not even a stationary point on the ridge separating reagents and products! Blake and Jorgensen have commented that the central role of tetrahedral intermediates in addition reactions is not as universal as is commonly a~sumed."~ A theoretical study of the reactivity of phosphonium and sulphonium methylides with formaldehyde has accounted for the preference of the phosphorus species to undergo the Wittig reaction yielding ethene whereas the sulphur compound favours the Corey-Chaykowsky reaction with oxirane as the prod~ct.'~' Miscellaneous Reactions.-A study of SN2reactions of hydroxide and hydroperoxide anions with methyl chloride has concluded that the a-effect is due to ~olvation.'~~ Pathways for nucleophilic substitution at silicon'80 and for the Reformatsky reac- tion181 have been examined.Unimolecular ring opening of protonated oxirane yields protonated acetaldehyde in a concerted process but bimolecular attack of water provides a gas-phase counterpart to the classical A2 mechanism for hydrolysis.''* Methylene insertions into molecular hydrogen,'83 ethane and cycl~propane'~~ have been studied.Calculations relevant to the mechanism of chemical carcinogenesis by N-nitrosamines have been ~erf0rmed.l~~ 174 A. Sevin J. Maddaluno and C. Agarni J. Org. Chem. 1987 52 5611. 175 I. Lee C. K. Kim and B. C. Lee J. Comput. Chem. 1987,8 794. 176 J.-W. A. Chang K. Taira S. Urano and D. G. Gorenstein Tetrahedron 1987 43 3863. 177 J. F. Blake and W. L. Jorgensen J. Am. Chem. SOC.,1987 109 3856. 178 F. Volatron and 0. Eisenstein J. Am. Chem. SOC. 1987 109 1. 179 J. D. Evanseck J. F. Blake and W. L. Jorgensen J.Am. Chem. SOC. 1987 109 2349. 180 J. A. Deiters and R. R. Holrnes J. Am. Chem. SOC. 1987 109 1686 1692. 181 M. J. S. Dewar and K. M. Men J. Am. Chem. SOC. 1987 109 6553. 182 G. P. Ford and C. T. Smith J. Am. Chem. Soc. 1987 109 1325. 183 M. Ortega J. M. Lluch A. Oliva and J. Bertran Can. J. Chem. 1987 65 1995. 184 M. S. Gordon J. A. Boatz D. R. Gano and M. G. Friederichs J. Am. Chem. SOC. 1987 109 1323. 185 C. A. Reynolds and C. Thornson Znt. J. Quantum Chem. 1987,32 123; J. Chem. SOC.,Perkin Trans. 2 1987 1337; THEOCHEM 1987,34,345; M. T. Nguyen and A. F. Hegarty J. Chem. SOC.,Perkin Trans. 2 1987 345; M. Poulsen D. Spangler and G. H. Loew MoZ. Toxicol. 1987 1 35. I. H. Williams 6 Solvation Jorgensen has exemplified the use of statistical perturbation theory in Monte Carlo simulations of the conformation of butane in water,'86 the pK of ethane in water,'87 and the hydration and energetics of t-Bu+CI- ion pairs in aqueous solution.'88 Free-energy calculations of solvation of organic molecules by computer simulation have been reviewedlS9 and a dynamical approach based on a combined quantum and molecular mechanics potential has been applied'" to the SN2reaction C1- + CH,Cl the advantages of this method are that it avoids the need for extensive parameterization of the reaction pathway and that it permits the effect of solvation upon the electronic structure of the solute to be ascertained.'" Tautomeric equilibria of 2-oxopyridine 2-oxopyrimidine and cytosine in aqueous solution have been studied by free-energy perturbation methods giving about 4 kJ mol-' uncertainty in the solvation contribution to free-energy differences.'" The results of an ab initio MO study of bifunctional catalysis of 2-oxopyridine tautomerism by one or two specifically solvating water molecules were not greatly affected by the additional treatment of bulk solvation by a reaction field continuum m0de1.l~~ Specific solvation effects upon ketonization of vinyl 1,3-proton shift of nitr~samine,'~~ carbinolamine formation,42 formic acid dehydration and decarboxylati~n,'~~ COz h~dration,'~~ have also been studied by ab initio and 1,l-addition to is~cyanides'~~ methods.Burshtein has described a modified point dipole model to simulate solvent effects*98 and has applied it to studies of carbonyl addition,'98 proton transfer,'99 and SN2 reactions.*'' 1ti6 W.L. Jorgensen and J. K. Buckner J. Phys. Chem. 1987 91 6083. 187 W. L. Jorgensen J. M. Briggs and J. Gao J. Am. Chem. SOC.,1987 109 6857. 188 W. L. Jorgensen J. K. Buckner S. E. Huston and P. J. Rossky J. Am. Chem. Soc. 1987 109 1891. I R9 P. A. Bash U. C. Singh R. Langridge and P. A. Kollrnan Science 1987 236 564. 190 P. A. Bash M. J. Field and M. Karplus J. Am. Chem. SOC.,1987 109 8092. 191 P. Cieplak P. A. Bash U.C. Singh and P. A. Kollman J. Am. Chem. SOC.,1987 109 6283. I92 M. J. Field and I. H. Hillier J. Chem. SOC.,Perkin Trans. 2 1987 617. 193 0. N. Ventura A. Lledos R. Bonaccorsi J. Bertran and J. Tomasi Theor. Chim.Acta 1987 72 175. 194 C. A. Reynolds and C. Thornson J. Chem. SOC.,Faraday Trans. 2 1987,83,485. 195 P. Ruelle J. Am. Chem. SOC.,1987 109 1722. 196 M. T. Nguyen A. F. Hegarty and T.-K. Ha THEOCHEM 1987 35 319. 197 M. T. Nguyen and A. F. Hegarty J. Chem. SOC.,Perkin Trans. 2 1987 1675. 19R K. Ya. Burshtein THEOCHEM 1987,38 195. 199 K. Ya. Burshtein THEOCHEM 1987 38 203. 200 K. Ya. Burshtein THEOCHEM 1987 38 209.

ISSN:0069-3030    

DOI:10.1039/OC9878400025

出版商:RSC    

年代:1987

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (i) Pericyclic Reactions By D. W. JONES Department of Organic Chemistry The University Leeds LS2 9JT 1 Cycloaddition Reactions Secondary deuterium isotope effects support non-synchronous but concerted Diels- Alder addition of isoprene to acrylonitrile fumaronitrile and methyl trans$ -cyanoacrylate.' Hehre has extended his electrostatic model for Diels- Alder regioselectivity described last year' to the question of diastereofacial selectivity cycloaddition of electron-rich dienes and electron-poor dienophiles should occur preferentially onto the more nucleophilic diene face and the more electrophilic dienophile face." An MM2 model has been devised which adequately predicts syn-anti selectivity in additions to e.g. (1). The increased stereoselectivity in addi- tions catalysed by Lewis acids is thought to arise from 'earlier' rather than 'tighter' transition states (TS's).The earlier TS's have flatter addends and there is closer approach of out-of-plane substituents.'d The use of camphor derivatives as chiral auxiliaries in asymmetric synthesis has been reviewed.Ie Theoretical studies show that the s-cis- conformation (2) is slightly favoured over the s-trans-conformation (3) for uncomplexed acrylates but that Lewis acid complexation strongly stabilizes the s-trans-conformation relative to the s-cis.If This explains why the observed enantiomer from si-and re-face directing acrylates can be predicted only if the s-trans conformation of the acrylate is assumed. The assertion reported last year'b that vinyl sulphoxides add dienes via the cisoid conformer (4)to the face opposite the sulphur lone pair has been challenged.Ig The ground-state conformation of vinyl sulphoxides varies widely depending on substituents; in the addition of cyclopen- tadiene to (5) the incorrect stereoisomer is predicted using the original proposal.The present authorsIg favour addition to the s-cis-conformer of (5) on the side of the sulphur lone-pair to give (6). In the presence of Lewis acid the conformer involved changes to s-trans due to a chelation effect (or more stable s-trans-conformer of the complex cf ref. If) and addition on the side of the sulphur lone-pair now gives the product of opposite absolute stereochemistry (7),as observed. ' (a) J. J.Gajewski K. B. Peterson and J. R. Kagel J. Am. Chem. Soc. 1987 109,5545; (b) D. W. Jones Annu. Rep. Bog. Chem. Sect. B Org. Chem. 1986,83,29; (c) S. D. Kahn and W. J. Hehre J. Am. Chem. Soc. 1987 109 663; (d) F. K. Brown K. N. Houk D. J. Burnell and Z. Vaienta J. Org. Chem. 1987 52 3050; (e) W. Oppolzer Tetrahedron 1987 43 1969; (f) R. J. Loncharich T. R. Schwartz and K. N. Houk J. Am. Chem. Soc. 1987 109 14; D. P. Curran B. H. Kim H. P. Piyasena R. J. Loncharich and K. N. Houk J. Org. Chem. 1987 52 2137; (g) T. Koizumi Y. Arai H. Takayama K. Kuriyama and M. Shiro Tetrahedron Leu. 1987 28 3689 (h) D. A. Evans K. T. Chapman D. T. Hung and A. T. Kawaguchi Angen. Chem. In?. Ed. Engl. 1987 26 1184; (i) H. Hartman and G. Helmchen Angew. Chem. Int. Ed. Engl. 1987 26 1143.41 D. W. Jones iA 'R (3) anti (4) (1 \ TolSO L /-S qJhi, EtO,C Tol' CO2Et CO2EtTo1 A study of the change in diastereo-face selectivity in the Et,AICl-catalysed additions of isoprene to the crotonates (8) as R is varied was undertaken to define more closely the nature of rr-stacking.lh Addition to the face of the double bond opposite R in the conformation shown was favoured in all cases. However a purely steric explanation for facial selectivity was discounted as [8; R = CHZ(c-C6Hl1)] gave (9) and (10) in a 9.68:l ratio whilst for (8; R = CH,Ph) the ratio was 20.7:l. Other evidence showed that rr-stacking is not associated with charge transfer and the electronic component was attributed to dipole-dipole and van der Waals attractions.Since some substrates will not readily tolerate Lewis acids the availability of dienophiles capable of high diastereoface selection in uncatalysed additions is important. It is now shown that the diester of fumaric acid with (S)-ethyl lactate gives 98% (11) in an uncatalysed addition to cyclopentadiene; the TiC1,-catalysed reaction on the other hand gives 95% of the diastereoisomer (12)." Although the reverse Diels-Alder reaction (13; arrows) has been carried out under vigorous conditions (450 "C) it has now been shownZa that the hydrochloride of (13) dissoci-ates reversibly in water at 50 "C. In the presence of N-methylmaleimide the cyclopen- tadiene- N-methylmaleimide adduct is obtained in 80% yield. The iminium salt Diels-Alder addition and its reverse give rise to a method for N-methylation e.g.of dipeptides.2b The iminium salt prepared from an imine hydrochloride and formaldehyde is trapped as a cyclopentadiene adduct which is reduced (via reverse (a) P. A. Grieco D. T. Parker W. F. Fobare and R. Ruckle J. Am. Chem. SOC.,1987 109 5859; (b) P. A. Grieco and A. Bahsas J. Org. Chem. 1987 52 5746; (c) P. Magnus P. M. Cairns and J. Moursounidis J. Am. Chem. SOC.,1987 109 2469; (d) A. J. H. Klunder A. A. M. Houwen-Claason M. G. Coy and B. Zwanenberg Tetrahedron Left. 1987 28 1329; (e) P. G. Gassman D. A. Singleton J. J. Wilwerding and S. P. Chavan J. Am. Chem. SOC. 1987 109 2182. Reaction Mechanisms -Part (i) Pericyclic Reactions Diels-Alder reaction) by Et3SiH in an acidic medium giving the N-methylated amine.Reverse Diels-Alder reaction is some 95 times faster for I( 14; X = SiMe,) than for (14; X = H) suggesting a build up of positive charge p to the silicon in the TS.2' The easier reverse Diels-Alder reactions of furan adducts (15; X = 0) than of related endo-cyclopentadiene adducts permits preparation of the epoxy- cyclopentenones (16) without their partial rearrangement to pyrones which accompanies fragmentation of the cyclopentadiene adducts.2d A R*02cb H \H C02R* C02R* The ally1 cation (17) generated reversibly from the acetal (18) in the presence of CF,S03H is a good dienophile and gives the cyclohexadiene adduct (19) in 94% yield.2e Since acrolein additions seldom proceed well the method should prove useful.Cation-radical pericyclic reactions have been reviewed3" and a detailed mechanis- tic study has verified the cation-radical chain mechanism for the aminium salt (Ar,") initiated cy~loaddition.~' These reactions show extremely small activation energies ((5 kcal mol-') and enormous accelerations (ca. compared to corre- sponding purely thermal reactions. Rate retardation by added (p-BrC6HJ3N is specific for the cation-radical chain mechanism. Of several examples studied the Diels- Alder dimerization of 1,1,3-trimethylbutadienewas the only example which ' (a) N. L. Bauld D. J. Bellville B. Horirchian K. T. Lorenz R. A. Pabon D. W. Reynolds D. D. Wirth H.-S. Chiou and B. K. Marsh Acc. Chem. Res. 1987,20 371; (b) K. T. Lorenz and N.L. Bauld J Am. Chem. Soc. 1987 109 1157; (c) D. W. Reynolds K. T. Lorenz H.3. Chiou D. J. Bellville R. A. Pabon and N. L. Bauld J. Am. Chem. SOC.,1987 109 4960; (d)J. Mlcoch and E. Steckhan Terrahedron Lett. 1987 28 1081. D. W Jones proceeded by acid-catalysis rather than through a cation-radical chain process. Only the dimerization of 1,1,3-trimethylbutadienewas unretarded by added triar~lamine.~~ In the electrochemically induced cation-radical addition of 3,4-dimethoxystyrene with (20) it is the radical-cation of (20) rather than that of the styrene which is invol~ed.~ Me0 0 This year has seen the synthesis or generation of many new dienophiles and dienes. These include the Fischer carbene complexes (21),4" several thiocarbonyl and selenocarbonyl hetero-dienophile~,~' the thioaldehyde S-oxide (22),4' and the intermediate (23) generated by dissociation of (24) at 30 OC.ld Diatomic sulphur can be generated and trapped by dienes as Diels-Alder-type ad duct^.^' The olefin (25) is a very reactive dienophile in inverse electron-demand reactions; addition to phthalazine occurs at 0 "C to give the apparently stable o-quinodimethane (26).4' EtO,C \ c=s H/ No % Ar A route to 1,1,2,3-tetra-substituteddienes like (27) uses Peterson eliminati~n.~" Unlike 2-1-methylbutadiene (27) reacts satisfactorily with acrolein.Presumably the cisoid conformation of (27) is more stable compared to its trunsoid counterpart (a) R. Aumann and H. Heinen Chem. Ber. 1987 120 537; (b) E.Vedejs C. L. Fedde and C. E. Schwartz J. Org. Chem. 1987 52 4269; J. Nakayama K. Akimoto J. Niijima and M. Hoshino Tetrahedron Lett. 1987 28 4423; P. T. Meinke G. A. Krafft and J. D. Spencer ibid. 1987 28 3887; P. T. Meinke and G. A. Krafft ibid. 1987 28 5121; (c) A. A. Freer G. W. Kirby and R. A. Lewis J. Chem. Soc. Chem. Commun. 1987 718; (d) L. D. Quin A. N. Hughes and B. Pete Tetrahedron Lett. 1987 28 3783; (e) M. Schmidt and V. God Angew. Chem. Int. Ed. Engl 1987 26. 887; W. Ando H. Sonobe and T. Akasaka Tetrahedron Lett. 1987 28 6653; (f)U. Gruseck and M. Heuschmann Tetrahedron Lett. 1987 28 6027. (a) P. H. Brown R. V. Bonnert P. R. Jenkins and M. R. Selim Tetrahedron Left. 1987 28 693; R. V. Bonnert and P. R. Jenkins J. Chem. SOC.,Chem. Commun. 1987 1540; (b) R.V. Bonnert and P. R. Jenkins Tetrahedron Lett. 1987 28 697; (c) H. Mayr and V. W. Heigl J. Chem. Soc. Chem. Commun. 1987 1804; (d) T. Chou H.-H. Tso Y.-T. Tao and L. C. Lim J. Org. Chem. 1987 52 244; (e) H. H. Tso T. Chou and W.-C. Lee J. Chem. SOC.,Chem. Commun. 1987,934; (f)P. J. Harrington and K. F. Difiore Tetrahedron Lett. 1987 28 495; (g) S.4. Chou S.-Y. Liou C.-Y. Tsai and A.-J. Wang .I. Org. Chem. 1987 52 4468; (h) H.-H. Tso T. Chou and S. C. Hung J. Chem. SOC.,Chem. Commun. 1987 1552; (I)S. Yamada H. Suzuki H. Naito T. Nomato and H. Takayama 1.Chern. SOC.,Chem. Commun. 1987 332; 6)T.-S. Chou S.-J. Lee H.-H. Tso and C.-F. Yu J. Org. Chem. 1987 52 5082. Reaction Mechanisms -Part (i) Pericyclic Reactions than is the case for cisoid 2-1-methylbutadiene.This could be due to destabilization of transoid (27) by interaction of the C-1 2-methyl with the C-3 methyl In the diene (28) T' + rZa addition to diphenylketene is sterically inhibited and (28) gives instead products of Diels-Alder addition to both double bonds of the ketene.5c Butadiene sulphone (29) is proving a useful building block for diene synthesis it may be trimethylsilylated at either C-2 or C-3,5d alkylated and dialky- lated at C-2,5e and ar~lated~~ at the double bond. The C-2 anion or ~ulphenylated~~ of (29) can also be acylatedSh or added to aldehydes and ketones or to the C=C bond of a$-unsaturated carbonyl compound^.^' Extrusion of SO2 from these products may be carried out by thermlysis or by treatment with LiAlH,; E-dienes are the usual products.The 3,4-dimethyl derivative of (29) can be alkylated at C-2 and C-5 by the di-iodide (30) to give (31) which gives (32) with LiAlH,.5J (29) (30) (31) (32) The hitherto rather inaccessible diene (33) is now available in two steps starting with the DABCO-catalysed addition of methyl acrylate to methyl pyruvate;6" it reacts with both electron-rich and electron-deficient olefins.6b The dienes [34; X = BR, B(OR),I6' and (34; X = have also become available. Reaction of the diacetylenes (35) with 'Cp2M' (M = Ti Zr) gives complexes (36) converted by acids into dienes of type (37).6' The heterocyclic analogues of o-quinodimethane (38; X = 0)6e and (38; X = S)6r have been generated. The use of o-quinodimethanes in lignan synthesis has been reviewed6g and the long sought route to podophyllotoxins uia intramolecular addition to an o-quino- dimethane (39; arrows) has been accomplished in fine style.6h In this intramolecular addition destabilization of the endo-C02H TS by the a-aryl group on the o-quinodimethane is not as acute as in related intermolecular additions so that the desired stereoisomer with the aryl and C02H groups cis predominates.The tendency of an a-aryl group in an o-quinodimethane to induce exo-addition can be turned '(a) C. Grundke and H. M. R. Hoffmann Chem. Ber. 1987 120 1461; (b) B. Tarnchompoo C. Thebtaranonth and Y.Thebtaranonth Tetrahedron Lett. 1987 28 6671; (c) M. Vaultier F. Trucket B. Carboni R. W. Hoffmann and 1. Denne Tetrahedron Lett. 1987 28 4169; (d) A.J. Bloom and J. M. Mellor J. Chem. SOC.,Perkin Trans. 1 1987 2737; W. A. Nugent D. L. Thorn and R. L. Harlow J. Am. Chem. SOC.,1987 109 2788; (e) N. Munzel and A. Schweig Angew. Chem. Inr. Ed. Engl. 1987 26 471; (f) D. J. Chadwick and A. Plant Tetrahedron Lert. 1987 28 6085; (g) J. L. Charlton and M. M. Alauddin Tetrahedron 1987,43 2873; (h) D. I. Macdonald and T. Durst J. Org. Chem. 1986 51,4749; (i) D. W. Jones and A. M. Thompson J. Chem. Soc. Chem. Commun. 1987 1797. D. W. Jones to advantage addition of dimethyl fumarate to the stable o-quinodimethane (40) gives mainly (41) in which the trans relationship at C-1 and C-2 can be corrected to that in natural lignans by lactone hydrogenolysis with inversion of C-1 over palladium.6' X (C H e M\ cP2 KH$ R R X (35) (37) (38) 0 A0 NH ArCO2H Ar (39) (40) (41) Ar = 3,4,5-trimethoxyphenyl Several examples of the intramolecular Diels- Alder reaction take advantage of the special reactivity of allenes as dien~philes.~" The allene (42) undergoes spon- taneous addition during its preparati~n.~' Type-2 intramolecular Diels- Alder reac- tions (tether attached at diene C-2) are capable of producing very strained bridgehead 01efins.~' In the example (43; the product of endo-addition of the tether (44) is the exclusive product.For the additions depicted in (45; n = 1 or 2) the endo-COR adduct is increasingly favoured as the carbonyl group increases in electrophilicity (CONR2 < C02Me < COMe < CHO) and the additions are even more selective if Et2AlCl catalysis is Some substituent effects on diastereo- (a) Y.Yarnbguchi H. Yamada K. Hayakawa and K. Kanematsu J. Org. Chem. 1987 52 2040; J. Chem. SOC.,Chem. Commun. 1987 515; L. S. Trifonov S. D. Simova and 0.S. Orahovats Tetrahedron Lett. 1987 a,3391; H. M. Saxton J. K. Sutherland and C. Whaley J. Chem. SOC.,Chem. Commun. 1987 1449; (b) K. Hayakawa T. Yasukauchi and K. Kanematsu Tetrahedron Lert. 1987,28 5895; (c) K. J. Shea and L. D. Burke Tetrahedron Lert. 1987 28 735; (d) K. J. Shea W. M. Fruscella R. C. Carr L. D. Burke and D. K. Cooper J. Am. Chem. SOC.,1987,109,447; (e) W. R. Roush A. P. Essenfeld and J. S. Warmus Tetrahedron Lett. 1987 28 2447; (flJ. A. Marshall J. Grote and J. E. Audia J. Am. Chem. SOC.,1987 109 1186; (g) B.Harirchian and N. L. Bauld Tetrahedron Lett. 1987 28 927; (h) J. C. Medina R. Cadilla and K. S. Kyler Tetrahedron Lett. 1987,28 1059; (i) K. Baettig C. Dallaire R. Pitteloud and P. Deslongchampes Tetrahedron Lett. 1987 28 5249; K. Baettig A. Marinier R. Pitteloud and P. Deslongchampes ibid. 1987 28 5253; G. Berube and P. Deslongchampes ibid. 1987 28 5255; (j) J. M. Mellor and A. M. Wagland Tetrahedron Lett. 1987 28 5339. Reaction Mechanisms -Part ( i) Pericyclic Reactions face selectivity in the Lewis acid-catalysed endo-selective addition (46; arrows) have been unc~vered:~~ a 7-OSiBui group induces selective addition to the face of the diene syn to the silyloxy group to give e.g. (47). On the other hand a methyl group at C-4 induces addition to the diene face anti to the methyl group to give e.g.(48). 02cUc O2 ), 0P C02CH2CH2CI &% OSiBu Rl& OHC k3* R,aH OHC R3 Me (45) (46) (47) (48) First examples of intramolecular Diels- Alder additions involving radical cation^'^ and an a~o-dienophile~~ have appeared. Transannular Diels- Alder reaction in a macrocycle is proposed as a powerful strategy for constructing polycyclic molecule^.^' The two conformations (49) and (50) of a trans- trans-cis-macrocycle undergo spontaneous transannular addition to give (51) and (52) upon generation of the macrocycle via malonate alkylation; a related intramolecular addition (just one tether binding diene and dienophile) failed to proceed at 210°C. The sometimes troublesome tethering together of diene and dienophile for intramolecular addition Y&-WE Y = CHzOCH2Ph (49) X = OCH,OMe E = C02Me y&E H H - H H (51) (52) D.W. Jones is delightfully simple in some cases e.g. the amide (54) with a trans ring-junction is formed on standing (53) and dichloromaleic anhydride at 0 'C.'' -H Me NHCH2Ph (53) Several theoretical studies have been concerned with 1,3-dipole~.~" Reverse 1,3- dipolar cycloaddition (55; arrows) provides a route to the thiocarbonyl S-sulphide (56);*' (56) is also generated by sulphur atom transfer from the thiirane (57) to thiobenzophenone at 25 "C when it adds to thiobenzophenone to give (55). Singlet methylene generated by photolysis of diazomethane adds to acetone to give the carbonyl ylide (58) which can be trapped e.g.by acrylonitrile to give mainly the regioisomer (59).*' Decomposition of the diazoketone (60) catalysed by Rh2(OAc), gives the transient 1,3-dipole (61) which can be intercepted by dipolarophiles but in the presence of D20gives the interesting product (62).8dThe full paper dealing 0 with the generation and cycloadditions of (63) has appeared." The azomethine ylide (64) prepared by deprotonation of (65) at -78°C can be cyclized to the aziridine (66) by adding its cold solution to hot toluene containing some pyridine.8f Oxazolidin-5-ones (67) are proposed intermediates in the generation of 1,3-dipoles (67; arrows) from a-amino acids and aldehydes; the dipoles produced by this route are formed highly stereoselectively.8g The route to 1,3-dipoles (69) by tautomerism (a) S.D. Kahn W. J. Hehre and J. A. Pople J. Am. Chen. SOC.,1987 109 1871; J. J. W. McDouall M. A. Robb V. Niazi F. Bernardi and H. B. Schlegel ibid. 1987 109 4642; F. Bernardi M. Olivucci J. J. W. McDouall and M. A. Robb ibid. 1987 109 544; L. Grierson M. J. Perkins and H. S. Rzepa J. Chem. SOC.,Chem. Commun. 1987 1779; (6) R. Huisgen and J. Rapp J. Am. Chem. Soc. 1987 109 902; (c) N. J. Turro and Y. Cha Tetrahedron Len. 1987 28 1723; (d) A. Padwa and P. D. Stull Tetrahedron Lett. 1987 28 5407; (e) P. G. Sarnrnes and R. J. Whitby J. Chem. Soc. Perkin Trans 1 1987 195; (f)E. Vedejs S. Dax G. R. Martinez and C. K. McLure J. Org. Chem. 1987 52 3470; (g) R.Grigg J. Idle P. McMeekin and D. Vipond J. Chem. SOC.,Chem. Commun. 1987,49; (h) P. Armstrong R. Grigg and W. J. Warnock J. Chem. Soc. Chem. Commun. 1987 1325; (i) P. Armstrong R. Grigg S. Surendrukumar and W. J. Warnock J. Chem. SOC.,Chem. Commun. 1987 1327. Reaction Mechanisms -Part (i) Pericyclic Reactions of imines hydrazones and oximes (68) has been less successful for oximes as they generally prefer Michael-type addition to dipolarophiles (CH2=CHX) to give zwitterionic adducts (70). These subsequently undergo internal proton transfer (70; Ph \/CHC0,Et Ph \ +/CH,CO,Et COzEt Ph/C=N\ Ph Me Ph (67) (68) (69) (70) arrows) to give 1,3-dipoles which promptly add a further molecule of the dipolarophile. In this kind of Michael addition-cycloaddition sequence both stages can occur either inter- or intra-molecularly giving four possible classes of reaction.The sequence is therefore capable of wide variations. Thus (71) and phenyl vinyl sulphoxide gives the masked a-amino acid (72),8h and reaction of (73) with hydroxylamine gives the tricyclic compound (74).8i Intramolecular nitrile oxide addition to chiral ally1 ethers has been studied both experimentally and the~retically.~" The theoretical study followed Houk's approach the CNO-ethylene fragment being frozen in the geometry found by ab initio calcula-tion for the HCNO-ethylene addition and the substituents were then fully optimized by MM2. For E-alkenes the TS (75) with the medium sized allylic substituent (OR') inside the largest allylic group anti to the forming C-0 bond and the smallest group (H) outside is favoured as for the intermolecular reaction reported last year.' For Z-allylic olefins the TS (76) is preferred.This avoids both steric congestion and repulsion between the oxygen atoms of the alkoxy and nitrile oxide groups. The experimental results agree quite well with these predictions. Whilst the chair-like TS (77) is preferred for the intramolecular nitrile oxide addition shown (77; arrows) '(a) R. Annunziata M. Cinquini F. Cozzi and L. Raimondi J. Chern. SOC.,Chern. Comrnun. 1987 529; R. Annunziata M. Cinquini F. Cozzi C. Genarri and L. Raimondi J. Org. Chern. 1987 52 4674; (b) K. S. K. Murthy and A. Hassner Tetrahedron Lerr. 1987 28 97; ibid. 1987 28 4097; (c) J.Baran and H. Mayr J. Am. Chern. Soc. 1987 109 6519. D. W. Jones where the tether consists of two methylenes (n = l) the alternative TS (78) is preferred when n = 2.9b The sterically shielded olefin (28) gives the formal 7r4 + 7r4 adduct (79) as well as products of 7r2 + 7r2 addition with the nitrone biradical intermediates are energetically possible for these additions to dienes where one radical centre is allylically stabilized. * R' OR1 (75) (76) Me Ph H (77) (78) (79) (80) The thermal conversion of (81) into benzene and an anthracene is forbidden as a reverse 7r4s + 7r45process. Whilst (81; X = H or Me) decompose without light emission cycloreversion of (81; X = C02H) is chemiluminescent."" It is suggested that the reactions proceed via a biradical intermediate which in the presence of an electronegative carboxyl group might have enhanced zwitterionic character (82).The intermediate could follow a path leading to an ion-pair of benzene radical-cation -and anthracene radical-anion. But if this path becomes endothermic the surface could intersect that of singlet excited (81) which then leads to benzene and an excited anthracene. The dissociation of the syn-benzene dimer (83) to benzene is more difficult than the corresponding dissociation of its anti-isomer.'Ob The negative activation entropy for decomposition of (83) is consistent with either dissociation to ground state and triplet benzene molecules or disrotatory ring-opening of (83) (a) N. C. Yang and X. Yang J.Am. Chem. Soc. 1987 109 3804; (6) N. C. Yang B. J. Hmjez and M. G. Homer J. Am. Chem. Soc. 1987 109 3158; (c) A. Gilbert and P. Heath Tetrahedron Lett. 1987 28 5909; (d) K. B. Costick M. G. B. Drew and A. Gilbert J. Chem. Soc. Chem. Commun. 1987 1867; (e) P. J. Wagner and K. Nahm J. Am. Chem. Soc. 1987 109 6528; (f)J. J. McCullough Chem. Reu. 1987,87 811; (g) P. A. Wender and C. R. D. Correia J. Am. Chem. Soc. 1987 109,2523; P. A. Wender and M. L. Snapper Tetrahedron Lett. 1987 28 2221; P. A. Wender and N. C. Ihle hid. 1987,28 2451. Reaction Mechanisms -Part (i) Pericyclic Reactions to (84) which is known to give the anti-isomer of (83) and then benzene below -10°C. Several efficient photochemical 7r2 + 7r2 additions have been observed for alkoxybenzenes substituted with an ortho CN CO,Me or COMe group.Thus irradiation of 2-methoxycyanobenzene in ethylvinylether led uia the non-isolable (85) to (86) which underwent photochemical ring-closure to (87)."' The specificity (85) (86) (87) for ortho-cycloaddition is not observed for 4-cyanoalkoxybenzenes except in an intramolecular variant.lod Photoadditions of aromatic compounds have been reviewed.'0f Formal intramolecular 7r4 + 7r4 cycloadditions induced by sensitized photolysis or Nio catalysis provide convenient routes to eight-membered rings.'Og 2 Sigmatropic Reactions An ab initio study of the suprafacial 1,3-hydrogen shift in the propene radical-cation suggests that radical-cations will undergo sigmatropy much more easily than neutral molecules."' The 1,3-rearrangement (88; arrows) is particularly easy and proceeds with inversion.'lb The distorted geometry of (88) is suggested particularly to favour suprafacial-inversion rearrangement.Thus the C(8) -C( 5)-C(6)-C( 10) dihedral angle is reduced to ca. 60" greatly favouring inversion at C-5. Moreover the torque applied about the C(5)-C(6) bond twists the norbornene ring reducing the C(5)-C(2) distance. X-Ray and neutron diffraction studies show that methylene- cyclopropane (89) is distorted in the manner depicted in (89) in exaggerated form;'lC the exocyclic methylene is displaced from the bisector of the C(2)-C( 1)-C(3) NH2 2 10 HA ,HB (88) (89) " (a) T. Clark J. Am. Chem. Soc. 1987 109 6838; (b) G. B. Clemens and J.K. Blaho J. Org. Chem. 1987 52 1621; (c) D. G. Van Derveer J. E. Baldwin and D. W. Parker J. Org. Chem. 1987 52 1173; (d) X. Creary M. E. Mesheikh-Mohamadi and S. McDonald J. Org. Chem. 1987 52 3254; (e) L. A. Paquette F. Pierre and C. E. Cottrell J. Am. Chern. Soc. 1987 109 5731. D. W. Jones angle and HBlies below HA. This ground-state distortion predisposes the molecule to the 1,3-shift shown. Indeed (90) is known to equilibrate with (91). On the basis D D (90) (91) that the methylenecyclopropane rearrangement of (92) to (93) involves a biradical intermediate the variation of rearrangement rate as para- and meta-substituents in the aryl ring are changed has been used to construct a u*scale."d Anion-accelerated rearrangement of (94) gives both the Cope product (95) and the product (96) of a formal 1,3-shift proceeding antarafacially with retention.'Ie Since the epimeric anion (97) also gives (96) and no Cope product the 1,3-shifts must be two-step reactions.The failure of the proposed intermediate (98) to ring-close to give the anti-isomer of (96) is attributed to steric factors. / High level quantum mechanical calculations indicate that tunnelling is not in- volved in the 1,Shydrogen shift in cis-penta-1.3-diene and that the preferred TS is of the type depicted in (99) rather than The dienol (101) generated by enzymic hydrolysis of its phosphate is much longer lived than related dienols (102) which can revert to the keto-form by 1,Sshift (102; arrows).12b 1,SMigration of boron-centred groups in cyclopentadienes is rapid; the derivatives (103) with R = (99) (100) (101) (102) (103) *'(a) F.Jensen and K. N. Houk 1.Am. Chem. SOC.,1987 109 3139; (b) R. M. Duhaime and A. C. Weedon J. Am. Chem. Soc. 1987 109 2479; (c) P. Jutzi B. Krato M. Hursthouse and A. J. Howes Chem. Ber. 1987 120 565; (d)J. E. Baldwin and V. P. Reddy J. Am. Chem. SOC.,1987 109 8051. Reaction Mechanisms -Part ( i) Pericyclic Reactions alkyl rearrange with activation energies <5 kcal mol-'. Rearrangement is progress- ively slower as the electron donor ability of the R groups increases R = Me > R = OMe > R = NMe which suggests involvement of a vacant orbital at boron in the rearrangement TS.l2' Primary kinetic isotope effects (kH/ k,) for the 1,7-hydrogen shift (104; arrows) are in the range 6.4-7.7 suggesting that an earlier value of 45 measured for Vitamin D derivatives is in error.12d (104) The 2,3-Wittig ring-contraction (105; arrows) has been used in the synthesis of aristolactone; generation of (105) using an optically active base gives the optically active natural 2,3-Sigmatropy of zirconium enolates proceeds via the bicylo[3.3.0]octane-like TS (106) in which the R group prefers a less hindered exo-position.These Wittig rearrangements are therefore atypical in giving Z-pro- ducts ( 107); they proceed with high syn-selectivity and excellent chirality tran~fer.'~ H OH \ OPr' (106) The two possible TS structures (108) and (109) for both boat and chair Cope rearrangement have been explored by theoretical calculation.13' Structure (109) is regarded as a biradicaloid rather than a biradical because of coupling of the radical sites through the C(l)-C(6) and C(3)-C(4) bonds.Because of shorter C(l)-C(6) and C(3)-C(4) bond distances in (109) than in the aromatic TS (108) the boat biradical TS is selectively destabilized by eclipsing interactions and boat Cope rearrangement prefers the aromatic TS (108). The chair TS on the other hand is (108) (109) l3 (a) J. A. Marshall and J. Lebreton Tetrahedron Left. 1987 28 3323; (b)-S.Kuroda T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1987 28 803; (c) M. J. S. Dewar and C. Jie J. Chem. SOC.,Chem. Commun. 1987 1451; J. Am. Gem. SOC.,1987 109 5893; (d) M. Coates B. D. Rogers S. J. Hobbs D.R. Peck and D. P. Curran J. Am. Chem. SOC.,1987 109 1160; (e) J. J. Gajewski J. Jurayj D. R. Kimbrough M. E. Gande B. Ganem and B. K. Carpenter J. Am.Chem. SOC., 1987 109 1170; (f) W. J. Guilford S. D. Copley and J. R. Knowles J. Am. Chem. SOC.,1987 109 5013; (g) T. Clarke J. D. Stewart and B. Ganem Tetrahedron Lett. 1987 28 6253. D. W. Jones calculated to prefer the biradicaloid TS. The 'looser' aromatic TS is associated with a less negative calculated activation entropy (-11.O e.u.) than the biradicaloid TS and indeed AS' for boat-like Cope rearrangements are less negative than for chair-like rearrangements. A methoxy group at C-4 or C-6 accelerates Claisen rearrangement (110; arrows) by ca. lo2 and 10 respectively whilst a C-5 methoxy retards rearrangement by a factor of 40.'3d These observations have suggested that the C-4 and C-6 substituents lead to enolate-oxonium ion dipolar character in the TS.This view is supported by solvent-rate effects particularly in protic solvents. In going from benzene to methanol the rearrangement rate of the 5-OMe compound is little changed but the 4-and 6-OMe derivatives rearrange 18 and 68 times more rapidly. 30& 4U6 5 (110) Several substituent effects on Claisen rearrangement have been studied in conjunc- tion with the chorismic acid into prephenic acid conversion (111; arrows). In a collaborative eff01-t'~~ the two groups agree that the TS structure is dissociative in character but the Cornell group gives heavier emphasis to a dipolar TS and uses this to explain the rate-retarding effect ofthe hydroxyl group.In the enzyme-catalysed reaction a nucleophilic site on the enzyme is thought to aid C-0 bond cleavage by association with C* thus creating greater enolate character in the enol ether moiety.13f The model (112) for the chorismic acid to prephenic acid TS is a potent inhibitor of chorismate m~tase.'~~ CO,H I OH OH (111) (112) Oxyanion acceleration of 3,3-shifts continues to be exploited ~ynthetically.'~" In what may be a related radical-catalysed process (113) gives (114) (62%) upon OH (113) (114) (a)L. A. Paquette J. L. Romine and H.-S. Lin Terruhedron Lett. 1987 28 31; J. A. Oplinger and L. A. Paquette ibid. 1987 28 5441; (b) L. M. Harwood A. J. Oxford and C.Thomson J. Chem. Soc. Chem. Commun. 1987 1615; (c) M. Sworin and K.X. Lin J. Org. Chem. 1987 52 5640. Reaction Mechanisms -Part ( i) Pericyclic Reactions heating in aqueous methanolic potassium hydr0~ide.l~' The reaction requires atmos- pheric oxygen is quenched by a radical trap and accelerated by potassium ferri- cyanide. In an interesting extension of oxy-Cope rearrangement (1 15) gives the enol (1 16) which is trapped intramolecularly (1 16; arrows).14' 3 Electrocyclic Reactions As predicted by theory and demonstrated earlier'5a for a more substituted case a 3-formyl substituent in a cyclobutene prefers to rotate inwards during conrotatory ring-~pening;'~'(117) gives >98% of the 2-product (118) on heating. This result stands in contrast both to the prediction that a CN group will rotate outwards and the demonstrated very strong preference of a fluorine atom for outward r0tati0n.l~~ Optically active (1 19) undergoes thermal racemization uia disrotatory opening to the extended carbonyl ylide ( 120).'5dThe racemization proceeds at a similar rate to the epimerization of the 6-methyl derivative of (119).Relatives of (119) with S and N replacing 0 undergo ring-opening 63 100 and 72 times faster respectively than (1 19) showing that these heteroatoms stabilize carbonyl ylide-like intermediates very differently. Evidence for the ring-opening of (121; X = H) to (122; X = H) is provided by the thermal conversion of (121; X = D) into (123; X = D).15' Conversion of (124) into (126) uia disrotatory ring-opening and bond relocation (125; arrows) proceeds at the same rate as racemization of (124) uia (125) showing that bond relocation is faster than the ring-closure of (125) to return (124).The difference in activation free-energy for electrocyclic ring-opening of (124) and (127) is 10.1 kcal mol-' rather than the 25 f 1 kcalmol-' expected if the aromaticity were completely sacrificed at the TS for ring-opening. Accordingly benzo-annelated pericyclic TS's retain more '' (a) S. Ingham R. W. Turner and T. W. Wallace J. Chem. SOC.,Chem. Commun. 1985 1164; (b) K. Rudolf D. C. Spellmeyer and K. N. Houk J. Org. Chem. 1987,52,3708;(c) W. R. Dolbier H. Koroniak D. J. Burton P. L. Heinze A. R. Bailey G. S. Shaw and S. W. Hansen J. Am. Chem. SOC.,1987 109 219; (d) F.-G.Klarner and D. Schroer Angew. Chem. Int. Ed. Engl. 1987 26 1294; (e) W. Grimme J. Lex and T. Schmidt Angew. Chem. Int. Ed. Engl 1987 26 1268; (f)P. W. Groundwater C. Struthers-Sample and J. T. Sharp J. Chem. Soc. Chem. Commun. 1987 1367; G. V. Boyd J. Cobb P. F. Lindley J. C. Mitchell and G. A. Nicolaou ibid. 1987 99; P. W. Groundwater and J. T. Sharp Tetrahedron Lett. 1987,28 2069; (g) C. A. Barron N. Kahn and J. K. Sutherland J. Chem. Soc. Chem. Commun. 1987 1728. D. W. Jones \ / x X X than half their aromatic stabilization. This idea helps to explain fairly easy electro- cyclic ring-closures like (128; arrows).lSf (128) New ways of using electrocyclic reactions in synthesis include exploitation of the benefit of including an sp-rather than an sp2-hybridized carbon centre as one bonding terminus; ketenes of the type (129) undergo efficient ring-closure (129; arrows) when generated from corresponding acid chloride^.'^^ The electrocyclic ring-closure (130; arrows) was used in a second approach to steroid synthesis.'6" Reaction also proceeds if a thiophene ring replaces the cyclopentene ring in (130); cyclization is followed by a 1,5-hydrogen shift that restores the aromaticity of the thiophene ring.16' Ring-closure of ketenes generated by cyclobutenone ring-opening and involving disruption of an aromatic ring were described in last year's Report.Ib This sequence has been further explored,i6c and a variant using the benzo- (a) T.L. Gilchrist and J. E. Stanford J.Chem. SOC. Perkin Trans. I 1987 225; (b)T. L. Gilchrist and R. J. Summersell Tetrahedron Lett. 1987 28 1469; (c) S. T. Perri and H. W. Moore Tetrahedron Lett. 1987 28 4507; M. W. Reed and H. W. Moore J. Org. Chem. 1987 52 3491; (d) 0. H. W. Decker and H. W. Moore J. Org. Chem. 1987 52 1174. Reaction Mechanisms -Part (i) Pericyclic Reactions cyclobutenone (131) has been described.'6d Upon heating at 138 "C(131) undergoes ring-opening to (132) which ring-closes to (133) through the unusual process shown in (132; arrows). OTHP OMe A

ISSN:0069-3030    

DOI:10.1039/OC9878400041

出版商:RSC    

年代:1987

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (ii) Polar Reactions By D.L. H. WILLIAMS Department of Chemistry University of Durham Durham DH1 3LE 1 Introduction A number of useful review articles relating to aspects of organic reaction mechanisms (polar reactions) have appeared this year. One of the most comprehensive is a volume entitled Nucleophilicity,’ published by the American Chemical Society and based on a symposium held in 1985. There are thirty one chapters covering a wide range of topics written by acknowledged experts. The usefulness of the Reactivity- Selectivity Principle has again been discussed.2 The authors conclude that it has only a limited applicability ( a view which is now fairly widespread) and should be replaced as a model for the explanation of structure-reactivity relationships by three-dimensional reaction co-ordinate diagrams.Shaik has earlier3 put the case in detail in favour of the state correlation diagram model. Other review articles discuss the nature and analysis of substituent electronic effects substituent effects on ground-state molecule^,^ and theoretical studies of electronic substituent eff ects6 The stability and solvation of organic cations have been discussed’ in terms of their pK values in water and the sensitivity of the protonated base to the solvating power of the medium m*.This work covers a wide range of C N S 0,and anionic bases. Mandolini has reviewed (in an article dedicated to the late Professor G. Illuminati) the intramolecular reactions of chain molecules,* and Bunton and Savelli have summarized’ the present-day knowledge of organic reactions which take place in aqueous micelles including a discussion of the application of such reactions in synthesis and in analytical chemistry.Recent advances in the development and application of the concept of hard and soft acids and bases are discussed by Pearson,” including the derivation of new ideas of absolute electronegativity and hardness together with the theoretical justification of the principle. The details of the mechanisms of proton-transfer reactions between oxygen and nitrogen acids ’ ‘Nucleophilicity’ ed. J. M. Harris and S. P. McManus Advances in Chemistry Series Vol. 215 1987 American Chemical Society. ’ E. Buncel and H. Wilson J. Chem. Educ. 1987 64 475. S.S. Shaik Prog. Phys. Org. Chem. 1985 15 197. R. W. Taft and R. D. Topsom Prog. Phys. Org. Chem. 1987 16 1. R. D. Topsom Prog. Phys. Org. Chem. 1987 16 85. R. D. Topsom Prog. Phys. Org. Chem. 1987 16 125. ’ A. Bagna G. Scorrano and R. A. More O’Ferrall Rev. Chem. Insr. 1987 7 313. * L. Mandolini Adu. Phys. Org. Chem. 1986 22 1. C. A. Bunton and G. Savelli Adu. Phys. Org. Chem. 1986 22 213. R. G. Pearson J. Chem. Educ. 1987 64 561. 59 D. L. H. Williams and bases in water have also been reviewed." Other topics covered this year include the mechanisms of ring-closure reactions particularly as applied to heterocyclic syntheses," and the mechanisms of the reaction of p-lactam antibiotic^.'^ Other review articles will be discussed at appropriate points within the rest of this Report.One issue of the Canadian Journal of Chemistry is given over to papers in physical- organic chemistry and is dedicated to Professor J. T. Edward on the occasion of his 65th birthday. The year has seen the publication of another book on physical organic chemi~try'~ and 1988 sees the birth of a new journal of physical-organic chemistry. This is not the place to discuss the merits or otherwise of the introduction of new journals but for those who believe that there is a genuine shortage of journals I would suggest that they undertake the task of a Reporter for Annual Reports! 2 Solvolysis and Carbocations A review arti~le'~ on solvolysis in water updates the material presented by one of the authors in 1967.The emphasis is on interpretation of trends in activation parameters (including ACp*) and also the interpretation of kinetic isotope effects. A theoretical paper16 (dedicated to Professor H. C. Brown on the occasion of his 75th birthday-dedications seem plentiful this year) calculates the free-energy profiles for the separation of the t-butyl cation and the chloride ion in dilute aqueous solution. A 2 kcal mol-' barrier is found between the contact and solvent-separated ion pairs and the treatment is taken as support for the existence of contact ion pairs as discreet species. The hydrolysis of benzoyl fluoride has been found to be inhibited by added fluoride ion." The kinetic results are in quantitative agreement with the mechanism outlined in Scheme 1 involving reversible unimolecular heterolysis to give the acylium ion which then reacts with water to give the final product.Some reactions are however enhanced by added fluoride ion and it is suggested that fluoride ion (and the solvent) can act as a general base catalyst for nucleophilic attack by water in these cases. Scheme 1 'I F. Hibbert Adv. Phys. Org. Chem. 1986 22 113. 12 A. R. Katritzky D. L. Ostercamp and T. I. Yousaf Tetrahedron 1987 43 5171. 13 M. I. Page Adv. Phys. Org. Chem. 1987 23 165. 14 N. S. Isaacs 'Physical Organic Chemistry' Longman 1987. l5 M. J. Blandamer J. M. W. Scott and R. E. Robertson hog. Phys. Org. Chem. 1985 15 149. 16 W. L. Jorgensen J. K. Buckner S. E. Huston and P. J. Rossky J. Am.Chem. SOC.,1987 109 1891. B. D. Song and W. P. Jencks J. Am. Chem. SOC., 1987 109 3160. Reaction Mechanisms -Part (ii) Polar Reactions Previously rate constants for sulphonate hydrolyses in a wide range of solvents have been correlated in a two parameter equation with YoTs(the solvent ionizing power) and NoTs(the solvent nucleophilicity). Now this equation has been applied to the rate constants for ester hydrolyses in &70% aqueous sulphuric acid.’* This kinetic approach is an alternative for these reactions to the more usual correlation with acidity functions and activity coefficients. The silver ion-promoted solvolyses of a series of tropenium ion analogues of bromobenzonorbornenes [e.g. (l)] have been examined.” The kinetic and stereochemical results are best explained in terms of anchimeric assistance by the tropenium group-the first example of assistance by this group.Another first example reported is that of Ac0-7 neighbouring group participation,20 in the reaction of some diol diacetates with anhydrous aluminium chloride at ca. 100 “C.One of the acetoxy groups is displaced by chlorine and ‘*O experiments show that the displace- ment involves acetoxonium intermediates e.g. (2). The identification of the products (tetrahydrofuran formaldehyde and propene) together with kinetic results for the pyrolysis of 4-chlorobutan- 1-01 in the gas phase21 indicate that anchimeric assistance occurs here too in this case by the -OH group. This extends the earlier findings by these authors of -0Me participation in a similar system.The reaction mechanism is conveniently written in terms of a polar mechanism with an intimate ion-pair intermediate. Although these are not examples of solvolysis reactions they are nevertheless included in this Section because of the close analogy with neighbouring group participation in solution chemistry. The reaction mechanism details of ether hydrolysis continues to attract attention. Kirby has shown” that intramolecular proton-transfer catalysis is an important feature (see equation 1). The same effect (characterized by a large rate constant increase of > 1000) occurs in an acetal hydrolysi~,~~ in this case involving proton X I? 0 0 18 T. W. Bentley S. Jurczyk K. Roberts and D. J. Williams J.Chem. SOC.,Perkin Trans. 2 1987 293. 19 J. W. Wilt C. George and M. Peeran J. Org. Chem. 1987 52 3739. 20 S. H. Wilen L. Delguzzo and R. Saferstein Tetrahedron 1987 43 5089. 21 G. Chuchani and I. Martin Znt. J. Chem. Kinef. 1987 19 183. 22 S. E. Barber and A. J. Kirby J. Chem. SOC.,Chem. Commun. 1987 1775. 23 A. J. Kirby and J. M. Percy J. Chem. SOC., Chem. Commun. 1987 1774. D. L. H.Williams transfer from nitrogen [see (3)]. Kresge has discussed the unusual reactivity of prostacyclin (a naturally occurring inhibitor of blood-clotting) particularly with reference to intramolecular catalysis of vinyl ether hydr~lysis.~~ The kinetics of acid-catalysed hydrolysis of some heterocyclic methyl enol ethers together with the solvent isotope effects and deuterium exchange experiments show that with these substrates C-protonation is rapid and reversible and that the rate limiting step is attack of the intermediate cation by water.25 Following last year's report of the preparation of the triphenylsilyl cation Apeloig and Stanger26 have now produced another example of an organic cation with the positive charge located on silicon (a silicenium ion).This was made from an a-silyl cation generated solvolytically from an adamantyl derivative which underwent a 1,2-methyl shift (see equation 2) and was identified by characterization of the SiMe3 product obtained after solvent capture. The silicenium ion was claimed to behave in an unusual way but Ke~i11~~ has rationalized the formation of products in terms of solvent capture of both intermediates when they are at the solvent-separated ion pair stage.The electronic substituent effect of the SiMe3 group has been measured.28 The solvolysis of 1-bromoadamantane is activated by a factor of 8.6 by a y-SiMe3 substituent. 3 Other Nucleophilic Substitutions Space does not permit a detailed account of the contents of the ACS publication entitled Nucleophilicity.' The individual chapters are grouped under the general headings Marcus theory alkyl transfer gas-phase reactions Rransted equation hard-soft acid-base theory factors in nucleophilicity linear free-energy relation- ships for solvent nucleophilicity novel nucleophiiic reactions and finally enhance- ment of nucleophilicity. The book as a whole makes a timely appearance and gives an excellent up-to-date coverage of the many recent developments in an area of chemistry which continues to attract much attention.24 A. J. Kresge Acc. Chem. Res. 1987 20 364. 25 B. Capon and F.-C. Kwok Tetrahedron 1987 43 69. 26 Y. Apeloig and A. Stanger J. Am. Chem. SOC.,1987 109 272. 21 D. Kevill J. Chem. Rex (S) 1987 272. 28 C. A. Grob and P. Sawlewicz Tetrahedron Lett. 1987 28 951. Reaction Mechanisms -Part (ii) Polar Reactions 63 Jorgensen and co-~orkers~~ have generated a mechanistic model for all nucleophilic reactions in the form of a computer program from which is is possible to make predictions as to the outcome of such reactions. This has been achieved by applying the known mechanistic rules and arguments deduced from the consider- able accumulated results in the literature.The model it is claimed will be of assistance in assessing the feasibility of synthetic routes and also in helping to identify likely side-products. At the moment the model does not always live up to expectation particularly with regard to the minor products but can be refined as more experimental results become available. Discussion and arguments continue as to the role and involvement of the single electron transfer (SET) mechanism in nucleophilic substitution. Pearson3' finds little correlation of reactivity of a range of nucleophiles (in reaction with methyl iodide) with one-electron oxidation potentials -a finding which does not support some recent ideas3 On the other hand Shaik3' has subsequently found a good correlation of reactivity of nucleophiles towards the pyronoin cation with the vertical ionization potential of the nucleophile.Bordwell and co-workers in two papers32 also attempt to distinguish between SET and conventional SN2by oxidation potential correlations. They claim that some reactions (with fluorenide ions) show characteristics of both and are thought to be hybrid SET-SN2 reactions. In a different approach,33 evidence in favour of SET comes from reactions with optically active alkyl halides. The reactions cannot be classic sN2 reactions since they do not proceed with 1OO0/o inversion of configuration; the authors conclude that when the substrate is difficult to reduce then substitution follows the sN2 pathway whereas when this reduction is easy (a smaller negative reduction potential) the reaction occurs by SET.In the past the unexpectedly high SN2 reactivity of a-halogenocarbonyl com- pounds has been explained theoretically in terms of a lowering of the energy barrier by a contribution to the transition state structure by the enolate form. Yousaf and now provide experimental evidence for this including a comparison of the p values for the substitution reactions and the p values of the equilibrium constants. Lewis and co-~orkers~~ have also extended their well-known studies on methyl transfer reactions to include those between aryl selenide ions (equation 3). These ArSeMe + PhSe-__ ArSe-+ PhSeMe (3) reactions are much faster than are the corresponding thiophenoxide reactions with aryl methyl sulphides.One unusual feature is that now the charge on the methyl group in the transition state is -0.24. Full details have now appeared on the kinetics of the reaction of benzylazoxytosyl- ate (4)in aqueous trifluoroethanol with added nucleophiles and bases. The results 0-PhCH,N+/ (4) %OTs 29 P. Metivier A. J. Gushurst and W. L. Jorgensen J. Org. Chem. 1987 52 3724. 30 R. G. Pearson J. Org. Chem. 1987 52 2131. 3' S. S. Shaik J. Org. Chem. 1987 52 1563. 32 F. G. Bordwell and C. A. Wilson J. Am. Chem. SOC.,1987 109,5470; F. G. Bordwell and J. A. Harrelson Jr. ibid. 1987 109 8112. 33 E. C. Ashby and T. N. Pham Tetrahedron Lett. 1987 28 3183. 34 T. I. Yousaf and E.S. Lewis J. Am. Chem. SOC.,1987 109 6137. 35 E. S. Lewis T. I. Yousaf and T. A. Douglas J. Am. Chem. SOC.,1987 109 2152. 64 D. L. H. Williams are rationaped mechanistically by the intermediate formation of the benzyl cation species PhCH2N20 OTs- which is then trapped either by a nucleophile or by the solvent.36 The rates of some reactions of ammonia with alkyl and aryl halides are increased by the use of phase-transfer catalyst^.^' Even ammonia can be extracted from the aqueous (or gas) phase with various organic solvents (e.g.toluene) using quaternary ammonium salts. 4 Elimination Reactions Reactions which are well-known in solution continue to be explored in the gas phase. Two papers report the results of the base-induced gas phase elimination of ethers38 and thi~ethers~~ (see equations 4and 5).These reactions have been examined B-+ EtOEt +EtO-+ BH + C2H4 (4) B-+ EtSEt +EtS-+ BH + C2H4 (5) kinetically by Fourier transform ion cyclotron resonance mass spectrometry; kinetic isotope effects and leaving group effects have been established as functions of base strength. Both systems appear to have the characteristics of the E 2 mechanism and all feature can be explained by the variable E2 transition state model (e.g.increasing the base strength results in a change in the transition state structure towards E 1cB). Not unexpectedly the energy profiles are quite different from those found for reactions in solution but it seems that the transition state structure parallels that in the solution state model.Elimination reactions of bromo esters also in the gas phase provide evidence of anchimeric assistance by the -COOMe group.40 The reaction mechanism is given in terms of formation and reaction of intimate ion-pair intermediates. Another gas phase study reports the elimination of fluoride ion from the carbanion (CF3),CH- Le. a ElcB-type reaction.41 The work concentrates on the effect of added alcohols and concludes that ROH becomes co-ordinated at two different sites (a) at C-2 which accounts for the D/H exchange observed and (b) at a fluorine atom which accounts for the ROH assistance found. In solution imine-forming eliminations have been investigated using the reaction of N-(arylsu1phonoxy)- N-benzyl-methylamines with methoxide ion in methanol (equation 6),and also with ben~ylamine.~~ The arenesulphonate behaves as a better XC6H4cH2N(OSO2C6H4Y)CH XC6H,CH=NCH3 + YC6H4OSo2-+ MeOH (6) leaving group than the halogens and a change to a relatively weak base moves the transition state towards the El borderline as deduced from the p value and kinetic isotope effect.Increasing the size of the alkyl group R in imine-forming elimination 36 H. Maskill and W. P. Jencks J. Am. Chem. SOC.,1987 109 2062. 37 G. Borak and Y. Sasson J. Chem. SOC. Chem. Commun. 1987 1267. 38 L. J. de Koning and N. M. M. Nibbering J. Am. Chem. SOC.,1987 109 1715. 39 W. W. van Berkel L. J. de Koning and N. M. M. Nibbering J. Am. Chem. SOC.,1987 109 7602. 40 G. Chuchani and R. M. Dominguez J. Phys.Chem. 1987 91 1883. 41 R. N. McDonald W. D. McGhee and A. K. Chowdhury J. Am. Chem. SOC.,1987 109 7334. 42 B. R. Cho S. Y. Pyun and T. R. Kim J. Am. Chem. Soc. 1987 109 8041. Reaction Mechanisms -Part (ii) Polar Reactions from XC6H4CH2N(Cl)R in reaction with methoxide ion reduces the reactivity; this is interpreted in terms of a repulsive interaction between R and the base in the transition state.43 Elimination from alkanesulphinyl derivatives (equation 7) leads MeO-ArAr'CHS(O)OCH -ArAr'C=S=O + CH,OH (7) MeOH to sulphine formation with the mechanistic characteristics of irreversible E 1cB or E2 mechanisms.44 This contrasts with the behaviour of arylmethanesulphonates which gave sulphenes (ArCH=S02). The different behaviour is thought to stem from the fact that sulphines are much more stable than are sulphenes.An interesting stereochemical point arises in the base-induced (Et,N) elimination from PhCHC1CHC1CO2Me and other dihalogeno esters which results in the forma- tion of alkene esters.45 The observed kinetic dependence upon the electron-with- drawing ability of the leaving group and also the stereochemical results suggest that elimination from the erytho diastereoisomer occurs by way of the irreversible E 1cB mechanism whereas the threo compound reacts via the concerted E2 pathway. This difference is explained in terms of the most likely conformational structure for each diastereoisomer as predicted by structural models and also from vicinal coupling constants. Four papers have been published by Stirling's group4-' dealing with further mechanistic aspects of nucleophilic eliminative fission from cyclic systems.Cyclopro- pyl systems react by the reversible ElcB mechanism i.e. where the rate-limiting step is the fission of the carbanion. This enables the effect of strain on the nucleofugal- ity to be measured directly for the first time. For the cyclopropane system it appears that the strain decreases considerably in the early stages of bond breaking. Structural effects have also been studied for these three-membered ring fission reactions (equation 8) including the relative activating effects of the nitro and sulphonyl Z-R" groups the effect of gem-dimethyl substitution and the comparison of the reaction of a thiirane with that of oxiranes and with unstrained systems.Ring strain turns out as expected to be an important feature which increases the nucleofugality of the leaving group sufficiently to change the stepwise mechanism (found for the unstrained systems) to a concerted mechanism. Cycloalkanol ring fission gives as expected acyclic aldehyde or ketone products (equation 9) and the cyclobutanol 43 B. R. Cho J. H. Maeng J. C.-Yoon and T. R. Kim J. Org. Chem. 1987 52 4752. 44 J. L. Kice and J. J. Rudzinski J. Am. Chem. SOC.,1987 109 2414. 45 M. C. Cabaleiro and R. 0.Garay J. Chem. SOC.,Perkin Trans. 2 1987 1473. 46 S. Hughes G. Griffiths and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1987 1253. 47 P. P. Piras and C. J. M. Stirling J. Chem. Soc. Perkin Trans.2 1987 1265. 48 H. A. Earl and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1987 1273. 49 A. Bury H. A. Earl and C. J. M. Stirling J. Chem. Soc. Perkin Trans. 2 1987 1281. D. L. H. Williams derivatives are much less reactive than are the cyclopropanols. Similar behaviour has been noted for cyclobutanes and cyclopropanes. Calculated energy profiles agree well with the experimental results. 5 Addition Reactions Although the stepwise nature of electrophilic halogenation (and other reactions) is very well established features of the mechanism continue to be unravelled. A recent examples0 occurs in the study of the bromination of stilbenes in dichloromethane and in chloroform with HBr and with Br,. Kinetics and product studies including stereochemical aspects argue in favour of the reversible formation (and subsequent reaction) of the two tribromide and bromide ion pairs (5) and (6).The same group \ / \c-c / ')&!+ has isolated and characterized an intermediate from a syn-brorninati~n.~' 1,3-Dioxolan-2-ylium cations have previously been suggested as possible intermediates in some electrophilic halogenations.One such example has now been isolated (from CC14 at -30 "C)as outlined in equation 10. The original salt is the bromide which OCOAr Br is not sufficiently stable for structure analysis; a more stable salt was obtained by exchanging X-= Br- for X = BF,. Micellar catalysis in alkene bromination has been analy~ed.~* The conclusions are that the effect on the rate of reaction arises from a micellar charge effect and also from a change in the equilibrium constant between Br and Bri (both electrophilic brominating agents).A number of trimethylsilyl enol ethers have previously been chlorinated using N-chlorosuccinimide. Now the intermediate cations (siloxycarbinyl cations) have been trapped by azide ion and also by methanol and the final products have been ~haracterized.~~ Three papers have appeareds4 presenting the results of a theoretical study which accounts for the regio- and stereo-chemistry of electrophilic addition to chiral double bonds in allylic systems. Calculated conformational profiles obtained by standard 50 G. Bellucci C. Chiappe and F. Marioni J. Am. Chem. SOC.,1987 109 515. 51 G. Bellucci R.Bianchini and S. Vecchiani J. Org. Chem. 1987 52 3355. 52 G. Cerichelli C. Grande L. Luchetti G. Mancini and C. A. Bunton J. Org. Chem. 1987 52 5167. 53 K. Ohkata M. Mase and K. Akiba J. Chem. SOC.,Chem. Commun. 1987 1727. 54 S. D. Kahn C. F. Pau A. R. Chamberlin and W. J. Hehre J. Am. Chem. SOC.,1987 109 650; S. D. Kahan and W. J. Hehre ibid. 1987 109 666; A. R. Chamberlin R. L. Mullholland Jr. S. D. Kahn and W. J. Hehre ibid. 1987 109 672. Reaction Mechanisms -Part (ii) Polar Reactions 67 non-empirical molecular orbital methods provide a more sensitive and a more easily interpretable model than do calculations based on frontier molecular orbital theory. Acid-catalysed hydration of acetylene derivatives (equation 11) has been examined kineti~ally.~~ The authors find general acid catalysis and a kinetic isotope effect H+ PhCrCOMe -PhCH,CO,Me (11) H2O kH+/k,+ of 1.59 indicating that rate-limiting proton transfer from the solvent occurs.Acid-catalysed isomerization of the 4-methyl group in butan-2-01 between the 1-and 4-positionsY is faster than the dehydration reaction to give but-2-ene. This means that isomerization occurs by hydride transfer (C-3to C-2) as well as by the formation and rehydration of but-2-ene. Thus the oxygen exchange reaction in butan-2-01 and the hydration of the alkene do not (as one would pre-suppose) pass through a common carbocation intermediate. In this paper56 Jencks reminds us that it is not enough for a transition state to be found to be ‘carbocation-like’ for us to assume that such a reaction proceeds via a carbocation intermediate (e.g.&l) but that such a mechanism should be supported by direct evidence that the carbocation species is indeed formed. The first systematic comparison of structural effects on the reactivity of the acid- and base-induced hydration of alkylketenes has been rep~rted.~’ The reactants were generated by flash photolysis of diazoketones. The OH-(or H,O)-induced reactions take place by nucleophilic attack in the ketene plane whilst protonation takes place in a direction perpendicular to the ketene plane. Kinetic measurements of the acid-catalysed addition of methanol to a -methoxy-styrenes are complicated by the partial hydrolysis of the acetal products to give acetophenones.’* However the rate limiting step for the addition is shown clearly to be proton attack to give an oxocarbocation which is then trapped by the methanol.Bernasconi and his group continue to study nucleophilic addition to alkenes. Results from kinetic studies of the addition of amines to a-nitr~stilbenes~~ show strong similarities to those found earlier for the (Y -nitrostyrenes particularly as regards to the large imbalance between P:uc and a&. Substituent and solvent effects are discussed for the related reaction of amines with benzylidene Meldrum’s acid!’ One of the conclusions is that resonance is not the major feature in the stabilization of Meldrum’s acid anion (see later in Section 8 for a further discussion of this point). Two papers have also appeared from Rappoport and co-workers in this area continuing their study of nucleophilic vinylic substitution.Reactions of mixed halogeno derivatives of fluorene and ethylene [(7)and (S)] with thiolate and cresolate anions were studied and the [chloro]/[bromo] ratios of the products measured as a function of the solvent. The ratio (the intramolecular element effect) is almost independent of the P-activating group the nucleophile and the solvent. The results are rationalized in terms of carbanion formation with an early transition state for 55 N. Banait M. Hojatti P. Findlay and A. J. Kresge Can. J. Chem. 1987 65 441. 56 P. E. Dietze and W. P. Jencks J. Am. Chem. Soc. 1987 109 2057. 57 A. D. Allen A. J. Kresge N. P. Schepp and T. T.Tidwell Can. J. Chem. 1987 65 1719; A. D. Allen and T. T. Tidwell J. Am. Chem. SOC.,1987 109 2774. 58 J. Toullec M. El-Alaoui and R. Bertrand J. Chem. SOC.,Perkin Trans. 2 1987 1517. 59 C. F. Bernasconi and R. A. Renfrow J. Org. Chem. 1987 52 3035. 60 C. F. Betnasconi and M. Panda J. Org. Chem. 1987 52 3042. D. L. H. Williams HC1 c Br 7' (4- N02C6Hd)zC -C \Br the subsequent halide expulsion.61 In another study the stereochemistry of nucleophilic vinyl substitution is probed62 by analysis of the products of reaction of ArO- ArS- and MeO- with the two benzylidene malonates (9) and (10). Again it is believed that a carbanion is formed and the extent of stereoconvergence (the retention/conversion) ratio is determined by competition between 60" and 120" internal rotations in the carbanion.Nucleophilic attack at the C=N double bond has been examined in the reaction of benzohydrazonyl halides with amine~.~~ The kinetic substituent effects for the overall substitution reaction are consistent with rate-limiting attack of the amine at the carbon atom with a late transition state on the reaction profile. 6 Aromatic Substitution and Rearrangements The debate continues as to whether electrophilic aromatic substitution is best represented by the well-known two-step process involving an intermediate u-complex (or Wheland intermediate) or whether single electron transfer processes are important with the possible involvement of radical cations. An excellent article by Eberson and Radner@ reviews the evidence for the latter but does not claim that the problem is resolved one way or the other.On the other hand Baciocchi and Mandolini maintain65 at least as far as the reactions of methylbenzenes are concer- ned that all known facts on the effects of structure on the reactivity of electrophilic attack (for a range of electrophiles) can be reconciled by the cr-complex mechanism whereas not all of the data are consistent with the single electron transfer process. It is however now well established that the nitrous acid-catalysed pathway for the nitration of aromatic amines and phenols does involve the formation of radical-pair intermediates although not all features of the mechanism are fully understood. The evidence mainly kinetic but also from 15N CIDNP effects is fairly conclusive.Now 61 B. Avramovitch P. Weyerstahl and 2.Rappoport J. Am. Cbem. SOC.,1987 109 6687 62 2.Rappoport and A. Gazit J. Am. Cbem. SOC.,1987 109 6698. 63 A. F. Hegarty P. Rigopoulos and J. E. Rowe Ausr. J. Cbem. 1987 40,1777. 64 L. Eberson and F. Radner Acc. Cbem. Res, 1987 20 53. 65 E. Baciocchi and L. Mandolini Tetrahedron 1987 43 4035. Reaction Mechanisms -Part (ii) Polar Reactions Ridd and co-workers66 report for the first time the 13Cnuclear polarization of the aromatic component of the radical pair in the nitrous acid-catalysed nitration of phenols thus strengthening the mechanistic picture. An interesting example of electrophilic substitution occurring at an enclosed site has been reported.67 A series of 1,3-bridged naphthalenes [(1l) cyclophanes] were synthesized with the alkyl bridge containing 7 8 or 10 methylene groups and with tritium substituted at the 2- or 4-positions [X or Y in (1l)].The partial rate factors for tritium exchange at both positions were measured as a function of ring size and have been explained in terms of the size of the bridge and the consequent buckling effect on the aromatic ring. Reaction at the 2-position is an example of electrophilic substitution occurring ‘through a hole’ and is the first example of such a reaction taking place at an enclosed site. Acid-catalysed detritiation reactions have also been studied for other cyclic reactants including azulene.6s The extremely high reactivity of some of these compounds is attributed to the creation of aromaticity in the transition states.The gas-phase nitration of benzene derivatives has been studied with MeO’(H)N02 using a combination of mass spectral methods and a complementary radiolytic te~hnique.~~ A good Hammett plot (with a+)was obtained except for the more reactive species (anisole etc.) where the reaction rate constant tended towards a limiting value which is taken to be the encounter limit. The authors stress the fundamental similarities between gas-phase and liquid-phase nitrations. In solution rate constants have been measured for aromatic nitration by N205 in nitric acid.70 This system is of some interest for possible large scale application in industrial processes since there have been recent improvements in the production of N205- HN03 solutions by electrochemical procedures.The N205 reactions are significantly faster than are those using HN03-H2S04 as the reagent. This is not easy to reconcile with the production of a new reagent more reactive than NO,+; the explanation may be that a medium effect is responsible for the rate difference. In general the normal nitration products were formed but in some cases cyclohexadiene derivatives also appeared probably by a mechanism involving ips0 attack. Olah and co-~orkers~~ have established that the CF30-group is o/p directing in electrophilic aromatic substitution in nitration halogenation acylation and alkyla- tion reactions. Some meta product is formed in ethylation probably by an 66 M.Ali J. H. Ridd J. P. B. Sandall and S. Trevellick J. Chem. Soc. Chem. Commun. 1987 1168. 67 A. P. Laws A. P. Neary and R. Taylor J. Chem. Soc. Perkin Trans. 2 1987 1033. 68 A. P. Laws and R. Taylor J. Chem. Soc. Perkin Trans. 2 1987 591. 69 M. Attina F. Cacace and M. Yanez J. Am. Chem. Soc. 1987 109 5092. 70 R. B. Moodie and R. J. Stephens J. Chem. SOC.,Perkin Trans. 2 1987 1059. 71 G. A. Olah T. Yarnato T. Hashirnoto J. G. Shih N. Trivedi B. P. Singh M. Piteau and J. A. Olah 1.Am. Chem. SOC.,1987 109 3708. 70 D. L. H. Williams intramolecular rearrangement of the alkylarenium ion before the final proton loss. The CF,O-group is overall deactivating (as are the halogen substituents) and a u+ value of +0.067 was established from the nitration measurements.It has been claimed that there is now kinetic evidence for the intermediacy of a T-complex in electrophilic chlorination in acetic Under first-order conditions with [ArH] >>[ClJ, the measured first-order rate constant is not a linear function of [ArH], but curves downwards as [ArH] increases. The data fit a double reciprocal plot which is consistent with the situation given in Scheme 2. The plots enable values of K and k to be obtained. However it must be noted that the results are K ArH +C1 er-complex fast r-complex A a-complex -products Scheme 2 Me COQH +Clz e Me CQOCl +C1-+H+ Me CQOCl +ArH products Scheme 3 equally consistent with a reaction scheme (Scheme 3) in which the formation of the true electrophilic reagent (possibly chlorine acetate) becomes partly rate-limiting.This is more likely to occur with the very reactive aromatic substrates used in this study. The kinetic effect of added C1- should distinguish the two possibilities. More selective para-chlorination of anisole and phenol has been achieved using N-chlorodialkylamines and N-chlorotrialkylammonium salts in trifluoroacetic acid as the electrophilic reagents.73 Cyclohexadiene intermediates have previously been observed during the bromina- tion of phenols but often they react (ie.enolize) too rapidly for convenient study. However the reaction of the intermediate formed during the bromination of 1-naphthol (equation 12) can be followed without The kinetic results show d2@@ \/ \ I l-(12) H Br Br the same features as those observed for the bromination of 2,6-dimethylphenol ie.base catalysis is quite normal whereas the acid-catalysed enolization is rather unusual with BrGnsted cy -0 and probably involves a termolecular reaction involv- ing the dienone H20 and the general acid HA. Not unexpectedly the nitrosation of 2-naphth01~~ shows the same general features as does the nitrosation of phenol. Reaction conditions have been established where 72 0. M. E. El-Dusouqui K. A. M. Mahmud and Y. Sulfat Tetrahedron Lett. 1987 28 2417. 73 J. R. Lindsay Smith L. C. McKeer and J. M. Taylor J. Chem. SOC. Perkin Trans. 2 1987 1533. 74 0. S. Tee and N. R. Iyengar Can. J. Chem. 1987 65 1714. 75 A. Castro E. Iglesias J. R. Leis M.Mosquera and M. E. Pefia Bull. SOC.Chim. Fr. 1987 83. Reaction Mechanisms -Part (ii) Polar Reactions nucleophile (halide ion etc.) catalysis occurs and also where base catalysis (of the final proton loss) occurs. Another facet of the benzidine rearrangement has recently been examined using I3C kinetic isotope effects.76 There is in fact no KIE in the reactions of 4,4'- dichloro[2,2' 6 6'-'3C,]hydraz~benzene which lead to o-semidine p-semidine and disproportionation products. The result provides another example (now common in the benzidine rearrangement) of an apparently non-concerted reaction which is known (at least here for the o-semidine product) to be intramolecular. In spite of the large amount of mechanistic information now available for this reaction par- ticularly that derived from the more recent elegant kinetic isotope effect experiments from Shine's group features of this rearrangement still remain obscured.Substituted 2-nitroanilines (and other nitroanilines) rearrange in concentrated sulphuric acid at 110 "C to give products of a 1,3 rearrangement of the 2-nitro group. These reactions appear to be intramolecular and show first-order kinetics with no significant dependence upon the A reasonable outline mechanism is given in Scheme 4. The details of the actual rearrangement step may involve radical pairs such as ArNHz'NO; as has been postulated in the acid-catalysed rearrangement of N-nitroanilines. Scheme 4 A number of papers dealing with nucleophilic aromatic substitution have appeared.A review discusses the vicarious nucleophilic substitution of H in aromatic systems by carbanions which contain a leaving group X which is eliminated as HX. New reactions studied include the reaction of 1,4-dinitrobenzene with alkaline hydrogen peroxide.79 Evidence is presented in favour of the formation (for the first time) of an aryl hydroperoxide (equation 13) which decomposes to give the phenolate anion. The displacement of a nitro group by phenoxide ion is reported again using 1,4-dinitrobenzene in dry DMSO at 90 "Cfor 16 hours.80 This is recommended as a good procedure for the synthesis of substituted diphenyl ethers. 76 E. S. Phee and H. J. Shine J. Org. Chem. 1987 52 5633. 77 J. T. Murphy and J. H. Ridd J. Chem. SOC.,Perkin Trans.2 1987 1767. 78 M. Mokosza and J. Winiarski Acc. Chem. Res. 1987 20 282. 79 R. A. Heller and R. Weiler Can. J. Chem. 1987 65 251. 80 P. G. Sammes D. Thetford and M. Voyle J. Chem. SOC.,Chem. Commun. 1987 1373. D. L. H.Williams Phenylazobenzothiazolium dyes containing a 4‘-amino group undergo a nucleophilic substitution in alkaline solution to give a quinone imine which results in a dye fading (equation 14). Substituent effects (kinetic) in both aromatic rings have been measured,8’ so that the fading rates can be predicted for a range of substituents. The dye complexes with aromatic carboxylate aromatic sulphonate and phenolate ions giving an unreactive (towards nucleophilic substitution) species thus inhibiting dye fading.82 Me Me I I The activating effects of nitro groups in various positions in the naphthalene system have been established by kinetic measurements of the 36Cl isotope exchange between LiCl and 1-chloronaphthalene derivatives in s~lpholane.~~ Kinetic solvent effects for the reaction of 1-fluoro-2,4-dinitrobenzene and piperidine suggest that in aprotic solvents the rate-limiting step is loss of the leaving group and not a proton transfer.84 Base catalysis occurs in the reaction of 1,2-dinitrobenzene with amines in n-he~ane.~’ Micellar catalysis in nucleophilic aromatic substitution is discussed quantitatively for single- and twin-tailed ionic surfactants and also for reactions in solutions of cationic bolaform surfactants.86 7 Other Electrophilic Reactions This short section is added this year to cater for some reaction types not covered elsewhere.Thiourea reacts with aqueous bromine to give urea at pH > 2 and to give NH4+ and SO4’-at pH < 2. The reaction mechanism is complex but the essential features have been shown to be two successive electrophilic attacks by bromine at the sulphur atom of thi~urea.~’ It is well-known that tertiary aliphatic amines (and other nitrogen compounds particularly heterocyclic systems) react with halogens to give solid complexes which themselves can be used as sources of electrophilic halogen. The complex with tribenzylamine has been reinvestigatedg8 and has been shown not to be a single 1:l N-bromo bromide salt as hitherto believed but rather a mixture of two tribromide salts tribenzylammonium and N,N-dibenzylbenzylidenaminium (equation 15).Kinetic studies in 1,2-dichloroethane indicate the presence of a transient intermediate probably a 1 1 tribenzylamine:Br charge-transfer complex which undergoes an oxidation-reduc- ni A. P. D’Rozario A. Williams and B. Parton J. Chem. SOC.,Perkin Trans. 2 1987 1781. n2 A. P. D’Rozario A. Williams and B. Parton J. Chem. SOC.,Perkin Trans. 2 1987 1785. 83 M. Attia P. M. Gore and D. F. C. Morris J. Chem. Res. (S) 1987 160 and 200. 84 N. S. Nudelman P. M. E. Mancini R. D. Martinez and L. R. Voltero J. Chem. SOC.,Perkin Trans. 2 1987 951. ns S. M. Chiacchiera J. 0.Singh J. D. Anunziata and J. J. Silber J. Chem. SOC.,Perkin Trans. 2 1987,987. 86 A. Cipiciani R.Germani G. Savelli C. A. Bunton M. Mhala and J. R. Moffat J. Chem. SOC.,Perkin Trans. 2 1987 541; A. Cipiciani M. C. Fracassini R. Germani G. Savelli and C. A. Bunton ibid. 1987 547. 87 R. H. Simoyi and I. R. Epstein J. Phys. Chem. 1987 91 5124. 88 G. Bellucci R. Bianchini. and R. Ambrosetti J. Chem. SOC.,Perkin Trans. 2 1987 39. Reaction Mechanisms -Part (ii) Polar Reactions 73 PhCH,),NH Br,-f (PhCH,),N + Br (15) L (PhCH,) k=C H Ph Br,-tion reaction leading to the formation of fhe benzylidenaminium ion. This is not then an example of a simple electrophilic substitution at nitrogen but is nevertheless included here since it was formerly regarded as such. The nitrosation of thioproline has been examined kineti~ally.~~ The final product is the N-nitrosamine (equation 16).The kinetics however suggest that when the L-j + L-j HOzC N HOzC N (16) I I H NO reagent is H,NOl or NOf the initial reaction occurs at sulphur and that this is followed by an intramolecular migration of the NO group to the nitrogen atom. This is now the second example where sulphur can act as an internal catalyst in this way. Interestingly in the presence of C1- Br- or SCN- when the effective reagents are respectively ClNO BrNO and ONSCN reaction occurs directly at the nitrogen atom. This adds to the growing number of examples in the recent literature of different electrophilic nitrosating species reacting initially at different sites within a molecule that can be rationalized in terms of HSAB theory.Another example where a sulphur-containing compound acts as an intermolecular catalyst in nitrosation is provided by the kinetic results of the nitrosation of an amine in the presence of dimethyl sulphide.” This is the first reported example of catalyse by a sulphide (cf:thiourea) and probably involves the equilibrium formation of Me,SNO which then acts as a nitrosating agent (equation 17). The nitrosation Amine Me,S + HNO + H+e Me,S60 __* Nitrosamine (17) of t;butylhydrazine occurs by two par$lel pathways one involving reaction of Bu‘NH2NH2 and the other of Bu‘NHNH3 .91 Phenylurea apparently undergoes nitrosation at the oxygen atom initially to give an unstable nitrite which again rearranges to the N-nitroso compound.92 8 Carbanions and Proton Transfer Terrier and co-~orkers~~ have measured Bransted coefficients and the (Marcus) intrinsic rate constants for the ionization of 2,2’,4,4’-tetranitrodiphenylmethane (equation 18) in two solvents.All the data can be rationalized in terms of Bernasconi’s 89 A. Castro E. Iglesias J. R. Leis J. V. Tato F. Meijide and M. E. Peha J. Chem. SOC.,Perkin Trans. 2 1987 651. 90 T. Bryant and D. L. H. Williams J. Chem. Res. (S) 1987 174. 91 G. Stedman and N. Uysal J. Chem. Res. (S),1987 376. 92 F. Meijide J. V. Tato J. Casado A. Castro and M. Mosquera J. Chem. SOC.,Perkin Trans.2,1987 1759. 93 F. Terrier J. Lelievre A.-P. Catrousse R. Schaal and P. G. Farrell Can. J. Chem. 1987 65 1980. D. L. H. Williams Principle of Imperfect Synchronization discussed in previous Reports.Protonation of the carbanion reveals a very short-lived species thought to be the nitronic acid formed by oxygen protonation. Arnett and Harrel~on~~ have examined the question of the acidity of Meldrum’s acid (12). Comparison with other structurally related compounds notably dimethyl malonate dimedone and other esters ketones and lactones reveals that the acidity of Meldrum’s acid (pK,4.83 in water 7.32 in DMSO) is unusually large and cannot be attributed solely to its cyclized structure. The major effect responsible arises as a result of the restricted rotation of the ester linkage in the bislactone. The authors conclude with the claim that this effect ‘must represent one of the largest stereoelectronic effects in the literature of organic chemistry’.OX0 Guthrie’s group has extended the method (based on diffusion-controlled chlorina- tion of the enolate ion) for the determination of pK values of simple ketones to a series of p-substituted ace top hen one^.^^ Incidentally acetophenones generally yield mandelic acids under alkaline conditions and not the textbook products (benzoic acids). The reaction is probably similar to that obtaining in the chlorination of acetone described in last year’s Report. The pK value for acetophenone itself is 18.38 * 0.52 in good agreement with that reported by the Kresge using their inherently more precise procedure involving the generation of the enol by flash photolysis. The Guthrie method does require the assumption of a value for the rate constant of a diff usion-controlled process but is much more conveniently carried out experimentally.A method has been developed for the a priori calculation of pK values of organic com’pounds in water.97 This should be valuable for the very weakly basic species for which an experimental determination is very difficult. The procedure is based on the calculation of the differences in free energies of hydration for the anions and the neutral species and the difference in the gas-phase acidities. The value for ethane is computed as 50.6 f 2 which compares with the range of experimental values in the literature of 42-60. The ion-pair acidities of some phenyl alkyl ketones have been measured by an indicator method.98 It is found that the equilibrium caesium ion-pair acidity of 94 E.M.Arnett and J. A. Harrelson J. Am. Chem. SOC.,1987 109 809. 95 J. P. Guthrie J. Cossar and A. Klym Can. J. Chem. 1987 65 2154. 96 Y. Chiang A. J. Kresge and J. Wirz J. Am. Chem. SOC.,1984 106 6392, 97 W. L. Jorgensen J. M.Briggs and J. Gao J. Am. Chem. Soc. 1987 109 6857. 9x M.J. Kaufman and A. Streitweiser Jr. J. Am. Chem. SOC.,1987 109 6092. Reaction Mechanisms -Part (ii) Polar Reactions ketones decreases as the equilibrium enolate concentration is increased. This can be readily attributed to aggregation of the enolates which can be measured and which depends both on electronic and steric effects. The unusually large pK value of 1,8-bis(dimethylamino)naphthalene (13) has been discussed previously in terms of the difference in strain energy between the amine and its protonated form involving a twist of the NMez groups and a consequent distortion of the ring system.This effect has now been further examined99 by determination of the effect of the introduction of methylene bridges linking the two nitrogen atoms as in (14). When the ring size is small (n = 2 or 3) there is little difference in the strain energy between the acid and base forms and the rates of proton transfer are higher and the basicities lower than for (13). When the ring size is larger however the protonated form can more readily form an intramolecular hydrogen bond and there is much less strain resulting in lower rates of proton transfer and higher basicities.Similarly the introduction of 2-and 7-substituents has a large effect of increasing the basicity and decreasing the rate of proton transfer in these systems.'00 Again the results can be explained partly by the increase in the strain energy in these highly substituted diaminonaphthalenes. 9 Carbonyl Derivatives and Tetrahedral Intermediates The spate of interest in the synthesis characterization and reactions of simple stable enols continues and is even growing. A range of 1-aryl-2,2-dimesitylethenols has been made by reaction of a Grignard reagent with dimesityl ketene."' Values of Keno,were determined directly in hexane solvent. It seems that the large mesityl groups substantially stabilize the enol form in the aromatic series. The trend in Keno has been analysed in terms of a decrease in stabilization of the keto form by electron-withdrawing substituents in the (Y -aryl substituent.The tricyclic enol (15) was readily obtained quantitatively by treatment of the corresponding ketone with methoxide in methanol-THF and quenching with water; its structure was established by X-ray analysis.lo2 Structural analysis again reveals that the unusual stability of the enol form is due to factors which destabilize the keto form. The first a-silicon- substituted simple enol (16) has been synthesized from dime~itylketene."~ Its extreme stability relative to the keto tautomer is ascribed to the large stabilizing effect of the silyl substituent. 99 F. Hibbert and G. R. Simpson J. Chem. SOC.,Perkin Trans. 2 1987 613.100 F. Hibbert and G. R. Simpson J. Chem. SOC.,Perkin Trans. 2 1987 243. 101 E. B. Nadler and Z. Rappoport J. Am. Chem. SOC.,1987 109 2112. 102 D. V. Pratt and P. B. Hopkins J. Am. Chem. SOC.,1987 109 5552. I03 E. B. Nadler Z. Rappoport D. Arad and Y. Apeloig J. Am. Chem. SOC..1987 109 7873. D. L. H. Williams Ar Ar /OH \C=C \C=C Ar ' /OH Ar / 'OH 'OR Acid and ester enols have previously been postulated as reactive intermediates but have now been isolated for the first time [(17) and (18)].'04 Again use is made of large bulky (this time using pentamethylphenyl) groups in order to stabilize these enol forms. Here the enols tautomerize relatively slowly over several hours to give respectively the carboxylic acid and the ester.The Kresge group continues its studies on simple enols generated by flash photoly- sis. This year they repodo5 on the generation of the parent enol vinyl alcohol by photoelimination of 5-hydroxypentan-2-one and measure its isomerization to acetal- dehyde which as expected is catalysed by H+ OH- and general acids. Rates of enolization of acetaldehyde were also measured by iodine scavenging and yielded a value for Kenolof (5.89 f0.81) x lo-' and also values for pKF of 10.50 f 0.02 (for the oxygen acid) and pK," of 16.73 f0.06 (for the carbon acid). The stereochemistry of the ketonization of enols has been reviewed.'06 The normal mechanism is by ionization to give the enolate anion followed by C-protonation. The transition state is assumed to be close to being sp2 hybridized so that the major effect controlling the stereochemistry is steric hindrance to the approach of the proton donors-an effect which will be more pronounced for large proton donor molecules.Other workers have described a method for the direct measurement of the rates of ketonization of dienolate anions produced transiently by photochemical enolization of P-alkyl a$-unsaturated ketones in aqueous basic solution. The results show that ketonization occurs by carbon protonation of the dienolate or by way of a 1,Shydrogen shift in the dienol."' Another study favours the latter explanation.108 Rappoport finds an excellent linear free-energy correlation between Kenolvalues for stable p,P -dirnesityl- and unstable p,p-unsubstituted a -substituted enols i.e. between pKenol [Mes2C=C(OH)R] and pKenol [H2C=C(OH)R]. This plot can then be used to predict pKeno values for simple enols which are not easily measured.'09 L 04 P. O'Neill and A. F. Hegarty J. Chem. Soc. Chem. Commun. 1987 744. 105 Y. Chiang M. Hojatti J. R. Keeffe A. J. Kresge N. P. Schepp and J. Wirz J. Am. Chem. SOC.,1987 109 4000. 106 H. E. Zimmerman Acc. Chem. Res. 1987 20 263. 107 R. M. Duhaime and A. C. Weedon 1.Am. Chem. SOC.,1987 109 2479. 108 R. M. Pollack J. P. G. Mack and G. Blotny J. Am. Chem. SOC.,1987 109 3138. 109 Z. Rappoport J. Am. Chem. SOC.,1987 109 4730. Reaction Mechanisms -Part (ii) Polar Reactions It has been shown conclusively that the nitrosation of simple ketones occurs by electrophilic attack of the enol form (see equation 19).'1° This is in spite of a report to the contrary over thirty years ago.Under certain experimental conditions (e.g. at high [Br-1 which generates reasonably high concentrations of the reagent BrNO) reaction with acetone and other ketones is zero-order in the nitrosating agent BrNO Me,CO eCH,=C(OH)Me -CHCOMe (19) II NOH concentration and the measured first-order rate constants for enolization are iden- tical (within experimental error) with those obtained much earlier in the classical experiments with halogenation. When the rate of reaction by the nitrosating agent is reduced (by lowering its concentration or by deactivating the enol) the other limiting rate form takes over when the attack by the reagent is rate limiting (first order in [HNO,]).Thus nitrosation joins the large group of reactions of ketones which take place uia the enol form. Acid-catalysis of C-H bond breaking in the enolization of the heterocyclic ketone (19) occurs by N-protonation rather than by 0-protonation of the carbonyl group."' The explanation involving N-protonation is favoured since related ketones without the heterocyclic nitrogen atom react ca. lo6 more slowly. In nucleophilic displacements at the carbonyl group questions concerning the intermediacy of a tetrahedral intermediate continue to be asked. Results are presented for acyl transfer reactions in 4-nitrophenyl acetate by a series of phenolate anions which argue in favour of a concerted reaction with a single transition state or possibly a mechanism involving intermediate formation but with a very low barrier towards decomposition.' l2 Interestingly a very similar conclusion was reached in a study of the reaction of RCOCl + C1- in the gas phase.'13 In this case RCOC1,- is either a transition state or possibly a very unstable intermediate.Substantial "0 exchange occurs during the acid-catalysed hydrolysis of acetanilide and also N-cyclohexylacetamide.' l4 This (with one notable exception) is contrary to all earlier literature results pertaining to acid-catalysed amide hydroly- sis. Consequently the mechanism must involve reversible formation of a tetrahedral intermediate contrary to the presently accepted mechanism. In ester hydrolysis acetylcholinesterase has been found to behave as a simple general acid-base catalyst for the reactions of phenyl acetate acetyl esters and other ester^."^ 110 J.R. Leis M. E. Peiia and D. L. H. Williams J. Chem. SOC.,Chem. Commun. 1987 45. 111 A. Argile A. R. E. Carey R. A. More O'Ferrall B. A. Murray and M. G. Murphy J. Chem. SOC.,Chem. Commun. 1987 1847. 112 S. Ba-Saif A. K. Luthra and A. Williams J. Am. Chem. SOC.,1987 109 6362. 113 C.-C. Han and J. I. Brauman J. Am. Chem. SOC.,1987 109 589. 114 H. Slebocka-Tilk R. S.Brown and J. Olekszyk J. Am. Chem. SOC.,1987 109 4620. 115 S. A. Acheson D. Dedopoulou and D. M. Quinn J. Am. Chem. SOC.,1987 109 239. 78 D. L. H. Williams Splrensen and Jencks (in a paper dedicated to Professor R.P. discuss the acid- and base-catalysed decomposition of acetaldehyde hydrate and hemiacetals. The results are consistent with a fully concerted reaction mechanism for both catalysts. The conclusions are derived from arguments involving differences in Brflnsted coefficients between these and the corresponding formaldehyde reactions and their description in terms of normalized interaction coefficients. Very large catalytic effects by Ni2+ Co2+ and Zn2+ have been noted in the hydrolysis of a number of acetals,"' even though the binding of metal ions to acetals is known to be very weak. Catalysis is thought to occur by stabilization of the leaving group in the transition state of the C-0 bond breaking reaction. There are very strong resemblances between these metal ion-catalysed reactions and the hydrolysis reac- tions of acetals catalysed by general acids.Volumes of activation (A V) have been measured (from the variation of equilibrium constants with pressure) for a hydroxyketone hemiacetal equilibrium and also for a thiol addition to acetyl cyanide.Il8 These two examples represent the formation of tetrahedral species which might be regarded as possible models for the B,,2 mechanism for ester hydrolysis. In fact although the volumes of reaction are both negative they are very different in that the A V for the unimolecular reaction of the hydroxyketone is much less negative than it is for the bimolecular reaction. The results highlight the important contribution to AV (and also to AV* for ester hydrolysis) of molecular association which takes place before bond formation.In the base-catalysed rearrangement of hydroxyketones there is an intramolecular hydride transfer. Good agreement is found between the experimentally measured kinetic isotope effect (kH/kD) and that calculated by ab inifio MO calculations in these reactions."' 10 Some Probes of Polar Mechanisms A number of probes have of course been discussed in the various sub-sections e.g. probes for an SET component in nucleophilic substitution etc. This section deals with more general aspects and with examples which do not fit conveniently into the earlier sections. Isotopes continue to play an important part in reaction mechanism studies. Another volume has appeared this year in the 'Isotopes in Organic Chemistry' series which deals with aspects of secocdary and solvent kinetic isotope effects.12' A technique has been described for the measurement of the 11C/14C kinetic isotope eff ect.12' The advantages (relatively large mass ratio) and disadvantages (detection equipment and short half-life) of the use of the "C isotope (a positron emitter with a half-life of 20.34 min) are discussed.Values of kll/k,4 were obtained for the reaction of a tertiary amine with labelled methyl iodide. Typical values are in the region of 1.23. A correlation has been found between n.m.r. isotope shifts (D for 1 I6 P. E. S~rensen and W. P. Jencks J. Am. Chem. SOC.,1987 109 4675. 117 T. H. Fife and T. J. Przystas J. Chem. SOC.,Perkin Trans. 2 1987 143. I18 N.S. Isaacs H. S. Rzepa R. N. Sheppard A. M. Lobo S. Prabhakar and A. E. Merbach J. Chem. SOC.,Perkin Trans. 2 1987 1477. 119 M. J. Field I. H. Hillier S. Smith M. A. Vincent S. C. Mason S. N. Whittleton I. F. Watt and M. F. Guest J. Chem. SOC.,Chem. Commun. 1987 84. 120 'Isotopes in Organic Chemistry' Vol. 7 ed. E. Buncel and C. C. Lee Elsevier 1987. 121 B. S. Axelsson B. Lingstrom and 0. Matsson J. Am. Chem. SOC..1987 109 7233. Reaction Mechanisms -Part (ii) Polar Reactions H or 13C for "C) and secondary kinetic isotope effects in the alkaline hydrolysis of esters.'22 It is suggested that all kinetic-n.m.r. relationships derive from a common ground-state feature which in this case might be the ground-state conformation of the esters and the corresponding acids.The Baker-Nathan order of electronic effects of alkyl groups attached to an aromatic ring has been established for a series of P-substituted styrenes by measurement of the I3C n.m.r. chemical shifts of the P-~arbon.'~~ The order is unchanged through a range of solvents which suggests that the effect is truly a hyperconjugation effect and cannot be explained as a solvent effect as has been claimed. In the same area deuterium isotope effects on I3C chemical shifts correlate with n-bond orders for aromatic systems containing a fully deuterated t-butyl group. The sign of the effect changes with CD3 and this is taken as evidence supporting C-C hyperc~njugation.'~~ A probe for the absence of a resonance contribution of an a-aryl group to a cationic transition state arises from the observed inverse order of solvolysis of highly-crowded benzylic tosylates containing electron withdrawing groups.125 In a number of cases the para-substituted reactant was more reactive than the meta- isomer arising from the lack of planarity on these systems between the aryl ring and the sp2 orbital of the carbocation thus restricting the operation of the resonance effect.The Ingold-Taft equation has been used to estimate the contribution of the common A,,2 mechanism in situations where other mechanisms may be operating simultaneously.126A four-parameter equation has been presented in an attempt to quantify solvent effects. The parameters are n*,the solvent dipolarity; a,the solvent hydrogen-bond acidity; p the solvent hydrogen-bond basicity; and a the solvent cohesive energy density.Simpler earlier correlations based on Y and N parameters are now shown to be limiting forms of the more general eq~ati0n.l~~ Cox has reviewed the excess acidity method for the quantitative treatment of reactivity of acid-catalysed reactions in sulphuric acid.'28 The method is based on the assumption that activity coefficient ratios are linear functions of one another. This is more reliable than the assumption made in the Zucker-Hammett treatment regarding the cancelling of some activity coefficient terms. A range of reactions (mostly hydrolysis) carried out in sulphuric acid have already been successfully treated by this method and A-1 and A-2 mechanisms clearly differentiated.I22 I23 124 12s 126 I27 I 28 M. S. Malta D. E. Broadway and M. K. Stroot J. Am. Chem. SOC.,1987 109 4916. B. T. Cooney and D. A. R. Happer Ausf.J. Chem. 1987 40 1537. S. Berger B. W. K. Diehl and H. Kunzer Chem. Ber. 1987 120 1059. K.-T. Liu and M.-Y. Kuo J. Chem. SOC.,Chem. Commun. 1987 640. L. T. Kanerva and E. K. Euranto J. Chem. SOC.,Perkin Trans. 2 1987 441. M. H. Abraham R. M. Doherty M. J. Kamlet J. M. Harris and R. W. Taft J. Chem. SOC. Perkin Trans. 2 1987 1097. R. A. Cox Acc. Chem. Rex 1987 20 27.

ISSN:0069-3030    

DOI:10.1039/OC9878400059

出版商:RSC    

年代:1987

数据来源: RSC

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4 Reaction Mechanisms Part (iii)Free-radical Reactions By D. CRlCH Department of Chemistry University CollegeLondon 20 Gordon Street London WC1H OAJ 1 Synthesis Cyc1izations.-1987 saw the publication of numerous examples of the now classical 5-hexenyl-cyclopentylmethyltype rearrangement in the synthesis of natural and other products only a limited number of examples of radical cyclizations of a more unusual nature are presented here. Treatment of bromide (1) with tri-n-butylstannane and azoisobutyronitrile (AIBN) in benzene at reflux allowed Wehle and Fitjer to prepare' (3) the first example of a new class of polycyclic hydrocarbons-the coronanes albeit in low yield (7% ). Side products included the reduction product (2) (8%) and the regioisomer (4) (32%).(1) X = Br (3) (4) (2) X = H Bachi demonstrated* that provided the double bond is activated carbapenams can be formed by treatment of an appropriate halide with tri-n-butylstannane (Scheme 1). Similar results were obtained for cyclization onto alkynes. H Scheme 1 ' D. Wehle and L. Fitjer Angew. Chem. Int. Ed. Engl. 1987 26 130. ' M. D. Bachi A. De-Mesmaeker and N. Stevenart-De-Mesmaeker Tetrahedron Lett. 1987 28 2637 2887; also see G. Just and G. Sacripante Can. J. Chem. 1987 65 104. 81 82 D. Crich Walton observed3 that treatment of cyclohept-4-enylmethyl bromide with tri-n- butylstannane gives mixtures of 5-methylcycloheptene and bicycle[3,2,l]octane and that the yield of the latter increases with temperature. On the other hand Bloodworth took advantage4 of the relatively slow transannular cyclization of the cyclo-oct-4-enyl radical to prepare cyclo-oct-4-enyl hydroperoxide by working in the presence of oxygen and a thiol.The key step in a synthesis of the avermectin southern part accomplished5 by the Julia group was one of several 1987 examples of vinyl radical cyclizations initiated by stannyl radical addition to an alkyne (Scheme 2). X C0,Me I,Yl Bu,SnH AIBN ll0"C X I C02MeBu3snwX = H 30% X = SiMe 50-60°!0 Scheme 2 Bu,SnH AIBN. ll0"C OAc Scheme 3 Danishefsky and Panek generated6 a regiospecific enol ether by the radical cyclization with elimination (S,2') procedure outlined in Scheme 3. Subsequent to their 1986 rediscovery (Annu. Rep. Progr. Chem.Sect. B 1986,83 67) of the efficient cyclization of hexan-6-alyl radicals to cyclohexyloxyl radicals Fraser-Reid and co-workers have shown' that this cyclization is more rapid than the more usual 5-hexenyl-cyclopentylmethyl type (Scheme 4). OH Scheme 4 F. MacCorquodale and J. C. Walton J. Chem. SOC.,Chem. Commun. 1987 1456. A. J. Bloodworth D. Crich and T. Melvin J. Chem. Soc. Chem. Commun. 1987 786. J. Ardisson J. P. Fkrtzou M. Julia and A. Pancrazi Tefrahedron Lett. 1987 28 2001. S. J. Danishefsky and J. Panek J. Am. Chern. Soc. 1987 109 917. 'R. Tsang J. K. Dickson H. Pak R. Walton and B. Fraser-Reid J. Am. Chem. SOC.,1987 109 3484; this particular radical cyclization was first demonstrated in 1976 F. Flies R. Lalande and B. Maillard Tetrahedron Lett.1976 439. Reaction Mechanisms -Part (iii) Free-radical Reactions Curran has expanded the range of his atom-transfer cyclizations to include esters of 2-iodohept-6-enoic acid' and even a tandem radical addition-cyclization process.' Fragmentations and Rearrangements.-Crimmins and Mascarella treated" the iodide (5) with tri-n-butylstannane and AIBN in benzene at reflux and obtained the angular triquinane (7) together with the alkane (6). The ratio of (6) to (7) was found to with reaction conditions and a more expeditious process involved the Curran atom-transfer method. Thus photolysis of (5) and 10 mole YO hexabutyldistannane in benzene at reflux gave the iodide (8) in 85% yield so providing a rare example of the efficient ring-opening of a cyclobutylmethyl radical.(5) x = I (7) X = H (6) X = H (8) X = I Rearrangements involving alkyl or aryl radical addition to ketones or nitriles followed by fragmentation of the adduct radical have been p~blished'~"*'~ by three groups. Examples of intermediate 3- 5- and 6-membered rings were given (Schemes 5 and 6). C0,Me Scheme 5 Scheme 6 Maillard and co-workers ob~erved'~ an interesting radical rearrangement when upon photolysis of the iodide (9) with chlorotributylstannane/sodium borohydride in the presence of acrylonitrile they obtained the ring-expanded products (10) and (11) together with the expected product (12) in 24 35 and 28% yields respectively. D. P. Curran and C.-T. Chang Tetrahedron Lett. 1987 28 2477. D. P.Curran and M.-H. Chen 1. Am. Chem. Soc. 1987 109 6558. lo M. T. Crimmins and S. W. Mascarella Tetrahedron Lett. 1987 28 5063. " A. L. J. Beckwith D. M. O'Shea S. Gerba and S. W. Westwood J. Chem. SOC.,Chem. Commun. 1987 666. 12 P. Dowd and S.-C. Choi 1.Am. Chem. Soc. 1987 109 3493 6548. 13 B. Arregey San Miguel B. Maillard and B. Delmond Tetrahedron 1987 28 2127. rn 8D. Crich COzMe COzMe (9) CN ;J-i" COzMe Et (11) Radical-induced fragmentations of fused bicyclic tertiary alcohols and lactols as a route to medium and macrocyclic ketones and lactones figured largely in 1987. Thus Suginome and Yamada ~ynthesized'~ exaltone from cyclododecanone; the key step was the fragmentation outlined in Scheme 7. Muscone was prepared in an analogous manner from methylcyclododecanone.The relationship between this reasonably well established methodology and that developed by Beckwith and Dowd (Schemes 5 and 6) is evident. 1. HgO I - 96% 2. hu :-ji Scheme 7 Spanish workers generally the combination iodoxybenzene diacetate- iodine to mercuric oxide-iodine for the generation of alkoxyl radicals in their fragmentation studies. Under oxygen at 10 atmospheres pressure the alkoxyl radical derived from (13) ~nderwent'~ a series of fragmentations additions of oxygen and hydrogen abstractions to give the A,A' ring system model (17) for limonin. In an approach to the A ring of the a-methylene-8-lactone vernolepin these workers also noted16 that the steroidal lactol (14) suffered indiscriminate cleavage of the 2,3 and 3,4 bonds to give the lactones (18) and (19) in 35 and 27% yields respectively.However inclusion of a radical leaving-group at the la position of the substrate I4 H. Suginome and S. Yarnada. Tetrahedron Lett. 1987 28. 3963; Tetrahedron 1987 43 3371. I5 R. Freire R. Hernandez M. S. Rodriguez and E. Suarez Tetrahedron Left. 1987 28 981. C. G. Francisco R. Freire M. S. Rodriguez and E. Suarez Tetrahedron Lett. 1987 28 3397. Reaction Mechanisms -Part (iii) Free-radical Reactions as in (15) and (16) channelled all the reaction into 2,3 bond cleavage giving (20) in 60 and 65% yields respectively. This observation is probably a reflection of the reversibility of the key fragmentation step rather than of a concerted fragmentation- elimination.Japanese workers also used17 lactol cleavage with subsequent stannyl radical elimination to generate unsaturated medium-ring lactones. AH17 (13) X = H,Y= Me (14) X = H,Y = H (15) X = SnBu,,Y = H (16) X = ySPh Y p= H H17 sH17 I I I I 0 H H I (19) (20) Giese has published’* further examples of his 2-deoxyglycoside preparation involving acyl migration from the 2-position to a glycosyl radical. Furthermore chemical evidence has now been provided” to support the claim that the stereoselec- tivity experienced in glucosyl radical reactions and in the above 2-deoxy sugar method is a result of the boat conformation adopted by glucosyl radicals. Thus tributylstannane treatment of (21) gave 53% of the cyclized products (22) indicating a boat or inverted chair conformation for the first-formed glucosyl radical; the latter of the two possibilities was eliminated when stannane treatment of (23) did not OAc c Aco&--j AcO-AcO-@-I OAc OAc OAc AcO OAc hl.Ochiai S. Iwaki T. Ukita and Y. Nagao Chem. Lett. 1987 133. B. Giese K. S. GrSninger T. Witzel H.-G. Korth and R. Sustmann Angew. Chem. Inr. Ed. Engl. 1987 26 233. K. S. Groninger K. F. Jager and B. Giese Liebigs Ann. Chem. 1987 731. D. Crich yield any cyclized product. Giese also reported2' on a novel benzoyl migration observed during the addition of alkyl radicals to a carbohydrate-based 2-benzoyl- oxyenone (Scheme 8). OCOPh OCOPh Bu,SnH -OCOPh 83% -OCoPh Bu'1,AlBN * PhCOO 0 b 0 OCOPh Scheme 8 Stereochemical Aspects.-Watanabe demonstrated2' that significantly improved stereoselectivities can be obtained in hetero-5-hexenyl type cyclizations by introduc- ing further halogen substituents at the radical centre and removing them after cyclization (Scheme 9).single diastereoisomer Scheme 9 RajanBabu reported22 a highly stereoselective 1-substituted 5-hexenyl cyclization in which the stereochemistry about the newly formed 1,5-bond was exclusively trans (Scheme 10) in contrast to the more usual preference for 1,2-cis-disubstituted cyclopentane formation in similar systems. It was readily demonstrated that the observed stereoselectivity was a result of the presence of the 1,3-dioxane ring and the suggestion was made that in the transition state for cyclization the dioxane ring takes up a boat conformation stabilized by a favourable SOMO-p C-0 u*orbital interaction.H. 07" f I Scheme 10 20 B. Giese and T. Witzel Tetrahedron Lett. 1987 28 2571. 21 Y. Watanabe Y. Ueno C. Tanaka M. Okawara and T. Endo Tetrahedron Lett. 1987 28 3953. 22 T. V. RajanBabu J. Am. Chem. SOC.,1987 109 609. Reaction Mechanisms -Part (iii) Free-radical Reactions Hanessian and Kametani have both looked23 at the formation of six-membered rings by radical addition onto ap-unsaturated esters and report good yields. In the case of substituted substrates cis/ trans mixtures of disubstituted cyclohexanes were usually obtained with some slight preference for the product resulting from cycliza- tion via a chair-like transition state with a maximum of equatorial substituents (Scheme 11).;,:;?H ov Br 3. Jones EtO2C CO2Et 96O/o trans :cis 4 1 Scheme 11 Ono made24 the observation that the elimination from P-phenylsulphonylnitroalk-ones on treatment with tri-n-butylstannane is stereospecific anti. It was concluded that the elimination proceeds uia an initial addition of the stannyl radical to the nitro group followed by fragmentation of the adduct radical and synchronous elimination of the phenylsulphonyl radical so eliminating the need for discrete carbon-centred radicals. This observation was used to refute claims that the reduction of nitroalkanes with stannanes involves an electron-transfer component.In the intermolecular radical addition field Barton noted2’ that complete diastereofacial selectivity was obtained on irradiation of the 0-acyl thiohydroxamate (24) derived from RR-tartaric acid with methyl acrylate giving the hexandioic acid esters (25). (24) (25) French workers demonstrated26 that the dibenzoyl peroxide initiated addition of bromotrichloromethane to diethyl malonate or fumarate leads to the same 3 :1 ratio of erythro threo adducts. The threo adduct is obtained exclusively when malonic anhydride is the radical trap. Japanese workers have studied2’ the radical addition 23 S. Hanessian D. S. Dhanoa and P. L. Beaulieu Can. J. Chem. 1987 65 1859; M. Ihara N. Taniguchi K. Fukurnoto and T. Karnetani J.Chem. Soc. Chem. Cornrnun. 1987 1438; also see G. Stork M. E. Krafft and S. A. Biller Tetrahedron Lett. 1987 28 1035. 24 N. Ono A. Karnimura and A. Kaji J. Org. Chem. 1987 52 5111. 25 D. H. R.Barton A. Gateau-Olesker S. D. Gero B. Lacher C. Tachdjian and S. Z. Zard J. Chem. Soc. Chem. Cornrnun. 1987 1790. 26 J.-Y. Nedelec D. Blanchet D. Lefort and J. Guilhem J. Chem. Res. (S) 1987 315. 27 M. Kaneyama N. Kamigata and M. Kobayashi J. Org. Chem. 1987 52 3312; M. Kaneyama and N. Karnigata Bull. Chem. Soc. Jpn. 1987 60,3687. 88 D. Crich of alkyl and arylsulphonyl chlorides as well as tetrachloromethane to styrene promoted by a ruthenium(r1) catalyst in the presence of the chiral ligand DIOP" and obtained enantiomeric excesses of up to 40% although the majority were significantly below 20%.This author has obtained28 diastereoselectivities of up to 66% by photoinitiated addition of 0-acyl thiohydroxamate esters to chiral esters of acrylic acid (Scheme 12). Et 75%; d.e. = 66% Scheme 12 However the most spectacular diastereoselective radical reaction reported29 in 1987 was that of Lomolder and Schafer in which photolysis of an asymmetric diacyl peroxide as a solid at -60°C gave almost complete retention of configuration at the radical centre involved (Scheme 13). The corresponding derivative of (*)-tartaric acid gave a d.e. of 89% in a similar reaction. 0 0 II II C-O-O-CCI1H23 CIIH23 H~+:; -60"C(solid)'H+::: H hw H COzMe COzMe Scheme 13 d.e. = 92% New Radical Sources.-It has been demonstrated3' that simple photolysis of alkyl-mercury bromides in the presence of diphenyl diselenide leads to alkyl radicals which are eventually trapped by a phenylselenide moiety (Scheme 14).4+ eeph C02Me C02Me C02Me 81 Yo SePh 13% Scheme 14 Pattenden has continued to expand the use of organocobalt(n1) complexes as radical sources in describing31 the use of acylcobaloximes as precursors for acyl radicals which were then added to Michael acceptors as outlined in Scheme 15. 28 D. Crich and J. W. Davies Tetrahedron Lett. 1987,28 4205. 29 R. Lomolder and H. J. Schafer Angew. Chem. Int. Ed. EngL 1987,26 1253. 30 T. Tom Y. Yamada E. Maekawa and Y. Ueno Chem. Lett. 1987 1827. 31 D.J. Coveney V. F. Patel and G. Pattenden Tetrahedron Lett.1987,28 5949. * 2,3-(isopropylidenedioxy)-2,3-dihydroxy-l,4-bis( dipheny1phosphino)butane 89 Reaction Mechanisms -Part (iii) Free-radical Reactions 40 Yo Minisci has presented3* several elegant methods for the preparation of alkyl radicals from alkyl iodides by a process closely related to Curran's atom transfer idea. Thus methyl radicals generated by a variety of means including (i) the action of hydrogen peroxide and iron(r1) salts on dimethyl sulphoxide (ii) action of iron(n) salts on tertiary butyl hydroperoxide and (iii) action of hydrogen peroxide on acetone abstract iodine from higher alkyl iodides giving higher alkyl radicals. These higher alkyl radicals then undergo efficient addition to protonated heteroaromatic bases aryl diazonium cations and a variety of other radical traps.2 Mechanism and Physical Addition to A1kynes.-In a series of elegant experiments Stork has demon~trated~~ that the regioselectivity observed in the addition of stannyl radicals to alkynes with subsequent cyclization of the so-formed vinyl radical (Scheme 16) is a consequence of the ease of reversibility of the addition of stannyl radicals to alkynes as well as to alkenes. OH 70% Scheme 16 Japanese workers have e~tablished~~ that triethylborane catalyses the addition of stannyl germyl and thiyl radicals to alkynes enabling such reactions to be carried out at ambient temperature without having recourse to photoinitiation. Radical Clocks and Probes.-The dangers inherent in the use of 1-halogenohex-5-enes as probes for radical intermediates and hence for electron-transfer processes in the formation of organometallic species has been well demonstrated by the atom-transfer cyclization reactions developed by Curran:8 the work of Ne~cornb~~ in which it is established that the rate of iodine abstraction from ethyl iodide by the octyl radical is between 1.7 and 3.4 x lo5 M-'s-l at 50 "C puts these dangers on a very real quantitative footing.32 F. Fontana F. Minisci and E. Visrnara Tetrahedron Lett. 1987 28 6373. 33 G. Stork and R. Mook J. Am. Chem. Soc. 1987 109 2829. 34 K. Nozaki K. Oshima and K. Utirnoto J. Am. Chem. Soc. 1987 109 2547; Bull. Chem. SOC.Jpn. 1987 60,3465; Y. Ichinose K. Wakarnatsu K. Nozaki and J.L. Birbaurn Chem. Lett. 1987 1647; Y. Ichinose K. Nozaki K. Wakarnatsu K. Oshirna and K. Utirnoto Tetrahedron Lett. 1987 28 3709. 35 M. Newcornb R. M. Sanchez and J. Kaplan J. Am. Chem. SOC.,1987 109 1195. 90 D. Crich The rates of cyclization of the radicals (26)36 and (27)” have been measured and found to be 1.0 x lo5s-’ and 2.9 x lo4s-’ for the cyclization of (26) to the cis and trans isomers respectively of the 2-methylcyclopentylmethyl radical at 298 K and 1.2 x lo6s-’ for (27) going to its ring-closed form at 230 K. Murphy has introduced38 the rapid C-C bond cleavage of 3-phenyl-2,3-epoxypropylradicals as a new radical probe. Although no quantitative data are available at present it was demonstrated by the exclusive formation of (29) on treatment of (28) with tri-n-butylstannane that this cleavage is significantly more rapid than the 5-hexenyl-cyclopentylmethyl rearrangement.Polar Effects.-The electrophilic t-butoxyl radical abstracts hydrogen regioselec- tively from the methylene group of ethyl acetate to give the 1-acetoxyethyl radical; in the presence of a catalytic amount of the trimethylamine-thexylborane complex this selectivity is completely reversed with hydrogen abstraction taking place from the acetate methyl group to give the ethoxycarbonylmethyl radical (Scheme 17). This elegant experiment was presented by Robert~’~ as an example of his concept of polarity-reversal catalysis and is explained in terms of preferential abstraction by the t-butoxyl radical from the amine-borane to give a nucleophilic amineboryl radical which itself abstracts the more electropositive hydrogen from the substrate.MeC02CH2Me * CH2C02CH2Me Me,N -,BH,+ hv Scheme 17 Minisci has investigated the effects of solvent polarity on the regiochemistry of radical addition to the pyridinium cation using radicals generated from a variety of sources. The general trend observed4’ was that the greater the nucleophilicity of the radical (and hence also the greater the stability) the greater the susceptibility to 36 J. Lusztyk B. Maillard S. Deycard D. A. Lindsay and K. U. Ingold J. Org. Chem. 1987 52 3509. 31 A. L. J. Beckwith and S. A. Glover Aust. J. Chem. 1987 40 157. 38 A. Johns J. A. Murphy C. W. Paterson and N. F. Wooster J. Chem.SOC.,Chem. Commun. 1987 1238. 39 V. Paul and B. P. Roberts J. Chem. SOC.,Chem. Commun. 1987 1322. F. Minisci F. Vismara F. Fontana G. Morini M. Serravalle and C. Giordano J. Org. Chem. 1987 52 730. Reaction Mechanisms -Part (iii) Free-radical Reactions solvent polarity. Thus whilst the n-butyl radical gave an a/yratio of 56.3:43.7 in water and 74.4:25.4 in benzene the t-butyl radical had a/?23.0:77.0 in water and 71.4:28.6 in benzene. It was suggested that the reversibility of radical addition to the cation was a factor although the solvation of polar transition states could not be ruled out. Capto-dative Effects.-Ruchardt has pointed that spin delocalization in capto- dative radicals as measured by the aHcoupling constant is not necessarily a good measure of radical stabilization and does not necessarily correlate with the enthalpy of activation for C-C bond cleavage of the dimer.Thus whilst the extent of delocalization in (31) decreased in the order X = OMe Y = CN > X = CN Y = Me > X = Y = CN > X = Y = OMe > X = OMe Y = Et the AH* for cleavage of (30) decreased in the order X = Y = OMe > X = Me Y = Et > X = OMe Y = Et > X = OMe Y = CN > X = CN Y = Me > X = Y = CN. It was suggested4' that aHpossibly only reflects the SOMO energy and not the total radical stability. xx X I 1 Ph -C -C -Ph I I YY /-Ph-C. 'Y Ruchardt went on to dispute42 the 1986 proposal of Katritzky that capto-dative stabilization is enhanced in polar solvents. The position of equilibrium (30) 2(31) (for X = OMe and Y = CN) was measured in mesitylene diphenyl ether ethylene glycol N-methylacetamide and succinic anhydride with only minor differences being found.41 H. Birkhofer J. Hadrich H.-D. Beckhaus and C. Ruchardt Angew. Chem. Int. Ed. EngL 1987,26 573. 42 H.-D. Beckhaus and C. Ruchardt Angew. Chem. Int. Ed. Engl. 1987 26 770.

ISSN:0069-3030    

DOI:10.1039/OC9878400081

出版商:RSC    

年代:1987

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 The synthesis of very long chain alkanes has been reported; chains of greater than 150 carbons undergo folding to the crystalline state. Methods for the synthesis of long chain alkanes with lateral side chains have also been developed. Throughout this work great emphasis was placed on the elimination from the reactants of minor constituents that would lead to unwanted by-products in the process of molecular doubling used to construct such systems.'-3 An interesting report of direct aliphatic fluorination has appeared! Careful fluorination at low temperature led to direct replacement of tertiary hydrogens; thus 3-methylnonane in 1 :1 CFCI3-CHCl3 at -78 "C afforded 3-fluoro-3-methylnonane (65% ).Protected alcohols of suitable structure e.g. p-nitrobenzoates also gave replacement products. Some selectivity was observed in the fluorination since the p-nitrobenzoate of 3,7-dimethyloctan-3-01 showed reactivity at the C- H remote from the ester function. A modified zeolite catalyst has been used in a study of alkane oxidation. Zeolite 5Acontaining either Fe" or Pd" acts as an inorganic mimic of the enzyme alkane-w- hydroxylase; for linear alkanes the primary :secondary oxidation ratio for the first three carbons is ca. 0.6.5 A further report of the Gif system for functionalization of saturated hydrocarbons has appeared with special reference to a cyclic system.6 The partial oxidation of methane (02-Si02) to form CH20 was contrasted with the complete oxidation achieved by N20.7 Regioselective photocatalysed formation of alk- l-enes from alkanes was noted when RhCI(CO)(PMe3)2 in an atmosphere of CO was used.8 Photolysis of bis- E.Igner 0.I. Paynter D. J. Simmonds and M. C. Whiting J. Chem. Soc. Perkin Trans. 1 1987. 2447. 'I. Bidd D. W. Holdup and M. C. Whiting J. Chem. SOC.,Perkin Trans. 1 1987 2455. E. A. Adegoke H. Ephraim Bassey D. J. Kelly and M. C. Whiting J. Chem. SOC.,Perkin Trans. I 1987 2465. 'S. Rozen and C. Gal 1.Org. Chem. 1987 52 4928. N. Herron and C. A. Tolman J. Am. Chem. SOC.,1987 109 2837. D. H. R. Barton J. C. Beloeil A. Billion J. Boivin J.-Y. Lallemand and S.Mergui Helu. Chim. Acta 1987 70 273. ' S. Kasztelan and J. B. Moffat 1.Chem. SOC.,Chem. Commun. 1987 1663. T. Sakakura T. Hayashi and M. Tanaka Chem. Lett. 1987 859. 93 94 B. K Smith diphosphine complexes of iron in the presence of e.g. pentane led to a mixture of pent-1 -ene and a bis-diphosphinepentenyl iron hydride.' Electrophilic conversions of methane have been reviewed." 2 Alkenes Synthesis.-Dehydration of 1-( p-alkoxyphenyl)-l,2-diphenylbutan-l-ols by CS and base is a stereoselective process in contrast to the acid-catalysed reaction. Thus (1) gave alkene with 2 E ratios of 21 1and 2 1 respectively. This selection was applied in the synthesis of 2-(2), Tamoxifen an anti-cancer drug whose activity is isorner- dependent.l1 Stereospecific deoxygenation of 1,2-diols via the 2-dimethylamino-l,3- dioxolane (3) and triflic anhydride in the presence of di-isopropylethylamine in toluene is an efficient process.12 No isomerization was detected during reaction; meso-dihydrobenzoin gave cis-stilbene in 85% yield and the (*)-isomer gave only the trans-alkene (94%).(11 (2) (3) Isotope labelling showed that the acid-catalysed isomerization of the 4-methyl group of 1,1,1,2,3,3-hexadeuterobutan-2-01between positions 1 and 4 occurs faster than dehydration to but-2-ene. l3 The results require that this isomerization occurs by hydride transfer as well as by hydration of the formed but-2-ene. Epoxides with iodine -Ph3P in moist MeCN form alkenes in good yields (>70%);the intermediate is presumed to be the i~dohydrin.'~ A simple efficient dehydrohalogenation of uic-dihalogenoalkanes was observed with silica gel and CCI4 in the dark; thus Ph,C(Br)CH2Br gave (lh) Ph,C=CHBr (96%).15 A general route to E-alkenes employs the sequence shown in Scheme 1.The method gave high yields and >99% isomer purity.16 A related route to E-1,2- R2 \ RI-CGC-X -i R1-x 2R1 B-OMe R' iiiuH n n n H BR H R2 H R2 X = Br or I Reagents i R$BH; ii NaOMe; iii H+(R3C02H) Scheme 1 M. V. Baker and L. D. Field J. Am. Chem. SOC. 1987 109 2825. 10 G. A. Olah. Acc. Chem. Rex 1987 20 422. " R. McCague J. Chem. SOC.,Perkin Trans. I 1987 1011. l2 J. L.King B. A. Posner K. T. Mak and N. C. Yang Tetrahedron Lett. 1987 28 3919. l3 P. E. Dietze and W.P. Jencks J. Am. Chem. SOC.,1987 109 2057. l4 L. Garlaschelli and G. Vidari Gazz. Chim. Ital. 1987 117 251. A. R. Suarez and M. R. Mazzieri J. Org. Chem. 1987 52 1145. l6 H. C. Brown D. Basavaiah S. U. Kulkarni H. D. Lee E. Negishi and J.-J. Katz J. Org. Chem. 1986 51 5270. Aliphatic Compounds -Part (i Hydrocarbons BBr2 R' Ri Reagents i R'ZnCI Pd'; ii R'X then base Scheme 2 disubstituted alkenes (Scheme 2) utilizes E-2-(bromoethenyl)dibromoborane(4) as an efficient prec~rsor.'~ By extension of the method synthesis of dienes and enynes was also realized with excellent isomer purities. There is still considerable interest in the Wittig and cognate reactions. Stereoselec- tion is one clear goal but modifications in method will be considered also.Stereo- control in the Horner-Wittig process has been usefully applied to the synthesis of specific en-01s." The known propensity of threo-(5) to form E-alkene by elimination of Ph2POS by action of base was exploited to prepare pure E-non-6-en-1-01 and E-dec-5-en- 1-01 which are pheromones. The Z-isomer of the latter compound was prepared from the erythro-precursor. Both these routes showed complete stereo- specificity. Extension of this approach was used as a route to E-/Z-trisubstituted alkenes and to Z-a-bisabolene (6) a perfume component. An extension of earlier work by Vedejs on the Wittig reaction of stabilized ylides has provided evidence against reversibility.'' The reactions studied provide evidence for kinetic control in reactions of aliphatic aldehydes and stabilized ylides.Addition of LiCH(PPh,)CO,Et to cyclohexanecarbo-aldehyde gave phosphines (7) and (8) (ca. 3 1); methylation of (7) (methyl triflate) and elimination of MePh,PO [using NaN(SiMe,),] gave the Z-alkene as major product. By using the labelled salt (9) it was concluded that deuterium-labelled Z-alkene (1 1) had been formed exclusively from an intermediate (10) by deprotonation at oxygen. The mixture of Z-and E-(11) which contained no deuterium was therefore considered to arise by a pathway FO2Et CO2Et ph2pYH Ph2p?H HOA HO+R k H H " S. Hyuga Y. Chiba N. Yamashima S. Hara and A. Suzuki Chem. Lett. 1987 1757. A. D. Buss N. Greeves R. Mason and S. Warren J. Chem. SOC.,Perkin Trans. 1 1987 2569.E. Vedejs T. Fleck and S. Hara J. Org. Chem. 1987 52 4637. B. V. Smith Me Me \ \ qO2Et Ph2PYD phzprD -O+H R involving dedeuteriation at the a-carbon. In no case was E-alkene containing a-D formed from (9). Therefore 'Wittig-reversal' is ruled out in this system and no other form of equilibration is occurring. It was surmized that an ylide such as Ph,P=CHCO,Et behaves in the same way as Ph,P(Me)=CHCO,Et which shows E-selectivity (95 :5) with C6H,,CH0 under kinetic control. Phosphorus ylides based on the dibenzophosphole ring system convert aldehydes into truns-disu bs t it u t e d ox a p h osp h e tan e s with good-to-excell en t se1e c tivity. Decomposition (70-1 10 "C) gave alkenes with E-/Z-ratios between 6 :1 and 100 :1 (see Scheme 3).,' A one-pot olefination of aldehydes utilizes an ylide derived from an allylic nitro-compound (12) and PBu,; addition of RCHO in the presence of base (BuLi) gave the product.21 R2 R ,R2 __* DBP -!+ DBP-Ph -!!+ DBP-Li DBP-0 DBP-0 Me VI VI 4 4 R' R' RZ DBP= opn% w \ / R2 Reagents i Ph4P+Br- LiNEt2; ii Li-THF; iii NaNH, 2eq.Et1 THF; iv R'CHO -78°C; v A 70°C (5-10 h) Scheme 3 Replacement of Ph3P by Ph2P(CH2)2C02H has been found to increase E-selec- tivity and produces a water soluble phosphine oxide Ph,P(O)(CH,),CO; in Wittig reactions.22 The use of solid-liquid systems for Wittig and Wittig-Horner (and Knoevenagel) reactions has shown that DMSO/MgO or HMPT/ZnO systems are effective catalysts for the Whig reactions and that MCl (M = Hg Cd) or ZnO are better for the Knoevenagel reaction.The E-/Z-ratio was however variable.23 20 E. Vedejs and C. Marth Tetrahedron Lett. 1987 28 3445. 21 R. Tamura M. Kato K. Saegusa M. Kakihana and D. Oda J. Org. Chem. 1987 52 4121. 22 H. Daniel and M. Le Corre Tetrahedron Lett. 1987 28 1165. 23 H. Moison F. Texier-Boullet and A. Foucaud Tetrahedron 1987 43 537. Aliphatic Compounds -Part ( i) Hydrocarbons The boron analogue of the Wittig reaction has shown interesting selectivity. Thus as shown in Scheme 4,appropriate choice of conditions can be used for production of E-or Z-isomers. An additional use of the intermediate (13) is as a precursor of erythro-1,2-di0ls.~~ Ar' iii Ar R u A HH I Ar H u n HR -f Reagents i ArCHO -78 "C THF; ii TFAA -1 10 "C;iii -110 "C 20 "C; iv Me,SiCI -78 "C; v aq.HF MeCN r.t.Scheme 4 A further attempt has been made to prepare tetra-t-butylethylene; reaction between (14) and an excess of Me2TiC12 gave only the bicyclic product (15).25 High E-/Z-ratios were reported for the olefination of aldehydes using a chromium reagent from a gem-di-iodoalkane and Cr"C12; thus C5H,,CH0 and MeCHI gave 94% of oct-2-ene (E/Z = 96 :4).26The modification of Peterson methylenation by using Ce"' helps to overcome the high basicity and lack of selectivity of the reagent Me3SiCH2Li and affords a useful route to methylene alkene~.~~ 24 A. Pelter D. Buss and E. Colclough J. Chem. Soc. Chem. Commun. 1987 297. 25 J.Dannheim W. Grahn H. Hopf and C. Parrodi Chem. Ber. 1987 120 871. 26 T. Okazoe K. Takai and K. Utimoto J. Am. Chem. Soc. 1987 109 951. 27 C. R. Johnson and B. D. Tait J. Org. Chem. 1987 52 281. B. V. Smith Regio-and stereo-selective coupling of 1,l-dichloroalk- 1 -enes with organo-magnesium or -zinc reagents may be achieved with catalysis by a palladium diphos- phine system. Coupling may be sequential; thus PhCH=CC12 affords first PhCH=C(Ph)Cl and then PhCH=CPh,.28 Other methods and products reported are decomposition of diazines in the presence of diazo-compounds leading to unsymmetrical hal~genoalkenes;~~ elimina-tion from glycolate and thioglycolate complexes of rhenium leading to simple alkene~;~' the palladium-mediated coupling of an aryl bromide and CH2=CHSnBu3 to form ArCH=CH2 31 (this method also allows use of functionalized aryl bromides); and the formation of 1-halogenoalk-1-enyl trimethyl~ilanes,~~ via use of LiNPr; Me3SiC1 and vinyl halides.The influence of hydrogen donor and temperature on the stereoselection of radical reactions has been considered. For the species (16) from PhC=CH and C6Hll the Z/E ratio reflects the difference in activation energy of hydrogen transfer; the 2-isomer is formed more easily.33 Me (Bu ')SiMS i(Bu ') Me2 The 'silicon alkene' R,Si=SiR has been prepared at low temperature. Oxidation (0,)gave an epoxide analogue and water added across the system.34 The hindered 2-1,2-bis-(t-butyldimethylsilyl)-1,2-bis(trimethylsilyl)ethylene ( 17) has been obtained.The central C=C bond length was measured as 1.369 A.An attempt to isomerize the double bond (24 E) was frustrated by decomposition of the material.35 Reactions.-Catalytic hydrogenation of olefins in biphasic water-liquid systems has been examined. A water-soluble catalyst derived from RhC13 and a tris-sulphonic acid based on triphenylphosphine allows reduction to take place at ordinary temperature and pressure.36 Ultrasound treatment of nickel powder generates a highly active hydrogenation catalyst capable of effecting reduction at atmospheric pressure. The increase in activity (estimated as a factor of lo5)was shown to arise from profound changes in surface structure rather than from an increase in surface area.37 A review of directed homogeneous hydrogenations has appeared.38 Enan- 28 A.Minato K. Suzuki and K. Tamao J. Am. Chem. Soc. 1987 109 1257. 29 M. P. Doyle A. H. Devia K. E. Bassett J. W. Terpstra and S. N. Mahapatro J. Org. Chem. 1987 52 1619. 30 W. A. Herrmann D. Marz E. Herdtweck A. Schafer W. Wagner and H.-J. Kneuper. Angew. Chem. Int. Edn. Engl. 1987 26 462. 31 D. R. McKean G. Parrinello A. F. Renaldo and J. K. Stille J. Org. Chem. 1987 52 422. 32 N. Shimizu F. Shibata and Y. Tsuno Bull. Chem. Soc. Jpn. 1987 60,777. 33 B. Giese J. A. Cionzilez-Gomez S. Lachheim and J. 0. Metzger Angew. Chem. Int. Edn. Engl. 1987 26 479. 34 S. Masamune Y. Eriyama and T. Kawase Angew. Chem. Znt. Edn. Engl. 1987 26 584. 35 H. Sakurai K. Ebata C. Kabuta and Y. Nakadaira Chem.Lett. 1987 301. 36 C. Larpent R. Dabard and H. Patin Tetrahedron Lett. 1987 28 2507. 37 K. S. Suslich and D. J. Casadonte J. Am. Chem. Soc. 1987 109 3459. 38 J. M. Brown Angew. Chem. Int. Edn. Engl. 1987 26 190. Aliphatic Compounds -Part (i) Hydrocarbons tioselective hydrogenation of allylic and homoallylic alcohols has been reported to occur in excellent yield and with high optical purities in the presence of the chiral catalyst (18).39 Thus geraniol gave citronellol in 97-100% yield (optical purity 96-98'/0). Use of (R) and (S) forms of the catalyst gave products of opposite enantioselectivity. Reduction of unsaturated (and cycloalkenyl) alcohols by LiAlH4 was studied as a function of solvent concentration and temperat~re.~' A number of papers have been published under the general heading of modelling chemical rea~tivity.~' They cover the regio- and stereo-chemistry of electrophilic addition to double bonds (especially in allylic systems) facial selectivity in Diels- Alder reactions and reactivity and stereoselectivity of chiral allylic alcohols and ethers and alkenes in electrophilic addition.The role of surfaces in the addition of HC1 to a simple alkene42 and in the production of alkyl iodides and vinyl iodides (from 12-alumina)43 has been stressed. Supported reagents enter into a facile selective two-phase addition to alkenes in which supported MX (M = Na K; X = SCN N3 OAc) and 12-CHC13 give high yields of adduct at room temperature; typically PhCH=CH2 gave PhCH(SCN)CH,I (79%).44 Evidence has been presented supporting the occurrence of a reversible step in electrophilic br~mination.~~ Reaction of erythro- and threo-2-bromo- 1,Z-diphenyl-ethanol with gaseous HBr (in C1CH2CH2Cl and CHC1,) gave intermediates which collapsed to form rneso-l,2-dibromo-l,2-diphenylethane; some release of bromine led to the production of trans-stilbene.cis-Stilbene was not produced in this way. Thus as shown in Scheme 5 the erythro-isomer (19) has a favourable arrangement of anti-phenyl groups such that protonation and bromine-induced loss of water can occur easily to generate (20). With the threo-isomer an unfavourable conformation would have to be achieved for such a process and hence cis-stilbene is not produced. Significantly the addition of bromine to both olefins was shown not to be stereo- specific and isomerization of cis-stilbene at incomplete conversion was confirmed.Detailed examination of product distributions of dibromides formed from the bromohydrins and from direct addition showed that the ratios of formed dibromides 39 H. Takaya T. Ohta N. Sayo H. Kumobayashi S. Akutagawa S. Inoue 1. Kasahara and R. Noyori J. Am. Chem. SOC.,1987 109 1596. 40 M. Vincens R. Fadel and M. Vidal Bull. SOC.Chim. Fr. 1987 462. 41 W. J. Hehre et al. J. Am. Chem. SOC., 1987 109 650 663 666 672. 42 J. Tierney F. Costello and D. R. Dalton J. Org. Chem. 1986 51 5191. 43 L. J. Stewart D. Gray R. M. Pagni and G. W. Kabalka Tetrahedron Lett. 1987 28 4497. 44 T. Ando J.H. Clark D. G. Cork M. Fujita and T. Kimura J. Chem. SOC.,Chem. Commun. 1987 1301. 45 G. Bellucci C. Chiappe and F. Marioni J. Am. Chem. SOC.,1987 109 515. 100 B. V. Smith I Br H Ph Conditions i H+,-H,O;ii -Br2; iii collapse of ion pair; iv +Br (unless removed) Scheme 5 were different; this is contrary to the expectation based on a common bridged intermediate. However the complete suppression of formation of (*)-dibromide in reaction of (19) with HBr argues that the reverse reactions of the trans-bromonium bromide ion-pair in Scheme 5 proceeds to a higher extent than might be inferred on the basis of recovered olefin. The isomerization (cis + trans) was rationalized in a similar way. Caesium fluoroxysulphate has been advocated for simple fluorination of alkene~.~~ Although some specificity (syn-addition) was noted for E-alkenes the 2-isomers gave non-stereospecific reaction.A convenient method for conversion of (cyc1o)alkenes into trans-fluoroiodo-derivatives uses the reagent I+( collidine),BFi ; the process is regio- and stereo-~pecific.~' Alkenes form vicinal fluoroiodides with polymer-supported HF in the presence of N-iodosuccinimide. The reaction exhibits Markovnikov-type regioselectivity and anti-stereospecificity and good yields are obtained; addition to alkynes is also In the presence of Mn"' acetate and chloride ions formation of either dichloro-adducts or monochloro(rep1acement) products occurs with a$ -unsaturated esters.49 The peroxide-mediated addition of a-bromoacids to alkenes leads to 4-alkanolides probably via a free-radical route.50 Synthetically valuable allylic sulphones have been prepared by iodosulphonylation of alkenes followed by treatment of the adduct with base.5' Hydration of terminal alkenes with Cl,AlH 02,and a catalytic quantity of PhB(OH) gives good yields of primary alcohols; e.g.,dodec-1-ene afforded dodecan- 1-01 (75%).52 There is still considerable interest in epoxidation reactions.Two papers explore the theoretical aspects; the first concentrates on the role of 0x0-iron p~rphyrins~~ and the second analyses the electronic and steric factors which determine the course of the asymmetric (Sharpless) epoxidation of allylic alcohols.54 46 S. Stavber and M. Zupan J. Org. Chem. 1987 52 919 47 R.D. Evans and J. H. Schauble Synfhesis 1987 551. da A. GregorCiC and M. Zupan Bull. Chem. SOC.Jpn. 1987 60,3083. 49 H. Yonemura H. Nishino and K. Kurosawa Bull. Chem. SOC.Jpn. 1987 60,809. 50 T. Nakano M. Kayarna and Y. Nagai Bull. Chem. SOC.Jpn. 1987 60 1049. 51 K. Inomata S. Sasaoka T. Kobayashi Y. Tanaka S. Igarashi T. Ohtani H. Kinoshita and H. Kotake Bull. Chem. SOC.Jpn. 1987 60 1767. 52 K. Maruoka H. Sano K. Shimoda and H. Yamarnoto Chem. Lerr. 1987 73. 53 K. A. J~rgensen,J. Am. Chem. SOC.,1987 109 698. 54 K. A. Jergensen R. A. Wheeler and R. Hoffrnann J. Am. Chem. Soc. 1987. 109 3240. Aliphatic Compounds -Part (i) Hydrocarbons 101 Incorporation of 3A or 4A molecular sieves into the methodology increases the scope of the asymmetric epoxidation of primary allylic alcohols.55 High conversion (>95%) and high e.e.(90-95%) was realised. In some cases cumene hydroperoxide was substituted for the usual t-BuOOH. Sharpless has explored the idea of in situ derivatization of low molecular weight water-soluble products of such reactions. Epoxidation of alkenes with dimethyl dioxirane shows sensitivity to steric factors; cis-alkenes are generally more reactive (8-10 times) than their trans-anal~gues.~~ Among other methods reported the cobalt-catalysed reaction of t-BuOOH and iodo~ylbenzene,~~ and the haemin-catalysed process (with some rearrar~gement),~~ the manganese porphyrin-t-BuOOH system59 may be mentioned. Inter-and intra-molecular epoxidation has been accomplished using silyl- protected peroxyesters and a copper salt.60 Thus oct-2-ene gave 83% of epoxide; all trans-farnesol gave a mixture of epoxides (82%; 6,7 10,ll = 1:4.5) but by changing conditions the amount of 6,7-epoxide was increased markedly.Sodium hypochlorite in the presence of alumina or montmorillonite smoothly epoxidizes alkenes which carry two electron-withdrawing groups.6' Cation radical-catalysed oxygenation of alkylated olefins (and dienes) has been reviewed.62 Conversion of an alkene into a primary amine is efficiently performed using a hydroboration (Me,BH)-amination (NH20S03H) sequence.63 Tosylisocyanate serves as a convenient equivalent for hydr~xyamination.~~ Sulphonation of oct-1-ene has been shown to furnish a p-sultone with one molar equivalent of SO,; with an excess of SO, a carbyl sulphate is produced.65 Similar work provided evidence for formation of these species as judged by n.m.r.evidence.66 Hydrocyanation in an anti-Markovnikov sense has been noted for an organozir- conium-mediated process as shown in Scheme 6.67Hydroformylation of phosphine- bearing terminal alkenes can lead to a reversal of regioselectivity (with respect to simple alkenes) in the presence of a rhodium catalyst.68 Synthesis of simple acids (and esters) from coupling of alkenes and COz brought about by zerovalent metal catalysts has been explored.69 Erythro-selective addition of PhSeH to E-nitroalkenes gave an intermediate which by elimination of benzeneselenic acid afforded the Z-i~omer.~~ Intramolecular palladium-catalysed cyclization of terminally unsaturated esters has been used as a route to large-ring lac tone^.^^ 5s Y.Gao R. M. Hanson J. M. Klunder S. Y. KO H. Masamune and K. B. Sharpless J. Am. Chem. SOC.,1987 109 5765. 56 A. L. Baumstark and C. J. McCloskey Tetrahedron Lett. 1987 28 3311. 57 J. D. Koola and J. K. Kochi J. Org. Chem. 1987 52 4545. 58 T. G. Taylor and A. R. Miksztal J. Am. Chem. SOC.,1987 109 2770. 59 P. N. Balasubramian A. Sinha and T. C. Bruice J. Am. Chem. SOC.,1987 109 1456. 60 1. Saito T. Mano R. Nagata and T. Matsuura Tetrahedron Lerr. 1987 28 1909. 61 A. Foucaud and M. Bakouetila Synthesis 1987 854. 62 S. F. Nelsen Acc. Chem. Res. 1987 20 269. 63 H. C. Brown K.-W. Kim M. Srebenik and B.Singaram Tetrahedron 1987 43 4071. 64 B. M. Trost and A. R. Sudhakar J. Am. Chem. Soc. 1987 109 3792. 65 B. H. Bakker and H. Cerfontain Tetrahedron Lett. 1987 28 1699 1703. 66 D. W. Roberts P. S. Jackson C. D. Saul and C. J. Clemett Tetrahedron Lett. 1987 28 3383. 67 S. L. Buchwald and S. J. La Maire Tetrahedron Lett. 1987 28 295. 68 W. R. Jackson P. Perlmutter and G.-H. Suh J. Chem. SOC.,Chem. Commun. 1987 724. 69 H. Hoberg K. Jenni K. Angermund and C. Kriiger Angew. Chem. Int. Edn. Engl 1987 26 153. 70 N. Ono A. Kamimura T. Kawai and A. Kaji J. Chem. SOC.,Chem. Commun. 1987 1550. 71 J. K. Stille and M. Tanaka J. Am. Chem. SOC.,1987 109 3785. 102 B. V. Smith R3 R' ii Cp,Zr(H)Cl Cp,Zr(Cl)/\r -RZ Cp2Zr Reagents i CH,=CR'R'; ii R3NrC; iii I2 Scheme 6 Donor-acceptor interactions as probed by olefins have been reviewed.72 It has been inferred that the similar rates of hydroboration and oxymercuration of alkenes point to similar steric requirements in the transition states of reaction.73 3 Polyenes Synthesis.-A stereocontrolled chemoselective synthesis of diene (and enyne) sys- tems relies on the palladium-catalysed coupling reaction between an alkenyl iodide and an alkynyl ~tannane.~~ High yields of conjugated enynes were obtained which furnished dienes in high isomer purity.By this route the pheromones 52,7E-dodeca- 5,7-dien-l-ol and the 5E,7Z-isomer were prepared in a high state of purity as shown in Scheme 7. A very general method for all possible geometric isomers of a 1,3-diene is the palladium-catalysed cross coupling of an E-or 2-vinyl halide with an E-or 2-vinylstannane; the geometry of each partner is reproduced in the product diene.75 The reaction is tolerant of functional groups in either partner and constitutes an extremely versatile and valuable method.By this methodology 2-l-iodohex-l-en-6-01 and E-1-trimethylstannylhex-1-enegave the 52,7E-isomer of the above named pheromone directly in 73% yield. A synthesis of dienes shown in Scheme 8 has I J Bu-E-SnMe3 + 1 1(cH2)40THP -../i-'i\ (CH2)rOH Reagents i (MeCN),PdCI, THF 22 "C; ii (Sia),BH; iii AcOH; iv NaOH H202; v Hf Scheme 7 '' Z. V. Todres Tetrahedron 1987 43 3839. 73 D. J. Nelson P. J. Cooper and J. M. Coerver Tetrahedron Lett.1987 28 943. 74 J. K. Stille and J. H. Simpson J. Am. Chem. Soc. 1987 109 2138. 75 J. K. Stille and B. L. Groh J. Am. Chem. Soc. 1987 109 813. 103 Aliphatic Compounds -Part ( i) Hydrocarbons Reagents i CH,=C(Me)MgBr THF 0°C; ii CrO, CSHsN; iii Me2C(SePh), BuLi THF -78°C; iv S0Cl2 2eq. Et,N CH2C12 r.t. Scheme 8 been published.76 Stereo-defined synthesis of conjugated dienes (and arylated alkenes) rests upon the Pd- or Ni-catalysed coupling of an alkenyl or aryl iodide with an alkenyl metal (M = Al Zr Zn).77 The palladium catalyst gave very high stereospecificity; with nickel partial scrambling was observed. Thus for E -C,H,,CH=CHAIBu; and 2-C,H9CH=CHI the formed diene showed isomer purity >98%. The [3-(diphenylphosphino)allyl]titanium reagent formed as shown in Scheme 9 reacted with aldehydes regio- and stereo-specifically to give 1,3-diene~.~~ OTiL, Reagents i Bu'Li; ii Ti(OPr'),; iii RCHO; iv Me1 Scheme 9 The intermediate invoked to explain such selectivity is chair-like (21); by changing reagent to that derived from Ph,P(O)CH(Me)CH=CH a higher yield of diene with greater E-selectivity was obtained compared to that from Ph2P(0)CH2CH=CH2.It was inferred that (22) was responsible for such selection. These methods taken together thus form useful additions to synthetic routes in the diene field. Extension of this approach as a route to a 1,4-dialkyl-1,3-diene was also described. WMe) &-PPh2 LnTi-'C-R H I 0-b L ,i.i.+6-R IH (21 1 (22) An interesting silicon-directed diene synthesis is shown in Scheme Another approach to 2,E-conjugated dienes uses a stepwise process in which an a#-unsaturated aldehyde is generated from [Ph,AsCH2CHO]+Br-and RCHO in good- to-excellent yield; a Wittig reaction with BuLi in HMPA-THF led to the desired diene.80 This route also gave an entry into the dienols and derivatives which are 76 R.V. Bonnert and P. R. Jenkins J. Chem. SOC.,Chem. Commun. 1987 1540. 77 E. Negishi T. Takahashi S. Baba D. E. Van Horn and N. Okukado J. Am. Chem. SOC.,1987,109,2393. 78 Y. Ikeda J. Ukai N. Ikeda and H. Yamamoto Tetrahedron 1987 43 723 731. 79 P. A. Brown R. V. Bonnert P. R. Jenkins and M. R. Selim Tetrahedron Lett. 1987 28 693. 80 Y.-Z. Huang L. Shi J. Yang and Z. Cai J. Org. Chem.1987 52 3558; cf Tetrahedron Lett. 1985 26 6447. 104 B. V. Smith Reagents i Me,SiCH,MgCl; ii PCC; iii &MgBr; iv AcOH AcONa Scheme 10 pheromones. Facile stereoselective synthesis of conjugated E,E-dienes including those carrying amine silane and stannane groups has also been reported as another variation of the theme.81 Self-coupling of an alkenyl stannane (23) [Pd(OAc), Bu'OOH-C,H,] led to a 1,3-diene whereas cross-coupling with an ally1 stannane (24) led to a 'methylene- interrupted' (non-conjugated) diene (25).82 R' R' --SIlR Successive treatment of a hindered alkene with BH,-THF (to form R,BH) followed by reaction with 1,4-dichlorobut-2-yne and alkyl-lithium gave 2-alkylbuta-l,3-dienes (see Scheme ll).83 R' CICH2CECCH2CI + c1 1iii L9 R'R2B R' H Reagents i RiBH; ii R'Li; iii -LiCI Scheme 11 Efficient and stereospecific syntheses of various dienyl alcohols have been presen- ted.A Wittig sequence involving an E-oxidoallylic phosphorane and an aldehyde R2CH0 led to dienol (26) as major product.84 In a related process a zirconium- mediated Wittig rearrangement followed by Peterson elimination was exploited to produce 2E,4Z-dienols (see Scheme 12).85 1-Oxygenated E,E-dienes have been T. Ishii N. Kawamura S. Matsubara K. Utimoto S. Kozima and T. Hitomi J. Org. Chem. 1987 52 4416. " S. Kanemoto S. Matsubara K. Oshima K. Utimoto and H. Nozaki Chem. Lett. 1987 5. 83 A. Arase and M. Hoshi J. Chem. SOC.,Chem. Commun. 1987 531. 84 A. Hosoda T. Taguchi and Y.Kobayashi Tetrahedron Lett. 1987 28 65. 85 S. Kuroda T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1987 28 803. Aliphatic Compounds -Part (i) Hydrocarbons R$i 0 ii iii *yOH 2R:Siq OH __* R:Si R2 R2 A R2 1iv v vi OH OTHP Reagents i Redal; ii BrCH2C02H;iii Me,CHI; iv LDA-THF; v Cp2ZrC12;vi DHP PTSA; vii LAH then H+; viii NaH Scheme 12 CO2Et OLi OLi 0~3 R15 i __* I - + R2 R' ii R,< iii Rl( R* R2 R2 [R3= SiMe or Ac] Reagents i LiCHBrz THF/TMP Bu"Li -78 "C + r.t.; ii LiH THF A; iii Me,SiCI or Ac,O Scheme 13 prepared stereospecifically from cqP-unsaturated esters in a one-pot reaction (see Scheme 13).86The reaction of 2,5-dihydroxythiophen S,S-dioxides and a carbonyl compound may lead to a-hydroxydienes such as (27) (X = Ph) or 28 (X = Me) after ring cleavage of the first-formed add~ct.~' The phenyl group (27) and the methyl group (28) were situated at C-3 in the ring.By this approach the naturally occurring E-tagetone (29) was prepared in a three-step process. x 86 C. J. Kowalski and G. S. Lal Tetrahedron Lert. 1987 28 2463. 87 S. Yamada H. Suzuki H. Naito T. Nomoto and H. Takayama J. Chem. SOC.,Chem. Cornmun. 1987 332. 106 B. V. Smith Synthesis of 2-alkylthiobuta- 1,3-dienes has been reported.88 1-Phenylthioalka-l,3- dienes (and 1,3,5-trienes) were obtained by cross-coupling either E-or 2-2-bromo-l- phenylthioalk-1-enes with alk-1-enyl or alka-1,3-dienyl-1,3,2-benzodioxaboroles in the presence of Pd(PPh3)4; excellent yields were obtained e.g.96% for (30).89 1,3-Dienes containing an allylic sulphone moiety have been characterized." Butadienes carrying a 1-dirnethylamino-gro~p~~ and captodative substituents9* have been prepared. A stereocontrolled approach to olefins and methylene-interrupted dienes relies upon the mediation of allylcerium corn pound^.^^ Several examples were given of this method which has the advantage of working smoothly with systems containing cis-double bonds. Thus (31) (whose acetate is found in certain algae) was synthesized in acceptable yield. Molybdenum hexacarbonyl has been shown to couple allylic acetates to produce 1,5-dienes; 2,2'-bipyridyl accelerated the rate of reaction.94 In such a process 3-acetoxyoct-1-ene gave hexadeca-6,lO-diene (48%) and 9-vinyl- tetradec-6-ene (52%) in 54% overall yield.Several examples have been given of nitrone cycloaddition and deamination sequences which led to E,E-1,5 -diene~.~~ 1,2-Dienes are formed in the palladium-catalysed hydrogenolysis of 3-methoxycar- bonyloxyalk-1-ynes (32) with ammonium formate in DMF.96 Allenyl silanes were produced from an N-phenylcarbamate e.g. (33),by sequential treatment with MeLi CuI and PhMe,SiLi to form (34).97 Elimination of Bu3Sn and OH from p-hydroxyvinylstannanes (35) by CF3S03H-THF gave the trimethylsilyldienes (36) in excellent (>go%) yields. The products (36) could be converted into 1,3-dienes with further acid treatment.98 Routes to cross-conjugated mono- and di-allenes have been explored.99 R2 R'X°Co2Me,@ KONHPh n8 M.Hoshi Y. Masuda and A. Arase J. Chem. SOC.,Chern. Commun. 1987 1629. 89 T. Ishiyama N. Miyaura and A. Suzuki Chem. Lett. 1987 25. 90 K. Hayakawa M. Takewaki I. Fujimoto and K. Kanematsu J. Org. Chem. 1986 51 5100. 9' B. Potthoff and E. Breitmaier Chem. Ber. 1987 120 255. 92 N. StCvenart-De Mesmaeker R. MerCnyi and H.G. Viehe Tetrahedron Lett. 1987 28 2591 93 €3.-S.Guo W. Doubleday and T. Cohen J. Am. Chem. SOC.,1987 109 4710. 94 Y. Masuyama H. Hirai Y. Kurusu and K. Segawa Bull. Chem. SOC.Jpn. 1987 60,1525. 9s J. J. Tufariello and A. S. Milowsky Tetrahedron Lett. 1987 28 263. 96 J. Tsuji T. Suguira and I. Minami Synthesis 1987 603. 97 I. Fleming K. Takaki and A. P. Thomas J. Chem. Soc. Perkin Trans. 1 1987 2269. 98 C.Nativi A. Ricci and M. Taddei Tetrahedron Lett. 1987 28 2751. 99 F. Lehrich and H. Hopf Tetrahedron Lett. 1987 28. 2697. Aliphatic Compounds -Part ( i) Hydrocarbons A stereoselective (98.2% ) route to 3 E,SZ-undeca-l,3,5-trienehas been realized via palladium-catalysed coupling of hept-1-ynyl zinc chloride and E-or 2-1,2-dibromoethene to form (37) in the first instance; (37) was then elaborated into (38) by sequential coupling with CH,=CHZnCl hydroboration of the product and generation of (38).'0° A related method for undeca-l,3,5-trienes relies on a sequence of coupling reactions mediated by Pdo-Cu' and Nio respectively."' Wittig coupling of oxiranylprop-2-enal (39) and RCH=PPh3 gave (40); (40) uia the episulphide and elimination formed triene (41) and by this approach fucoserratene [(41) R' = Et] was synthesized.Treatment of (40) with NaIO gave a dienal (42).'02 (37) (38) A number of methods were used in an assault on the synthesis of polyene pheromones of lepid~ptera."~ Reactions.-Addition of trifluoroacetyl nitrate to 1,3-dienes afforded a mixture of 1,2- and 1,4-nitrotrifluoroa~etates.~~~ Treatment of these adducts (KOAc or NaH) formed 1-nitro- 1,3-dienes which in turn underwent nucleophilic addition with PhNH2or PhSH-Et,N in ether. From l-nitrobuta-1,3-diene the major product from the latter example is (43). Functionalization of 2-(phenylsulphonyl)-1,3-dienesgives via Michael addition allylic sulphones which can enter irlto further nucleophilic addition catalysed by palladium or promoted by c~prates;"~ a range of compounds was prepared from those versatile starting materials.Sterically hindered manganese-containing porphyrins act as shape-selective catalysts for epoxidation of a range of dienes;Io6 analysis of product ratios suggests that there may be two pathways in such a process. An unusual reaction is the addition of a P-ketoacid to the monoepoxide of a 1,3-diene with decarboxylation; thus the monoepoxide of buta-l,3-diene and 3-oxopentan-l,5-dioic acid gave (44) (73% ; E/Z = 5 :2).'07 Ozonolysis of 2-chloro-3-methylbuta-l,3-diene gave (45) preferentially (>90% ).lo8 I00 B. P. Andreini M. Benetti A. Carpita and B. Rossi Terrahedron 1987 43 4591; cJ Tetrahedron Lett. 1986 27 4351. 101 V. Ratovelomanana and G.Linstrumelle Bull. SOC.Chim. Fr. 1987 174. I02 M. Goldback E. Jakel and M. P. Schneider J. Chem. Soc. Chem. Commun. 1987 1434. 103 H. J. Bestmann K. Roth K. Michaelis 0.Vostrowsky H. J. Schafer and R. Michaelis Liebigs Ann. Chem. 1987 417. 104 A. J. Bloom and J. M. Mellor J. Chem. Soc. Perkin Trans. 1 1987 2737. 105 J.-E. Backvall and S. K. Juntunen J. Am. Chem. SOC.,1987 109 6396. 106 K. S. Suslick and B. R. Cook J. Chem. SOC.,Chem. Commun. 1987 200. 107 T. Tsuda M. Tokai T. Ishida and T. Saegusa J. Org. Chem. 1986 51 5216. 108 K. Griesbaum and M. Meister Chem. Ber. 1987 120 1573. 108 B. V. Smith C1 R -No2 SPh Dimethyl(2,3-dimethylene)butane-l,4-dioatereadily takes part in a Diels-Alder reaction with an inverse electron demand.'" Addition of acryloylferrocene to 1- phenylbuta-l,3-diene is promoted by montmorillonites in which a certain amount of ionic replacement has occurred."' The role of metal reagents in stereo- and regio-selective functionalization of conjugated dienes has been reviewed.' '' Alkyl dichloro- and trichloro-acetates add to buta-l,3-diene under the influence of copper complexes e.g.with 1,lO-phenanthro- line.Trichloroacetates gave 1 :1 adducts (derived from 1,2-and 1,4-addition); generally the reactivity was higher for trichloro-substitution but was diminished by increasing length of the alkyl chain in the ester.'12 4-Bromo-2-sulpholenes serve as butadienyl cation equivalents and permit reaction with cup rate^."^ Thus (46) with Ph,CuLi then Et3N gave (47) in excellent yield and thereby 2-phenylbuta- 1,3-diene as the sole product.The following observations were published in 1987. Selective reduction of non- conjugated dienes uses H2-Pd-PhCH,CHO; virtually no saturated product was formed.' l4 The thermal rearrangement of 3-fluoro-hexa-1,5-diene shows no dramatic effect due to the fluorine atom.' l5 Acetoxybromodienes with remote double bonds are smoothly cyclized by Pdo- RiSnAlR; (to vinylcycloalkenes).' l6 A remarkable double diastereoselection was observed in iodolactonization of the hepta- 1,6-dien-4- oic acid derivative (48)."' The major product (49) was formed with group and face selectivity. 3-Alkyl- and 3,3-dialkyl-l-bromo-1,2-dienes react with organocuprates to yield either a terminal alkyne or an allene."* To some extent this depends on the cuprate used and refutes an earlier claim by Landor that only allene was formed.When R(CN)CuLi or RCuBr.MgLiX was used alkyne was obtained if R was a straight chain group; a tertiary group on the other hand favoured formation of allene in excellent yields. Although use of Ph(CN)CuLi gave allenes (70-80%) the use of 109 C. Grundke and H. M. R. Hoffmann Chem. Ber. 1987 120 1461. 110 S. Toma P. EleEko J. Gaiova and E. SolEaniovL Collect. Czech. Chem. Commun. 1987 52 391. 111 J.-E. Backvai Bull. Chem. SOC.Fr. 1987 665. 112 Z. Vit and M. Hajek Collect. Czech. Chem. Commun. 1985 52 1280. 113 T. Chou S. C. Hung and H.-H. Tso 1. Org. Chem. 1987 52 3394. 114 S.Nishimura M. Ishibashi H. Takamiya N. Koike and T. Matsunaga Chem. Lett. 1987 167. 115 W. R. Dolbier Jr. A. C. Alty and 0. Phanstiel IV J. Am. Chem. SOC.,1987 109 3046. 116 B. M. Trost and R. Walchli J. Am. Chem. Soc. 1987 109 3487. 117 M. J. Kurth and E. G. Brown J. Am. Chem. Soc. 1987 109 6844. 118 A. M. Caporusso C. Polizzi and L. Lardicci Tetrahedron Leu. 1987 28 6073. Aliphatic Compounds -Part (i) Hydrocarbons Ph( CuBr)MgBrLiBr gave excellent yields of phenyl-substituted alkynes. The stereochemistries of both processes were also examined. The nature of the di-lithium allenide from 1,1,3,3-tetraphenylallenehas been investigated and there is some evidence for the existence of two equilibrating structure^."^ Intramolecular addition of the OH group of a hemiacetal to an allene has been observed.'20 Allenic carboxylates and lactones undergo thermally induced 1,3 hydrogen shifts in the presence of CO~(CO)~ .121 Thus Ph2C=C=C(Me)C02R' (R' = Me or Et) gave initially Ph2C=CH-C(C0,R')=CH2 which subsequently entered into Diels- Alder cycloaddition.Lipase-mediated resolution of allenic alcohols generally gave low yields but in some cases the optical purity was high.'22 The reaction with acid R'C02H was carried out in hexane as 'solvent' with a lipase preparation obtained from a microbiological source (Candida cylindracea). This interesting reaction worked best for hindered alcohols; thus whilst (50a) R2 = Me R3 = Et R" = R5 = H) gave recovered alcohol of very low optical purity (<5%) the related (50b) (R2 = H R3 = R4 = R5 = Me) gave optical purity in the recovered alcohol of 70% albeit in low yield (12%).Allenes with an aldehyde RCHO enter into a photoreaction in the presence of Fe(C0)5to form trimethylenemethane tricarbonyl iron c~mplexes.'~~ Allenic nitriles with a diamine or aminoalcohol enter into Michael addition; the product eliminates MeCN at 300 "C forming a pyrimidine or oxazine deri~ative.'~~ Methylene ketenes R'R2C=C=C=0 have been obtained by treating R'R2C=C(Br)COCl with Mn(C0); at -78 "C; dimerization (by cycloaddition) was observed.'25 Two unusual trimers of diketene were prepared by interaction with Me,SiI .l 26 The spontaneous cyclodimerization of the butatriene (51)leads to the cyclobutane (52).'27 RZ Oxidation of 3,6-di-t-butyl-2,2,7,7-tetramethylocta-3,4,5-triene with MCPBA gave a methylenecyclopropanone as principal product.'28 An analogous methylene- cyclopropanone with P2S5 in pyridine gave a mixture containing some butatriene episulphide together with the triene Bu\C=C=C=CBu\ .129 I19 A.Rajca and L. M. Tolbert J. Am. Chem. SOC. 1987 109 1782. I20 N. 0. Nilsen L. Skattebd and Y. Stenstram Acta Chem. Scand. Ser. B 1987 40 459. I21 L. S. Trifonov A. S. Orahovats and H. Heimgartner Helu. Chim. Acta 1987 70 1070. 122 G. Gil E. Ferre A. Meou J. Le Petit and C. Triantyphylides Tetrahedron Lett. 1987 28 1647. 123 R. Aumann H.-D. Melchers and H.-J. Weidenhaupt Chem. Ber. 1987 120 17. I24 T. Z. Fozum A. Johnson S. R. Landor P.D. Landor J. T. Mbafor and A. E. Nkeng-fack J. Chem. Res.(S) 1987 188. 12s A. P. Masters T. S. Sorensen and P. M. Tran Can. J. Chem. 1987 65 1499. I26 I. Ernst H. Fritz and G. Rihs Helu. Chim. Acta 1987 70 203. I27 M. Kaftory I. Agmon M. Ladika and P. J. Stang J. Am. Chem. Soc. 1987 109 782. 128 J. K. Crandall G. E. Salazar and R. J. Watkins J. Am. Chem. Soc. 1987 109 4338. 129 W. Ando H. Hayakawa and N. Tokitoh Tetrahedron Lett. 1987 28 1803. 110 B. V. Smith 4 Alkynes Synthesis.-An efficient synthesis of 1-t-butoxyethyne relies on sequential addition of K0Bu'-Bu'OH and then Br to C2H2; elimination of HBr from BrCH,CH(Br)OBu' gave the desired pr~duct.'~' Sodium acetylides and I+(py),BF react smoothly to give good-to-excellent yields of l-i~doalkynes.'~' Chiral (S)-1-alkynyl-p- tolylsulph- oxides (53)have been prepared in high yields from an alkynyl magnesium bromide and (S)-(-)-menthyl-p-t~luenesulphinate.'~~ Stereoselective reduction of the alkyne furnished either an E-alk-1-enyl-( R)-sulphoxide (LAH-THF) or the 2-(R)-isomer [RhCl( PPh3)3-C6H6-H2].These are useful materials in synthesis. The preparation and characterization of the sulphonates R'CECOR' (R2 = S02Ar or S0,Me) has been rep01-ted.l~~ The synthesis of 1-nitro-2-(trialkylsilyl)alkyneshas been effected via nitronium salt nitration of suitable alkyne These compounds not surprisingly enter into Diels- Alder reactions e.g. with cyclopentadiene. Gentle thermolysis of 2,5-dialkynyl-3,6-diazido-1,4-benzoquinonesleads to an alkynylcyanketene (RC=C-C(CN)=C=O) which is reactive in cycloaddition and towards an alcohol (generating a cyanoallene ester).'35 A metal-mediated approach to enynes employs a palladium catalyst in the presence of a sterically hindered phosphine tris(2,6-dimethoxyphenyl)-phosphine.This method was used for coupling PhCECH and MeC=CCO2Me to form (54)and gave an excellent yield (92%); the role of the phosphine and the probable mechanism were disc~ssed.'~~ 0 (53) (54) Stannylation of 1-trimethylsilyl- 1,3-diynes has been developed for the synthesis of enynes (and dienes and alkene~).'~' Treatment of the diyne with 2.5eq. of (trimethylstanny1)copper in THF gave E-l-trimethylsilyl-3,4-bis(trimethyl-stannyl)alk-3-en-l-ynes.Transmetallation (MeLi) then produced enynyl lithium reagents which with electrophiles produced stereo-defined tri- and tetra-substituted enynes containing the reactive Me3Si group.Equally valuable was the transforma- tion via hydroalumination into 1-trimethylsilylbuta-1,3-dienes and the hydrobor- ation-oxidation sequence affording unsaturated acids. A one-pot synthesis of fluoroenynes has been reported in which an 'eliminative nucleophilic addition' forms a key step.'38 The lithioalkyne R'CECLi is added to 130 M. A. Pericas F. Serratosa and E. Valenti Tetrahedron 1987 43 2311. 131 J. Barluenga J. M. Gonzalez M. A. Rodriguez P. J. Campos and G. Asensio Synthesis 1987 661. 132 H. Kosugi M. Kitaoka K. Tagami A. Takahashi and H. Uda J. Org. Chem. 1987 52 1078. 133 P.J. Stang B. W. Surber Z.-C. Chen K. A. Roberts and A. G. Anderson J. Am. Chem. SOC.,1987 109 228. 134 R. J. Schmitt J. C. Bottaro R. Malhotra and C. D. Bedford J. Org. Chem. 1987 52 2294. 135 N. V. Nguyen K. Chow and H. W. Moore J. Org. Chem. 1987 52 1315. 136 B. M. Trost. C. Chan and G. Ruhter J. Am. Chem. SOC.,1987 109. 3486. I37 G. Zweifel and W. Leong J. Am. Chem. SOC.,1987 109 6409. 138 Y. Shen and W. Qiu J. Chem. SOC.,Chem. Cornmun. 1987 703. Aliphatic Compounds -Part (i) Hydrocarbons 111 the ketophosphonium compound Ph3PC( R2R3)CORf and with elimination of Ph,PO the enyne R2R3C=C(Rf)C=CR' is formed; with R' = R2 = Ph R3 = Me Rf = C2F5,44% of enyne (E/Z = 98/2) was produced. Symmetrically substituted 1,3-diynes (and dienes) were obtained in the copper( 11) nitrate-mediated coupling of organotins in THF.'39 By extension of this method symmetrical biaryls were synthesized.Finally the preparation of five naturally occurring polyacetylenes have been de~cribed.'~' Reactions.-The absolute configuration of (+)-But( Me)C(OH)C=CH. has been reassigned as (S) on the basis of chemical correlation with (S)-Bu'CH(OH)C_CH by applying an organocopper( I) reaction of known anti-stereochemistry." The value of chiral acetylenes as synthetic intermediates has been shown in the prepar- ation of chiral isoxazoles and pyrazole~.'~~ A copper( 1) hydride species prepared in situ from NaBH,-MgBr2-Et3N-CuC1 or NaH-MgBr,-CuC1 converts terminal alkynes cleanly into E,E-1,3-diene~;'~~ from C,H,,CECH there was formed 77% of the 1,3-diene.A hydroformylation protocol for alkynes which leads to an a$-unsaturated aldehyde is shown in Scheme 14.14 Reagents i HCN Ni[POPh314; ii DIBAH PhMe -78 "C Scheme 14 Some enhancement of the hydrogenation activity of Lindlar's catalyst was realized by treatment with lead acetate; sodium acetate was without Epitaxial palladium on a tungsten film has been shown to have enhanced semi-hydrogenation capability together with cis-selectivity for reduction of a1k~nes.l~~ This latter catalyst was claimed to be superior to Lindlar's catalyst. Propargylic esters enter into a Claisen rearrangement to form an ester of an allenyl acetic acid; the free acid on thermolysis (250 "C) forms a b~ta-1,3-diene.'~~ Yields in both steps are high; thus MeC_C-CH,OCOMe gave CH,=C=C(Me)CH( Me)C02H (70%) and finally MeCH=C(Me)CH=CH (100% from the immediate precursor).Alkynes R'C=CR2 with MeOH-PhI(0H)OTs form methyl phenylalkanoate~.'~~ Dichloroketene (Cl,C=C=O from Cl3CCOC1-Zn/Cu) and alkynes form dichlorocyclobutenones which are easily dechlorinated by zinc in acetic acid- I39 s.Ghosal G. P. Luke and K. s. Kyler J. Org. Chem. 1987 52 4296. 140 A. Carpita D. Neri and R. Rossi Gazz. Chim. Ital. 1987 117 481. 141 C. J. Elsevier and H. M. Mooiweer J. Org. Chem. 1987 52 1536. 142 M. Falorni L. Lardicci and G. Giacomelli Gazz. Chim. Ital. 1987 117 7. 143 S. A. Rao and M. Periasamy J. Chem. SOC.,Chem. Commun. 1987 495. 144 E. Campi N. J. Fitzmaurice W.R. Jackson P. Perlmutter and A. J. Smallridge Synthesis 1987 1032. 145 J. G. Ulan E. Kuo W. F. Maier R. S. Rai and G. Thomas J. Org. Chem. 1987 52 3126. 146 J. G. Ulan W. F. Maier and D. Smith J. Org. Chem. 1987 52 3132. 147 J. E. Baldwin P. A. R. Bennett and A. K. Forrest J. Chem. Soc. Chem. Commun. 1987 250. R. M. Moriarty. R. K. Vaid M. P. Duncan and B. K. Vaid Tetrahedron Lett. 1987 28 2845. 14' 112 B. V; Smith ~yridine.'~~ Addition of t-butylcyanketene Me,CC(CN)=C=O to a stannylethynyl ether (R'OCrCSnR:) leads to (stannyloxyviny1)yne ether.'50 Ethers of the type ClCH20R' (R' = Me or Et) were shown to add to alkynes carrying a phenyl group or to but-2-yne.15' The expected addition product was formed i.e. R'OCH,C( R2)=C(C1)R3 together with that resulting from replacement of the vinylic ether by C1.The process was inferred to proceed via a stepwise electrophilic mechanism (vinyl cations were implicated); the secondary product ClCH2C( R2)=C( C1)R3 was thought to arise from an allylic cation. The silver-assisted heterocyclization of acetylenic alcohols or acids affords an easy route to a-methylene oxygenated heterocycles. lS2 The alkyne complexes of early transition metals have been reviewed; diene alkene and alkyl complexes were also in~luded."~ Pyrolysis of acetylene serves as a thermal source of ~iny1idene.l~~ The effect of structure on the zirconium-promoted bicyclization of enynes has been examined.'55 Reductive cyclization of 1,6-and 1,7-enynes [by R,SiH-L2Pd( H)X catalyst] has been probed mechanistically and stereochemically.'56 The products (exocyclic alkenes) were formed in very good yields; in one case the reaction gave complete stereospecificity since (55) afforded (56) as a single diastereoisomer.Diynes cyclized smoothly to E,E-exocyclic diems with Ti or Zr reagents e.g. MeC=C(CH2),C~CMe gave (57) after cyclization followed by treatment with OMe acid.'57 Sodium methoxide was used to convert 5-chloro-5-methylhexa- 1,3-diyne into dimethylpentatetraenylidene (58) which further gave (59) and (60).15*It was presumed that (60) arose from internal return and (59) from solvent addition to (61). Finally 2-quinolone derivatives have been obtained by the cycloaddition of aryl isocyanates to amin~butadiynes.'~~ 149 A.Ammann M. Rey and A. S. Dreiding Helv. Chim. Acta 1987 70 321. G. Himbert and L. Henn Liebigs Ann. Chem. 1987 771. 151 F. Marcuzzi G. Melloni and M. V. Zucca Gazz. Chim. Ital. 1987 117 219. I52 P. Pale and J. Chuche Tetrahedron Lett. 1987 28 6447. 153 H. Yasuda and A. Nakamura Angew. Chem. In?. Edn. Engl 1987 26 723. I54 R. P. Duran V. T. Amorebieta and A. J. Colussi J. Am. Chem. SOC. 1987 109 3154. '55 E. Negishi D. R. Swanson F. E. Cederbaum and T. Takahashi Tetrahedron Lett. 1987 28 917. 156 B. M. Trost and F. Rise J. Am. Chem. SOC. 1987 109 3161. 157 W. A. Nugent D. L. Thorn and R. L. Harlow J. Am. Chem. Soc. 1987 109 2788. 158 S. Basak S. Srivastava and W. J. le Noble J. Org. Chem. 1987 52 5095. 159 M. Ban M. Fenstel G.Himbert and G. Maas Liebigs Ann. Chem. 1987 221.

ISSN:0069-3030    

DOI:10.1039/OC9878400093

出版商:RSC    

年代:1987

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5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By P. F. GORDON Process Technology Department ICI Fine Chemicals Manufacturing Organisation Huddersfield HD2 1 FF 1 Introduction The following discussion covers only a small proportion of the total number of publications which fall within the scope of this chapter. Nevertheless some of the major themes dominating work in this area particularly stereocontrolled reactions and the upsurge of interest in carbonylations are reflected in the sections that follow. 2 Alcohols and Ethers An important route to stereodefined chiral alcohols involves the reduction of the corresponding ketones. In a major study Brown and co-workers have taken ten ketones each representing a particular class of ketone and reacted them with six different reducing agents.On the basis of the results obtained a recommendation of the most efficient asymmetric reducing agent for each individual class of ketone has been made.’ More specifically in the P-ketoesters (l) the ester group has been designed so as to block the approach to one face of the ketonic carbonyl group. Hydride reduction then proceeds either uia the transition state in which the ester and ketone carbonyls are syn ZnC12-Zn(BH,)2 or alternatively uia the transition state in which the carbonyls are anti (Dibal BHT) thus allowing both configurations of the final alcohol to be selected.2 The Heathcock Group has explored diastereo- facial selectivity in reductions of a-disubstituted ketones and aldehydes in terms of trajectory analysis and not surprisingly can rationalize the results in terms of the direction of approach of the hydride ion.3 R2wR’ OH I But Me ’ H.C. Brown W. S. Park B. T. Cho and P. V. Ramachandran J. Org. Chem. 1987 52 5406. ’ D. F. Taber P. B. Deker and M. D. Gaul J. Am. Chem. Soc. 1987 109 7488. E. P. Lodge and C. H. Heathcock J. Am. Chem. SOC.,1987 109 2819. 113 114 P. E Gordon Li R3 An alternative route to chiral alcohols proceeds by selective attack of an organometallic reagent at an aldehyde group. Organozinc reagents in conjunction with various chiral catalysts have been studied extensively this year and give predictable and high levels of stereocontrol. For example Corey and Hannon have converted various chiral aminoalcohols e.g.ephedrine and prolinol into the corre- sponding tertiary aminophenolic alcohols (2) and then used the latter as very effective catalysts for the addition of dialkylzincs to aromatic aldehyde^.^",' Similarly methyl- substituted prolinol derivatives (3) have been used with good results,' as have chiral piperazines (4),6certain cinchona alkaloid^,^ and (polymeric) immobilized amino- alcohols (5).8 Interestingly the amino alcohols (6) catalyse asymmetric additions to both alkyl and aromatic aldehydes.' E and 2-y-Alkoxy siloxyallyltin reagents add to aldehydes stereoselectively to give the threo alcohols (7) thus complementing earlier reports of erythro selective additions of y-alkylallyltin reagents;" these results can be rationalized in terms of chelation control.In contrast erythro and threo alcohols can both be obtained from a-disubstituted aldehydes using tetrabutyl ammonium bromide and either an alkyl- lithium (threo) or a cuprate reagent (erythro)." Titanium reagents are preferred in the catalytic addition of optically active carbamates (8) to aldehydes.I2 In particular titanium(IV) isopropoxide promotes additions which go with retention of configur-ation whereas titanium( IV) trisdiethylamino chloride promotes additions going with inversion. Various organometallics can be added to the aldehyde group in a,@-epoxyaldehydes without interfering with the epoxide group. In this way the R' I I. NPr (a) E. J. Corey and F. J. Hannon Tetrahedron Lett. 1987 28 5237; (b) ibid.p. 5233. K. Soai S. Niwa Y. Yamada and H. Inoue Tefrahedron Lett. 1987 28 4841. ' K. Soai A. Ookawa K. Ogawa and T. Kaba J. Chern. SOC.,Chern. Cornrnun. 1987 467. ' A. A. Smaardijk and H. Wynberg J. Org. Chern. 1987 52 135. S. Itsuno and J. M. J. Frechet J. Org. Chern. 1987 52 4140. K. Soai S. Yokoyama K. Ebihara and T. Hayasaki J. Chern. SOC.,Chern. Cornrnun. 1987 1690. (a) M. Koreeda and Y. Tanaka Tefrahedron Lett. 1987 28 143; (b) G. E. Keck D. E. Abbott and M. R. Wiley ibid. p. 139; (c) G. E. Keck and S. Castellino ibid. p. 281; (d) S. D. Kahn G. E. Keck and W. J. Hehre ibid. p. 279. " Y. Yamamoto and K. Matsuoka J. Chern. SOC.,Chem. Cornrnun. 1987 923. '*T. Kramer and D. Hoffe Tetrahedron Lett. 1987 28 5149. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds corresponding epoxy alcohols can be obtained with moderate to high stereoselectivity with best results appearing to result from the use of tin reagents catalysed by boron-based Lewis acids in dichloroniethane.’3 The epoxy group itself can be induced to ring-open to yield the corresponding alcohol.Thus threo and erythro 2,3-epoxyalcohols are attacked by a range of nucleophiles to provide the corresponding diols in high yield. In this case the threo epoxyalcohols are found to react faster and with higher selectivity at the C-3 position than the corresponding erythro compound^.'^ In complete contrast organocuprates attack preferentially at the C-2 position to yield the corresponding diol in good yield.’’ Vinyloxiranes (9) are readily formed from the corresponding epoxyalcohol after oxidation to the aldehyde followed by a Wittig reaction.Organocuprates (LiMe,Cu) can then be used to open the epoxide in a predominantly anti SN2’ fashion to yield (E)-allylic alcohols ( E-and 2-2,3-epoxysilanes containing an isopropyl group on silicon provide a convenient access to threo and erythro 1,2-diols respectively. Once again the epoxide is attacked by a nucleophile to yield a silyl alcohol follow.ed by oxidation of the carbon silicon bond to give the corre- sponding stereodefined 1,2-di01.~’ This particular sequence has been .used in the synthesis of exobrevicomin. Silyl reagents have also been used in the conversion of 3-hydroxybutenolides (11) into P,y-epoxyesters (12) using trimethylsilyliodide fol- lowed by cyclization with silver oxide.’‘ In the same paper the esters (12) have been converted into the corresponding chiral p-hydroxyesters in high enantiomeric purity using organocuprate reagents.Alternatively P-hydroxyesters can be prepared from a&-epoxyesters using the currently in vogue reagent samarium iodide to reduce the epoxide function.” A somewhat less direct approach to stereodefined alcohols can be seen in the palladium-catalysed reaction between vinyl oxiranes ( 13) and tosylisocyanate to give oxazolidinones (14) which can then be hydrolysed to the corresponding amino- alcohol.20 The route is effectively a cis hydroxyamination procedure and has been applied to the synthesis of (-)-acosamine.Whereas the last reaction relied upon palladium to promote the epoxide ring-opening the epoxide ring in epoxyalcohol (15) is cleaved during the rearrangement step to hydroxy ketone (16).2’The overall rearrangement constitutes a new method for the construction of quaternary carbon centres in high yield. l3 G. P. Howe S. Wang and G. Proctzr Tetrahedron Lett. 1987 28 2629. I4 K. S. Kirshenbaum and K. B. Sharpless Chem. Lett. 1987 11. l5 J. M. Chong D. R. Cyr and E. K. Mar Tetrahedron Lerr. 1937 28 5009. J. A. Marshall and J. D. Trorneter Tetrahedron Letr. 1987 28 4985. ” K.Tamao E. Nakajo and Y. Ito J. Org. Chem. 1987 52 4412. ’‘ M. Larchevcque and S. Henrot Terrahedron Letr. 1987 28 1781. I’ K. Otsubo J. Inanaga and M. Yamaguchi 7etrahedron Left. 1987 28 4437.20 B. M. Trost and A. R. Sudhakar .I. Am. Chem. Soc. 1987 109 3792. *I M. Shimazaki H. Hara K. Suzuki and G.-i. Tsuchihashi Tetrahedron Lett. 1987 28 5891 116 P. F. Gordon References to the construction of diols have already been noted. However several papers have appeared detailing some elegant routes to polyols. For example diepoxides figure as intermediates in the syntheses of symmetrical and enantiotopi- cally differentiated polyols with the key step being a stereospecific ring-opening of the epoxide. Scheme 1 illustrates one approach**" whereas a quite different method starts from diepoxide (17) and relies upon a meso selective base-catalysed Payne rearrangement to generate the chiral polyol (18) a useful precursor for Teurilene.22b I OH OH OH OH fi Scheme 1 HO 0 OH (a)S.L. Schreiber M. T. Goulet and G. Schulte J. Am. Chem. SOC.,1987 109 4718; (b)T. R. Hoye and S. A. Jenkins ibid. p. 6196. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds A very powerful iterative strategy to polypropionates has been used in a rapid synthesis of the C( 19)-C(29) sector of Rifamycin S.23Two Lewis acid-catalysed cyclocondensation reactions form the key steps in the synthesis in which the successor aldehyde is fashioned from the anomeric carbon of its pyranoid pre- decessor (see Scheme 2). Both processes occur under essentially perfect diastereofacial (Cram-Felkin) selectivity. The first process is catalysed by titanium tetrachloride and exhibits cis selectivity whereas the second process relies on a boron Lewis acid catalyst and shows trans selectivity.Me Me Me I OMe TMs:<e OMe Me Me Me Me Scheme 2 Several catalysts have already been mentioned in the context of asymmetric additions to aldehyde. The nucleophile is frequently a metal carbanion though this is not always the case as demonstrated by the asymmetric allylation of aldehydes with allyltrimethyl~ilane.~~ The catalyst in this case is diphenylboryl triflate which promotes excellent yields and high enantiomeric excesses of the corresponding ethers (19). Another ether synthesis involving silyl derivatives is achieved using either trimethylsilyl triflate or trimethylsilyl iodide as catalyst and involves the reductive coupling of aldehydes with trialkyl~ilanes.~~ Symmetrical ethers are obtained with both catalysts in good yield.However if alkoxylsilanes are used with trimethylsilyl iodide catalyst then unsymmetrical ethers can be readily prepared. The cleavage of ethers has been studied extensively in the last decade with silyl compounds the most popular class of reagent for effecting the transformation. In 23 S. J. Danishefsky D. C. Myles and D. F. Harvey J. Am. Chern. Soc. 1987 109 862. 24 T. Mukaiyama M. Ohshima and N. Miyoshi Chem. Lett. 1987 1121. 25 M. B. Sassaman K. D. Kotian G. K. S. Prakash and G. A. Olah J. Org. Chem. 1987 52 4314. 118 P. F. Gordon this context diiodosilane (DIS) has been shown to be particularly effective in the cleavage and deoxygenation of ethers (and alcohols) and demonstrates a high selectivity for secondary alkoxy functions.2h In this respect it exhibits a complernen- tary reactivity to that found with trimethylsilyl iodide (TMSJ).For example primary alcohols are converted into the corresponding iodides almost two orders of magni- tudes faster with TMSJ than DIS whereas quite the opposite situation is observed for secondary alcohols. A related and useful reaction can be seen in the silyl promoted cleavage of spiroketals. This particular transformation has been used in the enan- tioselective functionalization of 2-substituted- 1,3-diols. The overall sequence is fairly simple and starts by reacting the diol with 1-menthone to give the ketal diastereoisomer in which the iarge substituent predictably occupies the equatorial position.After reaction with the trimethylsilyl enol of acetophenone the monoprotec- ted neomenthyl derivative is formed and then converted into monoprotected diol (20) with recovery of the chiral 'This method has been extended by the same authors to encompass the resolution of variously substituted 1,3-diol~.~",~ RI OR^ 2% X = OTHP OCPh, SPh R' R2 R2 OR^ The protection of alcohols is illustrated by the reported use of p-methoxybenzyl- oxymethyl chloride which protects alcohols under mild conditions and can be removed easily with DDQ.28 The diphenylmethylsilylether (DPMS) group also appears to be a useful addition to the range of available protecting groups.29 It is stable to Grignard and Wittig reagents and silicon gel chromatography yet can be removed under very mild basic conditions -far milder than those used for the removal of the t-butyldimethylsilyl protecting group.Finally in this section chiral acetals (21) are claimed to be convenient reagents for determining the enantiomeric purity of alcohols by NMR spectro~copy.~" 3 Alkyl Halides The conversion of alcohols into alkyl halides is one of the classic functional group transformations. However despite the great deal of attention this reaction has received there are still a few areas that demand attention such as in the preparation of sterically hindered alkyl chlorides from the corresponding alcohols a notoriously inefficient reaction. Scheme 3 provides an elegant solution to the problem and works for a range of sterically very hindered alcohol^.^' Asymmetric a-bromination of carboxylic acids is possible uia the chiral amides (22 X = H).32The amides are converted into the boron enolate in the first step and then treated with NBS to provide the bromo derivatives (22 X = Br) with very high 26 E.Keinan and D. Perez J. Org. Chem. 1987 52 4846. 27 (a) T. Harada T. Hayashi I. Wada N. lwa-ake and A. Oku J. Am. Chern. SOC. 1987 109 527; (b) T. Harada I. Wada and A. Oku Terrahedron Len. 1987 28 4181; (c) T. Harada H. Kurokawa and A. Oku ibid. p. 4843; (d) ibid. p. 4847. 28 A. P. Kozikowski and J.-P. Wu Telrahedron Lerr. 1987 28 5125. 29 S. E. Denmark R. P. Hammer E. J. Weber and K. L. Habermas J. Org. Chem. 1987 52 165. 30 T.H. Chan 0.-J. Peng D. Wang and .I.A. Guo J. Chern. SOC.Chem. Cornrnun. 1987 325. 31 D. Crich and S. M. Fortt S,ynthesis 1987 35. 32 D. A Evans J. A. Ellman and R. L. Dorow Tetrahedron Left. 1987 28 1123. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds A 0 Scheme 3 enantio~electivity.~~ The same paper describes a method for converting the chiral halogeno acids derived from (22) by hydrolysis into chiral amino acids using the simple two-step sequence of azide displacement and reduction. New ways to incor- porate a fluorine into a molecule are always to be welcomed especially in view of the ever increasing use of fluorine-containing molecules in the plant protection and pharmaceutical industries. In this context iodine 'fluoride converts hydrazones into the corresponding difluoro compounds in high yield.33 Bn (22) A number of variations upon the halogen exchange reaction have been published.For instance alkyl chlorides even sterically hindered ones can be converted into the bromide with hydrogen bromide catalysed by iron( 111) bromide,34 whereas aryl chlorides and bromides are readily converted into the iodide using alumina and charcoal-supported copper( I) iodide.35 Dehalogenation of alkyl and aryl halides can be accomplished with a sodium borohydride suspension in toluene using tributyltin chloride and polyether phase-transfer catalysts.36 Samarium iodide also effects the same transformation in quantitative yields.37 Finally in this section alkyl halides can be readily homologated in three steps via the sequence conversion into the Grignard reagent followed by treatment with an aminomethylether (R'OCH,NR:) and then ethylchl~roformate.~~ 4 Aldehydes and Ketones A convenient route to aldehydes and ketones is by direct conversion from carboxylic acids and their derivatives.The fact that the methods in current use are not entirely satisfactory is emphasized by the large number of new reagents and methods to accomplish the transformation. Some of these are highlighted in Scheme 4.39a-h 33 S. Rozen M. Brand D. Zamir and D. Hebel J. Am. Chem. Soc. 1987 109 896. 34 K. B. Yoon and J. K. Kochi J. Chem. Soc. Chem. Commun. 1987 1013. 3s J H. Clark and C. W. Jones J. Chem. Soc. Chem. Commun. 1987 1409. 36 D.E. Bergbreiter and J. R. Blanton J. Org. Chem. 1987 52 472. 37 J. Inanaga M. Ishikama and M. Yamaguchin Chem. Lett. 1987 1485. 38 E. Yankep and G. Charles Tetrahedron Lett. 1987 28 427. 39 (a) R. J. P. Corriu G. F. Lannean and M. Perrot Tetrahedron Lett. 1987 28 3941; (b) J. S. Cha J. E. Kim S. Y. Oh J. C. Lee and K. W. Lee Tetrahedron Lett. 1987,28 2389; (c) J. S. Cha J. E. Kim M. S. Yoon and Y. S. Kim ibid. p.6231; (d) J. S. Cha J. E. Kim S. Y. Oh and J. D. Kim ibid. p.4575; (e) J. S. Cha and S. S. Kwon J. Org. Chem. 1987 52 5486; cf) S. Collins and Y. Hong Tetrahedron Lett. 1987 28 4391; (g) C. Cardellicchio V. Fiandenese C. Marchese and L. Ronzini Tetrahedron Left. 1987 28 2053; (h) Y. Tominaga S. Kohra and A. -Hoxomi Tetrahedron Lett.1987 28 1529. 120 P. F. Gordon R' = li R' = alkyl R = aliphatic aromatic R' = alkyl R' = H ___. RCOCl RC0,R Several of the methods in Scheme 4 refer to the reduction of acids to aldehydes. An alternative approach is by oxidation of primary and secondary alcohols and this has now been successfully carried out using tetrabutylammonium per-ruthenate with morpholine-N-oxide as a mild catalytic oxidant; yields are typically in the range 80-90% .40 Homologation of ketones and aldehydes is also a sought after process and a particularly efficient route is shown in Scheme 5 and relies upon a new synthetic application of benzodithiolium cations.41 Scheme 5 40 W. P. Griffith S. V. Ley G. P. Whitcombe and A. D. White J.Chern. SOC.,Chem. Commun. 1987 1625. 41 M. Cerciti I. Degano and R. Fochi S-vnthesis 1987 79. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 121 In the past few years the upsurge of interest in carbonylation reactions has been quite marked. This year has seen several different approaches to the synthesis of aldehydes and ketones. For instance one paper describes the palladium-catalysed reductive carbonylation of esters to give aldehydes at low pressure using synthesis gas.42 In contrast organomanganese carbonyls are the source of the carbonyl group in two recently published papers. Methyl magnesium pentacarbonyl which is more reactive than the corresponding benzyl complex with regard to migratory aptitude inserts a carbonyl group into various activated and strained double and triple bonds to give organomanganese compounds (23).In the case of activated alkenes the selectivity of addition as might be expected is very high with the manganese (CO) moiety substituting alpha to the activating substituent. The manganese is readily removed by photodemetallation to yield the corresponding ketone.43a Alternatively for manganacycles derived from alkynes acid treatment gives a mixture of enones and furanone whereas reduction with DIBAL yields the butenolide via a further carbonyl insertion reaction.43b R3 H I Pr' &-mie OLi OR Pr' Li Over the past decade significant advances have been made in the art of controlling selectivity in the aldol reaction. This trend continues as exemplified by the diastereoselective reaction between simple aldehydes and the lithium enolate of N-propionylpyrrolidine to yield the anti-aldol product with catalytic quantities of a titanium reagent (Cp,TiC12).44The enantioselective aldol reaction of t-butylketone with benzaldehyde in the presence of the carefully selected chiral ligand (24) proceeds in excellent yield and with good enantiomeric excess.45 During studies into the total synthesis of macrolides an investigation into the diastereofacial selectivities of enolates (25) was ~ndertaken.~~ Several interesting points emerged from the study which centre around the nature of the 0x0-substituent (-OR).If the substituent is a hydroxy group i.e. R = H then si-facial selectivities are observed in the aldol reaction whereas the selectivity is totally reversed i.e.re-facial upon protection of the hydroxy group R # H. Thus without altering the nature of the backbone functionality especially at the chiral centres the diastereofacial selectivity can be predictably controlled. Allo-threonine and threonine have both been prepared in high enantiomeric excess (in a 1.7 1 ratio) by the aldol condensation between acetaldehyde and the zinc chelate of a Schiff base.47 Interestingly the Schiff base is prepared from glycine and 42 J. L. Graff and M. G. Romanelli J. Chem. SOC.,Chem. Commun. 1987 337. 43 (a) P. DeShoong G.A. Slough and A. L. Rheingold Tetrahedron Lett. 1987,28,2229; (b) P. DeShoong D. R. Sidler and G. A. Slough Tetrahedron Lett.1987 28 2233. 44 P. J. Murphy G. Procter and A. T. Russell Terrahedron Lett. 1987 28 2037. 45 A. Andro and T. Shioiri J. Chem. Soc. Chem. Commun. 1987 1620. 46 P. A. McCarthy and M. Kageyama J. Org. Chem. 1987 52 4681. 47 H. Kuzuhara N. Watanabe and M. Ando J. Chem. SOC.,Chem. Commun. 1987 95. 122 P. E Gordon a chiral pyridoxal like pyridinophene. The reaction therefore represents a "bio- mimetic" aldol reaction in which the zinc complex of the pyridine base is acting as an enzyme mimic. The aldol reaction can also be applied to a wide variety of different ketones and aldehydes; however cross-enolate additions with sterically hindered ketones are frequently troublesome. One approach which circumvents the problems is detailed in Scheme 6 and uses methylallylmagnesium chloride as a ~ynthon.~' Di-t-butylketone is used to illustrate the sequence.Bu' Bu'+ Bu' Me B u' OH Me . .. ... I II 1111 Bu' Reagents i 0,; ii Me2$ iii oxalic acid A Scheme 6 0 R' OR2 (26) (27) A more unusual route to aldol-type products (26) and (27) starts from acetals R3CH(OR2)2,and enolsilylethers or bistrimethylsiloxyalkenes respectively and is catalysed by electrogenerated acid derived from perchlorate Salka9 The yields of products (26) and (27) are generally excellent. Palumbo and co-workers have developed a new high yielding and general ketalization procedure which involves the use of a polystyryl diphenylphosphine- iodine complex.50 Yields are typically greater than reaction times are usually less than one hour and as might be expected with a polymerically immobilized reagent work-up is simple.An improved route to 1,3-dioxolan-4-ones (28) from carbonyl compounds has also been claimed. The silyl reagent (29) effects the transformation in excellent yield and works where many other reagents fail com- ~letely.~' The peroxysulphur compound formed from 2-nitrobenzenesulphonyl 48 W. H. Bunnelle M. A. Rafferty and S. L. Hodges J. Org. Chem. 1987 52 1603. 49 S. Torii T. Inokuchi S. Takagishi H. Horike H. Kuroda and K. Uneyana Bull. Gem. Soc. Jpn. 1987 60,2173. 50 R. Caputo C. Ferreri and G. Palumbo Synthesis 1987 386. 51 W. H. Pearson and M.-C. Cheng J. Org Chem.. 1987 52 1353. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds OSiMe3 Me3siorv 0 chloride and potassium peroxide converts tosylhydrazones into the corresponding ketones in almost quantitative yields at -30 0C.52 5 Carboxylic Acids and their Derivatives In common with ketones carboxylic acid esters form enolates readily and so many of the methods used for achieving stereospecificity in ketone enolate reactions are equally valid for ester enolates.Over the last few years an increasingly popular strategy for controlling the stereochemistry in aldol-type additions has been to employ “chelating” metals. A good illustration of what can be achieved can be seen in the synthesis of a,P-dihydroxy esters by reaction of the enolates of chiral glycolates (30) and (31) with aldehydes.53 By the appropriate choice of metal and chiral glycolate precursor any of the four possible stereoisomers of the resulting a$-dihydroxy esters (32) can be obtained in optically pure form.Zirconium is found to promote syn additions whereas the lithium ion favours the anti product. Little is known about the alkylation of P-amino acid esters. However a recent study has helped to highlight the very high 1,k-1,2-inductions possible in the a-alkylation of N-acylamino butanoates with lithium as c~unterion.~~ The same paper also contains several routes to the chiral starting material. The influence of the metal ion is critical in the reactions of dienolates (33) as determined in a recent Although the reactions of (33) are frequently lacking in both regio- and diastereo- selectivity it has been found that the y-tin derivative easily formed from (33) can give either the syn or anti forms of ester (34) with high diastereoselectivity by judicious choice of reaction conditions n .O OH 0 OH (33) (34) 52 Y.H. Kim H. K. Lee and H. J. Cheng Tetrahedron Left. 1987 28 4285. 53 W. H. Pearson and M.-C. Cheng J. Org. Chem. 1987 52 3176. 54 D. Seebach and H. Estermann Tetrahedron Leu. 1987 28 3103. 55 Y. Yamarnoto S. Hatsuya and J.4. Yarnada J. Chem. SOC.,Chem. Commun. 1987 561. 124 P. F. Gordon The upsurge of interest in carbonylation reactions has already been noted. This is further illustrated by the following references several of which have the distinct advantage of proceeding at atmospheric pressure.A novel method for the carbonyla- tion of aromatic halides has been developed which involves a photostimulated cobalt-catalysed carbonylatiori reactior under very mild conditions i.e. atmospheric pressure and ambient temperature to yield the corresponding carboxylic acids in high yield.56 Similary a cobalt salt is used in a facile carbonylation of benzyl halides giving the arylacetic acids in high yield.57 Once again mild conditions are employed although the catalytic system (CoC1,-NaBH,-CO-NaOH) is different. a-Hydroxy-carboxylic acids can also be formed very efficiently by carbonylation of both alkyl and aryl halides.58 In this case a palladium-phosphine complex is used as catalyst and the reaction conditions are rather more severe than in the previous two examples.The same catalyst combination i.e. palladium-phosphine is reported in another carbonylation; however the substrates phenols and aliphatic alcohols are quite different." Nevertheless yields of the corresponding carboxylic acids are still high and the reaction occurs at atmospheric pressure. In contrast carbonylation of alcohols with the catalyst combination copper chloride-di-t-butylperoxide results not in replacement of the hydroxy group by the carboxylic acid group as in the previous reference but rather leads to the formation of dialkyl carbonates.60 The preparation of synthetic a-amino acids is currently an area of topical interest. Evans and co-workers have generated chiral-a- halogeno-P-hydroxy carboxylic acids (35) by aldol additions ofthe chiral acid derivatives (36)(X = Cl) with aldehydes.61" The amino acid is then easily accessible by azidation and reduction (see also reference 32).A more general amino acid synthesis occurs via direct azide transfer to a chiral acid derivative (36 X = aryl alkyl) followed by reduction.61h A common feature in the last two syntheses is the formation of a chiral oxazolidinium azide in which the chiral auxiliary the oxazolidine ring has to be removed to generate the desired chiral azido carboxylic acid prior to reduction. The same authors have now shown that lithium peroxide is a far superior reagent for this exocyclic cleavage of the oxazolidine ring thus allowing the recovery of the chiral auxiliary.61' Furthermore the reagent works for all classes of oxazolidinone-derived carboximides encountered thus far Vederas has also developed an efficient entry into chiral a-amino acids which is effectively the functionalization of an existing amino acid serine.62 In the ,-, CI I, Ph Me Ph Me H2N COiH (35) (36) (37) 56 K.Kudo T. Shibata T. Kashimura S. Mori and N. Sugita Chem. Lett. 1987 577. 57 N. Satyanarayana and M. Periasamy Tetrahedron Lett. 1987 28 2633. 58 T.-a. Kobayashi T. Sakakura and M. Tanaka Tetrahedron Lett. 1987 28 2721. 59 R. E. Dolle S. J. Schmidt and L. I. Kruse J. Chem. Soc. Chem. Cornmun. 1987 59. 60 G. E. Morris D. Oakley D. A. Pippard and D. J. H. Smith J. Chem. Soc. Chem. Commun. 1987,410. 61 (a) D. A. Evans E. B. Sjogren A. E. Weber and R.E. Conn Tetrahedron Lett. 1987,28,39; (h) D. A. Evans and T. C. Britton .I. Am. Chem. Soc. 1987 109 6881; (c) D. A. Evans T. C. Britton and J. A. Ellman Tetrahedron Lett. 1987 28 6141. 62 L. D. Arnold J. C. G. Drover and J. C Vederas J. Am. Chem. Soc. 1987. 109 4649. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds first step serine is cyclized to its lactone which can then be attacked by Grignard reagents (RMgCI) to give amino acids (37) with complete retention of optical purity (>9996 ) after deprotection.62 The conjugate addition of phenyldimethylsilyl cuprate reagents to cinnamate and crotonate esters and amides of known chiral auxiliaries is highly diastereoselective and provides P-silylesters which are useful synthetic intermediates in their own right.43 Interestingly the sense of diastereoselection in the silyl cuprate addition is opposite to that normally observed.Chlorotrimethylsilane has been used in the asymmetric Michael addition of chiral enamines of a -alkyl-P-ketoesters to activated alkenes." In this particular instance the silane acts as an efficient catalyst for the addition reaction rather than as a co-reactant. A study of the diastereoselectivity of conjugate additions to y-substituted a$-unsaturated esters has demonstrated the importance of the double bond geometry and type of reagent in controlling the selectivity. Thus Lewis acid-mediated addition of organocuprate reagents to trans esters (38) gives the saturated anti isomer (39) whereas the cis ester provides access to the syn is~mer.~~',~ On the other hand organocopper reagents add in anti fashion regardless of the starting geometry.In the reaction between alkyl halides lithium amides and a,@-unsaturated carboxylic esters the unsaturation is retained with alkylation occurring at the a-position to give a-alkyl-a$-unsaturated carboxylic esters in good yield.64 In this example the lithium amide functions as a nucleophile rather than its more usual role as a strong base and adds to the unsaturated ester to give the anion at the a -position which can then be alkylated. In the final step the amine is eliminated to regenerate the unsaturated ester. Nu Y-co2R' R +co2R R (38) (39) A new solution to the formation of P-ketoamides (from P-ketoesters) has been published.This particular transformation is frequently plagued by problems such as competitive formation of the enamine poor yields and severe reaction conditions. A practical solution involves the prior formation of the thioester followed by silver trifluoroacetate-catalysed amidation under very mild reaction condition^.^' Yields are typically in the region of 6O-8O% and the method works even for non-basic amines. An alternative amidation though this time for simple esters only requires very mild thermal conditions and utilizes electrochemistry.68 The amidation reaction occurs in the cathodic compartment and works equally well for aliphatic and aromatic amines. 63 I. Fleming and N. D. Kindon J. Chem. SOC., Chem. Commun. 1987 1177. 64 K.Tomiska W. Seo K. Ando and K. Koga Tetrahedron Lett. 1987 28 6637. 65 (a) Y. Yamamoto S. Nistui and T. Ibuka J. Chem. SOC., Chem. Commun. 1987,464; (6) ibid. p. 1572. 66 T. Uyehara N. .4sao and Y. Yarnamoto J. Chem. SOC.,Chem. Commun. 1987 1410. 67 S. V. Ley and P. R. Woodward Tetrahedron Lett. 1987 28 3019. 68 K. Arai C.-h. Shaw K. Nozawa K.4. Kawai and S. Nakajima Tetrahedron Lett. 1987 28 441. 126 l? E Gordon A convenient route to nitriles proceeds by nucleophilic displacement of a halide with cyanide ion. For instance lithium cyanide in THF is very effective in converting alkyl halides and tosylates into the corresponding itri rile.^^ Significantly the corre- sponding sodium and potassium salts are almost totally ineftective.Malic acid figures in at least two reports this year. A convenient synthesis of (R)-malic acid is reported as starting from R,R-dimethyltartrate and proceeds uia the intermediacy of the thione (40) which yields the maleate upon treatment with tributyltin h~dride.~’ In the second malic acid is used to prepare a new chiral synthon (41) which has been used for the preparation of the chiral side-chain fragment of 24,25-dihydroxycalciferol.”Phenyl malonic acid can be asymmetrically decarboxylated to the monacid (42) in good yield using copper iodide-cinchona alkaloids as catalyst.’* Me0 CyC O2M e s (40) 0 (43) 6 Lactones and Lactams Samarium iodide is enjoying some topicality as a reagent and its application in the lactone area can be seen in the synthesis of chiral lactones (43).73 The role of the samarium iodide is twofold it promotes the efficient intramolecular Reformatsky reaction in (44) and controls the stereochemistry of ring-closure by co-ordination between the samarium cation and the oxygens from the ester enolate and the ketone.The yields are high and with the ready accessibility of the precursor (44) the method represents a useful and general synthesis of various polysubstituted lactones. More specifically optically active N-trityl homoserine lactone has been synthesized in just three steps from a cheap and readily available precursor (-)-aspartic acid as depicted in Scheme 7.74 The versatility of the asymmetric Michael reaction has already been demonstrated at several points in earlier sections and has now been applied to the synthesis of chiral 4-substituted lactones.The route is fairly simple and relies upon very familiar 69 S. Harusawa R. Yoneda Y. Ornori and T. Kurihara Terrahedron Lett. 1987 28 4189. 70 M. Alpegiani and S. Hanessian J. Org. Chem. 1987 52 278. ‘I J. Sterling E. Slovin and D. Rarasch Tetrahedron Lett. 1987 28 1685. 72 0. Toussaint P. Capdevielle and M. Maurny Tetrahedron Left. 1987 28 539. 73 G. A. Molander and J. B. Etter J. Am. Chern. Sac. 1987 109 6556. 74 J. E. Baldwin M. North and A. Flinn Terrahedron Left.. 1987 28 3167. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds FOIH (Co2Bn (Co2Bn Reagents i DIBAH; ii CF',CO,H Scheme 7 chiral auxiliaries.Thus Michael addition of metallated acetaldehyde RAMP and SAMP hydrazones to a,P-unsaturated esters yield 8-oxopentanoates. The latter can be reduced and cyclized to chiral lactones (45)in high enantiomeric excess typically >95% and in high chemical yield.75 The use of cheap chiral precursors is always an attractive option to take in producing more complex materials and often avoids the complications associated with using chiral auxiliaries. In the straightforward synthesis of (-)-lactones (46) glucose is the starting material. The particularly noteworthy aspects of this synthesis are the very mild oxidizing conditions which permit the use of relatively labile protecting groups the high yields and the high levels of chirality retained.76 R' The lactones prepared thus far are formed by conventional lactonization pro- cedures; however in one paper this year the ring-closure is effected by photolysis.This method is particularly useful in promoting the anti-Markovnikov intramolecular addition of a carboxylic acid to a double bond to give the five-membered ring lactone -a lactonization procedure which is difficult to achieve by standard synthetic method^.'^ The attention devoted to the lactone area is not confined merely to their construc- tion but also encompasses their use as chiral templates. Work in this latter respect has been extended to the construction of polypropionate chains by an iterative procedure involving the preparation of butenolide rings. Scheme 8 illustrates a 75 D. Enders and B.E. M. Rendenbach Chem. Ber. 1987 120 1223. 76 S. Valverde S. Garcia-Ochoa and M. Martin-Lomas 1. Chem. SOC. Chem. Commun. 1987 1714. P. G. Gassman and K. J. Bottorff J. Am. Chem. SOC.,1987 108 7547. '7 128 P. F. Gordon OH ~ WCOZH 0 .OH OH Reagents i LiC(SPh),; ii MeOPh; iii Ra-Ni; iv DEAD PPh, PhC02H; v K2C03 Scheme 8 typical sequence starting from a readily accessible butenolide and has been used by one group in the synthesis of the C(7)-C(13) fragment of erythronolide and shows the versatility of the approa~h.~~",~ The lactol ring system has also been used as a 'template' for chiral inductions in open-chain systems. Thus chiral y-and 6-lactols (47) are reduced to diols (48) by methyl titanium chloride representing highly selective 1,4 and 1,5 asymmetric inductions re~pectively.~~" If a Lewis acid catalyst is used with an organometallic reagent especially a zinc reagent then 2,5-disubstituted ethers are obtained instead.79h OH Finally in this section optically pure p-lactams have been produced via the intermediacy of hydroxylamines as outlined in Scheme 9." R* "a -o'r'y C02Me -3 R* 0 + * RNHOH Reagents i H2-Pd/C; ii Bu;NHSO4 MsCI; Na-NH Scheme 9 78 (a) G.Stork and S. D. Rychnovsky J. Am. Chem. Soc. 1987 109 1564; (b) S. Hanessian and P. J. Murray J. Org. Chem. 1987 52 1170. 79 (a) K. Tomooka T. Okinaga K. Suzuki and G.-i. Tsuchihashi Tetrahedron Lett. 1987 28,6335; (b) K. Tomooka K. Matsuzawa K. Suzuki and (3.4. Tsuchihashi ibid.p. 6339. S. W. Baldwin and J. Aubi Tetrahedron Left. 1987 28 179. no Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 7 Amines Imines and Other Nitrogen Compounds The general theme of asymmetric synthesis has been a recurrent one throughout each of the previous sections and it comes as no surprise to find several good examples in this section. For example in the synthesis of chiral amines (49) organocerium reagents are added to the familiar SAMP hydrazones (50) followed by reduction of the intermediate hydrazine to the amine.81 In this example organocerium reagents prove to be far superior to other organometallic reagents in the addition reaction to provide the hydrazine in high diastereoisomeric excess. There have been a host of references to the synthesis of amines and the following provides selected highlights; several of the references cover the use of azides in amine synthesis.t-Alkylchlorides can be converted into the corresponding t-alkyl- amines in two steps by azide transfer with trimethylsilyl azide catalysed by tin tetrachloride followed by reduction with triethylphosphite.82 Amines can be pre- pared from the alcohol directly in a convenient one-pot synthesis using hydrazoic acid di-isopropyl azodicarboxylate and triphenylpho~phine.~~ The azide group is also part of a sequence for converting amides (51) into amides (52) whilst avoiding drastic hydrolysis conditions as shown Dibutyltinhydride and the tin salt (PhS)3Sn-Et3N+H are two useful reagents for the reduction of azides to amines.The thiotin reagent is claimed to be the best reducing agent for azides reported thus far whereas dibutyltin hydride is not as powerful but can be used in common solvents even water and allows for a convenient mild w~rk-up.~~ RNHCOR + R-NCOR’ -+ R-N + RNHCOR’ I (51) NO (52) Protection of amines is an important reaction and every year seems to produce various new protecting reagents. The norbornene reagent (53) has been shown to be an excellent stable reagent for the introduction of the alkoxycarbonyl protecting group.86 ” S. E. Denmark T. Weber and D. W. Piotrowski J. Am. Chem. Soc. 1987 109 2224. 82 A. Koziara K. Osowska-Pacewicka S. Zawadzki and A. Zwierzak Synthesis 1987 487. 83 E. Fabiano B.T. Golding and M. M. Sadeghi Synthesis 1987 190. 84 J. Garcia and J. Villarasa Tetrahedron Lett. 1987 28 341. 85 M. Barta F. Urpi and J. Villarasa Tetrahedron Lett. 1987 28 5941. 86 P. Henklein H.-U. Heyne W.-R. Halatsch and H. Niedrich Svnthesis 1987 166. 130 P. F. Gordon Nitro groups are useful synthetic intermediates and so new methods to incorporate and remove nitro groups are always to be welcomed. Ranganathan and co-workers have reported a safe and practical route to the nitroethylene transfer reagent 2-nitroethylphenylsulphoxidewhich avoids the use of 2-nitroethanol as shown in Scheme -P HOCH,CH,OH PhSCH,CH,OH -* PhSCH,CH,Br 0 I I PhSCH2CH2N0 +-PhSCH,CH,NO Scheme 10 Nitronium tetrafluoroborate in sulpholane is an effective desilylative-nitrating reagent and the method is claimed to be the first effective nitrodesilylation at a saturated carbon.88 Finally triethylsilane proves to be an effective reagent for the reductive removal of the nitro group in a-or P-nitro~ulphides.~~ 8 Sulphur and Phosphorus Since the sulphur and phosphorus area is covered to some extent in other chapters in this volume this section will be kept brief.Optically active sulphur groups have proved very popular in asymmetric induction reactions over the last few years. Solladie and his group have now published improved procedures for preparing large scale quantities of optically pure methyl-p-tolyl sulphoxide which should greatly improve the use of these reagents." Chiral 1-alkynyl-p-tolylsulphoxidescan also be prepared in high yields from the corresponding alkynyl magnesium bromide and chiral menthyl~ulphinate.~~ As a further step the alkynic bond can be reduced to either the E or 2 alkenyl sulphoxides -useful intermediates in their own right.92 Several examples of the use of chiral sulphoxides are again evident this year as illustrated by the total synthesis of Talaromycins A and B which have been accom- plished by successive asymmetric inductions of all the chiral centres using a chiral sulphinyl group as outlined in Scheme ll.92"-' The trifluoromethyl compound (54) can be synthesized from ethyl trifluoroacetate and the corresponding methylsulphoxide in high yield and in good optical The sulphoxide (54) then provides easy access to various chiral trifluoromethyl- substituted compounds which will no doubt be of interest for the pharmaceutical and agrochemical industries.A convenient synthesis of menthyl sulphinate esters has been published and starts from the sulphonyl chloride and corresponding menthyl alcohol.94 High yields of material are assured if trimethyl phosphite is used as the co-reactant. 87 S. Ranganathan D. Ranganathan and S. K. Singh Tetrahedron Lett. 1987 28 2893. 88 G. A. Olah and C. Rochin J. Org. Chem. 1987 52 701. 89 N. Ono T. Hashimoto T. X. Jun and A. Kaji Tetrahedron Lett. 1987 28 2277. 90 G. Solladie J. Hutt and A. Girardin Synthesis 1987 173. 91 H. Kosugi M. Kitaoka K. Tagami A. Takaheshi and H. Uda J. Org. Chem. 1987 52 1078. 92 (a) C.Iwata M. Fujita Y. Moritani K. Hattori and T. Imanishi Tetrahedron Lett. 1987 28 3135; (b) C. Iwata Y. Moritani K. Sugiyama M. Fujita and I. Imanishi ibid. p. 2255; (c) C. Iwata M. Fujita Y. Moritani K. Sugiyama K. Hattori and T. Imanishi ibid. p. 3131. Y3 T. Yamazaki N. Ishikawa H. Iwatsubo and T. Kitazume J. Chem. SOC.,Chem. Commun. 1987 1340. 94 J. M. Klunder and K. B. Sharpless J. Org. Chem. 1987 52 2598. Aliphatic Compounds -Part ( ii) Other Aliphatic Conipounds 131 + \ OR 1 iv v 6 , RO 0 VIII. :34' foH,o -.no<*-c-IX OH ICHl <Ix J Reagents. i LiNEt? [O]; ii. K2C0, 18-crown-6; iii HCI; iv ZnCI,; v TFA benzyl bromide; vi Bu,NF; vii KH; viii TsCI Py;ix P(OMe)3; x Me,CuLi Scheme 11 Thioethers have been produced in excellent yields using a new methodology which involves the fluoride or cyanide ion destannylation of the sulphur-transfer reagents R,SnSSnR, or R3SnSR' in the presence of various alkyl and activated halide^.'^ The conditions are mild neutral and anhydrous and both symmetrical and unsymmetrical thioethers have been prepared.Phosphono-P -ketoesters (55 X = OEt) are valuable synthetic intermediates in the synthesis of (E)-4-alkenyl-3-oxoesters and oxomacrolides.96 The thioester start- 95 D. N. Harpp and M. Gingras Terrahedrori Letr. 1987 28 4373. 96 S. V. Ley and P. R. Woodward Tetrahedron Lett.. 1937 28 345. 132 P. F. Gordon ing material (55,X= SEt) for these reactions is readily obtained from diketene after bromination thiolation and an Arbuzov reaction.Finally in this section a general procedure for the near quantitative preparation of alkyldibenzyl phosphates has been developed and starts by treating alcohols with phosphoramide and methyl tetrazole.97 9 Reviews The following table lists some of the more relevant reviews published in 1987. Title Reference Cross-coupling reactions based on acetals 98 Stereoselective synthesis of building blocks with three consecu- 99 tive stereogenic centres. Important precursors of polyketide natural products Stereoselective aldol reactions with cu,P-unsubstituted chiral 100 enolates Direct homogeneous hydrogenation 101 Formylating reagents 102 Sultone chemistry 103 Camphor derivatives as chiral auxiliaries in asymmetric 104 synthesis Twenty-five years of dimethylsulphoxonium methylide 105 (Corey's reagent) Advances in the preparation of biologically active organo- 106 fluorine compounds Synthetic routes to tetrahydrofuran tetrahydropyran and 107 spiroketal units of polyether antibiotics and a survey of spiroketals of other natural products Asymmetric synthesis of carbon-carbon bonds using sulphinyl 108 cycloalkenones alkenolides and pyrones 97 J.W. Perich and R. B. Johns Tetrahedron Left.,1987 28 101. 98 T. Mukaiyama and M. Murakami Synthesis 1987 1043. 99 R. W. Hoffman Angew. Chem. In[. Ed. Engl. 1987 26 489. loo M. Braun Angew. Chem. Int. Ed. Engl, 1987 26 24. lo' J. M. Brown Angew. Chem. Int Ed. Engl. 1987 26 190. G. A. Olah L.Ohannesian and M. Arvanaghi Chem. Rev. 1987 87 671. D. W. Roberts and D. L. Williams Tetrahedron 1987 43 1027. lo4 W. Oppolzer Tetrahedron 1987 43 1969. 105 Y. G. Gololobov A. N. Nesmeyanov V. P. Lysenko and I. E. Boldeskul Tetrahedron 1987 43 2609. 1Oh J. T. Welch Tetrahedron 1987 43 3123. 107 T. L. B. Boivin Tetrahedron 1987 43 3309. lo* G. H. Posner Acc. Chem. Rex 1987 20 72.

ISSN:0069-3030    

DOI:10.1039/OC9878400113

出版商:RSC    

年代:1987

数据来源: RSC

摘要:

6 Alicyclic Chemistry By N. S. SlMPKlNS Department of Chemistry Queen Mary College Mile End Road London El 4NS 1 General A variety of caged and strained structures continue to attract attention. Both f4] paracyclophane (1)’ and [4]metacyclophane (2)* have been generated from the corresponding ‘Dewar isomers’ and identified by spectroscopic and trapping methods. The secohexaprismane (3) has been synthesi~ed,~ and Mehta and Padma have also reported the first synthesis of the 1,4-bishomohexaprismane (4) (‘gar~dane’).~ Other hydrocarbons which have been synthesized include the tetracycle (5),’ and [4.4.4]propellahexaene (6).6Treatment of the diketone (7) with Tio gave the compound (S) presumably uia the desired diene (9).7 (7) (9) (8) ’ T. Tsuji and S.Nishida J. Chem. SOC.,Chem. Commun. 1987 1189. * G. B. M. Kostermans P. van Dansik W. H. de Wolf and F. Bickelhaupt J. Am. Chem. Soc. 1987 109 7887. G. Mehta and S. Padma J. Am. Chem. SOC.,1987 109 2212. G. Mehta and S. Padma J. Am. Chem. SOC.,1987 109 7230. R. Gleiter and U. Steuerle Tetrahedron left. 1987 28 6159. L. Waykole and L. A. Paquette J. Am. Chem. SOC.,1987 109 3174. J. E. McMurry and R. Swenson Tetrahedron Lett. 1987 28 3209. 133 N. S. Simpkins A number of reports detail further investigations of ring-expansion methods using sulphur- or selenium-stabilized carbanions.' The method described previously by Cohen for transformation of adducts such as (10) into the ring-expanded a-phenylthiobutane products can now be conducted under basic conditions (Scheme l).9 Similar products are also available by a novel ring-expansion described by Trost." Both a-phenylthio- and a-methoxy ketones e.g.(1 l) were formed by Lewis acid-mediated rearrangement of the intermediate sulphones. SOzPh i H X = SPh or OMe (11) Scheme 1 74% Scheme 2 Overman has reported an expansion reaction which converts certain cyclic vinyl acetals into fused tetrahydrofurans (Scheme 2).11 A number of different systems and reaction conditions were examined in this reaction which is thought to proceed via sequential Prins cyclization-pinacol rearrangement. Two other notable ring- expansions proceed uia radicals to give a variety of cyclic keto-esters.12 Further reports concern the cyclization reactions of unsaturated organolithiums derived from alkyl vinyl and aryl halides.13 Cyclic 1,2-and 1,3-diones are available by reduction of epoxy acetals with Zn/ClSiMe and with LiAlH4 re~pective1y.l~ A new asymmetric transformation of cyclic enones which corresponds to conjugate n R.C. Gadwood I. M. Mallick and A. J. Dewinter J. Org. Chem. 1987 52 774; A. Krief and J. L. Laboureur Tetrahedron Lett. 1987 28 1545; A. Krief J. L. Laboureur and W. Dumont Tetrahedron Lett. 1987 28 1549. 9 W. D. Abraham M. Bhupathy and T. Cohen Tetrahedron Lett. 1987 28 2203. 10 B. M. 'Trost and G. K. Mikhail J. Am. Chem. SOC.,1987 109 4124. 11 P. M. Herrington M. H. Hopkins P. Mishra M. J. Brown and L. E. Overman J. Org. Chem. 1987 52 3711. 12 P.Dowd and S.-C. Choi J. Am. Chem. SOC.,1987 109 3493; ibid. p. 6548. 13 M. P. Cooke jun. and R. K. Widener J. Org. Chem.. 1987 52 1381; W. F. Bailey T. T. Nurmi J. J. Patricia and W. Wang J. Am. Chem. SOC.,1987 109 2442. 14 Y. D. Vankar N. C. Chaudhuri and C. Trinadha Rao Tetrahedron Lett. 1987,28 551. Alicyclic Chemistry 135 addition of the acetaldehyde enolate utilises chiral phospholidines (Scheme 3).15 Several other phospholidines were examined in this reaction including a diastereomer of the compound shown but these were less successful. The reaction also worked well using cyclohexenone or cycloheptenone giving good chemical yields and 88% and 95% e.e. respectively. A 79% 98% e.e. Scheme 3 2 Three-membered Rings Mash has published further papers concerning the diastereoselective cyclopropana- tion of unsaturated chiral ketals.I6 A new cyclopropanation procedure for allylic alcohols uses samarium metal and is characterized by high yields and good diastereoselectivities (Scheme 4).” The procedure appears cleaner and more stereoselective than the Simmons-Smith reaction in certain cases; notably isolated olefins appear to be inert.Smor Sm(Hg) 6 M e + ‘4Me ‘4 Me CH,I,,THF ’ Bu’ But -78°C to r.t. But OH OH OH >200 1 (9970 yield) Scheme 4 Stereoselective reduction of gem-dichlorocyclopropanes is possible by use of potassium diphenylphosphide in DMS0.I8 Nucleophilic opening of suitably acti- vated cyclopropanes has been studied further using amines” and selenolate anions2* (Scheme 5).The reaction with amines provided a variety of functionalized dihy- dropyrroles and could be extended to provide products capable of elaboration to azabicyclic alkaloids. The ring-opening reaction of MeSeNa with diactivated cyclo- propanes contrasts with the 0-alkyl bond cleavage observed with the monoactivated system. A new preparation of vinylcyclopropanes such as (12) was reported last year. These products undergo pyrolytic rearrangement to the corresponding cyclopen- D. H. Hua R. Chau-Yu-King J. A. McKie and L. Myer J. Am. Chem. SOC.,1987 109 5026. 16 E. A. Mash K. A. Nelson and P. C. Heidt Tetrahedron Letr. 1987 28 1865; E.A. Mash and K. A. Nelson Tetrahedron 1987 43 679. 17 G. A. Molander and J. B. Etter J.Org. Chem. 1987 52 3942. ” G. F. Meijs J. Org. Chem. 1987 52 3923. 19 J. P. Celerier M. Haddad D. Jacoby and G. Lhommet Tetrahedron Lett. 1987 28 6597. 20 A. Krief and M. Trabelsi Tetrahedron Lett. 1987 28 4225. N. S. Simpkins C02Me I Ref. 19 PCO2Me 1.3 eq. MeSeM C02Me C0,Me (M = Na or L,) ' MeSeqC02Me Ref. 20 Scheme 5 Scheme 6 tenes. Now this conversion can be conducted by treatment with TMSI followed by base-induced ring closure (Scheme 6).2' Interestingly the endo isomer of (12) could be converted quantitatively into (13) via its silyl enol ether. These transformations were studied on a variety of bi- and tri-cyclic cyclopropanes. Both the stereoselective synthesis22 and regioselective addi- tion reactions23 of doubly activated vinylcyclopropanes have received further atten- tion.Piers has used the palladium-catalysed coupling of cyclopropyl zincs with vinyl iodides to prepare vinylcyclopropanes.24 This method was used to synthesize the sesquiterpenoids (*)-prezizanol and (*)-prezizaene. Cyclopropane intermediates feature in a new synthesis of pederol in which the cyclopropane assists in a key photolytic rearrangement as well as functioning as a masked gem-dimethyl 3 Four-membered Rings 4,4-Dichlorocyclobutenonederivatives readily available from dichloroketene have previously resisted efficient dechlorination. A new method which employs Zn/ EtOH/ AcOH/TMEDA conducts this transformation cleanly in good yields (Scheme 7).26 84% Scheme 7 21 A. Fleming G.Sinai-Zingde M. Natchus and T. Hudlicky Tetrahedron Lett. 1987 28 167. 22 J. E. Backvall J. 0. Vagberg C. Zercher J. P. Genet and A. Denis J. Org. Chern. 1987 52 5430. 23 K. Burgess J. Org. Chem. 1987 52 2046. 24 E. Piers M. Jean and P. S. Marrs Tetrahedron Lett. 1987 28 5075. 25 M. C. Pirrung and P. M. Kenney J. Org. Chem. 1987 52 2335. 26 R. L. Danheiser and S. Savariar Tetrahedron Lett. 1987 28,3299. Alicyclic Chemistry The cleavage of cyclobutanes using radical methods has been used in a new synthesis of phthalide~~~ and also in a modification of Crimmins’ silphinene syn- thesis.28As last year a great amount of interest has focused on intramolecular 2 + 2 cycloadditions. A number of examples of this type of reaction are outlined in Scheme 8.bv CuSO,CF, Et,O b LI Ref. 30 0 0 Ref. 31 Scheme 8 Pirrung has conducted a more detailed investigation of the cyclooctenone cyclo- additions reported last year.32 4 Five-membered Rings Two reports detail further extensions of Canonne’s work on annelations using bis-Grignard reagents.33 The usefulness of samarium for the stereoselective construc- tion of functionalized cyclopentanes has also been further demonstrated. Thus ketoesters or ketoamides bearing suitable appendages can be cyclized in good yield and with high diastereoselectivity by use of SmIz (Scheme 9). A very attractive ene-type cyclization of triene ethers has appeared which uses an easily prepared Feo catalyst.36 Scheme 10 outlines this reaction which utilizes 27 K.Kobayashi M. Itoh and H. Suginome Tetrahedron Lett. 1987 28 3369. 28 M. T. Crimmins and S. W. Mascarella Tetrahedron Lett. 1987 28 5063; M. T. Crimmins and L. D. Could J. Am. Chem. SOC.,1987 109 6199. 29 W. T. Brady Y.4. F. Giang L. Weng and M. M. Dad J. Org. Chem. 1987 52 2216. 30 S. Ghosh S. R. Raychaudhuri and R. G. Salomon J. Org. Chem. 1987,52 83. 31 A. R. Math and D. J. McGarvey Tetrahedron Lett. 1987 28 5087; A. R. Matlin T. C. Leckta D. J. McGarvey P. W. Jacob and H.A. Picken ibid, p. 5083. 32 M. C. Pirrung and N. J. G. Webster J. Org. Chem. 1987 52 3603. 33 P. Canonne R. Boulanger and M. Bernatchez Tetrahedron Lett. 1987 28 4997; P. Canonne and M. Bernatchez J. Org. Chem. 1987 52 4025. 34 G. A. Molander and C.Kenny Tetrahedron Lett. 1987 28 4367. 35 G. A. Molander J. B. Etter and P. W. Zinke J. Am. Chem. SOC.,1987 109 453. 36 J. M. Takacs and L. G. Anderson J. Am. Chem. SOC.,1987 109 2200. N. S. Simpkins BU'OH Me-8-Me SOEt SIIII~ HO CO2Et -78 "C + r.t. Me-' 15Yo y80% Ref. 35 Scheme 9 A Ph l-7 v :yM; ~~/C/OH;H' 71. 15% bpy.fe" ' Me 62% overall Scheme 10 SnBu3 10-15 mol '/o of catalyst and which is highly diastereoselective. Changing the geometry of the allylic ether double bond allows access to isomeric products having truns-substitution about the newly formed C-C single bond. Cyclic acyliron complexes are available by reaction of a,@-unsaturated acylirons with allylstannanes (Scheme 1l).37 The results contrast with the simple Michael addition products obtained using allysilane.Trost has published several reports concerning recent explorations of palladium-mediated cyclizations. Reductive cyclization of 1,6-enynes occurs nicely using a combination of (dba)3Pd3CHC13/ HOAc/ PMHS,38 whereas the correspond- ing unsaturated product was obtained using Pd(OAc) (Scheme 12).39An alternative 37 J. W. Herndon J. Am. Chem. Soc. 1987 109 3165. 3X B. M. Trost and F. Rise J. Am. Chem. SOC.,1987 109 3161. 39 B. M. Trost and D. J. Jebaratnarn Tetrahedron Lett 1987 28 1611. Alicyclic Chemistry Reagent i Pd(OAc)2- ii (dba),Pd,CHCI, HOAc PMHS-. saturated C(1)-C(2) Scheme 12 system for enyne cyclization uses a polymer-supported nickel-chromium catalyst and enables the preparation OF five- and six-membered dienes."' Intramolecular carbenoid cyclization of a-diazocarbonyl compounds has now been extended to phosphonate phosphine oxide and sulphone containing systems (Scheme 13).N2 3(Et0)2P11 0 0 67Yo Ref. 41 &SO,Ph -Rh(OAc) Uo 75% iO2Ph Ref. 42 Scheme 13 An increasing number of attractive building blocks are available in optically active form from enzymic reactions. Scheme 14 illustrates two such recent reports utilizing racemic and prochiral starting materials. Further transformation of chiral cyclopen- tanones such as (14) to bicyclic products e.g. (19 attractive For further synthesis was also demonstrated. Krief has described a cyclization reaction of benzyllithiums generated from selenides (Scheme 15).45 Interestingly either (16) or (17) can be obtained in good d.e.(96%)by selection of suitable reaction conditions whilst selenide (18) was obtained by use of 0.1 eq. of BuLi. Corey has described a novel one-pot annulation which gave bicyclic enone (19) in good yield (Scheme 16).46The tricyclic product was also obtained by the same procedure. The ready availability of (19) enabled the first total synthesis of 40 B. M. Trost and J. M. Tour J. Am. Chem. SOC.,1987 109 5268; B. M. Trost and G. J. Tanoury ibid. p. 4753. 41 B.Corbel 0. Hernot J.-P. Haelters and G. Sturtz Tetrahedron Lett. 1987 28 6605; H. M. L. Davies and L. V. T. Crisco ibid. p. 371. 42 H. J. Monteiro Tetrahedron Lerr. 1987 28 3459.43 Z.-F. Xie H. Suemune and K. Sakai J. Chem. Soc. Chem. Cornmun. 1987 838. 44 D.W. Brooks and K. W. Woods J. Org. Chem. 1987 52 2036. 45 A. Krief and P. Barbeaux J. Chem. SOC.,Chem. Cornmun. 1987 1214. 46 E. J. Corey and W. Su Tetrahedron Leu. 1987 5241 N. S. Simpkins Pseudomonas jluorescens lipase ' 0, AcO C02Et HO' C02Et 42% yield >99% e.e. Ref. 43 0 -B;t:aes:'s .&OH -O W0 (14) 75% yield (15) Ref. 44 Scheme 14 fFe-Ph Me Ph Me Ph Me Ph Me &CH3 + b4-CH. SeMe &, U MaBui t Bu'CECC0,Ph -M@ Me02C 0 Me02C 0 OLi Scheme 16 (19) 70% 0 0 CI 1. AICI,(CH,CI) Zn'/PhH/DMSO 0 ::o HG 2. HCECH H2O R' R2 RZ R2 3243% overall Scheme 17 (*)-bilobalide a member of the gingkolide family.47 Another cyclopentenone prepar- ation which has appeared combines two previous procedures involving Lewis acid mediated chlorocyclopentenone synthesis followed by reductive dechlorination (Scheme 17).48 Finally an interesting ring cleavage-ring forming sequence occurs on treatment of certain cyclic diketones with excess ethylene glycol-BF,.OEt e.g.Scheme 18.49 The reaction is thought to proceed via an initial aldol process followed by acetal- 47 E. J. Corey and W. Su J. Am. Chern. SOC.,1987 109 7534. 48 C. J. Rizzo N. K. Dunlap and A. B. Smith 111 J. Org. Chem. 1987 52 5280. 49 H. Suemune K. Oda and K. Sakai Tetrahedron Lert. 1987 28 3373. Alicyclic Chemistry 141 BF,.OEt, 7eq. ___ 80 :20 78% combined yield Scheme 18 initiated ring fragmentation.Although mixtures of products are obtained the method provides easy access to some unusually substituted cyclopentenes and cyclohexenes. 5 Six-membered Rings Further reports have dealt with the construction of six-membered rings by means of tandem reaction sequences for example one-sot sequential double Michael reactions (Scheme 19). moLi A OMM CO,Me THF-78"C+ -4O"C 10h 86% Ref. 50 HO 52% (+stereoisomer) Ref. 51 Scheme 19 The top example shows the efficient use of a chiral Michael acceptor in an intermolecular proce~s.'~ The second intramolecular process gave the indicated tricyclic intermediate which was further elaborated to (*)-pentalenic acid." Two more examples of note in this category are outlined below in Scheme 20.The formation of tricycle (20) in 80% yield is the best result from the examples tried. Other substrates gave mixtures of compounds including minor products having cyclopropanes cyclobutanes and medium-ring ethers.52 The synthesis of nitro-substituted decalones is one of three methods examined which gave variable stereochemical result^.'^ 50 H. Nagaoka K. Kobayashi T. Okamura and Y. Yamada Tetrahedron Lett. 1987 28 6641. 'I M. Ihara M. Katogi K. Fukumoto and 'T.Kametani J. Chem. Soc. Chem. Commtm. 1987 721. 52 J.-F. Lavallee and P. Deslongchamps Tetrahedron Lett. 1987 28 3457. 53 F. Richter and H.-H. Otto Tetrahedron Lett. 1987 28 2945. N. S. Simpkins (20) SO% Ref. 52 H I NO2 NO2 1 :4 45% yield Ref.53 Scheme 20 A tandem Michael-Claisen condensation has also been reported,54 whilst Posner has adapted his previous rnulticomponent annulation procedure to convert cyclo- alkenones into ring-expanded alkenolide~.~~ Annulation of a carbohydrate-derived ketone has been possible for the first time using the Stork modification of the Robinson annulation pr~cedure.~~ Both enantiomers of 5-trimethylsilyl-2-cyclohexenoneare available through reac- tion of the racemate with p-toluenethiol in the presence of ~inchonidine.~' These compounds are potentially very versatile intermediates for the preparation of many chiral cyclohexenone systems. A more detailed account of the enantioselective conversion of anthranilic acid derivatives into chiral cyclohexanes has appeared.58 Here the Birch reduction of the diazepine derivative (21) followed by alkylation gave the desired products (22) in good d.e.(Scheme 21). Scheme 21 A further development of Molanders annulation chemistry allows extension to the preparation of chiral 1,2-cyclohexanediols (Scheme 22).59 Thus chiral epoxy aldehydes prepared using the Sharpless procedure combine with 3-iodo-2-[ (trimethylsilyl)methyl]propene under the influence of SnF to give 54 T. H. Chan and C. V. C. Prasad J. Org. Chem. 1987 52 110. 55 G. H. Posner E. Asirvatham K.S. Webb and S. Jew Tetrahedron Lett. 1987 28 5071. 56 R. V. Bonnert and P. R. Jenkins J. Chem. Sac. Chem. Commun. 1987 6. 57 M. Asaoka K.Shima and H. Takei Terrahedron Lett.1987 28 5669; M. Asaoka and H. Takei ibid. p. 6343. 58 A. G. Schultz P. J. McCloskey and J. J. Court J. Am. Chem. Soc. 1987 109 6493. 59 G. A Molander and D. C. Shubert J. Am. Chem. Soc. 1987 109 576. Alicyclic Chemistry yields 0-67% Scheme 22 (24) Reagents i PhCOCl NaOH; ii PBrJBr,; iii MeSCH,SOMe KH; iv H30; v HX vi chiral lithium amide Scheme 23 the indicated products in moderate to excellent d.e. Chiral cyclohexanes have also been obtained starting from (S)-(-)-3-methyl piperidine (23),60 and by use of a chiral lithium amide base on the prochiral acid (24) (Scheme 23).61 Interest in cyclitols continues and especially in phosphates of myo-inositol an important cellular secondary messenger thought to mediate the release of Ca2+ from intracellular stores.Both enantiomers of myo-inositol 1,4,5-triphosphate (25) are available via a protection and resolution sequence using camphanic acid chloride.62 Similar chemistry has been used to prepare the corresponding 1-phosphate and 4-ph0sphate.~~ Another cyclitol-pinitol (26) has been synthesized in racemic form starting from diol (27) (Scheme 24).64 The starting material (27) was obtained by microbial oxidation of benzene. This method appears to have great potential for synthesis especially if substituted chiral derivatives of (27) can be used. Enzymic enantioselective hydrolysis of epoxides (28) and (29) has been studied and the chiral products used to synthesize (-)-chorismic acid (30) and (-)-shikimic acid (31).6’ Again this year a large number of reports focus attention on various aspects of the Diels- Alder reaction.66 The use of 2-and E-phenylsulphonylacrylateshas been 60 A.Thurkauf P. Hillery A. E. Jacobson and K. C. Rice J. Org. Chem. 1987 52 5466. 61 C. Duhaniel A. Ravard J.-C. Plaquevent and D. Davoust Tetrahedron Lett. 1987 28 5517. 62 J. P. Vacca S. J. deSolrns and J. R. Huff J. Am. Chem. SOC.,1987 109 3478. 63 D. C. Billington R. Baker J. J. Kulagowski and I. M. Mawer J. Chem. Soc. Chem. Commun. 1987 314. 64 S. V. Ley F. Sternfeld and S. Taylor Tetrahedron Lett. 1987 28 225. 65 J. L. Pawlak and G. A. Berchtold J. Org. Chem. 1987 52 1765. 66 For a recent review of the TMDA see D. Craig Chem. SOC.Rev. 1987 1& 187. N. S.Simpkins HO&OP03 Hz 0~.. OBZ MeOaOBz MeOaOH ?H ?H + -+ a::: ORz OBz HO’ OH I (27) OH i26) Scheme 24 examined in more detail by Parsons. The two isomers give complementary regiochemical control in reactions with dienes such as (32) (Scheme 25).67 A variety of 2-phenylsulphinyl-1 -nitroalkenes has been prepared and used as nitroacetylene equivalents in Diels-Alder reactions:* Dienylboronates constitute an attractive new group of dienes which can be used in the Diels-Alder reaction (Scheme 26).69 OAc OAc n,,SO2Ph + nSOzPh OAc C02Me C02Me OAc OAc COzEt PhS02 Scheme 25 67 A. D. Buss G. C. Hirst and P. J. Parsons J. Chem. SOC.,Chern. Comrnun. 1987 1836. M. E. Jung and D. D. Grove J. Chem. SOC.,Chem. Commun. 1987,753; For a related paper concerning the nitro group as a Diels-Alder regiocontrol element see N.Ono H. Miyake A. Kamimura and A. Kaji J. Chem. SOC.,Perkin Trans. 1 1987 1929. 69 M. Vaultier F. Truchet B. Carboni R.W. Hoffmann and I. Denne Tetrahedron Lett. 1987 28 4169. Alicyclic Chemistry 145 A' Scheme 26 The cycloaddition reaction was demonstrated only with maleic anhydride or N-phenyl maleimide although an additional feature is the stereoselective reaction of the allylboronate adducts with aldehydes as shown. Arabinose-derived auxiliaries for acrylate dienophiles have been examined with modest results.'' Much better diastereoselectivity can be obtained using menthyl acrylates such as (33) as demon- strated in a synthesis of lactone (34) a key intermediate for carbonucleoside synthesis (Scheme 27).71 + 'S COzMen ow SOPy 0 (33 1 (34) Scheme 27 High asymmetric induction has been observed in a photolytic 4 + 2 cycloaddition using chiral methoxymethylpyrrolidines as chiral auxi1ia1-y.~~ Further reports con- cerning the cycloadditions of optically active fumarates have appeared,73 as well as the use of chiral Lewis acids to effect asymmetric Diels-Alder reaction.74 Optimiz- ation of the tandem ene/intramolecular Diels- Alder (IMDA) process between 1,4-~yclohexadiene and singly or doubly activated acetylenes has been described (Scheme 28).75The reaction shown using DMAD occurred much more rapidly using microwave heating than conventional methods.With singly activated acetylenes the use of ZnC1 to mediate reaction was optimal.'* T. K. M.Shing and P. Lloyd-Williams J. Chem. SOC.,Chem. Commun. 1987,423. 71 Y. Arai Y.Hayashi M. Yarnamoto H. Takayama and T. Koizumi Chem. Lett. 1987 185. 72 D. Dopp and M. Pies J. Chem. SOC. Chem. Commun. 1987 1734. 73 K. Furuta S. Hayashi Y. Miwa and H. Yamamoto Tetrahedron Lett. 1987 28 5841. 74 H. Takemura N. Komeshima I. Takahashi S. Hashimotq N. Ikota K. Tomioka and K. Koga Tetrahedron Lett. 1987 28 5687. 75 R. J. Giguere A. M. Namen G. Majetich and J. Defauw Tetrahedron Lefr. 1987 28 6553. 146 N. S. Simpkins The IMDA reaction of several suitably substituted furans was found to proceed more efficiently in 2.OM calcium chloride solution than under other recommended condition^.'^ A novel tandem reaction sequence involves a one-sot oxidative cleavage of a furan followed by IMDA reaction of the resulting ene dione (Scheme 29).77 PCC/CH,CI 40% Scheme 29 C02Me 3OO0C U 85% 85 Yo (N.B.in situ decarbomethoxylation) Scheme 30 Three consecutive communications describe preliminary investigations of the transannular Diels- Alder reaction. A variety of tricyclic systems were prepared from the appropriate macrocyclic trienes (Scheme 30).78In some cases the transannular reaction appears more facile than the corresponding acyclic IMDA process. 6 Larger Rings Another annulation process from the Molander group allows for facile construction of ether-bridged seven- and eight-membered carbocycles in excellent yields (Scheme 3 l).79The reaction involves the now familiar stannous fluoride mediated reaction of a bifunctional allylsilane with either 1,4-or 1,5-dicarbonyl compounds.Wender's [4 + 41 cycloaddition approach to the cyclooctadienyl products described last year has been the subject of photolytic modification.80 The method was used in a formal total synthesis of coriolin. Marshall has published a series of papers highlighting the synthetic utility of the Wittig ring-contraction of cyclic ethers including syntheses of (*) aristolactone epimukulol and desoxyasperdiol.81 Finally 76 B. A. Keay J. Chem. Soc. Chem. Commun. 1987 419. 77 H-J. Wu and K. Pan J. Chem. Soc. Chem. Commun. 1987 898. 78 K. Baettig C. Dallaiere R. Pitteloud and P. Deslongchamps Tetrahedron Lett.1987 28 5249; K. Baettig A. Marinier. R. Pitteloud. and P. Deslongchamps ihid.. p. 5253 G. Beruhe and P. Deslong-champs ibid.,p. 5255. 79 G.A. Molander and D. C. Shubert J. Am. Chem. Soc. 1987 109,6877. 80 P. A. Wender and C. R. D. Correia J. Am. Chem. SOC.,1987 109 2523. J. A. Marshall J. Lebreton B. S. DeHoff and T. M. Jenson J. Org. Chem.,1987,52,3883; J. A. Marshall J. Lebreton B. S. DeHoff and T. M. Jenson Tetrahedron Lett. 1987 28 723; J. A. Marshall and J. Lebreton Tetrahedron Lett. 1987 28 3323; J. A. Marshall T. M. Jenson and B. S. DeHoff J. Org. Chem. 1987 52 3860; For related studies see also; J. A. Marshall R. C. Andrews and L. Lebioda J. Org. Chem. 1987 52 2378. 147 Alicyclic Chemistry 100% >10:1 ratio of diastereoisomers Phu -Ph-d-'H 63'/o Scheme 31 further syntheses of muscone have appeared using either a silyloxy-Cope ring- expansion,82 or radical ring-expansion methods.83 7 Bicyclics and Polycyclics A variety of fused cyclopentenones are available via a Mn"'-promoted annulation reaction of enol ethers.84 A new stereocontrolled synthesis of either the cis-or trans-hydroazulene skeleton utilizes alkylative trapping of oxy-Cope intermediates (Scheme 32).85 Q2qq& H H H 81% Br (35) Scheme 32 Thus attempted anionic rearrangement of (35) using KH was unsuccessful giving ether (36) whilst the desired transformation could be cleanly effected thermally in the presence of an acid scavenger.Another addition to the repertoire of tropone cycloadditions is the [6 + 31 variant described by TroskX6 The reaction involves the palladium-catalysed cycloaddition of a trimethylenemethane (TMM) precursor with tropone (Scheme 33).The sequence was also explored with a variety of substituted tropones and TMM precursors giving mainly very good yields. A number of bicyclic skeletons are accessible from conjugate addition products such as sulphoxide (37) (Scheme 34).87 82 R. W. Thies and K. P. Daruwala J. Org. Chem. 1987 52 3798. 83 H. Suginome and S. Yamada Tetrahedron Leu. 1987 28,3963. 84 E. J. Corey and A. K. Ghosh Tetrahedron Lett. 1987 28 175. M. Sworin and K.-C. Lin J. Org. Chem. 1987 52 5640. 86 B. M. Trost and P. R. Seoane J. Am. Chem. SOC.,1987 109 615; B. M. Trost and D.T. MacPherson ibid. p. 3483. 87 R. K. Haynes and A. G. Katsifis J. Chem. Soc. Chem. Comun. 1987 340; see also R. K. Haynes and S. C. Vonwiller ibid. p. 92. N. S. Simpkins 68% Scheme 33 Scheme 34 Hence bicycloheptanone (39) was obtained by treatment of (37) with KOBu' in THF at room temperature whilst use of LDA at -78 "C gave bicyclo[3.2.l]octano1 (38) via kinetically preferred deprotonation of the vinyl sulphoxide. Bicyclo[3.2.l]oct-6-enes are available via a [3 + 21 cycloaddition process which combines allylic chlorides with acetylenes (Scheme 35).88 The reaction works best when the acetylene is substituted with a phenylthio group. The method was used to synthesize an epimer of helmintho~poral.~~ A synthesis of (*)-8,14-cedranoxide (40) has been achieved in which the carbon skeleton was constructed using an electrochemical key-step ('Scheme 36).90 PhS Ph 80% Scheme 35 OMe --*lF.2 Anodic Oxidation r 77 OH 0' [ 0- Scheme 36 88 B.D. Gray C. M. McMillan J. A. Miller and M. Moore Tetrahedron Lett. 1987 28 235; B. D. Gray C. M. McMillan J. A. Miller and G. Mustafa Ullah Tetrahedron Left. 1987 28 689. 89 B. D. Gray and J. A. Miller J. Chem. SOC.,Chem. Commun. 1987 1136. 90 Y. Shizuri Y. Okuno H. Shigemori and S. Yamamura Tetrahedron Lett. 1987 28 6661. Alicyclic Chemistry 8 Natural Product Synthesis Polycyclopentanoid natural products continue to attract synthetic attention. This year a number of reports describe full details of methods suitable for synthesis of such compounds based on y-0x0-a-ester en~lates,~~ the de Mayo reaction (hir- s~tene),~~ A different formal synthesis and Panson-Khand cyclization (q~adrone).~~ of quadrone uses a highly regioselective cyclopropane opening reaction possible due to participation of a neighbouring carboxyl group (Scheme 37).94The enantio- specific synthesis of a suitably functionalized taxol A-ring (41) has been reported using an intramolecular closure of an epoxy-allysilane (Scheme 38).95 \/ Scheme 37 J+ - L-Arabinose + HO / C0,Et TBDMSO- TMS HO J CO,Et TBDMs0-Q ko (41) Scheme 38 Fragment (41) is obtained after a rather laborious sequence of over 20 steps starting from L-arabinose.Other taxane studies have centred on rapid construction of bicyclic frameworks corresponding to either the AB or BC skeleton.Thus Swindell has described an interesting route to the BC unit (42) which utilizes cleavage of known vinylogous imide photoproducts (Scheme 39).96 91 J. P. Marino and E. Laborde J. Org. Chem. 1987,52 1. 92 B. W. Disanayaka and A. C. Weedon J. Org. Chern. 1987 52 2905. 93 P. Magnus L. M. Principe and M. J. Slater J. Org. Chem. 1987 52 1483; see also N. E. Schore and M. J. Knudsen J. Org. Chem. 1987 52 569. 94 T. Imanishi M. Matsui M. Yamashita and C. Iwata J. Chem. Soc. 1987 1802. 95 L. Pattersson T. Frejd and G. Magnusson Tetrahedron Lett. 1987 28 2753; see also J. Lin M. M. Nikaido and G. Clark J. Org. Chern. 1987 52 3745. 96 C. S.Swindell B. P. Patel S. J. deSolms and J. P. Springer J. Org. Chem. 1987 52 2346. N. S. Simpkins 0 + ISOMERS I f=J) +--pJ-J ti H 0 (42) Scheme 39 The key step involved initiation of cyclobutane ring cleavage by a suitable group on nitrogen (R) following prior conversion of the ketone into a suitable leaving group. On a similar theme a different cycloaddition-cleavage sequence has been described which aEords a simple AB-type subunit.97 Both AB- and BC-type bicyclic taxane models are available by the [4 + 41 cycloaddition approach of Wender highlighted last year (Scheme 40)?8 Scheme 40 A formal synthesis of forskolin (43)has been reported by Ziegler which involves modifications of an intermediate (44) obtained previou~ly.~~ A very neat synthesis of a precursor to the AB portion of forskolin involves a one-pot tandem Michael- aldol reaction of (45) (Scheme 41).'0° Another novel approach involves an anionic oxy-Cope rearrangement and pro- vides a model ABC compound."" Finally efficient elaboration of the C-ring has been demonstrated using a compound with a model AB system (SCheme 42).'02 97 G.A. Kraus P. J. Thomas and Y.4. Hon J. Chem. SOC.,Chem. Commun. 1987 1849. 98 P. A. Wender and M. L. Snapper Tetrahedron Lett. 1987 28 2221. 99 F. E. Ziegler B. H. Jaynes and M. T. Saindane J. Am. Chem. SOC.,1987 109 8115. loo E. R. Koft A. S. Kotnis and T. A. Broadbent Tetrahedron Lett. 1987 28 2799. 101 1. A. Oplinger and L. A. Paquette Tetrahedron Left. 1987 28 5441.lo* S. Hashimoto M. Sonegawa S. Sakata and S. Ikegami J. Chem. SOC.,Chem. Commun. 1987 24. Alicyclic Chemistry 0 Forskolin (43) Scheme 41 C02Me C02Me _-_ + OH H ,,,,0SiPh2 &. OH Scheme 42 The first synthesis of the phorbol skeleton has been rep~rted.''~ Compound (46) a hybrid of the tigliane and ingenane structural types was prepared using an IMDA process and an intramolecular aldol reaction in the key ring-forming steps (Scheme 43). A very straightforward synthesis of the basic tricyclic framework of the ingenanes has been accomplished.'04 Another model study uses an intramolecular dioxolenone photocycloaddition developed earlier to prepare the same ske1et0n.I"~ More advanced studies have been reported by Paquette in which the tricyclic system (47) I03 P.A. Wender R. M. Keenan and H. Y. Lee J. Am. Chem. Soc. 1987 109 4390. I04 G. Mehta and V. P. Pathak J. Chem. SOC.,Chem. Commun. 1987 876. J. D. Winkler K. E. Henegar and P. G. Williard J. Am. Chem. SOC.,1987 109 2850. 152 N. S. Sirnpkins H I \ Br -Me09 cHo-w Me0 OMe Me0 TMSO -0Bn -0Bn H H Br HO OH OH OBn (46) Scheme 43 Me--- HO (47) (48) Scheme 44 was advanced to keto-tetrol (48) having all the functionality present in the natural product ingenol (49) (Scheme 44).'06 The synthesis of a number of other product types possessing fused seven-membered rings has been addressed. Rigby has used cyclopropyl ketones as inter- mediates in a synthesis of (&)-grosshemin (50),'07 and in a construction of the ophiobolane ring system (Scheme 45).'08 The same group has detailed more efforts in the synthesis of guaianolide~,'~~ and other work in this area has led to a total synthesis of (*)-gnididione."' Massive synthetic interest continues to centre on the synthesis of the antiparasitic agents the milbemycins and avermectins.Attention has now largely turned from the 106 R. J. Ross and L. A. Paquette J. Org. Chern. 1987 52 5497. I07 J. H. Rigby and C. Senanayake 1. Am. Chem. Soc. 1987 109 3147. 108 J. H. Rigby and C. Senanayake J. Org. Chem. 1987 52 4634. 109 J. H. Rigby and J. A. Z. Wilson J. Org. Chem. 1987 52 34. 110 C. P. Dell and D. W. Knight J. Chem. Soc. Chem. Commun. 1987 349.Alicyclic Chemistry OCOBu' o+0 OAc Ophiobolin F Scheme 45 spiroacetal grouping to the oxahindrene portion and to problems of coupling various fragments to give the natural products. Jung has used an elegant cycloaddition strategy to prepare fragment (51) in racemic form (Scheme 46).'" The initial cycloaddition furnishes (52) which has the required skeleton as well as functionality at all the necessary positions; the remaining steps involve reduction of the C-4 ester to a methyl and inversion of configuration at C-5. Simpler systems have been prepared by White'12 and by Dani~hefsky;"~ each of these products lacked one key feature needed for the natural product. The efficient preparation of the monocyclic lower portion of milbemyin p1in chiral form has also been described (Scheme 47).' l4 111 M.E. Jung Y. Usui and C. T. Vu Tetrahedron Lett. 1987 28 5971. I12 J. D. White and A. P. Dantanarayana Tetrahedron Left. 1987 28 6417. 113 D. M. Armistead and S. J. Danishefsky Tetrahedron Lett. 1987 28 4959. '14 N. J. Anthony T. Clarke A. B. Jones and S. V. Ley Tetrahedron Lett. 1987 28 5755. N. S. Sirnpkins (52) 53% +isomer Scheme 46 + + 0 OH 0 0 .0 0 4' PhSO2 PhSO2 0,H i 0,H I 0 OMe Scheme 47 OR x -OR /-Partial structure 2-epimer of avermectin or ivermectin 0; %- H OR Me Conjugated isomer Scheme 48 Ahcyclic Chemistry A key deconjugation step in Hanessian's relay synthesis of avermectin B, has become the subject of some controversy.From two subsequent reports it now seems that deconjugation of either A2-avermectin or A*-ivermectin directly to the natural products does not occur.'15 Rather the primary product of such a process is the 2-epi-isomer and the natural system can then result under certain conditions by epimerization (Scheme 48). 0 Other significant targets which have received attention include phyllanthocin (53),Il6 fredericamycin A (54),"' and ikarugamycin (55).Il8 Notably Corey has devised a synthetic route to the limonoid system"' and achieved the first synthesis of a ginkgolide (*)-bil~balide.~' 11s S. Hanessian D. Dube and P. J. Hodges J. Am. Chem. Soc. 1987 109 7063; B. Fraser-Reid H. Wolleb R. Faghih and J. Barchi jun.J. Am. Chem. Soc. 1987 109 933. 116 A. B. Smith 111 and M. Fukui J. Am. Chem. Soc. 1987 109 1269; S. F. Martin M. S. Dappen B. Dupre and C. J. Murphy J. Org. Chem. 1987 52 3706. I17 M. A. Ciufolini and M. E. Browne Tetrahedron Lett. 1987 28 171; G. Mehta and D. Subrahmanyam Tetrahedron Lett. 1987 28 479; D. L. J. Clive A. G. Angoh and S. M. Bennett J. Org. C'hem. 1987 52 1339. 118 G. Mehta A. N. Murthy and D. S. K. Reddy Tetrahedron Lett. 1987 28 1467; L. A. Paquette J. L. Romine and H.-S. Lin Tetrahedron Left. 1987 28 31. 11Y E. J. Corey J. G. Reid A. G. Myers and R. W. Hahl J. Am. Chem. Soc. 1987 109 918.

ISSN:0069-3030    

DOI:10.1039/OC9878400133

出版商:RSC    

年代:1987

数据来源: RSC