ISSN:0069-3030    

DOI:10.1039/OC98986FX001

出版商:RSC    

年代:1989

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC98986BX003

出版商:RSC    

年代:1989

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 It seems appropriate that the third and final biennial review of mass spectrometry from this author covers the literature to the end of the 1980s a decade that has seen a transformation in mass spectrometry. Before 1980 despite a limited number of pioneering studies organic mass spectrometry was largely confined to the analysis of volatile compounds. Today the routine analysis of salts polar drug conjugates and biopolymers such as proteins and glycoproteins oligonucleotides and oligo- and polysaccharides is readily achievable. This has opened up mass spectrometry to the biological and medically related sciences to a degree that would have been inconceivable 10 years ago and I make no apology for biasing this Report heavily towards biochemical analysis.The other aspect of mass spectrometry that has changed dramatically is the diversity complexity and sophistication of the commercial mass spectrometers that are now in widespread use. Quadrupole and sector (magnetic) mass spectrometers have been supplemented by the quadrupole ion trap the Fourier transform mass spectrometer (derived from the previously little used ion cyclotron resonance spec- trometer) and the revitalized time-of-flight instrument. As multidimensional tech- niques have greatly broadened the scope of nuclear magnetic resonance so tandem methods have had a similar impact on mass spectrometry.New desorption modes of ionization that supplement electron impact and chemical ionization which include fast atom bombardment (ca. 8 keV bombardment) caesium ion bombardment (20 keV) synchrotron and fission fragment bombardment (MeV) and laser desorp- tion/multiphoton ionization have been further complemented by several liquid-to- vapour phase spray methods. 2 High Mass Analysis At the time of writing the previous review in this series at the end of 1987,' the concept of high mass in mass spectrometry related to an upper limit of -23 000 Da for proteins by fast atom bombardment (FAB) and -38 000 Da by 252Cf plasma desorption (PD). Within a few months there were conference reports of analyses ' M.A. Baldwin Annu. Rep. hog. Chem. Sect. B Org Chem. 1988 84 15. 19 M. A. Baldwin up to several hundred kDa and there are now two totally unrelated techniques that provide this sort of performance. Both methods are derived from techniques that had been in existence for some considerable time namely laser desorption (LD) and electrospray (ESP). Matrix-assisted UV-laser Desorption/Ionization.-The novel feature that has been introduced into LDMS is to disperse the sample at very low concentration (1 lo4-10’) in a matrix compound that absorbs at the laser frequency initially nicotinic acid absorbing strongly at 255 nm.2 Energy absorbed by the matrix is transferred to the analyte and ions are ejected into the gas phase thus giving laser desorption/ioniz- ation (LDI).The initial publication showed mass analysis at 67 000 Da and this was quickly extended to >250 000 Da.374 The study of such massive ions relies on two features the ability to create ions in the gas phase and the use of a time-of-flight (TOF) analyser which has no theoretical upper mass limit and is ideally suited to the pulsed ionization resulting from the laser pulses. Using 3 keV ion kinetic energy the TOF mass analyser gave a resolving power of only 50 but accuracy of mass measurement was 0.1-0.2%. The sensitivity was very high compared with FAB sub-pmol quantities being sufficient for spectra to be obtained successfully. Usually spectra are accumulated over 20-50 laser shots but adequate signals can be obtained from single shots.It is estimated that a single shot consumes only 10 amol of material. An alternative sample preparation method reported was to disperse the sample in a fine suspension of cobalt powder in a liquid matrix ionization being achieved with a 337 nm laser yielding spectra of proteins up to 25 000 Da with cluster ions up to 100000 Da.5 Further developments of UV-LDI have been made by Beavis and Chait who presented an analysis of factors affecting UV ionization and desorption of proteins including the use of alternative matrix compounds.6 The use of 20 keV ion energy and a reflectron increases the mass resolution and apparently increases the mass accuracy by up to one order of magnitude. Several derivatives of cinnamic acid e.g. ferulic acid (3-methoxy-4-hydroxycinnamic acid) have been used as alternative matrices.An advantage over nicotinic acid is a reduced tendency to form adduct ions by photochemical reactions and the greater mass difference between the protonated ion and the matrix adduct ion (+206 for ferulic acid and +123 for nicotinic acid) makes the separation of these peaks more fea~ible.~ 355 nm laser radiation is just as effective as that of 266nm with these different matrices.8 One of the most encouraging aspects of matrix-assisted UV-LDIMS is the very high sensitivity that is maintained throughout the working mass range,’ unlike FAB secondary ion mass spectrometry from liquids (LSIMS) and PD for which the ion M. Karas and F. Hillenkarnp Anal. Chem. 1988 60,2299. M.Karas U. Bahr and F. Hillenkamp lnt. J. Mass Spectrom. fon Processes 1989 92 231. M. Karas U. Bahr A. Ingendoh and F. Hillenkamp Angew. Chem. Int. Ed. Engl. 1989 28 760. K. Tanaka H. Waki Y. Ido S. Akita Y. Yoshida and T. Yoshida Rapid Commun. Mass Spectrom. 1988 2 151. R. C. Beavis and B. T. Chait Rapid Commun. Mass Spectrom. 1989 3 233. R. C. Beavis and B. T. Chait Rapid Commun. Mass Spectrom. 1989 3 432. R. C. Beavis and B. T. Chait Rapid Commun. Mass Spectrom. 1989 3 436. M. Karas A. Ingendoh U. Bahr and F. Hillenkamp Biomed. Mass Spectrom. 1989 18 841. Physical Methods and Techniques -Part (ii) Mass Spectrometry 21 currents drop very sharply with increasing mass. For peptides- in the range 500-5000 Da the protonated molecular ions decrease by several orders of magnitude for ionization with MeV particles in PDMS and for 8 keV FAB the drop-off is 1-2 orders of magnitude worse." Apparently there is no corresponding mass- related reduction in ionization efficiency for UV-LDIMS although it had been suggested that there could be a problem with very massive ions travelling so slowly and having insufficient momentum to produce secondary electrons at the electron mu1tipIier.l' An example of a protein studied by this method is catalase of measured molecular mass 236 230 Da which consists of four identical sub-units.The most intense signal was obtained for the single sub-unit measured as 59 060 Da. Doubly charged peaks were also observed for both the single sub-unit and the intact protein but it could be concluded that the peak at m/z 59 060 was not a quadruply charged species as there was no evidence of triply charged ions.4 Electrospray and Ionspray.-The last review in this series gave two references to a technique referred to as ionspray (ISP),'2,'3 in the context of HPLC interfacing rather than high mass analysis.In 1988 it became apparent that ISP and the associated method of ESP offered a new method of high mass analysis when Covey et al. demonstrated its use to analyse peptides proteins and olig~nucleotides.'~ A remark- able aspect of this work as applied to high mass analysis is that this performance was achieved with a 'low mass' quadrupole analyser. ESP and ISP both work by spraying a liquid solution of the analyte through a hypodermic needle held at a high potential into a chamber at atmospheric pressure.At low flow rates of -5 pl min-' the spray is nebulized with the formation of charged droplets. The spray is drawn via a pin-hole orifice through evacuated chambers into the mass spectrometer and as the solvent is stripped from the droplets isolated ions are formed. This technique developed originally by Dole and refined by Fenn," is ESP. ISP differs only in that a current of gas is used to assist the nebulization allowing higher liquid flow rates of 100-200 p1 min.-' Related atmos- pheric pressure ionization (API) methods at 1 ml min-' have been described.16 A quadrupole analyser can be used for the analysis of compounds of molecular mass perhaps fifty times greater than the nominal upper mass limit because mass analysers separate ions according to their mass/charge (m/z) ratios.If a protic solvent such as water/methanol/acetic acid is used for the spray as the solvent is stripped from the liquid droplets protons are transferred to basic sites of the analyte molecules forming multiply charged species. At a critical drop size ions can 'evaporate' from the surface and both ESP and IS? have been referred to as field-assisted ion 10 W. Ens D. E. Main K. G. Standing and B. T. Chait Anal. Chem. 1988 60,1494. A. Hedin P. Hakansson and B. U. R. Sundqvist Int. J. Mass Spectrom. Ion Processes 1987 75 275. A. P. Bruins T. R. Covey and J. D. Henion Anal. Chem. 1987 59 2642. l3 T. R. Covey A. P. Bruins and J. D. Henion Org. Mass Spectrom.1988 23 178. l4 T. R. Covey R. F. Bonner B. I. Shushan and J. D. Henion Rapid Commun. Mass Spectrom. 1988 2 249. l5 J. B. Fenn M. Mann C. K. Meng S. F. Wong and C. M. Whitehouse Mass Spectrom. Rev. 1990,9,37. l6 M. Sakairi and H. Kambara Anal. Chem.. 1989 61 1159. 22 M. A. Baldwin evaporation.” Thus a protein of mass 50 kDa which acquires 50 positive charges will pass through the mass analyser with an apparent mass of 1000 Da. Most proteins contain numerous sites that can be protonated a series of protonated species being formed generally having a maximum intensity at m/z -1000. Multiply charged negative ions can also be formed by multiple proton loss from compounds such as oligonucleotides. From the spacing of the multiply charged ion peaks in the mass spectrum the molecular mass of the protein can be determined.I8 The method is equally applicable to low mass ionic compounds and in the negative ion mode has successfully been used to study a series of anionic species such as ADP and ATP introduced as the trisodium salts.” Positive ion API of small molecules is controlled by gas-phase basicities (GB).The sensitivity for basic compounds (GB > 50 kJ mol-’) is relatively independent of compound class as protonation depends upon the kinetics of fast proton transfer from protonated water clusters whereas less basic compounds give weaker signals owing to the reduced stability of the intermediate species BH+(H20)n.20 These spray methods enjoy an advantage over the UV-LDI technique of extreme simplicity in sample introduction and the mode of ionization and perhaps greater accuracy of mass measurement.The multiple peaks allow a series of mass measure- ments to be made thereby improving the statistics of the final result. Personal experience by this reviewer has shown the mass accuracy for 10-20 kDa proteins to be within 1 Da. Limits of detection may be sub-pmol although typical sample loadings are 10-100pmol. The methods are also directly compatible with HPLC allowing direct introduction of the eluent into the liquid stream and they may offer unique advantages for peptide sequencing by tandem mass spectrometry. Both these aspects will be elaborated below. On the other hand UV-LDI appears to offer extreme sensitivity for both positive and negative ions,21 which could be important for the analysis of compounds such as oligonucleotides oligo- saccharides and phosphorylated sulphated or glycosylated proteins.It will be fascinating to see how these two very different methodologies develop and become established. From the commercial point of view there is clearly a strong bio- chemical market for a simple ‘molecular mass machine’ that can be operated by non-specialists as has been shown by the success of PDMS with a simple TOF analyser. 3 Other Soft Ionization Techniques Although the methods referred to in the previous section are begining to dominate the high mass area the other soft ionization techniques such as chemical ionization (CI) and the various desorption methods (FAB PD and LD) continue to have an essential role to play.” T. R. Covey B. I. Shushan B. A. Thomson and J. D. Henion Proceedings of the 37th ASMS Annual Conference on Mass Spectrometry and Allied Topics Miami Florida 1989 p. 558. 18 M. Mann C. K. Meng and J. B. Fenn Anal. Chem. 1989,61 1702. 19 K. W. M. Siu G. J. Gardner and S. S. Berman Org. Mass Spectrom. 1989 24 931. 20 J. Sunner G. Nicol and P. Kebarle Anal. Chem. 1988 60,1300. M. Salehpour I. Perera J. Kjellberg A. Hedin M. A. Islamain P. Hakansson and B. U. R. Sundqvist Rapid Commun. Mass Spectrom. 1989 3 259. Physical Methods and Techniques -Part (ii) Mass Spectrometry 23 Chemical Ionization.-An advantage of CI is the ability to match the reagent gas to the analyte under study thereby optimizing the analysis.Bartmess has presented a very comprehensive compilation of gas-phase thermochemical data such as basicities acidities and electron hydride and fluoride affinities.22 Electron capture negative ion chemical ionization (NICI) is a very sensitive and selective technique which has been widely used for the analysis of compounds such as biogenic amines in body fluids and tissues. Other compound classes less sensitive to NICI may be derivatized with a group that enhances electron capture e.g. the sensitivity for corticosteroids was increased tenfold by forming pentafluorobenzyloxime-trimethyl-silyl (TMS) derivatives rather than methoxime-TMS derivative^.^^ It is worth noting that derivatization is still an important component in many analyses even though desorption methods have largely removed the need for sample volatility.Anderegg has reviewed derivatization and has shown how it can enhance the molecular ion or fragment ions reduce the role of strongly directing groups be used for isomer differentiation and increase the information content of collision-induced Electron impact (EI) spectra are broadly reproducible and library searching is generally reliable for compound identification provided that an appropriate refer- ence spectrum is available whereas CI is perceived to be more variable. The reproducibility of NICI was tested for twelve compounds by six different laboratories. There was good agreement even between quadrupole and sector instruments differences arising through dissociative reactions and formation of ions such as (M + H -C1)+ from polychlorinated compounds e.g.end~sulphan.~~ Posi-tive ion CI (PICI) is generally best for generating high-intensity quasimolecular ions from a diverse range of samples whereas NICI is much more compound-specific and frequently gives high-intensity fragment ions associated with particular function- alities. Pulsed PICI/ NICI allows the optimum detection of specific compound classes in complex mixtures and has been used for the assay of organophosphorus pesticide residues in food.26 CI lends itself to interfacing with supercritical fluid chromatography (SFC) as the fluid used in the SFC separation can also act as the reagent gas. Ammonia CI has been employed for the SFC-MS analysis of polymers and derivatized oligosa~charides.~~ SFC- MS with helium charge exchange (CE) gives EI-like spectra which is valuable for interpretation as has been shown for a series of drugs and metabolites.28 CI can be viewed as part of the broader area of study of ion-molecule reactions developments having been encouraged by the increasing use of ion trap (IT) Fourier transform (FT) and tandem mass spectrometers.One novel variation of CI is to 22 J. E. Bartmess Mass Spectrom. Rev. 1989 8 297. 23 J. M. Midgley D. G. Watson T. Healey and C. N. J. McGhee Biomed. Environ. Mass Spectrom. 1989 18 651. 24 R. J. Anderegg Mass Spectrom. Rev. 1988 7 395. 25 E. A. Stemmler R. A. Hites B. Arbogast W. L. Budde M. L. Deinzer R. C. Dougherty J. W. Eichelberger R.L. Foltz C. Grimm E. P. Grimsrud S. Sakashita and L. J. Sears Anal. Chem. 1988 60 781. 26 H.-J. Stan and G. Kellner Biomed. Environ. Mass Spectrom. 1989 18 645. 27 X. X. Pinkston G. D. Owens L. J. Burkes T. E. Delaney D. S. Millington and D. A. Maltby Anal. Chem. 1988 60 962. 28 E. D. Lee S.-H. Hsu and J. D. Henion Anal. Chem. 1988 60,1990. 24 M. A. Baldwin select the reagent ion and collide it with the analyte in the collison cell of a triple quadrupole. Linked to GC this technique has been shown to give picogram sensi- tivity with a very high degree of specificity. An example is the CE ionization of 2,4-dimethylaniline for which Art' transfers sufficient energy to fragment the analyte ions whereas benzene+' transfers less energy and tends to give molecular ions only allowing the (CE) process to be separated from competing proton transfers and hydride abstraction reactions that occur in the conventional CI ion source.29 The dual cell FTmass spectrometer similarly prevents reactions between the analyte and the neutral reagent gas.30 Also using FTMS it has been shown that Fe+ forms bridged adducts with disubstituted benzenes that allow clear identification of the ortho isomers although the meta and para isomers were harder to distinguish.In a study of several such isomers xylene provided the only example that could not be identified.31 Many groups have investigated low-energy endothermic collisons between mass-selected ions and ammonia or amines. Protonated peptide ions for example form proton-bound adducts with ammonia that either lead to peptide fragment ions or eliminate the ammonium ion with formation of a neutralized peptide-potentially interesting species for study by neutralization/reionization mass spe~trometry.~~ Fast Atom Bombardment.-The mechanism of ionization in FAB and LSIMS is still not clear but Sunner has presented more evidence in support of the phase explosion model based on the concept of CI-like processes in the relatively high-pressure fluid at the interface between the liquid and the vacuum.The ionization can be modelled by classical gas-phase thermodynamic^.^^ Chemical reactions that occur in the liquid phase have been reviewed by Cooks and co-~orkers,~~ who have also shown that desorption of zwitterions induces intermolecular reactions that reduce the overall number of charges desorbed.This effect is reduced in proton-rich solvents.35 Reactions between the matrix and the analyte are a particular problem e.g. rn-nitrobenzyl alcohol can give a covalently bonded adduct of +133 Da with analytes containing amine functions such as peptides. This arises from oxidation of the alcohol to an aldehyde followed by Schiff base formation to give an imine.36 The nature of the matrix is important and ideally should be matched to the physical properties of the analyte in order to reduce discrimination e.g. dodecanol as a matrix for fatty acids reduces surface activity and micelle formation and gives a more linear response with varying c~ncentration.~~ For detection at the trace level 29 M.E. Hail D. W. Berberich and R. A. Yost Anal. Chem. 1989 61 1874. 30 R. B. Cody Anal. Chem. 1989 61 2511. 31 A. Bjarnason J. W. Taylor J. A. Kinsinger R. B. Cody and D. A. Weil Anal. Chem. 1989 61 1889. 32 R. Orlando C. Murphy C. Fenselau G. Hansen and R. J. Cotter Anal. Chem. 1990 62 125. 33 J. Sunner A. Morales and P. Kebarle Int. J. Muss Spectrom. Ion Processes 1988 86 169. 34 L. D. Detter 0. W. Hand R. G. Cooks and R. A. Walton Muss Spectrom. Rev. 1988 7 465. 35 0. W. Hand and R. G. Cooks Int. J. Mass Spectrom. Ion Processes 1989 88 113. 36 M. Barber D. J. Bell M. Morris L. W. Tetler M. D. Woods J. J. Monaghan and W. E. Morden Rapid Commun.Mass Spectrom. 1988 2 181. 37 K. A. Caldwell and M.L. Gross Anal. Chem. 1989 61 494. Physical Methods and Techniques -Part (ii) Mass Spectrometry 25 it may be necessary to increase surface activity at the expense of linearity e.g. formation of the more hydrophobic hexyl esters of peptides is significantly more effective than ethyl ester formation for detection at the pmol level.38 The time limit for an analysis as determined by the rate of evaporation of the liquid can be extended by pulsing the bombarding atom or ion beam which also allows the surface to be replenished between shots and increases the signal It has been reported that the nature of the support surface has a significant effect on the ion currents obtained. Nitrocellulose enhances the signal even using a liquid matrix.41 Organics can be ionized from a dry surface by SIMS but they are generally short-lived unless the flux of bombarding species is kept very low.Fragmentation has been found to decrease with increasing primary ion energy owing to a cubic relationship between the impact energy and the number of energized molecules; thus at higher impact energy the average internal energy per molecule is less.42 Continuous flow fast atom bombardment (CF-FAB) was described in the previous review in this series. A major reason for interest in this technique relates to the ability to interface it with HPLC etc. but it also offers advantages in its own right as a constantly replenished sample is available a wider range of solvents can be employed and there is less selectivity and suppression in the analysis of mixtures.Interference in the low mass region arising from matrix and other cluster ions is reduced allowing the analysis of sub-ng quantities of compounds in the 100-200 Da mass range. Sample recoveries were aided by the addition of a structural analogue or homologue as sample adsorption was reduced.43 The analysis of drugs of molecular mass < 500 Da has been described with cocaine being detected from the direct analysis of The measurement of accurate masses is achieved more readily by CF-FAB than by static FAB as the sample and reference materials can be injected sequentially. Even with a low resolution quadrupole analyser it proved possible to measure precise masses for the naturally occuring anticancer alkaloids vincristine and vinblastine with an accuracy of 6 p.p.m.for the base peak (M + H)+ at mlz 825.45 Plasma Desorption.-There is a perception that PD is essentially a high-mass tech- nique so it will be interesting to monitor its future progress in the face of competition from ESP and UV-LID. In reviewing PD-TOFMS Cotter has referred to its ‘coming of age’ and has shown that by comparison with other methods it offers impressive performance at a modest price. He describes the technique and the theory and chooses examples from peptides proteins glycolipids phospholipids and analyses 3n A. M. Falick and D. A. Maltby Anal. Biochem. 1989 182 165. 39 D. F. Hunt J. Shabanowitz J. R. Yates 111 N. Z. Zhu D. H. Russell and M. E. Castro Proc. Narl. Acad. Sci. USA 1987 84 620.40 R. E. Tecklenberg jun. M. E. Castro and D. H. Russell Anal. Chem. 1989 61 153. 41 R. B. van Breeman and J. C. Le Rapid Commun. Mass Spectrom. 1989 3 20. 42 B. E. Winger 0. W. Hand and R. G. Cooks Int. J. Mass Specrr$m. Ion Processes 1988 84 89. 43 T.-C. L. Wang M.-C. Shih S. P. Markey and M. W. Duncan Anal. Chem. 1989 61 1013. 44 W. E. Seifert jun. A. Ballatore and R. M. Caprioli Rapid Commun. Mass Spectrom. 1989 3 117. 45 J. Roboz J. F. Holland M. A. McDowall and M. J. Hillmer Rapid Commun. Mass Specrrom. 1988 2 64. 26 M. A. Baldwin from whole cells to demonstrate its power and ~ersatility.~~ PD-TOFMS is still being used effectively for peptide and protein analysis:’ but perhaps more impor- tantly in terms of competing with ESP it has also been shown to be successful for the analysis of lipo-oligosaccharides glycopeptidolipids and phenolic glycolipids from mycobacterial sources.48 Laser Desorption.-Lasers are used both for desorption and ionization sometimes simultaneously as in the matrix-assisted LDI experiments described above but not necessarily with a matrix and sometimes in two isolated steps with lasers operating at different wavelengths.Desorption without ionization is generally achieved with an IR laser although this will also sputter ions from appropriate samples. A UV laser is required for ionization in the gas phase. There have been two independent reviews of gas-phase multiphoton ionization (MUPI) by Grotemeyer and S~hlagg~~ and by L~bman.’~,’’ The number of commercial laser instruments in use is still relatively low but some very impressive results suggest that they will take an increasing role in routine mass spectrometric analysis.LDI from thin layer chromatography (TLC) plates has proved to be sensitive giving good spatial resolution. Although TLC-FABMS equipment is available com- mercially the focusing ability of the laser offers advantages over FAB particularly for incompletely resolved components on the TLC plate e.g. adenine and g~anine.’~ IR-LDI-FTMS was compared with FAB for the analysis of mixtures of amino acids and small peptides. LDI showed less selectivity all fifteen amino acids in a mixture being ionized to give (M + 2Na -H)+ ions but only ten being detected by conven- tional static FAB,53 although CF-FAB might have been more successful in this respect.There has also been a comparison of LDI with PD and FAB for the analysis of carbohydrates LDI offering significant advantages in giving fragment ions and thereby structural information which could only be obtained by derivatization or tandem methods using the other desorption methods.54 LDI can be carried out directly within an IT or FT mass spectrometer as has been shown for peptides and disaccharides in ITMS.” LDI from dry solids without a liquid matrix enjoys the advantage of being compatible with high-vacuum operation which is particularly important for ITMS. UV-LDI-ITMS of polymers was found to be superior to FAB or SIMS giving more regular distributions less fragmentation and less discrimina- tion for a series of alkoxylated pyrazoles and hydrazine~.~~ A second laser can be used for photodissociation of the ions formed by LDI e.g.IR-LDI-FTMS of 46 R. J. Cotter Anal. Chem. 1988 60,781A. 47 I. Jardine G. F. Scanlan A. Tsarbopoulos and D. J. Liberato Anal. Chem. 1988 60 1086. 48 I. Jardine G. Scanlan M. McNeil and P. J. Brennan Anal. Chem. 1989 61 416. 49 J. Grotemeyer and E. W. Schlagg Angew. Chem. Int. Ed. Engl. 1988 27 447. 50 D. M. Lubman Mass Spectrom. Rev. 1988 7 535. 51 D. M. Lubman Mass Spectrom. Rev. 1988 7 559. 52 A. J. Kubis K. V. Somayajula A. G. Sharkey and D. M. Hercules Anal. Chem. 1989 61 2516. 53 M. P. Chiarelli and M. L. Gross Anal. Chem. 1989 61 1895. 54 W. B. Martin L.Silly C. M. Murphy T. J. Raley jun. R. J. Cotter and M. F. Bean Int. J. Mass Spectrom. Ion Processes 1989 92 243. 55 D. N. Heller I. Lys R. J. Cotter and 0. M. Uy Anal. Chem. 1989 61 1083. 56 L. M. Nuwaysir and C. L. Wilkins Anal. Chem. 1988 60 279. Physical Methods and Techniques -Part (ii) Mass Spectrometry 27 tetrakis-(4-fluorophenyl)porphyrininvolved attachment of iron and UV-laser dis- sociation gave losses of the fluorphenyl groups not observed in the conventional mass spectrum.57 4 Liquid Chromatography and Electrophoresis Mass spectrometry is generally most successful when applied to the analysis of pure compounds rather than complex mixtures hence the emphasis on interfacing with chromatographic methods. There is continuing interest in SFC-MS for compounds of low volatility a system having been described for converting a GC-MS instrument into dual GC-SFC operation with simple modification^.^' The thermospray (TSP) interface has become the standard for conventional bore reverse-phase HPLC at flow rates of -1 ml min.-' 4study of drugs antibiotics and peptides was carried out in deuterated solvents showing characteristic mass shifts which revealed the number of acidic hydrogens on various f~nctionalities.~~ A similar study applied to nucleosides in D20 showed 97% exchange of acidic hydrogens.60 The optimum conditions for the chromatographic separation may not coincide with optimum TSP performance but this may be compensated for by post-column addition of solvent.Glutathione conjugates were shown to need a 0-20% acetonitrile gradient for separation but TSP required 30-60% acetonitrile.100% acetonitrile at 0.4ml min-' was added to the column eluent flowipg at 0.8 ml min,-' thereby optimizing both elements in the analysk6' TSP can also be used for monitoring reaction mixtures without chromatographic separation. The electrochemical oxidation pathways for uric acid were revealed by direct monitoring of the electrochemical and the kinetics of a Michael condensation between glutathione and the neurotoxin acry- lamide have been in~estigated.~~ A major demand in biochemical analysis is the separation detection and charac- terization of ever smaller quantities of compounds in complex mixtures. To this end there has been a move towards microbore HPLC techniques and the adoption of capillary zone electrophoresis (CZE),64 which offers very high resolution on very small quantities of charged species.CF-FAB and ESP are two alternative ionization modes for the continuous introduction and ionization of polar compounds in liquid solutions at flow rates in the pl min-' range. Microbore HPLC can be coupled with either technique with relative ease as the column outlet can be fed via a capillary directly to the end of the FAB target or directly to the hypodermic needle of the ESP. However neither ionization technique works effectively with all HPLC solvents and as with TSP it can be necessary to make up the flow with another liquid. One approach is to use coaxial tubes the column eluent flowing through the 57 L.M. Nuwaysir and C. L. Wilkins Anal. Chem. 1989 61 689. 58 H. T. Kalinoski and L. 0. Hargiss J. Chromatogr. 1989 474 69. 59 M. M. Siegel Anal. Chem. 1988 60 2090. 60 C. G. Edrnonds S. C. Pornerantz F. F. Hsu and J. A. McCloskey Anal. Chem. 1988 60 2314. 6' M. F. Bean S. L. Pallente-Morell D. M. Dulik and C. Fenselau Anal. Chem. 1990 62 121. 62 K. J. Volk R. A. Yost and A. Brajter-Toth Anal. Chem. 1989 61 1709. 63 M. E. Harrison and M. A. Baldwin Org. Mass Specirom. 1989 24 689. 64 A. G. Ewing R. A. Wallingford and T. M. Olefirowicz Anal. Chem. 1989 61 292A. 28 M. A. Baldwin inner tube and the additional liquid through the outer tube the two mixing on the FAB target. Using both open tubular and packed microcolumns at flow rates of <lo0 nl-min-' with the addition of 25% glycerol/75% water at 200 nl-min,-' single scan spectra can be obtained at the low fmol level and signal averaging brings this down to 500 amol.Examples quoted include peptides phospho- lipids oligosaccharides and unsaturated fatty acids6' A quantitative study of peptide neurotransmitters assayed in spinal cord by HPLC-CF-FAB gave results consistent with radioimmunoassay.66 In addition to reverse-phase chromato-graphy CF-FAB can be coupled with ion exchange ion pair and ion exclusion ~hromatography.~~ For interfacing CZE with mass spectrometry an additional problem is the preven- tion of flow of the separating medium through the capillary which occurs with direct coupling to the vacuum system with the inherent danger of laminar flow degrading the resolution (although this is minimized with the very low flow rates reported for the CF-FAB co-axial interface).68 In an alternative co-axial interface described by Smith et al.for ESP operation the inner tube which is the electrophoresis capillary does not enter the vacuum. Its low voltage end terminates close to a restriction at the end of the outer tube from which the spray is formed. This interface has a dead volume of only 10nl corresponding to <1 s at the flow rates employed for The same experimental arrangement was also shown to be compatible with isotachophoresis for which lo-'' M solutions were analysed with amol limits of dete~tion.~' This sensitivity for CZE is very similar to that obtained with 32P radiochemical detection72 and electrochemical detection.73 An alternative is a liquid- liquid junction interface in which the outlet of the electrophoresis column is held very close to the end of another capillary that takes the liquid flow to the mass spectrometer ionization region.The junction is immersed in the make-up liquid which is drawn through by the vacuum. Excellent electrophoretic separation has been obtained on a mixture of peptides from a tryptic digest of bovine somatotrophin fragment ion information on individual components being obtained from the triple quadrupole mass analy~er.~~ The resolution reported was greatly superior to that shown in the HPLC-CF-FAB separation of a digest from ribonuclease B although the use of single ion monitoring in the latter effectively enhanced the resolution ~onsiderably.~~ 65 L.J. Deterding M. A. Mosely K. B. Tomer and J. W. Jorgenson Anal. Chem. 1989 61 2504. 66 C. A. Lisek J. E. Bailey L. M. Benson T. L. Yaksh and I. Jardine Rapid Cornrnun. Mass Spectrom. 1989 3 43. 67 A. S. Al-Omair and J. F. J. Todd Rapid Commun. Mass Spectrom. 1989 3 405. 68 M. A. Moseby L. J. Deterding K. B. Tomer and J. W. Jorgenson Rapid Commun. Mass Spectrom. 1989 3 87. 69 R. D. Smith C. J. Baringa and H. R. Udseth Anal. Chem. 1988 60,1948. 70 C. G. Edrnonds J. A. Loo C. J. Baringa H. R. Udseth and R. D. Smith J. Chrornatogr. 1989,474,21. 71 H. R. Udseth J. A. Loo and R. D. Smith Anal. Chem. 1989 61 228. 12 S. L. Pentony jun.R. N. Zare and J. F. Quint Anal. Chem. 1989 61 1642. 73 R. A. Wallingford and A. G. Ewing Anal. Chem. 1989 61 98. 74 E. D. Lee W. Muck J. D. Henion and T. R. Covey Biorned. Environ. Mass Specrrom. 1989 18 844. 75 K. Mock J. Firth and J. S. Cottrell Org. Mass Spectrom. 1989 24 591. Physical Methods and Techniques -Part (ii) Mass Spectrometry 29 5 Tandem Mass Spectrometry By the end of the 1980s tandem mass spectrometers had made the transition from home-made research instruments in the laboratories of a few pioneers in the 1970s to become an established part of the analytical scene. This has been spurred on by soft ionization methods which generally give protonated molecular ions that are relatively stable and give little structural information unless fragmentation can be induced by the deposition of more internal energy i.e.by photoexcitation or more commonly by collisions with gas atoms or molecules. (Cooks and co-workers have also carried out a series of studies on collisions with a solid surface e.g. for more than seventy odd-electron organic ions.76) There is a hierarchy of instrument types based on cost starting with triple quadrupoles (QQQ) in which the initial and final quadrupoles are used for mass analysis with collisions taking place in the radio- frequency-only central quadrupole through the hybrids in which a double focusing two-sector instrument is followed by two quadrupoles (SS/QQ) finally to the double focusing/ double focusing four-sector (SS/ SS) high performance instruments.Inevitably the low-cost QQQ instruments are by far the most widely used whereas SS/SS instruments at about US $1000 000 each are relatively few and far between. Tandem experiments are also possible by trapping in instruments such as the IT and FT mass spectrometers. This diversity of instruments and their applications have been re~iewed.~' A quadrupole is a low resolution mass analyser compared with a double focusing spectrometer and is unable to separate isobaric ions of the same nominal mass whereas SS/SS combinations can provide high-resolution analysis of both parent and daughter ions. This is also true for FTMS which in a dual cell instrument with a pulsed gas valve with selective daughter ion excitation gave a mass resolution of 500 000 for daughter ions and a mass measurement error of <5 ~.p.m.~~ The ion kinetic energy in a quadrupole is 10-100 eV whereas sectors routinely operate at -lo4eV so the kinetic energy transferred into internal energy is substantially less for QQQ and SS/QQ (-5 eV) than for SS/SS (-30 eV).79 For peptide sequencing the backbone fragmentations can be monitored by any of these instrument types but the analytically useful high-energy fragmentations of the amino acid side-chains which for example allow differentiation of the isomers leucine and isoleucine are mostly only observed in SS/ SS experiments." High-energy collisons yield tandem mass spectra of peptides that are less dependent on amino acid type and although QQQ and SS/QQ combinations are successful for most small peptides and have been used in the 2000 Da region," many peptides of masses above -600 Da give little useful data compared with SS/ SS spectrometer^.^^.^^ One advantage of the 76 T.Ast M. A. Mabud and R. G. Cooks Int J. Mass Specfrom. Ion Processes 1988 82 131. 77 K. L. Busch G. L. Glish and S. A. McLuckey 'Mass Spectrometry/Mass Spectrometry. Techniques and Applications of Tandem Mass Spectrometry' VCH New York 1988. 78 R. B. Cody Anal. Chem. 1988 60,917. 19 L. Poulter and L. C. E. Taylor Znf. J. Mass Specfrom. Ion Processes 1989 91 183. 80 R. S. Johnson S. A. Martin and K. Biemann Inf. J. Mass Spectrom. Zon Processes 1988 86 137. *' D. F. Hunt J. R. Yates 111 J. Shabanowitz S. Winston and C. R. Hauer Roc. Nafl. Acad. Sci.USA 1986 83 6233. 82 A. J. Alexander and R. K. Boyd Int. J. Mass Spectrom. Ion Processes 1989 90 211. 30 M.A. Baldwin quadrupole mass analyser is its much greater acceptance angle giving higher sensitivity for QQQ or SS/QQ as ions are less likely to be scattered out of the beam.83 The sensitivity of high-performance SS/SS instruments can be enhanced by several orders of magnitude (but at considerable expense and with lowered resolving power) by an array detector that allows anything up to 50% of the mass range to be monitored sim~ltaneously.~~ For the sequencing of peptides tandem mass spectrometry is particularly useful for identifying modified amino acids either from a post-translational event or perhaps from xenobiotic modification.The addition of styrene oxide to haemoglobin was identified by the presence of a tryptic peptide 120 Da too high the site of modification being located at histidine by the identification of a so-called immonium ion which was shifted from 110 to 230 Da and the corresponding 120 Da shifts in the C-terminal ion series8’ Methods are being developed for computer interpreta- tion of peptide tandem mass spectra which offer considerable promise for fast and reliable sequencing.86 There are reported advantages in obtaining tandem spectra of alkali metal ion adducts rather than protonated species. FAB shows sodium binding to the site of highest alkali ion affinit~,~’ and an elimination from the C-terminal residue allows identification of the C-terminal amino acid.88 A very promising development is the use of ESP/QQQ studies on doubly charged ions.Tryptic peptides tend to be protonated on both N-and C-termini cleavage into two singly charged ions giving two overlaid fragment series. The high sensitivity and efficiency of ionization by ESP gives strong signals for quite large peptides such as a 19-residue example of mass 2314Da giving a doubly protonated ion at m/z 1158.89 The fragmentation into singly charged species causes half of the fragment ions to have higher m/z values than the doubly charged molecular species putting more demands on the mass range of the final quadrupole analyser. Nevertheless the fragmentation of melittin could be rationalized up to m/z 2800.90 Although tandem mass spectrometry is particularly successful for peptide sequenc- ing many other classes of biomolecules have been studied as has been reviewed by T~mer.~~.~~ Stereochemical effects are often seen only in tandem experiments in which ions of low internal energy can be sampled.Zaretskii has published a series of papers on steroid stereochemistry. A recent study involved the selection of the ions formed by the unimolecular or metastable loss of water and subjecting these to collisional dissociation (MS/MS/MS) to distinguish between epimers of the 83 S. J. Gaskell and M. H. Reilly Rapid Commun. Mass Spectrorn. 1988 2 139. 84 K. Biemann and J. A. Hill Proceedings of the 37th ASMS Conference on Mass Spectrometry and Allied Topics Miami Florida 1989 p. 27. 85 S. Kaur D.Hollander R. Haas and A. L. Burlingame J. Biol. Chem. 1989 264 16981. 86 R. S. Johnson and K. Biemann Biomed. Environ. Mass Spectrom. 1989 18 945. 87 D. H. Russell E. S. McGlohon and L. M. Mallis Anal Chem. 1988 60,1818. 88 W. Kulik W. Heerma and J. K. Terlouw Rapid Cornmun. Mass Spectrom. 1989 3 276. 89 D. F. Hunt N.-Z. Zhu ,and J. Shabanowitz Rapid Commun. Mass Spectrom. 1989 3 122. 90 C. J. Baringa C. G. Edmonds H. R. Udseth and R. D. Smith Rapid Commun. Mass Spectrom. 1989 3 160. 9’ K. B. Tomer Mass Spectrom. Rev. 1989 8 445. 92 K. B. Tomer Mass Spectrom. Rev. 1989 8 483 Physical Methods and Techniques -Part (ii) Mass Spectrometry 31 3-hydroxy sterols.93 It has been shown that cis/trans ring junctions at the B/C rings in morphinans can be distinguished by characteristic ions in the tandem mass spectra.94 Determining stereochemistry linkage position and branching in sac-charides and oligosaccharides has proved difficult or impossible by conventional mass spectrometry but the various stereoisomers of per-acetylated glucose and galactose have been identified by tandem mass ~pectrometry,'~ and the stereoiso- meric 2-deoxy-2-aminohexoses have been di~tinguished.~~ On the basis of peak intensity ratios it was possible to characterize 1,2- 1,3- 1,4- and 1,6-linked disaccharides using negative ion FAB/MS/ MS; peaks which were strong in some cases being completely absent in others9' Laine et al.combined theoretical calculations with tandem methods to study linkage position in trisa~charides.~~ Tandem mass spectrometry was used to correct an earlier structure for high- mannose sugars isolated from Saccharomyces cerevisiae in which the branching had been wrongly interpreted by chemical and NMR methods.It is noteworthy that the revised structure would not be distinguishable by 1H NMR from that proposed rigi in ally.^^ Unusual Chemical Species.-Mass spectrometry can often yield information on unusual chemical species. In recent years there have been many examples identified of 'distonic' ions ie. odd-electron ions in which the charge and radical sites are separated corresponding formally to the removal of an electron from a zwitterion. In reviewing these species Hammerum has pointed out that they are both 'common and stable' existing in condensed phase both solid and solution often as intermedi- ates in organic synthesis as well as the isolated gas phase prevailing in the mass spectrometer."' As explained in the previous review in this series the 'existence and stability of some of the corresponding hypervalent or non-classical neutrals can be investigated by neutralization/reionization mass spectrometry (NRMS) in which the ions are collisonally neutralized and then reionized some 4 x lop7 s later.'" NRMS has also been used to demonstrate the stability of some unusual radical species.Protonation of some aromatics showed species such as the benzenium radical C6H7',an intermediate in the Birch reduction to be stable.'02 Ligand-deficient electronically unsaturated half-sandwich complexes such as FeC,H were also shown to exist as stable neutrals within the lifetime of the experiment.The abundance of 93 Z. V. I. Zaretskii J. M. Curtis D. Ghosh and A. G. Brenton Znt. J. Muss Spectrom. Ion Processes 1988 86 121. 94 B. Charles and J.-C. Tabet Rapid Commun.Mass Spectrom. 1988 2 86. 95 R. Guevremont and J. L. C. Wright Rapid Commun.Muss Spectrom. 1988 2 47. 96 R. Guevremont and J. L. C. Wright Rapid Commun. Muss Spectrom. 1988 2 50. 97 A. Ballistreri G. Montaudo D. Garozzo M. Giuffrida and G. Impallomeni Rapid Commun.Mass Spectrom. 1989 3 302. 98 R. A. Laine K. M. Panichi A. D. French R. W. Hall S. A. Abbas R. K. Jain and K. L. Matta J. Am. Chem. SOC.,1988 110 6931. 99 L. M. Hernandez L. Ballou E.Alvarado B. L. Gillece-Castro A. L. Burlingame and C. E. Ballou J. Biol. Chem. 1989 264 11 849. 100 S. Hammerum Muss Specfrom. Rev. 1988 7 123. 101 J. L. Holmes Muss Spectrom. Rev. 1989 8 513. 102 A. W. McMahon F. Chadikun A. G. Harrison and R. E. March Int. J. Muss Spectrom. Ion Processes 1989 87 275. M. A. Baldwin survivor ions was in the order FeCp < CoCp < NiCp the reverse of the ther- mochemical stability. The breakdown products identified in the reionization spec- trum included species such as FeC3H3+ as well as abundant hydrocarbon ions.lo3 The interpretation of such experiments is not always trivial and earlier claims concerning the stability of some hypervalent species have now been dismissed for H30',lo4 and also for CH5' which can only be formed in high Rydberg states followed by rapid disso~iation.'~~ 103 T.Drewello and H. Schwarz Int. J. Muss Spectrom. Ion Processes 1989 93 177. 104 R.E. March and A. 9. Young Int. J. Muss Spectrom. Ion Processes 1988 85 237. 105 J. Bordas-Nagy J. L. Holmes and C. E. C. A. Hop Inr,J. MQSSSpectrom. Ion Processes 1988,85 241.

ISSN:0069-3030    

DOI:10.1039/OC9898600019

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

3 Theoretical Organic Chemistry By I. H.WILLIAMS School of Chemistry University of Bath Bath BA2 7AY A comprehensive review of the year’s literature in this thriving area might fill the remainder of this volume the latest supplement to the bibliography of ab initio calculations alone has 1842 entries.’ What follows in this report is necessarily very selective and subjective but aims to highlight significant theoretical developments as applied to organic chemistry. 1 Computational Methods Despite the increasing capabilities of ab initio quantum-chemical methods on ever more powerful computers (e.g. calculation of the SCF electrostatic potential around an undecapeptide cyclosporin derivative with 199 atoms and 1000 basis functions2) semi-empirical MO methods remain important tools for the study of organic and bio-organic molecules.The AM1 method has been parameterized for halogens3 and phosph~rus,~ and is even included as an option in the GAUSSIAN38 suite of ab initio programs. Besides being useful in its own right for explorations of energy surfaces AM1 provides an economical means of obtaining geometries for species whose energies may then be determined by single-point calculations using high-level ab initio method^.^ A new and efficient technique for optimization of the parameters in semi-empirical MO methods has been developed and applied by Stewart to the modified neglect of diatomic overlap scheme.6 The result is PM3 (parametric method three following MNDO and AMl) available in MOPAC version 5.0 for the elements H C N 0 F Al Si P S C1 Br and I.The average difference between calculated and experimental heats of formation for 657 compounds is 33 kJ mol-I (CJ 58 and 53 kJ mol-’ respectively for MNDO and AMl) with the most dramatic improve- ments being for hypervalent compounds. Since PM3 probably represents an optimum parameterization (within the limitations of accuracy of the reference data employed) errors which remain -e.g. square-planar cyclobutadiene -are likely to be errors associated with the form of the Hamiltonian itself.6 PM3 hydrogen bonds are linear6 and the utility of this new method has been demonstrated by its use in a study of reaction pathways and specific solvation effects upon phosphoryl transfer reactions.’ ’ Quantum Chemistry Literature Database.Supplement 8. Bibliography of ab initio calculations for 1988 ed. K. Ohno K. Morokuma and H. Hosoya THEOCHEM 1989 62 1. ’S. L. Price R.J. Harrison and M. F. Guest J. Comput. Chem. 1989 10 552. M. J. S. Dewar and E. G. Zoebisch THEOCHEM 1988,49 1. M. J. S. Dewar and C. Jie THEOCHEM 1989 56 1. ’ M. J. S. Dewar A. J. Holder E. F. Healy and S. Olivella J. Chem. Soc. Chem. Commun. 1989 1452. J. J. P. Stewart J. Compur. Chem. 1989 10 209 221. ’H. S. Rzepa and M. Y. Yi J. Chem. Soc. Chem. Commun. 1989 1502. 33 34 I. H.Williams PM3 energy surfaces for the Beckmann rearrangement of oximes' and for additions of phosphaalkenes and phosphonium ylides to formaldehyde are in good agreement with the results of ab initio methods.' On the subject of third editions Allinger's heralded MM3 molecular mechanics force field for hydrocarbons has arrived; lo this corrects known deficiencies of MM2 and provides reliable estimates of many properties including vibrational frequencies for the purpose of evaluating absolute and relative entropies.The MM3 van der Waals parameters for C and H make these atoms slightly larger and softer than in MM2 and the introduction of a torsion-stretch interaction term enables the lengths of eclipsed C-C bonds to be evaluated correctly as in norbornane and dodeca- hedrane." MM2 parameters have been reported for furan thiophene and related compounds siloxanes nitriles organoselenium and tellurium compounds,12 chlorosilanes and di~ilanes,'~ epoxides,16 and pentacoordin- amides,14 di~xetanes,'~ ate phosphorus compounds." In applying computational quantum chemistry to organic molecules using ab initio methods three major areas of difficulty arise basis sets electron correlation and the multidimensional nature of potential energy surfaces.Practical schemes intended to provide accurate results must consider all three aspects. The use of second-order Moller-Plesset theory (MP2) to estimate electron correlation effects on molecular geometries is becoming standard; for this purpose it is necessary to include polarization basis functions on non-hydrogen atoms," as in the MP2/6-3 lG* method. Basis sets specifically designed for correlated molecular calculations have been reported;" the 6-311G basis is not of triple-zeta quality (as claimed) in the valence region." Pople et al.have prescribed a general procedure for predictions of total energies of molecules at equilibrium geometries using methods implemented in GAUSSIAN88 with accuracies of *8 kJ mol-' in atomization energies for molecules containing two first-row atoms.21 This 'Gaussian- 1' procedure treats electron correla- tion effects at the MP4SDTQ level (with single double triple and quadruple excitations) using the 6-31 1G** basis for geometries optimized at the MP2/6-31G* level and then augments this by corrections (assumed to be additive) for zero-point energy additional diffuse sp and higher polarization basis functions on non-P. A. Hunt and H. S. Rzepa J. Chem. SOC.,Chem. Commun. 1989 623. H. S. Rzepa J.Chem. Soc. Perkin Trans. 2 1989 2115. 10 N. L. Allinger Y. H. Yuh and J.-H. Lii J. Am. Chem. SOC.,1989 111 8551; J.-H. Lii and N. L. Allinger ibid. pp. 8566 8576. N. L. Allinger H. J. Geise W. Pyckhout L. A. Paquette and J. C. Gallucci J. Am. Chem. Soc. 1989 111 1106. 12 J. C. Tai J.-H. Lii and N. L. Allinger J. Comput. Chem. 1989 10 635; M. R. Frierson and N. L. Allinger J. Phys. Org. Chem. 1989 2 573; E. Goldstein and N. L. Allinger THEOCHEM 1989 57 149; N. L. Allinger J. A. Allinger and L. Q. Yan ibid. 1989 60,363. l3 S. G. Cho R. J. Unwalla F. K. Cartledge and S. Profeta J. Compul. Chem. 1989 10 832; S. Profeta R. J. Unwalla and F. K. Cartledge ibid. p. 99. 14 D. M. Schnur Y. H. Yuh and D. R. Dalton J. Org. Chem. 1989 54 3779. l5 W.H. Richardson J. Org. Chem. 1989 54 4677. 16 B. L. Podlogar and D. J. Raber J. Org. Chem. 1989 54 5032. G. Robinet M. Barthelat V. Gasni and J. Devillers J. Chem. Soc. Chem. Commun. 1989 1103. l8 H. Guo and M. Karplus J. Chem. Phys. 1989,91 1719. 19 T. H. Dunning J. Chem. Phys. 1989,90 1007. 20 R. S. Grev and H. F. Schaefer J. Chem. Phys. 1989 91 7305. 21 J. A. Pople M. Head-Gordon D. J. Fox K. Raghavachari and L. A. Curtiss J. Chem. Phys. 1989,90 5622. Theoretical Organic Chemistry 35 hydrogen atoms so-called quadratic C1 and for 'higher-level' effects. A scheme has also been presented for simultaneous optimization of wavefunction and geometry by an efficient quadratically convergent method.22 It is well known that the UHF method for open-shell species does not in general give pure spin states this causes problems when using perturbation methods to determine correlation energies.Spin projection techniques have been proposed by several groups recently to annihilate the contaminating spin states either as part of the SCF procedure,23 or afterwards giving PMPn 24 or PUMPn 25 wavefunctions. Configuration interaction is an important method for evaluating electron correla- tion effects but it suffers from a lack of size consistency; this feature introduces significant errors into calculated interaction energies26 and barrier heights2' for associative or dissociative reactions. This problem can be side-stepped by treating the dissociated species not as isolated molecules but as a supermolecule whose components are separated by a large distance.Coupled-cluster methods are being used increasingly and have the great advantage of being guaranteed size consistent;28 These methods differ from Moiler-Plesset methods (which are also size consistent) in that they treat certain classes of excitation to all orders of perturbation theory whereas the MPn methods treat all classes of excitation to a certain order n. The importance of higher-than-double excitations in determining chemical reaction barriers is illustrated by a study29 of the unimolecular triple dissociation of glyoxal into 2CO + H2.CI with single and double excitations reduced the activation energy from its SCF value by 29 kJ mol-' but the coupled-cluster singles-and-doubles method reduced it by 56 kJ mol-' and inclusion of triple excitations caused a further reduction of 24 kJ mol-'.If the SCF wavefunction provides a qualitatively adequate description for a molecule and if the perturbation series converges well then MP4SDQ and MP4SDTQ give roughly equivalent results to CCSD and CCSDT re~pectively.~' As yet however high-level methods such as these can be applied in practice only to systems containing no more than four first-row atoms. Schlegel has reported3' an improved algorithm for reaction-path following (as implemented in GAUSSIAN88) and Koseki and Gordon have discussed32 modifications to intrinsic reaction coordinate methods (available in the Iowa/ North Dakota version of GAMESS) suitable for very flat potential energy surfaces.Ab initio reaction paths may be interfaced with calculations of chemical reaction rate constants using the POLYRATE program for variational transition-state theory and semiclassical tunnelling calculation^.^^ A strategy for dealing with branching points on such reaction paths has been devised.34 22 M. Head-Gordon J. A. Pople and M. J. Frisch Int. J. Quantum Chem. Symp. 1989 23 291. 23 J. Baker Chem. Phys. Lett. 1988 152 227; J. Chem. Phys. 1989 91 1789. 24 H. B. Schlegel J. Phys. Chem. 1988 92 3075; J. J. W. McDouall and H. B. Schlegel J. Chem. Phys. 1989 90 2363. 25 P. J. Knowles and N. C. Handy J. Chem. Phys. 1988 88 6991. 26 J. E. Del Bene and I. Shavitt Int. J. Quantum Chem. Symp. 1989 23 445. 27 T. P. Hamilton and H.F. Schaefer J. Chem. Phys. 1989 90,6391. 28 R. J. Bartlett J. Phys. Chem. 1988 92 1697. 29 G. E. Scuseria and H. F. Schaefer J. Am. Chem. Soc. 1989 111 7761. 30 J. F. Stanton R. J. Bartlett D. H. Magers and W. N. Lipscomb Chem. Phys. Lett. 1989 163 333. 3' C. Gonzales and H. B. Schlegel J. Chem. Phys. 1989 90 2154. 32 S. Koseki and M. S. Gordon J. Phys. Chem. 1989 93 118. 33 K. K. Baldridge M. S. Gordon R. Steckler and D. G. Truhlar J. Phys. Chem. 1989 93 5107. 34 E. Bosch M. Moreno J. M. Lluch and J. BertrLn Chem. Phys. Lett. 1989 160 543. I. H. Williams 2 Structure Bonding and Properties Orbital based schemes for population analysis of wavefunctions (Mulliken analysis or natural population analysis) predict oxygen atomic charges of about -0.6 in a range of oxygenated compounds whereas spatially based analyses (integrated Bader populations or integrated projected populations) predict charges about twice this size implying very polar C-0 bonds; the charge is not centred on the oxygen nucleus and is not spherically di~tributed.~~ Bader analysis of phosphorus com- pounds indicates polarization in the sense -C-P+ i.e.opposite to that for C-N bonds.36 Correlation effects do not significantly affect the topological and atomic properties of electron density distributions and MP2 provides a practical method for many molecule^.^' In natural population analysis correlation at the MP2 level acts consistently to reduce charge ~eparations.~' A new population analysis based on atomic polar tensors has been proposed.39 Allen has suggested an extension of the formula for Lewis-Langmuir formal atomic charges providing a more realistic manifestation of bond polarity a more natural balance between covalent and ionic extremes is achieved by a fractional weighting using the electronegativities of the atoms.40 Furthermore he has proposed an alternative definition of electronegativity as the average one-electron energy of the valence-shell electrons in ground-state free atoms.41 Pearson has discussed the application to organic chemistry of the concepts of absolute electronegativity and absolute hardness,42 and Parr has used the latter quantity (together with relative hardness with respect to an acyclic reference) to assess aromaticity in cyclic conjugated molecules.43 A study of rr-electron delocalization in azines suggests there is essentially the same delocalization in all the compounds considered and essentially the same resonance energies for benzene pyridine pyrazine and ~yrimidine.~~ The authors disagree with the assertion of Shaik and Hiberty that electron delocalization is seldom a driving force in conjugated systems involving C N and 0 atoms.However Wiberg et al. have elsewhere discussed the limitations of resonance interactions in acyclic systems pointing out for example that the barrier to internal rotation in allyl cation arises from electron delocalization and electrostatic contributions but in allyl anion is largely electrostatic in origin.45 The spin-coupled descriptions of the .rr-systems of na~hthalene~~ are similar to that of benzene.and heteroar~matics~' The bonding in hypervalent molecules such as sulphuranes can be described qualitatively without invoking d-orbital participation in the valence shell by either 35 S. M. Bachrach and A. Streitwieser J. Comput. Chem. 1989 10 514. 36 S. M. Bachrach J. Comput. Chem. 1989 10 392. 37 R. J. Boyd and L.-C. Wang J. Comput. Chem. 1989 10 367; L.-C. Wang and R. J. Boyd J. Chem. Phys. 1989 90,1083. 38 J. E. Carpenter M. P. McGrath and W. J. Hehre J. Am. Chem. SOC.,1989 111 6154. 39 J. Cioslowski J. Am. Chem. SOC.,1989 111 8333. 40 L. C. Allen J. Am. Chem. SOC.,1989 111 9115. 41 L. C. Allen 1.Am. Chem. SOC.,1989 111 9003. 42 R. G. Pearson J. Org.Chem. 1989 54,1423. 43 Z. Zhou and R. G. Parr J. Am. Chem. SOC. 1989 111 7371. 44 K. B. Wiberg D. Nakaji and C. M. Brenernan J. Am. Chem. SOC.,1989 111 4178. 45 K. B. Wiberg C. M. Breneman K. E. Laidig and R. E. Rosenberg Pure Appl. Chem. 1989 61 635. 46 M. Sironi D. L. Cooper J. Gerratt and M. Raimondi 1.Chem. Soc. Chem. Commun. 1989 675. 47 D. L. Cooper S. C. Wright J. Gerratt and M. Raimondi J. Chem. SOC.,Perkin Trans. 2 1989 255 263. 7'heoretica1 Organic Chemistry 37 MO or VB models.48 A VB analysis suggests two types of hypercoordinated XH,+I radicals those involving an avoided crossing between Lewis-structure curves only and those which additionally involve an 'intermediate' curve.49 This model attributes the bonding in bipyramidal SiH,- to efficient use of the axial Si-H (T*orbitals (in contrast to the situation in CH5-) rather than to hypervalency associated with d-~rbitals.~' Integrated population analysis of bonds between silicon and common non-metals indicates extensive polarization in the sense +Si-X-.In contrast to carbon the ionic nature of these bonds allows silicon to expand its coordination sphere to form stable pentacoordinate species.51 A P-SiH3 substituent stabilizes secondary and tertiary carbenium ions by 93 and 67 kJ mol-' respectively three times the effect of a P-CH group whereas both substituents have about the same influence on radical stabilitie~.~~ The tendency for hyperconjugative stabilization in carbenium ions causes the 2-pr0pyl~~ and cyclopen- ty154 cations to be chiral and distorts 2-adamantyl cation (1) away from the classical C, geometry.55 The 7-norbornyl cation (2) has a C,-symmetrical non-classical structure.56 The extremely short central C-C single bond in bitetrahedryl (3) and in bicubyl (4) is associated with increased s-character arising from the bending H (1) (2) (3) (4) back of the substituents on those atoms.57 cis-Butadiene slightly prefers a gauche c~nformation:~' conjugation is little affected by torsion of up to about 40".3 Reactivity and Mechanism Pericyclic Reactions.-A perturbational MO analysis of the C,-symmetrical transition structure for the synchronous concerted Diels- Alder addition of ethene to butadiene suggests that the barrier (AH' = 107 kJ mol-' at the MP4SDTQ/6-31G* level) is largely due to closed-shell repulsions between filled orbitals on the addends.59 The Cope rearrangement of 3,3-dicyanohexa- 1,Sdiene is predicted by RHF/ AM 1 calcu- lations to proceed by a synchronous concerted mechanism involving an aromatic 4H J.G. Angyin THEOCHEM 1989 55 61; F. Volatron ibid. p. 167. 49 A. Demolliens 0. Eisenstein P. C. Hiberty J. M. Lefour G. Ohanessian S. S. Shaik and F. Volatron J. Am. Chem. SOC.,1989 111 5623. G. Sini P. C. Hiberty and S. S. Shaik J. Chem. Soc. Chem. Commun. 1989 772. '' S. Gronert R. Glaser and A. Streitwieser J. Am. Chem. Soc. 1989 111 3111. 52 M. R. Ibrahim and W. L. Jorgensen J. Am. Chem. SOC.,1989 111 819. 53 P. von R. Schleyer W. Koch B. Liu and U. Fleischer J.Chem. Soc. Chem. Commun. 1989 1098. 54 W. Koch B. Liu and P. von R. Schleyer J. Am. Chem. Soc. 1989 111 3479. 55 R. Dutler A. Rauk T. S. Sorensen and S. M. Whitworth J. Am. Chem. SOC.,1989 111 9024. 56 M. Bremer K. Schotz P. von R. Schleyer U. Fleischer M. Schindler W. Kutzelnigg W. Koch and P. Pulay Angew. Chem. In?. Ed. Engl. 1989 28,,1042. 57 P. von R. Schleyer and M. Bremer Angew. Chem. Int. Ed. EngL 1989 28 1226; Y. Xie and H. F. Schaefer Chem. Phys. Lett. 1989 161 516. 5R J. E. Rice B. Liu T. J. Lee and C. M. Rohlfing Chem. Phys. Lerr. 1989 161 277; I. A. Alberts and H. F. Schaefer Chem. Phys. Lert. 1989 161 375. 59 R. D. Bach J. J. W. McDouall H. B. Schlegel and G. J. Wolber J. Org. Chem. 1989 54 2931. 38 I. H. Williams transition structure rather than the more usual biradicaloid path:’ Pericyclic reac- tions with small exo- or endothermicities are likely to occur by both the syn- chronous/aromatic and non-synchronous/biradicaloidpaths representing distinct mechanisms as for either boat or chair Cope rearrangements.Claisen rearrangements of ally1 vinyl ethers owing to their large exothermicities occur mostly by a single merged mechanism of intermediate type.6‘ Epiotis suggests that stabilizing charge alternation in the transition structures for allowed concerted reactions may be promoted by weak polarizable bonds in the underlying a-system. Thus the balance between concerted and stepwise biradical mechanisms may be determined by the a-bonds and replacement of first-row atoms by heavier ones (e.g.substitution of Si for C) should favour concerted mechanisms.62 Asymmetric Diels-Alder additions between substituted butadienes and ethenes are predicted by RHF/AMl to be concerted but are stepwise processes at the UHF/AMl RHF/AMl and RHF/3-21G calculations for cycloadditions of butadiene and cyclopentadiene to various cyanoalkenes correctly predict substituent effects on activation energies and indicate limited asynchronicity in the transition structures but incorrectly predict the ex0 mode of addition to be favoured.64 Similarly RHF/AMl gives a generally good account of the Diels-Alder reaction between cyclopentadiene and P-angelica lactone (whereas MNDO overestimates the barrier and gives a very asynchronous transition structure) but fails to predict the observed preference for the endo addu~t.~’ An AM1 study of addition of acrolein to ethene (yielding dihydropyran) could not rule out the possibility of a biradicaloid intermediate,66 but ab initio RHF studies on the Diels-Alder addition of butadiene to acrolein (yielding 4-formylcyclohexane) correctly predict the observed endo preference and an’ appreciable asynchronicity in the concerted transition str~cture.~’ Thermal decarboxylations of 2-oxetanones are formally forbidden 7~2s+ 7~2s processes which are predicted to proceed by concerted mechanisms involving highly asynchronous zwitterion-like transition structures; AM1 calculations reproduce experimental substituent effects The corresponding acid-catalysed reactions are stepwise processes involving a carbocationic intermediate whose conformation allows the observed stereochemical outcome to be interpreted.Diastereofacial selectivity in Diels-Alder additions may be considered theoreti- cally in terms of (a) electrostatic interactions between reactants in their equilibrium geometries (b) frontier MO arguments or (c) direct calculations on transition structures. Full optimization at the RHF/AMl level of all possible transition struc- tures for additions of ethene acrolein and methyl propiolate to pentadienes with stereogenic substituents at the terminal position -for attack at each face of the diene there are three rotamers -suggests that stereoselectivity is determined by a subtle 60 M. J. S. Dewar and C.Jie J. Chem. SOC.,Chem. Commun. 1989 98. 61 M. J. S. Dewar and C. Jie J. Am. Chem. SOC.,1989 111 511. 62 N. D. Epiotis J. Org. Chem. 1989 54 953. 63 J. Y. Choi and 1. Lee J. Chem. Soc. Faraday Trans. 2 1989 85 867. 64 K. N. Houk R. J. Loncharich J. F. Blake and W. L. Jorgensen J. Am. Chem. SOC.,1989 111 9172. 6S M. Sodupe A. Oliva J. Bertrkn and J. J. Dannenberg J. Org. Chem. 1989 54 2488. 66 L. F. Tietze J. Fennen and E. Anders Angew. Chem. Znf. Ed. Engl. 1989 28 1371. 67 R. J. Loncharich F. K. Brown and K. N. Houk J. Org. Chem. 1989,54 1129; K. N. Houk Pure Appl. Chern. 1989 61 643. 68 A. Moyano M. A. Pericas and E. Valenti J. Org. Chem. 1989 54 573. Theoretical Organic Chemistry 39 combination of specific steric and electronic interaction^.^^ No single effect domi- nates and electronic effects are not clearly manifested in any simple parameter such as HOMO/ LUMO properties charges or 7r-densities.Predictions made on the assumption that undistorted reactant properties are reflected at transition-state level are not uniformly c~rrect,~~’~~ and this lack of reliability emphasizes the importance of full geometry optimization for transition structures. Dewar has criticized frontier MO theory as ‘.. . unsound unnecessary and unreliable and there are no chemical problems that cannot be solved in simpler more effective ways.’ 70 A Woodward-Hoffmann (WH) allowed pericyclic reaction involving migration of hydrogen is likely to be synchronous owing to the propensity of hydrogen to form three-centre bonds.61 AM 1 calculations for dihydrogen transfer reactions between various donors and acceptors predict synchronous concerted mechanisms whereas the MNDO method tends to favour stepwise mechanisms involving radical- pair intermediates7’ The alternative concerted and stepwise mechanisms have com- parable barriers in AM 1 for dihydrogen elimination reactions whereas MNDO again favours the latter.72 The transition structure for the concerted ene reaction between methyl acrylate and propene has less asynchronous character at the RHF/6-31G level than for the parent reaction of ethene with propene and a lower barrier.73 ‘Torquoselectivity’ is the term coined for the stereochemical preference of elec- trocyclizations to involve twisting in one direction rather than the other.Ring- opening of cyclobutene-3-carboxylic acid and its conjugate base should proceed to the outside-substituted butadiene (Scheme l),but protonation of the acid is predicted X Scheme 1 to reverse the stereochemistry leading to the inward-substituted product involving the strong 7r-electron-withdrawing -C( OH),+ Similarly resonance-donor substituents are predicted to stabilize the transition structure for electrocyclization of pentadienyl cation when attached to the 1-position on the outside but resonance- acceptor substituents should stabilize the transition structure more effectively when in the inside position.75 WH forbidden reactions require multiconfigurational treatments for qualitatively correct descriptions and careful theoretical studies76 have indicated that concerted 69 N.Kaila R. W. Franck and J. J. Dannenberg J. Org. Chem. 1989 54 4206. 70 M. J. S. Dewar THEOCHEM 1989 59 301. 71 D. K. Agrafiotis and H. S. Rzepa J. Chem. Soc. Perkin Trans. 2 1989 475. 72 D. K. Agrafiotis and H. S. Rzepa J. Chem. SOC.,Perkin Trans. 2 1989 367. 73 T. Uchimara S. Tsuzuki K. Tanabe and Y. Hayashi J. Chem. Soc. Chem. Commun. 1989 1861. 74 A. B. Buda Y. Wang and K. N. Houk J. Org. Chem. 1989 54 2264. ’’E. A. Kallel and K. N. Houk J. Org. Chem. 1989 54 6006. 76 J. Breulet and H. F. Schaefer J. Am. Chem. SOC.,1984 106 1221; F. Bernardi A. Bottoni M. A. Robb H. B. Schlegel and G. Tonachini ibid. 1985 107 2260; F. Bernardi M. A. Robb H. B. Schlegel and G.Tonachini hid. 1984 106 1198. I. H. Williams pathways do not actually exist for WH forbidden disrotatory ring opening of cyclobutene 7r2s + 7r2s ethene dimerization and suprafacial 1,3-hydrogen migra- tion in propene. However a transition structure for concerted forbidden suprafacial 1,3-hydrogen migration in cyclopropene does exist at the CASSCF HF and MP2 levels although its energy is very close to the dissociation limit for cyclopropenyl radical plus atomic hydrogen.77 Multiconfigurational SCF calculations predict the walk rearrangement of bicyclo[ 2.1 .O]pent-2-ene to proceed preferentially by the allowed concerted mechanism with inversion at the methylene carbon in a transition structure with -50% biradical character; the forbidden rearrangement with retention of configuration is disfavoured by only 32 kJ mol-’ and occurs via a pure biradical i~~termediate.’~ A CASSCF and MP4 study shows the degenerate thermal rearrange- ment of methylenecyclobutane also to be a stepwise process involving a biradical intermediate stabilized by 7r-electron delocalization in the allylic m~iety.’~ Intramolecular reactivity of the carbene species cyclopropylmethylerie is determined by conformation the cis conformer (5) undergoes ring expansion to cyclobutene whereas the trans conformer (6) preferentially fragments to ethene and ethyne.80 H I Additions to Unsaturated Systems.-Cieplak et al.have discussed three categories of theoretical models for stereoelectronic effects in 7r-facial diastereoselectivity of additions to carbonyl groups viz.those which consider (a) ground-state distortior:s or (b) transition-state torsional interactions or (c) electron donation into the vacanl u+*orbital associated with the incipient bond. They have argued that only the latter Cieplak’s model can accommodate observations on the effects of electron- withdrawing and -releasing substituents in reagents and in cyclohexane-based sub- strates.” Ab initio MO studies of nucleophilic addition of organometsllic reagents to acrolein show that methyllithium prefers (charge-controlled) 1,2-addition whereas methylcopper prefers (orbital-controlled) 1,4-addition via a six-membered cyclic transition structure giving a metal enolate rather than an a-cuprio ketone.82 Stereoselectivities of addition of methylcopper to chiral a$-unsaturated carbonyl compounds are determined by a combination of steric and electronic effects there are similarities to nucleophilic addition to the carbonyl group particularly in regard to the steric requirements for addition to the E-isomers of substituted ensis.but the electronic characteristics are quite different with substituent effects being more in line with expectations for electrophilic reactions.83 Conjugate addition of dialkyl- cuprates to electron-deficient C=C bonds is predicted to involve pre-complexation 77 F. Jensen Chem. Phys. Lett. 1989 161 368. 78 F. Jensen J. Am. Chem. SOC.,1989 111 4643. 79 P. N. Skancke N. Koga and K. Morokuma J. Am. Chem. SOC.,1989 111 1559. 80 P.B. Shevlin and M. L. McKee J. Am. Chem. SOC.,1989 111 519. A. S. Cieplak B. D. Tait and C. R. Johnson J. Am. Chem. SOC.,1989 111 8447. 82 A. E. Dorigo and K. Morokuma J. Am. Chem. SOC.,1989 111 4635. 533 A. E. Dorigo and K. Morokuma J. Am. Chem. SOC.,1989 111 6524. Theoretical Organic Chemistry 41 of copper implying an acute angle of attack onto the double bond which may explain the opposite stereoselectivities observed in the reactions of dialkylcuprates on the one hand and of alkylcopper reagents (and other conventional nucleophiles) on the other.84 The relative reactivities of acrylic acid methacrylic acid acrylonitrile and acrolein towards Michael addition may be predicted by the values of the Laplacian of the electron density distribution which manifests the sizes of the regions of charge depletion on the electrophiles at the site of nucleophilic attack.85 An intramolecular Michael addition has a higher barrier than its intermolecular counterpart owing to the stereoelectronic requirements in forming the six-membered cyclic transition structure.86 The chair transition structure for allylboration of formaldehyde is predicted to be 34 kJ mol-’ lower in energy than the twist-boat transition ~tructure.~’ Spin-projection (see above) halves the barrier heights calculated at the MP4 level for methyl radical addition to ethene and to formaldehyde and gives values agreeing well with experimental activation energiess8 The potential energy barrier for addition of dichlorocarbene to ethene is calculated to be very low (2.5 kJ mol-’ at MP2/6-31G*) and the free energy of activation 49 kJ mol-’ as determined by variational transition-state theory arises largely from the entropic term which is probably responsible for the selectivity of carbene additions.89 The inclusion of diffuse basis functions has a dramatic effect upon the potential energy surface for alkylation of acetaldehyde enolate anion by methyl fluoride and permits unambiguous distinction between the kinetic ( 0-alkylation) and thermody- namic ( C-alkylation) reactions.” The activating/deactivating abilities of substituent groups and their directing effects upon electrophilic aromatic substitution may be predicted by topological analysis of the electron density distributions of substituted phenyl compounds; these effects are not reflected in the total charges of the phenyl group or of its individual atoms but rather in the Laplacian of the total charge distribution in the n-populations and quadrupole moments of the ring carbons and in the ellipticities of the C-H bonds of the phenyl group.” The energetics of formation of arenium ion intermediates in electrophilic aromatic substitution may be interpreted similarly.’* The orientation of electrophilic substitution in non-alternant polycyclic fluoranthrene hydrocarbons have been predicted using a revamped PPP semi-empirical method parameterized for 7r-electrons only.93 SN2Displacements.-Topological electron density analyses at the RHF and MP2 levels with extended basis sets for SN2 methyl transfers involving a range of simple leaving groups and anionic nucleophiles demonstrate that the charges on the incoming and outgoing groups do relate to the position of the transition structure along the reaction ~oordinate;~~ however in the transition structures they do not 84 A.E. Dorigo and K. Morokuma J. Chem. SOC.,Chem. Commun. 1989 1884. as M. T. Carroll J. R. Cheeseman R. Osman and H. Weinstein J. Phys. Chem. 1989 93 5120. 86 C. I. Bayly and F. Grein Can. J. Chem. 1989 67 2173. 87 Y. Li and K. N. Houk J. Am. Chem. SOC.,1989 111 1236. 88 C. Gonzalez C. Sosa and H. B. Schlegel J. Phys. Chem. 1989 93 2435. 89 J. F. Blake S. G. Wierschke and W. L. Jorgensen J. Am. Chem. Soc. 1989 111 1919. 90 E. S. Marcos and J. Bertran J.Chem. SOC.,Furuduy Trans. 2 1989 85 1531. 91 R. F. W. Bader and C. Chang J. Phys. Chem. 1989 93 2946. 92 R. F. W. Bader and C. Chang J. Phys. Chem. 1989 93 5095. 93 M. J. S. Dewar and R. D. Dennington J. Am. Chem. SOC.,1989 111 3804. 94 Z. Shi and R. J. Boyd J. Am. Chem. SOC.,1989 111 1575. 42 I. H. Williams have equal magnitudes contrary to the assertions of Shaik and Pross. A quantitative VB computation of a curve-crossing diagram in the manner of those latter workers' qualitative VB model has been carried out for the SN2reaction H-+ CH based upon local fragment orbital^.^' A barrier height of 239 kJ mol-' in the adiabatic potential curve was calculated and the quantum-mechanical resonance energy in the transition state i.e.the magnitude of the avoided crossing interaction was 67 kJ mol-'. MP4SDTQ and coupled-cluster energies agree to within 1 or 2 kJ mol-' for the ion-molecule complex and 4 or 5 kJ mol-' for the transition structure of the reaction H-+ CH3F; the inclusion of triple excitations was found to be essen- tia1.96 The shape of the energy profile calculated for the dihydrated reaction shown in equation 1 is closer to that for aqueous solution (from Jorgensen's simulation Cl-(H,O) + CH,Br -[HOH--(Cl--CH,--Br)--HOH]-, ClCH + Br-(H,O) (1) for C1- + CH3Cl) than to the gas-phase reaction.97 A MNDO effective charge a generalized Born dielectric continuum and the RISM integral equation methodloo have each been applied to the C1- + CH3Cl reaction and an analysis of discrete continuum and discrete-continuum models of solvation effects on SN2reactions has been presented."' Miscellaneous.-Jorgensen has reviewed his work on free energy calculations which illustrates the power and potential of molecular dynamics and statistical mechanics simulations for modelling organic chemistry in solution.102 For example Monte Carlo simulations and statistical perturbation theory can yield free energies of hydration which with use of a thermochemical cycle lead to calculated pK values for various organic acids.'03 Many-body solvation effects are important in describing the nature of the transition state for the Meyer-Schuster reaction in aqueous solution.'04 Dewar has discussed the nature of desolvation barriers to reactions in solution which are barrierless in the gas phase.'05 The degenerate double proton transfer in the formamidine dimer (7) is predicted to be a concerted process (in the gas phase),'" whereas the double proton shift in azophenine (8) proceeds by a stepwise rnechani~m.'~' Shaik and Pross have argued that in general cation radicals are likely to be less reactive than cations (of the same acceptor ability) towards nucleophilic attack; the former reactions involve product electronic configurations which are doubly excited with respect to the reactants (and so are 'forbidden') whereas the latter involve singly excited product configurations (and so are 'allowed').lo* 95 G. Sini S. S. Shaik J.-M. Lefour G. Ohanessian and P. C. Hiberty J. Phys. Chem. 1989 93 5661.96 M. Urban G. H. F. Diercksen 1. CernuSak and Z. Havlas Chem. Phys. Lett. 1989 159 155. 97 K. Hirao and P. Kebarle Can. J. Chem. 1989 67 1261. 98 T. Kozaki K. Morihashi and 0. Kikuchi J. Am. Chem. Soc. 1989 111 1547. 99 S. C. Tucker and D. G. Truhlar Chem. Phys. Left. 1989 157 164; J. Phys. Chem. 1989 93 8138. 100 S. E. Huston P. J. Rossky and D. A. Zichi J. Am. Chem. Soc. 1989 111 5680. 101 C. AICman F. Maseras A. Lledbs M. Duran and J. Bertran J. Phys. Org. Chem. 1989 2 611. I02 W. L. Jorgensen Acc. Chem. Res. 1989 22 184. 103 W. L. Jorgensen and J. M. Briggs J. Am. Chem. SOC.,1989 111 4190. 104 0. Tapia J. M. Lluch R. Cardenas and J. Andres J. Am. Chem. SOC.,1989 111 829. I05 M. J. S. Dewar and D. Storch J. Chem. SOC. Perkin Trans.2 1989 877. 106 P. Svensson N.-A. Bergman and P. Ahlberg Z. Naturforsch. A 1989 44 473. 107 M. K. Holloway C. H. Reynolds and K. M. Men J. Am. Chem. SOC.,1989,111,3466; H. Rumpel and H.-H. Limbach ibid. p. 5429. lo* S. S. Shaik and A. Pross J. Am. Chem. Soc. 1989 111 4306. Theoretical Organic Chemistry I H (7) Along a minimum-energy reaction path the principle of conservation of bond order is valid to a good approximation using ab initio bond orders computed according to Meyer’s definition.”’ The Hammond postulate and the notion of molecular similarity have been investigated by topological analysis of molecular shape changes occurring along reaction paths.”’ Menger has contended that transition-state modelling does not always model transition states better correlation with experimental activation energies for some degenerate intramolecular hydride transfers being achieved using ground-state struc- tures having all their bonds intact than using transition-state models with partial bonds and charges ‘The ability of “transition-state modelling” to predict rates in solution does not depend on the accuracy or even the existence of a transition state but rather on how closely the associated parameters coincide with one of many parameter sets that happen to provide a high correlation.’”’ G.Lendvay J. Phys. Chem. 1989 93 4422. I10 G. A. Arteca and P. G. Mezey J. Phys. Chem. 1989,93 4146. Ill M. J. Sherrod and F. M. Menger J. Am. Chem. Soc. 1989 111 2611.

ISSN:0069-3030    

DOI:10.1039/OC9898600033

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (i) Pericyclic Reactions By R. J. BUSHBY School of Chemistry The University Leeds LS2 9JT This year the IUPAC Commission on Physical Organic Chemistry has published new recommendations for the symbolic representation of reaction mechanisms.’ Under this scheme Ingold’s sN2 becomes ANDN (A = association D = dissociation N = nucleophile or nucleofuge) and a limiting SN1 mechanism becomes D + AN ( + =stepwise). For this and other simple mechanisms the system is admirably clear laying the emphasis correctly on the number nature and order of the basic steps. The system is also more flexible than Ingold’s nomenclature but it rapidly becomes cumbersone. Few authors will prefer IUPAC’s ‘rococo’ Ah + AN + A D + D + D to Ingold’s ‘plain’ AA,2.Concerted pericyclic mechanisms are designated by the prefix ‘cyclo-’. Hence cycloadditions are cyclo- AA cyclorever- sions cyclo-DD electrocyclic ring closures cyclo- A electrocyclic ring openings cyclo-D and sigmatropic reactions cyclo-AD. If the reactions are stepwise the ‘ + ’ symbol is used. Hence a Diels- Alder reaction through a biradical intermediate becomes A + intra-AR (R = homolytic). It is unfortunate that different symbols are required for 27r + 27~(cyclo-AA) and 27r + 2a (cyclo-AAD) cycloaddition reactions and the suggested addition of N and E (E = electrophilic or electrofugic) subscripts to the descriptors for pericyclic reactions seems suspect. For example reaction (1) is designated c~c~o-ANA, but what do ‘nucleophile’ and ‘electrophile’ or the authors’ claim that the subscripts indicate ‘a polarized transition state’ really mean in this context? \ \ f/ \1/c=c,J /c=c\ (1) Despite some admirable features the justification for this new system seems far from clear.Experience shows that rather than unifying and clarifying it will further fragment a literature that is already overburdened with jargon. ’ R. D. Guthrie Pure Appl. Chem. 1989 61 23; R. D. Guthrie and W. P. Jencks Acc. Chem. Res. 1989 22 343. 45 R. J. Bushby 1 Cycloaddition Reactions The cycloaddition reactions of N-acyl imines2 and of heteroaromatic six-membered rings (e.g.3-0xopyridinium)~have been reviewed. Of more direct mechanistic interest have been a review of cation radical cycloaddition reaction^,^ a very useful update tabulating volumes of a~tivation,~ and a survey by Houk of MO results for Diels- Alder and ketene-olefin cycloaddition reactions6 From the standpoint of the ordinary organic chemist it is difficult to derive clear mechanistic guidance from such MO calculations since the predictions tend to divide along computational lines.Ab initio RHF calculations have an in-built bias favouring synchronous pathway^^-^ whereas UHF and semi-empirical calculations have an in-built bias favouring biradical intermediates.",' On the other hand MCSF calculations treat both closed and open shell systems on an equal footing. It is interesting to note that these seem to predict concerted mechanisms for Diels- Alder reactions and for 1,3-dipolar cyclo- addition reactions but a stepwise pathway for 27r + 277 cycloaddition reactions.12 Perhaps the view of most experimentalists is that although many Diels- Alder reactions are non-synchronous most are concerted and this has received support from KIE studies of the addition reactions of ['H,]- [2H2]- and [2H,]i~~prene.13 The fact that these reactions have large negative volumes of activation5 has also been claimed as supporting a concerted mechanism.However this interpretation has been challenged by Firestone who has suggested that the negative volumes of activation reflect changes in solvation at the transition state and that these reactions actually involve biradical intermediate^.'^ Certainly some Diels- Alder reactions do involve biradical intermediates for example the dimerization of the sterically hindered diene (2) which gives a mixture of formal 27r + 47r (3) and 477 + 477 (4) (2) (3) 2 S.M. Weinreb and P. M. Scola Chem. Rev. 1989 89 1525. 3 A. R. Katritzky and N. Dennis Chem. Rev. 1989 89 827. 4 N. L. Bauld Tetrahedron 1989 45 5307. 5 R. van Eldik T. Asano and W. J. le Noble Chem. Rev. 1989,89 549. 6 K. N. Houk Pure Appl. Chem. 1989 61 643. 7 R. J. Loncharich F. K. Brown and K. N. Houk J. Org. Chem. 1989 54,1129. 8 K. N. Houk;R. J. Loncharich J. F. Blake and W. L. Jorgensen J. Am. Chem. SOC.,1989 111 9172. 9 M. L. McKee and C. M. Rohlfing. J. Am. Chem. SOC.,1989 111 2497. 10 J. Y. Choi and 1. Lee 1. Chem. SOC.,Faraday Trans. 2 1989 85 867; L. F. Tietze J.Fenneu and E. Anders Angew. Chem. Int. Ed. Engl. 1989 28 1371. 11 M. Sodupe A. Oliva J. Bertran and J. J. Dannenberg J. Org. Chem. 1989 54,2488; N. Kaila R. W. Frank and J. J. Dannenberg ibid. p. 4206. 12 R. D. Bach J. J. W. McDouall H. B. Schlegel and G. J. Wolber J. Org. Chem. 1989 54,2931; F. Bernardi A. Bottoni M. Olivucci J. J. W. McDouall M. A. Robb and G. Tonachini THEOCHEM 1988 42 341. 13 J. J. Gajewski K. B. Peterson J. R. Kagel and Y. C. J. Huang J. Am. Chem. SOC.,1989 111 9078. 14 R. A. Firestone and G. M. Smith Chem. Ber. 1989 122 1089. Reaction Mechanisms -Part (i) Pericyclic Reactions products.” It may however be significant that the volume of activation for this ‘biradical’ reaction (ca. -15 cm3 mol-’) is much less than that for a ‘normal’ Diels- Alder reaction (between -25 and -40 cm3 mol-’) .’ Diels- Alder reactions involving radical ion intermediates have also been found for example the reaction between the very electron-rich dienes (5) and very electron-poor dienophiles.16 However Me2N-CH=CH-CH=CH-NMe2 (5) this study has shown that such mechanisms can only occur in a few special cases.A concerted mechanism has been invoked for the reaction of allene (6) with N-phenylmaleimide to give the adduct (7). The stereochemistry is explained not by orbital symmetry factors but by the need for the dienophile to approach from the least hindered face and for the termini of the diene to twist in a disrotatory sense to maximize orbital overlap (8).” The rates of Diels-Alder reactions tend to Me I Ph c, C,-H But be dominated by enthalpic factors and in the case of retro-Diels-Alder reactions such as those shown in formulae (9) and (lo) there is a good correlation between activation energies and heats of reaction.This has also been interpreted as evidence that the mechanisms are concerted. Elimination of naphthalene from ‘adduct’ (9) is much faster than from ‘adduct’ ( 10).l8 l5 J. Baran H.Mayr H.V. Ruster and F.-G. Klarner J. Org. Chem. 1989 54 5016. 16 R. Sustrnann K. Lucking G. Kopp and M. Rese Angew. Chem. Znt. Ed. Engl 1989 28 1713. D. J. Pasto and S.-H. Yang J. Org. Chem. 1989 54 3978. 18 W. Grirnme P. Honer H. T. Kammerling R. Waldraff and J. Wirtz Angew. Chem. Znt. Ed. Engl. 1989 28 1353.R. J. Bushby There have been several interesting studies of the effect of solvent on the rate of the Diels-Alder reaction. These have stressed the role of solvent in lowering the energy of LUMO of the dienophile'' (or diene20i21). This role is reminiscent of that ascribed to various Lewis acid catalysts and although there are several ways of accelerating Diels-Alder reactions22T23 it is the use of such catalysts that is most imp~rtant.~~-~~ Remarkably high asymmetric induction can be obtained by using optically active catalysts,25 and asymmetric induction/ facial selectivity can also be greatly enhanced by making use of the fact that Lewis acid catalysed reactions can be performed at low temperature^.^^'^^ Specific stereochemical/conformational models have been advanced to try to explain the stereochemistries of some of these reactions.27928 However attempts to provide a simple general explanation of the related phenomena of facial selectivity" and endo/ ex0 selectivity' through MO calculations have failed.Attempts to develop simple theories of facial selectivity were discussed in some detail in last year's Report.29 This year there has been little or no support for Hehre's electrostatic arguments but there has been backing for Cieplak and le Noble's hyperconjugation theory,30 and two crystal diffraction studies bear in different ways on various orbital tilting and orbital distortion argument^.^^,^^ A neutron diffraction study of the norbornene derivative (11) shows a downward displacement of the vinyl hydrogens (7.2') which is twice that of most estimate^.^' On the other hand an X-ray diffraction study of the syn-sesquinorbornene (12) at 103 K shows that despite the fact that the vinyl carbons are pyramidalized by 17.2"' there is remarkably little distortion of the 7r-electron di~tribution.~~ There have been 19 G.Desimoni G. Faita P. Righetti N. Tornaletti and M. Visigalli J. Chem. Soc. Perkin Trans. 2 1989 437. 20 M. Burdisso G. Desimoni G. Faita P. Righetti and G. Tacconi J. Chem. Soc. Perkin Trans. 2,1989,845. 21 A. C. Coda G. Desimoni G. Faita P. Righetti and G. Tacconi Tetrahedron 1989 45 775. 22 N. K. Sangwan and H.-J. Schneider J. Chem. Soc. Perkin Trans. 2 1989 1223; J. Lee and J. K. Snyder J. Am. Chem.SOC.,1989 111 1522. 23 D. Hilvert K. W. Hill K. D. Nared and M.-T. M. Auditor J. Am. Chem. Soc. 1989 111 9261. 24 P. V. Bonnesen C. L. Puckett R. V. Honeychuck and W. H. Hersh J. Am. Chem. Soc. 1989 111,6070. 25 K. Furuta A. Kanematsu H. Yamamoto and S. Tukaoka Tetrahedron Lett. 1989 30 7231; K. Furuta S. Shimizu Y. Miwa and H. Yamamoto J. Org. Chem. 1989 54 1481. *' M. C. Carreno J. L. G. Ruano and A. Urbano Tetrahedron Lett. 1989 30 4003; A. I. Meyers and C. A. Busacca ibid. pp. 6973 6977; T. Poll A. F. Abdel Hady P. Karge G. Linz J. Weetman and G. Hehnchen ibid. p. 5595. 27 I. Alonso J. C. Carretero and J. L. G. Ruano Tetrahedron Lett. 1989 30,3853. 28 R. C. Gupta D. S. Larsen R.J. Stoodley A. M. Z. Slawin and D. J. Williams J. Chem. Soc. Perkin Trans.I 1989,739; C. Siege1 and E. R. Thonton Tetrahedron Lett. 1988,29,5225; A. Brandi P. Cannavo K. M. Pietrusiewics M. Zablocka and M. Wieczorek J. Org. Chem. 1989 54 3073. 29 R.J. Bushby Annu. Rep. Prog. Chem. Sect. B,Org. Chem. 1989 85 39. 30 A. M. Naperstkow J. B. Macaulay M. J. Newlands and A. G. Fallis Tetrahedron Lett. 1989,30 5077; A. S. Cieplak B. D. Tait and C. R. Johnson J. Am. Chem. Soc. 1989 111 8447. See also ref. 78. 31 0. Ermer P. Bell and S. A. Mason Angew. Chem. Int. Ed. Engl. 1989 28 1239. 32 H. Irngartinger J. Deuter P. Charumilind and L. A. Paquett J. Am. Chem. Soc. 1989 111 9236. Reaction Mechanisms -Part (i) Pericyclic Reactions several interesting experimental studies of facial sele~tivity.~’,~~,~~ In some cases it has been suggested that hydrogen bonding is significant but this has not been borne out by more recent studies.For example the addition of N-phenylmaleimide to the diene (13) proceeds predominantly (87 :13) anti to the -CH20H group.34 Studies of endolexo selectivity have shown that this can be affected by Lewis acid catalysis3’ and by pressure,36 and deuterium labelling has confirmed that the addition of cyclopropene to butadiene involves an endo transition state.37 Me CHzOH x One prediction of theoretical chemists that experimental chemists have found difficult to accept is that many 1,3-dipoles have substantial 1,3-biradical character. In an interesting theoretical study the difference between RHF and UHF energies has been used as a measure of the biradical character of 1,3-dipoles and the effect of solvent has been accounted for by the SCXF method.This shows that for most 1,3-dipoles the 1,3-biradical character all but disappears in polar solvents but for symmetrical 1,3-dipoles (e.g. O3 and HNONH) substantial 1,3-biradical character remains even in the most polar solvent^.^' The chemistry of azomethine ylides has been reviewed,39 and routes to 1,3-dipoles described using de~ilylation,~~’~~ prototropic rearrangement,43-46 decarb~xylation,~~ 33 M. Ishida T. Aoyama and S. Kato Chem. Lett. 1989 663; P. G. McDougal J. MY Jump C. Rojas and J. C. Rico Tetrahedron Lett. 1989 30,3897; J. R. Gillard and D. J. Burnell J. Chem. Soc. Chem. Commun. 1989 1439. 34 L. A. Paquette C.Vanucci and R. D. Rogers J. Am. Chem. SOC.,1989 111 5792. 35 H. Lamy-Schelkens D. Giomi and L. Ghosez Tetrahedron Lett. 1989 30 5887 5891. 36 M. Buback W. Tost T. Hubsh E. Voss and L. F. Tietze Chem. Ber. 1989 122 1179. 37 J. E. Baldwin and V. P. Reddy J. Org. Chem. 1989 54 5264. 38 T. Steinke E. Hansele and T. Clark J. Am. Chem. Soc. 1989 111 9107. 39 0.Tsuge and S. Kanemassa Adv. Heterocyl. Chem. 1989 45 231. 40 A. I. D. Alanine and C. W. G. Fishwick Tetrahedron Lett. 1989 30,4443; C. W. G. Fishwick A. D. Jones and M. B. Mitchell ibid. p. 4447; A. 1. D. Alanine C. W. G. Fishwick and C. Szantay ibid. p. 6573. 41 A. Padwa G. E. Fryxell J. R. Gasdaska M. K. Venkatrarnanan and G. S. K. Wong J. Org. Chem. 1989 54 664. 42 C. A. Maryanoff C.B. Karash I. J. Turchi E. R. Corey and B. E. Maryanoff J. Org. Chem. 1989 54 3790; R. Grigg D. Henderson and A. J. Hudson Tetrahedron Lett. 1989 30,2841. R. J. Bushby rhodium-catalysed deazetation of diazoketone~,~' deaze-ring opening of thiirane~,~' tation of thiadiazoline~,~~ and the addition of electrophiles to dehydr~genation,~' oxime~.~' In some cases the formation or reaction of 1,3-dipoles is metal-ion dependent. Sometimes the metal ion (hydrate) acts as a Brdnsted acid promoting prototropic rearrangement^:^ but in other cases it is implemented in a more active way.41,44The reaction of ninhydrin with a-amino acids goes via the 1,3-dipole (14) which can be trapped with dipolarophiles. The importance of such intermediates is underlined by the observation (X-ray crystal structure) that protonated Ruhemann's Purple is a stable N-protonated 1,3-dipole (15).46 1,3-Dipoles are also involved in the reaction of a-amino acids (esters) with pyridoxal.In the case of the ester (16) the resultant 1,3-dipole is trapped in an intramolecular manner (17). It may be that natural E-alkenyl-a-amino acids such as S-allylcysteine sulphoxide have an antibio- tic function related to this reaction acting as suicide substrates for pyridoxal phosphate depend+ent enzymes.43 The ring opening of thiiranes to give 1,3-dipoles of the type CH2=S-CH2 normally cannot compete with the elimination of sulphur. However thiiranes (18) and TCNE form coloured complexes which give good yields of the adducts (19)48on photolysis.The reaction is thought to go through the radical ion pair (18)+' TCNE-'. 43 R. Grigg and W. P. Armstrong Tetrahedron 1989 45 7581. 44 D. A. Barr R. Grigg and V. Sridharan Tetrahedron Lett. 1989,30 4727; D. A. Barr G. Donegan and R. Grigg J. Chem. SOC.,Perkin Trans. 1 1989 1550; R. Grigg G. Donegan H. Q. N. Gunaratne D. A. Kennedy J. F. Malone V. Sridharan and S. Thianpatanagul Tetraheadron 1989 45 1723. 45 K. Amornraksa D. Barr G. Donegan R. Grigg P. Ratananukul and V. Sridharan Tetrahedron 1989 45 4649. 46 R. Grigg J. F. Malone T. Mongkolaussavaratana and S. Thianpatanagal Tetrahedron 1989 45 3849. 47 A. Padwa R. L. Chinn S. F. Hornbuckle and L. Zhi Tetrahedron Lett. 1989 30 301; D. C. Dean K. E. Krumpe and A. Padwa J.Chem. Soc. Chem. Commun. 1989 921; A. Padwa D. C. Dean and L. Zhi J. Am. Chem. SOC.,1989 111 6451. 48 M. Kamata and T. Miyashi J. Chem. Soc. Chem. Commun. 1989 557. Reaction Mechanisms -Part (i) Pericyclic Reactions Most 1,3-dipole-a1kene cycloaddition reactions are probably concerted but like Diels- Alder reactions (see above) 1,3-dipolar cycloadditions can be diverted into biradical or zwitterionic pathways. The observation that the addition of nitrile oxides to the sterically hindered diene (2) involves a stepwise mechanism is not surprising.52 Less expected is the observation that the addition of the C,N-diphenylnitrone (20) to various simple dienes also proceeds through biradical intermediates. For example the addition to 1,2-dimethylenecyclopentaneproceeds via the biradical (21) to give a mixture of the adducts (22) and (23).53By way of contrast zwitterionic intermedi- 0' ates [e.g.(25)]are involved in the addition of the sterically hindered thiocarbonyl ylides (24) to very electron-deficient alkene~.~~ Another intriguing observation is the spectroscopic detection and characterization of a complex between ozone and ethylene (26);in this the molecules lie in parallel planes.55 The complex is thought of as a local minimum on the energy surface prior to the transition state leading to the primary ozonide and the formation of such a complex has been predicted by MO cal~ulations.~ Bu' \+ c=s /\ But CH2 I C-CFI F3C-C -/ \ CN / But NC (24) (25) 49 V. A.Montero I. T. Hernandez J. de P. Teresa J. R. Moran and R. Olabarrieta J. Org. Chem 1989 54 3664; G. Mloston E. Langhals and R. Huisgen Tetrahedron Lett. 1989 30 5373. 50 R. Grigg and F. Heaney J. Chem. Sac. Perkin Trans. 1 1989 198. 51 G. Donegan R. Grigg F. Heaney S. Surendrakumar and W. J. Warnock Tetrahedron Lett. 1989 30 609; R. Grigg and J. Markandu ibid. p. 5489. 52 J. Baran and H. Mayr J. Org. Chem. 1989 54 5012. 53 J. Baran and H. Mayr J. Org. Chem. 1989 54 5774. 54 R. Huisgen and G. Mloston Tetrahedron Lett. 1989 30,7041. 55 J. Z. Gillies C. W. Gillies R. D. Suenram F. J. Lovas and W. Stahl J. Am. Chem. Sac. 1989 11 3073. R. J. Bushby Singlet tetramethylene is thought of as existing in a very shallow energy minimum which is perhaps only protected by entropic barriers.56 Triplet 1,4-biradicals gener- ated in Norrish type I1 photoreactions can however be trapped with oxygen.57 1,4-Dioxybutane biradicals generated in the thermal retro 27r + 27r reaction of the dioxetane (27) can be trapped with hydrogen atom sources5* and 1,4-biradical intermediates in the 27r + 27r photoaddition of alkenes to cyclohexenones can also be trapped in an intramolecular manner using a cyclopropyl s~bstituent.~~ -P a (27) (28) A remarkable example of a thermal 27r + 27r cycloaddition has been provided by the reaction of cyanoacetylene with the paracyclophane (28)60One of the products is the adduct (30) which is assumed to be formed through an initial dimerization of cyanoacetylene to give the cyclobutadiene (29).There have been several very interesting studies of the cycloaddition reactions of biradi~als.~l-~~ The reactivity order of the singlet biradicals (31; X = 0 or S) with alkenes quantitatively parallels that for the Diels- Alder reaction of a typical diene 56 C. Doubleday M. Page and J. W. Mclver THEOCHEM 1988 40 331. ” W. Adam S. Grabowski and R. M. Wilson Chem. Ber. 1989 122 561. 58 W. H. Richardson M. B. Lovett and L. Olson J. Org. Chem. 1989 54 3523. 59 D. Becker N. Haddad and Y. Sahali Tetrahedron Lett. 1989,30 2661. 60 B. Witulski L. Emst P. G. Jones and H. Hopf Angew. Chem. Znt. Ed. Engl. 1989 28 1279. 61 K. J. Stone M. M. Greenberg S. C. Blackstock and J. A. Berson J. Am. Chem. SOC.,1989 111 3659. 62 J.C. Scaiano V. Wintgens K. Haider and J. A. Berson J. Am. Chem. SOC.,1989 111 8732. 63 S. Yamago and E. Nakamura J. Am. Chem. SOC.,1989 111 7285. 64 N. A. Le M. Jones F. Bickelhaupt and W. H. de Wolf J. Am. Chem. SOC.,1989 111 8491; P. A. Kraakman W. H. de Wolf and F. Bickelhaupt ibid. p. 8534. 65 K. B. Wiberg and A. Chaves J. Am. Chem. SOC.,1989 111 8052. 53 Reaction Mechanisms -Part (i) Pericyclic Reactions (cyclopentadiene).61 This is despite the fact that the biradical addition reactions are 10'' times faster and that whereas the rate order for the Diels-Alder reactions is determined by enthalpic factors that for the biradicals is determined by differences in the entropy term. (The enthalpic barrier for the biradical additions is negligible.62) Evidence has been advanced to show that formal 1,4-addition of carbenes to cisoid dienes does involve true carbene intermediate^.^^ In the case of the diene (32) dibromocarbene gives the adduct (33) consistent with a disrotatory linear concerted mechanism.64 Another interesting but unexplained observation is that treatment of the dibromide (34) with methyllithium gives mainly a product (35) in which the stereochemistry of the double bond has been in~erted!~' D D H-l:i: *D 2 Sigmatropic Reactions Various studies of 1,3-~igmatropic shifts have received very different interpretations.The vinyl cyclopropane rearrangement (36) gives mainly the si product (37) and this together with measurements of secondary isotope effects was interpreted in terms of a concerted mechanism.66 MCSF calculations also predict a concerted si mechanism for the 'walk' rearrangement of bi~yclopentene.~' On the other hand the rearrangement of compound (38; X = F) like the corresponding rearrangement of compound (38; X = Me) gives a mixture of products interpreted in terms of M:+p But D (36) (37) 66 J.J. Gajewski and M. P. Squicciarini J. Am. Cfiem. SOC.,1989 111 6717. 67 F. Jenson J. Am. Chem. Soc. 1989 111 4643. R. J. Bushby initial homolysis of the 1,7-bond to give a biradical intermediate,? and calculations (6-31G + CI) on the rearrangment of methylenecyclobutane also support a stepwise biradical mechanism.69 Thermal 1,3-shifts of silicon proceed in a si manner and have been interpreted as concerted 'allowed' reactions.However when the optically active compound (39; Ar = a-naphthyl) (a' = -3.6') is photolysed it gives compound (40) and when this is converted back into compound (39) by heating the rotation is almost unchanged (a = -3.5"). Clearly one of the reactions is proceeding in a 'disallowed' manner either the thermal reaction is proceeding with retention of configuration at silicon or (more likely) the photochemical reaction involves inversion at silicon.70 I Tr:ph Aliphatic Claisen rearrangements have been reviewed." Just as the rearrangements of these systems are sometimes formulated as involving a cyclohexa-l,4-diyl inter- mediate so the rearrangement of yn-en-yn systems (41) can give rise to p-benzyne derivatives (42).This mechanism is thought to be important in the action of calicheamicin and esperamicin antibiotics.72p73 In the case of the model compound (43) it is the intramolecular Michael addition shown that triggers the cyclization. In the presence of a hydrogen atom source the main product is compound (44).73 W. R. Dolbier and 0. Phanstiel J. Am. Chem. SOC. 1989 111 4907. 69 P. N. Skancke N. Koga and K. Morokuma J. Am. Chem. Soc. 1989 111 1559. 70 M. Kira T. Taki and H. Sakurai J. Org. Chem. 1989 54 5647. 71 F. E. Ziegler Chep. Reu. 1988 88 1423. 72 J. P. Snyder J. Am. Chem. SOC.,1989 111 7630. 73 J. N. Haseline and S. J. Danishefsky J. Am. Chem. SOC.,1989 111 7638. Reaction Mechanisms -Part (i) Pericyclic Reactions In a similar manner cyclization of the yn-en-allene system (45) gives rise to the reactive biradicals (46),74,75 and it has been shown that this can be accelerated by methyl or more particularly thio substituents at the allene terminus.75 Interest in anion accelerated 1,3-76 and 3,3-~hifts~~*~' continues and in the case of the adamantane derivative (47) the facial selectivity is as shown.The new a-bond is formed anti to the electron-rich 3,lO and 1,8 cr-b~nds.~' Some Claisen rearrange- ments [e.g. for compound (48)] are accelerated in water and in this way a number of useful but otherwise inaccessible reactions become pos~ible.~' Carbon- 13 labelling experiments have shown that the rearrangement of compound (49) to (50) on treatment with butyllithium involves a 2,5-sigmatropic shift," and measurement of the volume of activation for the 1,9-sigmatropic shift (51) shows that this is similar to that for 1,5-sigmatropic shifts suggesting a concerted mechanism.*l 74 A.G. Myers E. Y. Kuo and N. S. Finney J. Am. Chem. Soc. 1989 111 8057. 75 A. G. Myers and P. S. Dragovich J. Am. Chem. Soc. 1989 111 9130. 76 G. Subramanian V. T. Ramakrishnan and K. Rajagopalan Tetrahedron Lett. 1989 30 3833. 77 S. E. Denmark M. A. Harmata and K. S. White J. Am. Chem. Soc. 1989 111 8878; K. Thangaraj P. C. Srinivasan and S. Swaminathan Tetrahedron Lett. 1989 30 4427. 78 M.-H. Lin and W. J. le Noble J. Org. Chem. 1989 54 997. 79 P. A. Grieco E. B. Brandes S. McCann and J. D. Clark J. Org. Chem. 1989 54 5849.80 D. W. Jones and R. J. Marmon Tetrahedron Lett. 1989 30 5467. 81 S. Sugiyama A. Mori N. Kato and H. Takeshita Bull. Chem. Soc. Jpn. 1989 62 1143. R. J. Bushby 3 Electrocyclic Reactions Thermal electrocyclic ring closure of the allene (6) occurs in the expected disrotatory sense to give a 9 1 mixture of the cyclobutenes (52) and (53).82Like the cyclobutene- butadiene reaction the cydopentenyl cation-pentadienyl cation reaction is predicted to show torquoselectivity. Hence electron-donating substituents (OH F NH,) should rotate outwards whereas acceptor substituents (CHO BH,) should rotate inwards.83 In the case of the photocyclization of the triene (54) the torquoselectivity Me seems to be an expression of the NEER (Non-Equilibration of Excited-state Rotomers) prin~iple.~~ Largely as a result of a steric interaction between the ethyl group and the adjacent vinyl substituent the preferred rotomer is as shown (54) and conrotatory ring closure occurs with diastereoselectivity to give mainly the product (55).84 4 Miscellaneous Pericyclic Reactions AM 1 calculations tend to favour a concerted mechanism for the reduction of alkenes with cis-diimide and suggest that in the case of strained alkene acceptors a hydrogen bonded complex is formed.85 Whereas the simplest mechanism for the thermal conversion of benzobicyc- lononatriene (56) into benzobarbaralane (57) is an intramolecular ene reaction labelling and other studies have shown that this is not the case.Rather a complex sequence of pericyclic reactions is proposed starting with a Cope rearrangement.86 a2 D.J. Pasto and S.-H. Yang J. Org. Chem. 1989 54 3544. 83 E. A. Kallel and K. N. Houk 1.Org. Chem. 1989 54 6006. a4 J. K. Whitesell M. A. Minton and V.D. Tran. J. Am. Chem. SOC.,1989 111 1473. 85 D. K. Agrafiotis and H.S. Rzepa J. Chem. SOC.,Perkin Trans 2 1989 475. 86 D. W. Jones J. Chem. SOC.,Chem. Commun. 1989 1481.

ISSN:0069-3030    

DOI:10.1039/OC9898600045

出版商:RSC    

年代:1989

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 DHl 3LE 1 Introduction After 10 years of deliberation the IUPAC Commission on Physical Organic Chemistry has produced its recommendations regarding the system for the rep- resentation of reaction mechanisms.' Rather than modify the widely used system based on the Ingold notation the working party has decided to recommend a totally new system. Basically the system lists the bonds made and broken (as association A or dissociation D) with subscripts to indicate the apportionment of electrons. This has the advantage of being a more precise method and removes some of the ambiguities inherent in the presently used system. However since it represents such a major change it is bound to stimulate much discussion and argument.Time will tell whether physical organic chemists will take kindly to the recommendations. The feeling of this reviewer is that chemists who have been unwilling to abandon the kcal in favour of kJ are unlikely to make the change and that SN2etc. will be with us for some time to come. A summary of the new method is given along with a number of specific examples by Guthrie and Jencks.* The 1989 volume of Advances in Physical Organic Chemistry includes an article on the mechanisms and catalysis of nucleophilic substitution in phosphate ester^.^ The authors discuss dissociative and addition-elimination mechanisms together with the biological chemistry of phosphate esters The same volume includes a contribu- tion on perchloro-organic chemistry," which deals with aspects of the structure spectroscopy and reaction pathways of polychlorinated organic systems.Jorgensen' claims a breakthrough in the modelling of organic reactions in solution. He uses molecular dynamics and statistical mechanics simulations as a basis for free energy calculations from which solvent effects can be studied theoretically more quantitatively than previously. Abraham and co-worker8 have also produced a review of their ideas and treatment of solvent effects in organic chemistry (in a 1988 article which arrived too late for inclusion in last year's Report). Their treatment in terms of multiple linear regression analysis has been applied to a wide range of ' IUPAC Commission on Physical Organic Chemistry Pure Appl.Chem. 1989 61 23 57. R. D. Guthrie and W. P. Jencks Acc. Chem. Rex 1989 22 343. G. R. J. Thatcher and R. Kluger Adu. Phys. Org. Chem. 1989 25 99. M. Ballester Adv. Phys. Org. Chem. 1989 25 267. W. J. Jorgensen Acc. Chem. Res. 1989 22 184. M. H. Abraham P. L. Grellier J.-L. M. Abboud R. M. Doherty and R. W. Taft Can. J. Chem. 1988 66 2673. 57 D. L. H.Williams processes including solubility of gases as well as both equilibrium and rate constants of chemical reactions. The equations derived by Koppel and Palm and by Abraham Kamlet and Taft cope satisfactorily. Steric effects on amine basicity have been reviewed by Alder.' The result of angle strain and steric inhibition of solvation is base weakening for monoamines whilst for a number of diamine systems base strengthening can occur due to the formation of an intramolecular hydrogen bond in the monoprotonated cation.The need for more quantitative work in this area is stressed. 2 Solvolysis and Carbocations All the kinetic evidence (including the common-ion effect) and the results of azide trapping experiments are consistent with an ionization mechanism giving a carboca- tion intermediate in the solvolysis (equation 1) of 2-chloromethyl- 1-methyl- imidazole.* It is suggested that the carbocation (and so the transition state leading HNyNMe ZNyNMe -NyNMe F I7 m CH2Cl CHiCl CH2OH to its formation) is stabilized by the 2-imidazoyl ring by way of extensive delocaliz- ation of the positive charge.Further work' in the area of solvolysis of benzoyl halides has revealed that the fluorides undergo a dissociative mechanism (&I) only when there are powerful electron-releasing groups present (e.g. 4-dimethylamino) otherwise an associative addition-elimination mechanism prevails. Conversely ben- zoyl chlorides generally react via the dissociative route but a change to the associa- tive mechanism can be brought about with strongly electron-attracting substituents (e.g. 4-nitro). These differences are readily recognized experimentally by the sign of p (or p+) the dependence on the leaving group the solvent isotope effect and the common-ion effect. Bentley and Roberts" have extended the study of solvent effects on SN1reactivity to include two new leaving groups trifluoroacetate and heptafluorobutyrate.The relatively low reactivity witnessed in fluorinated solvents is explained in terms of nucleophilic solvent assistance for reactions in the more nucleophilic solvents. A good correlation is reported for the solvolyses of substituted benzyl p-toluenesul- phonates in eleven solvents using the extended Grunwald- Winstein equation." The results including the magnitude of the I and rn values suggest an sN2 mechanism with a variable transition state structure for all except one of the esters. Large anchimeric effects by y-aryl groups are reportedI2 for the solvolysis of organosilicon iodides which are not found in the corresponding carbocation reac- tions. The difference is explained in terms of severe steric hindrance to solvation of cationic centres in the transition state of the organosilicon iodide reactions.R. W. Alder Chem. Rev. 1989 89 1215. J. L. Bolton and R. A. McClelland Can. J. Chem. 1989 67 1139. 'B. D. Song and W. P. Jencks J. Am. Chem. SOC.,1989 111 8470. lo T. W. Bentley and K. Roberts J. Chem. SOC.,Perkin Trans. 2 1989 1055. " D. N. Kevill and H. Ren J. Org. Chem. 1989 54 5654. '*C. Eaborn K. L. Jones and P. D. Lickiss J. Chem. SOC.,Chem. Commun. 1989 595. Reaction Mechanisms -Part (ii) Polar Reactions By varying substituents X and Y in both rings in substituted benzene azoxyarenesulphonates it has been shown that solvolysis occurs (equation 2) by synchronous concerted bond heter~lysis.'~ x I X A full account has been p~blished'~ describing intramolecular proton transfer catalysis of nucleophilic catalysis in acetal hydrolysis using 8-dimethylamino-l- methoxymethoxynaphthalene ( 1).The principal feature of intramolecular catalysis is the formation of an intramolecular hydrogen bond with the leaving group oxygen atom which is absent in the reactant but strong in the transition state (and the product). The same effect is believed to be involved in the hydrolysis of 8-hydroxy-l- methoxymethoxynaphthalene (2).15 The solvolysis of acetals of propionaldehyde derivatives proceeds via very short-lived oxocarbenium ions as outlined in equation 3. The lifetimes of these intermediates have been determined from kinetic measure- ments with added azide ion and are found to be too short to allow for diffusion to nucleophilic reagents so that substitution reactions with nucleophiles (other than the solvent) must occur by a concerted bimolecular pathway.16 The selectivity Br-/C1- as measured by the ArBr/ArCl product ratios in the capture of aryl cations produced by the dediazoniation of three arenediazonium l3 I.M. Gordon and H. Maskill J. Chem. SOC.,Chem. Commun. 1989 1358. 14 A. J. Kirby and J. M. Percy J. Chem. SOC.,Perkin Trans. 2 1989 907. F. Hibbert and K. J. Spiers J. Chem. SOC.,Perkin Trans. 2 1989 377. 16 T. L. Amyes and W. P. Jencks J. Am. Chem. SOC.,1989 111 7888 7900. D. L. H. Williams ions is independent of the viscosity of the solvent;” this suggests that the aryl cation reactions with halide ions are diffusion controlled.Experimental evidence has been presented18 that hyperconjugation with strained bonds [in the cyclopropyl phenyl cation (3)] produces a very large stabilization effect in this case by at least 27.6 kcal relative to the phenyl cation. The prop-2-yl cation (4) is believed to be chiral. The prediction is made by ab initio calculations and supported by the correspondence of the experimental and calculated I3C NMR chemical shifts for that conformation (a twisted structure with C symmetry).’’ R McClelland and co-workers have generated the xanthylium cations (5) by flash photolysis of the corresponding 9-xanthenols and have measured the rate constants for reaction with a number of nucleophiles.20 Some show a correlation with the Ritchie N equation but the reactions of the more reactive cations may be diffusion controlled or desolvation controlled.Further results reported by the same group2’ have been obtained on the reaction of 18 triarylmethyl and 10 diarylmethyl cations (generated in the same way) with water. There is a better correlation of the rate constants with ac+ (obtained from analysis of NMR spectra of carbocation sol- utions) than with a+. 3 Other Nucleophilic Substitutions The question of SET involvement in nucleophilic substitution reactions continues to be addressed though apparently not with the same intensity as in recent years. Bordwell and Harrelson22 have used the Eberson approach of calculating kET using a Marcus-type equation and comparing it with the experimental second-order rate constant kobs.Application of this test to reactions of benzyl chloride with some carbanions substituted phenoxide ions and thiophenoxide ion gave very large values for the kobs/kET ratio and hence no evidence for an SET pathway. A test of the method gave ratios of -1 for the well-known SET acceptor 1,l-dinitrocylohexane. However with benzhydryl chloride and seven 9-(dialky1amino)fluorenideions there was close agreement between kobsand kET. These results together with unexpectedly low rate constant ratios for PhCH,Cl/ Ph2CHCI support the view that the reactions of Ph2CHCI with these fluorenide ions take place by SET mechanism^.^^ J. P. Lorand Tetrahedron Lett. 1989 52 7337. 18 E. Uggerud D.Arad Y.Apeloig and H. Schwartz J. Chem. SOC.,Chem. Commun. 1989 1015. 19 P.von R. Schleyer W. Kcch B. Liu and U. Fleischer J. Chem. SOC.,Chem. Commun. 1989 1098. 20 R. A. McClelland N. S. Banait and S. Steenken J. Am. Chem. SOC.,1989 111 2929. 21 R. A. McClelland V.M. Kanagasabapathy N. S. Banait and S. Steenken J. Am. Chem. SOC. 1989 111 3966. 22 F. G. Bordwell and J. A. Harrelson J. Org. Chem. 1989 54,4893. 23 F. G. Bordwell and J. A. Harrelson J. Am. Chem. SOC.,1989 111 1052. 24 E. S. Lewis J. Am. Chem. SOC.,1989 111 7576. Reaction Mechanisms -Part (ii) Polar Reactions stresses the distinction between the two mechanisms particularly with regard to methyl transfer reactions and concludes that they are rarely competitive SET occurring only with highly reducing nucleophiles.A three-variable system has been studied in the reaction of 2-substituted benzyl X-substituted benzenesulphonates (6) with Y-substituted N,N-dimethylanilines (7) in acetone for a Menschutkin-type SN2reaction.25 The three p values were measured and the interaction terms pxy,pyz and pzx obtained which are claimed to give the degree of bond making and breaking and hence are indicative of mechanistic changes from SN2 to sN1. In the continuing debate regarding changes in structure-reactivity parameters and transition state structure in bimolecular substitution reactions Dietze and Jencks26 have presented results of a study with 4-nitrobenzylsulphonates. They find a small increase in selectivity with decreasing reactivity but stress that a large range of reactivity may be required (in both the nucleophile and the leaving group) in order to detect the selectivity change.Analysis of the aminolysis reactions of benzoyl fluorides in water (equation 4) suggests that the reaction mechanism is one of concerted sub~titution,~~ although it is not possible to rule out completely the possibility of a stepwise reaction involving a tetrahedral intermediate. RNH,+ArCOF -+ RNHCOAr+H++F-(4) The secondary a-D kinetic isotope effect (KIE) and substituent effects in the reaction of substituted thiophenoxides with tetraalkylammonium ions (equation 5) X o S -+ PhCH2kMe,Ph -PhCHzS O X + MezNPh (5) are larger when the nucleophile is the free ion than when it is a solvent-separated ion pair complex (produced by addition of 1S-~rown-5-ether).~' The explanation is that one gets a tighter transition state (and hence smaller secondary KIE) for the solvent-separated ion pair resulting from a reduction of charge on the sulphur atom brought about by the sodium ion of the complex.The secondary-D KIE is unaffected by a change from protic to aprotic solvents (for the reaction of n-butyl chloride with PhS-).29 This confirms an earlier proposed 'solvation rule' for SN2reactions 25 S.-D. Yoh Y. Tsuno M. Fujio M. Sawada and Y. Yukawa J. Chem. SOC.,Perkin Trans. 2 1989 7. 26 P. Dietze and W. P. Jencks J. Am. Chem. SOC.,1989 111 5880. 21 B. D. Song and W. P. Jencks J. Am. Chem. SOC.,1989 111 8479. 28 Z.-G. Lai and K.C. Westaway Can. J. Chem. 1989 67,21. 29 K. C.Westaway and Z.G. Lai Can. J. Chem. 1989 67,345. 62 D. L. H. Williams namely that a change of solvent will not lead to a change in transition state structure if the charges on the two nucleophiles in the transition state are the same. Evidence has been presented that the metaphosphate monoanion is not an inter- mediate in the reaction of various oxygen nucleophile species with three phosphory- lated pyridine rnonoanion~.~~ The same authors discuss the nature of the transition state and electrostatic repulsions in phosphoryl transfer reactions to anionic oxygen nucleophiles and the implications for enzyme-catalysed phosphoryl transfer reac- tion~.~~ Catalysis by metal ions in nucleophilic displacement at phosphoryl centres (equation 6) has been interpreted in terms of reaction via the free nucleophile OEt- and also metal ion-OEt- ion pairs.32 0 0 I1 II OEt-+ Ph,POAr -+ Ph,POEt + OAr-Two theoretical accounts have been published one dealing with nucleophilic attack at cation radical and cation centres using the curve crossing the other with the analysis of solvent effects in SN2 reactions by different theoretical 4 Elimination Reactions Elimination reactions in the gas phase continue to attract attention from the mechanistic view point.Speranza and co-workers have published two paper^^',^^ which begin a series on base-induced eliminations in onium intermediates in the gas phase. In the first FT-ICR mass spectrometry is used to study the reaction of amines with diethylmethyloxonium ions (see equation 7) generated from diethyl HhR + C2H + MeOEt NR + CH,CH&Et -(7) I Me ether and dimethylchloronium ion (MeCIMe+).Both substitution and elimination takes place the latter being favoured with increasing base strength. At high encounter excitation energies other (novel) reactions occur involving one-electron transfers. In the second paper of the series a radiolytic method is used to investigate the stereochemistry and orientation in alkene formation from halonium ions in the gas phase. These high pressure studies allow comparisons to be made with solution studies. Other workers3’ have shown that methoxide ion reacts in the gas phase with 1-bromopropane to give only the products of elimination (equation 8) in contrast to the solution state reaction where substitution is the preferred pathway.Chuchani 30 D. Herschlag and W. P. Jencks J. Am. Chem. Soc. 1989 111 7579. 31 D. Herschlag and W. P. Jencks J. Am. Chem. SOC.,1989 111 7587. 32 E. J. Dunn and E. Buncel Can. J. Chem. 1989 67 1440. 33 S. S. Shaik and A. Pross J. Am. Chem. Soc. 1989 111 4306. 34 C. Aleman F. Maseras A. Lledos M. Duran and J. Bertran J. Phys. Org. Chem. 1989 611. 35 G. Occhiucci M. Speranza L. J. de Koning and N. M. M.Nibbering J. Am. Chem. Soc. 1989,111,7387. 36 G. Angelini G. Lilla and M. Speranza J. Am. Chem. SOC.,1989 111 7393. 37 M. E. Jones and G. B. Ellison J. Am. Chem. SOC.,1989 111 1645. Reaction Mechanisms -Part (ii) Polar Reactions 63 and co-workers have investigated the elimination of 2-chloropropionic acid38 and -0Me +CH,CH,CH,Br + MeOH +CH,CH=CH +Br-(8) primary alkyl methanes~lphonates,~~ again in the gas phase.Both reaction mechan- isms are discussed in terms of the formation of intimate ion-pair intermediates. In the case of the sulphonates steric factors are important and the data correlate with several steric parameters. In two papers Bunnett and Migda14* compare the reactivities of EtS- and MeO- in elimination reactions in DMSO-MeOH solvent mixtures. In the methanol-rich solvents EtS- is the more reactive species whilst in the DMSO-rich solvents the reverse is true. It is argued that these results are fully compatible with an E2 mechanism with a variable transition state structure and that there is no necessity to invoke an E2C mechanism.Another report41 examines the effect of the nature of the leaving group on the transition state structure of the E2 mechanism of the reaction of 1-phenylethylammonium ions with EtO- in EtOH. There is no linear correlation between reactivity and the basicity of the leaving group. The results together with those of KIE measurements suggest that leaving group ability is determined mainly by steric effects which in turn determines the transition state structure. For the poorer leaving groups the proton is more than half transferred in the transition state whereas it is less than this for the better leaving groups. 5 Addition Reactions Bernasconi has produced a timely Tetrahedron Report42 on the kinetics and mechan- ism of nucleophilic addition to alkenes.In the past such reactions have been overshadowed particularly with regard to mechanistic studies by their electrophilic counterparts but recent work by a number of research groups (over the past 14 years) has shed much light in this area. The report discusses the addition of H20 OH- amines RS- CN- N3- F- RO- and carbanions and there is a chapter on structure-reactivity relationships that includes a discussion of Bernasconi’s own ‘principle of non-perfect synchronization’ together with factors affecting nucleophi- licity and nucleofugality. Intermediates are often deduced from kinetic and other measurements. Bernasconi and have now reported the first direct observation by its UV absorption spectrum of an intermediate in a nucleophilic addition reaction of thiolate ion with a nitrostilbene derivative (equation 9).Russian workersM have found a rate equation Ph NO2 Ph NO Ph NO \ ’+RS-& \/ -/c=c\w\ ’+MeO-(9) /Ic-c Me0 /c=c\w Me0 I \Ph RS SR 38 G. Chuchani and A. Rotinov Int. J. Chem. Kinet. 1989 21 367. 39 G. Chuchani S. Pekerar R. M. Dominguez A. Rotinov and I. Martin J. Phys. Chem. 1989 93 201. 40 J. F. Bunnett and C. A. Migdal J. Org. Chem. 1989 54 3037 3041. 41 P. J. Smith and M. Amin Can. J. Chem. 1989 67 1457. 42 C. F. Bernasconi Tetrahedron 1989 45 4017. 43 C. F. Bernasconi R. B. Killion J. Fassberg and Z. Rappoport J. Am. Chem. SOC.,1989 111 6862. 44 A. F. Popov 1. F. Perepichka and L.I. Kostenko J. Chem. Soc. Perkin Trans. 2 1989 395; I. F. Perepichka L. 1. Kostenko A. F. Popov and A. Yu. Chervinski Zh. Org. Khim. 1988 24 822. D. L. H. Williams (equation 10) for the reaction of a nitroethylene with amines in acetonitrile which includes a component representing a pathway catalysed by the reactant amine and also by added tertiary amines. There is a negative measured activation energy for this step which suggests the rapid equilibrium formation of an intermediate (with a negative AH") as outlined in equation 11. kobs= k + kb[Amine] (10) R'CH=CHNO + R,NH R'CH-CHNO I R,NH Uncatalysed The reaction of enolate ions with perfluoropropene in the gas phase shows a C vs. 0 regio~electivity.~~ Most enolates derived from aldehydes ketones esters and amides react at oxygen whilst those with a-acceptors of .rr-donor type central substituents react mainly via carbon.The excess acidity method has been used to analyse the kinetic results for the acid-catalysed hydration of alkenyl esters of the type CH,=C(OX)R for X = Bz and Ts!~ The results indicate the familiar A42 mechanism with rate-limiting proton transfer to the double bond. Toullec4' has examined the relation between the equilibrium and rate constants for H+ transfer to a-methoxystyrenes (equation 12). Slightly curved plots of log k us. pK are found; analysis using the Marcus relation gives results consistent with synchronous and concerted CH bond formation and OH bond cleavage. The correlation of alkene .rr-ionization potentials with relative rate constants for hydroboration bromination and oxymercuration show that hydroboration and oxymercuration behave in a similar fashion in which steric effects are dominant whereas this is not the case for br~mination.~~ Nitrosation of acetylacetone (8) and the two fluorinated derivatives (9) and (10) using either alkyl nitrites in acetonitrile or nitrous acid in water takes place via the enol form only for (8) simultaneously uia the enol and enolate anion for (9) and wholly via the enolate anion for (10).All of the results are consistent with the deactivating effect of the CF3 groups on electrophilic addition and the acid- strengthening property of the CF3 groups for enol i0nization.4~ 45 M. D. Brickhouse and R.R. Squires J. Phys. Org. Chem. 1989 389. 46 R. A. Cox M. McAllister K. A. Roberts P. J. Stang and T. T. Tidwell J. Org. Chern. 1989 54 4899. 47 J. Toullec J. Chern. SOC.,Perkin Trans. 2 1989 167. 48 D. J. Nelson P. J. Cooper and R. Soundararajan J. Am. Chern. SOC.,1989 111 1414. 49 M. J. Crookes P. Roy and D. L. H. Williams J. Chern. SOC.,Perkin Truns. 2 1989 1015. Reaction Mechanisms -Part (ii) Polar Reactions CH,C=CHCOCH CF,C=CHCOCH C F3C =C HCOC F3 I I I OH OH OH (8) (9) (10) 6 Aromatic Substitution and Rearrangements Effenberger" has reported the synthesis for the first time of 1,3,5-tris (dialkylamino) benzene derivatives (1 l) which are models for intermediates in electrophilic aro- matic substitution. The stabilization by three amino substituents is analogous to the stabilization of the corresponding anionic a-complexes by three nitro groups.The salts have been isolated and their structure established by X-ray crystallography. It is expected that the study of such ions will lead to a better understanding of energy profiles in electrophilic aromatic substitution. A nitrating agent has been produced by mixing Bu,NN03 and (CF3C0)20 and used to measure selectivity in a range of aromatic compounds in a number of organic solvents.51 This results in the following selectivity order MeN02 < MeCN d sulpholane < CH2ClCH2Cl < CHzC12 d EtOAc d Pr'Br = BuCl = BuBr d CHC13. Both products of electrophilic chlorination and nitration are obtained in competing processes when reaction of aromatics takes place with nitric acid and chlorine or hydrogen chloride in sulphuric acid or 01eum.~* Chlorination is the less selective process but it is not yet known what the effective chlorinating agent is.Further evidence has been given53 which shows that the mechanism of aromatic nitration in aqueous nitric acid is identical to that in aqueous sulphuric acid. The rate equation for the nitrous acid-catalysed nitration of naphthalene contains a term which is second order in the aromatic.54 All the evidence points to an electron transfer mechanism; the second-order term is thought to arise .from the formation and subsequent reaction with NO2 of the dimeric radical cation . The bromination of phenols in water in the pH range 0-7 involves reaction of both the phenol and the phenoxide ion.55 For 16 phenoxide ions values of the second-order rate constants are all in the range (1-9) x lo9dm3 mol-' s-l showing that the reactions are diffusion controlled.Kinetic and chemical trapping experiments with the highly selective chlorination of electron-rich aromatic compounds with N-chloroamines in CF3C02H fit with 50 F. Effenberger Acc. Chem. Res. 1989 22 27. 5' B. Masci Tetrahedron 1989 45 2719. 52 M. W. Melhuish and R. B. Moodie J. Chem. Soc. Perkin Trans. 2 1989 667. 53 D. J. Belson and A. N. Strachan J. Chem. SOC.,Perkin Trans. 2 1989 15. 54 J. R. Leis M. E. Peiia and J. H. Ridd Can. J. Chem. 1989 67,1677. 55 0. S. Tee M. Paventi and J. M. Bennett J. Am. Chem. Soc. 1989 111 2233.D. L. H. Williams the arenium ion mechanism for the majority of substrates but the reaction of 1,4-dimethoxybenzene may have an electron transfer chain reaction component to its reaction.56 The first example has been reported of a rate-limiting proton transfer in elec- trophilic substitution in pyrroles as witnessed by the observation of an amplified isotope effect in the chlorination of l-methylpyrr~le.~~ Substitution by aryldiazonium ions in imidazole takes place via the anion form present in very low concentration (see equation 13).58The product or product mixture was not fully described. The behaviour of imidazole contrasts with that of pyrrole which reacts via the nbutral form. These experiments bear out a suggestion made by Ridd and co-workers in 1953.59 N2Ar Nudelman6' has presented a review of the dimer mechanism for aromatic nucleophilic substitution by amines in aprotic solvents.The unusual experimental findings (compared with the same reactions in protic solvents) are explained in terms of simultaneous initial attack by the free amine and by its dimer. In water and aqueous DMSO (12) and (13) respectively give a-adducts with hydroxide ion at unsubstituted positions whilst attack at the C atom bearing X (X = halogen) leads to the formation of 2,4,6-trinitro- or 2,4-dinitrophenolate ions by nucleophilic substitution.61 No evidence was found for the previously reported r-complex or radical pair intermediates discussed in last year's Report. Shine in an article62 dedicated to Professor M.J. S. Dewar on the occasion of his 70th birthday has reviewed the current position regarding the mechanisms of the benzidine rearrangement. In particular he discusses the part played by Dewar most notably in the 1950s when he advanced his then revolutionary ?r-complex theory. The review stresses the value of these early ideas especially in stimulating research in this area and comments on their present-day relevance. 56 J. R. Lindsay Smith L. C. McKeer and J. M. Taylor J. Chem. SOC.,Perkin Trans. 2 1989 1529. 57 M. De Rosa and M. Marquez J. Chem. SOC.,Chem. Commun. 1989 1466. 58 L. M. Anderson A. R. Butler C. Glidewell D. Hart and N. Isaacs J. Chem. SOC.,Perkin Trans. 2 1989 2055. 59 R. D. Brown H. C. Duffin J. C. Maynard and J.H. Ridd 1. Chem. SOC.,1953 3937. 6o N. S. Nudelman J. Phys. Org. Chem. 1989 1. 61 M. R. Crampton A. B. Davis C. Greenhalgh and J. A. Stevens J. Chem. SOC.,Perkin Trans. 2,1989,675. 62 H. J. Shine J. Phys. Org. Chem. 1989 491. Reaction Mechanisms -Part (ii) Polar Reactions 7 Proton Transfer and Carbanions The gas-phase acidities of 47 aliphatic carboxylic acids have been measured by pulsed electron high-pressure mass spectrometry calibrated with a reference com- pound.63 There is a good correspondence with earlier work for some of the acids measured by the ion cyclotron resonance technique. The results are discussed in terms of substituent effects. Similarlya the gas-phase acidities of 15 simple alkanes have been obtained in a flowing afterglow-selected ion flow tube using a kinetic method in which alkyltrimethylsilanes react with OH-.Generally methyl substitu- tion is found to stabilize the anion form. Han and Bra~man~~ have studied the gas-phase proton transfer from toluenes to benzyl anions (equation 14) and have established the energetics of the systems. PhCH,-+ ArCH + PhCH +ArCH,-(14) Literature data for the ionization in solution of a number of carbon acids with various bases have been analysed by the use of variable intrinsic barriers in the Marcus equation.66 This allows the prediction of Q and p Bransted values over a wide range of reactivity. Proton transfer from amides has not been much studied but a recent discusses the results of pK measurements and of kinetic studies (by the T-jump method) of the proton transfer reactions from l-benzoylaminonaph- thalenes (14) and related compounds to hydroxide ion in 70% DMSO-H20.The HNCOCtjHs rate constants are -lo2 smaller than expected possibly due to the formation of an intramolecular H-bond in the amide anion. The same group6* has examined the effect of substituents on the strength of the internal H-bond in salicylate ions. The H-bond is strengthened by electron-releasing substituents and by the change from H20 to 50% DMSO-H20 solvent. At high [OH-] the opening of the H-bond is partially rate-limiting. Hydrogen bromide in CBr2F2 is a powerful acid solvent for the protonation of weak bases.69 In a study with P-diketones NMR evidence shows that the proton is located between the two keto groups in a very strong intramolecular H-bond.Phenylynol (PhCECOH) has been generated and observed in solution for the first time as the first intermediate formed in the flash photolysis of phenylhydroxy- 63 G. Caldwell R. Renneboog and P. Kebarle Can. 1. Chem. 1989 67 611. 64 C. H. De Puy S. Gronert S. E. Barlow V. M. Bierbaum and R. Damrauer J. Am. Chem. SOC.,1989 111 1968. 65 C.-C. Han and J. I. Brauman J. Am. Chem. SOC.,1989 111 6491. 66 J. W. Bunting and D. Stefanidis 1. Am. Chem. Soc. 1989 111 5834. 67 N. E. Briffett and F. Hibbert J. Chem. SOC.,Perkin Trans. 2 1989 1261. F. Hibbert and K. J. Spiers J. Chem. SOC.,Perkin Trans. 2 1989 67. 69 D. R.Clark J. Emsley and F. Hibbert J. Chem. SOC., Perkin Trans.2 1989 1299. D. L. H. Williams cyclopr~penone.~~ It is more acidic than the corresponding enol PhCH=CHOH by at least 7 pK units. This is predicted to be true also in the gas phase,71 and is attributed both to the stabilization of the ynolate anion and the destabilization of the neutral ynol relative to the enol situation. The rate constants for detritiation of some common anaesthetics (CF3CHClBr CH30CF2CHC12 and CHF,OCF,CHFCl) in dilute hydroxide ion solution have been obtained. The Bransted plot suggests normal acid behaviour which prompts the thought that the H-bonding acceptor ability is an important factor governing the power of the anae~thetic.~~ The reaction of malononitrile with nitrous acid in aqueous acid buffers takes place uia the carbanion in a rate-limiting reatction with the nitrosating agent XNO (equation 15).73 For X=Br- SCN- and SC(NH2)* the reaction occurs at the encounter limit making the carbanion from malononitrile the most reactive species studied in a nitrosation reaction.I CH,(CN) CH(CN) HON=C(CN)2 (15) 8 Carbonyl Derivatives The Kresge group has determined for the first time the temperature dependence of the rate constants for the acid-catalysed enolization of acetone and the ketoniz- ation of the enol in aqueous solution and also in a~etonitrile.~~ This enables the AH* and AS* values along with the overall AH" and AS"values to be obtained. There is a remarkable similarity to the corresponding values of the parameters obtained in the gas phase for the keto eenol system.Acta Chemica Scandinauica is published from 1989 onwards as a single journal rather than in the familiar series A and B sections. In the first issue an article describes kinetic studies on the keto-enol system of 2-carboxycyclohexanone in aqueous solution using the bromi- nation method.75 Because of a fortuitous overlap of spectra and the values of the rate constants it turns out to be possible to follow the zero-order (in bromine) enolization at the start of each experiment and the restoration of the perturbed keto-enol equilibrium towards the end of the experiment. Thus rate and equilibrium constants can be obtained from a single experiment. There is a continuing interest (though not at the level of recent years) in the generation of unstable enol tautoders.Capon and Wu76 have observed and character- ized 2,5-dihydroxythiophene as an intermediate in the hydrolysis of 2,5-bis [(trimethylsilyl)oxy]thiophene (in a deuterated solvent) which finally yields thiosuc- cinic anhydride (see equation 16). The same has carried out a more extensive 70 Y. Chiang A. J. Kresge R. Hochstrasser and J. Wirz J. Am. Chem. SOC.,1989 111 2355. 71 B. J. Smith L. Radom and A. J. Kresge J. Am. Chem. SOC.,1989 111 8297. 72 A. L. Brown Y. Chiang A. J. Kresge Y.3. Tang and W.-H. Wang J. Am. Chem. SOC.,1989 111,4918. 73 E. Iglesias and D. L. H. Williams J. Chem. SOC.,Perkin Trans. 2 1989 343. 74 Y. Chiang A.-J. Kresge and N. P. Schepp J. Am. Gem. SOC.,1989 111 3977. 7s H. Groth-Andersen and P.E. Seirensen Acta Chem. Scand. 1989 43 32. 76 B. Capon and Z.-P. Wu J. Org. Chem. 1989 54 1211. 77 B. Capon and F. C. Kwok J. Am. Chem. SOC.,1989 111 5346. Reaction Mechanisms -Part (ii) Polar Reactions study of monohydroxy derivatives of five-membered 0 N and S (benzo) heterocycles such as 3-hydroxybenzofuran (15). Again the enols were generated by hydrolysis of their trimethylsilyl derivatives in DC1 and the kinetics of ketonization and the KE values determined. Ketonization is found to be both general acid and general base catalysed and mechanisms for both are discussed. The first report of a direct observation in solution of hydroxyacetylenes has a~peared.~' These are ynols the triple bond analogues of enols and are the tautomers of ketenes (see equation 17).The flash photolysis of phenylhydroxycyclopropenone yields pheny- lacetic acid uia two intermediates the first identified as phenylhydroxyacetylene and the second as phenylketene. Rate constants were obtained for the acid-catalysed ynol -* ketene reaction. RCrCOH RCH=C=O (17) Acid-catalysed proton exchange in amides has been studied by NMR techniques including the application of quantitative 2D exchange NMR.78 Two mechanisms have been established one involving the intermediate formationpf the imidic acid RC(OH)=NR' the other the N-protonated intermediate RCONH2R'. Generally amides with electron-donating substituents exchange via N-protonation whereas those with electron-withdrawing substituents (including peptides and proteins) involve the imidic acid.Experimental evidence has been presented for co-operative catalysis (or synergistic catalysis) well known in esters and amides containing the C02H group in amide hydrolysis by neighbouring C02- at moderately high pH.79 The case has been argued for a concerted pathway in acyl group transfer reactions in solution," as well as the stepwise (dissociative and associative) routes. It is believed that the concerted pathway is more common than previously supposed. The full paper has been published" on AM1 calculations for reactions of a number of anions with eight carboxylic acid derivatives. The formation of tetrahedral intermediates are computed to occur without activation in an exothermic reaction. In solution therefore the energy barriers must arise from the energy of desolvation of the anion before the reactant can approach.9 Other Reactions The diazotization (and protonation) of 2-aminothiazole (16) at high acidity takes place by NO+ (or H+) attack at the ring nitrogen.82 In this case the overall reaction 78 C. L. Perrin Acc. Chem. Res. 1989 22 268. 79 M. N. Khan J. Chem. Soc. Perkin Trans. 2 1989 233. 80 A. Williams Acc. Chem. Res. 1989 22 387. 81 M. J. S. Dewar and D. M. Storch J. Chem. SOC. Perkin Trans. 2 1989 871. 82 H. Diener B. Gulec P. Skrabal and H. Zollinger Helu. Chim. Acta 1989 72 800. 70 D. L. H. Williams is reversible and these results present the first quantitative evidence for reversibility in diazotization reactions. It is known that diazotization of 1,2-diamino aromatic systems lead to triazole formation.Kinetic experiments have shown that 2,3- diaminonaphthalene reacts via the unprotonated and also the monoprotonated forms of the diamine (equation 18).83Nucleophilic catalysis is well established in t-rnN% .+It \ / " I H diazotization (and nitrosation generally). The most recently discovered catalyst is thiosulphate ion,84 from which the NOS203-species is thought to be the effective reagent. Its reactivity towards anilines has now been e~tablished;~~ the results confirm that NOS203-is significantly less reactive than the other well-known NOX species. In dilute acid solution P-aminopyridines (17) react directly with acidified nitrous acid at the exocyclic nitrogen atom whereas y-aminopyridines (18) react initially at the aromatic nucleus (cJ anilines at high acidity) probably owing to substantial positive charge on the exocyclic nitrogen atom in the latter case.86 NHR I;HR H (17) A range of alkyl nitrites8' react readily with cysteine and other thiols in water at pH 6-12 to give the corresponding thionitrites (or nitrosothiols) by a direct reaction with the thiolate anion.Another example has been published88 of initial attack at 83 S. M.N. Y. F. Oh and D. L. H. Williams J. Chem. Res. (S) 1989 264. 84 T. Bryant D. L. H. Williams M. H. A. Mi and G. Stedman J. Chem. SOC.,Perkin Trans. 2 1986 193. 85 L. Abia A. Castro E. Iglesias J. R. Leis and M. E. Peha J. Chem. Res. (S) 1989 106. 86 E. Kalatzis and L.Kiriazis J. Chem. SOC. Perkin Trans. 2 1989 179. 87 H. M. S. Pate1 and D. L. H. Williams J. Chem. Soc. Perkin Trans. 2 1989 339. 88 A. Coello F. Meijide and J. V. Tato J. Chem. SOC.,Perkin Trans. 2 1989 1677. Reaction Mechanisms -Part (ii) Polar Reactions 71 sulphur in nitrosation followed by an intramolecular rearrangement of the nitroso group to nitrogen in this case in the reaction of thiomorpholine. It is suggested that rearrangement occurs in a boat conformation of an intermediate. Two papers have been published describing reactions of N-methyl-N-nitrosotoluene-p- sulphonamide with nucleophiles in basic solution. The fird9 shows that a direct reaction occurs with cysteine and other thiols in their thiolate anion forms resulting in thionitrite formation.The second” discusses the reaction with a number of nitrogen-containing nucleophilic species; ammonia hydroxylamine hydrazine and amines. Again reactions occur at the nitroso nitrogen atom resulting in a transnitrosation reaction. This contrasts with the reaction of hydroxide ion which attacks the sulphur atom and gives products of hydrolysis. The reactions of the related N-nitroamides in aqueous buffer solution (equation 19) have also been RCON(Me)N02 + H20 + RC02H + MeNHN02 (19) studied.” The kinetic results and the observation of an absence of I80-exchange during the reaction are all consistent with a mechanism involving rate-limiting nucleophilic attack at the carbonyl carbon atom to give a tetrahedral intermediate which then breaks up rapidly.This is different from the common hydrolysis mechan- ism for amides and must arise because of the enhanced leaving group ability of -N(Me)NO; . Cyclization of N-substituted hydantoic acids (equation 20) has been examined as part of model studies of biotin action.92 It is an example of attack by ureido anion nitrogen on the carboxylate anion which is general acid/ base catalysed. 0 Me N NR Sulphonyl transfer reactions (equation 21) have been reviewed.93 The evidence is very much in favour of mechanisms which are concerted bimolecular displacements at the sulphonyl group. RS02X + Y-(or HY) + RS02Y + X-(or HX) (21) 10 Some Probes of Polar Mechanisms Activation volumes and reaction volumes are increasingly used as mechanistic probes.We now have a review of the complete listings of A V’ and A V values for reactions in solution covering the span January 1977 to the end of 1986.94 (This updates an earlier review by two of the authors which was published in 1978.) The a9 S. M. N. Y. F. Oh and D. L. H. Williams J. Chem. SOC.,Perkin Trans. 2 1989 755. 90 A. Castro J. R. Leis and M. E. Pefia J. Chem. SOC.,Perkin Trans. 2 1989 1861. 91 B. C. Challis E. Rosa F. Norberto and J. Iley J. Chem. SOC.,Perkin Trans. 2 1989 1823. 92 I. B. Blagoeva 1. G. Pojarlieff D. T. Tashev and A. J. Kirby J. Chem. SOC.,Perkin Trans. 2 1989 347. 93 I. M. Gordon M. Maskill and M.-F. Ruasse Chem. SOC.Rev. 1989 18 123. 94 R. Van Eldick T. Asano and W. J. LeNoble Chem. Rev. 1989 89 549. D.L. H. Williams extensive list is presented in tabular form for both inorganic and organic reactions. Over 1000 organic reactions are listed. The isokinetic relationship (IKR) has been reviewed.95 The subject is examined historically and the authors emphasize the problem that generally E and 1nA values are derived from the same set of data and are therefore not statistically independent and suggest how this may be overcome. The connection between IKR and linear free energy relationships is brought out. It is clear that more experimental results are needed on the IKR itself and on the measurement and interpretation of far-IR spectra since an isokinetic temperature can only be found within discrete regions corresponding to the absorbance bands of the vibrational spectra of the solvent.Buncel and co-~orkers~~ have developed a new approach for obtaining Brdnsted correlations. Instead of varying the pK of the nucleophile by changing the sub- stituents the effect is achieved by changing the solvent composition of DMSO-water mixtures. This procedure it is claimed allows a greater range of pK values and more data points to be obtained. Pross and S~haik~~ have questioned the value of Brflnsted coefficients as quantitative measures of transition state structure. They conclude that they cannot provide a quantitative measure since inter alia (a) some factors govern the energetics of the transition state but do not operate on equilibrium processes (e.g. solvent effects and energies of excited configurations which are important in rate processes but absent in equilibrium processes) and (b) giving a single Brflnsted coefficient to a single transition state is unsatisfactory since it is derived from a reaction series with varying transition state structures.Pearson9* has reviewed the application of the concepts of absolute electronega- tivity and absolute hardness to well-known chemical reactions. Good agreement is claimed with the experimentally known behaviour of common reactions in terms of electrophilic and nucleophilic reagents; the treatment also allows predictive power. A new scale of solvent polarity (+&,) has been obtained from measured solvato- chromic changes of six new merocyanine dyes in 29 solvents.99 The T& values are similar to the T*values of Kamlet et a1.l'' Finally the application of the Savage- Wood additivity of group interactions procedure to reaction mechanisms has been used to yield quantitative data which allow mechanistic interpretation based on medium effects for organic reactions in water-rich solvents."' 95 W.Linert and R. F. Jameson Chem. SOC.Rev. 1989 18 47. 96 E. Buncel I. H. Um and S. Hoz,J. Am. Chem. SOC.,1989 111 971. 97 A. Pross and S. S. Schaik Now. J. Chim. 1989 13 427. 98 R. G. Pearson J. Org. Chem. 1989 54 1423. 99 E. Buncel and S. Rajagopal J. Org. Chem. 1989 54,798. loo M. J. Kamlet J.-L. M. Abboud and R. W. Taft J. Am. Chem. SOC.,1977 99 6027. S. A. Galema M. J. Blandamer and J. B. F. N. Engberts J. Org. Chem. 1989 54 1227.

ISSN:0069-3030    

DOI:10.1039/OC9898600057

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Free Radicals By J. A. MURPHY and M. S. SHERBURN Department of Chemistry University of Nottingham University Park Nottingham NG7 2RD The year has seen advances in many aspects of the chemistry of free radicals. The development of alternative reagents as sources of carbon radicals and of modified ways of performing radical reactions has continued apace. Curran has published full details of atom-transfer reactions of hexynyl iodides' and of iodoesters2 (includ- ing iodomalonates). The utility of the atom-transfer approach is seen in the reactions of the iodoester (I) (Scheme 1). Treatment of this molecule with tributyltin hydride and a radical initiator led to the acyclic product (4) but no lactone (3); however reaction with hexabutylditin under photochemical activation gave the iodolactone (2) which was isolated and could then be reduced with tributyltin hydride to the desired target (3).0 0 Reagents i Bu,SnH AIBN; ii Bu3SnSnBul hu Scheme 1 The use of tris(trimethylsily1)silane has been further investigated (see 1988 Report) as an alternative to tributyltin hydride by Gie~e.~ The greater strength of the Si-H bond in this molecule (79 kcal mol-' versus 74 kcal mol-' for Sn-H in tributyltin hydride) makes it a poorer H-atom donor. A range of reactions of carbon radicals including cyclizations rearrangements and addition to activated alkenes have now been shown to proceed well using this silane. Tris( trimethylsily1)silane is a 'special' silane. Roberts4 has examined the possibility of using the less esoteric triethylsilane as a reducing agent for alkyl halides (Scheme ' D.P. Curran M.-H. Chen and D. Kim J. Am. Chem. SOC.,1989 111 6265. * D. P. Curran and C. T. Chang J. Org. Chem. 1989 54 3140. B. Giese B. Kopping and C. Chatgilialoglu Tetrahedron Lett. 1989 30,681. R. P. Allen B. P. Roberts and C. R. Willis J. Chem. Soc. Chem. Commun. 1989 1387. 73 J. A. Murphy and M. S. Sherburn 2). Reactions (1) and (2) are necessary propagation steps in this process. The reaction (2) is normally very sluggish and this renders silanes incapable of sustaining the radical chain reaction. However Roberts has suggested that the sluggishness of the reaction is due to polar factors in the free radicals concerned i.e.that a nucleophilic carbon radical would be slow to abstract an electron-rich hydrogen from a Si-H bond. His analysis has led him to suggest a thiol/silane couple as a means of overcoming this replacing reaction (2) by reactions (3) and (4) and indeed he has demonstrated that the presence of thiol works well in catalysing alkyl halide reduc- tions by radical chain mechanisms. Et,Si' + RHal Et,SiHal + R' (1) R' + Et,SiH aRH + Et,Si' (2) R' + XSH 5RH + XS' (3) XS' + Et,SiH -@+ XSH + Et,Si' (4) Scheme 2 Reactions of radicals which are followed by rapid trapping by an oxidant or metallo-radical have drawn much attention. Minisci' has developed an atom-transfer route for substitution of protonated heterocycles (Scheme 3). The interaction of hydroxyl radicals (generated by reaction of hydrogen peroxide with ferrous salts) with dimethyl sulphoxide is known to produce methanesulphinic acid and methyl radicals.6 The methyl radicals interact exothermically with other alkyl iodides to produce iodomethane and an alkyl radical and as most alkyl radicals are much more nucleophilic than methyl radicals this leads to a rapid addition to a pyridinium salt.The resulting radical cation undergoes proton loss followed by facile oxidation resulting ultimately in an overall substitution of the heterocycle. The selectivity against methyl group substitution is shown by the fact that even when primary alkyl iodides are used it is predominantly the primary alkyl group which is found on the product pyridine; less than 2% of methylated product is detected.0 '0 OH II \/ HO' + MeSMe -MeSMe -MeS0,H + Me' Me' + R-I -Me1 + R' H H H H Scheme 3 F. Minisci E. Vismara and F. Fontana J. Org. Chem. 1989 54 5224. D. Veltwisch E. Janata and K. D. Asmus J. Chem. SOC. Perkin Trans. 2 1980 146. Reaction Mechanisms- Part ( iii) Free-radical Reactions The use of manganese(II1) acetate in the presence of cupric salts has been further investigated. Bertrand' reports on the cyclizations of malonate diesters. The remark- able point about these reactions (Scheme 4) is that the kinetic cyclization products can be trapped with ease by added cupric ion; where the possibility exists for 5-ex0 versus 6-endo cyclization to occur the five-membered ring products are observed.Thus in the example shown the initial cyclized radical (9) is rapidly oxidized to cation (10) and then cyclopropane formation occurs. Snider' reports a detailed evaluation of the structural features required for successful intermolecular addition of radicals derived from malonates and P-ketoesters to alkenes using manganese( 111) acetate. In effect an electron-rich alkene is required; the reaction is also very sensitive to steric effects at the site of cyclization. 0 __. I. 00 0U O M e i I. Scheme 4 Giese9 has used [CpFe(CO),] to generate organic radicals. That this reagent functions as a source of radicals was inferred from the products formed in its reactions (Scheme 5). However the formation of alkenes (11) as well as saturated products (12) is reminiscent of the chemistry of organocobalt reagents where ' H.Ournar-Mahamat C. Moustrou J.-M. Surzcr and M. P. Bertrand J. Org. Chem. 1989 54 5684; Tetrahedron Lett. 1989 30 331. B. B. Snider and B. 0. Buckman Tetrahedron 1989 45 6969. G. Thorna and B. Giese Tetrahedron Lett. 1989 30 2907. J. A. Murphy and M. S. Sherburn $[CpFe(CO),] -[CpFe(CO),]' +R' + CpFe(C0)2X I iii RCH=CYZ + RCH,CHYZ 2RCH,kYZ (11) (12) Reagents i hv;ii RX;iii H,C=CYZ; iv CpFe(C0); Scheme 5 trapping of intermediate radicals by cobalt( 11) species followed by dehydrocobalta- tion leads to unsaturated products. Product analysis has also recently been used to deduce the nature of intermediates in the photolysis or thermolysis of aryl- and alkylcobalt(~r~) The conclusions drawn are that these processes produce free radicals which function essentially independently of the metal.Organocobalt chemistry has developed well since the initial experiments featuring models of the biological chemistry of coenzyme B12.This year has seen (a) further modelling of these biological reactions and (b) the development of synthetic methods some of which are inspired by the B, rearrangement reactions. Pattenden" has developed a synthesis of p- y- and &lactams from acylcobalt salophens. The synthesis of the p-lactams (Scheme 6) is particularly interesting in view of the pharmaceutical importance of these compounds. Trapping of the cyclized radical by Co" is obviously important in efficiently forming these strained products.OR' n = 1,2,3 Scheme 6 Dowd13 Widdo~son,'~ and Golding15 have all made contributions to the B12 modelling experiments. The methylaspartate-glutamate rearrangement (Scheme 7) has been examined by Dowd who has proposed a mechanism for this (Scheme 8) in which methylaspartate forms an imine (13) which then tautomerizes to (14). This is then converted into the radical (15) by coenzyme B1 and rearranges. In the model lo A. J. Clark and K. Jones Tetruhedron Lett. 1989 30,5485. B. Giese J. Hartung J. He 0. Hutter and A. Koch Angew. Chem. Int. Ed. Engl. 1989 28 325. G. B. Gill G. Pattenden and S. Reynolds Tetrahedron Lett. 1989 30,3229. l3 S.-C. Choi and P. Dowd J. Am. Chem. SOC.,1989 111 2313. l4 W.M.Best and D. A. Widdowson Tetrahedron 1989 45 5943. *' S. Ashwell A. G. Davies B. T. Golding R.Hay-Motherwell and S. Mwesigye-Kibende J. Chem. Soc. Chem. Commun. 1989 1483. Reaction Mechanisms- Part (iii) Free-radical Reactions H02CJNH2 H02CqNH2 ~ CO2H CO2H Scheme 7 "02TH2 HO2C /N-R -.JC02H CO2H (17) I COzEt (18) \ iii / (19) Reagents i B,,-dependent enzyme; ii vitamin Biz, room temperature EtOH 5 min; iii Bu3SnH AIBN A Scheme 8 experiments the halide (18) acts as a precursor for a radical analogous to (15); this gives the rearranged product (19) on treatment with either tributyltin hydride or vitamin B,2s. The methylmalonyl coenzyme A mutase reaction continues to inspire discussion of its mechanism. A full report of the modelling experiments conducted by Widdow- son has appeared.14 Although model thioesters do not rearrange well p-ketoesters do undergo a radical-induced rearrangement efficiently.The scope of this rearrange- ment as a synthetic method has now been extended by the synthesis of ring-expanded heterocycles by Dowd16 (Scheme 9). Modelling of biological processes has also been the motivation behind Whiting's recent investigation of reactivity of aryloxymethyl radicals;" it is proposed that the carbon atom of methoxy groups may be used biosynthetically to form carbon-carbon bonds by a radical mechanism and a series of experiments has been carried out 16 P. Dowd and S.-C. Choi Tetrahedron Lett. 1989 30 6129; Tetrahedron 1989 45 77. 17 A.J. Walkington and D. A. Whiting Tetrahedron Lett. 1989 30 4731; S. A. Ahmad-Junan A. J. Walkington and D. A. Whiting J. Chem. SOC.,Chem. Commun. 1989 g13. J. A. Murphy and M.S. Sherburn Bu,SnH AIBN Etozcao L I Ph \ Ph Scheme 9 OMe OMe I S Q OMe OMe Scheme 10 using radical chemistry to mimic this (Scheme 10). One precursor of such a radical was (21). The isolation of the unsaturated compound (23) as the main product is interesting and presumably indicates the intermediacy of the pyridine (22). Keeping with radicals of biological interest leads us to one of the most interesting developments this year namely the study of the related DNA-cleaving agents calicheamicin esperamicins and neocarzinostatin. These molecules are thought to undergo an initial activation by addition of thiol (or possibly thiyl radical2* i,n the case of neocarzinostatin) followed by spontaneous cyclization to form biradicals which in vim abstract two H-atoms from deoxyribose units on complementary Reaction Mechanisms- Part ( iii) Free-radical Reactions strands of duplex DNA.This leads to double-strand cleavage. The reaction is shown here for neocarzinostatin (Scheme 11). The complex structures of the molecules has meant that an enthusiastic search has started for reagents which perform the same function but have simpler structures. Among the contributors this year have been Magnust’ Danishefsky,” Saito,20 Hirama,” Ellestad,22 Snyder,23 Myers,24 and Nic~laou.~~ Simpler model compounds have been shown to mimic the cyclization chemistry.Scheme 12 shows the models (24)24 and (27).18 ArC0,-0-sugar 0-5ugar 1 ArC02-ArC02--W /-OH 0-sugar H 0-sugar Scheme 11 Reports on stereochemical control of free-radical chemistry are prominent. Rajan- babu has continued his studies on the stereochemistry of bicyclization reactions which allow the effects of conformation and substitution pattern to be assessed. Firstly,26 he has identified that for non-flipping cyclohexanes cyclization can occur onto either an axial or an equatorial substituent bearing an appropriate functional in P. Magnus and R. T. Lewis Tetrahedron Lett. 1989 30 1905. 19 N. B. Mantlo and S. J. Danishefsky J. Org. Chem. 1989 54 2781; J. N. Haseltine S. J. Danishefsky and G.Schulte J. Am. Chem. Soc. 1989 111 7638. 20 I. Saito H. Kawabata T. Fujiwara H. Sugiyama and T. Matsuura J. Am. Chem. SOC.,1989 111 8302; R. Nagata H. Yamanaka E. Okazaki and I. Saito Tetrahedron Lett. 1989 30,4995. 21 M. Hirama K. Fujiwara K. Shigematu and Y. Fukuzawa J. Am. Chem. Soc. 1989 111 4120. 22 N. Zein W. J. McGahren G. 0. Morton J. Ashcroft and G. A. Ellestad J. Am. Chem. Soc. 1989 111 6888. 23 J. P. Snyder J. Am. Chem. Soc. 1989 111 7630. 24 A. G. Myers and P. S. Dragovich J. Am. Chem. Soc. 1989 111 9130; A. G. Myers and P. J. Proteau ibid. p. 1146. 25 K. C. Nicolaou G. Skokotas P. Maligres G. Zuccarello E. J. Schweizer K. Toshima and S. Wendeborn Angew. Chem. Int. Ed. Engl. 1989 28 1272. 26 T. V. Rajanbabu and T.Fukunaga J. Am. Chem. Soc. 1989 111 296. J. A. Murphy and M. S. Sherburn 0 \OR H \?R 0\c 0 Reagent i cyclohexa-1,4-diene Scheme 12 1,5 cis trans 22 60 1,5 cis :trans g0 :13 Scheme 13 group (Scheme 13). A full investigation of the stereochemistry of products of cyclization of a series of sugar acetals (Scheme 14) has been published.27 This should prove very useful in predicting the stereoselectivity of related cyclizations of sugar-derived molecules. Although most of the emerging radical chemistry of sugars involves direct attack by tributyltin radicals on a halide or chalcogen Fraser-Reid has used nitrate esters as sources of oxy-radicals which cause intramolecular hydro- gen transfer reactions and so functionalize otherwise unreactive sites on glycals with control of stereochemistry.** On the other hand the ease with which hydrogen Ph’ -LV OBn -Ph’ c;;q OBn OBn OBn Bn = benzyl exclusively trans Scheme 14 21 T.V. Rajanbabu T. Fukunaga and G. S. Reddy J. Am. Chem. SOC.,1989 111 1759. 28 J. C. Lopez R. Alonso and B. Fraser-Reid J. Am. Chem. Soc. 1989 111 6471. Reaction Mechanisms- Part (iii) Free-radical Reactions OBn Bu,SnH b AIBN L Bn = benzyl I OBn BnO -BnO Scheme 15 transfer occurs in sugar radicals has posed problems in De Mesmaeker’s studies on formation of fused-ring (Scheme 15). The stereochemistry of free-radical processes features in a different way in the work of Here attempts at inducing stereochemistry in intramolecular and intermolecular reactions have met with partial success (Scheme 16).Radical additions to activated alkenes of this sort resulted in moderate stereochemical induction. 0 0 14 :1 stereoisomeric ratio Scheme 16 In the fragmentation reactions reported by Bald~in~~ in which medium and large rings are generated the stereochemistry of the final alkene is markedly affected by the orientation of substituents in the starting material (Scheme 17). This is indicative of a concerted radical fragmentation a useful and very rare event in radical chemistry. 29 A. De Mesmaeker P. Hoffmann B. Ernst P. Hug and T. Winkler Tetrahedron Lett. 1989 30 6307. 30 A. De Mesmaeker P. Hoffmann and 9. Ernst Tetrahedron Lett. 1989 30,57. 31 N.A. Porter 9. Lacher V. H.-T. Chang and D. R. Magnin J. Am. Chem. Soc. 1989 111 8309. 32 N. A. Porter D. M. Scott 9. Lacher 9. Giese H. G. Zeitz and H. J. Lindner J. Am. Chem. Soc. 1989 111 8311. 33 J. E. Baldwin R. M. Adlington and J. Robertson Tetrahedron Lett. 1989 30 909 82 J. A. Murphy and M. S. Sherburn 0 eseph 0.1 equiv. Bu,SnH AIBN SnBu 89% 85% Scheme 17 The formation of macrocycles by direct cyclizations has been extended to the synthesis of a natural product -the cembranoid mukulol- by Pattenden34 (Scheme 18). mukulol Scheme 18 Two interesting reactions of macrocycles bearing radicals have appeared. Thus Suarez3’ has studied the transannular functionalization of medium-sized lactams with diacetoxyiodobenzene and has efficiently generated bicyclic products in some cases e.g.the amide (30) produces the isomeric products (31) and (32) in a total yield of 96% (Scheme 19). The cyclization of the radical (33) has been shown36 to Scheme 19 give large amounts of the bridged bicycle (34),which is of interest because of its occurrence in taxane diterpenes (Scheme 20). Unfortunately considerable amounts of non-cyclized reduced product (35) were also seen. The Z-isomer of (33) gave a much higher ratio of (34):(35)than did the E-isomer. 34 N. J. G. Cox G. Pattenden and S. D. Mills Tetrahedron Lett. 1989 30,621. 35 R. L. Dorta C. G. Francisco and E. Suarez J. Chem. Soc. Chem. Commun. 1989 1168. 36 J. D. Winkler V. Sridar and M. G. Siegel Tetrahedron Lett.1989 30.4943. 83 Reaction Mechanisms- Part (iii) Free-radical Reactions Scheme 20 The radical chemistry of small rings continues to feature prominently in the development of synthetic method^.^'-,^ Feldman38 has extended his earlier work to give a synthesis of (*)-yashabushitriol (Scheme 21). The crucial part of this sequence of reactions was the trapping of a peroxyl radical (36) to give specifically the syn stereochemistry in the dioxolane product. Peroxyl radicals have also featured in Bloodworth's studies of cyclization reactions of hydroperoxides?' His experiments have led him to propose that in cyclizations mediated by N-iodosuccinimide a radical chain mechanism prevails (Scheme 22); this contrasts with the case for N-bromosuccinimide which proceeds by a polar mechanism.- O-o* SPh i Ph Ph (34)I 0-0 Ph Ph -Ph Ph yashabushitriol Reagents i O, Ph,S, AIBN hv Scheme 21 0. OH Scheme 22 A review of the chemistry of thiocarbonyl compounds has been written by Cri~h.~~ Several advances have been made involving radical chemistry of sulphur and selenium compounds. Crich has ~ynthesized~~ a model of the A ring of la,25-dihydroxy vitamin D ,developing his earlier work on acyl radical cyclizations from 37 D. L. J. Clive and S. Daigneault J. Chem. Soc. Chem. Commun.,1989 332. K. S. Feldman R. E. Ruckle jun. and A. L. Romanelli Tetrahedron Lett. 1989,30 5845; K. S. Feldman and R. E. Simpson ibid. p. 6985; K. S. Feldman and T. E. Fisher ibid. p. 2969. 39 A.Johns J. A. Murphy and M. S. Sherburn Tetrahedron 1989,45 1625. 40 A. J. Bloodworth and R. J. Curtis J. Chem. Soc. Chem. Commun. 1989 173; A. J. Bloodworth R. J. Curtis and N. Misty ibid. p. 954. 41 D. Crich and L. Quintero Chem. Rev. 1989 89 1413. 42 D. Batty D. Crich and S. Fortt 1.Chem. SOC.,Chem. Commun.,1989 1366. J. A. Murphy and M. S. Sherburn i+ I Scheme 23 acylselenides. Yamamoto has investigated radical cyclizations of homoallylic xan- thate~~~ (Scheme 23) and cyclizations of various derivatives of thionocarbonic acids have been explored44 as routes to thionolactones. During this last study examples of ips0 substitution on aromatic rings were encountered (Scheme 24) e.g.the reaction of (37) gives the expected product (39) in low yield and the anomalous compound (38) as the major product.The proposed route to (38) is shown. This type of substitution has also been seen in Clive’s study of the formation of cis-fused cyclopentanoids by Michael addition and radical cycli~ation~~ (Scheme 25). In this case aromatic sulphones suffered attack and substitution. A novel and very useful means of removing aromatic sulphones in p-ketosulphones using tributyltin hydride has been discovered by Smith;46 these sulphones are frequently difficult to remove by alternative reactions. (37) OKoph -ph% (38) 47% (39) 9% S Ph +pkf (37) Scheme 24 The determination of rate conslants has continued with the publication of values for many important radical processes this year.These figures are extremely helpful in determining the feasibility of synthetic proposals featuring potentially competing reactions. Two examples of cyclopropylalkyl radical ring openings (Scheme 26) serve to show the effect of structure on the rate of reactions in the same series. Thus 43 M. Yamamoto T. Uruma S. Iwasa S. Kohmoto and K. Yamada J. Chem. SOC.,Chem. Commun. 1989 1265. 44 M. D. Bachi and E. Bosch J. Org. Chem. 1989 54 1234. 45 D. L. J. Clive and T. L. Boivin J. Org. Chem. 1989 54 1997. 46 A. B. Smith 111 K. J. Hale and J. P. McCauley jun. Terruhedron Leu. 1989 30 5579. Reaction Mechanisms- Part ( iii) Free-radical Reactions Scheme 25 (41) Scheme 26 the bicyclic compound (40)47 undergoes ring opening with a rate constant of 2.4 x lo9s-l at 37 "C.This has been used to probe the remarkable speed of 'OH rebound' in cytochrome P-450 and hence to help explain how hydroxylation with P-450 can proceed through free radical intermediates and yet feature retention of stereochemistry at the reacting carbon.48 The very much more stabilized radical (41) on the other hand undergoes ring opening with a rate constant of 3.6 x lo5s-' at 22 0c.49 47 V. W. Bowry J. Lusztyk and K. U. Ingold J. Am. Chem. SOC.,1989 111 1927. 48 P. R. Ortiz de Montellano and R. A. Steams J. Am. Chem. SOC.,1987 109 3415. 49 J. Masnovi E. G. Samsel and R. M. Bullock J. Chem. SOC.,Chem. Commun. 1989 1044.

ISSN:0069-3030    

DOI:10.1039/OC9898600073

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (i) Hydrocarbons By L. HILL and S. E. THOMAS Department of Chemistry University of Warwick Coventry CV4 7AL 1 Alkanes Functionalization of alkanes continues to attract the attention of many research groups. It has been demonstrated for example that asymmetric hydroxylation of ethylbenzene by iodosylbenzene occurs in the presence of catalytic amounts of a homochiral binaphthyl iron porphyrin to give a 40% yield of 1-phenylethanol of 41% e.e.' New methods for inserting an oxygen atom into carbon-hy,drogen bonds include the use of a novel dioxirane species methyl(trifluoromethyl)dioxirane,* catalytic oxidation with RuO generated in situ from RuC13 and Na10,,3 and the use of the oxidizing solution formed when fluorine is passed through wet a~etonitrile.~ All these methods work efficiently and exhibit good regioselectivity for tertiary carbon-hydrogen bonds.It has been reported that in the presence of SbF5 excess dichloromethane or dibromomethane will chlorinate or brominate respectively saturated hydrocarbon^,^ and caesium fluoroxysulphate has been used to fluorinate saturated hydrocarbons.6 2 Alkenes Synthesis.-The Wittig reaction and related processes have once again been the subject of numerous reports. A review covering developments in the area since 1978 has been published.' a$-Unsaturated esters and ketones have been synthesized in good yield and with high E-stereoselectivity by a reaction which is heralded as the first example of a catalytic Wittig-type reaction.8 The products were generated by adding various aldehydes to methyl bromoacetate or a-bromoacetophenone at room temperature in the presence of triphenyl phosphite potassium carbonate and catalytic amounts of tri-n-butylarsine (Scheme 1).The tri-n-butylarsine is thought to be regenerated by reduction of the tri-n-butylarsine oxide by the triphenyl phosphite. Stoichiometric amounts of tri-n-butylarsine and zinc powder have also ' J. T. Groves and P. Viski 1. Am. Chem. Soc. 1989 111 8537. R. Mello M. Fiorentino C. Fusco and R. Curci J. Am. Chem. SOC.,1989 111 6749. A. Tenaglia E. Terranova and B. Waegell Tetrahedron Lett. 1989 30,5271. S. Rozen M. Brand and M. Kol. J. Am. Chem. SOC.,1989 111 8325. G. A. Olah A.-H. Wu and 0. Farooq J. Org. Chem. 1989 54 1463.S. Stavber and M. Zupan Tetrahedron 1989 45 2737. ' B. E. Maryanoff and A. B. Riitz Chem. Rev. 1989 89 863. * L. Shi W. Wang Y. Wang and Y.-Z. Huang J. Org. Chem. 1989 54 2027. 87 L. Hill and S. E. Thomas + P(OPh) A R + OP(OPh), R+O + BrnX -x R = alkyl aryl 61-87'/0 X = COzMe COPh Reagents i cat. BuiAs K,CO been shown to mediate the conversion of aldehydes and methyl bromoacetate into a,P-unsaturated esters.' Use of the base sodium hexamethyldisilazane to generate iodomethylenetriphenylphosphoranefrom the phosphonium iodide (1) facilitated the development of a high-yielding stereoselective procedure for the synthesis of (Z)-l-iodoalk-l-enes.'o~'' (Ph,PCH,I) I-The reductive dimerization of aldehydes and ketones by low-valent titanium species to give alkenes is the subject of two reviews published this ear.'^,'^ An optimized procedure for this reaction has also been reported in an attempt to reduce the confusion which has arisen as a result of the numerous reducing systems used for the tran~formation.'~ TiCI3 is converted into the crystalline complex TiC13(dimethoxyethane)l.5, which is then used as the titanium source in the coupling reaction.The results are reproducible even when aged batches of TiC13 are used and the complex is by far the most effective titanium source employed to date. For example coupling of diisopropyl ketone to produce tetraisopropylethene proceeds to give 12% yield using TiC13/LiA1H4 37% yield using TiC13/Zn-Cu and 87% yield with TiC13(dimethoxyethane)l,5/Zn-Cu.It has been discovered that 3-hydroxycarboxylic acids readily undergo an oxidative decarboxylation-deoxygenation process on heating with oxophilic vanadium com- plexes (Scheme 2).15 It is of note that the reactivity provides a direct link between 'aldol-type' products and alkenes. Conversion of acyclic ketone enamines into either a 2-or an E-alkene may be determined by choice of reagents for a hydroboration-elimination sequence.I6 For R OH R R R = alkyl aryl Reagents i CI,V=O or CI,V=NTol A Scheme 2 Y. Shen B. Yang and G. Yuan J. Chem. SOC.,Chem. Commun. 1989 144. 10 G. Stork and K. Zhao Tetrahedron Lett. 1989 30,2173. H. J. Bestmann H. C. Rippel and R. Dostalek Tetrahedron Lett. 1989 30 5261. 12 J. E. McMurry Chem.Rev. 1989 89 1513. D. Lenoir Synthesis 1989 883. 14 J. E. McMurry T. Lectka and J. G. Rico J. Org Chem. 1989 54 3748. l5 I. K. Meier and J. Schwartz J. Am. Chem. SOC.,1989 111 3069. I6 B. Singaram C. T. Goralski M. V. Rangaishenvi and H. C. Brown J. Am. Chem. SOC.,1989 111 384. Aliphatic Compounds- Part (i) Hydrocarbons example hydroboration of (E)-1-morpholino-1-phenylprop-1-ene by 9-BBN fol-lowed by methanolysis affords an 80% yield of (2)-1-phenylprop-1-ene whereas hydroboration by borane-methyl sulphide followed by methanolysis and oxidation with alkaline hydrogen peroxide gives a 50% yield of (E)-1-phenylprop-1-ene -(Scheme 3). . .. m 80% Ph ...... Ph>-\ I 111 II IV ~ 50% Ph Reagents i 9-BBN; ii MeOH; iii H3B SMe,; iv alkaline H202 Scheme 3 Reviews of synthetic and theoretical aspects of pyramidalized alkenes17 and bridgehead alkenes" have been published.Reactions.-Further uses of the reagent N-acetoxyaminoquinazolonein aziridination reactions have been reported. Vinylsilanes and vinylstannanes have been aziridi- nated19 and the vinylsilane derivatives converted into azirines (Scheme 4). In contrast to peracid epoxidation of cyclohex-3-en-1-01 which occurs with poor stereoselec- tivity aziridination of cyclohex-3-en- 1-01 occurs with high stereoselectivity to give the cis derivative (2) in 70% isolated yield.20 Q %Me3 I =( 2&SiMe3 -Ph Ph Ph = Q-NHOAc; ii CsF I NHOAc Scheme 4 Linked bis-tartrate esters (3) have been used as ligands in the Sharpless epoxidation reaction in order to gain information about the structure of the active catalytic species.21 The conclusions drawn from results obtained with these ligands are in agreement with conclusions from kinetic studies and support the hypothesis that the substrate is epoxidized by a C2-symmetric dimer and not by a monomeric species W.T. Borden Chem. Rev. 1989 89 1095. 18 P. M. Warner Chem. Rev. 1989 89 1067. 19 R. S. Atkinson and B. J. Kelly J. Chem. Soc. Chem. Commun. 1989 836. 20 R. S. Atkinson B. J. Kelly and C. McNicolas J. Chem. Soc. Chem. Commun. 1989 562. P. R. Carlier and K. B. Sharpless J. Org. Chem. 1989 54 4016. L. Hill and S. E. Thomas present even in a small equilibrium amount. Transition-metal-catalysed epoxidations have been reviewed.22 Asymmetric dihydroxylation of alkenes has been intensely studied this year.Further examination of the osmium-catalysed process in which Cinchona alkaloid derivatives are used as chiral ligands revealed that two diol-generating catalytic cycles are involved (Scheme 5).23 The first cycle turns over faster and produces diol ‘A HO OH Scheme5 in high enantiomeric excess whereas the second cycle turns over more slowly and exhibits low/opposite enantiofacial selectivity. Thus slow addition of the alkene to the reaction mixture minimizes production of diol by the second cycle and increases the enantiomeric excess of the product. Under ‘slow addition’ conditions the scope of this asymmetric dihydroxylation process is much increased and includes simple hydrocarbon alkenes aromatic alkenes allylic alcohols a$-unsaturated esters etc.22 K. A. Jorgensen Chem. Rev. 1989 89 431. 23 J. S. M. Wai I. Marko J. S. Svendsen M. G. Finn E. N. Jacobsen and K. B. Sharpless J. Am. Chem. SOC.,1989 111 1123. Aliphatic Compounds- Part ( i) Hydrocarbons Chemical yields for these reactions are 80-95% and enantiomeric excesses are 50-89Y0.~~ The homochiral diamine (4)25 and the homochiral bipyrrolidine ( 5)26 both give high yields and enantiomeric excesses in stoichiornetric osmium tetroxide dihydroxylations (8 1-95% chemical yield 92-98% e.e. and 79-97% chemical yield 82-97% e.e. respectively). Optically active 1 -arylalkanols have been generated by asymmetric hydroboration of styrenes under cationic rhodium catalysis (Scheme 6).27The observed Markov- nikov selectivity is ascribed to q3-benzylrhodium intermediates formed by addition of a cationic rhodium hydride species to the styrenes.Investigations into the stereochemical outcome of hydroboration-oxidation of chiral allylic alcohol deriva- tives28 and allylic amine derivative^^^ using either 9-BBN or a catechol-borane/ rhodium catalyst system for the hydroboration step reinforce previous observations that the two methods may give complementary stereochemical results. An efficient procedure for the conversion of terminal alkenes into one-carbon homologated primary alkanenitriles has been developed (Scheme 7).30 **,/ + HB’*n ‘0 OH Yield 7698% e.e.76-96% Reagents i cat. [Rh(COD),ICBF, cat. (+)-BINAP; ii H202 NaOH Scheme 6 R = alkyl H 72-98% Reagents i (cyclohexyl)2 BH; ii CuCN; iii Cu(OAc),. H20 Cu(acac) Scheme 7 24 B. B. Lohray T. H. Kalantar B. M. Kim C. Y. Park T. Shibata J. S. M. Wai and K. B. Sharpless Tetrahedron Lett. 1989 30 2041. 25 E. J. Corey P. D. Jardine S. Virgil P.-W. Yuen and R. D. Connell J. Am. Chem. Soc. 1989 111 9243. 26 T. Oishi and M. Hirama J. Org. Chem. 1989 54 5834. 21 T. Hayashi Y. Matsumoto and Y. Ito J. Am. Chern. Sac. 1989 111 3426. 28 K. Burgess and M. J. Ohlmeyer Tetrahedron Lett. 1989 30,395. 29 K. Burgess and M. J. Ohlmeyer Tetrahedron Lett. 1989 30 5857. 30 Y. Masuda M. Hoshi and A. Arase J. Chem. SOC.,Chem. Commun. 1989 266. L.Hill and S. E. Thomas Interesting results have been obtained using an electroreductive intermolecular coupling of alkenes and ketones.31 For example coupling of ketone (6) with 4-methylpenta-l,3-diene using a carbon fibre cathode in DMF gave bisabolol (7) in 80% yield. The reaction of butan-2-one with hexa- 1,Sdiene could be controlled to give either the 1 :1 adduct (8) or the 2 1 adduct (9) by altering the amount of electricity used. HO Me HO Me (8) Synthetic routes to the R-and S-enantiomers of the sulphonimidamide (10) have been published. Both enantiomers were converted into reagents thought to be the corresponding chiral selenium diimide reagents (1 1) which were then used in allylic amination reactions of alkene~.~~ The diastereoisomeric excesses generated were modest [amination of methylenecyclohexane with (1 1) gave allylic amide (12) in 42% d.e.1 but significant.n (1 1) [derived from (R)-(lo)] 3 Polyenes Synthesis.-It has been demonstrated that the [2,3] Wittig rearrangement may be used for the synthesis of chiral allenes of high optical purity and predictable absolute c~nfiguration.~~ For example conversion of the propargylic alcohol (13) (prepared in 93% e.e. by reduction of the corresponding ketone with Darvon alcohol/LiAlH,) into the stannylmethyl ether (14) followed by treatment with Bu"Li at -78 "C gave allene (15) of 93% e.e. in 62% yield based on (13). The results provide evidence in support of a non-dissociative pathway for this type of rearrangement.31 T. Shono S. Kashimura Y. Mori T. Hayashi T. Soejima and Y. Yamaguchi J. Org. Chem. 1989 54 6001. 32 S. Tsushima T. Yamada T. Onami K. Oshima M. 0. Chaney N. D. Jones and J. K. Swartzendruber Bull. Chem. SOC.Jpn. 1989 62 1167. 33 J. A. Marshall E. D. Robinson and A. Zapata J. Org. Chem.. 1989 54 5854. Aliphatic Compounds- Part (i) Hydrocarbons 93 H <OH H / Bu-= Me \ Me Bu)c=c=c.Me A review of the chemistry of cyclic allenes (ten-membered to five-membered rings and bicyclic systems) and cyclic butatrienes (ten-membered to five-membered rings) has been published this year.34 Once again numerous syntheses of substituted buta-l,3-dienes have been reported. Substituted 2,5-dihydrothiophene S,S-dioxides which are stable precursors of the corresponding buta-l,3-dienes have been prepared uia reactions of 3-methylene-2,3-dihydrothiophene S,S-dioxide with electrophiles and nu~leophiles.~~ The method was applied to the synthesis of (*)-ipsenol (Scheme 8).New approaches to sulphur-substituted buta-1,3-dienes (16) (17),36(18),37 and ( 19)38 have been published. ji-/1-ry i ii-iv o//S\\ S“o (*)-ipsenol 50% 0 50% Reagents i Me2CHCH,CH,N02 1,1,3,3-tetramethylguanidine; ii H202/ K2CO3;iii NaBH,; iv A Scheme 8 SPh R = alkyl aryl vinyl R = alkyl aryl vinyl (16) (17) S02Tol + R R = H,SO,Ph R = alkyl CH=CHMe OAc C1 (18) (19) Intermolecular coupling of two alkynes to give buta- 1,3-dienes has been achieved.39 Hydrozirconation of one alkyne with Schwartz’s reagent [(qS-CSH5)2ZrHC1] yields a chlorovinylzirconocene which is converted into a methylvinylzirconocene using either methyllithium or methylmagnesium bromide.Loss of methane occurs at room 34 R. P. Johnson Chem. Rev. 1989,89,1111. 35 T.Nomoto and H. Takayama J. Chem. SOC.,Chem. Commun. 1989 295. 36 W.H. Pearson K.-C. Lin and Y.-F. Poon J. Org. Chem. 1989,54 5814. 37 A. Padwa B. Harrison S. S. Murphee and P. E. Yeske J. Org. Chem. 1989,54 4232. 38 T.G.Back E. K. Y. Lai and K. R. Muralidharan Tetrahedron Left. 1989,30 6481. 39 S.L. Buchwald and R. B. Nielsen J. Am. Chem. SOC., 1989.111 2870. L. Hill and S. E. Thomas R1 R' 11 ... &R2 .. 111 ___ CP& 'c1 Me CH4 R2 R3 U R' R' J/ \\R4 45-74% cp2zr$R2 2 R3 53-87% Reagents i Cp,ZrHCl; ii MeMgBr or MeLi; iii TMSCI; iv R3-E-R4; v H30+; vi I2 Scheme 9 temperature to give an alkyne complex which couples with a second alkyne to form a metallacyclopentadiene.The metallacycle is converted into a diene on treatment with aqueous acid or a 1,4-diiododiene on treatment with iodine (Scheme 9). In most cases the sequence can be carried out as a one-pot procedure and in many cases only a single regioisomer is observed. Insect pheromones containing an E,Z or Z,Econjugated diene have been synthe- sized by adding (2)-dialkenylcuprates to phenylthioacetylene and then cross-coup- ling the resulting alkadienyl sulphides with Grignard reagents in the ,presence of a nickel(11) cataly~t.~' the pheromone of For example (557E)-dodeca-5,7-dien-l-ol the forest tent caterpillar Malacosoma disstria was synthesized in 57% yield and 98% isomeric purity from phenylthioacetylene (Scheme 10).--SPh 2EEO-SPh 74% .. ... 11. 111 \ HO EE = ethoxyethyl Yield 77% -5Z,7 E 98% Reagents i EEO-),CuLi; ii -MgBr NiC12(dppe); iii p-TsOH Scheme 10 Symmetrically functionalized 1,3-dienes have been efficiently generated using a palladium(I1)-catalysed homocoupling of 1-alkenyl~tannanes.~~ 40 V. Fiandanese G. Marchese F. Naso L. Ronzini and D. Rotunno Tetrahedron Lett. 1989 30,243. 41 G. A. Tolstikov M. S. Miftakhov N. A. Danilova Y. L. Vel'der and L. V. Spirikhin Synthesis 1989,633. Aliphatic Compounds- Part ( i) Hydrocarbons Nickel( 0)-catalysed couplings of Grignard reagents with 5-alkyl-2,3-dihydrofurans have been elegantly exploited in a stereoselective iterative approach to isoprenoid chains.42 Each cycle involves alkylation of 5-lithio-2,3-dihydrofuranwith a homoally- -lic iodide nickel(o)-catalysed coupling with methylmagnesium bromide and conver- sion of the alcohol thus produced to the corresponding iodide (Scheme 11).The dihydropyran Wenkert reaction has been applied to the synthesis of (2)-undec-Cen-1-01 (20) an intermediate in syntheses of the insect pheromones heptacosa-7,ll- diene nonacosa-7,ll -diene and pentacosa-7,l 1-diene.43 y1i_ 97% .. . 11-IV 1 84% 98% .. . I 11-IV 81% 90% 11 I Reagents i ; ii MeMgBr Ni'; iii MeS02CI; iv NaI Li Scheme 11 Reactions.-Efficient addition of a propynylic moiety to the P position of an a,P-unsaturated carbonyl compound using metal derivatives is difficult as the reaction tends to give a mixture of 1,2- and 3,4-addition pxoducts and a mixture of propynylic and allenic products.It has been reported however that triphenylstan- nylallenes (21) may be regarded as effective propynylic anion equivalents as they 42 P. Kocienski S. Wadman and K. Cooper J. Org. Chem. 1989 54 1215. 43 T. L. Davis and D. A. Carlson Synthesis 1989 936. L. Hill and S. E. Thomas RC H =C =C H SnPh R R = H Me R = H Me (211 (22) add to cyclic and acyclic a$-unsaturated ketones in the presence of titanium tetrachloride to give P-prop-2-ynylic ketones (22) in good yield (59-8~4.~~ The silver( 1)-catalysed cyclization of a series of optically active allenic amines (23) has been examined.45 The product 2-substituted pyrrolidines (24) were formed in up to 80% diastereoisomeric excess (X = CONHMe and CH,NHMe) and the degree of asymmetric induction observed appeared to reflect the ability of the stereocentre to co-ordinate silver( I) ions.c\\c,\ NH PhAx Ph4 X = Me CO,Me CH,OH CONHMe CH,NHMe (23) (24) A double asymmetric hydrogenation of a conjugated diene has been Thus hydrogenation of buta- 1,3-diene-2,3-dicarboxylic acid (25) in the presence of catalytic quantities of Ru2Cl4{( R)-binap},NEt gave (S,S)-2,3-dimethylsuccinic acid (26) in 98% d.e. 96% e.e. and 77% yield. Reduction of anhydrous magnesium chloride with lithium in tetrahydrofuran using naphthalene as an electron carrier gives highly reactive magnesium.Addition of 1,3-dienes to this reagent produces substituted but-2-ene-l,4-diylmagnesiumcom-pounds e.g. (27) which react with electrophiles to give either 1,2- 1,4-,or 2,l-addition products depending on the substrate/electrophile employed.47 Two transition-metal-assisted reactions which lead to 1,4-functionalization of 1,3-dienes have been reported. Reduction of the bis[tricarbonylchromium(~)]com-44 J.-I. Haruta K. Nishi S. Matsuda Y. Tamura and Y. Kita J. Chern. SOC.,Chern. Cornrnun. 1989 1065. 45 D. N. A. Fox D. Lathbury M. F. Mahon K. C. Molloy andT. Gallagher J. Chern. Soc. Chern. Cornrnun. 1989 1073. 46 H.Murarnatsu H. Kawano Y. Ishii M. Saburi and Y. Uchida J. Chern. Soc, Chern. Cornrnun. 1989,769. 47 H. Xiong and R. D. Rieke J. Org. Chern. 1989 54 3247. 97 Aliphatic Compounds- Part ( i) Hydrocarbons plex (28) with lithium naphthalenide followed by reaction of the resulting dianion with alkyl halides and finally oxidative cleavage of the tricarbonylchromium( 0) groups gives rise to substituted 1,4-diphenylbut-2-enes (29) in 49-89'/0 yield.48 Stirring iodomethane with 1,3-dienes in the presence of Bu,NFe(CO),NO followed by addition of carbon nucleophiles leads to 1,4-acylation/alkylationand the produc- tion of alkenes (30) in 35-60% yield.49 &Nu 0 R = H,alkyl \/ Nu = CH(CO,Me), CH(COMe)CO,Me R = alkyl ally1 CMe( CO,Et) (29) (30) Examination of zirconium-mediated cyclizations of 1,6- and 1,7-dienes has revealed some very interesting results.Treatment of hepta-l,6-diene with ( q5-C5H5)2ZrC12 and butyllithium followed by bromination gave trans-1,2-bis(bromomethy1)cyclopentane. However treatment of the same diene with ( 7'-C5Me5)ZrC1 and sodium amalgam followed by bromination gave the isomeric cis-dibromide (Scheme 12).50 This contrast in stereochemical outcome was also observed with substituted hepta-l,6-dienes but application of the ( T~-C~H,),Z~C~,-,-: mediated reaction to octa-1 ,7-diene prod~cts.~~*~'- gave predominantly cis disubstituted Q:r 97%88% trans \ iii ii Q:r 78% 99% cis Reagents i (V~-C~H~)~Z~CI~, BuLi; ii Br,; iii ( ~15-CSMe,)ZrC1, Na/Hg Scheme 12 4n R.D. Rieke K. P. Daruwala and M. W. Forkner J. Org. Chem. 1989 54 21. 49 K. Itoh S. Nakanishi and Y. Otsuji Chem. Lett. 1989 615. 50 W. A. Nugent and D. F. Taber J. Am. Chem. SOC.,1989 111 6435. 51 C. J. Rousset D. R. Swanson F. Lamaty and E.-I. Negishi Tetrahedron Lett. 1989 30,5105. L. Hill and S. E. Thomas The reaction of tetraarylhexapentaenes (3 1) with catalytic quantities of Nio has been investigated and found to give the novel [4]radialene system (32) in 40-64% yield.52 Ar Ar Ar Ar Ar )=c=c=c=c< Ar Ar (31) Several successful palladium-catalysed cyclizations of trienyl triflates have been reported. For example heating trienyl triflates (33) in the presence of catalytic quantities of palladium gave the spirotricyclic dienones (34) in 72% (n = 1) and 70% (n = 2) yield re~pectively.~~ 4 Alkynes Synthesis.-Hydroxyalkynes or ynols are tautomers of ketenes and triple bond analogues of enols.The first direct observation of an ynol was made in 1986 when ethynol was generated in the gas phase and characterized by its mass spectrum. Ethynol (35) has been prepared again this year by irradiation of 3-hydroxy- cyclobuten- 1,2-dione (semisquaric acid) in an argon matrix and its infrared spectrum recorded.54 The synthetic approach to ethynol was then adapted to generate and observe ynols in solution for the first time.55 Phenylynol was generated by flash photolysis of phenylhydroxycyclopropenone (36) (or its methyl ether) and mesity- 52 M. Iyoda Y.Kuwatani and M. Oda J. Am. Chem. SOC.,1989 111 3761. 53 N. E. Carpenter D. J. Kucera and L. E. Overman J. Org. Chem. 1989 54 5846. 54 R. Hochstrasser and J. Win Angew. Chem. Int. Ed. Engl. 1989 28 181. 55 Y. Chiang A. J. Kresge R. Hochstrasser and J. Win J. Am. Chem. Soc. 1989 111 2355. Aliphatic Compounds- Part (i) Hydrocarbons lynol was obtained from mesitylhydroxycyclopropenone (or its methyl ether) in an analogous manner. Alkynyl phosphate esters (37) have been prepared by decomposi- tion of readily available alkynyl(pheny1)iodonium phosphates (38)? 0 II 0 II OR2 R',R2 = alkyl + R'-1Ph *\'O0' R2 0R2 Optically active 3-hydroxyalkynes have been synthesized from allyl alcohol precur- sors. Treatment of optically active CU,~ -epoxy alcohols obtained from allyl alcohols by the Sharpless epoxidation with triphenylphosphine and carbon tetrachloride gave a,P -epoxy chlorides which on exposure to butyllithium were transformed into 3-hydroxyalkynes without loss of stereochemical integrity (Scheme 13).57 - HO R'&\ LR1&\ R1-&= R2 OH R2 c1 R2 67-91% Yield 7694% e.e.71-96% Reagents i PPh, CCI,; ii BuLi Scheme 13 Ketones activated by P-carbonyl or phenyl groups have been efficiently dehydrated to alkynes using (Ph3P+),0 20Tf and trieth~lamine,~~ and a convenient method for preparing 1-iodoalk- 1 -ynes which involves treating terminal alkynes with bis(trimethylsily1) peroxide and zinc iodide in the presence of butyllithium has been reported.59 Cycloalkynes such as cycloheptyne cyclohexyne benzyne and cyclopentyne which are transient molecules in the free state are stabilized by co-ordination either to mononuclear electron-rich transition metal fragments or by formation of dinuclear or polynuclear metal complexes.The chemistry of these complexes has been reviewed.60 The enediyne (39) has been synthesized by coupling the dibromide (40) with trimethylsilylethyne and alkyne (41),61 and syntheses of enediynes (42) and (43) have been reported.62 A three-component synthesis of 1,5-dien-3-ynes has been designed.63 The process utilizes a palladium-catalysed coupling of an alkenyl iodide with the carbon-tin 56 P. J. Stang T. Kitamura M. Boehshar and H. Wingert J. Am. Chem. SOC.,1989 111 2225.57 S. Takano K. Samizu T. Sugihara and K. Ogasawara J. Chem. SOC.,Chem. Commun. 1989 1344. 58 J. B. Hendrickson and M. S. Hussoin Synthesis 1989 217. 59 A. Ricci M. Taddei P. Dembech A. Guerrini and G. Seconi Synthesis 1989 461. 60 M. A. Bennett and H. P. Schwemlein Angew. Chem. Int. Ed. EngL 1989 28 1296. 6' A. G. Myers M. M. Alauddin M. A. M. Fuhry P. S. Dragovich N. S. Finney and P. M. Harrington Tetrahedron Letr. 1989 30,6997. 62 R. Gleiter and R. Merger Tetrahedron Lett. 1989 30,7183. 63 Y. Hatanaka K. Matsui and T. Hiyama Terrahedron Left. 1989 30. 2403. L. Hill and S. E. Thomas TBDMSO ? \ TMS EtO,Cs YOMe )=\ OMe Br Br (39) n = 1,2 n = 1,2 (42) (431 bond of trimethylstannyl( trimethylsily1)ethyne followed by a second coupling reac- tion between the resulting intermediate and a second alkenyl iodide.The reaction proceeds with retention of the double bond geometry of the alkenyl iodides and has been used to synthesize several conjugated (E,E)-,(E,Z)-,and (2,Z)-1,5-dien-3-ynes including a naturally occurring polyenyne isolated from Grindelia humilis Hook (Scheme 14). -58% Reagents i Ac0-l cat. Pd(PPh,),; ii I (Et2N)$+ Me,SiF; (TASF) Scheme 14 Reactions.-A convenient chemoselective method for semihydrogenation of alkynes has been reported.64 A combination of acetic acid and the silicon hydride tetramethyl- dihydrodisiloxane in the presence of a palladium( 0)catalyst results in rapid reduction of alkynes to alkenes. Although the &-selectivity observed with some substrates is not universal it is of note that the chemoselectivity is such that the method may be used in the presence of conjugated alkenes and nitro groups.A ‘heterogenized homogeneous’ catalyst consisting of a palladium complex anchored in montmoril- lonite clay has also been reported to be useful for semihydrogenation of alkyne~.~~ Alkynes have been efficiently silylformylated using dimethylphenylsilane and carbon monoxide in the presence of catalytic quantities of €UI,(CO),~(Scheme 15).66 It was observed that the terminal carbon of alk-1-ynes is silylated specifically and that bulky substituents on the alkyne inhibit the silylformylation process. 64 B. M. Trost and R. Braslau Tetrahedron Lett. 1989 30 4657.65 G. V. M. Sharma B. M. Choudary M. R. Sarma and K. K. Rao J. Org. Chem. 1989 54 2997. 66 I. Matsuda A. Ogiso S. Sato and Y. Izumi J. Am. Chem. Soc. 1989 111 2332. Aliphatic Compounds- Part ( i) Hydrocarbons R’ R2 R1-E-RZ + Me,PhSiH >=( OHC’ ‘SiMe2Ph R’ = H alkyl SiMe, Ph 43-99% R2= H Me Ph CO,R Reagents i CO (30kg cm-’) cat. Rh,(CO),2 Et3N Scheme 15 Alkyl radicals and perfluoroalkyl radicals have been generated from alkyl iodides and perfluoroalkyl iodides respectively by reaction with triethylborane and then added to alkynes to give either alkenyl iodides or fluorinated alkenyl iodide^.^',^^ NbC13( dimethoxyethane) reacts with alkynes to give complexes which on hydroly- sis yield cis-alkenes. Thus the complexes may be regarded as 1,2-alkene dianion equivalents.This relationship has been exploited in a regioselective synthesis of 2,3-disubstituted-l-naphthols which involves coupling alkynes with 1,2-aryldial- dehydes in the presence of NbCl,(DME) (Scheme 16).69 R’ = alkyl aryi R2 = alkyl aryl SiR 53-87% Reagents i NbC13(DME); ii KOH Scheme 16 Several interesting transition-metal-promoted cyclizations of 1 n-diynes have been reported this year. 1,6- 1,7- and 1,8-Diynes with alkyl aryl or trimethylsilyl terminal substituents have been shown to undergo cyclization with 2,6-dimethylphenyl isocyanide in the presence of a stoichiometric amount of bis(cyc1o-octadiene)nickel(o) to form bicyclic iminocyclopentadienes (44).70 A nickel(0)-catalyzed synthesis of bicyclic pyrones (45) from 1,6- and 1,7-diynes and carbon dioxide which was previously only effective with dialkyl-substituted diynes has been extended to unsubstituted diynes by changing the phosphine incorporated into the catalyst.71 A successful nickel(o)-catalysed hydrosilylation of 1,7-diynes to give 1,2-dialkylidenecyclohexaneswith a (2)-vinylsilane moiety (46) has been reported,72 @N*r (yJ0 KSi(0EtL R’ R R’= Et Ph SiMe (44) (45) (46) 67 Y.Ichinose %-I. Matsunaga K. Fugami K. Oshima and K. Utimoto Tetrahedron Lett. 1989 30,3155. 68 Y. Takeyama Y. Ichinose K. Oshima and K. Utimoto Tetrahedron Lett. 1989 30 3159. 69 J. B. Hartung and S. F. Pedersen J. Am. Chem. Soc. 1989 111 5468. 70 K. Tamao K. Kobayashi and Y. Ito J. Org. Chem.1989 54 3517. 7‘ T. Tsuda S. Morikawa and T. Saegusa J. Chem. Soc. Chem. Commun. 1989 9. 72 K. Tamao K. Kobayashi and Y. Ito J. Am. Chem. Soc, 1989 111. 6478. L. Hill and S. E. Thomas and 1 ,n-diynes have been cyclized to macrocyclic enynes under palladium catalysis.73 For example diyne (47) was cyclized to the 26-membered lactone (48) in 70% yield. The S,S-acetal (49) has been cyclized to the tetracyclic product (50).74Removal of the chiral auxiliary gave material of 90% e.e. 0 *do** f-7-C02 E COZEt 0 (47) C <SiMe3 It 73 B. M. Trost S. Matsubara and J. J. Caringi J. Am. Chem. Soc. 1989,111 8745. 74 D. Guay W. S. Johnson and U. Schubert J. Org. Chem. 1989,54 4731.

ISSN:0069-3030    

DOI:10.1039/OC9898600087

出版商:RSC    

年代:1989

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5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry King's College London Strand London WC2 2/23 1 Alcohols and Ethers As an alternative to the traditional reagents the use of sodium percarbonate for oxidation of organoboranes to alcohols has been recommended.' The reagent is inexpensive easy to handle and gives yields comparable with those of the usual methods. Catalytic asymmetric hydroboration of styrenes by the catecholborane (1) in the presence of [Rh(cod),]BF and (+)-BNAP in THF is notable for reversal of regiochemistry and selectivity; thus 4-MeC6H4CH=CH2 in DME at -78 "C gave 77% of the 1-01 (94% e.e.) of R-configuration.2 Very low yields of the 2-01 were detected. An efficient chiral reagent for enantioselective synthesis of secondary and deuterated primary alcohols is (3) prepared from (2) with BH,; thus Bu'COMe QpH 0' &:;Nap NH H BI (1) (2) (3) gave an alcohol of -91% e.e.and PhCOMe afforded an alcohol of -98% e.e.3 Chiral organosilicon compounds afford an entry into the arylcarbinol series via an efficient and selective route shown in Scheme l.4 Oxygenation of simple alkenes [O,-PhSiH,-Co(acac),] constitutes a simple route to secondary alcohols; some ketone is also formed. In a similar way the system Co[ (CF3C0),CH2] with 0,-Et,SiH was regioselective for syntheses of secondary alcohols (a little ketone also being f~rmed).~ Mukaiyama has also reported that under slightly different conditions the alcohols are smoothly oxidized in good yield in the presence of these complexes.6 Allylic alcohols are obtained from chemoselec- tive hydrogen transfer from a simple alcohol to a,P-unsaturated ketones catalysed I G.W. Kabalka P. P. Wadgaonkar and T. M. Shoup Tetrahedron Lett. 1989 30 5103. ' T. Hayashi Y. Matsumotu and Y. Ito J. Am. Chem. SOC.,1989 111 3426. E. J. Corey and J. 0. Link Tetrahedron Lett. 1989 30 6275. T. H. Chan and A. Pellou J. Am. Chem. SOC.,1989 111 8737. S. Isayama and T. Mukaiyama Chem. Lett. 1989 1071. S. Isayama and T. Mukaiyama Chem. Letr. 1989 569; T. Mukaiyama and T. Yamada ibid. p. 519 103 104 B. V. Smith HO Ph Reagents i OMe ; ii Bu'Li-THF; iii RX; iv H,O,-KF-KHCO \ H Scheme 1 by MgO. In this way hex-5-en-2-one gave 90% of alcohols (with only 4% of the P,y-isomer).' The reaction of ally1 bromide with a carbonyl compound in the presence of zinc and chloramine using C,,-coated silica as a solid organic co-solvent was compared with the selectivity of the corresponding Grignard reaction.Yields were variable but the method did provide some useful compounds.8 Acetoxy- selenylation of alkenes was used as a route to vinylic and allylic acetates; 1,2-disub- stituted and terminal alkenes reacted smoothly. In this way C5H,,CH=CH2 gave C5Hl IC( OAc)=CH2 (7 1%).9 Chiral organosilicon compounds have been used in enantioselective syntheses of homoallylic alcohols; pyrrolidinylmethylallylsilanes (4;R = C02Me) gave with 2 equivalents of Lewis acid and an aldehyde good yields of product but with only modest e.e.(50'/0).'~ A regio-reversed addition of allylic stannanes to aldehydes in the presence of CoC12 at the a-position has been used to generate linear homoallylic alcohols." A chemoenzymatic approach to synthesis of the enantiomers of sulcatol ' J. Kaspar A. Trovarelli M. Lenarda and M. Graziani Tetrahedron Lett. 1989 30 2705. ' S. R. Wilson and M. E. Guazzaroni J. Org. Chem. 1989 54,3087. L. Engman J. Org. Chem. 1989 54,884. lo T. H. Chan and D. Wang Tetrahedron Lett. 1989 30 3041. J. lqbal and S. P. Joseph Tetrahedron Lett. 1989 30 2421. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds (5) an insect pheromone has been reported.I2 An efficient coupling/allylic substitu- tion by a terminal alkyne (6)with a halide has been achieved e.g.(7) gave (8) (88%).13 The diastereoselective synthesis of a-allenic alcohols from propargylic epoxides and Grignard reagents has been studied as a function of catalysis by Cu’; optimized conditions were defined for ‘anti’ and ‘syn’ routes (see Scheme 2).14 (E)-Bis(tributylstanny1)ethylene and dilithio methyl(thieny1)cyanocuprate were reacted Hex Hex syn ‘OH anri + *do H H Ill Hex H H Reagents i Pent-MgCI-Et20; ii Pent-MgBr 5% CuBr 2PBu,-Et20 Scheme 2 to form an ‘in situ’ cuprate which afforded a geometrically pure p-hydroxyvinylstan- nane (9).15 Hydrostannylation catalysed by Pd’ of alkynes occurred smoothly to Busn&; (9) give vinylstannanes in high yield. In this way the symmetrical alkyne AcOCH2C~CCH20Ac gave 93%yield; unsymmetrical alkynes gave the syn-adduct as the major product.16 Samarium-catalysed electrochemical coupling of simple carbonyls is a good route to 1,2 diols.” A convenient catalytic two-phase method for dihydroxylation of alkenes has been described; a quaternary salt of a tungsten heteropolyacid mediates the reaction in a C6H,-H20 system.Yields ranged between 71 and 88%.’* A most useful summary paper on the scope of asymmetric dihydroxylation has appeared; I* C. M. Alonso M. T. Barros L. Godhino and C. D. Maycock Tetruhedron Lett 1989 30 2707. l3 T. Jeffery Tetrahedron Lett. 1989 30 2225. 14 A. Alexakis 1. Marek P. Mangeny and J. F. Normant Tetrahedron Lett. 1989 30,2387. l5 J. R. Behling J. S. Ng K. A. Babiak A. L. Campbell E.Elsworth and B. H. Lipshutz Tetrahedron Lett. 1989 30 27. 16 H. Miyake and K. Yamamura Chem. Lett. 1989 981. E. Leonard E. Dunach and J. Perichon J. Chem. Soc. Chem. Commun. 1989 289. 18 C. Venturello and M. Gambaro Synthesis 1989 295. 106 B. V. Smith over 20 examples are given and emphasis is placed on the role of Cinchona alkaloids as chiral ligands.'' Two papers highlight the interest and scope of the Os0,-mediated dihydroxylation of alkenes. Corey and co-workers have developed a method notable for achieving three desirable objectives (i) high and predictable enantio- and diastereoselectivity (ii) clarification of mechanism and (iii) recovery and recycling of osmium.20 The chiral ligand (10) (from the diamine and 2,4,6-Me,C,H2CHO) followed by reduc- PhhPh MesCH,HN NHCH2Mes (10) tion forms a 1 1 complex with OsO which reacts cleanly at -90 "C to give the desired diol; e.g.PhCH=CHC02Me gave 83% of the (2R,3S)-diol (92% e.e.) and MeCH=CH(CH,),OTBDPS gave the (2S,3S)-diol (95% e.e.). The interpretation of this remarkable selectivity centres on the formation of a bidentate octahedral complex of (10) which favours a [3 + 21 cycloaddition at the si,si-face; the model proposed accommodates the lower selectivity observed with 2-alkenes and trisub- stituted types. Replacement of the mesityl group of (10) by benzyl gave lower optical yields presumably because of greater rotational flexibility. Significantly the antipode of (10) gave opposite selectivity. This method offers considerable scope for exploita- tion in diol synthesis.High levels of asymmetric induction have been realized with the chiral ligand (1 1) and OsO,; thus (E)-hept-2-ene with (S,S)-(1 1)-OsO afforded 93% diol (98% e.e.).,' I I R R (11) a-Chloroboronic esters ( 12) of high diastereomeric excess (98-99%) were con- verted into a-tributylstannylboronic esters (13) and then into (aR)-a-tributylstannyl alcohols (14); the derived (aR)-a-lithioethers (19 on coupling with (12) gave BuSn (12) (13) (14) (15) (16). Treatment with H202 followed by hydrolysis of the intermediate gave the known (17) (96% d.e.).22 This method introduces the novel concept of coupling a chiral carbocation equivalent and a chiral carbanion equivalent in a stereospecific ly B.S. Lohray 'T. H. Kalantar B. H. Kim C. Y. Park T. Shibata J. S. M. Wai and K. B. Sharpless Tetrahedron Lett. 1989 30,2041. 20 E. J. Corey P. D. Jardine S. Virgil P.-W. Yuen and R. D. Connell J. Am. Chem. Soc. 1989 111,9243. " T. Oishi and M. Hirama J. Org. Chem. 1989 54 5834. 22 D. S. Matteson P. B. Tripathy A. Sarkar and K. H. Sadhu J. Am. Chem. SOC. 1989 111 4399. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds way. The role of DIPED is crucial in directing reaction and the potential of the process is seen in assembling (18) which has four chiral centres. BUn40CH20Me (16) (17) (18) A stereoselective synthesis of optically active anti-1,3-polyols relies on the coup- ling of (19) and (20); the resultant (21) after treatment with MeI-CaCO and a diastereoselective reduction with LiAlH(OBu')3 gave (22).23 Starting with a y-(21) (22) menthyloxy-2[ 5HI-furanone a practicable route to optically active butanediols and y-lactones has been developed as shown in Scheme 3; the first asymmetric synthesis of (23) has thus been recorded.24 An enzymatic hydrolysis of a prochiral diacetate RZ R' (M eS1 X (M eS 13C H (R' = R2 = H) (R' = Me,R2 = H) iil Me Me Me (23) Reagents i LiC(SMe), THF -90 "C; ii Ni-Al MeOH-THF then LAH; iii MeI -90 to 45 "C Scheme 3 23 Y.Mori and M. Suzuki Tetrahedron Lett. 1989 30 4383. 24 J. F. G. A. Jansen and B. L. Feringa Tetrahedron Lett. 1989 30 5481. 108 B. V. Smith fOR2 O-O-Ph I 0~3 SiPh2Bu' (24) (25) did not lead to an 'asymmetrized tris' (24) which is a chiral building block but an alternative approach (Scheme 4) yielded the protected derivative (25) in 52%yield.25 OAc li I OAc I OSiBu'Ph2 Iv I - /O\/OVPhI I vi,vii H O q Ho+ OSiBu'Ph OSiBu' Ph2 Reagents i Porcine lipase; ii ClSi BU'Ph, imidazole DMF; iii KOH-MeOH; iv CICH20CH2Ph Pr2NEt; v 03,2Me2S 3 NaBH,; vi TsCI Et,N DMAP; vii NaBH, DMSO Scheme 4 The identity of this sample with one derived from (S)-(+)-methyl 3-hydroxy-2- methylpropanoate was proved.The diethylisopropylsilyl protecting group is capable of attachment at primary secondary and tertiary alcoholic OH groups and offers some scope for discrimina- tion in deprotection steps. In AcOH-H,O-THF primary DEIPS ethers are distin- guishable from TBDMS- TES- and THP-protected primary alcohols.At secondary sites DEIPS ethers are easily distinguished from THP ethers and fairly well from TBDMS and TEP protection.26 Selective deprotection of the Me,SiBu' group in the presence of Ph,SiBut has been achieved in high yield by using PPTS; selectivity as high as 96.5% was noted.27 A new oxidatively removable protection strategy uses the p-anisyloxymethyl group; an alcohol is easily derivatized by base-promoted reaction and deprotection is 25 G. Guanti L. Banfi and E. Narisano Tetrahedron Lett. 1989 30 2697. 26 K. Toshima S. Mukaiyama M. Kinoshita and K. Tatsuta Tetrahedron Lett. 1989 30 6413. 21 C. Prakash S. Saleh and I. A. Blair Tetrahedron Lett. 1989 30 19. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 109 smoothly achieved by CAN in aqueous MeCN.Protected alcohols are stable to base but labile in acid.*’ A very interesting account of kinetic resolution of rac-alcohols (or rac-acyl halides) by esterification in the presence of a chiral base has been published.29 1 mol of achiral RCOCl and 2 mols of rac-ROH in the presence of various t-amines gave esters and alcohols with optical purities up to 60-70%. It was found that the alcohol-derived portion of the ester and the unchanged alcohol were of opposite configuration. Analogously 2 equivalents of rac-acyl halide and 1 equivalent of rac- ROH gave a high degree of optical induction; opposite configurations were again noted for the ester and the acid.Selective oxidation of allylic benzylic and saturated secondary alcohols is brought about by BaMn04-A1203-CuS04 even in the presence of primary OH groups.30 In this system the diol PhCH=CH(OH)(CH,),OH gave 80% of PhCH=CHCO(CH2),0H. Metallic nitrates supported on silica gel are useful oxidants and effect oxidative cleavage of ethers.31 Good-to-excellent yields of enones were formed from the corresponding alcohols with NiS04-K2S208. In competition between PhCH=CHCH20H and 3-phenylpropan-1-01 97% of the latter was recovered and 91% of cinammaldehyde was isolated.32 In a similar way primary allylic alcohols were shown to react faster than secondary analogues. A facile one-pot conversion of ROH into RNH2 is shown in Scheme 5; for R = C5Hll 61% of the amine was isolated.33 Palladium-catalysed allylation of OH ..... RCH,OH -RCH,X -RCH,N=P(OEt) -RCH2NH2 Reagents i Ph3P CBrCI, C6H,; ii NaN, DMF; iii P(OEt),; iv HCI; V NaOH Scheme 5 groups with allyl ethyl carbonate is a useful method particularly in the carbohydrate series; the anomeric OH is selectively ethe~-ified.~~ A new synthesis of benzyl ethers (and N-benzylamines) employs the HBF4-catalysed reaction of PhCHN2 and the alcohol (or amir~e).~~ The synthesis of both enantiomers of benzyl glycidyl ether has been reported; allyl alcohol via Sharpless oxidation tosylation and benzylation gave the intermediate (26) easily transformed into the desired product. For (27) the measured optical purity is the highest ever recorded. The enantiomer was prepared in the same way (95%e.e.).36 A synthesis of (27) from 0-benzylserine uia a multistep route has been a~hieved.~’ The enantiomer was obtained from the same starting material using a Mitsunobu inversion at a key stage.A chemoenzymatic 28 Y. Masaki I. Inata 1. Mukai H. Oda and H. Nagashima Chem. Lett. 1989 659. 29 P. J. Weidert E. Geyer and L. Homer Liebigs Ann. Chem. 1989 533. 30 K. S. Kim S. Chung I. H. Cho and C. S. Hahn Tetrahedron Left. 1989 30 2559. 3’ T. Nishiguchi and F. Asano J. Org. Chem. 1989 54 1531. 32 S. Yamazaki and Y. Yamazaki Chem. Lett. 1989 1361. 33 A. Koziara J. Chem. Res.(S) 1989 296. 34 P. Lakhmiri P. Lhoste and D. Sinou Tetrahedron Lett. 1989 30 4669. 35 L. J. Liotta and B. Ganem Tetrahedron Lett. 1989 30 4759.36 H.4. Byun and R. Bittmann Tetrahedron Lett. 1989 30 2751. 37 P. De Witt D. Misiti and G. Zappa Tetrahedron Lett. 1989 30 5505. 110 B. V. Smith (26) (27) route to give epoxides in high optical purity has been described.38 Attempted acylation of a P-hydroxytosylate [lipase-MeCO,C( Me) =CH,] was extremely slow; better results were obtained with enantioselective cleavage of RCH( OCOPr)CH,OTs in the presence of butanol separation of products and ring closure to the desired compound. Enantioselective lipase-mediated hydrolysis of esters of epoxy secondary alcohols is seen as an alternative to standard Sharpless methodology and in some cases the enantiomeric excess is very high. In one specific example however the e.e. was disappointingly As another alternative to Sharpless methodology photo- oxygenation of alkenes in the presence of titanium alkoxides has been shown to be a general process; selectivity is high in some cases but shows dependence on the titanium species.40 MCPBA epoxidation of liquid alkenes takes place in deionized water at pH 8.3 in good yield.41 Enantiodivergent ring opening of styrene oxide with Me3SiN3-Ti(OPri)4 was solvent dependent; the major product (28) had S-configuration in hexane (72% e.e.) or in DME-0.1% H,O (74% e.e.) but in dry DME the R-isomer (83% e.e.) pred~minated.~,It was suggested that an intramolecular pathway uia an intermediate such as (29) could account for this unexpected reversal.Ph Ph h h N3 OSiMe3 Me3Si0 N3 (28) (29) Titanium-mediated opening of 2,3-epoxy-l-ols at the 3-position uses R2NH2+C1-as the source of halide ions.43 By this route (30) was converted into a mixture of (31) and (32) (X = C1 78% 78:22; X = Br 87% 90 10).(30) (31) (32) a-Methylene cyclic carbonates have been prepared by reaction of alk-2-yn-1-01s with C02 under pressure in the presence of a phosphine catalyst.& [2,3]-Wittig rearrangements of the lithio anions of ally1 propargyl ethers show considerable 38 C.-S. Chen and Y.-C. Liu Tetrahedron Lett. 1989 30 7165. 39 B. A. Marples and M. Rogers-Evans Tetrahedron Lett. 1989 30 261. 40 W. Adam M. Braun A. Griesbeck V. Lucchini E. Staab and B. Will J. Am. Chem. Soc. 1989,111,203. 41 F. Fringnelli R. Germani F. Pizzo and G. Savelli Tetrahedron Lett.1989 111 1427. 42 K. Sutowardoyo M. Emziane and D. Sinou Tetrahedron Lett. 1989 111 4673. 43 L. Gao and A. Murai Chem. Lett. 1989 357. 44 J. Fournier C. Bruneau and P. H. Dixneuf Tetrahedron Lett. 1989 30,3981. 111 Aliphatic Compounds- Part (ii) Other Aliphatic Compounds diastereoselectivity and afford a route to unsaturated alcohols with three contiguous chiral centres. By this route ether (33) gave (34); the cis-ether gave 87% of product as a single isomer. Rearrangement of (35) to (36) was completely ~tereospecific.~’ d SiMel d I ow+’ - +O OH In the presence of KOBu‘ primary alkyl groups migrate to the y-position in Wittig rearrangements thus forming (2) -silyl enol ethers which are easily hydrolysed to aldehydes.46 2 Alkyl Halides Boron tribromide or stannic chloride are effective reagents for conversion of alcohols into the respective alkyl halide.47 Direct transformation of THP ethers into alkyl bromides uses PPh,-CBr4-CH2C12 and is effective for saturated and unsaturated types; it is noteworthy that a tertiary ether (37) gave 62% of the corresponding bromide (with 1525% eliminati~n).~~ A catalytic method for producing RX (X =Br or I) from RCl employs HX-FeX,.The process had wide sc0pe.4~ Tetramethyl-a- halogenoenamines act as halogenating agents for alcohols under neutral conditions. Under mild conditions high yields (>95%) of RX (X =C1 Br I) were ob~erved.~’ Although secondary alcohols were reactive competition showed that primary groups reacted much more readily.From a mixture of butan-1-01 and octan-2-01 with Me2C=C(C1)NPri only BuCl was produced. Light-initiated halogenative decar- boxylation of thiohydroxamic acids gave high yields of RX (X =C1 Br I) from primary secondary and tertiary substituted carboxylic acids.51 Ph& OTHP (37) In a series of papers on vinylic boranes Brown has developed specific methods for (2)-A wide range of (2)-1-iodoalkenes is and (E)-l-halogenoalk-l-ene~.~~ 45 R. Bruckner Chem Ber. 1989 122 193. 46 M. Schiosser and S. Strunk Tetrahedron 1989 45 2649. 47 A. Amrollah-Madjdabadi T. N. Pham and E. G. Ashby Synrhesis 1989,614. 48 A. Wagner M.-P. Weitz and C. Mioskowski Tetrahedron Lett. 1989 30 557. 49 K. B. Yoon and J. K. Kochi J.Org. Chem. 1989 54 3028. 50 F. Munyemana A.-M. Frisque-Hesbain A. Devos and L. Ghosez Tetrahedron Left. 1989 30 3077. 51 W. G. Dauben B. A. Kowalczyk and D. P. Bridon Tetrahedron Lett. 1989 30,2461. 52 H. C. Brown et al. J. Org. Chem. 1989 54 6064 6068 6075 6079 6085. 112 B. V. Smith accessible via the Wittig reaction of iodomethylenetriphenylphosphoranesand an aldehyde. Some di-iodo compounds were produced as by-product^.^^ Addition of secondary and tertiary iodoalkanes to alkynes under the influence of triethylboron gave iodoalkenes with a variable stereoselectivity except for Me,SiC=CH (EtI 84% E:Z = 0:lOO) and Et0,CCECH (Bu‘I 81% E:Z = 92:s). An intramolecular example was achieved (94%) with (38).54 Allylic alcohols with R NBF-Et3N.3HF gave vic-fluorobromohydrins which with base formed epifluorohy- drin~.~~ Alkenes with PhSeBr- AgF in CH2C12 under ultrasonication formed adducts derived from fluoroselenylation and bis-~elenylation.~~ Griller’s ‘Green Reagent’ [(Me3Si)$iH] smoothly dehalogenates alkyl halides and is considered superior to the more traditional Bu,SnH especially in view of the toxicity of tin compo~nds.~’ By using NaBH to regenerate the reagent the silane can be used in catalytic amount; irradiation of the reaction mixture at 254 nm with added anisoyl peroxide causes rapid reaction under such conditions.A reinvesti- gation of the Pd-catalysed cross-coupling of an iodoalkane and a Grignard reagent has been published and the findings were held to be contrary to the original proposals.58 Ab initio calculations on the Finkelstein S,2 reaction in the gas phase showed that for R = Me Et and Pr’ there was a good agreement in the observed trends in E compared with the solution-phase reaction.59 3 Aldehydes and Ketones Carbonyl compounds seem to sustain a high level of activity in both synthesis and reactivity; consequently this section of the Report is once again the longest.One-electron oxidants cause an isomerization of epoxides to ketones.60 The reaction may proceed via a radical cation chain mechanism. The preparation of isomerically pure alkylboranes derived from 9-BBN has been used to advantage in syntheses of homologated ketones (and esters and nitriles) in very high e.e.61 Enantioselective hydrolysis of enol esters by a yeast (Pichia rniso) produced some remarkable results; in each case the enantiomeric excess was >8O%.The face selectivity was attributed to formation of a complex such as (39); (40) gave highest selectivity (goo/ e.e.).62 Similar work with Bacillus coagulans gave variable optical 53 H. J. Bestrnann H. C. Rippel and R. Dostalek Tetrahedron Lett. 1989 30 5261. 54 Y. Ichinose S. Matsunaga K. Fugami K. Oshima and K. Utimoto Tetrahedron Lett. 1989 30 3155. 55 I. Chehidi M. M. Chaabouni and A. Baklouti Tetrahedron Lett. 1989 30 3167. 56 S. Tomoda and Y. Usuki Chem. Lett. 1989 1235. 57 M. Lesage C. Chatgilialoglu and D. Griller Tetrahedron Lett. 1989 30,2733. 58 K. Yuan and W. J. Scott Tetrahedron Lett. 1989 30 4779; cf P.L. Castle and D.A. Widdowson ibid. 1986 27 6013. 59 K. Hirao and P. Kebarle Can. J. Chern. 1989 67 1261. 60 L. Lopez and L. Troisi Tetrahedron Lett. 1989 30 3097. 61 H. C. Brown N. N. Joshi C. Pyun and B. Singaram J. Am. Chem. Soc. 1989 111 1754. 62 K. Matsumoto and H. Ohta Chem. Lett. 1989 1589. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds (39) (40) yields in some instances; it is clear that this approach is capable of extension and gives promise of extension to a valuable series of compounds not always easily accessible by the more conventional methods.63 A route to a-alkoxy- a-allyloxy- and a-benzyloxy-aldehydes and -ketones has been reported; the key step is substitu- tion of the sulphinyl group in for example (41) by ROH in the presence of Me1 or PPTS.64 Enantioselective synthesis of P-hydroxyketones depends upon the forma- tion and desulphurization of 2-( 2-methyl- l ,3-dithiolan-2-yl)ethanolintermediates.In this way (42) was prepared in 83% yield (70% e.e.).65 R’ A new protocol for the synthesis of various a-fluorinated ketones (and alcohols) relies on acylation of lithium derivatives of enantiomerically pure sulphoxides and later desulphurization.66 Oxidation of 2,2-difluoroalkenylboranes by H,O,-NaOMe (to suppress protonolysis) is a practicable route to difluoromethylketones in good yield.67 Ethyl 4,4,4,-trifluoroacetate reacts with an allylic alcohol in the presence of distannoxane affording an allylic ester which suffers Pd-catalysed decarboxyallyla- tion to form a trifluoromethylketone.68In this way (43) was prepared in 79% yield.CF3LPh (43) Epoxysilylethers with the reagent (44) are transformed into P-siloxyaldehydes with a rigorous chirality transfer; e.g. (45) gave (46) only (87Y0).~~ Methyl s-alkyl ketones have been shown to undergo ‘double a-hydroxylation’ by peracid oxidation of their enol silyl ethers.” Monoacetals of malonaldehyde have been obtained uia a selective hydrolysis or transacetalization of 1,1,3,3-tetramethoxypropane as a general method.’l 63 K. Matsumoto and H. Ohta Chem. Lett. 1989 1109. 64 P. Pflieger C. Mioskowski J. P. Salaun D. Weissbart and F. Durst Tetrahedron Lett. 1989 30 2791. 65 I. Stahl F. Wrabletz and J. Gosselek Chem. Ber. 1989 122 371. 66 P. Bravo E.Piovosi and G. Resnati J. Chem. Res.(S) 1989 134. 67 J. Ichikawa T. Sonoda and H. Kobayashi Tetrahedron Lett. 1989 30 5437. 1. Shimizu H. Ishii and A. Tasaka Chem. Lett. 1989 1127. 69 K. Maruoka T. Ooi and H. Yamamoto J. Am. Chem. SOC.,1989 111 6431. 70 Y. Horiguchi E. Nakamura and I. Kuwajima Tetrahedron Lett. 1989 30,3323. 71 P. Shi-Qi and E. Winterfeldt Liebigs Ann. Chem. 1989 1045. 114 B. V. Smith (44) (45) (46) A divergent synthesis of 1,3-and 1,4-diketones from P-methoxy-y-phenylthioketones is a novel and valuable route to such compounds (from the same starting material).'* As shown in Scheme 6 the 1,3-dione can be considered to arise I Reagents i BuLi,; ii AcCl or MsCI; iii R2CH=C(OSiMe3)R3; iv MCPBA; v A NaHC03; vi H30f; vii BU'OK Analysis of reaction pathways RCH + -C+ + yR' I1 -1,3-diketone 0 0 RCHO MeOCHzSPh OSiMe -YR1 +FO ?CH2 -+ 1,Cdiketone R 0 Scheme 6 from coupling between a carbocation and a carbonyl 1,l-dipole and an enolate; the 1,4-compound is derived from a methylene dipole equivalent coupling with an enolate and an acyl cation.Unsymmetrical 1,4-diketones have been obtained from T. Sato M. Inoue S. Kobara J. Otera and H. Nozaki Tetrahedron Lett. 1989 30,91. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds 115 Ce'"-mediated cross-coupling of a mono- and a 1,2-disubstituted trimethylsilyl enol ether.73 A new synthesis of a$-unsaturated aldehydes proceeds from a carbonyl com- pound and the new reagent (47) [N-methoxy-N-methyldiethylphosphonoacetamide 0 II (EtO),PCH CO N(0Me)M e (47) prepared from C1CH2COC1 and MeNHOMe then P(OEt)3].74 Typically PhCHO gave 84% yield E :2 = 95 :5.2-Ynols were isomerized to (2E) -enals by a ruthenium complex [RuC~~(P~~P)~] in the presence of a trialkylph~sphine.~' Efficient silylformylation of an alkyne occurred with co-Rh4(co) 12-C6H6-Et3N under pressure; for example Pr'CECH gave (48) (93% 2:E = 90 Pr H OHC SiR (48) A facile stereospecific synthesis of (244 E )-dienals has been disclosed by addition of an organometallic reagent to a pyrylium salt followed by ring opening of the formed 2H-pyran. Selectivity was high (>95%) although there was some depen- dence upon reagent Propargylic alcohols are rearranged by an iridium pentahydride complex to furnish (~,P-enones.'~ Inthis way (49) gave a mixture of (50) and (51) [81 19 respectively; (51) can be arranged to (50)].The same catalytic system will isomerize an cY,P-ynone OH (49) (50) (51) to an a,P :y,S-dienone in high yield.79 In syntheses of divinT1 ketones in a one-pot sequence (52) [from R'CHO and Ph,P=CHC( =NPh)CH2PPh3 Br-] was reacted sequentially with BuLi R2CH0 and H30+ to yield (53) (88%) presumed to arise NHPh 13 E. Baciococchi A. Caw and R. Ruzziconi Tetrahedron Lett. 1989 30 3707. 14 J.-M. Nuzillard A. Boumendjel and G. Massiot Tetrahedron Left. 1989 30 3779. 75 D. Ma and X. Lu J. Chem. SOC.,Chem. Commun. 1989 890. 76 I. Matsuda I. Ogiso S. Sato and Y. Izumi J.Am. Chem. SOC.,1989 111 2332. 77 M. Furber J. M. Herbert and R. J. K. Taylor J. Chem. SOC.,Perkin Trans. I 1989 683. 18 D. Ma and X. Lu Tetrahedron Lett. 1989 30 2109. 19 D. Ma Y. Lu and X. Lu J. Org. Chem. 1989 54 1105. 116 B. V. Smith uia a 2-vinyl aza-l,3-diene intermediate.80 Regioselective 1,4-acylation/alkylation of 1,3-dienes via q3-1 -acetonylallylic Fe(CO),NO complexes has been developed as a practicable method." Bu3SnH-HMPA is an effective reducing agent for aldehydes in the presence of other reducible groups (including ketone and nitro); reductive alkylation was also observed in which R'CHO and R2CH0 formed R1CH20CH2R2.82 A useful summary of the relative reactivity of carbonyl compounds towards reduction by NaBH has been published.83 Reduction by NaBH in the solid state produces surprisingly high yields of alcohols from ketones; with an enone some reduction of the double bond was noted and there was some selectivity with cyclic ~ysterns.'~ Improved selectivity in the reduction of prochiral aliphatic ketones has followed from the introduction of new chiral b~ranes.~~ t-Butylchloroborane gave an adduct with nopol benzyl ether which effectively (but slowly) reduced 3-methylbutan-2-one; the lowering in the rate of reaction was attributed to 0 + B co-ordination in the adduct.It was noted that (54) showed greater reactivity. Chiral reducing agents from SnCl, optically active (54) piperazines and diisobutylaluminium hydride have been shown to reduce prochiral ketones; yields and enantiomeric excesses were variable however.86 The stereochemistry of reduction of ketones by optically active alkyl metals has been thoroughly re~iewed.~' A novel carbonyl-protecting group is the 1,5-dihydro-3 H-2,4-benzodioxepine cleaved by catalytic hydrogenolysis.Yields are generally good (70-98%). 7-bromoheptanone gave the 0-protected derivative (70%) which reacted with (55) to afford (56); this was then desulphurized by Raney nickel to give undecan-Cone (96?'0).~~The synthesis and consecutive double a1 kylation of (2-siloxyallyl)silanes no J. Barluenga I. Merino and F. Palacios Tetrahedron Lett. 1989 30 5493. 81 K. Itoh S. Nakanishi and Y. Otsuji Chem. Lett. 1989 615. 82 I. Shibata T. Yoshida A. Baba and H. Matsuda Chem. Lett.1989 619. 83 D. E. Ward and C. K. Rhee Can. J. Chem. 1989 67 1206. 84 F. Todo K. Kiyoshige and M. Yagi Angew. Chem.,Int. Ed. Engl. 1989 28 320. H. C. Brown and P. V. Ramachandran J. Org. Chem. 1989 54,4504. 86 M. Falorni L. Lardicci G. Giacomelli and M. Marchetti Tetrahedron Lett. 1989 30 3551. 87 M. Falorni L. Lardicci and G. Giacomelli J. Org. Chem. 1989 54 2383. 88 N. Machinaga and C. Kibayashi Tetrahedron Lett. 1989 30 4165. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 117 has been noted; such a reagent functions as the synthetic equivalent of the acetone ~,a'-dianion.*~ In a typical example (57) with Me2CHCH2(0Me)2 gave 88% of the dialkylation product. o SiR3 SiR3 (57) An interesting conversion of an aldehyde into a ketone via the boron-Wittig reaction has been reported.A suggested pathway is shown in Scheme7. Several examples were given; yields were low in some cases and excellent in others." Mes2BCH-R' Li' 2Mes2BCHR' &Mes,B--CHR' CF3 -CFSCHO H-C-R~ 0-C-H CO-0 I b'nIn I I I O-Li+ R2 COCF I OBMes2 Mes2BCHR' 111 R' CH2C0R2 -I -I R'CH=CR~ O=C-R2 R'CH=CR~ I &Y OCOCF3 Reagents i R'CHO; ii TFAA; iii H,O+ Scheme 7 Stereospecific E-olefination of an aldehyde was claimed for reaction of a bisbenzy- lic arsonium ylide anion in HMPA as exemplified by (58) and CSH,,CHO which Ph Ph at -78°C gave 91% of product (E:Z =>99 l).91 High E-selectivity was also claimed for the Bu,As-catalysed olefination of aldehydes in the presence of (Ph,PO)P-K,CO,; thus BuCHO and PhCOCH,Br gave the product in 80% yield with E :Z =>98 :2.92 89 A.Hosomi H. Hayashida and Y. Tominaga J. Org. Chem. 1989 54 3254. 90 A. Pelter K. Smith S. Elgendy and M. Rowlands Tetrahedron Lett. 1989 30,5643. 91 B. Boubia C. Mioskowski and F. Bellamy Tetrahedron Lett. 1989 30 5263. 92 L. Shi W. Wang Y. Wang and Y.-Z. Huang J. Org. Chem. 1989 54 2027. 118 B. V. Smith Bis-silyloxydienes have been prepared from 1,2- and 1,3-diketones by reaction with Me,SiCl-LiBr in dry THF.93 Deprotonation of ketones by M+ (SiMe3)2N- is regio- and stereoselective and shows considerable differences from that induced by LDA.94 With PhCH,COMe LDA gave typically a mixture of enolates after equilibration but NaH( SiMe3)2 furnished a single product (formulated as the 22-isomer) after 20 h.With 4-methyl- pent-3-en-2-one a similar clean reaction was claimed; the initial product after standing (24 h) contained (59) (95%). (59) The first observation of non-chelate controlled addition to a carbonyl group has been noted for 1-bromo-1-lithioalk-1-enes and 0-protected la~taldehydes.’~ In this way (60) gave (61) (85% d.e.) and then (62) (corresponding to formal addition of-CH20H). A chiral carbenoid gave higher d.e. (95% raised to >98% by further manipulation). OMEM MeIEM I CHO Me Br M e y o H MEM$Me OH OH (60) (61) (62) a-Chlorocrotylboronates were used to obtain a-phenoxy- and a-methoxyboron- ates capable of entering into aldol reactions with aldehyde^.^^ The E-and 2-pentenylboronates react to give aldol products with good-to-excellent diastereoselec- tion; thus (E)-(63) with EtCHO afforded (64) and (65) (81% 35 :65 re~pectively).~’ OH OH (63) (64) (65) Total stereoselectivity was observed in reaction of (S,S,S,)-(66)with PhCHO (aldol product 99%enantiomeric p~rity).~’ Variation in the leaving group in the conversion of ketones into E-or 2-enolborinates has been used to advantage since it is easier to handle dialkylboron chlorides than the analogous triflate~.~~ The choice of R and X in R2BX and the choice of amine (Et3N us.PriNEt) are therefore important and 93 L. Hansson and R. Carlson Acta Chem. Scand. 1989 43 304. 94 M. Gaudemar and M. Bellassoued Tetrahedron Lett.1989 30 2779. 95 M Braun and H. Mahler Angew. Chem. Znt. Ed. Engl. 1989 28 896. 96 R. W. Hoffman and S. Dresely Chem. Ber. 1989 122 903. 97 M. W. Andersen B. Hildebrandt G. Koster and R. W. Hoffman Chem. Ber. 1989 122 1777. 98 R. W. Hoffman K. Ditrich G. Koster and R. Sturmer Chem. Ber. 1989 122 1783. 99 H. C. Brown R. K. Dhar R. K. Bakshi P. K. Pandiarajan and B. Singaram J. Am. Chem. Soc. 1989 111 3441. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 119 R Me Me (66) modify the E/Z ratio. Brown and co-workers showed that with PhCOEt Et3N and Chx2BC1 (Chx = cyclohexyl) the product (67) was >99% E [with PhCHO furnish- ing 95% anti-aldol (68)] whereas 9-BBN-BCl and Pr';NEt gave (69) [with PhCHO forming 98% syn-aldol (70)].0B-9 -BBN OBChxz / PhGPh \ Ph @ & phg (67) (68) (69) (70) An important diastereoselective aldol reaction has been achieved via the inter- mediacy of acylsilanes.'OO Thus Pr'CHO with EtCOSiBu'Me gave (71) and (72) (>20 l) but the overall yield was rather low. If a chiral aldehyde was used e.g. (73) the percentage yield was improved but the syn:anti ratio was not. a#-(71) (72) (73) Unsaturated aldehydes uia umpolung with Me3SiCN have been reacted with chiral aldehydes and ketones; modest selectivity was observed and good chiral induction was dependent on the presence of an a-phenyl group in the carbonyl component."' Examples have been given of the use of Me,SiCN-umpolung with saturated com- pounds.'02 Aldol+rea;ctions of silyl enol ethers with aldehydes/acetals in the presence of the salt [Ph3POPPh,][triflateI2 furnish adducts in good yield.Ether (74) and OSiMe3 PhCHO afford the expected product (98% syn :anti 71 :29).'03 Michael addition with enones was noted. An interesting and facile reaction of Me,SiCN with orthoesters or acetals derived from a,P-unsaturated carbonyls led to a-cyano deriva- tives in excellent yields; catalytic quantities of NiC12 CoCl2 or PdC12 were nece~sary.'~~ LOO D. Schinzer Synthesis 1989 179. 101 S. Hunig C. Marschner K. Peters and H. G. von Schnering Chem. Ber. 1989 122 2131 102 S. Hiinig and C. Marschner Chem. Ber. 1989 122 1329. 103 T. Mukaiyama S. Matsui and K. Kashiwagi Chem. Lett. 1989 993. 104 T. Mukaiyama T.Soga and H. Takenoshita Chem. Lett. 1989 997. 120 B. V. Smith Fresh experiments have been quoted in a reinterpretation of the pathway involved in addition of allyltributylstannane to a1deh~des.l'~ Keck et al. have shown by *19SnNMR that (75) and SnCl form a tight bidentate chelate and therefrom the (75) product; hence it is not necessary to invoke a transmetallation product (allyltri- chlorostannane). The same is true of 2:l complexes of (75) for example which are also formed at low temperature and in the absence of free SnCl,. No 'burst' of Bu3SnC1 which Denmark's mechanism requires was observed. The reason for the discrepancy between the two sets of experiments is not clear. The BF3.0Et2-mediated rearrangement of an (S)-a-alkoxyallylstannane gives rise to a y-alkoxystannane which enters into clean aldol addition with aldehydes to afford syn-1,2-diols in high yield and in excellent enantiomeric excess.1o6 Virtually complete chirality transfer was observed with for example (76) and C6H13CH0 which gave syn :anti (77) in the ratio 87 13; syn-(77) had e.e.>95%.'07 (76) (77) 'Perfect stereochemical control' appears to have been achieved in a synthesis of syn-a-methyl+- hydroxythioesters. The silyl enol ether of (S)-ethyl propanethioate and an aldehyde is directed by a chiral promoter [from a chiral diamine-Sn(OTf),- Bu3SnF] with exceptional selectivity. PhCHO and (78) with (79) as the diamine afforded (80) (86%' 100% syn!). The enantiomeric excess was also high and this (78) (79) (80) process will no doubt be developed as another valuable method in asymmetric synthesis.It was further shown that with Sn(OTf) alone this type of reaction proceeded in 74% yield but the e.e. was zero.lo8 It is considered that activation in a chiral environment is due to a complex such as (81). The same type of chiral promoter has been successfully employed in reaction of achiral aldehydes and achiral ketene silyl acetals; the enantiomeric excess was variable but at -95"C 105 G. E. Keck M. B. Andrus and S. Castellino 1. Am. Chem. SOC.,1989 111 8136; cJ S. E. Denmark T. Wilson and T. M. Willson ibid. 1988 110 984. 106 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1989 30,2183. '07 T. Mukaiyama H. Uchino and S. Kobayashi Chem. Lett 1989 1001. 108 T.Mukaiyama and S. Kobayashi Chem. Lett. 1989 297. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds I . -.' 0 /sn II Tfo ; 0-S-CF3 FSn---0II (81) 89% e.e. was realized."' The addition of PhCHO to (E)-but-2-en-l-o1 mediated by PdCl,. (PhCN),-SnC1 ,shows a strong solvent-dependence on selection; DMSO gave principally syn-selection but in THF the opposite was seen."' Addition of water to DMSO markedly affected the selection. This behaviour was rationalized on the geometry of different transition state structures (82) and (83) which were held to operate in THF and DMSO respectively. R Diastereoselective aldol addition of a silyl enol ether to a chiral fluorinated aldehyde takes place with moderate-to-excellent diastereomeric excess.In this way (84) and CH2=C(Bu')OSiMe3 formed (85) (83% threo erythro = 78:22)."' The HxOCH2Ph 0 (84) enantioselective allylation of carbonyl compounds by Ti-carbohydrate complexes is a new way to exert control. CpTiC13 and for example 1,2:5,6-diisopropylidene-glucose form CpTi(OR),; this reacts with C3H5MgCl to give CpTi(C3H5)(OR) . Reaction of the latter with for example PrCHO gave an allylation product with 93% e.e."' Very high diastereoselectivity was found for Ti-mediated reactions of silyl ethers; e.g. (86) and aldehydes in the presence of LDA. The extent of selection 0si ButMe v 109 S. Kobayashi T. Sano and T. Mukaiyama Chem. Lett. 1989 1319. 110 Y. Masuyama J. P. Takahara and Y. Kurusu Tetrahedron Lett. 1989 30,3437.111 T. Yamazaki T. Yamamoto and T. Kitazune J. Org. Chem. 1989 54 83. 112 M. Riediker and R. 0.Duthaler Angew. Chem. Znt. Ed. Engl. 1989 28 494. 122 B. V. Smith was dependent on the nature and amount of Ti reagent; Ti(OPr') was nearly as effective as ClTi(OPr') . Addition of 12-crown-4 also had a marked effe~t."~ The levels of asymmetric induction in 'Mukaiyama aldol' reactions of chiral silyl ketene acetals in the presence of a chiral auxiliary (e.g. N-methylephedrine) are attributable to the influence of stereocentre 1 in the aminoalcohol; stereocentre 2 has only a minor r01e.I'~ Electrophilic condensation reactions of silyl ethers derived from homopropargyl alcohols such as (87) and aldehydes mediated by TiC14 proceed to form two possible products (88) and (89); whilst EtCHO gave a mixture (1:9) with (90) it gave only (89).I15 Ketene silyl acetals react smoothly with a,p-enones in the presence (87) (88) (89) (90) of [1,2-benzenediolato- O,O']oxotitanium to form Michael adducts.'16 Cp2ZrC12- CH2Br2-Zn forms a reactive organometallic species which rapidly methylenates aldehydes ketones and enones.No reaction was observed in the absence of the zirconium compound nor with esters or lactones under normal conditions. 1,l- Dibromopentane did not form any alkene; it was surmised that elimination had occurred.' l7 Careful control allows preparation of a Grignard reagent from a P-halogenoacetal which will then react with a carbonyl group regardless of halogen or acetal struc- ture.I18 2-Acyl- 1,3-dithiane 1 -oxides undergo diastereoselective addition of Grignard reagents; the products can be easily desulphurized.' l9 Autoxidation of R2Zn precedes conjugate addition to a$-enones which undergo epoxidation uia alkylperoxospecies.Selectivity was good; thus (91) with BuJn-0,- PhMe at room temperature gave 77% of (92) (erythro:threo = >99 1).120 A chiral OBu OBu Pri 0 (91) erythrol threo- (92) promoter (93) caused selectivity in the addition of organozincs to alkynals; e.g. alcohol (94) had 78% e.e.'*' Double alkylation of a$-unsaturated acetals by I13 C. Siege1 and E. R. Thornton J. Am. Chem. SOC.,1989 111 5722. 114 C. Gennari F. Molinari P.-G. Cozzi and A. Oliva Tetrahedron Lett. 1989 30,5163. T.-H. Chan and P.Arya Tetrahedron Lett. 1989 30,4065. T. Mukaiyama and R. Hara Chem. Lett. 1989 1171. 117 J. M. Tour P. V. Bedworth and R. Wu Tetrahedron Lett. 1989 30 3927. A. Greiner Tetrahedron Lett. 1989 30,3547. 119 P. C. B. Page D. Westwood A. M. Z. Slawin and D. J. Williams J. Chem. SOC.,Perkin Trans. 1 1989 1158. 120 K. Yamamoto and N. Yamamoto Chem. Lett. 1989 1149. 121 K. Soai and S. Niwa Chem. Lett. 1989 481. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds R'C3 CCH( OH)R2 I Me (93) (94) (i) RZnBr-NiBr,-Bu3P and (ii) Me1 gave modest yields; it was possible to run the reaction in a one-pot system.'22 Allyl-allenyl zinc reagents undergo rearrangement to form allylic bis-metallic species; electrophiles react with high regioselectivity affording a route to functionalized vinylzinc reagents.Selectivity in reaction with carbonyl groups has been exp10red.l~~ One potential advantage of this method is that an ester will react only as far as the ketone stage. A copper-catalysed conjugate addition of an organomanganese reagent to an a$-enone in THF is claimed as superior to cuprate addition; low temperatures are avoided no stabilizing or solubilizing additives are needed MnC1 is cheap and work-up is convenient especially on a large scale.'24 Me2C=CHCOMe obtained by this route with BuMnCl gave 94%adduct. RMnBr has also been used to advantage in such reactions. Acetylenic ketones add halide ion in a conjugate manner uia the agency of CeX,-R,SiCl-NaX/hN+ X-in MeCN; HCECCOC5HIl formed (E)-ICH=CHCOCSH1 (890/,),whereas HCECCONEt gave predominantly the 2-iodo adduct.'*' Coupling of Co complexes of alkynylaldehydes and silyl enol ethers is promoted by a Lewis acid; liberation of the organic product is achieved by CAN.'26 Complex (95) and EtC(OSiMe,)=CHMe produced (96) (79% syn :anti = 32 1).Ph c) 4CO13 (95) (96) l,l-Dichlorobut-2-ene and PhCHO with CrC1 in THF-DMF gave threo-(2) -4-chloro-2-methyl-1-phenylbut-3-en-1-01 (96% threo :erythro = 97 :3 2:E = 97 :3). Other examples showed similar high or very high ~e1ection.l~~ Stereohomogeneous (E)-and (2)-crotyltrifluorosilanes were prepared and gave highly diastereoselective reactions with aldehydes leading to erythro-P-methyl homoallylic alcohols in good- to-very good yields.128 Thus (E)-MeCH=CHCH2SiF3 and C8H17CH0 gave (97) (96% 99% isomerically pure) with CsF-THF.(97) I22 A. Yanagisawa S. Habaue and H. Yamamoto J. Am. Chem. SOC.,1989 111 366. 123 J. F. Normant J. C. Quirion A. Alexakis and Y. Masuda Tetrahedron Lett. 1989 30,3955. 124 G. Cahiez and M. Alami Tetrahedron Lett. 1989 39 3541. 12' T. Fujisawa A. Tanaka and Y. Ukaji Tetrahedron Lett. 1989 30 1255. I26 J. Ju B. R. Reddy M. Khan and K. M. Nicholas J. Org. Chem. 1989 54 5426. I27 K. Takai Y. Kataoka and K. Utimoto Tetrahedron Lett. 1989 30 4389. I28 M. Kira T. Hino and H. Sakurai Tetrahedron Lett. 1989 30 1099. 124 B. V. Smith P-Substituted allylsilanes behave as nucleophiles in the presence of fluoride not as anionic 1,3-dipoles in reaction with RCHO; e.g.CH2=C(SiMe3)CH2SiMe3 and CsF-DMF gave a quantitative yield of (98).'29 nR X OH X = Ph or SiMe (98) 4 Carboxylic Acids Esters and Lactones Alkenes are oxidized to acids by reaction with aqueous H202-H2W04; the yield was low for oct-1-ene (some diol was formed as well) but for 1-methylcyclohexene 72% of 6-oxoheptanoic acid was is01ated.l~' A specific route to chiral deuterated phenyldodecanoic acids (required for study of metabolic pathways of fatty acids) has been described via microbial reduction of the enoic acids.'31 Enantioselective reaction of MeC02Bu' and a Ti-carbohydrate complex led to P-hydroxyesters in good chemical and optical yield (see Scheme 8).'32 A stereospecific route to chiral CI I OLi R'O-Ti-OR' OH 0 A AOBul 0 I 0R' Reagents i LDA Et20 -70°C; ii CPT~CI(OR*)~ -30°C; iii RCHO -70°C; iv TFA (R' = But -+ R = H) Scheme 8 alkyl chloroalkanoates relies on displacement of mesylate derivatives in reaction with AlC13.133 It was suggested that (99) or similar is responsible for selectivity.Perfluoroalkyl iodides undergo carbonylation-hydration in the presence of a Pd Co or Rh catalyst; alcohols gave esters and amines formed arnide~.'~~.'~~ (99) '29 S. Pernez and J. Hamelin Tetrahedron Lett. 1989 30 3419. 130 T. Oguchi T. Ura Y. Ishii and M. Ogawa Chem. Lett 1989 857. 131 G. Gorger W. Boland U. Preiss and H. Simon Helo. Chim. Acta 1989 72 917. 132 R.0. Duthaler P. Herold W. Lottenbach K. Oertle and M. Riediker Angew.Chem. In?. Ed. Engl. 1989 28 495. 133 U. Azzena G. Delogu G. Melloni and 0.Piccolo Tetrahedron Lett. 1989 30,4555. 134 H. Urata 0. Kosukegawa Y.Ishii H. Yugari and T. Fuchikami Tetrahedron Left. 1989 30 4403. 13' H. Urata Y. Ishii and T. Fuchikami Tetrahedron Left. 1989 30 4407. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds An interesting enantioselective hydrogen transfer to a-methylenesuccinic acid has given high optical yields in the preparation of (100). Formic acid and an amine (which can be chiral) with rhodium and a chiral phosphane gave >85% e.e.; with (S)-PhCH(Me)NH, >97% e.e. was a~hieved.',~ Stereospecific carbonylation of vinyl bromides/chlorides in PTC conditioiis led to a,P-unsaturated acids.'37 A nickel cyanide catalyst was employed and it was suggested that a cyano-tricarbonyl nickelate anion was the effective agent.Ethoxyethyne and B-iodo-9-borabicyclo[3.3.l]nonanes formed a halogenoboration adduct which with an aldehyde gave an (E)-a$-unsaturated ester in good yield and configurational purity.13* Pd-mediated addition of allylic chlorides to carbon nucleophiles gives rise to unsaturated esters. By such means (101) and (102) afforded (103) (62Y0).',~ The fluorosulphone ( 104) reacted with ethyl 3-methylbut-2-enoate with NaOEt-DMF to form ethyl chrysanthemate in modest ~ie1d.I~' a,P-Ynoic esters are isomerized in refluxing toluene with a catalytic amount of Bu3P and 1rH5(Pr\P) to a,P y,S-dienoic ester~.'~' Eleven examples were given. Diallyl a-oxalcarboxylates and HC02H-Pd2( DBA),-PPh,-Et,N furnished a-ketocarboxylates in good yield.If HC02H was omitted decarboxylation-allylation was ~bserved.'~' A new monofunctionalization of malonic acid is based on reaction of Meldrum's acid and silylated amines lactams or alcohols to form silyl esters readily converted into substituted P-ket0a~ids.l~~ The procedure referred to in ref. 138 when applied to an @-enone is a useful route to a 6-ketoester. MeCOCH=CH gave a 93% yield of MeCO(CH,),CO,Et and surprisingly C1(CH2)3COMe gave 95% of product; cyclohex-2-enone was inertla Chiral acetylureas react after deprotonation with an aldehyde to form P-alkyl-P-hydroxypropionyl ureas; separation of isomers and methanolysis gave optically pure methyl P-alkyl-P- hydroxypropionates.By such means PhCH(OH)CH,CO,Me was prepared in 97% yield and with e.e. > 99'/0.'~~ 136 H. Brunner E. Graf W. Leitner and K. Wutz Synthesis 1989 743. 137 H. Alper I. Amer and G. Vasapollo Tetrahedron Lett. 1989 30 2615. 138 Y. Satoh T. Tayano S. Hara and A. Suzuki Tetrahedron Lett. 1989 30 5153. 139 G. Mignani F. Gross M. Aufrand and D. Marel Tetrahedron Lett. 1989 30 2383. 140 M. Hanack A. Auchter C. Wunde and T. Stoll Liebigs Ann. Chem. 1989 853. 141 D. Ma and X. Lu Tetrahedron Lett. 1989 30 843. 142 I. Shimizu T. Makuta and M. Oshima Chem. Lett. 1989 1457. 143 B. Rigo D. Fasseur P. Cauliez and D. Couturier Tetrahedron Lett. 1989 30 3073. I44 F. Kawamura T. Tayano Y. Satoh S. Hara and A. Suzuki Chem.Lett. 1989 1723. 145 K. Kishikawa M. Yamamoto S. Kohmoto and K. Yamada Chem. Lett. 1989 787. 126 B. V. Smith Claisen rearrangement of chiral ally1 thioethers has provided a route to chiral P-branched @-unsaturated thi0e~ters.l~~ Kinetic resolution of (*)-a-arylcarboxylic acids has been achieved by decomposi- tion of the 2-pyridinethiol ester in Pr'OH with a chiral 1,4-diol; PhCH(Et)C02Pri was prepared in 69% yield (91% e.e.).14' A versatile enzymatic resolution of 3-butanoylalkanoates of varying chain length provides a method for obtaining chiral hydroxyalkanoic acids valuable as intermediates in synthesi~.'~' Further upgrading of optical purity was possible by crystallization of dicyclohexylammonium salts. Some useful resolutions of (*)-P y-epoxyesters with porcine liver esterase provide chiral ester and acid; the former e.g.(105) (as a single isomer from the esterase- mediated resolution of the racemic ester) with HC02H was transformed into a y-lactone (106) but (107) of opposite configuration from MeOH-HC1.'49 By conversion of a$-unsaturated (butyl) esters into diols and thence into esters of 2,2-dimethyl-1,3-dioxolane-4-carboxylicacids chiral building blocks can be obtained from lipase-mediated hydrolysis of racemic esters e.g. (1O8).l5O Double diastereoselection occurred in the sulphoxide piperidine and carbonyl (SPAC -an acronym the writer feels has little to commend it) reaction of sulphinyl acetate esters and an a-unsubstituted aldehyde; y-hydroxy-a#-unsaturated esters were produced in good-to-excellent yield and with high ~electivity.'~' Reaction of y-mesyloxy-a-alkyl-a$-enoates and an organocyanocopper with BF3 brings about 1,3-chirality transfer and is a method for construction of chiral quaternary centres.'52 In this way (109) gave (1 10) (99 :1 S :R isomer).OTBS OTBS (109) (110) I46 R. Oehrlein R. Jeschke B. Emst and D. Bellus Tetrahedron Lett. 1989 30 3517. 147 K. Narasaka F. Kanai M. Okudo and N. Miyoshi Chem. Lett. 1989 1187. 148 C. Feichter K. Faber and H. Griengl Tetrahedron Lett. 1989 30 551. 149 P. Mohr L. Rosslein and C. Tamm Tetrahedron Lett. 1989 30 2513. I50 M. Pottie J. Van der Eycken and M. Vandewalle Tetrahedron Lett. 1989 30 5319. 151 K. Burgess.and I. Henderson Tetrahedron Lett.1989 30,4325. I52 T. Ibuka N. Akimoto M. Tanaka S. Nishii and Y. Yamamoto J. Am. Chem. Soc. 1989 111 4864. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds Enantiomerically and diastereomerically pure threo-3-aryl-2,3-dihy-droxypropanoic acid derivatives have been prepared via a sequence starting with cyanohydrins of aryl aldehydes which are transformed into cyanodiols and then into the products.153 Selective Claisen and Dieckmann ester condensations are promoted by dichlorobis(trifluoromethy1sulphonate)Ti'". MeCH2C02Me and PhCHO did not form a crossed product but gave MeCH,COCH(Me)CO,Me (36%). The best cyclization was achieved with molecular sieves; Me02C(CH2),C02Me at 0 "C gave 80% ketoe~ter.''~ A highly diastereoselective Michael addition was effected by reaction of an enamine and the 2,2-dimethoxyethyl esters of a$-unsaturated acids using TiC1 as an activator.The process was characterized by syn selection (111) gave (112) (82%; syn :anti = 93 :7) probably uia a chair-like transition state (1 13).'" The dienolate of (1 14) -a synthetic equivalent of acetoacetic ester dianion -adds selec- tively to enals and enters into highly selective aldol addition^.''^ (113) (114) Diethyl ketomalonate serves as an equivalent of C02 in Diels- Alder reactions with simple (unactivated) azadienes. This is the first report of such a reaction. Diester (1 19 from appropriate precursors,- gave only (1 16) on hydrolysis; the structure of the latter was confirmed by an independent route.''' (115) (116) Intramolecular asymmetric lactonization of a prochiral bis-acid chloride with a chiral auxiliary has been examined (RJ?)-1,2-diphenylethane-l,2-diamine and acid I53 B.R. Matthews H. Gountzos W. R. Jackson and K. G. Watson Tetrahedron Lert 1989 30,5157. 154 Y. Tanabe Bull. Chem. SOC.Jpn. 1989 62 1917. 155 Y. Hashimoto S. Machida K. Saigo J. Inoue and M. Hasegawa Chem. Lett. 1989 943. 156 D. Seebach U. Misslitz and P. Uhlmann Angew. Chern. Int. Ed. Engl. 1989 28 472. 157 J. Barluenga F. J. Gonzalez and S. Fustero Tetrahedron Left. 1989 30 2685. 128 B. V. Smith chloride (117) gave the bis-amide cleaved and re-cyclized by TFA to (118) (>96% e.e.).15* The synthesis of analogues of mevalonolactone via silylcuprate chemistry has been used to confirm the structure of a rare urinary metab~lite.'~' ClCO( CH,),CH(OAc)(CH,),COCl (1 17) Lipase-mediated hydrolysis of a prochiral diacetate precursor has led to (S)-(-) -paraconic acid (119) and by further steps to the A-factor.16' Carbonylation of 2-bromo-1 -phenylbuta-1,3-diene is a route to a methylene-a-ketolactone and hence by reaction with Si02 ketobutenolide.'61 07c02H 0 5 Amines and Amides Facile reduction of azides occurs with hydrazine in the presence of a Pd catalyst.Reaction is quite rapid and yields are >70%.'62 A convenient one-pot conversion of an azide into a BOC-protected amine gives very good yields and is useful for a range of chiral corn pound^.'^^ Amides when treated with the calculated quantity of PhCH2Me3N+ Br; and alkali are transformed into amine~.'~~ Yields in excess of 70% were obtained.A powerful versatile reducing agent (LiBH,-NaBH4-Me,SiCl) efficiently converts amides nitriles and nitro compounds into arnine~.'~~ The sa2e reagent reduces acids (alcohols) and sulphoxides (sulphides). A new synthon (= CH2NH2) has been utilized by reaction of N-triphenylphosphorylidene-1-(benzotriazol-1-y1)methyl-amine (120) and an alkyllithium or a Grignard reagent and can be illustrated by the preparation of C13H27NH3 Cl-(87?40).'~~ 158 N. Baba A. Sakamoto M. Mimura Y.Yamamoto K. Uchida and J. Oda Chem. Lett. 1989 889. 159 I. Fleming S. K. Armstrong and R. J. Pollitt J. Chem. Res.(S) 1989 19. 160 K. Mori and N. Chiba Liebigs Ann.Chem. 1989 957. H. Alder and G. Vasapollo Tetrahedron Lett. 1989 30 2617. A. A. Malik S. B. Preston T. G. Archibald M. P. Cohen and K. Baum Synthesis 1989 450. 163 S. Saito H. Nakajima M. Inaba and T. Moriwake Tetrahedron Lett. 1989 30 837. 164 S. Kajigaeshi K. Asano S. Fujisaki T. Kakinami and T. Okamoto Chem. Lett. 1989 463. 165 A. Giannis and K. Sandhoff Angew. Chem. Znt. Ed. Engl. 1989 28 218. 166 A. R. Katritzky J. Jiang and L. Urogdi Tetrahedron Lett. 1989 30 3303. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds Direct regio- and stereoselective lithiation of secondary and methyl-allylamines allows the preparation of a new versatile y-aminated organolithium reagent reactive towards electrophilic centres.'67 This method was adapted to produce a$-unsatur- ated butyrolactams.Regio- and chemoselective nucleophilic addition of amines to oxiranes was promoted by Ph4Sb+OTf- and is a good route to P-aminoalcohols.'68 Methoxy- selenation or -bromination of chiral 3-acyl-2-oxazolones with a chiral auxiliary constitutes the basis for a highly stereoselective formation of chiral synthons for P-aminoalcohols; the best results were secured with (121) which gave 96% d.e. (121) (PhSeC1) and 89% d.e. [Br2-MeC(OMe)3].'69 A stereoselective synthesis of threo- and erythro-P-aminoalcohols proceeds via hetero-Diels-Alder addition of an N-protected a-aminoaldehyde to a reactive diene promoted by Eu(hfc) . Reaction proceeds in a manner consistent with chelation control (anti-Cram) with formation of (122) and (123) from the appropriate diene (threo erythro = 80:20); however a reversal was noted for (124) in the presence of Et,AlCl (threo erythro = < 1:99).l7' /J 3 R3 OMe R3 OMe N(CH2PhI2 NR1R2 N R' R~ (122) (123) (124) Ylides CH2=SMe2 and CH2=AsPh3 react with doubly protected a-amino-aldehydes to form aminoalkyl epoxides with high diastereofacial selectivity (in the range 86 14 to >95 5).The configuration of the products was determined by ring opening with Me,CuLi affording N-protected P-aminoalcohols whose configuration was established rigor~usly.'~' Homochiral allylic amines with 9-BBN-catechol- borane and a rhodium catalyst give an entry into syn-3-aminomethyl-substituted alcohols. The best catalytic system appeared to be Rh(cod)C12-4P(OEt),; (125) N(phthaloy1) 167 J.Barluenga F. Foubelo F. J. Fananas and M. Yus J. Chem. Res.(S) 1989 200. 168 M. Fujiwara M. Imada A. Baba and H. Matsuda Tetrahedron Lett. 1989 30 739. 169 T. Ishizuka S. Ishibuchi and T. Kunieda Tetrahedron Lett. 1989 30 3449. 170 M. M. Midland and M. M. Alfonso J. Am. Chem. SOC.,1989 111,4368. M. T. Reetz and J. Binder Tetrahedron Lett. 1989 30,5425. 171 130 B. V. Smith under these conditions showed syn :anti selectivity of 98 :2.'72 An interesting tandem aldolization/ lactonization/dyotropic rearrangement of a-aminoaldehydes has been uncovered by Reetz and co-worker~.'~~ The essential features are shown in Scheme 9. (126) R = Me or Bu Reagents i 4OSiMe3,MgCI, CH2CI,; ii spontaneous OPh Scheme 9 The configuration of (126) was established unequivocally by reaction of (127) (from L-isoleucine] with the silyl ketene acetal.N-Protected a-amino aldehydes are transformed into y-aminoesters in a two-stage process first the aldehyde was converted into an a$-unsaturated ester and thence with R2CuLi-Me,SiC1 into syn/anti-(128) with a 94 6 syn preferen~e.'~~ N( CH2P h)2 syn/ anti-(128 ) Ring-opening of N,N'-bis-protected 2-aminomethylaziridines produced 3-substituted 1,2-diaminopropanes carrying various functionality at C3.17* Alkylation of Ph,C=NCH,CO,R with ally1 bromide in a phase-transfer system and in the presence of a chiral quaternary salt gave only low e.e. (5% with R = CH,Ph). An improvement was noted for the t-butyl ester; the best result of all was from the neopentyl ester and 4-ClC,H4CH,Br which gave after work-up 4-chlorophenylalanine (>99% e.e.).176 Phosphorus ylides and t-butylamino (diphenylmethylene) oxamate react to form 2-aza-1,3-dienes reduced with NaBH3CN to protected a-amin~acids.'~~ The lithium enolate of ethyl [2-(2,2,5,5- tetramethyl-l-aza-2,5-disila)cyclopent-l-yl]acetate underwent slow transmetallation with CpTiCl(OR),; subsequent aldol reaction of aldehydes showed an astonishingly high stereoselectivity in formation of D-threo-P-hydroxy-a-aminoacids.The per- ceived advantages of the method are simplicity use and recovery of reagents and selection. in the example shown in Scheme 10 (R2 = H BOC or CHO) the product had enantiomeric and diastereomeric excesses of 98%.'78 Total stereochemical purity 172 K.Burgess and M. J. Ohlmeyer Tetrahedron Lett. 1989 30,5861. 173 M. T. Reetz A. Schmitz and X. Holdgriin Tetrahedron Lett. 1989 30 5421. I74 M. T. Reetz and D. Rohrig Angew. Chem. Int. Ed. EngL;1989 28 1706. 175 D. S. Jones A. Srinivasan S. Kasina A. R. Fritzberg and D. W. Wilkening J. Org. Chem. 1989,54,1940. 176 M. J. O'Donnell W. D. Bennett and S. Wu J. Am. Chem. SOC.,1989 111 2353. 177 J. P. Bazureau D. Person and M. Le Corre Tetrahedron Lett. 1989 30 3065. 178 G. Bold R. 0. Duthaler and M. Riediker Angew. Chem. Int. Ed. Engl. 1989 28 497. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds Reagents i LDA -78 "C;ii CpTiCI(OR), THF-U,O; iii R'CHO -78 "C -+ r.t.Scheme 10 was achieved in the synthesis of (129) a component of microbial cell walls. A new synthesis of a-aminoacid-(E)-P,y-enol ethers is an E-selective process; a P-alkoxyaldehyde and (MeO),POCH( NHZ)CO,Me (Z = COPh CHO Ac etc.) with OH NHz (129) KOBu' generate ROCH,CH=C( NHZ)CO,Me in turn isomerized to the P,y-isomer by LDA-THF at -70 0C.179 DEAD and Li dienolates or Sn/Ge masked dienolates furnish either a-or y-aminoacid derivatives; (E)-MeCH=CHCO,Me in HMPA-THF at -78 "C gave principally the y-adduct whereas Bu3SnCH2C(OSiMe3)=CHC02Et showed opposite selectivity with ZnC1 An unusual organometallic-mediated aldol reaction from (2R,4E)-2-methylhex-4-enal and NCCH,CO,Et has given a route to some unusual unsaturated hydroxyaminoacids.'81 Dienic a-aminoacids have been synthesized from the Pd-mediated addition of LiCH(C02Me)N=CPh2 to allenes.'82 -1mines react with+ke$ene silyl acetals under the catalytic influence of the bisphosphonium salt Bu3POPBu3 thereby forming aminoesters in good yield.'83 Facile formation of amides by reaction of an acid and an amine in the presence of molecular sieves has been A one-pot reaction leading to amides (and esters by using alcohols) has been developed; yields were consistently good-to- e~cellent.'~~ An improved method for the Ritter reaction is applicable to primary and secondary substrates rather than the tertiary ones usually employed.Alcohols 179 M. Daumas L. Vo-Quang Y. Vo-Quang and F. Le Goffic Tetrahedron Lett.1989,30 5121. 1x0 Y. Yamamoto S. Hatsuya and J. Yamada Tetrahedron Lett. 1989 30,3445. A. Togni S. D. Pastor and G. Rihs Helv. Chim. Act4 1989,72 1038 1471; cf J. Am. Chem. SOC.,1989 111 1471. 1x2 N. Kopola B. Friess B. Gazes and J. Gore Tetrahedron Lett. 1989 30,3963. 183 T. Mukaiyama K. Kashiwagi and S. Matsui Chem. Lett. 1989 1397. 184 J. Cosy and C. Pale-Grosdemange Tetrahedron Lett. 1989 30,2771. I X5 J. M. Jaszay 1. Petnehazy and L. Toke Svnrhesis 1989 745. 132 B. V. Smith were converted into triflates and thence into amides by carbocation addition to a nitrile.lS6 Yields in the range 50-98% were obtained. Enzymatic syntheses of propargylamides from the esters and arylamines with microbial lipase gave yields >8O% and worked well in organic solvents.'87 Secondary amides with (CF3C0)20-Bu4N+ NO; in CH2C12 underwent N-nitra- tion in good yield; some N-nitrosation was also noted.'" Secondary amines with CO and 10 mol% Se S and an alkylating agent form R'R2NCOSR3; it was presumed that the S-alkylthiocarbamate was produced via a seleno~arbamate.'~~ Two papers describe a detailed exploration of the chemistry of carbamate~.'~~ In the first- electrophilic sulphonylation of allylic carbamates led to 1 -(p-toluenesulphony1)-2-alkenyl carbamates whose achiral Li derivatives reacted with carbonyl groups in the usual way; chiral titanium derivatives added at the y-position affording a new class of homoenolate reagents.Selectivity and reactivity of matched/unmatched pairs was also examined.The nucleophilic alkenoylation of protected chiral a-oxy- and a-aminoaldehydes by lithiated tosylcarbamates showed complete syn-stereoselectivity in production of a,/?-difunctionalized ap-enones. 6 Other Nitrogen Compounds TiC14-SnC12 serves as a mild reagent for cleavage of aldoximes and ketoximes possibly via an imine intermediate.'" Dichloro- and dibromoformaldoximes react with alkenes to form 3-halogenoisoxazolines in a convenient one-pot reaction; the latter may be transformed into P-hydroxynitriles [by Fe(CO),] or /?-hydroxyesters (methoxylation and catalytic reduction). With ally1 alcohols and allylamines a method was devised for butyrolactones and ~~-3-hydroxy-4-aminoacids, respec-tive~~.'~~ Oxidative conversion of aliphatic nitro compounds by sodium chlorite (NaC102) forms carbonyl compounds in good yields; primary nitro groups give aldehydes and secondary compounds form ketones [e.g.MeCH( N02)CH2CH2COMe gave the 1,4-diketone (78Y0)].'~~ Other functional groups were compatible. Asymmetric reduc- tion of nitroalkenes by baker's yeast gives significant enantiomeric excess in the formed nitroalkanes; for example (E)-(130) gave (131) (58% yield 83% e.e.).194 The 2-isomer of (130) gave lower e.e. (66%). Alkyl nitronates and aldehydes with 186 A. G. Martinez R. M. Alvarez E. E. Vilar A. G. Fraile M. Hanack and R. Subramanian Tetrahedron Lett. 1989 30 581. 187 F. Rebolledo R. Brieva and V. Gotar Tetrahedron Lett. 1989 30,5345. I88 E. Carvalho J. Hey F. Norberto and E.Rosa J. Chem. Res.(S) 1989 260. 189 N. Sonoda T. Mizuno S. Murakame K. Kondo A. Ogawa I. Ryu and N. Kambe Angew. Chem. In&. Ed. Engl. 1989 28 452. 190 M. Reggelin P. Tebben and D. Hoppe Tetrahedron Lett. 1989 30 2915 2919. 19' R. Balicki L. Kaczmarek and M. Malinowski Liebigs Ann. Chern. 1989 1139. 192 K. Halling I. Thomsen and J. B. G. Torssell Liebigs Ann. Chem. 1989 985. 193 R. Ballini and M. Petrini Tetrahedron Lett. 1989 30,5329. 194 H.Ohta N. Kobayashi and K. Ozaki J. Org. Chem. 1989 54 1802. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds Pr'OTiCl formed satisfactory yields of erythro-@-nitroalcohols.'9s The a-nitro group of nitroketones is smoothly replaced on reaction with Na2S204-Et3SiH in HMPA-H,O (or D20).These reagents are preferred to any containing Sn'V.'96 Very high yields of nitriles have been prepared in a one-pot reaction of an aldehyde and NH,Cl-Cu powder-0 in pyridine.The method is applicable to tertiary struc- tures e.g. t-C,H,CHO gave 90% of the 11itri1e.l~~ a,@-Unsaturation was not a drawback but the method failed with enolizable compounds. Similar methodology was used to convert primary amines into nitriles in excellent ~ie1ds.I~' Asymmetric hydrocyanation of aldehydes with chiral titanium reagents gave very high selectivity in formation of cyanohydrins (e.e. > 90'/0).'~~ An intriguing C-ethylation during yeast-mediated reduction of MeCOCH2CN [which formed synlanti-MeCH(OH)CH(Et)CN] has been reported. MeCOCH(Et)CN was isolated after shorter reaction time and is the logical inter- mediate.', @-Phenylthio- and P-methylthioacetoxynitriles were good substrates for kinetic recognition by lipase and were transformed into @-hydroxynitriles in excel- lent optical yield.200 Steric control in addition of cyanide ion to Schiff bases was secured by use of a modified haemin co-polymer; the formed a-aminoacids had much enhanced e.e.(~O-~~YO).~O' 7 Phosphorus and Sulphur Compounds This section does not attempt to give comprehensive coverage of pertinent literature scanned being limited by reason of space. The fate of the oxaphosphetanes formed from Bu'CHO and Bu,P=CHPr has been carefully studied; at the beginning of reaction at -55 "C the cis :trans ratio is 40 60. By measurement of the 3'P NMR signal it was shown that the concentration of the trans-isomer increased at the expense of the cis-compound and before product formation this change was essentially complete.The E :2 isomer ratio of the formed alkenes was 96 :4.,02 Kinetic factors were dominant in Wittig reactions of conjugated ylides and reversal of oxaphosphetane formation was insignificant (<5%).,03 Only oxaphosphetanes are needed to describe overall alkene formation. Exceptional E-selectivity was observed with dibenzophosphole (132) which gave E :2 ratios (132) 195 A. G. M. Barrett C. Robyr and C. D. Spilling J. Org. Chem. 1989 54 1233. 196 A. Kamimura K. Kurata and N. Ono Tetrahedron Lett. 1989 30,4819. 197 P. Capdevielle A. Lavigne and M. Maumy Synthesis 1989 451 453.198 H. Minamikawa S. Hayakawa T. Yamada N. Iwasawa and K. Narasaka Bull. Chem. SOC.Jpn. 1989 61 4379. 199 T. Itoh Y. Takagi and T. Fujisawa Tetrahedron Lett. 1989 30,3811. 200 T. Itoh and Y. Takagi Chem. Lett. 1989 1505. 201 K. Saito and K. Harada Tetrahedron Lett. 1989 30,4535. 202 B. E. Maryanoff A. B. Reitz D. W. Graden and H. R. Almond jun. Tetrahedron Lett. 1989 30,1361. 203 E. Vedejs and T. J. Fleck J. Am. Chern. SOC.,1989 111 5861. 134 B. V. Smith as high as 99 1. Phosphorane ylides react with succinic anhydrides to generate enol lactones; reaction takes place preferentially at the less hindered carbonyl except when an adjacent methoxy group directs attack via an intramolecular complex.2o4 In this way (133) gave (134) as a single isomer.0 0 (133) (134) Mesityl(prop-2-eny1)phosphine is rearranged by heating at 100 "C to the isopro- pylidene analogue (80-90% yield).205Phosphinomethylenetriphenylphosphoranes and BF etherate form 2-phosphonio-1 -phosphaalkenes.206 Photorearrangement of ally1 diphenyl phosphate may occur via a Norrish type I1 reaction and proceed uia phosphoranyl 1,3-biradi~als.~~' The isolated product was (135). Preparation of (E)-1 -alkenyl phenyl sulphides from vinylic bromides with high selectivity has been recorded.208 An efficient route to chiral t-butyl sulphoxides uses the method shown in Scheme 11 .209 Optical purity of the final product was dependent Reagents i SOClz NEt,; ii R'M; iii R2M Scheme 11 204 M. M. Kayser and L.Brean Can. J. Chem. 1989 67 1401. *05 F. Mercier C. Hugel-Le Goff and F. Mathey Tetrahedron Lett. 1989 30 2397 '06 H. Griitzmacher and H. Pritzkow Angew. Chem. Int. Ed. EngL 1989 28 740. 207 D. R. Anderson and C. N. Eley Tetrahedron Lett. 1989 30 4059. 208 A. Carpita R. Rossi and B. Scamuzzi Tetrahedron Lett. 1989 30,2699. 209 F. Rebiere and H. B. Kagan Tetrahedron Lett. 1989 30,3659. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds upon choice of R2M but for three examples (PhLi BuLi vinylMgC1) 100% e.e. was attained. An approach to homochiral sulphoxides relied on lipase-mediated cleavage of racemic esters R(SO)CH2C02Me (R = aryl alkyl or cyclic).21o Direct asymmetric oxidation of acetylated or silylated S-methyl+- hydroxysulphides fol- lowed by deprotection gave S-methyl-P- hydroxysulphoxides in reasonable optical purity and which could be further upgraded by crystallization.211 The oxidant used was Bu'OOH-Ti(OPr'),-DET.Active methylene compounds react with Corey-Kim reagent (136) to form stable S-ylides.212 a,P-Epoxysulphides and LiMe2Cu generate an enolate which is reactive towards aldehydes with high regio~electivity.~~~ Claisen rearrangement of allylic ethers is markedly accelerated by an arylsulphon- methide group at C2. This reaction offers a method for construction of vicinal chiral quaternary A general account of the structure of lithium derivatives of compounds containing sulphur (sulphones sulphoxides thioethers) and nitrogen (nitriles nitro derivatives and hydrazones) has been published.215 8 Miscellaneous A multiauthor review entitled 'Emerging Organic Reactions' has ca.80% of its material in the area of interest of this Recent advances in the field of Reformatsky reactions have been surveyed.217 A very wide-ranging review of allylic 1,3-strain as a controlling factor in stereoselective transformations has been published by R. W. Hoffman.218 The usefulness of acylsilanes in synthesis has been reviewed.219 A massive review of the Wittig reaction and its modifications has been compiled by Maryanoff and Reitz."' 210 K. Burgess and I. Henderson Tetrahedron Lett. 1989 30 3633. 211 V. Conte F. DiFuria G. Licini and G. Modena Tetrahedron Lett. 1989 30 4859. 212 S. Katayama T. Watanabe and M.Yamauchi Chem. Lett. 1989 973. 213 T. Satoh A. Sugimoto M. Itoh and K. Yamakawa Bull. Chem. Soc. Jpn. 1989 62 2942. 214 S. E. Denmark M. A. Harmata and K. S. White J. Am. Chem. Soc. 1989 111 8878. 21s G. Boche Angew. Chem. Znt. Ed. Engl. 1989 28 297. 216 See Issue No. 7 Chem. Rev. 1989 89 1411-1617. 217 A. Furstner Synthesis 1989 571. 218 R. W. Hoffmann Chem. Rev. 1989 89 1841. 219 A. Ricci and A. D'Innocenti Synthesis 1989 647. 220 B. E. Maryanoff and A. B. Reitz Chem. Rev. 1989 89 863.

ISSN:0069-3030    

DOI:10.1039/OC9898600103

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

6 Alicyclic Chemistry By P. QUAYLE Department of Chemistry University of Manchester Manchester M 139PL 1 Introduction Once again this area of chemistry has proven to be highly productive. In particular the application of pericyclic radical and organometallic-based strategies have proven to be extremely fruitful. Reviews detailing the seminal contributions of a number of workers have appeared.'-4 2 General Angle' has demonstrated that the p-quinomethide (1) (sometimes isolable) may be trapped in an intramolecular fashion to afford a range of functionalized carbocyclic ring systems (Scheme 1) in good overall yield (circa 70%). Rearrangement reactions have been utilized to good effect in the synthesis of cis-fused hydrindanes hydroazulenes and bicyclo-[6.3.O]-undecanes via a pin-nacol-type process6 (Scheme 2).In a related pro~ess,~ reaction of the bis-TMS enol ether (2) with an appropriate ketal in the presence of an excess of a suitable Lewis acid (BF3.0Et2) affords directly spirocyclic diketones (Scheme 3). In a similar manner reaction of the protected carbinols (3) with a suitable electrophilic trigger' results in a smooth rearrangement reaction to afford a variety of fused carbocyclic systems (Scheme 4).Derivatization' of the aldehydes (4)with TMS-SMe followed by activation with a strong Lewis acid (TMS triflate) affords the ring expanded systems (5) (Scheme 5) in good isolated yield for n = 5,8,12. In the case of n = 6 preferential migration of the TMS-methyl group is observed. Subsequent loss of trimethylsilanol affords the exocyclic thio-ether (6).However in the case of the unsaturated derivative (7) vinyl migration becomes more facile affording the cycloheptadiene (8) in excellent yield' (83%). Carbon-centred radical cyclizations have been put to good use in the synthesis of a number of carbocyclic systems. Of particular interest is the development" of ' B. M. Trost Angew. Chem. Int. Ed. Engl. 1989 28 1173. W. Oppolzer Angew. Chem. Int. Ed. Engl. 1989 28 38. For an interesting compilation of modem synthetic methodology see J. A. Gladysz and J. Michl (ed.) Chem. Rev. 1989,89 1413-1617. B. Geise Angew. Chem. Int. Ed. Engl. 1989 28 969. S. R. Angle and K. D. Turnbull J. Am. Chem. Soc. 1989 111 1136. G. C. Hirst P. N. Howard and L. E. Overman J.Am. Chem. Soc. 1989 111 1514. 'Y.-J. Wu and D. J. Burnell Tetrahedron Lett. 1989 30 1021. S. Kim and J. H. Park Tetrahedron Lett. 1989 30 6181. K. Tamino K. Sato and I. Kuwajima Tetrahedron Lett. 1989 30,6551. D. P. Curran M.-H. Chen and D. Kim J. Am. Chem. Soc. 1989 111 6265. 137 138 P. Quale 73% (1.8 1) Reagents i Ag,O CHC13 r.t.; ii ZnCI Scheme 1 TMSO qk -ib I OMe CH(OMe)2 H 82% 1 + -..,OM, H 80% 0 75% Reagents i SKI, CH2C12 -78 "C Scheme 2 Alicyclic Chemistry 139 81% Reagents BF3.0Et2 (excess) Scheme 3 OTBDMS i,ii --+ But&S;h B u' 96% Reagents i PhSCl; ii AgBF4 Scheme 4 TMsGHo i,ii 6'"' (7) (8) 83% Reagents i,TMS-SMe; ii TMS-OTf Scheme 5 140 I? Quale atom transfer processes leading to the preparation of functionalized hence poten- tially synthetically useful products (Scheme 6).Since the isolation of the novel antitumour antibiotic Fredericamycin A a number of strategies have appeared for the preparation of spirocyclic carbocyclic systems. A general method for the preparation of a number of such systems has appeared this year" based upon the intramolecular acylation reactions of a sulphoxide anion (9) (Scheme 7). 1 A R R = Me,E:Z = 54~44 Reagents i BuSnH (cat.)/PhH Scheme 6 0 Reagents i LDA THF -78 "C; ii PhS(CH,),CHO; iii NaIO,; iv Mn02 Scheme 7 The application of organometallics in organic synthesis continues to be an area of intense chemical interest.In particular the utilization of palladium-mediated carbon-carbon processes appears to be highly attractive due to the mild reaction conditions employed functional group compatability and potential for stereocon- trol. A recent example detailing tandem alkylation reactions is particularly M. Pohmakotr S. Popuang and S. Chancharunee Tetrahedron Lett. 1989,30 1715. Y. Zhang and E-i. Negishi J. Am. Chem. SOC.,1989 111 3454. Alicyclic Chemistry 141 noteworthy12 (Scheme 8) in that it illustrates the variety of ring systems which may be readily accessed from relatively simple substrates. An area of increasing interest is the utilization of electrochemical techniques to synthetic processes. For example electrochemical red~ction'~ of the mesylates (10) readily affords a variety of bicyclic substrates generally in good yield (Scheme 9) although cyclization to cyclobutanes is a particularly poor yielding reaction.0 &Ji& -72% yR EE 78% TMS E = CO,Et 56% Reagents i Pd'; ii CH,CHC02Me Scheme 8 3 Cyclopropanes Metallati~n'~ of the readily available cyclopropene (11) with Bu"Li in THF and subsequent trapping with ethylene oxide afforded the alcohol (12) in good yield. Oxidation of (12) to the acid was accomplished using Jones' reagent. 13 P. G. Gassman and C. Lee Tetrahedron Lett. 1989 30,2175. 14 N. D. Lenn Y. Shih M. T. Stankovich and H-W.Liu J. Am. Chem SOC.,1989 111 3065. 142 P. Quale COzEt CO2Et 88% COzEt 6% YOzEt ,COzEt H 81% Scheme 9 65% Reagents i BuLi/THF; ii fro; iii CrO,/H,SO,/AcOH Gassman has developed a number of routes to functionalized cyclopropanes.Conver~ion'~ of the sulphide (14) to the trans-cyclopropane (15) was accomplished in moderate overall yield by way of a Ramberg-Backlund reaction. Alternatively,16 electrochemical reduction of the vinyl phosphates (e.g. 16) readily affords the bicyclic cyclopropane (17) in moderate yield 58%. Presumably the reaction proceeds via a S.E.T. reaction to afford the radical anion (18) which upon fragmentation to the radical (19) cyclizes to the observed product. Reaction of di-iodomethane with esters in the presence of samarium metal provides rapid access to functionalized cyclopro- panes" (Scheme 10).H H Reagents i NCS; ii MCPBA; iii KO'Bu Is P. G. Gassman S. M. Bonser and K. M. Majerski J. Am. Chem. Soc. 1989 111 2652. l6 P. G. Gassman and C. Lee J. Am. Chem. Soc. 1989 111 739. l7 T. Imamoto Y. Kamiya T. Hatajima and H. Takahashi Tetrahedron Lett. 1989 30,5149. 143 Alicyclic Chemistry R OH RCOX 2 e.g. R = Ph 70% Reagents i Excess CH,12/Sm Scheme 10 wco2Me -0 C02Me 90% Reagents i KOH/MeOH/PhI(OAC)2; ii CuCl Scheme 11 Iodonium ylids18 are found to undergo efficient intramolecular cyclopropanation reactions when reacted with copper(1) chloride at 0 "C (Scheme 11). Vinyl boronic19 esters undergo smooth cyclopropanation to afford the cyclopro- panes (20). The synthesis of the novel cyclopropy12' amino acid (22) has been reported starting from the unsaturated amine (21).Reaction of the glucal (23) with (22) 18 R. M. Moriarty 0. Prakash R. K. Vaid and L. Zhao J. Am. Chem. Soc. 1989 111 6443. 19 P. Fantani B. Corboni M. Vautier and R. Came Tetrahedron Lett. 1989 30,4815. 20 R. C. Petter Tefrahedron Lett. 1989 30,399. 144 P. Quale (25) 81% NHTMS Reagents i EtAlC12; ~~o,,s = (24) a suitable nucleophile (24) afforded the unusual cyclopropanes (25) as a 1 :1mixture of diastereoisomers in high yield.21 Unexpectedly reaction of the diene (26) with an oxa-TMM equivalent afforded the cyclopropane (27) in moderate yield 56%.22 The synthesis of the plant growth regulator (29) from the imine (28) has been reported.23 Reagents KOBu'/THF/A The functionalization of 1,l -dihalocyclopropanes has been achieved by a number of worker^^^.^^ (Scheme 12).The synthesis of cyclopropanes with very high levels of diastereoselectivity has been the subject of a number of investigations. Hence Simmons-Smith cyclopropana- tion of the enol ether (30) proceeds in fair yields with excellent diastereoselectivity26 Scheme 12 21 M. Okabe and R-C. Sun Tetrahedron Lett. 1989,30 2203. 22 B. M. Trost and S. Schneider J. Am. Chem. SOC.,1989 111 4430. 23 N.De Kimpe P. Sulmon and N. Schamp Tetrahedron Lett. 1989 30 5029. 24 M. G. Banwell G. L. Gravatt J. S. Buckleton G. R. Clark and C. E. F. Rickard J. Chem SOC.,Chem Commun. 1989 865. 25 T. Harada K. Hattori T. Katsuhira and A. Oku Tetrahedron Lett.1989 30 6035. 26 T. Sugimura T. Futagawa M. Yoshikawa and A. Tai Tetrahedron Lett. 1989 30 3807. Alicyclic Chemistry (30) Reagents Et2Zn/CH212; -40 to 0 "C (>98%). Alternatively reaction of the homochiral Meldrum's acid derivative (31) occurs with complete facial selectivity to afford the chiral cyclopropanes (32) after removal of the chiral au~illary.~' Finally functionalized cyclopropanes have a rich and varied chemistry; for example the cyclopropyl carbene complex (33) upon reaction with olefin affords the isomeric cyclopropanes (34).28 R' R (32) E = CO,Me OMe R' R' < u (33) (34) ca. 60% Cyclopropanes such as (35) undergo oxidative ring cleavage to afford the peroxides (36) which upon reduction with SmI afford the syn-1,3-diols (37) with high levels of dia~tereoselectivity.~~ .via R R' R LR' (36) (37) Reagents i 02/Ph2S2; ii Srn12 27 M. Sato H. Hisamichi C. Kaneko N. Suzaki,T. Faruya and N. Inukai Tetrahedron Lett. 1989,30,5281. 28 J. W. Herndon and S. U. Turner Tetrahedron Lett. 1989,30 4771. 29 K. S. Feldman and R. E. Simpson Tetrahedron Lett. 1989 30 6985. 146 P. Quale 4 Cyclobutanes The chemistry of cyclobutanes has enjoyed a renaissance during the last year partly due to the quest for novel anti-viral agents. For example the di-acid (38) was converted in a one-pot procedure to the chloro-derivative (39). The acid (39) serves as a useful intermediate in the preparation of ‘surrogate’ n~cleosides.~~ Nternatively reaction of diethyl fumarate with the keten acetal (40) afforded the cyclobutane derivative (41) in 53% yield which again was transformed into a nucleoside analogue3 (42) (Scheme 13).I OH Reagents i SO,CI,/PhH 190-200 “C CO2Et Et02C OEt i_ bo+ CO,Et OEt I CO2Et (40) Conditions i ‘BuOH/A / 53% (41) HOW/’ (42) Scheme 13 has shown that photolysis of the chromium carbene complex (43), Heged~s~~ followed by aerial oxidation affords fair yields of the cyclobutanone (44).Further-more oxidation of the cyclobutanone (44)afforded the lactone (45) in moderate ’O G. A. Jacobs J. A. Tino and R. Zahler Tetrahedron Lett. 1989 30,6955. 31 W. A. Slusarchyk M. G. Young G. S. Bisacchi D. R. Hockstein and R. Zahler Tetrahedron Lett.1989,30 6453. 32 M. A. Sierra and L. S. Hegedus 1.Am. Chem. SOC.,1989 111 2335. Alicyclic Chemistry (44) 43% (45) 30% Reagents i hv/CH,CN; ii O2 Scheme 14 (30%) yield (Scheme 14). Cy~loaddition~~ of the amides (46) with the thioether (47) in the presence of a catalytic quantity of the chiral ligand (48) and TiC1 (0-iR) affords- the cyclobutanes (49) in high chemical (60-90%) and optical yields (>80% ee) (Scheme 15). This report represents the first example of a catalytic asymmetric cycloaddition reaction leading to a cyclobutane. (46) (49) SMe Reagents ==( (47) Ph f( OH)Ph2 (48) 90%; 93% e.e. SMe C(0H)PhZ Scheme 15 Unsaturated sugars have proven to be ideal substrates for achieving high levels of diastereoselection in [2 + 21-cycloaddition reactions with dichloroketen as illus- trated in Scheme 16 the sense of facial selectivity being determined by the nature of the substituent proximal to the vinyl ether moiety.34 Reagents i Cl,C=C=O; ii Zn/HOAc Scheme 16 33 Y.Hayashi and K. Narasaka Chern. Lett. 1989,793. 34 H. Redlich J. B. Lenfers and J. Kopf Angew. Chern. Ini. Ed. Engi. 1989 28 777. 148 P. Quale The synthesis of a range of cyclobutanones (50) has been disclosed by Pirr~ng~~ by way of a photolytic [2 3-21 cycloaddition strategy. Substrates such as (50) serve as useful intermediates as they undergo synthetically useful rearrangements upon phot~lysis,~~ (Scheme 17). An intramolecular [2 + 21-cycloaddition fragmentation strategy has been utilized in the synthesis of (-)-perhydrohistrionic~toxin~~ (51) (Scheme 18).H @Ow-!+ ( 1" ij ijj @+f (50) MeOzC Reagents i hvlacetone; ii MCPBA; iii MeONaIMeOH Scheme 17 I + 6kf 0 Ho J J (51) Reagents i hv 95% Scheme 18 Reaction of p-naphthols with ethylene at low temperature in the presence of aluminium chloride affords high yields of the corresponding cyclobutane derivative (52).38 3s M. C. Pirrung V. K. Chang and C. V. De Amicis J. Am. Chem. SOC 1989 111 5824. 36 C$ S. S. Rahrnan B. J. Wakefield S. M. Roberts and M. D. Dowle J. Clem. SOC.,Chem. Commum. 1989 303; 1696. 37 J. D. Winkler and P. M. Hershberger J. Am. Chem. SOC.,1989 111 4852. 38 M. Ue M. Kinugawa K. Kakiuchi Y. Tobe and Y. Odaira Tetrahedron Lett.1989 30,6193. Alicyclic Chemistry 149 Reagents i CZH4 AlC13 95% (52) A synthesis of (*)-1-fluorograndisol (54) has been accomplished from the cyclo- propane (53).39 5 Cyclopentanes The development of general strategies for the synthesis of 5-and 6-membered rings continues unabated. Motherwella has shown that the cyclopropene (55) undergoes an intramolecular cyclopentanullation reaction in the presence of Pd'. The homo- Diels- Alder reaction has received scant attention by synthetic chemists. However 5; i_ 40% MeOiC MeO& E (55) E = CO,Me E Reagents i Pdo Lautens4' has shown that certain nickel catalysts promote the cycloaddition reaction and thereby provide ready access to a number of polycyclic ring systems (Scheme 19).i!b+70Lto 62% (endo :ex0 = 2 :1) Reagents i Ph3P Et3AI Ni(acac)2 Scheme 19 39 S. Kanemoto M. Shimizu and H. Yoshioka J. Chem SOC.,Chem Commun. 1989,690. 40 S. A. Bapuji W. B. Motherwell and M. Shipman Tetrahedron Lett. 1989 30 7107. 41 M. Lautens and C. M. Crudden Tetrahedron Lett. 1989 30,4803; M. Lautens and L. G. Edwards Tetrahedron Lett. 1989 30 6613. 150 P. Quale The metallo-ene reactions continue to be actively investigated as a means of preparing highly functionalized polycyclic systems from acyclic precur~ors,~*~*~ (Scheme 20). I + E-gE I 0 AcO 74% 75% E:Z = 4:l 75% (1.3:1) Reagents i Pd(dba),/PPh,/HOAc/CO/MeOH/A; ii Pd(PPh,),/CH,CN/h Scheme 20 The Pa~son-Khand~~ reaction has been successfully utilized in the synthesis of furan-ether B.The reaction proceeded smoothly to afford a 2 1 mixture of exo-adducts which were processed into the title compound (56). 64% (2:1) I (56) Reagents (i) CH,CCH CO~(CO)~ CO PhH; reflux 44h 42 (a) W. Oppolzer T. H. Keller M. Bedoya-Zurita and C. Store Tetrahedron Lett. 1989 30 5883. (b) E-i. Negishi S. Iyer and C. J. Rousset Tetrahedron Lett 1989 30 291. M. E. Price and N. E. Schore Tetrahedron Lett. 1989 30,5865. 43 Alicyclic Chemistry Hernd~n~~ has demonstrated functionalized cyclopentanes may be prepared uia the reaction of ally1 stannanes with acyl iron complexes in the presence of aluminium trichloride (Scheme 2 1). SnBu3 Reagents i AlCl, r.t.; ii NBS/BnOH; iii Br,; iv NH,/MCPBA Scheme 21 OTBDMS OTBDMS 67% (4.2 1) Reagent i ‘TMM’-Pd Scheme 22 Trost has published a number of papers concerning additional applications of the TMM approach to cy~lopentanes,~~~~~ (e.g.Scheme 22). Dotz4’ has shown that upon reaction of the chromium carbene complex (57) with phenyl acetylene in refluxing di-n-butyl ether the indene complex (58) is produced in 45% yield as a single diastereoisomer with the phenyl moiety cis to the bulky chromium tricarbonyl moiety which is complexed to the aromatic portion of the indanone (Scheme 23). A number of reports have appeared concerning the cyclization of ene-ynes di-ynes and w-unsaturated imines (Scheme 24). 44 J. W. Herndon and C.Wu Tetrahedron Lett. 1989 30 6461. 45 B. M. Trost S. A. King and T. Schmidt J. Am. Chem. SOC.,1989 111 5902. 46 B. M. Trost and M. Acemoglu Tetrahedron Lett. 1989 30 1495. 47 K. H. Dotz H. G. Erben and K. Harms J. Chem. SOC.,Chem. Commun. 1989 692. 152 P. Quale Reagents i PhCCH Bu20 A Scheme 23 50% Reagents i ZrCp,; ii CO \ Br88% (~97% frans) Br 78% (>99% cis) Reagents i Cp,Zr BuLi; ii Br2; iii Cp*ZrCI -0' (Ref.50) 53% Reagents i Cp,Zr/n-BuLi; ii CO; iii I2 NHNMe -(Ref. 51) R qNNMe2 CL 71% R Reagents i Cp2Zr( Bu"Li) Scheme 24 48 E-i. Negishi P. J. Holmes J. M. Tour J. A. Miller F. E. Cederbaum D. S. Swanson and T. A. Takahashi J. Am. Chem. Soc. 1989 111 3336. 49 W.A. Nugent and D. F. Taber J. Am. Chem. Soc. 1989 111 6435. 50 C. J. Rousset D. R. Swanson F. Lamatay and E.4. Negishi Tetrahedron Lett. 1989. 30,5105. 51 M. Jenson and T. Livinghouse 1.Am. Chem. Soc. 1989 111 4495. Alicyclic Chemistry Tandem intramolecular 'Heck'-vinylation reactions prove to be highly effective for the construction of fused ring (Scheme 25). In a related reaction,54 treatment of the vinyl lithium (58) with MeZrCp2C1 afforded the zirconium complex (59) which upon reaction with the protected unsaturated alcohol (60) afforded the bicyclic ketone (61) as the sole product in 47% isolated yield (Scheme 26). Reagents i Pdo PhZnCl R = CO,Et 91% I (2:E= 8:l) R' Reagents i P~(OAC)~/P~~P, NaCH(CN)2 Scheme 25 +i -ZrCp 47% % (58) (59) OTBDMS (61) Reagents i MeZrCpzC1/PR3; ii CO (60) OTBDMS Scheme 26 Thermoly~is~~ of the w-acetylenic chromium carbene complexes (62) in the pres- ence of a suitable acetylene affords reasonable yields of the functionalized cyclopen- tenones (63) (Scheme 27).Clearly a reaction of some synthetic potential. Iron complexes56 of the type (64) undergo C-H insertion reactions upon reaction with Meerwein's reagent at ambient temperature. In certain cases high stereoselec- tivity is exhibited in such processes (Scheme 28). The intramolecular cis-carbolithiation of acetylenes and alkenes has been investi- gated in some detail by Bailey.57 For example reaction of the iodide (65) with Bu'Li 52 B. Bums R. Grigg V. Sridharan P. Stevenson S.Sukirthalingam and T.Worakun Tetrahedron Lett. 1989,30 1135. 53 R. Grigg and V. Sridharan Tetrahedron Lett. 1989.30 1139. 54 S. L. Buchwald R. T. Lum,R. A. Fisher and W. A. Davis J. Am. Chem. SOC.,1989. 111 9112. 55 Y.-C. Xu,C. A. Challener V. Dragisich T. A. Brandvold G. A. Peterson W. D. Wulff and P. G. Williard J. Am. Chem. SOC 1989 111 7269. 56 S.-K. Zhao C. Knors and P. Helquist J. Am. Chem. Soc. 1989 111 8527. 57 W. F. Bailey and K. Rossi J. Am.Chem. SOC.,1989 111 765; W. F. Bailey T. V. Ovaska and T. K. Leipert Tetrahedron Lett. 1989 30 3901. 154 P. Quale OMe (62) ca. 40% n = 1,2 Reagents i PhH A R'CCR' Scheme 27 O Fe(CO)2CP r Reagents i Me,OBF, CH,Cl, 0°C Scheme 28 rI- 1 Li 84% & Ai ii iv E (69) E = H SiMe, CO,H 60-80% Reagents i Bu'Li -78 "C; ii TMEDA -78 "C to r.t.; iii MeOH; iv E+ Scheme 29 at low temperature affords the lithio compound (66) which undergoes a tandem cyclization process to afford the spirocycle (67) in high yields (84%) (Scheme 29).Similarly,57 reaction of the iodide (68) with Bu'Li followed by a suitable electrophile (e.g. COz)affords good yield of the tricycles (69). Reactions performed on acetylenic iodides afford the corresponding exocyclic alkenes in good yield (8O%) (Scheme 30) with a high degree of stereochemical control.57 Alicyclic Chemistry CIR -mR E 80% Reagents i Bu'Li -78 "C; ii E+ Scheme 30 The synthesis of prostaglandins and related substances remains an area of intense interest.For example,58reaction of the diol (70) and the vinyl iodide (71) with a catalytic quantity of a Pdo catalyst (prepared in situ) provides a particularly concise approach to cyclopentanones of the type (72) (Scheme 31).Alternati~ely,~~ coupling of the vinyl iodide (73) with the stannane (74) proceeds smoothly to afford the prostanoid (75) with retention of stereochemistry about the olefinic side chain (Scheme 32). OH 0 HO (70) OTBDMS (72) 70% Scheme 31 (CH2)6C02Et (CH2)6CO?Et I I (73) OTBDMS (75) 75% Reagents trans-Bn(Cl)(Ph,P),Pd BuoSn 7 OTBDMS (74) Scheme 32 Radical cyclizations have been extensively used to prepare cyclopentanes a few examples are given in Figure l.6069 A significant advance has been the realization that heavily functionalized acyclic substrates derived from sugars can be cyclized under radical conditions to afford 58 R.C. Larock F. Kondo K. Narayanan L. K. Sydnes and M.-F. H. Hsu Tetrahedron Lett. 1989,30,5737. 59 J. K. Stille and M. P. Sweat Tetrahedron Lett. 1989 30 3645. 60 Y. Taura M.Tanaka K. Funakoshi and K. Sakai Tetrahedron Lett. 1989 30 6349. 61 H. Hemmerle and H.-J. Gais Angew. Chem. Znt. Ed. EngL 1989 28 349. 62 E. J. Enholm and G. Prasad Tetrahedron Lett. 1989,30 4939. 63 V. Yadav and A. G. Fallis Tetrahedron Lett. 1989 30 3283. 64 E. Lee C.-U. Hur and J.-H. Park Tetrahedron Letf. 1989 30 7219. 156 P. Quale (Ref. 60) 85% (cis :trans = 6 1) Reagents i TsCI (PhCO)20 PhH reflux TBDMSO TBDMSO s *I \ c!,' I Bu,SnH/AIBN/PhH reflux (Ref.61) Q Ow0 OW0 C02Me BU3SnH/AIBN/PhH 'O-b ,,+, %(Ref. 62) C02Me 81% HO Bu,SnH/NBN/PhH reflux 3+2 Q4-OH (Ref.63) 0 74% 0 i Bu,SnH/AIBN/PhH; ii H,O+ .g (Ref. 64) Pr' 80% (Ref. 65) Ph,S,/ NBN/ PhH/ hv & A-B (Ref. 66) ' R' R2 Trans-isomers major product Figure 1 Examples of cyclopentanes prepared by radical cyclization 65 A. P. Neary and P. J. Parsons J. Chem SOC.,Chem. Commun. 1989 1090. 66 K. S. Feldman R. E. Ruckle and A. L. Romanelli Tetrahedron Lett. 1989 30,5845. Alicyclic Chemistry (Ref. 67) 31% 40% CO2Me Sm12.THF/MeOH/-78"C ' [Ref. 69( a)] W""' 87% (>250 1) /v 60-70% (1,2-cis :trans >20 :1) Figure 1-continued D-(-)-Arabinose 30'' i Sml,/THF/MeOH/-78 "C 69% Bu,SnH/AIBN/PhH reflux+ ph-(IgR OV0 OBn tI 1,5-trans :cis =77 :23 Ph 32% Scheme 33 67 V.Reutrakul C. Poolsanong and M. Pohmakotr Tetrahedron Lett. 1989 30,6913. 68 T. Uruma S. Iwasa S. Kohmoto and K. Yamada J. Chem. Soc. Chem. Commun. 1989 1265. 69 (a) E. J. Enholm and A. Trivellas Tetrahedron Lett. 1989,30 1063; (b)G. A. Molander and C. Kenny J. Am. Chem. Soc. 1989 111 8236. 158 P. Quale functionalized cyclopentanes with a high degree of stereochemical control,70971 (Scheme 33). Alternative methods of 5-membered ring synthesis included intramolecular epoxide ring opening with an ally1 silane7* (Scheme 34) and tandem Michael addition reactions to a,P-unsaturated e~ter~~'~' (Schemes 35 and 36).OH +OH H -7 TMS 82% (trans cis) = 4 1 Reagents i SnCl2/CH2C1, -90 "C Scheme 34 qC02Et. YO2Et + TO2" CO2Et CO2Et c02et 26~7464% Reagents i LiN(Bn)TMS; ii Me1 Scheme 35 c02et TBDMSO \ C02Et . TBDMSO COzEt + 6-TBDMSO'cC02Et TBDMSO' R e.g. R = Me,92%(>99%d.e.) Reagents i RMgBr/CuI Scheme 36 Intramolecular acylation of the vinyl carbanion (76)" afforded the cyclopentenone (77) in moderate yield (50%) (Scheme 37). has demonstrated that intramolecular nitrone cycloaddition reactions can proceed with excellent diastereofacial selectivity affording functionalized cyclopentanes in high yield (Scheme 38). Ti~s~~ has developed a novel cationic cyclopentannulation procedure as exemp- lified in the recent synthesis of (*)-xanthocidin [Scheme 39(a)].70 E. J. Enholm and A. Trivellas J. Am. Chem. SOC.,1989 111 6463. 71 T. V. RajanBabu T. Fukunaga and G. S. Reddy J. Am. Chem. SOC.,1989 111 1759. 72 S. Hatakeyoma K. Osani H. Numata and S. Takano Tetrahedron Lett. 1989 30 4845. 73 T.Uyehara N. Shida and Y. Yamamoto J. Chem. SOC.,Chem. Commun. 1989 113. 74 S. Saito Y. Hirohara 0. Narahara and T. Moriwake J. Am. Chem. SOC.,1989 111 4533. '' M. T. Crimrnins and J. B. Thomas Tetrahedron Lett 1989 30 5997. 76 T. K. M. Shing D. A. Elsley and J. G. Gillhouley 1.Chem. SOC.,Chem. Commun. 1989 1280. 77 M.A. Tius and D. P. Astrab Tetrahedron Lett. 1989 30 2333. Alicyclic Chemistry OMOM (76) OMOM (77) 50% Reagents i LDA/THF/-78 "C Scheme 37 O"0 \ 94% Scheme 38 I1 Ph C02H A Ph Ph 72% Reagents i 2,6-lutidine/TFAA -10 to 0 "C Scheme 39(a) Meyers" has developed a particularly effective protocol for the synthesis of homochiral cyclopentenones from the lactam (78) as exemplified in [Scheme 39(b)].A~ymmetric'~ deprotonation of the meso-ketone (79) with a chiral base and subsequent trapping with TMSCl afforded the enol ether (80) in 94% enantiomeric excess (Scheme 40). 78 A. I. Meyers and C. A. Busacca Tetrahedron Lerr. 1989 30,6977. 79 H. Izawa R. Shirai H. Kowasaki H.-d. Kim,and K. Koga Tetrahedron Lett. 1989 30,7221. 160 I? Quale (78) O 0 0 Reagents i ,ZnBr / Y Scheme 39(b) n n E+ I,.I1 .. -H EH -H@E v OTMS 0 (80) 93% 94% ee (1S,5 R) Reagents i MeN' Ph; ii TMSCI NLi But Scheme 40 NC OTBDMS -i +TBDMs (81) 96% ee 'C N (82) 74% Reagents i LHMDS/THF/-78 "C Scheme 41 Finally,80 the functionalized cyclopentane (82) was obtained in good yield from the homochiral epoxy-nitrile (81) upon exposure to LHMDS (Scheme 41). 6 Cyclohexanes The stereocontrolled functionalization of polyhydroxylated cyclohexanes has been the subject of intense interest due to the pharmacological properties of myo-inositol phosphates. This area of chemistry has been comprehensively reviewed.81 A number of reports concerning the preparation/reactivity of novel dienes/dienophiles have appeared a selection of which are included in Figure 2 (references 82-1 02).S. G. Levin and M. P. Bonner Tetrahedron Lett. 1986 30,4567. " D. C. Billington Chem. SOC.Rev. 1989 18 83. Alicyclic Chemistry \ (Ref. 82) 4-L so (Ref. 86) OR 6 (Ref. 89) (Ref. 92) PhSOz (Ref. 83) II A TMS SOPh (Ref. 90) P SePh 1R (Ref. 85) (Ref. 84) SMe (Ref. 91) 0 (Ref. 93) 0 (Ref. 94) Figure 2 Novel dienes and dienophiles 82 C. W. Bird and A. Lewis Tetrahedron Lett. 1989 30 6227. 83 J. E. Backvall and F. Rise Tetrahedron Lett. 1989 30 5347. 84 J. P. Konopelski and M. A. Boehler J. Am Chem. SOC.,1989 111 4515. M. Ishida T. Aoyama and S. Kato Chem. Lett. 1989 663. 86 A. M. Naperstkow J. B.Macauly R. J. Newlands and A. G. Fallis Tetrahedron Lett. 1989 30 5077. ” J. R. Bull and K. Bishofberger J. Chem. Soc. Chem. Commun.,1989 1405. Y. Haazawa M. Suzuki and Y. Kobayashi Tetrahedron Lett. 1989 30 571. 89 F. Kiengle J. Stadweiser and I. Mergelslberg Helv. Chim Actu 1989 72 348. 90 R. V. Williams and X. Liu J. Chem SOC.,Chem Commun. 1989 1872. 91 J.-L. Boucher and L.Stella J. Chem. SOC,Chem Commun. 1989 187. 92 M,. Sato C. Oris J.4. Sakaki and C. Kaneko J. Chem SOC.,Chem. Commun. 1989 1435. 93 P.G. McDougal J. M. Jump C. Rojas and J. G. Rico Tetrahedron Lett. 1989 30,3897. 94 M. C. Carreno J. L. G. Ruano and A. Urbano Tetrahedron Lett. 1989 30,4003. 95 A. Schoning and W. Friedrichsel Chem. Ber. 1989 122 1119. 96 J. Matlay J. Mertes and G.Maer Chem. Ber. 1989 112 327. 97 J. Lee and J. K. Snyder J. Am. Chem. SOC,1989 111 1522. 162 P. Quale 0 (Ref. 96) (Ref. 97) PhSOz \ TQCOzMe (Ref. 99) (Ref. 98) (Ref. 100) 0 QqPh 0 0 (Ref. 101) (Ref. 102) Figure >continued Wenderlo3 has shown that Diels- Alder reactions occur readily with unactivated substrates when suitable transition metal catalysts are added (Scheme 42). A number of catalysts have been developed which enable asymmetric Diels- Alder reactions to be carried out with good enantiomeric excess (Scheme 43). Gassmanlo6 has reported that orthoesters undergo 'ionic' Diels- Alder reactions under mild conditions (Scheme 44). y0TBDMS @OTBDMS TMS TMS 98% Reagents i Ni(COD) (10 mol YO),r.t.Scheme 42 98 A. H. Davidson and B. A. Maloney J. Chem. SOC.,Chem. Commun. 1989 445. 99 P. M. Fresneda and M. Vaultier Tetrahedron Lett. 1989 30 2929. 100 K. A. Parker and S. M. Ruder J. Am. Chem. SOC.,1989 111 5948. lo' A. I. Meyers and C. A. Busacca Tetrahedron Lett. 1989 30 6973. 102 A. Waldner Tetrahedron Lett. 1989 30 3061. 103 P. A. Wender and T. E. Jenkins J. Am. Chem. SOC.,1989 111 6432. 104 K. Narasaku N. Iwasawa M. Inoue T. Yamada M. Nakashima and T. Sugimori J. Am. Chem. SOC. 1989 111 5340. 105 E. J. Corey R. Imwinkelreid S. Pikul and Y. B. Xiang J. Am. Chem. SOC.,1989 111 5493. '06 P. G. Gassman and S. P. Chava J. Chem. SOC.,Chem. Commun. 1989 837. Alicyclic Chemistry 00 C02Me (Ref.104) a *CONR2 85% ee Ph Ph Reagents i 3PhH; r.t.; ii cat. Ph Ph CONR2 92% 91%ee cat. = CF3S02N ,NS02CF3 A1 I Me Scheme 43 CO2H 74% Reagents i BF3.0Et2; ii HCl/H20 -72" to 0 "C Scheme 44 S~therland''~has utilized an electrocyclic ring closure reaction to afford highly functionalized systems possessing structural similarities to the quassinoids (Scheme 45). The Diels-Alder reaction is an immensely powerful reaction and there is little wonder that a number of groups have used this basic strategy in approaches to forskolin."* Reagents i Mukaiyama's reagent CH2Cl, Et,N r.t. 72% Scheme 45 L. Larsen and J. K. Sutherland J. Chem. Soc. Chem. Commun. 1989 784. e.g. B. M. Trost and R. Holcomb Tetrahedron Lett. 1989 30 7157; E.J. Corey and P. Da Silva Jardine Tetrahedron Lett. 1989 30 7297; K. Kanematsu and S. Nagashima J. Chem. SOC.,Chem. Commun. 1989 1028. 164 I? Quale The IMDA reaction of furan as a potential route to polyoxygenated systems is usually hampered by the reversible nature of this reaction. However Keay"' has investigated the subtle effects of substituents on the course of this reaction and demonstrated that under mild conditions and correct substitution pattern the reaction can be of some synthetic utility (Scheme 46). 0 c 1 Reagents i Florid CH2C12 Scheme 46 The IMDA reaction has been used successfully to construct the tricycles (83) and (84) which serve as model compounds for the synthesis of the manzarnines1lo and quassinoids"' respectively (Scheme 47).Scheme 47 The use of a novel homochiral catalyst in an asymmetric IMDA reaction leading to the isolation of the bicycle (85) in 92% enantiomeric excess (84% yield) has been disclosed,"2 (Scheme 48). A paper detailing the synthetic utility of cation-radical promoted Diels-Alder reactions has also a~peared."~ Carle~s"~ has illustrated the utility of the diol (86) in the synthesis of inositol derivatives (Scheme 49). 109 B. A. Keay and P. W. Dibble Tetrahedron Lett. 1989,30 1045; C. Rogers and B. A. Keay Tetrahedron Lett. 1989 30 1345. 110 K. M. J. Brands and V. K. Pandit Tetrahedron Lett. 1989 30 1423. 111 T. K. M. Shing Y. Tang and J. F. Malone J. Chem. SOC.,Chem. Commun. 1989 1194. 112 K. Furuta A.Kanematsu H. Yamamoto and S. Takaoda Tetrahedron Lett. 1989 30,7231. 113 B. Harirchian and N. L. Bauld J. Am. Chem. SOC.,1989 111 1826. H. A. J. Carless and 0. Z. Oak Tetrahedron Lett. 1989 30 1719. Alicyclic Chemistry (85) 84% 92%ee (99 :1 endo :exo) Reagents i 10 mol. % cat. CH2C12 -40 "C cat. = Scheme 48 aoH ?H + + i ii aoH CH ' OH OH I OH I Reagents i loz;ii Thiourea Major product OH Scheme 49 (+)-Albicanol Scheme 50 A synthesis of (+)-albicanol demonstrates the potential for stereochemical control in intramolecular nitrile oxide cycloaddition reactions,' Is (Scheme 50). Radical cyclizations have also been used to good effect to prepare functionalized cyclohexanes. For example,'16 the sugar derivative (87) underwent cyclization to the carbocycle (88) in moderate yield (50%).Crich"' has prepared the ketone (go) an intermediate for the synthesis of vitamin D3 uia cyclization of the acyl radical (89) (Scheme 51). Chirality transfer by way of pericyclic processes have been used extensively. Hence,' l8 the functionalized cyclohexane (92) a component of FK506 was prepared via an Ireland-Claisen rearrangement of the lactone (91). An example' l9 of remote asymmetric induction is nicely exemplified by orthoester- Claisen rearrangement of the alcohol (93) to the ester (94) (Scheme 52). 115 K. Shishido Y. Tokunaga N. Omachi K. Hiroya K. Fukumoto and T. Kametani J. Chem. Soc. Chem Cornmun.,1989 1093. 116 B-W. A. Yeung J. L. M. Conlettes and B.Fraser-Reid J. Chem. Soc. Chem Commun. 1989 1160. 117 D. Batty D. Crich and S. M. Fortt J. Chem. Soc. Chem. Commun. 1989 1366. 118 S. L. Schreiber and D. B. Smith J. Org. Chem. 1989 54 9. 119 P. M. Wovkalich P. C. Tang N. C. Chadha A. D. Batcho J. C. Barrish and M. R. Uskokovic J. Am. Chem. Soc. 1989 111 2596. 166 P. Quale OR OR 0 I PhS SePh --PhS RO Reagents i Bu,SnH/AIBN/PhH reflux (90) 91% Scheme 51 Ho2cuoM 0qMe-(91) (92) Scheme 52 Pearson12' has prepared a number of functionalized cyclohexanones effectively utilizing the stereodirecting effect of the .rr-allyl-Mo(C02)Cp moiety (Scheme 53). In a similar manner,'21 the use of a sterically demanding but readily released TMS group has been utilized in the synthesis of homochiral cyclohexenones (Scheme 54).gSPh OH Nu- Scheme 53 A. J. Pearson and R. Motezaei Tetrahedron Lett. 1989 30 5049. M. Asaoka T. Aida S. Sonada and H. Takei Tetrahedron Lett. 1989 30 7075. Alicyclic Chemistry TMS' R2 Scheme 54 In an extension of earlier work Frater'22 has shown that alkylation of the dianion (95),derived from readily available P-hydroxy esters (in optically pure form) affords diastereomerically pure products (961 (Scheme 55). Reagents i 2 x LDA; THF;-78 "C;ii E+ Scheme 55 7 Cycloheptanes A novel [4 + 31 cycloaddition reaction has been disclosed'23 enabling the facile preparation of functionalized cycloheptanes (97) (Scheme 56). (97) 70% Reagents i [(PriO),P],Pdo (cat.) PhH reflux AcO &TMS Scheme 56 Lewis acid promoted reaction of the Chan diene (98) with p-dicarbonyl com- pounds afforded the [3 + 41 adducts in good overall yield,'24 (Scheme 57).12' G. Frater W. Gunther and U. Miller Helu. Chirn. Acfa 1989 72 1846. 123 B. M. Trost and S. Schneider Angew. Chem. Inf. Ed. Engl. 1989 28 213. 124 G. A. Molander and S. W. Andrews Tetrahedron Lett. 1989 30,2331. 168 P. Quale 0 TMSO OMe + R 1 y A &-R C02Me -oms R Rl-0 (98) 7680% Reagents i TiCL, -78 "C (R R' = various) Scheme 57 The synthesis of hydrazulenes has been achieved by rearrangement of either the cyclopropyl ~arbinols'~~ (99) or via an oxy-Cope rearrangement'26 of the 1,5-dienes (100). In the latter case the trans-[6.4.0] system was isolated upon treatment with base (Scheme 58).d q H (99) Ii @ (32 H R 8690% 80% Reagents i NaH/THF; ii 210°C; iii NaOH Scheme 58 8 Cyclooctanes B~eckman'~~ has reported that cyclooctanes may be prepared via a methoxide induced Grob fragmentation of a bicyclo-[3.3.1] system (Scheme 59). Alterna-tively,12* an intramolecular Barbier coupling reaction of the iodo-aldehyde (101) afforded the cyclooctane (102) in good yield as a single diastereoisomer (Scheme 60). Reagents i NaOMe/MeOH [R= (CH2)2C02Me] 73% Scheme 59 125 V. Reydellet and P. Helquist. Tetrahedron Lett. 1989 30,6837. 126 M. Sworin and K.-C. Lin .L Am. Chem. Soc. 1989 111 1815. 127 R. K. Boeckman A. Arvantis and M. E. Voss J. Am. Chem. Soc. 1989 111 2737.128 M. Rowley M. Tsukamoto and Y.Kishi J. Am. Chem. Soc. 1989 111 2735. Alicyclic Chemistry ?Ho R - I 73% PhzBu'SiO (101) Reagents i CrCIJ NiCI Scheme 60 9 Larger Ring Systems A few reports have detailed the preparation of medium-sized ring systems via organometallic and radical ring closure methodologie~.'~~ A notable example is the synthesis of an analogue of Neocarzinostatin via an intramolecular palladium coupling rea~tion,'~' (Scheme 61). 72% Reagents i Pd(Ph,P), THF reflux Scheme 61 10 Natural Products A number of outstanding contributions have appeared this year including the total synthesis of (*)-~eroplastol,'~~ (+)-ophiobotin,'28 and sarcophytol B,13' phorb01,'~~ (*)-pleur~mutilin.'~~ The synthesis of model compounds related to the unusual calicheamicin/esperamicin family of antibiotics continues at a high level of interest.'34 129 J.E. McMurray and J. G. Rico Tetrahedron Lett. 1989 30 1169; J. E. McMurray Chem Rev. 1989 89 1513; N. A. Porter B. Lacher V. K.-T. Chang and D. R. Magnin J. Am. Chem SOC.,1989 111 8309; B. M. Trost S. Matsubara and J. J. Caringi J.-Am. Chem. Soc. 1989 111 8745; N. J. G. Cox G. Pattenden and S. D. Mills Tetrnhedron Lett. 1989 30,621. 130 M. Hirama K. Fujiwara K. Shigematu and Y. Fukazawa J. Am. Chem SOC.,1989 111,4120. 131 J. E. McMurray J. G. Rico and Y-n. Shish Tetrahedron Lett. 1989 30 1173. 132 P. A. Wender H.Y. Lee R. S. Wilhelm and P. P. Willcom J. Am. Chem. SOC.,1989 111 8954. 133 R.K. Boeckman D. M. Springer and T. R. Alessi J. Am. Chem. SOC. 1989 111 8284. 134 cf J. N. Haseltine S. J. Danishefskey and G. Schulte J. Am. Chem SOC.,1989 111 7838.

ISSN:0069-3030    

DOI:10.1039/OC9898600137

出版商:RSC    

年代:1989

数据来源: RSC