ISSN:0069-3030    

DOI:10.1039/OC98885FX001

出版商:RSC    

年代:1988

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC98885BX003

出版商:RSC    

年代:1988

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (ii) Computer Graphics (Computer Aids to 0rga n ic C h em istry) By D. E. JACKSON Department of Pharmaceutical Sciences University of Nottingham Nottingham NG7 2RD 1 Introduction The explosive growth in computer technology over the past decade which allows modern computer systems to communicate rapidly over long distances to handle and store large amounts of information and to carry out calculations with ever increasing speed has revolutionized data acquisition and management procedures. A prerequisite of any system which is to be of benefit to users other than the computer specialist is an easy-to-use (user-friendly) interface between operator and machine. As the graphical capabilities of hardware systems continue to develop coupled with the chemist’s traditional use of pictorial representations to describe molecules there has been an increasing use of computer graphics to provide just such an interface for applications in chemistry.Graphically orientated programs are now used for various tasks from the storage and retrieval of information through to the display of molecular properties derived from the more traditional computa- tional chemistry packages. Evolving from these traditional computational techniques are new molecular simulation methodologies for the investigation and representation of molecular behaviour which are at least beginning to address the long-standing questions of molecular recognition and co-operative molecular actions. The increasing importance of these computational and graphical techniques has been reflected in both the formation of a Molecular Graphics Society and the introduction of specialist journals including the Journal of Molecular Graphics and more recently the Journal ofcomputer-Aided Molecular Design.A further recognition of their growing importance to the organic chemist is the inclusion of ‘computer graphics’ in Annual Reports for the first time. However the rather diverse nature of the topic does mean that an initial Report of this nature must be somewhat selective in the areas covered and cannot be regarded as a comphrehensive survey of the literature. What this Report will endeavour to do given those provisos is give the organic chemist who is not a specialist in this area an indication of recent developments in graphically orientated applications and highlight the areas in which such techniques may contribute.Selected references from earlier work will be quoted where relevant. 17 D. E. Jackson 2 Molecular Modelling Drug Design.-The steadily increasing interest in computer-aided molecular modelling (CAMM) over the past several years has been due in the main to the application of such techniques in the area of drug design. In response to the consequent upsurge in reported applications involving CAMM the Provisional Section Committee on Medicinal Chemistry of IUPAC' is currently publishing a survey on the availability of both hardware and software appropriate for CAMM together with guidelines on the standards to be adopted for publications reporting computer modelling in medicinal chemistry.2 This latter step more than any other probably represents the 'coming of age' of CAMM as an investigative tool in drug development.A cautionary note may be appropriate here however as a recent perspective by Dearing3 on the development of CAMM as an everyday tool for the non-expert has highlighted the problem that many of the methodologies may not yet be sufficiently well developed and robust that they can be applied without error by those who may not be experts in the field. Several articles and reviews covering the techniques and methodologies4 involving computer graphics and computational chemistry which can be applied to the study of molecular recognition' and drug action6 have appeared.A recent article by Marshall7 on computer-aided drug design divided the approaches into those where the active site of the drug is known those where it can be constructed by homology with known structures or predicted from the known amino acid sequence and finally those where the active site must be inferred from a comparison of properties seen in a series of ligands. Many such examples of computer-aided contributions to molecular recognition and drug design involving known active sites,8 predicted active sites and ligand comparisons" have been reported over the past year. The identification of quantitative structure-activity relationships (QSAR) in a series of compounds has long been an important computational tool for the develop- ment and optimization of biologically active materials.In recent years the incorpor- ation of three- and four-dimensional numerical data into QSAR studies has resulted from the introduction of graphical techniques in QSAR A new ' J. G. Topliss J. Med. Chem. 1988 31 2229. P. Gund D. C. Barry J. M. Blaney and N. C. Cohen J. Med. Chem. 1988 31 2230. A. Dearing J. Cornput.-Aided Mol. Design 1988 2 179. (a) 'Topics in Pharmacology Vol. 3' ed. A. S. V. Burgen G. C. K. Roberts and M. S. Tute Elsevier Amsterdam 1986; (6) A. E. Howard and P. A. Kollman J. Med. Chem. 1988,31 1669; (c) W. F. van Gunsteren Protein Engineering 1988 2 5. P. Zielenkiewicz and A. Rabczenko Biophys. Chem. 1988 29 219. (a) P. J. Goodford J. Med. Chem. 1984 27 557; (6) J.G. Vinter Chem. Brit. 1985 21 33; (c) C. H. Hassall ibid. 1985 21 39; (d) A. Krohn in 'Second SCI-RSC Medicinal Chemistry Symposium' ed. J. C. Emmett Royal Society of Chemistry London 1984 p. 109; (e) A. J. Hopfinger J. Med. Chem 1985,28 1133; (g) W. Ripka New Scientist 1988 54. ' G. R. Marshall Annu. Rev. Pharmacol. Toxicol. 1987 27 193. (a) H.A. Schreuder W. G. J. Hol and J. Drenth J. Biol. Chem. 1988 263 3131; (b) S. Neidle L. H. Pearl P. Herzyk and H. M. Berman Nucleic Acids Res. 1988 16 8999; (c) .C. Mukhopadhyay and V. S. R. Rao Znt. J. Biol. Macromol. 1988 10 217. (a)M.-J. Santoni C. Goridis and J. C. Fontecilla-Camps J. Neuroscience Res. 1988,20 304; (b)W. V. Williams H. R. Guy D. H. Rubin F.Robey J. N. Meyers T. Kieber-Emmons D.B. Weiner and M. 1. Greene Proc. Nutl. Acad. Sci. USA 1988 85 6488. (a) B. V. Cheney J. Med. Chem. 1988 31 521; (b) D. Mayer C. B. Naylor I. Motoc and G. R. Marshall J. Cornput.-Aided Mol. Design 1987 1 3. " A. K. Ghose and G. M. Crippen J. Med. Chem. 1985 28 333. Physical Methods and Techniques -Part (ii) Computer Graphics 19 approach using the technique of comparative molecular field analysis (CoMFA) has been described recently.12 This involves sampling steric and electrostatic fields surrounding a set of ligands in a similar manner to the probe interaction grids described earlier by G~odford,’~ and using molecular field comparisons to quantify structure and biological activity. A related microcomputer-based technique involving the generation of a hypothetical active site lattice (HASL) has been described recently by D0~eyko.l~ In this approach four-dimensional molecular lattices derived from Cartesian co-ordinates and a physicochemical descriptor such as hydrophobic- ity or electron density are used for the quantitative comparison of molecules.The merging of information from selected structures gives a composite lattice of points (the HASL) which may reflect the shape and binding properties of an active site. Molecular Mechanics.-At the foundation of any molecular modelling package is a procedure for the calculation of molecular energies. Currently only those tech- niques involving the use of molecular mechanics offer a sufficiently quick method to satisfy the requirements of the interactive molecular modeller.In principle molecular mechanics assumes that the energy of a system can be described by the sum of the energies of various mechanical (stretching bending torsional and van der Waals) and electrical terms such that Etotal = Estr + Ebend + Etor + EvdW + Ecoulombic (1) The exact mathematical nature of the individual terms together with the parameteriz- ation of the atom types constitutes the ‘force field’.’’ At present no force field exists which is capable of dealing with all atom combinations; therefore careful consider- ation must be given as to the accuracy of a given force field for a given situation. Clearly the development of accurate forms of the potential energy function to simulate wide-ranging molecular behaviour is crucial to the advancement of modelling techniques.To this end the Biosym Consortium has pooled academic and industrial resources for the development of more accurate force field parameters. As part of this research effort Hagler has recently described a method for determining force constants and optimal forms of the energy function for small molecules by the use of ab initio molecular energy surfaces.16 At present there are several commonly used force fields which have been described in the literature. These include CHARMM,17 MM218 and more recently MM3,19 AMBER,20 and the Consistent Valence Force Field (CVFF) used in Discover.21 The I* R. D. Cramer 111 D. E. Patterson and J. D. Bunce J. Am. Chem. Soc. 1988 110 5959. l3 P. J. Goodford J. Med. Chem.1985 28 849. 14 A. M. Doweyko. 1. Med. Chem. 1988 31. 1396. l5 (a) ‘Molecular Mechanics’ ACS Monograph Series 177 ed. U. Burkett and N. L. Allinger American Chemical Society Washington DC 1982; (6) D. B. Boyd and K. B. Lipkowitz J. Chem. Educ. 1982 59. 269. 16 J. R. Maple U. Dinur and A. T. Hagler Proc. Natl. Acad. Sci. USA 1988 85 5350. (a) B. R. Brooks R. E. Bruccoleri B. D. Olafson D. J. States S. Swaminathan and M. Karplus J. Comput. Chem. 1983 4 187; (6) L. Nilsson and M. Karplus ibid. 1986 7 591. la J. T. Sprague J. C. Tai Y. Yuh and N. L. Allinger J. Comput. Chem. 1987 8 581. 19 N. L. Allinger and J. H. Lii J. Compur. Chem. 1987 8 1146. 20 (a) S. J. Weiner P. A. Kollman D. A. Case U. C. Singh C. Ghio G. Alagona S.Profeta and P. Weiner J. Am. Chem Soc. 1984 106 765; (6) S. J. Weiner P. A. Kollman D. T. Nguyen and D. A. Case J. Compur. Chem. 1986 7 230. 21 (a) A. T. Hagler P. Dauber and S. Lifson J. Am. Chem. SOC 1983 101 5131; (6) ‘Discover Users Manual V2.4’ Biosym Technologies Inc. 10065 Barnes Canyon Rd Suite A San Diego CA 92121. 20 D. E. Jackson force field used in the COSMIC molecular modelling package has recently been described.22 A modification to the parameter set of CHARMM has been reported23 for the simulation of carbohydrate pyranose rings and its performance compared with the most developed carbohydrate potential energy surface PEF 422.24 The OPLS (optimized potentials for liquid simulations) potential function for proteins in which inter- and intramolecular non-bonded interactions expressed through coulombic and Lennard-Jones terms for peptide residues has been described.25 When combined with the bond stretch angle bend; and torsional terms from AMBER the AMBER/OPLS force field appears to be more accurate than AMBER alone in crystal simulations of cyclic peptides and the protein crambin although further validation in non-crystalline environments is necessary.One of the difficulties in molecular mechanics is its application to systems containing delocalized electrons; this is because of the need to determine a specific parameter set for each delocalized bond in the system. A method developed by Allinger uses an SCF calculation on the 7-electron system to determine bond orders of the conjugated system.From the relationship between bond orders and force field parameters it is possible to deduce parameters for specific bonds as they occur. Such techniques for dealing with conjugated hydrocarbons and ketones have been included in MM2( 82) with an extension to include conjugated nitrogen heterocycles in MM2(85),26 although limitations with the latter application have been recognized. Molecular Dynamics (MD).-In recent years attention has focused on the dynamic aspects of macromolecular structure and function. A combination of experimental X-ray and neutron diffraction crystallography together with a number of spectro- scopic techniques has increased our understanding of the dynamic behaviour of such systems. Alongside such experimental procedures theoretical studies involving molecular dynamic simulation methods have aided our understanding of macro-molecular atomic motions.Using an analytical potential of the type described above to express the energy of a system the negative derivative of the potential with respect to the co-ordinate gives the force on each atom F = ma = -dV/dr or -dV/dr = m d2r/dt2 where rn = mass of atom a = acceleration r = Cartesian co-ordinates of atom i. Thus by solving Newton’s second law of motion for each degree of freedom for all atoms [see equation (2)] it is possible to compute a trajectory for each atom as a function of time (ca. s steps). Several reviews on the techniques and applica- tions of MD simulations in the study of macromolecules have appeared.27 Berendsen 22 (a) J.G. Vinter A. Davis and M. R. Saunders J. Cornput.-Aided Mol. Design. 1987 1 31; (b) R. J. Abraham and I. S. Haworth ibid. 1988 2 125. 23 S. N. Ha A. Giammona and M. Field Carbohydrate Rex 1988 180 207. 24 K. Rasmussen Acta Chem. Scand. Ser. A 1982 36 323. 25 W. L. Jorgensen and J. Tirado-Rives J. Am. Chem. Soc. 1988 110 1657. 26 J. C. Tai and N. L. Allinger J. Am. Chem. Soc. 1988 110 2050. 27 (a) P. Kollman and W. F. van Gunsteren in ‘Methods in Enzymology’ Vol. 154 ed. R. Wu and L. Grossman Academic Press New York 1987 p. 430; (b) M. Karplus A. T. Brunger R. Elber and J. Kuriyan Cold Spring Harbor Symp. 1987,52,381; (c) R. Bruccoleri M. Karplus and J. A. McCammon Biopolymers 1986 25 1767; (d) A.T. Hagler in ‘The Peptides’ Vol. 7 Academic Press New York 1985 p. 213. Physical Methods and Techniques -Part (ii) Computer Graphics 21 has recently summarized the methods available for MD simulation and its applica- tions to complex molecular systems.28 Conformational studies on several ~eptide~~ and nucleic acid3' structures have recently been described along with enzyme active site sir nu la ti on^.^^ The dynamic behaviour of molecules in the crystalline environ- ment is now the subject of investigation. Recent reports include the study of despentapeptide insulin32 and P-cy~lodextrin.~~ Molecular dynamic simulations have also been used to study conformational differences between molecules in different environments. a-Cyclodextrin has been studied in aqueous solution and in crystalline form.3' Studies on the cyclic peptide ~yclo-(Ala-Pro-D-Phe)~ in the isolated and crystalline states have shown the energy of the crystal conformer to be in the order of 8 kcal mol-' higher than an isolated theoretical minimum.35 Even more interesting is the observation that as a result of these conformational differences the methyl groups of the alanine residue rotate more freely in the crystal structure than in the isolated ~eptide.~~ This example in particular serves to highlight the greater awareness of the dynamic nature of molecules even in the crystalline state and further serves to demonstrate the fact that crystal conformations do not necessarily reflect solution conformations nor the bioactive conformation of a drug molecule.With the continuing advances in n.m.r. techniques solution conformations of peptides and small proteins can now be determined. By the application of two- dimensional NO! experiments in particular many approximate interproton dis- tances up to ca. 5 A can be determined.37 By the inclusion of another harmonic term in the potential energy function3* such that where En,m,r, constrains the interproton distances to the experimentally determined values it is possible to drive the molecular refinement using energy minimization and molecular dynamics in accordance with experimentally observed data. Several reports describing the use of restrained molecular dynamics have appeared recently. These include conformational studies on the lipopeptide myc~subtilin,~~ the poly- peptides secretin:' human growth hormone releasing factor:' and potato car-b~xypeptidase~~ inhibitor and a cyclic peptide somatostatin analogue.43 Refinements 28 H.J. C. Berendsen J. Cornput.-Aided Mol. Design 1988 2 217. 29 (a) R. S. Struthers J. Rivier and A. T. Hagler Annu. Rev. New York Acad. Sci. 1985 439 81; (6) J. R. Somoza and J. W. Brady Biopol-vmers 1988 27 939; (c) R. Rone N. Manesis M. Hassan M. Goodman A. T. Hagler D. H. Kitson and V. A. Roberts Tetrahedron 1988,44 895. 30 M. Hirshberg R. Sharon and J. L. Sussman J. Biomol. Stmct. Dynamics 1988 5 965. 31 (a) A. D. MacKerell jun. L. Nilsson R. Rigler and W. Saenger Biochemistry 1988,27,4547; (6) F. K. Brown and P. A. Kollman J. Mol.BioL 1987 198 533. 32 S. Yun-Yu Y. Ru-Huai and W. F. van Gunsteren J. Mol. Biol. 1988 200 571. 33 J. E. H. Koehler W. Saenger and W. F. van bunsteren Eur. Biophys. J. 1987 15 211. 34 J. E. H. Koehler W. Saenger and W. F. van Gunsteren J. Mol. Biol. 1988 203 241. 35 D. H. Kitson and A. T. Hagler Biochemistry 1988 27 5246. 36 D. H. Kitson and A. T. Hagler Biochemistry 1988 27 7176. 37 D. M. LeMaster L. E. Kay A. T. Brunger and J. H. Prestegard FEBS Lett. 1988 236 71. 38 H. Kessler C. Griesinger J. Lautz A. Muller W. F. van Gunsteren and H. J. C. Berendsen J. Am. Chem. Soc. 1988 110 3393. 39 M. Genest D. Marion A. Caille and M. Rak Eur. J. Biochem. 1987 169 389. 40 G. M. Clore M. Nilges A. Brunger and A. M. Gronenborn Eur. J. Biochem.1988 171 479. 41 A. T. Brunger G. M. Clore A. M. Gronenborn and M. Karplus Protein Engineering 1987 1 399. 42 G. M. Clore A. M. Gronenborn M. Nilges and C. A. Ryan Biochemistry 1987 26 8012. 43 H. Pepermans D. Tourwe G.van Binst R. Boelens R. M. Scheek W. F. van Gunsteren and R. Kaptein Biopolyrners 1988 27 323. 22 D. E. Jackson in the solution conformations of several nucleic acids have also been reported.44 A combined distance geometry (DG) and restrained MD procedure has been applied to the lac repressor DNA binding domain to produce three-dimensional structures that satisfied NOE distance constraint^.^' Difficulties in using n.m.r. data and restrained molecular dynamics may arise however when multiple conformations of the molecule generate an n.m.r.parameter set which cannot be satisfied by just one conformation of the molecule. This has been found to be the case in the cyclic decapeptide anatamanide where at least two solution conformations are required.46 A new dynamics simulation methodology based on the combination of quantum and molecular mechanics potentials has recently been described by Karpl~s.~’ This method has been implemented within the context of thermodynamic perturbation theory48 using a modification of the CHARMM program to include quantum mechanical contributions evaluated by the MOPAC program suite. Applications range from the dynamic simulation of SN2reactions in solution through to ligand binding and enzyme-mediated transformations. Finally on the subject of dynamic motion in biomacromolecules the low- frequency collective motion which is now believed to be present in such systems has recently been reviewed.49 Although modelling of such motion is not yet possible the identification of low-frequency collective macromolecular motion may herald significant developments in our understanding of aspects of molecular recognition processes which are poorly understood at present.Molecular Orbital Calculations.-The second method for the computation of molecular energies and properties involves molecular orbital techniques. Several of the modelling packages (e.g. CHEM-X COSMIC) offer graphical interfaces to various MO programs thereby making techniques which were once the provision of the theoretician alone available to the organic chemist.The most commonly used MO programs range from semi-empirical (e.g. CNINDO,” AMPAC”) through to ab initio (e.g. Gaussian5*) calculations. No further discussion on MO techniques will be included here. A perspective on CAMM and MO calculations has recently appeared53 and an excellent practical guide to the application of these programs aimed particularly at the non-specialist is available in A Handbook of Computational Chemistry.54 44 (a) C. S. Happ E. Happ G. M. Clore and A. M. Gronenborn FEBS Lett. 1988 236 62; (b) C. S. Happ E. Happ M. Nilges A. M.Gronenborn and G. M. Clore Biochemistry 1988 27 1735; (c) G. M. Clore H. Oschkinat L. W. McLaughlin F. Benseler C. S. Happ E. Happ and A. M. Gronenborn ibid. 1988 27 4185.45 J. de Vlieg R. M. Scheek W. F. van Gunsteren H. J. C. Berendsen R. Kaptein and J. Thomason Proteins 1988 3 209. 46 H. Kessler C. Griesinger J. Lautz A. Muller W. F. van Gunsteren and H. J. C. Berendsen J. Am. Chem. SOC. 1988 110 3393. 47 P. A. Bash M. J. Field and M. Karplus J. Am. Chem. SOC.,1987 109 8092. 48 (a) G. M. Torrey and J. P. Valleau Chem. Phys. Lett. 1974 28 578; (b) P. Kollman S. Rao F. Brown V. Daggett G. Seibel and U. C. Singh in ‘Protein Structure Folding and Design 2’ ed. D. L. Oxender Alan R. Liss Inc. New York 1987 p. 215. 49 K.-C. Chou Biophys. Chem. 1988 30,3. 50 J. A. Pople and D. L. Beveridge ‘Approximate Molecular Orbital Theory’ McGraw-Hill New York 1970. 51 Dewar Research Group QCPE Bull.1986 6 4 (AMPAC QCPE 506). 52 J. S. Binkley R. A. Whiteside K. Raghavachari R. Seeger D. J. DeFrees H. B. Schlegel M. J. Frisch J. A. Pople and L. R. Kahn ‘Gaussian82’ Carnegie-Mellon University Pittsburgh 1982. 53 P. von R.Schleyer J. Cornput.-Aided Mol. Design 1988 2 223. 54 T. Clark ‘A Handbook of Computational Chemistry’ Wiley New York 1985. Physical Methods and Techniques -Part (ii) Computer Graphics 23 Software.-A comprehensive review55 by Vinter in 1986 on modelling systems contains details on both the hardware and software available for applications in drug design X-ray crystallography electron density fitting and molecular dynamics. TOM,56 a subpackage of one such electron density fitting program FRODO has subsequently been described for protein-ligand docking with interactive energy minimization.Other software packages developed for the mainframe/minicomputer systems and not covered by the earlier review include MACROMODEL,57 for use with small organic molecules through to large biopolymers using MM2( 85) AMBER and the AMBER/OPLS force fields; CHEM-X,58 which offers a range of modules for modelling various molecular structures from small organic organometallic and inorganic through to macromolecular proteins; COSMIC and ASTRAL which represent comprehensive computational chemistry and display packages used primarily for investigating the properties of small organic molecules as an aid to drug design and based on the COSMIC force field; BRAGI,59 a protein modelling system with interface to the AMBER force field; QUANTA6’ (based on the CHARMM force field) a comprehensive open architecture modelling package for application to small organic molecules biological polymers and inorganic materials; MOLCAD,61 an interactive three-dimensional molecular display package with inter- faces to other program systems including AMPAC and GRID; MOL3D,62 a modular interactive graphics program for the display and conformational analysis of molecules containing up to 256 atoms; MANOSK,63 for the display manipulation and analysis of both small and large molecular systems; PEPCRE,@ for the interac- tive modelling of oligopeptides.The development in recent years of powerful desktop ‘personal computers’ has allowed the transfer of some molecular modelling techniques from mainframe/mini systems to PCs.A comparative review of molecular modelling software for the IBM PCs covering CRYS-X ALCHEMY CAMSEQ/M CAMSEQ/PC MGP MOL- GRAF and PROMODELER I has recently been written.65 Other software packages available for this system and which have been reviewed include ChemCad,66 an interactive graphics program which can be used to create input files for MM2 and the AMPAC suite of programs; a Molecular Mechanics Package (MS-DOS Com- puters):’ consisting of a structure input program an energy minimize program based on Allingers MM2 force field and a draw program for viewing the structures 55 J. G. Vinter in ‘Topics in Pharmacology Vol. 3’ ed. A. S. V. Burgen G. C. K. Roberts and M. S. Tute Elsevier Amsterdam 1986 p.15. 56 C. Cambillau and E. Horjales J. Mol. Graph. 1987 5 174. 57 C. Still ‘MacroModel Version 1.5’ Columbia University Department of Chemistry 507 Havemeyer Hall New York NY 10027 1986. 58 ‘Chem-X’ Chemical Design Ltd Unit 12 7 West Way Oxford. 59 D. Schomburg and J. Reichelt J. Mol. Graph. 1988 6 161. 60 ‘Quanta’ Polygen Corporation 200 Fifth Avenue Waltham Massachusetts 02254. 61 J. Brickmann ‘Molcad’ Technische Hochschule Darmstadt Petersenstrasse 20 D-6100 Darmstadt West Germany. 62 D. Pattou and B. Maigret J. Mol. Graph. 1988 6 112. 63 J. Cherfils M. C. Vaney I. Morize E. Surcouf N. Colloc’h and J. P. Mornon J. Mol. Graph. 1988 6 155. 64 C. W. van der Lieth J. Palm A. Sundin R. E. Carter and T. Liljefors J.Mol. Graph. 1987 5 119. 65 M. Sadek and S. Munro J. Cornput.-Aided Mol. Design 1988 2 81. 66 E. L. Clennan J. Am. Chem. SOC.,1987 109 2229. 67 M. M. Midland J. Am. Chem. SOC.,1986 108 5042. 24 D. E. Jackson and producing hard copy; Molecular Graphics on the IBM PC microcomputer,68 a version of which is also available for the Apple rnicro~omputer,~~ and pdViewer7’ are drawing and visualization packages for the three-dimensional representation of molecules; Visual Molecules and Molecular Parameters7’ generate graphical display from crystallographic data and allow output of tabulated molecular parameters such as bond lengths and bond angles. Other systems which are known to be available for the IBM PC include Desktop Molecular M~deller.~~ For the Apple Macintosh Chem3D is a limited molecular modelling display program which has been reviewed.73 A molecular graphics system (MGC) for the BBC microcomputer is also available74 in which a dedicated graphics display co-processor has been developed to enhance the graphics capabilities of the BBC.Limited molecular mechanics routines have been included to form the basis of a molecular modelling teaching aid. 3 Computer Aids to Synthesis Planning Several databases have been developed to handle literature reports of chemical reactions. Typically a graphical interface is used to construct a full structure or fragment specification for searching the database for reactions conditions and bibliographic entries. Examples of organic reaction databases include ORAC,75 SYNLIB,76 and REACCS.77 In addition to straightforward databases several ‘knowl- edge-based systems’ or ‘expert systems’ have been developed.Characteristically these combine a knowledge base with a number of concepts models and generalized rules such that by the application of identifiable transforms (disconnections) the program works retrospectively from product to possible starting materials. Examples of ‘expert systems’ include LHASA78 and SYNCHEM II.79 A number of programs have also been developed which implement a generalized set of rules governing reactivity for different classes of organic reactions in order to predict the outcome of a proposed step given starting materials and reaction conditions. Such systems which include EROS,” SYNGEN,81 and CAMEO have no reliance on any database and cannot therefore be used to search for literature data.A recent report on the development of CAMEO8* indicates that this program can now evaluate various reaction types including nucleophilic electrophilic peri- cyclic oxidative and reductive. A comprehensive coverage of reactions used in the synthesis of heterocyclic compounds has also been included. 68 M. A. Fox and D. Shultz J. Am. Chem. SOC.,1986 108 7882. 69 D. R. Dalton and G. R. Webster jun. J. Am. Chem. SOC.,1987 109 2862. 70 J. V. Paukstelis J. Am. Chem. SOC.,1988 110 4098. 71 C. J. Burrows J. Am. Chem. SOC.,1987 109 5056. 72 ‘Desktop Molecular Modeller’ Oxford Electronic Publishing Oxford University Press Walton Street Oxford.73 D. S. Allen J. Am. Chem. SOC.,1988 110 7261. 74 ‘Chemdata Molecular Graphics System’ Chemdata Ltd Wendron Helston Cornwall. 75 A. P. Johnson Chem. Brit. 1985 21 59. 76 J. Boother Chem. Brit. 1985 21 68. 77 ‘REACCS’ Molecular Design Ltd 2132 Farallon Drive San Leandro CA 94577 U.S.A. 78 E. J. Corey A. P. Johnson and A. K. Long J. Org. Chem. 1980,45 2051. 79 H. L. Gelernter A. F. Sanders D. L. Larsen K. K. Agarwal R. H. Boivie G. A. Spritzer and J. E. Searleman Science 1977 197 1041. 8o J. Gasteiger and C. Jochum Top. Curr. Chem. 1978 93. 81 J. B. Hendrickson and E. Braun-Keller J. Comput. Chem. 1980 1 323. 82 M. G. Bures and W. L. Jorgensen J. Org. Chem. 1988 53 2504. Physical Methods and Techniques -Part (ii) Computer Graphics CHIRON83 is an interactive program for the analysis and perception of stereochemical features in molecules and the selection of chiral precursors in organic synthesis.4 Other Chemical Databases For general chemical queries using a simple graphical interface to generate structures or sub-structures it is possible to search the chemical literature by using the CAS ONLINE system available through STN International or using the DARC system through Telesystemes Q~estel.~~ Both are based on the CAS Registry System which was developed in the 1960s to index chemical substances reported in the literature. A more recent addition to the on-line chemical information which is available is the Beilstein databa~e.’~ The first release in the last quarter of 1988 via STN International contains the Handbook heterocyclic compounds from volumes 17-27 of the Basic Series to the supplementary Series E IV inclusive.Software for use on local PCs for the creation of search files for this database has also been described.86 An alternative to the on-line database is a structure analysing program SANDRA87 (Structure and Reference Analyser Program for the Beilstein Handbook of Organic Chemistry) available for the IBM PC. This program allows a graphical input to query where the compound ought to be located in the 340 or so volumes of the Beilstein Handbook thereby alleviating the need to understand the specific indexing system used by Beilstein. Several MEDCHEM QSAR databases are under development at Claremont within the MEDCHEM Project at Pomona College.88 These include programs for the estimation of log P (CLOGP) and molar refractivity (CMR) and a generalized chemical information database (THOR).An expansicn of THOR into a database (MENTHOR)89 for the storage and retrieval of three-dimensional co-ordinate and charge information as well as the more traditional biological and physical properties has recently been described. The Cambridge crystallographic database” and the Brookhaven protein data bank” remain the major depositories for crystallographic data and are important sources of information to both crystallographers as well as molecular modellers. 83 S. Hanessian ‘CHIRON’ University of Montreal Department of Chemistry Quebec Canada.84 P. Rhodes Chem. Brit. 1985 21 53. 85 ‘Beilstein Brief No. 2’ Springer-Verlag Tiergartenstr. 17 Heidelberg FRG 1988. 86 ‘Molkick version l.O’ Springer-Verlag Dept. New Media/ Handbooks Tiergartenstr. 17 Heidelberg FRG 1988. 87 S. R. Heller J. Am. Chem. Soc. 1987 109 5055. 88 ‘MEDCHEM’ Medicinal Chemistry Project Pomona College Claremont CA U.S.A. 89 Y. C. Martin E. B. Danaher C. S. May and D. Weininger J. Cornput.-Aided Mol. Design 1988 2 15. 90 F. H. Allen S. H. Bellard M. D. Brice B. A. Cartwright A. Doubleway H. Higgs T. Hummelink B. G. Hummelink-Peters 0. Kennard W. D. S. Motherwell J. A. Rogers and D. G. Watson Acta Crystallogr. B 1979 35 2331. 91 F. C. Bernstein T. F. Koetzle G. J. B. Williams E. F. Meyer jun. M. D. Brice J. R. Rogers 0.Kennard T. Shimanouchi and M. Tasumi J. Mol. Biol. 1977 112 535.

ISSN:0069-3030    

DOI:10.1039/OC9888500017

出版商:RSC    

年代:1988

数据来源: RSC

摘要:

3 Theoretical Organic Chemistry By I. H. WILLIAMS School of Chemistry University of Bristol Bristol BS8 1TS 1 Introduction The growth in this area of the chemical literature has continued there are 1846 entries in the 1987 bibliography of ab initio calculations’ which of course does not include semi-empirical and molecular mechanics calculations nor results of the ‘pencil and paper’ variety. The aim of this chapter is not to report comprehensively on all areas but to highlight the various themes of interest and importance which have emerged from the year’s published literature. 2 Computational Methods The development of analytical gradient methods for ab initio wavefunctions has been crucial to the application of computational quantum chemistry to organic chemical problems.Owing to the importance of geometry optimization and potential energy (PE) surface exploration the practical utility of any method is severely limited until analytical first (and maybe second) derivatives of the energy are available. Moreover it is becoming increasingly apparent that the treatment of many interesting problems in even a qualitatively correct manner requires the inclusion of electron correlation. It has been suggested that this might soon become an essential requirement for publication of theoretical studies on molecules with up to five first-row atoms; good agreement with experimental geometries and vibrational frequencies is obtained for ‘medium-sized’ organic molecules (three first-row atoms!) using second-order Moller-Plesset perturbation theory (MP2) and configuration interaction with all single and double excitations (CISD) approaches to electron correlation.* Large-scale calculations with the third-order MP3 method are not recommended it is better to use MP2 with a large basis.3 Analytical gradients have been developed for full MP4 wavefunctions (including triple excitations)? The CISD method is neither size-consistent (the energy of a supermolecule AB with A and B at infinite separation is not equal to the sum of the individual energies of two fragments A and B) nor size-extensive (the energy does not scale linearly ’ Quantum chemistry literature database.Supplement 7. Bibliography of ab initio calculations for 1987 ed. K. Ohno and K. Morokuma THEOCHEM 1988,51 1.E. D. Simandiras R. D. Amos N. C. Handy T. J. Lee J. E. Rice R. B. Remington and H. F. Schaefer J. Am. Chem. SOC.,1988 110 1388. I. L.Alberts and N. C. Handy J. Chem. Phys. 1988 89 2107. J. Gauss and D. Cremer Chem. Phys. Lett. 1988 153 303; G. W. Trucks J. D. Watts E. A. Salter and R. J. Bartlett ibid. p. 490. 27 28 I. H. Williams with the number of electrons). There is current interest in methods which overcome these deficiencies such as the coupled-pair functional (CPF) method' and the quadratic configuration interaction (QCISD) method,6 for both of which analytical gradients are now available and the family of coupled-cluster methods e.g. CCSD,7 CCSDT,' etc. which are superior to CI methods for equivalent truncation levels. The above methods are appropriate -at varying degrees of cost! -for the evalu- ation of the dynarnical electron correlation for closed-shell molecules in which the wavefunction is dominated by a single reference determinant i.e.a single pattern of occupation of molecular orbitals by electrons. There is growing awareness however that a single electronic configuration is qualitatively inadequate for the description of many bond breaking and bond making processes and for structures involving highly stretched bonds in these instances a multiconfigurational method is necessary to treat the non-dynamical electron correlation effects. Examples are given in later sections. However there still remains the need to evaluate dynamical correlation arising from a multideterminantal reference.To this end a simple MCSCF perturbation theory -orthogonal valence bond second-order Moller- Plesset (OVB MP2)9-has been described and a unitary multiconfigurational coupled cluster method" has been developed for chemically accurate studies of PE hypersurfaces on which the electronic configurations providing the essential description of the wavefunction change with nuclear geometry. Algorithms have been described for following reaction paths over PE surfaces by steepest descent methods," by gradient extremal walking,I2 and by the local quad- ratic appro~imation,'~,'~ for determining accurate paths leading away from saddle points,13 and for the location of branching points (at which it is energetically favourable for a system to break symmetry) on reaction paths." A novel method for finding saddle points has been suggested,16 involving the generation of an 'image' surface on which valley floors become cols and vice versa; the saddle region therefore possesses all positive curvatures on the image surface and may be found by standard minimization techniques.It is recommended that the 'precise' ~ption'~ and the BFGS Hessian update schemeI8 should always be employed in geometry optimiz- ations using the popular MOPAC and AMPAC programs for semi-empirical MO calculations. The AM1 semi-empirical method has been found to give good results for geometries and for many properties but opinions differ as to its ability to describe hydrogen bonds. Some find it an unreliable tool which 'fails to reproduce the energy J.E. Rice T. J. Lee and N. C. Handy J. Chem. Phys. 1988 88 7011. J. Gauss and D. Cremer Chem. Phys. Lett. 1988 150 280. T. J. Lee and J. E. Rice Chem. Phys. Lett. 1988 150 406. G. E. Scuseria and H. F. Schaefer Chem. Phys. Lett 1988 152 382. J. J. W. McDouall K. Peasley and M. A. Robb Chem. Phys. Lett. 1988 148 183. 10 M. R. Hoffmann and J. Simons J. Chem. Phys. 1988 88 993. 'I B. C. Garrett M. J. Redmon R. Steckler D. G. Truhlar K. K. Baldridge D. Bartol M. W. Schmidt and M. S. Gordon J. Phys. Chem. 1988 92 1476. 12 P. Jprrgensen H. J. A. Jensen and T. Helgaker Theor. Chim. Acfa 1988 73,55. l3 M. Page and J. W. McIver J. Chem. Phys. 1988 88 922. 14 J. Ischtwan and M. A. Collins J. Chem. Phys. 1988 89 2881.J. Baker and P. M. W. Gill J. Comput. Chem. 1988 9 465. 16 C. M. Smith Theor. Chim. Acta 1988 74 85. l7 D. B. Boyd D. W. Smith J. J. P. Stewart and E. Wimmer J. Comput. Chem. 1988 9 387. W. Thiel THEOCHEM 1988 40 415; D. K. Agrafiotis and H. S. Rzepa J. Chem. Res. fS). 1988 100. Theoretical Organic Chemistry 29 and structure of hydrogen bonds in charged systems with useful acc~racy”~ and suggest that ‘conclusions regarding its efficacy . . .need reconsideration’,20 whereas others find its energetic predictions qualitatively acceptable*l and indeed quite adequate for the description of (NH,+) nNH clusters.22 Dannenberg finds the gas-phase hydration energies of protonated diamines to be good and regards the predicted bifurcated hydrogen bonds as genuine; moreover he finds trifurcated structures for the water dimer very similar the AM1 geometry in high-level ab initio calculations and suggests that the experimental geometry may be determined entr~pically.~~ Thiel has provided an overview of the current status of and perspectives for semi-empirical MO methods outlining their theoretical justification and suggesting various options for future improvements but Lindholm has different views regarding the way to develop better methods.24 Watch this space for news of the recently announced PM3 method from J.J. P. Stewart! MM2 molecular mechanics parameters have been reported for hydrogen bonds conjugated nitrogen-containing heterocycles silanes divinyl ethers and aromatic halide derivative^,^^ and for peptides and penicillins.26 Various schemes have been devised for obtaining charges for molecular mechanics calculation^.^^ 3 Structure Bonding and Properties In its diamond jubilee year the concept of hybridization is alive and well.It does not explain molecular geometry but it does ‘happen’ in response to physical interactions between atoms and is therefore not an arbitrary concept; allowing for optimal non-orthogonal hybrids leads to a picture of chemical bonding incorporating most of the familiar concepts of qualitative chemistry such as the VSEPR theory of molecular geoxetry.28 Equally the physical basis for the latter may be found by the analysis of the Laplacian of the electronic charge density local concentrations of charge in the valence shell of an atom in a molecule faithfully duplicate the spatially localized electron pairs of the VSEPR The spin-coupled descrip- tion of methane yields ‘hybridization without preconception^'^' -the optimized orbitals on carbon are sp3-like but are not orthogonal their overlap with each other being 0.48.Bent bonds are a common occurrence and angles between bond paths (the paths of maximum electron density between atoms) are in good accord with common hybridization arguments. Thus the FCH angle in fluoromethane is expected 19 A. A. Bliznyuk and A. A. Voityuk THEOCHEM 1988 41 343. 20 W. C. Herndon and T. P. Radhakrishnan Chem. Phys. Lett. 1988 148 492. 21 G. Buemi F. Zuccarello and A. Raudino THEOCHEM 1988 41 379. 22 S. Galera J. M. Lluch A.Oliva and J. BertrPn THEOCHEM 1988 40 101. 23 J. J. Dannenberg and L. K. Vinson J. Phys. Chem. 1988 92 5635; J. J. Dannenberg ibid. p. 6869. 24 W. Thiel Tetrahedron 1988 44,7393; E. Lindholrn ibid. p. 7461. 2s N. L. Allinger R. A. Kok and M. R. Iman J. Comput. Chem. 1988,9 591; J. C. Tai and N. L. Allinger J. Am. Chem. Soc. 1988 110 2050; M. R. Frierson M. R. Iman V. B. Zalkow and N. L. Allinger J. Org. Chem. 1988,53,5248; J. P. Bowen V. V. Reddy D. G. Patterson and N. L. Allinger ibid.,p. 5471. 26 S. Wolfe D. F. Weaver and K. Yang Can. J. Chem. 1988 66 2687; S. Wolfe M. Khalil and D. F. Weaver ibid. p. 2715. 27 R. J. Abraham and G. H. Grant J. Cornput. Chem. 1988 9 244 709; R. J. Abraham and P. E. Smith ibid. p. 288; J. Mullay ibid. pp. 399 764; L.-G.Hammarstrom T. Liljefors and J. Gasteiger ibid. p. 424. 28 D. B. Cook THEOCHEM 1988 46 79. 29 R. F. W. Bader R. J. Gillespie and P. J. MacDougall J. Am. Chem. Soc. 1988 110 7329. 30 F. Penotti J. Gerratt. D. L. Cooper and M. Rairnondi THEOCHEM 1988 46 421. 30 I. H. Williams to be less than the tetrahedral value since the electronegative fluorine atom should prefer to bond to a carbon hybrid orbital with considerable p character. In reality it is 109.2”,but the angle between the CF and CH bond paths is indeed only 106.7’; such comparisons frequently reveal the nature of intramolecular interaction^.^' Altona and co-workers use non-orthogonal strictly local molecular orbitals as the basis for analysis of intramolecular interactions -such as the anomeric effect -in terms of ‘quasi-classical’ (overlap independent) and ‘interference’ (overlap depen- dent) contribution^.^^ Weinhold however argues for the importance of maintaining strict orbital orthogonality in applying perturbation-style analysis to the physical interpretation of wave function^.^^ In his view natural bond orbitals defined by a simultaneous requirement for maximum electron occupancy and orthonormality correspond better to the classical concept of a transferable localized bond than does a localized molecular orbital; the breakdown of bond transferability may be regarded as arising from interactions between a localized bond and its chemical environment namely rehybridization (Bent’s rule) effects orthogonality (steric) effects and chemical delocalization (hyperconjugative) eff e~ts.~~ Whereas classical valence bond (VB) theory would describe the C-Li bond in methyl lithium as a mixture of covalent and ionic structures involving orbitals localized on each centre the spin-coupled VB method uses a different language in describing this bond as a purely covalent interaction between orbitals allowed to be delocalized.By projecting their spin-coupled VB wavefunction on to a classical VB basis of localized atomic orbitals however Hiberty and Cooper have shown that the ‘covalent’ picture for methyl lithium with delocalized orbitals implicitly contains ionic structures and reveals about 76% ionic character for the C-Li bond (organic chemists will be reassured to learn!).35 Why are carboxylic acids stronger acids than are alcohols? The standard textbook answer (‘because the carboxylate anion is stabilized by resonance delocalization’) is wrong say Siggel Thomas and Streit~ieser.~~ Normal inductive effects which polarize the acid account for most of the enhanced acidity of a carboxylic acid.Different methods of electron population analysis all agree that the carbonyl group in carboxylic acids is highly polarized and is the major factor affecting their acidity relative to alcohols. The total charge in the carboxylate anion is delocalized but the carbonyl oxygen is already so negatively charged in the acid that it can accept very little extra charge by allylic resonance in the v-system as conventionally represented. Not surprisingly this proposition has aroused some debate!37 The question of the origin of the anomalously high acidity of Meldrum’s acid (l),which the previous year had been suggested as ‘a worthy target for theoretical el~cidation’,~~ has been answered much less contr~versially.~~ The syn conformation of an ester 31 K.B. Wiberg and M. A. Murcko THEOCHEM 1988 46 355. 32 G. F. Smits M. C. Krol and C. Altona Mol. Phys. 1988 65 513. 33 F. Weinhold and J. E. Carpenter THEOCHEM 1988 42 189. 34 J. E. Carpenter and F. Weinhold J. Am. Chem. SOC.,1988 110 368. 35 P. C. Hiberty and D. L. Cooper THEOCHEM 1988,46 437. 36 T. D. Thomas M. R. F. Siggel and A. Streitwieser THEOCHEM 1988 42 309; M. R. F. Siggel A. Streitwieser and T. D. Thomas J. Am. Chem.SOC.,1988 110 8022. 37 0. Exner J. Org. Chem. 1988 53 1810; T. D. Thomas T. X. Carroll and M. R. F. Siggel ibid. p. 1812. E. M. Arnett and J. A. Harrelson J. Am. Chem. SOC.,1987 109 809. X. Wang and K. N. Houk J. Am. Chem. Soc. 1988,110,1870; K. B. Wiberg and K. E. Laidig ibid. p. 1872. 38 39 Theoretical Organic Chemistry such as methyl acetate is preferred over the anti because of a more favourable orientation of the carbonyl and ester-oxygen dipoles. The main effect of deproton- ation is to transfer negative charge not to the carbonyl oxygen but to the carbonyl carbon atom thereby reducing the carbonyl dipole and attenuating the syn-anti energy difference by 23 kJ mol-’. The presence of two syn ester moieties in Meldrum’s acid therefore leads to an enhancement of acidity by about 46 kJ mol-’ relative to malonic ester.Wiberg also notes however that the acidity of esters is due to the strong polarization of the carbonyl group in complete accord with the results of Siggel and Thomas for carboxylic acids. The pros and cons of the concept of a-aromaticity have been critically assessed by Cremer. Application of the same criteria commonly used to define maromaticity reveals that the properties of cyclopropane qualify it as a a-aromatic system the term cannot be rejected simply on the grounds that aromaticity is a property of v-electrons only.40 Electron count rules for a-aromaticity in small cyclic compounds have been form~lated.~~ Stabilization of a quasi-cyclic ‘bent’ hydride-transfer transi- tion structure (2) by 68 kJ mol-’ relative to an acyclic ‘linear’ geometry has been rationalized in terms of five-centre six-electron b~nding;~’ transition state a-aroma- ticity? H,C...H* *.C/ \\ I1 N :N H / H (2) Haddon has reviewed the topic of welectrons in three dimensions arguing that ?r-orbital overlap in non-planar conjugated organic molecules may be vastly improved at the small cost of slight rehybridi~ation.~~ Use of his POAV method and 3D-HMO theory allows for analysis of valence tautomers of 1,6-methano[ 101an- nulene and of structures along the reaction path for the Cope rearrangement jn terms of hybridization changes in the making and breaking bondsM These methods have been applied45 to the homotropylium cation (3) which has also been studied 40 D.Cremer Tetrahedron 1988 44 7427. 41 V. I. Minkin M. N. Glukhovtsev and B. Ya. Simkin THEOCHEM 1988 50 93. 42 A. E. Pain and I. H. Williams J. Chem. SOC.,Chem. Commun. 1988 1367. 43 R. C. Haddon Acc. Chem. Res. 1988 21 243. 44 R. C. Haddon Tetrahedron 1988,44 7611. 45 R. C. Haddon J. Am. Chem. Soc.. 1988 110 1108. I. H. Williams by others.46 Calculations at the SCF level suggest a double-minimum potential in the 1,7-bond co-ordinate but electron correlation changes the shape of the surface to a broad single minimum with a 1,7-bond length somewhere between 1.7 and 2.0 A; (3) is described as the ‘ideal homoaromatic species’.45 Prizes for the most highly strained molecules might go to structures (4)-(7) related to bicycle[ 1 .l.l]pentane all of which are predicted by high-level calculations (MP2/6-3 lG* optimizations with zero-point energies evaluated using HF/6-3 lG* vibrational frequencies) to be stable in low-temperature inert gas mat rice^.^' Three-membered silane rings are more highly strained than four-membered silane rings which are also less strained than their carbocyclic analogues.48 Unsaturated silicon hydrides have a tendency to pucker unlike their hydrocarbon analogues due to a smaller difference between sp2 and sp3 hybridization for Si than for C; Sax et al.regard aromaticity as a feature of the exceptional behaviour of first-row elements.49 Although hexasilabenzene is planar at the SCF level CI calculations predict a puckered Qdstructure the puckering being due to correlation effects on the 0-framework; the lowest energy Si6H6 isomer is hexa~ilaprismane.~~ 4 Reactivity and Mechanism Theories of Reactivity.-Arteca and Mezey have formulated conditions for the validity of the Hammond postulate in terms of bounds on the internal forces and force constants of nuclear arrangements along a reaction path and have identified a broad class of constraints under which it would be ~iolated.~’ Formosinho has also examined the validity of several reactivity relationships (including the Ham- mond postulate and the reactivity-selectivity principle) according to his intersecting- state model and has discussed various factors leading to their breakdown5’ Murdoch has shown how transformation from Cartesian to bond order co-ordinates reveals many molecular phenomena as low-order perturbations.Scaling relationships can be found which map energies and interatomic distances on to a ‘universal’ bond dissociation curve. Bond order transformations enable PE surfaces for reacting systems to be expressed in simple low-order forms obeying Marcus-like relationships. The intrinsic (non-thermodynamic) contributions to reaction barriers arise from interactions not present in the isolated reactants and products. The transferability of intrinsic contributions between different reactions highlights the low-order nature 46 M. Barzaghi and C. Gatti THEOCHEM 1988,43,431; ibid. 1988,44,275; R. V. Williams H. A. Kurtz and B. Farley Tetrahedron 1988 44 7455.47 V. Balaji and J. Michl Pure Appl. Chem. 1988 60 189. 48 S. Nagase and M. Nakano Angew. Chem. Int. Ed. Engl. 1988,27,1081;S. Nagase and T. Kudo J. Chem. SOC.,Chem. Commun. 1988 55. 49 A. F. Sax J. Kalcher and R. Janoschek J. Compuf.Chem. 1988 9 564. 50 G. A. Arteca and P. G. Mezey J. Comput. Chem. 1988 9 728. 51 S. J. Formosinho J. Chem. Soc. ferkin Trans. 2 1988 839. Theoretical Organic Chemistry 33 of many chemical reactions and is useful for constructing new PE surfaces from existing calculations and experimental data.52 Warshel and co-workers have used their empirical VB method together with the free-energy perturbation technique to perform simulations of free-energy relation- ships (and dynamics) of SN2reactions in aqueous solution; a Marcus-like relation- ship was found between the thermodynamic free energy of reaction and the solvent contribution to the activation free energy.53 A Marcus-theory treatment of MP2/6-3 lG*//HF/3-21G calculated energetics for several hydrogen atom transfer reactions has shown that the coefficient a (=dAE*/dAE) is an index of selectivity but not always a reliable measure of transition state structure.Variation in the Marcus intrinsic barrier is an important factor in determining the magnitude of a whose value may become anomalously sizeable when a new interaction occurs between the reacting fragments in the transition state.54 An AM1 theoretical simulation of a Bransted correlation for an acyl transfer reaction has shown that a linear rate-equilibrium correlation is not incompatible with the ‘Bema Hapothle’ and with variable transition state structure and that Brfinsted coefficients are not direct measures of transition state structure; a transformation to bond order co-ordinates is the key feature of a simple intersecting curves model which reproduces this behaviour in predicting an essentially constant value for a and a variable transition state location along the reaction ~o-ordinate.’~ A novel theoretical analysis of substituent effects has been proposed and applied to Hammett and Bransted and related plots.Structural changes along the reaction co-ordinate are controlled by a requirement to make charge transfer between the species joined by the making/breaking covalent bond as facile as possible.Changes in electronic structure do not smoothly follow geometrical changes and as a consequence the global pattern of rate-equilibrium and rate-rate relationships is not expected to be very simple. However the permissible changes in electronic structure suggest that this pattern should exhibit certain simple local features notably straight lines with slopes close to particular values.56 The idea that a chemical reaction may be considered in terms of the interaction between reactant-like and product-like ‘diabatic’ states just as in the Heitler-London VB method the hydrogen molecule is treated in terms of coulomb and exchange interactions between hydrogen atoms was originally proposed by M. G. Evans in 1938.Now rigorous methods have been developed by which adiabatic PE surfaces may be ‘diabatized’ to enable their analysis within this simple VB scheme. Bernardi et al. have described a procedure for transforming an accurate complete-active-space self-consistent-field (CASSCF) wavefunction to this Heitler-London VB form uia an effective Hamiltonian and have applied their method to some previously com- puted transition structures for cycloaddition reaction^.^' Malrieu and co-~orkers~~ have used a different method to obtain nearly diabatic surfaces from MO CI 52 J. R. Murdoch THEOCHEM 1988 40 447. 53 J.-K. Hwang G. King S. Creighton and A. Warshel J. Am. Chem. Soc. 1988 110 5297. 54 H. Yamataka and S. Nagase J. Org. Chem. 1988 53 3232. 55 I. H. Williams Bull.Soc. Chim. Fr. 1988 192; R. B. Hammond and I. H. Williams J. Chem. SOC.,Perkin Trans. 2 1989 59. 56 G. F. Fadhil and M. Godfrey J. Chem. SOC.,Perkin Trans. 2 1988 133; M. Godfrey ibid. p. 139. 57 F. Bernardi M. Olivucci J. J. W. McDouall and M. A. Robb J. Chem. Phys. 1988 89 6365. sx 0. K. Kabbaj F. Volatron and J.-P. Malrieu Chem. Phys. Lerr. 1988 147 353. 34 I. H. Williams calculations for the simplest sN2 process H-+ HZ,which support Shaik’s qualita-tive VB model for this system. The relationship between reaction barriers and transition state looseness defined both thermochemically and geometrically has been discussed.59 SN2Reactions.-Shaik et al. have analysed HF/4-3 1G geometrical and energetic data for methyl transfer between a range of nucleophiles and leaving groups and have found extended linear correlations between (a) the magnitude of the barrier and the fractional elongation of the carbon-to-leaving-group bond in the transition structure and (b) the sum of the forward and reverse barriers and the transition state ‘looseness’.The more extensive the bond cleavage in the transition structure the higher the barrier to reaction.60 Electron correlation has a very substantial influence on sN2 barrier heights. Single and triple excitations make important contributions to reducing barriers for reactions of a range of nucleophiles with methyl fluoride at the MP4SDTQ level.61Multi-reference-determinant CI calculations62 confirm this for the reaction H--CH3F-CH4 * * -F-.The barrier for this same reaction is very basis-set dependent at the SCF level; electron correlation by MPn methods tends to decrease the barrier but the convergence with the order n of the perturbation expansion is not smooth. Transition state structures optimized at the MP2/6-311G** level are similar to those at the HF/3-21G level; C, symmetry is not maintained all along the reaction path which trifurcates in the product region on its way to a vertex-bound CH3-H --F-ion-molecule complex. Energy profiles have been calculated also with MCSCF + CI and CEPA methods. Calculated rate constants agree with experi-ment when based on MP2 and MP4 theoretical barrier heights but not on the MCSCF + CI value.63The CEPA-1 method predicts the D3,,trigonal bipyramidal structure for CH,-to be not a saddle point but a local minimum;64the degenerate transition structures for its sN2 formation and breakdown were not determined.Additions to Double Bonds.-Ab initio HF/3-2 1G studies65for gas-phase halogena-tion of ethene predict three-centre halonium-ion-like transition structures (8) for C12 and Br, but an asymmetric four-centre transition structure for concerted syn addition of F2.Quasi-classical trajectory calculations66for the ethene + F2 reaction have shown that 1,2-difluoroethane is only an intermediate on the way to X- + ...f X .. ,.. . . ............. 59 S. S. Shaik J. Am. Chern. Soc. 1988 110 1127. 60 S. S. Shaik H. B. Schlegel and S. Wolfe J. Chem. SOC.,Chem. Commun.,1988 1322. 61 I.cernuiak and M. Urban Collect. Czech. Chem. Commun.,1988 53 2239. 62 R. Vetter and L. Zulicke THEOCHEM 1988 47 85. 63 Z. Havlas A. Merkel J. Kalcher and R. Zahradnik Chem. Phys. 1988 127 53; A. Merkel Z. Havlas and R. Zahradnik J. Am. Chem. SOC.,1988 110 8355. 64 J. Kalcher THEOCHEM 1988 44 235. 65 S. Yamabe T. Minato and S. Inagaki J. Chem. SOC.,Chem. Commun. 1988 532. 66 L. M. Raff J. Phys. Chem. 1988.92. 141. Theoretical Organic Chemistry 35 CH,=CHF + HF products. Bromochlorination involves a bromonium-ion-like transition structure.67 Bridged structures are predicted for chloronium ions from ethene and cis- and trans-but-2-ene whereas those from propene but-1-ene 2-methylpropene and 2-methylbut-2-ene have open structures (in accord with experiment) at the HF/3-21G level; however contrary to observation an open structure is predicted at this level for the chloronium ion from 2,3-dimethylbut-2- ene.68 These results might be expected to be rather sensitive to the inclusion of electron correlation together with a more flexible basis set.Addition of C1+ or Br+ to cyclopropane leads to a four-membered ring intermediate which may rearrange in a zigzag fashion to a 3-halogenopropyl cation.69 In contrast to nucleophilic addition of OH- approach of SH- to formamide involves only an ion-molecule complex and does not lead to formation of a tetrahedral adduct; thiolate addition to amides probably proceeds by initial O-prot~nation.’~ Hydride addition to formaldehyde has been the prototype of nucleophilic addition to a carbonyl group; previous SCF calculations have suggested no barrier to gas-phase formation of methanolate.However inclusion of diffuse basis functions leads to the prediction of a maximum in the SCF PE profile. Electron correlation has an appreciable effect (even for this closed-shell system) in reducing this barrier to less than 4 kJ mol-* and shifting the location of the transition structure by 0.4 A along the reaction co-~rdinate.~~ Hydroxide addition to formaldehyde and to ethene has been treated by MCSCF calculations which permit the description of both heterolytic and homolytic processes; it is found that the constraints implicit in SCF treatments are not serious qualitatively but do lead to quantitatively different energies and geometries7 The kinetic stereoelectronic effect of antiperiplanar lone pairs assisting hydride transfer from methanimine to formonitrilium is revealed only by calculations which include electron ~orrelation.~~ Multibond Reactions.-The issue of synchronicity in multibond pericyclic processes has been reviewed with emphasis on the discrepancies between the predictions of semi-empirical and a6 initio MO methods.73 Dewar’s AM1 results for the Cope rearrangement of hexa-1,5-diene have suggested distinct mechanistic pathways involving a non-synchronous biradicaloid transition structure for the boat rearrange- ment and a higher-energy synchronous aromatic transition structure for the chair rearrangement.An a6 initio CASSCF study involving all singlet configurations of six electrons in six active orbitals has now been performed with full geometry optimization and with each critical point being characterized by its Hessian (energy second derivatives).The transition structures for both the boat and chair rearrange- ments are found to have 10-15% more biradical character than the reactant but are each still very much closed-shell species. The C2,,chair transition structure has the lower energy. A second C, critical point with biradical character and a very short interallylic separation is found to be a local minimum at much higher energy.74 67 S. Yamabe and T. Minato Bull. Chem. SOC.Jpn. 1988 61 4449. 68 S. Yamabe T. Tsuji and K. Hirao Chem. Phys. Lett. 1988 146 236. 69 S. Yamabe T.Minato M. Seki and S. Inagaki J. Am. Chem. SOC.,1988 110 6047. 70 A. E. Howard and P. A. Kollman J. Am. Chem. SOC.,1988 110 7195. 71 C. I. Bayly and F. Grein Can. J. Chem. 1988 66 149. 72 F. Bernardi M. Olivucci G. Poggi M. A. Robb and G. Tonachini Chem. Phys. Letr. 1988 144 141. 73 W. T. Borden R. J. Loncharich and K. N. Houk Annu. Rev. Phys. Chem. 1988,39 213. 74 K. Morokuma W. T. Borden and D. A. Hrovat J. Am. Chem. SOC.,1988 110 4474. I. H. Williams According to Morokuma et al.,the boat and chair Cope rearrangements are therefore both concerted and synchronous. AM 1 calculations for Cope rearrangements of bullvalene (9) and related molecules in which the boat geometry is enforced predict typical aromatic transition structures while a second biradicaloid transition structure occurs at higher energy." A CASSCF/4-31G study of the Diels-Alder addition of ethene to butadiene shows the synchronous transition structure for the concerted mechanism to be favoured by about 8 kJ mol-' over the non-synchronous transition structure leading to the syn-gauche intermediate in the stepwise mechanism; dynamic electron correlation would probably further favour the synchronous addition path.Minimal basis CASSCF/ STO-3G calculations however lead to quite different prediction^.^^ A perturbational evaluation of this reaction shows the importance of frontier-orbital interactions; they account for 70% of the covalent stabilization term.77 The observed behaviour of isocyanates in 1,3-dipolar cycloadditions to olefins is reproduced in a perturbational analysis only if the distortions of the reactants to their transition state geometries are considered; misleading results are obtained if undistorted isolated-molecule geometries are used.78 0 A synchronous concerted mechanism for decarbonylation of (10) is predicted at the MP2/4-3 1G level with a C, symmetrical transition structure whereas UHF/ STO-3G predicts a non-synchronous path; the large exothermicity of this reaction manifests itself in a low activation energy.79 Other cheletropic processes are predicted to be non-synchronous by semi-empirical but synchronous by ab initio calculations." MCSCF computations of analytical Hessians for 2s + 2a cycloaddition 'transition structures' of ethene with ethene ketene and singlet oxygen reveal these to be 75 M.J. S. Dewar and C. Jie Tetrahedron 1988 44 1351. 76 F. Bernardi A. Bottoni,'M. J. Field M. F. Guest I. H. Hillier M. A. Robb and A. Venturini J. Am. Chem. Soc. 1988 110 3050. 77 R. Sustmann P. Daute R. Sauer and W. Sicking Tetrahedron Lett. 1988 29 4699. 78 R. Sustmann and W. Sicking Tetrahedron 1988 44 379. 79 D. M. Birney K. B. Wiberg and J. A. Berson J. Am. Chem. Soc. 1988 110 6631. 80 J. J. Quirante J. F. Arenas and F. J. Ramirez THEOCHEM 1988 47 233. *' H. S. Rzepa J. Chem. Rex (S) 1988 224. Theoretical Organic Chemistry 37 second-order saddle points with two imaginary frequencies and cast doubt upon whether a supra-antara path actually exists for these reactions.82 Thermally 'forbidden' pericyclic reactions require at least a two-configuration treatment to provide a satisfactory description.A two-configuration SCF MIND0/3 semi-empirical method has been developed to permit the re-evaluation of earlier SCF and 2 x 2 CI MIND0/3 studies by Dewar and co-workers; the new results differ considerably from the old but are in qualitative agreement with those of ab initio MCSCF methods for ethene dimerization and for disrotatory ring opening of cyclobutene for which no transition structure exists.83 The AM1 method and electron-correlated ab initio MPn methods yield barrier heights for conrotatory ring opening of cyclobutene in agreement with experiment whereas this barrier is overestimated by the MNDO MIND0/3 and ab initio RHF methods.84 The barrier to automerization of rectangular cyclobutadiene by means of the square-planar anti-aromatic transition structure has been calculated by various ab initio methods; proper inclusion of non-dynamical electron correlation with a two-configuration wavefunction is found to be superior to extensive inclusion of dynamic correlation by the sophisticated CCSDT-1 method with a single-determinant referen~e.'~ The gauche conformer of the tetramethylene singlet biradical is probably the only significant intermediate in stepwise ethene dimerization; there is no PE barrier to its fragmentation but a small free-energy barrier owing to the decrease in entropy associated with a tightening of the terminal CH2 rotations as fragmentation pro- ceeds.86 Trimethylene singlet biradical does not exist as a free-energy intermediate at accessible temperatures but the possibility of a free-energy minimum at a PE maximum may occur for substituted derivative^.^^ Michl and BonaEiC-Kouteck9 have provided a unified view of biradicals and biradicaloids with examples including a-bond dissociation pericyclic reactions and geometrical isomerization.88 Solvation.-At least two specifically solvating water molecules are required to catalyse the thermal decarboxylation of p-aminosalicylic acid in aqueous solution.89 Supermolecular calc~lations~~ suggest that the Meyer-Schuster rearrangement of propargyl alcohol to asrolein is a solvent-assisted reaction with many-body bulk solvent effects having a passive role.Solvation by bulk water treated by a modified reaction-field method does not alter the conclusions of earlier supermolecular calculations of specific solvation effects on reactions of ~-nitrosamines~l or on tautomerism of dimethylpyra~ole.~~ Jorgensen has developed a set of optimized potentials for liquid simulations (OPLS) to describe intermolecular interactions particularly for proteins in their 82 F.Bernardi A. Bottoni M. Olivucci M. A. Robb H. B. Schlegel and G. Tonachini J. Am. Chem. SOC. 1988 110 5993. 83 J. M. Bofill J. Gomez and S. Olivella THEOCHEM 1988 40 285. 84 D. C. Spellmeyer and K. N. Houk J. Am. Chem. SOC. 1988 110 3412. 85 P. earsky R. J. Bartlett G. Fitzgerald J. Noga and V. Spirko J. Chem. Phys. 1988 89 3008. 86 C. Doubleday M.Page and J. W. McIver THEOCHEM 1988,40 331. 87 C. Doubleday M. Page and J. W. McIver J. Phys. Chem. 1988 92 4367. 88 J. Michl and V. BonaEit-Kouteck9 Tetrahedron 1988 44,7559. 89 P. Ruelle U. W. Kesselring H. Nam-Tran E. Ben-Rayana and A. Seddas J. Chem. Res. (S) 1988 90. 90 J. Andres R. Cardenas E. Silla and 0.Tapia J. Am. Chem. SOC.,1988 110 666. 91 R. Bonaccorsi J. Tomasi C. A. Reynolds and C. Thomson J. Compur. Chem. 1988,9 779. 92 M. HodoSEek D. Kocjan and D. Hadii THEOCHEM 1988.42 115. I. H. Williams native en~ironment.~~ Their use in Monte Carlo simulations of aqueous solvation of N-methylacetamide shows the sensitivity of such methods to the details of the potential functions; the unmodified parameters gave an incorrect result for the effect on the cis- trans energy difference in the peptide bond.94 Kollman has also developed many-body potentials for molecular interaction^,^' for use with the AMBER force field and has demonstrated the calculation of free energies of non-covalent associ- ation of nucleic acid bases in aqueous solution by free-energy perturba- tion/molecular dynamics methods.96 Redox potentials for benzoquinones have been calculated by a combination of methods MP2/6-31G* and AM1 to evaluate gas- phase free-energy differences and the free-energy perturbation method to calculate the hydration free-energy differences.Richards and co-workers suggest that ‘as the free-energy perturbation calculations and the ab initio calculations .. .require similar computational resources it appears that some treatment of hydration should now be carried out in all quantitative ab initio studies of energies of reaction in s~lution.’~’ 93 W.L. Jorgensen and J. Tirado-Rives J. Am. Chem. Soc. 1988 110 1657. 94 W. L. Jorgensen and J. Gao J. Am. Chem. SOC. 1988 110 4212. 95 A. E. Howard U. C. Singh M. Billeter and P. A. Kollman J. Am. Chem. Soc. 1988 110 6984. 96 P. Cieplak and P. A. Kollman J. Am. Chem. SOC.,1988 110 3734. 97 C. A. Reynolds P. M. King and W. G. Richards J. Chem. SOC.,Chem. Commun. 1988 1434; Nature (London) 1988 334 80.

ISSN:0069-3030    

DOI:10.1039/OC9888500027

出版商:RSC    

年代:1988

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 1 Cycloaddition Reactions The problem that has perhaps stimulated most interest in the past year is that of facial selectivity. A bold general solution to this problem was recently proposed by Hehre.' This involves mapping electrostatic potentials on the faces of the reacting molecules using an H+ or an H- ion as a probe. For a normal Diels-Alder reaction Hehre suggests there will be a match between the more electron-rich (nucleophilic) face of the diene and the more electron-poor (electrophilic) face of the dienophile as shown in diagram (1). Examples have been cited which follow this rule,'-3 but ELECTROPHILICITY H I Low NUCLEOPHILICITY ' S.D. Kahn and W. J. Hehre Tetrahedron Lett. 1986 27 6041; J. Am. Chem. SOC.,1987 109 663 and references therein. ' R. M. Ortuno M. Ballesteros J. Corbera F. Sanchez-Ferrando and J. Font Tetrahedron 1988,44 1711. M.J. Fischer W. J. Hehre S. D. Kahn and L. E. Overman J. Am. Chem. SOC.,1988 110 4625. 39 R. J. Bushby more have been found which do In the reaction between the sulphoxide (2) and N-phenylmaleimide,3 the failure to obtain the predicted syn-endo transition state is attributed to the local electrostatic interaction between sulphoxide and maleimide oxygens shown in (3). This illustrates one obvious drawback of using small structureless ions as probes for surface reactivity but Hehre's whole approach i.e. in using an electrostatic index for reactions which in other senses are FMO controlled is open to que~tion.~ -0S+ I 0-(2) In many cases of course steric factors dominate.For example in 27r + 47r additions to the allene-enes (4; 2 = H or ButMe,SiO-) the bulk of the substituents X and Y directs facial selectivity." Steric factors also seem to be important in additions of 1,3-dipoles to the bicyclo[3.2.0]-systems (5). These adopt the boat-like conformation shown and the degree of folding of the three-atom bridge can affect the ease of syn Another factor invoked to explain facial selectivity in 27r + 47r cycloaddition reactions of cyclobutene derivatives is out-of-plane bending of the vinyl hydrogens. Distortions of the type shown in formula (6) favour syn attack and those in formula (7) anti atta~k.~,~ The equivalent 'orbital tilting' explana- tion of Paquette and Gleiter has been invoked to explain the effect of substituents X on the facial selectivity in the reaction of compound (8) with (2)-1,2-bis(phenylsul- X R D.P. Curran and S. A. Gothe Tetrahedron 1988 44 3945. J. C. Lopez E. Lameignerc and G. Lukacs J. Chem. Soc. Chern. Comrnun. 1988 706; R. Tripathy R. W. Franck and K. D. Onan J. Am. Chem. Soc. 1988 110 3257. M. Burdisso R. Gandolfi P. Pevarello and A. Rastelli J. Chem. SOC.,Perkin Trans. 2 1988 753. ' M. Burdisso R. Gandolfi M. Lucchi and A. Rastelli J. Org. Chem. 1988 53 2123. H. Landen B. Margraf and H.-D. Martin Tetrahedron Lett. 1988 29 6593; H. Landen B. Margraf H.-D. Martin and A.Steigel ibid. p. 6597; H. Hake H. Landen H.-D. Martin,B. Mayer and A. Steigel ibid p. 6601. W.-S. Chung N. J. Turro S. Srivastava H. Li and W. J. le Noble J. Am. Chern. Soc. 1988 110 7882. lo J. B. Macaulay and A. G. Fallis J. Am. Chem. SOC.,1988 110 4074. H. J. Reich E. K. Eisenhart W. L. Whipple and M. J. Kelly J. Am. Chem. SOC.,1988 110 6432. Reaction Mechanisms -Purr (i) Pericyclic Reactions X I phonyl)ethylene.12 Addition syn to the -CH2-bridge is normally preferred but this preference is modulated by some substituents particularly those with a strong +M effect such as Me2N- and MeO-. In another intriguing study adamantane derivatives of type (9) have been used.' These eliminate the complications that normally arise from steric factors.Both in the thermal 27r + 47r reaction of the thione (9; X = S) with 2,3-dimethylbutadiene and in the photochemical 277 + 27r reaction of the ketone (9; X = 0) with fumaronitrile addition syn to the fluorine is observed. This was attributed to a hyperconjugative interaction between the developing u*bonds and the electron-rich trans-periplanar 1/8 and 3/ 10 bonds. Whilst it is not claimed that this hyperconjuga- tion argument constitutes a universal theory of facial selectivity other examples that can be treated in this way are cited. In a systematic study of Diels-Alder reactions of the cyclopentadienes (10; X = various S- 0-,and N-containing groups) facial selectivity was attributed to a mixture of effects." Particularly noteworthy is the change from syn selectivity in the cases X = OH and OMe to anti selectivity for the cases X = SMe SOMe and S02Me (reaction with maleic anhydride).The system X = SH gives an almost equal synlanti mixture. Me X 10& F Me Me Ab initio MO calculations have been reported for various thermal 2u + 2u,13 2a + 27r,14 and 27r + 27r" cycloaddition reactions and it is disturbing to note that ab initio/3-31G calculations find no true transition state for 7r2s + 7r2a cycloaddition of ketene to ethylene. The authors suggest that concerted pathways of this type do not exi~t.'~ Conversely thermochemical arguments suggest that some thern,al 2u + 2u (retro 7r2s + ~2s) reactions follow a concerted symmetry-forbidden pathway16 12 L. A. Paquette and M. Gugelchuk J.Org. Chem. 1988 53 1835; cf R. Gleiter and L. A. Paquette Acc. Chem. Res. 1983 16 328. 13 P. B. Shevlin and M. L. McKee J. Am. Chem. Soc. 1988 110 1666. 14 S. Yamabe T. Minato and S. Inagaki J. Chem. Soc. Chem. Commun. 1988 532. IS F. Bernardi A. Bottoni M. Olivucci M. A. Robb H. B. Schlegel and G. Tonachini J. Am. Chem. SOC. 1988 110 5993. 16 W. v. E. Doering W. R. Roth R. Breukmann L. Frigge H.-W. Lennartz W.-D. Fessner and H. Prinzbach Chem. Ber. 1988 121 1. R. J. Bushby rather than involving a 1,4-biradical intermediate. Studies of the effect of geometry on the 1,4-biradicals (1 1) generated photochemically in rigid crystalline media” show that biradicals in geometry (12) give mostly cleavage product and biradicals in geometry (13) cyclization product.This also neatly explains the tendency of cyclohexanone to give trans fused 27~ + 27r photoadducts without needing to invoke an initial cis/trans isomerization of the cyclohexanone double bond. Only biradicals whose geometries are analogous to (13) will give adducts. Those whose geometry is analogous to (12) will revert to starting materials. H H Studies of the singlet state 27r + 27r photodimerization of p-MeOC,H,CH=CHMe show that this too proceeds through 1,4-biradical intermedi- ates rather than a concerted 7~2s+ 7r2s pathway. The E precursor gives a product (14) in which the stereochemistries of both olefins are preserved but the 2 precursor gives products (15) and (16) in which one stereochemistry is inverted.18 Intramolcular ketene and keteniminium cycloadditions have been reviewed” and there have been several interesting studies of intramolecular Diels- Alder and 1,3- l7 S.Ariel S. V. Evans M. Garcia-Garibay B. R. Harkness N. Ornkaram J. R. Scheffer and J. Trotter J. Am. Chem. Soc. 1988 110 5591. ’* F. D. Lewis and M. Kojirna J. Am. Chem. Soc. 1988 110 8660. B. B. Snider Chem. Rev. 1988,88 793. Reaction Mechanisms -Part (i) Pericyclic Reactions dipolar cycloaddition reaction^.^'-^^ In the case of the furan derivatives (17) reac- tivity is shown to relate to the effect of substituents R on the population of relevant rotomeric states.20 In the intramolecular cycloaddition reaction of the yne-dienes (18; X or Y = -0-or -CH,-) steric interactions between the centres marked with an asterisk are a controlling factor.Hence reaction for the systems Y = -0-is considerably faster than for those where Y = -CH2-.” Molecular mechanics calculations for the intramolecular 1,3-dipolar additions (19) show a correlation between product ratios and product stabilities suggesting a late transition state.22 * CH,-X-CH,-Y-CH2-C=C-C02Me hO+C02Me RRO Me As usual there have been many reports of ways of speeding up 27r + 47r cycloaddi-tion reactions. These include the use of pres~ure,~~,~~ water formamide or ethylene glycol as solvent,26927 catalysis with aluminium trichloride28 or shift reagents,29 and the use of ultras~und.~~ In the case of reaction (20) (Pht = phthalide) it was shown NPht 2o M.E. Jung and J. Gervay Tetrahedron Lett. 1988 29 2429. 21 K. J. Shea L. D. Burke and W. P. England J. Am. Chem. SOC.,1988 110 860. 22 A. Hassner K. S. Murthy A. Padwa W. H. Bullock and P. D. Stull J. Org. Chem. 1988 53 5063. 23 E. C. Angell F. Fringuelli F. Pizzo A. Taticchi and E. Wenkert J. Org. Chem. 1988 53 1424; S. Lamothe A. Ndibwami and P. Deslongchamps Tetrahedron Lett. 1988 29 1639 1641; G. R. Krow Y.B. Lee R. Raghavachan P. V. Alston and A. D. Baker Tetrahedron Lett. 1988,29,3187; A. Marinier and P. Deslongchamps Tetrahedron Lett. 1988 29 6215; L. F. Tietze T. Brumby S. Brand and M. Bratz Chem. Ber. 1988 121 499. 24 A. Sera M. Ohara T. Kubo K. Itoh H. Yamada Y. Mikata C. Kaneto and N. Katagiri J. Org. Chem. 1988 53 5460; R. M. Ortuno A.Guingnant and J. d’Angelo Tetrahedron Lett. 1988 29 6989; D. L. Boger and K. D. Robage J. Org. Chem. 1988 53 3373. 25 L. F. Tietze T. Hubsch E. Voss M. Buback and W. Trost J. Am. Chem. SOC.,1988 110 4065. 26 S. Colonna A. Manfredi and R. Annunziata Tetrahedron Lett. 1988 29 3347. 27 A. G. Griebeck Tetrahedron Lett. 1988,29 3477; T. Dunams W. Hoekstra M. Pentaleri and D. Liotta ibid. p. 3745; R. Breslow and T. Guo J. Am. Chem. SOC.,1988 110 5613. 28 E. Wenkert P. D. R. Moeller and S. R. Piettre J. Am. Chem. SOC.,1988 110 7188. 29 R. P. Gandhi M. P. S. Ishar and A. Wali J. Chem. SOC.,Chem Commwn. 1988 1074. 30 D. R. Borthakur and J. S. Sandhu J. Chem. Soc. Chem. Comun. 1988 1444. R. J. Bushby that the diastereoselectivity is also significantly pressure dependent,25 whereas for reaction (21) in water a degree of asymmetric induction (38% ee) is obtained by adding bovine serum albumin.26 There have also been reports that 27r + 47r cyclo-addition reactions can be accelerated by adsorption of the reactants on chromato- graphic supports.31 4-31G Ab initio MO calculations on the reaction between ethylene and butadiene suggest that it is synchronous but that this energy surface is not far separated from that for a non-synchronous mechanism.32 Experimental evidence for the synchronous nature of the Diels-Alder reaction has been adduced from an LFER study of the reaction between cyclopentadiene and the sulphones (22).33 Secondary isotope effects for 2a + 2a + 27r cycloadditions of quadricyclane and 27r + 271-+ 27r cyclo-additions of norbornadiene suggest that these reactions are non-synchronous but concerted,34 and calculations on the reaction of nitrile oxides with acetylene also suggest non-synchronous bond formation.35 Ar’ -SO,-CH=CH -SO,-ArZ (22) It has recently been suggested that endo selectivity in the Diels-Alder reaction is the result of steric rather than secondary orbital factors.Indeed steric effects seem satisfactorily to account for endo selectivity in the 271-+ 47r addition of thioaldehydes to ~yclopentadiene.~~ However a detailed study of Diels- Alder reactions of trans-penta-1,3-diene has come down in favour of the ‘more traditional’ secondary orbital interaction interpretation of the stere~chemistry.~’ Among interesting routes to reactive 47r system^^^-^' are the generation of the azomethine ylides (23; R = H alkyl or aryl) by decarboxylative addition of aromatic 3’ V.V. Veselovsky A. S. Gybin A. V. Lozanova A. M. Moiseenkov W. A. Smit and R. Caple Tetrahedron Lett. 1988 29 175; M. Koreeda D. J. Ricca and J. I. Luenge J. Org. Chem. 1988 53 5586. 32 F. Bernardi A. Bottoni M. J. Field M. F. Guest I. H. Hillier M. A. Robb and A. Venturini J. Am. Chem. Soc. 1988 110 3050. 33 R. A Hancock and B. F. Wood 1.Chem. SOC.,Chem. Commun. 1988 351. 34 L. A. Paquette M. A. Kesselmayer and H. Kiinzer J. Org. Chem. 1988 53 5183. 35 R. Sustmann and W. Sicking Tetrahedron 1988 44,379. 36 E. Vedejs J. S. Stults and R. G. Wilde J. Am. Chem. SOC.,1988 110 5452. 37 0.F. Giiner R. M. Ottenbrite D. D. Shillady and P. V. Alston J. Org. Chem. 1988 53 5348. 38 R. Grigg S. Surendrakurnar S. Thianpatanagul and D. Vipond J. Chem. SOC.,Perkin Trans. 1 1988 2693; R. Grigg J. Idle P. McMeekin S. Surendrakumar and D. Vipond ibid. p. 2073. 39 A. Padwa and B. H. Norman Tetrahedron Lett. 1988 29 2417. 40 C. W. G. Fishwick A. D. Jones M. B. Mitchell and C. Szhntay Tetrahedron Lett. 1988 29 5325; Y. Terao A. Aono and K. Achiwa Heterocycles 1988 27 981. 41 A. Padwa and P. E. Yeske J. Am. Chem. SOC.,1988 110 1617. Reaction Mechanisms -Part (i) Pericyclic Reactions 45 R I A=+ N+\-N+ CR'R" R2CH '*-+ CH,=CH-C( OEt) aldehydes to amino the generation of the nitrones (24) by the reaction of vinyl sulphones and ~ximes,~~ various desilyation routes to 1,3-dip0les,4~ and the formation of the ally1 anions (25) by the addition of X-(CN- NO2- or PhS02-) to CH2=C=CHS02Ph?1 The reactive 27r system S2can be obtained by thermolysis of the disulphide (26),42 and further evidence has been advanced of remarkably high reactivity of cation (27) in 27r + 47r cycloaddition reactions.43 2 Sigmatropic Reactions The 1,3-sigmatropic rearrangement leading from compound (28) to compound (29) proceeds as shown with predominant inversion at the migrating carbon although some ST product is also obtained.The stereochemistry of this reaction was assessed directly from small amounts of (29) isolated from the reaction mixture and also on the major product ethylene which is formed by a retro-Diels- Alder reaction.The stereochemistry was explained in terms of competing concerted and biradical pathways.44 An equivalent biradical pathway for the 1,3-sigmatropic rearrangement of bicyclo[3.1 .O]hex-2-ene (30) would give the symmetrical intermediate (3 1). Previous studies have failed to detect such a symmetrical intermediate but clear evidence has been provided for an equivalent vinyl-TMM intermediate (32) in the rearrangement of derivatives of the 6-methylene compound (33)."' The 'forbidden' 1,3-sigmatropic rearrangement of compound (34) can be greatly accelerated by forming the radical cation with a small amount of Ar3Nt SbF6-.46 42 W. Ando H. Sonobe and T. Akasaka Tetrahedron Lett. 1987 28 6652. 43 P. G. Gassman and S.P. Chavan J. Org. Chem. 1988 53 2393. 44 J. E. Baldwin and K. D. Belfield J. Am. Chem. SOC.,1988 110 296; F.-G. Klarner R. Drews and D. Hasselmann ibid.,p. 247. 45 S. Pikulin and J. A. Berson J. Am. Chem. Soc. 1988 110 8500. 46 J. P. Dinnocenzo and D. A. Conlon J. Am. Chem. SOC.,1988 110 2324. R. J. Bushby An interesting example of regioselectivity in a 1,Shydrogen shift is shown by compound (35; Ar = 3,4,5-trimethoxyphenyl),where the hydrogen indicated is the one to migrate. The conformation required for this particular 1,5-shift is easy to attain but that required for a 1,5-shift of the neighbouring hydrogen results in a severe steric interaction between the Ar and C02Me grouping^.^' The endo conforma-tion shown (36) is that required for the observed formation of cis-hexa-1,4-diene by a homodienyl 1,5-shift.Ab initio MO calculations at the 3-21G level confirm that this should be the case.48 Discrepancies between the calculated and experimental kinetic isotope effects for the simplest 1,Shydrogen shift (37; L = H or D) have been explained by the assumption that some tunnelling OCCU~S,~~ and experimental evidence for such tunnelling has been claimed in a study of the 1,7-hydrogen shift (38; L = H or D) for which kH/k = 7.0 at 60"C.50 The claim of a remarkably high kinetic isotope effect (kH/kD -45 at 80 "C) for the 1,7-hydrogen shift in the conversion of previtamin D into vitamin D3 has now been withdrawn" and new measurements for a 19,19,19-trideuteriated derivative give the more acceptable value of k,/kD -6.1 at 80 0C.52 Several reinvestigations of the vitamin D system have been reported this A measurement of the volume of activation for the conversion of previtamin D3 into vitamin D, A V# = -5.14 cm3 mol-' at 20 0C,54 is taken as evidence for a concerted 1,7-hydrogen shift and n.m.r.studies have challenged previous claims that previtamin D3 exists entirely in the S-cis-S-cis conformation (39) providing evidence for significant population of the S-trans-S-cis conformation (40).55 47 D. W. Jones and A. M. Thompson J. Chem. SOC.,Chem. Comrnun. 1988 1095. 48 R. J. Loncharich and K. N. Houk J. Am. Chem. Soc. 1988 110 2089. 49 M. J. S. Dewar E. F. Healy and J. M. Ruiz J. Am. Chem. SOC.,1988 110 2666. 50 J. E. Baldwin and V.P. Reddy J. Am. Chem. SOC.,1988 110 8223. 51 Y. Mazur and M. Sheves in ref. 52. 52 W. H. Okamura C. A. Hoeger K. J. Miller and W. Reischl J. Am. Chem. SOC.,1988 110 973. 53 W. G. Dauben P. E. Share and R. R. Ollmann J. Am. Chem. Soc. 1988 110 2548. 54 W. G. Dauben B. A. Kowalczyk and D. J. H. Funhoff Tetrahedron Lett. 1988 29 3021. 55 W. G. Dauben and D. J. H. Funhoff J. Org. Chem. 1988 53 5376. Reaction Mechanisms -Part (i) Pericyclic Reactions R R 14C and l80kinetic isotope effects have been measured for the aromatic Claisen rearrangement (41). Together with previous measurements of *H kinetic isotope effects it is claimed that these show a concerted non-synchronous mechanism in which the C,-0 bond is 50-60% broken and the C,-Co bond 10-20% formed in the transition state.56 A rather similar picture with a concerted non-synchronous mechanism and appreciable C-0 bond breaking was arrived at from ab initio MO calculations for the corresponding aliphatic Claisen rea~angement.~’ Calculations on the Cope rearrangement (including CI) suggest that it is concerted and syn- chrono~s.’~ Despite these indications that 3,3-sigmatropic rearrangements are con- certed the suggestion that such rearrangements involve 1,4-biradical intermediates still attracts attention providing cause for lively debate and innovative experimenta- tion.It has been argued that the stereospecificity of the 3,3-sigmatropic rearrange- ment (42) is only consistent with a concerted mechanism or the 1,4-biradical (43) if involved being exceedingly short lived.59 Further evidence against a 1,4-biradical intermediate in the Cope rearrangement has come from a comparison of the normal reaction and that of the radical cation.60 By way of contrast to the normal reaction these radical cation reactions do proceed through a 1,4-radical cation which can be trapped.This is shown by the isolation of peroxide (44) from the catalysed rearrange- ment of compound (45).61 The 1,4-biradical mechanism for 3,3-sigmatropic re- 04“. / 56 L. Kupczyk-Subotkowska W. H. Saunders and H. J. Shine J. Am. Chem. SOC.,1988 110 7153. 57 R. L. Vance N. G. Rondan K. N. Houk F. Jenson W. T. Borden A. Komornicki and E. Wimmer J. Am. Chem. SOC.,1988 110 2315. 58 K. Morokuma W.T. Borden and D. Hrovat J. Am. Chem. SOC.,1988 110 4474. 59 K. A. Owens and J. A. Berson J. Am. Chem. SOC.,1988 110 627. 60 Q.-X. Guo X.-Z. Qin J. T. Wang and F. Williams J. Am. Chem. SOC.,1988 110 1974. 61 T. Miyashi A. Konno and Y. Takahashi J. Am. Chem. SOC.,1988 110 3676. R. J. Bushby arrangements represents one end of the mechanistic spectrum. The other end of this spectrum is a mechanism in which bond breaking precedes bond formation and a pair of allyl radicals is involved. Possible evidence for such a mechanism has been provided from studies of the 1,5-diene (46; E = C0,Me). When this is heated in the presence of oxygen the peroxides (48) and (49) are isolated which can be formulated as arising from the di-ally1 radical (47).62 Undeterred by exceptions to his facial selectivity rule for cycloaddition reac- tion~,~-"Hehre has suggested that a similar treatment can explain asymmetric induction in 3,3-sigmatropic rearrangement^.^^ In Ireland-Claisen rearrangements the oxyallyl portion is treated as being nucleophilic and the allyl portion as elec- trophilic.Mapping electrostatic potentials on the surface of each portion and matching the more electron-rich surface of the ester enolate to the more electron-poor surface of the allylic olefin leads to the chair-like transition state (50). Hence the fact that compound (52) is the predominant diastereoisomer obtained by rearrange- ment of the diene (51) (THP = tetrahydropyranyl) is interpreted by Hehre in terms of the transition state (53) in which (provided the C-H bond eclipses the C=C bond) the electron-poor face of the allylic portion is uppermost.NUCLEOPHILICITY ELECTROPHILICITY (50) 62 R. Iyengar R. Pina K. Grohmann and L. Todaro J. Am. Chem. Soc. 1988 110 2643. 63 S. D. Kahn and W. J. Hehre J. Org. Chem. 1988 53 301. Reaction Mechanisms -Part (i) Pericyclic Reactions O(THP) (53) The 3,3-sigmatropic rearrangement of chorismate (54; R = H) to prephenate is normally catalysed by the enzyme chorismate mutase. It has been shown that this enzyme will also accept the methylated analogue (54; R = Me) and the stereochemistry of the product confirms previous indications that the enzyme- catalysed rearrangement proceeds through a chair-like transition state.64 It has also been shown that the stereospecific 3,3-sigmatropic rearrangement of chorismate (54; R = H) can be catalysed by an antibody elicited against a chorismate mutase inhibit~r.~’ Labelling studies have now confirmed that the thermal rearrangement of the bicyclo[4.1 .O]-system (55) proceeds by the 3,5-sigmatropic shift mechanism shown and not a 1,3-sigmatropic mechanism.66 3 Electrocyclic Reactions The electrocyclic ring opening of cyclobutene has been used as a test case in a comparison of a wide range of MO methods.A6 initio MO calculations using large basis sets give results that compare well with experimental data but in this test semi-empirical and STO-3G a6 initio methods perform rather p~orly.~’ In this reaction C3 or C4 alkoxy substituents tend to rotate outwards and a dramatic demonstration of this rotational preference is provided by the t-butyl-substituted systems (56; R = Me and Me,Si) where the products obtained were the olefins (57)? 64 D.Lesuisse and G. A. Berchtold J. Org. Chem. 1988 53 4992. 65 D. Hilvert and K. D. Nared J. Am. Chem Soc. 1988 110 5593. 66 P. J. Battye D. W. Jones and H. P. Tucker J. Chem. Soc. Chem. Commun. 1988,495. 67 D. C. Spellmeyer and K. N. Houk J. Am. Chem Soc. 1988 110 34-12. 68 K.N. Houk D. C. Spellmeyer C. W. Jefford C. G. Rimbault Y. Wang and R.D. Miller J. Org. Chem. 1988 53 2125. R. J. Bushby 40R I But Bu' Perhaps the most interesting finding of the past year however has been that in reactions of this sort there is a different kinetic secondary isotope effect for the hydrogens rotating inwards and those rotating outwards.For the conversion of (58) into (59) kH/kD = 1.04 * 0.03 (140 "C),while for (58) -+ (60) kH/kD = 1.15 * 0.03; for the conversion of (61) into (63) kH/kD = 1.05 0.03 while for (62) -+ (63) kH/kD = 0.88 f 0.06. These kinetic secondary isotope effects can be fitted to calcu- lated values from which it is seen that the differences arise from various causes. In the four-electron electrocyclic reaction the major factor is differences in the p-character of the C-H bonds but in the six-electron electrocyclic reaction the difference is one of steric comp~ession.~~ 4 Miscellaneous Pericyclic Reactions Ab initio MO calculations on the thermal elimination of carbon monoxide from 9-ketonorbomadiene (64) suggest a linear suprafacial process which is concerted and synchrono~s.~~ When this molecule is generated in a vibrationally excited state it tends to eliminate carbon monoxide spontaneously.This occurs when the pyrazo- line (65) is photolysed in an argon matrix at 10 K. However when the pyrazoline (65) is photolysed in a frozen toluene matrix at 195 K much less decarbonylation occurs and quite a high yield of the ketone is isolated. The explanation given to %JN CN I1 N=N CN 69 J. E. Baldwin V. P. Reddy B. A. Hess and L. J. Schaad J. Am. Chem. SOC 1988 110 8554 8555. D. M. Birney K. B. Wiberg and J. A. Berson J. Am. Chem. Soc. 1988 110 6631. Reaction Mechanisms -Part (i) Pericyclic Reactions this seeming paradox is that a frozen toluene matrix has vibrational modes which can couple with those of the ketone (64) effectively removing excess vibrational energy but equivalent vibrational modes are not present in an argon matrix.” A study of the dehydrogenation of cyclohexa-l,4-diene derivatives with tetracyanoethylene has concluded that the first step is normally an ene reaction giving (from the parent system) compound (66),which then probably breaks down by a heterolytic route.Some reaction may however occur through a stepwise electron-proton transfer me~hanism.’~ 71 B. F. LeBlanc and R. S. Sheridan J. Am. Chem. SOC.,1988 110 7250. 72 B. M. Jacobson P. Soteropoulos and S. Bahadori J. Org. Chern 1988 53 3247.

ISSN:0069-3030    

DOI:10.1039/OC9888500039

出版商:RSC    

年代:1988

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 DHI 3LE 1 Introduction Volume 24 of Advances in Physical Organic Chemistry contains three chapters of interest. Nibbering' discusses the gas-phase reactions of organic ions the review covers the formation of such species as well as many of their reactions including H/ D exchange addition/elimination elimination cycloaddition etc. and stresses the major progress made in the past decade principally resulting from the develop- ment of the necessary sophisticated equipment. Hydride shift and transfer reactions are covered by Watt,* including metal-to-carbon transfers and both anionic and cationic carbon-to-carbon hydride transfers and shifts.The third contribution by Sinnott3 is possibly more controversial and discusses the relative merits of the theory of the principle of least nuclear motion (PLNM) and the antiperiplanar lone pair hypothesis (ALPH) as explanations of factors responsible for stereoelectronic control of reactions. The author argues the case for the former principle mainly on the grounds that the latter is too fundamental and does not cater for observed exceptions to the hypothesis which can be accommodated by PLNM. Two other review articles deal with simple enols one by Capon and co-workers discusses their generation in solution their kinetic stability and also KE determina-tion; the other by Rappoport and Biali' (and dedicated to Professor Saul Patai on the occasion of his 70th birthday) covers the chemistry of sterically crowded simple enols.Here since KE values are generally large the problem in their determination is the accurate measurement of low concentrations of the keto form (the reverse of the more commonly encountered situation). Steric effects alone do not appear to be able to account for the thermodynamic stability of these enols. Two reviews of the importance of SET reactions in organic chemistry have been published. Ashby6 argues that it is a major pathway even for some so-called SN2 processes (but in some cases a2companying the classical mechanism). The SET mechanism is particularly important for substitution in alkyl iodides and is also a major route in reactions of aromatic (but not aliphatic) ketones with some ' N.M. M. Nibbering Adv. Phys. Org. Chem. 1988 24 1. * C. I. F. Watt Ado. Phys. Org. Chem. 1988 24 57. ' M. L. Sinnott Adv. Phys. Org. Chem. 1988 24 113. B. Capon B.-Z. Guce F. C. Kwok,A. K. Siddhanta and C. Zucco Acc. Chem. Res. 1988 21 135. Z. Rappoport and S. E. Biali Acc. Chem. Rex 1988 21 442. E. C. Ashby Acc. Chem. Res. 1988 21 414. 53 D. L. H. Williams nucleophiles. The main experimental evidence comes from the use of well-known cyclizable radical probes. Kochi7 considers all nucleophiles and electrophiles as electron donors and acceptors respectively. Marcus theory is used to produce generalized free energy relationships for electron transfer and their applicability is demonstrated over a wide range of reaction types; the approach confirms for example that a radical-ion pair is a possible intermediate in electrophilic aromatic nitration.The new Journal of Physical Organic Chemistry was first published in 1988; reference will be made to individual papers later in this Report. One issue of Bulletin de la Socie'te' Chimique de France is given over to the proceedings of a successful conference in Paris (July 1987) entitled 'Organic Reactivity'; again individual references will be made later. 2 Solvolysis and Carbocations Previously measurement of the magnitude of the volume of activation AV* has failed to distinguish clearly between sN1 and SN2 mechanisms because at the relatively low pressures used the AV* term is dominated by the electrostriction of the solvent resulting from the high dipole moment of the activated complex.Con- sequently AV* values are negative for both mechanisms. Now it is argued' that at very high pressures (typically up to 70 kbar) the compressibility of the solvent becomes very small and likewise the electrostriction effect. Therefore at these very high pressures A V' for sN1 reactions should become positive whilst for SN2 reactions it remains negative. Results are presented for the reactions of methyl iodide and t-butyl chloride in glycerol which bear out these predictions experimentally. The value of A V* stays negative for the former up to 70 kbar whilst for the latter A V' becomes positive above 16 kbar. The symmetrically bridged structure for the 2-norbornyl cation (1) was first deduced by Winstein and Trifan over 30 years ago and there has been much controversy over it since.The high exo/ endo rate ratio in the 2-norbornyl sulphonates has now been shown to be electronic in origin and much influenced by remote substituents evidence which supports non-classical stabilization of the 2-norbornyl cation. The possibility of homoallylic participation previously predicted by theoreti- cal calculations has now been demonstrated experimentally lo as a large destabilizing effect in the transition state leading to the cyclopent-3-en-1-yl cation in the solvolysis of the sulphonate. Solvolysis of 2-(2-methoxyethoxy)ethyl tosylate occurs by two 'J. K. Kochi Angew. Chem. Int. Ed. Engl. 1988 27 1227. C. Cameron P. S. P. Saluja M. A. Floriano and E.Whalley J. Phys. Chem. 1988 92 3417. 'D. Lenoir Y. Apeloig D. Arad and P. von R. Schleyer J. Org. Chem. 1988 53 661. T. W. Bentley B. Irrgang H. Mayr and P. von R. Schleyer J. Org. Chem. 1988 53 3492. Reaction Mechanisms -Part (ii) Polar Reactions competing pathways," one involving RO-6 neighbouring group participation the other solvent-assisted displacement. The observation of a large kinetic isotope effect (kH/kD = 1.15) for the solvolysis of cis- and trans-2-aryl cyclopentyl tosylates (with D substitution in the 2 position) in HC02H; AcOH and EtOH solvents has been rationalizedI2 in terms of classical intimate ion-pair formation followed by dissoci- ation to a solvent-separated ion pair without participation by the solvent the 2-aryl group or a hydrogen atom at C2.It is argued that 2-adamantyl substrates would make better models for a Y solvent ionizing power scale than t-butyl substrates because the rigid cage structure in the former prevents any backside solvent nucleophilic attack. Such a YPFss scale has now been produced from kinetic data on the solvolysis of 2-adamantyl penta- fluorobenzenesulphonate and the relative merits of such scales discussed.' The kinetics of solvolysis of RC6H,CH(CSNMe2)02CCF3 show that the thioamide group CSNMe2 is very effective at stabilizing the developing positive charge in the transition ~tate.'~ This can occur by formation of cyclized structures and/or by charge delocalization to the sulphur atom. The experimental evidence in the literature as to the relative stabilities of a-oxy- and a-thiocarbocations is inconclusive.Calculations by ab initio methods have shown that both are stabilizing to a comparable degree the net effect of the oxygen substituent being slightly the greater." The importance of the (often neglected) ground state energies of the neutral precursors is stressed. Carbocation stabilization by a-Si- a-Ge- and a-Sn- containing groups has been demonstrated experimentally by the hydrolysis of the a-metalloidal vinyl ethers (equation l) where protonation is rate limiting.I6 The observed sequence is CMe > SnMe,> GeMe > SiMe > H. H+ CH,=C(OMe)MMe3 -CH,&(OMe)MMe (1) Studies on the hydrolysis of the vinyl ether group in homoprostacyclin (2) show that intramolecular catalysis by the carboxy group is much less than it is in the naturally occurring prostacyclin itself (3) which differs structurally only by one I OH OH S.P. McManus R. M. Karaman B. A. Hovanes M. S. Paley and J. M. Harris J. Org. Chem. 1988 53 681. 12 G. Ronco J. P. Petit R. Guyon and P. Villa Helv. Chim. Actq 1988 71 648. l3 D. C. Hawkinson and D. N. Kevill J. Org. Chem. 1988 53 3857. 14 X. Creary and T. E. Aldridge J. Org. Chem. 1988 53 3888. lS Y. Apeloig and M. Karni J. Chem. SOC.,Perkin Trans. 2 1988 625. 16 J. A. Soderquist and A. Hassner Tetrahedron Lett. 1988 29 1899. D. L. H.Williams methylene group,l7 This suggests that prostacyclin has obtained by natural evolution the correct lifetime (in hydrolysis) to be effective as an inhibitor of blood platelet aggregation in the physiological mechanism for the control of bleeding.Surprisingly the extra rigidity of an aromatic over an aliphatic system does not improve the efficiency of intramolecular catalysis (measured by its EM) in vinyl ether hydroly- sis.'* It is suggested that the expected gain from the rigidity of the aromatic system is offset by the reduced conjugation between vinyl ether group and the aromatic ring in the transition state. Abraham and co-worker~'~ have presented a complete analysis of solvent effects for the solvolysis of t-butyl halides for 20-30 solvents using thermodynamic methods. The effect on AG* AH* and AS* has been separated into contributions due to the initial state and the transition state.The decrease in AG* due to solvent dipolarity and also to solvent hydrogen bond acidity arises from a transition state effect. Solvent hydrogen-bond basicity has little effect and the large effects of the solvent Hildebrand solubility parameter largely cancel each other out in the initial and transition states. Solvolysis of thiophene-2-sulphonyl halides in water and acetone-water mixtures (equation 2) shows many mechanistic features in common with the corresponding X 4 xn SOzHal + HzO S03H + HHal S S reactions of benzoyl halides and involves concurrent nucleophile-sulphur bond making and sulphur-halogen bond breaking.20 3 Other Nucleophilic Substitutions Katritzky and Brycki2' have reviewed the mechanistic borderline area between sN1 and S,2.Kinetic evidence with substrates having neutral leaving groups argues in favour of the view that both mechanisms occur independently and simultaneously in the mechanistic borderline region. The results for the sN1 reactions studied can all be accommodated by a mechanism involving either intimate ion-molecule pair or free carbocation intermediates. The dominant reactions of 2-(alky1thio)ethyl derivatives with nucleophiles involve participation by the neighbouring sulphur atom ( kA).A direct sN2 reaction has now been achieved for the first time by the use of very powerful nucleophiles (2-naphthalenethiolate and p-aminothiophenolate) in DMSO solvent.22 Second-order kinetics were found together with the absence of rearranged products using D-labelled reactants.Y. Chiang and A. J. Kresge J. Chem. Soc. Perkin Trans. 2 1988 1083. 18 A. J. Kresge and Y. Yin J. Phys. Org. Chem. 1988 1 247. 19 M. H. Abraham P. L. Grellier A. Nasehzadeh and R. A. C. Walker J. Chem. Soc. Perkin Trans. 2 1988 1717. 2o A. Arcoria F. P. Ballistreri E. Spina G. A. Tomaselli and E. Maccarone J. Chem. Soc. Perkin Trans. 2 1988 1793. 21 A. R. Katritzky and B. E. Brycki J. Phys. Org. Chem. 1988 1 1. 22 M. R. Sedaghat-Herati S. P. McManus and J. M. Harris 1. Org. Chem. 1988 53 2539. Reaction Mechanisms -Part (ii) Polar Reactions 57 The argument concerning the importance of SET in nucleophilic substitution reactions continues. Ashby has reviewed his position.6 Newcomb et ~1.’~ have argued that the earlier results of Ashby and Pham24 do not in fact support the SET mechanism but rather the traditional sN2 pathway; new and literature rate constants for the reduction of alkyl iodides with lithium aluminium hydride are subjected to a detailed kinetic analysis which it is claimed fit the classical mechanism that takes place in competition with a slower radical chain initiation reaction.Reaction of 9-bromoanthracene with thiolate anions in tetraglyme gives in addi- tion to the 9-(phenylthio) derivative anthracene (equation 3).25The presence of the Br SR latter is rationalized in terms of a SET mechanism which is believed to occur in competition with the expected SNAr mechanism. An experimental evaluation of the VBCM model of Shaik and Pross has been attempted.26 Rate constants (k) for reaction between conjugated nucleophiles and alkyl and benzyl halides were measured by cyclic voltammetry.The SET uersus sN2 character of the transition state was obtained from k/k, ratios where &Ex is the rate constant for reaction between an anion radical A-‘ with the same oxidation potential as the nucleophile and alkyl halide in question. The main conclusion is that the VBCM model has reasonably good predictive power for reactions where the transition state is SET-like. The reaction of acetyl chloride with tetraethylammonium fluoride in acetic acid yields an equilibrium concentration of acetyl fluoride. The reaction has been studied kinetically using I9F n.m.r.” The results are in accord with a sequence of reactions set out in equations 4-6 involving rapid formation of acetic anhydride and hydrogen AcCl +AcOH e Ac20+ HCl (4) HCl+F-HF+CI-(5) Ac20+HF * AcF+AcOH (6) fluoride which then react to give acetyl fluoride.The reactions of acyl chlorides with methanol and phenol have also been studied kinetically in acetonitrile solvent.’* Methanolysis is believed to occur by the SN2 mechanism with a loose transition state whereas phenolysis occurs by an electrophilically assisted ionization mechanism. Kevill and F~jimoto*~ have produced a new nucleophilicity scale for anions based on their reactions with the triethyloxonium ion in ethanol. 23 M. Newcornb J. Kaplan and D. Curran Tetrahedron Lett. 1988 29 3451. 24 E. C. Ashby and T. N. Pharn Tetrahedron Lett.1987 28 3197. 2s S. D. Pastor Helu. Chim. Acta 1988 71 859. 26 T. Lund and H. Lund Acta Chem. Scand. Ser. B,1988 42 269. 27 J. Emsley V. Gold F. Hibbert and W. T. A. Szeto J. Chem. SOC.,Perkin Trans. 2 1988 923. 28 D. N. Kevill and C.-B. Kim J. Chem. Soc. Perkin Trans. 2 1988 1353; Bull. SOC.Chim. Fr. 1988 383. 29 D. N. Kevill and E. K. Fujimoto J. Chem. Res. (S) 1988 408. D. L. H. Williams 4 Elimination Reactions Chuchani and his group continue their investigations of elimination reactions in the gas phase. Kinetic measurements on the pyrolysis elimination of methyl 4-bromocr~tonate~~ reveal that the carbomethoxy group provides anchimeric assist- ance to reaction; this and other results are consistent with a polar mechanism now well established for such reactions in the gas phase.Also in the gas phase elimination reactions of cyclic thioethers have been studied by Fourier transform ion cyclotron re~onance.~~ Three reactions occur (in varying proportions depending on the ring size) E2 a’$-elimination and SN2 substitution. The E2 and a’,P-elimination reactions are stereoelectronically controlled (as they are in solution) and the gas-phase acidity of the sulphides decreases as the sulphide becomes more strained. Rate measurements deuterium exchange experiments and kinetic solvent isotope effects show that the elimination reactions of P-cyano thioethers takes place via a carbanion E 1cB mechanism32 (equation 7). The rate-limiting step changes with the HH H NC H II I NC-C-C-R 5NC-C-C-R ‘C=C/ +RS-(7) A‘ AR BH+ A‘ 4R R‘/ ‘R pK of the thiol derived from the leaving group.The second of the two papers discusses the lifetime of the carbanion intermediate. The elimination of hydrogen chloride from fluorene derivatives is discussed with reference to the E lcB-E2 mechanistic b~rderline.~~ Kinetic isotope effects and Brdnsted p-coefficients are measured and the change from ElcB to E2 rationalized in terms of structural changes in the leaving group and the acidity of the substrate proton. A theoretical paper uses ab initio MO calculations to establish transition state geometries of both E2 and SN2 reactions involving ethyl halides and halide ions.34 The transition states are thought to be different as a result of the repulsion of an attacking base from the C,-C region in the E2 case by the incipient .rr-electron cloud.In a communication entitled ‘Isotope Effects on Isotope Effects’ secondary tritium isotope effects have been measured in the E2 reactions of ArCLTCH2X and ArCL2CH2X(L = H or D) and discussed in terms of a contribution due to tunnel- ling.35 Earlier calculations had predicted that the tunnel correction should be smaller when the transferred atom is deuterium rather than protium. This is now supported by the experimental results. 5 Addition Reactions Ab initio MO calculations of the transition state structures in the addition of molecular halogens to ethene have been pre~ented.~~ The results show that the 30 G. Chuchani and I. Martin Int.J. Chem. Kinet. 1988 20 1. 31 L. J. de Koning and N. M. M. Nibbering J. Am. Chem. Soc. 1988 110 2066. 32 J. C. Fishbein and W. P. Jencks J. Am. Chem. Soc. 1988 110 5075 5087. 33 A. Thibblin J. Am. Chem. Soc. 1988 110,4582. 34 T. Minato and S. Yamabe J. Am. Chem. SOC.,1988 110 4586. ’* M. Amin R. C. Price and W. H. Saunders J. Am. Chem. Soc. 1988 110 4085. 36 S. Yamabe T. Minato and S. Inagaki J. Chem. Soc. Chem. Commun. 1988 532. Reaction Mechanisms -Part (ii) Polar Reactions 59 fluorine reaction proceeds via a four-centre transition state whilst both chlorine and bromine react via zwitterionic three-centre transition states. This accounts for the observed stereoselective anti addition of chlorine and bromine and of syn addition for the fluorine reaction.Last year’s Report contained details of the argument in favour of the reversible formation of the bromonium ion in electrophilic bromination. Now the same group3’ has confirmed this view by showing that bromonium ions react with bromide ion at the bromonium Br+ to give free bromine and the corresponding alkene (see equation 8). Br Br + Br2 I X It has been suggested that N-bromosuccinimide and N-bromoamides react with a,P-unsaturated ketones by removing acid and so causing a change from the acid-catalysed mechanism to one involving bromonium ion intermediate formation.38 The evidence is based on the increase in the product ratio Markovnikov anti- Markovnikov as the concentration of the N-bromo reactant is increased.Halogenation of simple enols has been thought of as a classical diffusion- controlled reaction. This view has now been challenged and results presented39 for bromine reactions in water. Using the more accurate recent values for KE it is possible to obtain the second-order rate constants for reaction with the enol with more reliability than hitherto. Although the values for a range of enols are large (typically 14 x lo9 M-’ s-I) they are not quite at the calculated limit and further- more show some substrate selectivity in the expected sense for a ‘chemically’ controlled reaction. Specifically the rate constants increase as the electron-releasing capacity of substituents in acetophenone enols is increased. The catalytic role of the solvent in electrophilic bromination of alkenes has been examined4’ by consideration of rate data on the bromination of methylideneadaman- tane in various protic solvents and the Y scales of the solvents.The authors conclude that the solvent is involved in the rate-limiting step providing electrophilic assistance as well as a medium effect. The full details have appeared confirming that nitrosation of simple ketones such as acetone takes place via the enol form.41 Either the enolization or the attack of the enol can be rate limiting depending on the enol structure and the experimental conditions. Dimedone which exists primarily in the enol form contains a sufficiently acidic proton as to allow nitrosation even under mildly acidic conditions to occur 37 G. Bellucci R.Bianchini C. Chiappe F. Marioni and R. Spagna J. Am. Chem. Soc. 1988 110 546. 38 V. L. Heasley T. J. Louie D. K. Luttrull M. D. Millar H. B. Moore D. F. Nogales A. M. Sauerbrey A. B. Shevel T. Y. Shibuya M. S. Stanley D. F. Shellhamer and G. E. Heasley J. Org. Chem. 1988 53 2199. 39 R. Hochstrasser A. J. Kresge N. P. Schepp and J. Win J. Am. Chem. SOC.,1988 110 7870. 40 M. F. Ruasse and S. Motallebi Bull. SOC.Chim. Fr. 1988 349. 41 J. R. Leis M. E. Pefia D. L. H. Williams and S. D. Mawson J. Chem. Soc. ferkins Trans. 2 1988 157. D. L. H.Williams (9) XNO\ /XNO NOH via both the enol and enolate forms42 (equation 9) with the latter the more reactive as expected. Nitrosation of aliphatic nitro compounds occurs via the nitronic acid (4) with no contribution from the nitronate anion but kinetic evidence is presented in favour of initial reaction at the oxygen atom followed by rearrangement of the nitroso group to carbon.43 OH +/ R(H)C= N '0-(4) Enol ketonization is currently a much studied reaction and other examples will be discussed in section 8 of this Report.It is worth noting the mechanistic study of the ketonization of a conjugated trienol in a steroidal structure." The kinetics show the expected pH profile for a reaction showing acid- and base-catalysis. Two products are formed (see equation 10). The rate constant for double bond protonation is -200 times less than it is for the corresponding reaction of 1-cyclohexenol presum- ably owing to the extended conjugation in the trienol.J 42 P. Roy and D. L. H. Williams J. Chem. Res. (S) 1988 122. 43 E. Iglesias and D. L. H. Williams J. Chem. SOC.,Perkin Trans. 2 1988 1035. 44 G. D. Dzingeleski S. Bantia G. Blotny and R. M.Pollack J. Org. Chem. 1988 53 1540. Reaction Mechanisms -Part (ii) Polar Reactions 61 Bernasc~ni~~ continues his study of nucleophilic addition to alkenes with kinetic results for the reversible addition of thiolate ion to substituted a-nitrostilbenes (equation 1 l) which are compared with the earlier results with amine nucleophiles. Br@nstedp -coefficients indicate that development of resonance and solvation at the nitro group lags behind carbon-sulphur bond formation in the transition state. COtH / / d eCo2" X X Cyclization of substituted 4-methyl-4-( 2-hydroxyphenyl)pent-2-enoic acid deriva- tives in water (equation 12) results from intramolecular nucleophilic attack on the activated double bond by the phenolate oxygen.46 Activation by C02-and C02H over H are 4000 and lo8 respectively.The stereochemistry of the general acid- catalysed (by protonated amines) reactions contrasts with that of the water-catalysed reaction. The proposed mechanism involves rate-limiting protonation of the mono- or di-anion of the carboxylic acid enolate structures. 6 Aromatic Substitution and Rearrangements A quantitative study is reported of the competitive nitration of benzene and toluene in the gas phase by a range of protonated alkyl nitrates using mass spectrometric and radiolytic technique^.^' The results are consistent with an electrophilic process and the final proton loss is not rate-limiting.The same positional and substrate selectivity is found as for the solution-phase reactions and it is also possible to arrange the conditions such that reactions occur at the encounter rate when substrate selectivity is lost. This is another example in a growing list where well-known mechanistic features of reactions in solution are reproduced in the gas phase. The nitration of aryl iodides in acetic anhydride by nitric acid results in the formation of aryliodine( 111) derivatives rapidly and reversibly by oxidation.48 This accounts for the slowness of the nitration of aryl iodides in this medium whereas in other solvents the expected reactivity pattern is seen.A new kinetic form for nitrous acid-catalysed nitration of naphthalene which is second order in [naphthalene] has 45 C. F. Bemasconi and R. B. Killian J. Am. Chem. Soc. 1988 110 7506. 46 T. L. Amyes and A. J. Kirby J. Am. Chem. Soc. 1988 110 6505. 4' M. Attina and F. Cacae Gazz. Chim. Ztal. 1988 118 241. 48 G. W. Bushnell A. Fischer and P. N. Ibrahim J. Chem. SOC.,Perkin Trans. 2 1988 1281. D. L. H. Williams been observed to occur alongside a first-order term.49 The second-order term has been interpreted in terms of the formation and subsequent reaction of a radical cation containing two naphthalene structures (equations 13-1 5). ArH+ArH+NO+ G (ArH)l’+NO (13) NO+NOl & NO++NO (14) (ArH) +NO + ArNO +ArH +H+ (15) The identification of cyclohexadienone intermediates in electrophilic reactions of phenol continues to attract attention.They have now been identified in brominations using N-bromosuccinimide in CH2C12 and other aprotic solvents.50 Metal ion catalysis has been found in the decomposition of 2-carboxy-2,5-cyclohexadiones in water.’l The origin of the catalysis by Cu2+ and Fe3+ is strong metal ion binding to the incipient di-anion. In aromatic nucleophilic substitution Bunton and co-workers in two papers,52 have proposed radically that the familiar classical S,Ar mechanism involving rate limiting a-complex formation be replaced by a mechanism which includes single electron transfer. This is prompted by the experimental observation of two intermedi- ates which are believed to be (a) a .rr-complex of substrate and OH-and (b) a charge transfer complex of an arene radical ion and OH’ which then forms the u (Meisenheimer) complex.A multistep reaction treatment based on relaxation theory has been developed and the resulting calculated rate and equilibrium constants agree well with the experimental values. The Reporter suspects that not all workers in the field will be convinced by this evidence. In the spiro Meisenheimer complex formation from 3,6-dimethylcatechol 2,4,6-trinitrophenyl ether,53 the kinetics are consistent with the operation of two concurrent mechanisms (a) a trapping mechan- ism with diff usion-controlled proton transfer between a phenolic OH and carboxylate ions and cyclization or ring-opening with no catalysis and (b) a pre-association mechanism in which cyclization/ring-opening involves buffer catalysis by hydrogen bonding.A facile amine-amine exchange has been noted in aromatic nucleophilic substitution reactions of 1-dialkylamin0-2,4-dinitronaphthalene.~~ The dial kylamine group is readily replaced by primary amines and also by pyrrolidine at 30 “C simply by mixing the reactants. Shine’s group have extended their heavy-atom kinetic isotope methods so success-ful in analysis of the benzidine rearrangement to the related quinamine rearrange- ments and also to the Claisen rearrangement. In the former55 (see for example equation 16) the major pathway for the acid-catalysed reaction is a concurrent concerted process ie.is a [5,5J-sigmatropic rearrangement. There is a minor pathway leading to a number of products all derived from a [3,3]-sigmatropic rearrangement. The analogy with the benzidine rearrangement is discussed. 49 J. R. Leis M. E. Pefia and J. H. Ridd J. Chem. SOC.,Chem. Commun. 1988 670. Y. L. Chow D.-C. Zhao and C. I. Johansson Can. J. Chem. 1988,66 2556. 51 0. S. Tee and N. R. Iyengar Can. J. Chem. 1988,66 1194. 52 R. Bacaloglu C. A. Bunton and F. Ortega 1. Am. Chem. SOC.,1988 110 3503 3512. 53 C. F. Bernasconi and D. E. Fairchild J. Am. Chem. Soc. 1988 110 5498. 54 S.Sekiguchi T. Hone and T. Suzuki J. Chem. SOC.,Chem. Commun. 1988 698. 55 B. Boduszek and H. J. Shine J. Am. Chem. SOC.,1988 110 3247. Reaction Mechanisms -Part (ii) Polar Reactions Me o Br P N I -O AceticHCIacid -* H2N 0 (16) Br The Claisen rearrangement of ally1 phenyl ether has been studied by labelling at oxygen a-carbon y-carbon and ~rtho-carbon.~~ The results reveal that in the transition state the C,-0 bond is 50-60% broken whereas the Cy-Corthobond is only 10-20% complete.The 1,3-nitro group rearrangements of nitrocyclohexadienones shown in equations 17 and 18 have been examined for 15Nnuclear polarization using "N-labelled nitro compounds in acetic anh~dride.~' Strong "N nuclear polarization was observed in the first case (equation 17) indicating that the reaction involves a radical pair intermediate but polarization was absent in the second case (equation 18) so the mechanism here (not yet elucidated) must be quite different.7 Proton Transfer The generally accepted view is that carboxylic acids and phenols are stronger acids than alcohols because of a greater degree of stabilization of their anions. Exner5* arrives at this conclusion also using simple thermodynamic ideas and so contradicts a recent alternative view by Siggel and Thomas where the difference was attributed to an unusually high energy content of the undissociated acid molecule. Now further calculation^^^ predict that only 616% of the acidity difference can be attributed to the contribution of resonance to the stabilization of the anions and claim that about 80% of the acidity difference can be accounted for by carbonyl inductive effects. The proposal last year of Arnett and Harrelson:' attributing the high acidity of Meldrum's acid to the unfavourable anti conformations that the ester groups are forced to adopt has prompted two theoretical studies in the quest for the origin of the effect.61962 Both attribute the effect to electrostatic (dipole-dipole) repulsions 56 L.Kupczyk-Subotkowska W. H. Saunders and H. J. Shine J. Am. Chem. SOC.,1988 110 7153. 57 J. H. Ridd J. P. B. Sandall and S. Trevellick J. Chem. SOC.,Chem. Commun. 1988 1195. 58 0.Exner J. Org. Chem. 1988 53 1810. 59 M. R. F. Siggel A. Streitweiser and T. D. Thomas J. Am. Chem. SOC.,1988 110 8022. 60 E. M. Arnett and J. A. Harrelson J. Am. Chem. SOC.,1987 109 809. 61 X. Wang and K. N. Houk J. Am. Chem. SOC.,1988 110 1870.62 K. B. Wiberg and K. E. Laidig J. Am. Chem. SOC.,1988 110 1872. 64 D. L. H. Williams which result in both ester groups in the dilactone taking up the anti conformation thereby decreasing the deprotonation energy sufficiently to account for the acidity. Both show that the loss of a proton from the E-rotamer is easier (by 4.7 kcal in one study and 5.4 kcal in the other) than it is for the 2-rotamer. Acidity measurements in DMSO illustrate the large acid-strengthening effects of polyfluoroaryl sub~tituents.~~ For example C6F5CH2CN is more acidic than is C6H5CH2CN by 5.9 pK units resulting from the powerful field/inductive effects of the five fluorine atoms. The Bordwell group has also measured the acidities of aniline and 26 derivatives in DMSO using an overlapping indicator method.64 A large range is covered from 15.9 for 2,4-dinitroaniline to 30.7 for aniline itself.The meta substituents correlate well with the Hammett u constants; the deviation for a number of para substituents is believed to be due to enhanced solvation of the substituents resulting from a direct conjugation with the anilide ion. Albery Bernasconi and Kre~ge~~ have discussed the nitroalkane anomaly (for example Bronsted a values >1 for the ionization of ring-substituted phenyl nitromethanes) in terms of Marcus-Grunwald theory. The incorrect prediction of the theory can be remedied if solvent reorganization is added to electronic rearrange- ment as the second reaction progress variable. In a multi-author paper66 the quantitative effect of annelation on the acidity and basicity of azoles is discussed both for gas-phase and aqueous solution proton transfers.Annelation increases the acidity by more than it does the basicity possibly because the azoles are electron-rich systems which can more readily accommodate positive rather than negative charge. The sterically hindered 2,6-di-t-butylpyridine is an unusually weak base in DMSO (pK 0.81) whereas its gas-phase basicity is much greater.67 It is argued that this arises from the much reduced hydrogen bonding between the sterically hindered protonated form and a relatively large DMSO solvent molecule. Generally it is agreed that the oxygen atom is the more basic site in amides. However it is now suggested68 that in hindered amides the nitrogen atom becomes protonated first.The evidence comes from the position of charge transfer bands and from comparison of the formation constants for I,-amine and I,-amide complexes. The explanation offered is that steric hindrance reduces conjugation of the CO and NR2 groups in N,N-disubstituted amides and so reduces the basicity of the oxygen atom sufficiently to allow protonation at nitrogen. The very high basicity of aromatic diamine proton sponges is discussed in a review article.69 The abnormal basicity is discussed in terms of the extreme steric strain in these systems and of the destabilizing effect of the overlap of the nitrogen lone pair of the neutral diamine and the strong N--H--N hydrogen bonds formed on monoprotonation which leads to much reduced steric strain.63 F. G. Bordwell J. C. Branca J. E. Bares and R. Filler J. Org. Chem. 1988 53 780. 64 F. G. Bordwell and D. J. Algrirn J. Am. Chem. Soc. 1988 110 2964. 65 W. Albery C. F. Bernasconi and A. J. Kresge J. fhys. Org. Chem. 1988 I 29. 66 J. Catalan R. M. Clararnunt J. Elguero J. Laynez M. Menendez F. Anvia J. H. Quian M. Taagepera and R. W. Taft J. Am. Chem. Soc. 1988 110 4105. 67 R. L. Benoit M. Frkchette and D. Lefebvre Can. J. Chem. 1988 66 1159. 68 G. Guiheneuf J.-L. M. Abboud and A. Lachkar Can. J. Chem. 1988 66 1032. ’’ H. A. Staab and T. Saupe Angew. Chem. In?. Ed. Engl. 1988 27 865. 65 Reaction Mechanisms -Part (ii) Polar Reactions Finally in this section it is worth noting that the basicities of a number of common dipolar non-hydroxylic solvents have been determined by an n.m.r.technique which measures the protonation equilibrium in aqueous sulphuric acid.70 A relative basicity scale -amides > DMSO > acetone >> acetonitrile > sulphones > nitromethane -has been established. 8 Carbonyl Derivatives A theoretical treatment of nucleophilic reactivity in addition reactions to the carbonyl group has been given.71 The value of AG* for XF attack in esters correlates with the vertical ionization potentials of XF. This is interpreted to mean that an important aspect of the activation process is the single electron transfer from XT to the substrate. The structures and some properties of the adducts between HO-and MeO- and a range of carbonyl compounds have been studied by FT-ICR mass spe~trometry.~~ The main conclusion is that tetrahedral intermediates are involved (confirming an earlier theoretical prediction); here is another example of similarities between gas-phase and solution reactions.Nucleophilic addition of aniline to methyl formate has been studied mechanisti- ally.^^ The kinetic results are explained in terms of the trapping mechanism given in the reaction scheme 19. Steps 1 2 or 3 can be made rate-limiting by varying the strength of the base. General base catalysis occurs together with diff usion-controlled proton transfer. Terrier and co-~orkers~~ have examined the reaction of a-keto-aldoximate ions with p-nitrophenyl acetate (equation 20) particularly with reference to the effect of solvation on the reactivity of a-nucleophiles in aqueous solution./\ +I I H-N + C=OeH-N-C-O-\/ II U. B (step 1) \BH++ / IN-C-0-I fast \ I / I Y N-C-OH+B 02N-(3- OCOCH3 + RCH2COCH=NO- (20) __+ 04CH3C + O2N 0 0 - ON=CHCOCH2R At low pK values (cf:phenoxide anions) the Brsnsted plot is linear but at pK > 7.8 there is a very strong downward curvature. This is explained in terms of the need for desolvation of the oximate anion before nucleophilic attack and the fact that desolvation is more difficult with the more basic oximate anions. 70 A. Bango and G. Scorrano J. Am. Chern. Soc. 1988 110,4577. 7' E. Buncel S. S. Shaik I.-H. Urn and S. Wolfe J. Am. Chem. SOC.,1988 110 1275. 72 H. van der We1 and N.M. M. Nibbering Red. Trau. Chim. Pays-Bas 1988 107 491. 73 C. C. Yang and W. P. Jencks J. Am. Chem. SOC.,1988 110 2972. 74 F. Terrier F. Degorre D. Kiffer and M. Laloi Bull. SOC.Chim. Fr. 1988 415. D. L. H.Williams The measurement of the acidity of the keto-enol system continues to attract a lot of attention. Estimates of the pK values for the OH acidity in protonated simple carbonyl compounds (equation 21) have been made7s from KE values and CH acidity constants obtained by the application of the Marcus equation to the ketoniz- ation process. Two gro~ps'~,~~ have independently measured the acidity of 2- indanone (equation 22) from measurements of the rate of enol formation. The acidity (pK 12.2) is much higher than expected and is attributed to the extra stabilization of the enolate by interaction of the Ph and 0-groups via the enolate double bond.It is estimated that the intrinsic electronic effect of a Ph group upon ketone acidity is ca. 106-107. The Marcus equation has been applied to the deprotonation of some unusually acidic benzylic ketoces [e.g. (5) and (6)],78which constitute examples of the principle of non-perfect synchronization presented by Bernasconi in recent years. Various aspects of ester hydrolysis have been examined. The ElcB mechanism is now established for the hydrolysis of esters containing acidic protons at the LY -position (e.g.acetoacetates malonates etc.).Additional evidence for this pathway comes from the sign of the volume of activation (AV") for such reactions,79 which is positive whereas A V' is negative for the more common B,,2 mechanism.Alkynyl benzoates tosylates and phosphates have recently been prepared and their hydroly- sis mechanisms investigated.80 A number of interesting pathways have been estab- lished including those involving both electrophilic and nucleophilic attack of the triple bond. Hydrolysis of esters of phosphorous acid have also been studied.*l Trialkyl phosphites hydrolyse in alkali hundreds of times faster than do the corre- sponding phosphates whilst in acid solution the phosphites are ca. lo'* times faster than the phosphates; the enormous effect in the acid-catalysed reactions is thought 75 J. Toullec Tetrahedron Lett. 1988 29 5541. 76 J. R. Keeffe A. J.Kresge and Y. Yin J. Am. Chem. Soc. 1988 110 1982. 77 A. M. Ross D. L. Whalen S. Eldin and R. M. Pollack J. Am. Chem. Soc. 1988 110 1980. 78 J. W. Bunting and D. Stefanidis J. Am. Chem. Soc. 1988 110 4008. 79 N. S. Isaacs and T. S. Nagem J. Chem. Soc. Perkin Trans. 2 1988 557. 8o A. D. Allen T. Kitamura K. A. Roberts P. J. Stang and T. T. Tidwell J. Am. Chem. Soc. 1988 110 622. " F. H. Westheimer S. Huang and F. Covitz J. Am. Chem. Soc. 1988 110 181. Reaction Mechanisms -Part (ii) Polar Reactions to stem from the existence of an unshared pair of electrons on the phosphorous atom in the phosphite. Intramolecular participation by both the amide and hydroxy groups in ester hydrolysis reactions of naphthalene structures has been as has the effect of metal ions (Cu2+ Ni2+ Co2+,and Zn2+) on the intramolecular participation by the acetamido In the latter case a general mechanism for metal ion catalysis in reactions where C-0 bond breaking is rate limiting has been proposed which contains a transition state where the metal ion is simultaneously bound to two oxygen atoms and a nitrogen atom of a heterocyclic system.In the same area the effect of neighbouring pyridinium groups on the base-catalysed hydrolysis of arylbenzoates has been examined.8s The ortho substituents are more effective than the para and the catalytic effect is based on interaction of a negatively charged site in the transition state with an electron deficient 7r-system of the pyridinium ring. Novel methods for the generation of simple enols continue to be found.One such procedure involves the photo-oxidation of alcohols by carbonyl compoundsB6 (equation 23). This procedure led to KE values in good agreement with other recent determinations. A simple stable enol has also been produced by isomerization (equation 24) using a rhodium carbonyl triphenylphosphine complex.87 Again ketonization rate constants are in agreement with literature values. Both (Z)-and (E)-1-hydroxybutadienes have been generated in solution for the first time from their trimethylsilyl derivatives in slightly acidic aqueous acetonitriIe.88 Both were characterized by n.m.r. and the kinetics of the ketonization reported. Further studies with 2-indanone are reported leading to a pKE value of 3.84 and a pK value of 8.36 for the enol acting as an oxygen acid.89 Enol addition equilibria and keto-enol tautomerization of 9-formylfluorene have also been examined.” The enol of aceto-phenone has been generated by photohydration of phenylacetylene and photoelimi- nation and rates of ketonization obtained;” the results have been analysed by Marcus theory and comparisons made with an earlier treatment with the enol of isobutyrophenone.The reactivity (in enolization) of amino ketones is much greater than that of simple unsubstituted ketones. Kinetic analysis9* reveals that two factors 82 F. Hibbert and R. J. Sellens J. Chem. Soc. Perkin Trans. 2 1988 399. 83 F. Hibbert and K. J. Spiers J. Chem. Soc. Perkin Trans. 2 1988 571. 84 T. H. Fife T. J. Przystas and M.P. Pujari J. Am. Chem. Soc. 1988 110 8157. 85 J. F. J. Engbersen G. Geurtsen D. A. DeBie and H. C. Van der Plas Tetrahedron 1988,44 1795. 86 J. R. Keeffe A. J. Kresge and N. P. Schepp J. Am. Chem. Soc. 1988 110 1993. 87 C. S. Chin S. Y. Lee J. Park and S. Kim J. Am. Chem. Soc. 1988 110 8244. 88 B. Capon and B. Guo J. Am. Chem. Soc. 1988 110 5144. 89 J. R. Keeffe A. J. Kresge and Y. Yin J. Am. Chem. Soc. 1988 110 8201. 90 M. P. Harcourt and R. A. More O’Ferrall Bull. Soc. Chim. Fr. 1988 407. 91 Y. Chiang A. J. Kresge J. A. Santaballa and J. Win J. Am. Chem. Soc. 1988 110 5506. 92 B. G. Cox P. DeMaria and L. Guerzoni J. Chem. Soc. Perkin Trans. 2 1988 163. 68 D. L. H. Williams are responsible (a) the influence of the positive charge in the N-protonated (or methylated) derivatives and (b) intramolecular general base catalysis by the neutral nitrogen atom which is at a maximum for the &substrates when a six-membered ring transition state is possible.Enolization rate constants for malonic acid and methylmalonic acid have been obtained by an isotopic exchange reaction followed by ‘Hn.m.r.93 Finally here the preparation ionization energies and heats of formation of unstable enols in the gas phase have been described.94 9 Other Reactions The kinetics of the N-chlorination of secondary amines by N-chlorosuccinimide show that the process is reversible and second order in both direction^.'^ The results are consistent with a process which involves direct transfer of chlorine to the amine and do not support a mechanism involving a prior hydrolysis of N-chlorosuccinimide.The Ar+--N2 pair which is the first intermediate form in the dediazoniation reactions of arenediazonium ions can be trapped with carbon monoxide in water to give arenecarboxylic acids.96 This is a model for the reverse of dediazoniation since CO is isoelectronic with N2. The yields from substituted diazonium ions correlate with the Taft dual substituent parameters to give positive pF and negative pR reaction constants as expected for addition of N to aryl cations. A book has been published entitled ‘Nitr~sation’~’ which describes the various reagents that can bring about nitrosation with discussion (mainly from a mechanistic viewpoint) of nitrosation at C N 0 S and metal sites.The kinetic identification of NO+ as the effective reagent in dilute acid solution has been achieved for the nitrosation of alcohols and a thiol using cither alkyl nitrites or nitrous acid as the reagent.98 Reactions in acetonitrile solvent are truly zero order in the nitrosatable substrates and so must involve rate-limiting formation of some species such as NO+. The analogy with the well-known situation in aromatic nitration is obvious. The solvent kinetic isotope effect on the equilibrium formation of NO+/H2N02+ in water (K,/K,) has been determined as 2.55 * 0.28 in the pH range 1-5.99 Two pathways have been identified in the nitrosation of phenylureas,loO one leading to the N-nitroso derivative and the other to diazonium ion formation.The reaction between nitrous acid and N,N’-dialkylthioureas occurs by S-nitrosation followed by a slow re- arrangement to give the N-nitroso product.”’ The possibility of a direct N-nitrosa- tion is ruled out. In a re-examination of the nitrosation (diazotization) of aniline at high acidity it is proposed102 that deprotonation of the di-cation complex occurs before and not after the NO+ group rearrangement to nitrogen (equations 25 and 93 E. W. Hansen and P. Ruolf J. Phys. Chem. 1988,92 2641. 94 F. Turecek L. Brabec and J. Korvola J. Am. Chem. SOC.,1988 110 7984. 95 J. M. Antelo F. Arce J. Franco M. C. G. Lopez M. Sanchez and A. Varela Znt. J. Chem. Kinef. 1988 20 397. 96 M. D. Ravenscroft P. Skrabal B. Weiss and H. Zolinger Hefv.Chim. Acta 1988 71 515. 97 D. L. H. Williams ‘Nitrosation’ Cambridge University Press 1988. 98 M. J. Crookes and D. L. H. Williams J. Chem. SOC.,Chem. Commun. 1988 571. 99 A. Castro M. Mosquera M. F. R.Prieto J. A. Santaballa and J. V. Tato J. Chem. SOC.,Perkin Trans. 2 1988 1963. 100 A. Castro M. Gonzalez F. Meijide and M. Mosquera J. Chem. SOC.,Perkin Trans. 2 1988 2021. 101 F. Meijide and G. Stedman J. Chem. SOC.,Perkin Trans. 2 1988 1087. 102 H. Zollinger Helv. Chim. Acta 1988 71 1661. Reaction Mechanisms -Part (ii) Polar Reactions NO+ NO+ I I I NO+ 26). The carbanion of ethyl cyanoacetate reacts with the nitroprusside ion in two stages (equations 27 and 28) to give the oxime pr~duct."~ Intramolecular nucleophilic catalysis by neighbouring OH has been demonstrated in the acid- and base-catalysed hydrolysis of aromatic sulphonamide~'~~ (equation 29).There is a large Thorpe-Ingold gem-dialkyl effect where relief of initial-state steric strain is a major effect. .OH &02NMe2 -OSO2+Me2NH Primary and tertiary nitronate ions react with sulphonyl halides to give various products which depend on the nature of the halide the nitronate structure and the Some of these reactions take place by single electron transfer mechanisms as the addition of p-dinitrobenzene (a single electron acceptor) results in the inhibition of some products. 10 Some Probes of Polar Mechanisms Jencks'06 urges caution in the interpretation of structure-reactivity coefficients since solvation or desolvation of a reacting group often plays a part and the effects of substituents in different parts of a molecule often lead to imbalances between estimates of reaction progress in the transition state.Additional information regard- ing the nature of the transition state (which can be described by theoretical reaction 103 A. R. Butler A. M. Calsy and C. Glidewell J. Chem. SOC.,Perkin Trans. 2 1988 1179. I04 A. Wagenaar and J. B. F. N. Engberts J. Org. Chem. 1988,53 768. lo' P. E. Pigou and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1988 725. 106 W. P. Jencks Bull. SOC.Chim. Fr. 1988 218. 70 D. L.H. Williams surfaces or by empirical energy-contour diagrams) can however be obtained from changes in structure-reactivity coefficients i.e.from the second derivatives of log k The limitation of the use of Hammett p values in assessing relative bond tightness in transition states has previously been stressed. Now Lee and co-~orkers''~ argue that the cross-interaction constant pxy (given by equation 30) can be used more reliably to characterize the transition state structure. Experimental results for some nucleophilic substitution reactions are analysed in these terms. log(kxYlkH*) = PXUX+ PYUY + PXYUXUY (30) Fadhil and GodfreyIo8 examine the theory behind quantitative linear substituent correlations and conclude that the pattern of deviations is remarkably simple if the choice of standard substituent constants is based on I3Csubstituent chemical shifts at the /3 site in ring-substituted styrenes.This can also be put in the more familiar language of field and resonance substituent effects if it is realized that the resonance effect modifies the field effect by an amount that can vary up to a maximum. This approach indicates that there are serious flaws in commonly used dual substituent parameter equations. The same authors extend these ideas to cover Brflnsted and related plot^.''^ Taft and (many) co-workers"' have examined the effects of molecular structure on gas-phase proton transfer equilibria. The summation of simple product terms for substituent inductive polarizability and resonance effects fit well with the observed substituent effects over a wide range of structures. The reactivity-selectivity principle continues to attract attention.Johnson and Stratton"' argue that such a link between selectivity and reactivity is not necessary since variations in the slope of linear free energy relationships can account for the range of observed selectivity ratios. A review discusses the physical basis of intramolecularity. A simple extra-thermodynamic treatment of enthalpy and entropy changes for cyclization of short-chain compounds both for gas-phase and solution-phase reactions offers a ready interpretation of the magnitude and variation of the observed 'effective molarities'. Unusually large kinetic isotope effects often coupled with anomalous temperature dependences of these effects are usually thought to result from quantum tunnelling. Thibblin"3 has shown that these effects can also arise from reaction branching i.e.from partitioning of an intermediate. This may be the explanation in some cases. 107 I. Lee C. S. Shim S. Y. Chung H. Y. Kim,and H. W. Lee J. Chem. Soc. Perkin Trans. 2 1988 1919. 108 G. F. Fadhil and M. Godfrey J. Chem. Soc. Perkin Trans. 2 1988 133. '09 G. F. Fadhil and M. Godfrey J. Chern. Soc. Perkin Trans. 2 1988 139. I10 R. W. Taft J. L. M. Abboud F. Anvia M. Bertheiot M. Fujio J.-F. Gal A. D. Headley W. G. Henderson I. Koppel J. H. Qian M. Mishima M. Taagapera and S. Ueji J. Am. Chem. Soc. 1988 110 1797. 'I1 C. D. Johnson and B. Stratton J. Chem. Soc. Perkin Trans. 2 1988 1903. L. Mandolini Bull. Soc. Chim. Fr. 1988 173. A. Thibblin J. Phys. Org. Chem. 1988 1 161.

ISSN:0069-3030    

DOI:10.1039/OC9888500053

出版商:RSC    

年代:1988

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Free-radical Reactions By D. CRICH Department of Chemistry University College London 20 Gordon Street London WClH OAJ 1 Synthesis Intramolecular Processes.-1988 was an encouraging year for the free-radical chemist with the publication of several exciting innovations. In the first instance and following on from the work of Hanessian and Kametani (see last year's Report) several papers have been published illustrating the possibility of preparing six- membered rings as opposed to the more usual five-membered rings by radical cyclizations' as exemplified in Schemes l2 and 23. / /hBz Bu,SnH. AlBN ( II 82% Scheme 1 Scheme 2 70% A further example (Scheme 3) however draws attention to the fact that caution must be exercised and that rearrangements can cause such cyclizations to take an unexpected co~rse.~ Thus the aryl bromide (1) on treatment with tributyltin hydride (TBTH) under standard conditions led presumably uia radicals (3) and (4) to the phenanthrene (2) and not to the anticipated isomeric product (5).T. Sugawara B. A. Otter and T. Ueda Tetrahedron Lett. 1988 29 75; T.Rajamannar and K. K. Balasubramanian ibid. p. 5789; S. A. Ahmad and D. A. Whiting 1. Chern. SOC.,Chern. Cornrnun.,1988 1160; S. Hatakeyama N. Ochi H. Numato and S. Takano ibid. p. 1202. ' M. Kim R. S. Gross H. Sevestre N. K. Dunlop and D. S. Watt J. Org. Chern. 1988 53 93. T. Ghosh and H. Hart J. Org. Chern. 1988 53 2396. N. S. Narasimhan and J. S. Aidhen Tetrahedron Leu. 1988 29 2987.71 72 D. Crich ro ro 0 OH Bu,SnH AlBN b +-Me0 Me0 80"C Me0 Me0 Me0 OMe OMe OMe (5) (1) (2) 23% I T -Me0 Me0 I OMe OMe (3) (4) Scheme 3 Returning to the formation of the more familiar five-membered rings a high yield example of an apparent 5-endo-trig cyclization (Scheme 4) has been published without ~ornrnent.~ Scheme 4 Several authors have studied amides as linkages for the formation of five-membered nitrogen heterocycles by radical cyclizations with widely varied results. Thus successful cyclizations were reported by Yamaguchi6 (Scheme 5) and by Dittami'" (Scheme 6; R = Me). However by simply substituting benzoyl for acetyl in the latter example Togo7' obtained an alternative mode of cyclization (Scheme 6; R = Ph) demonstrating the susceptibility of such reactions to substituent effects.A. Gepalsamy and K. K. Balasubramanian,J. Chem. SOC.,Chem. Commun. 1988 28. R. Yamaguchi T. Hamasaki and K. Utimoto Chem. Lett. 1988 913. ' (a)J. P. Dittami and H. Ramanathan Tetrahedron Lett. 1988,29,45; (b) H. Togo and 0.Kikuchi ibid. p. 4133. Reaction Mechanisms -Part (iii) Free-radical Reactions 0 0 62Yo Scheme 5 Bu,SnH 80"C Bu SnH 80°C -P R= Me R=Ph I Ac 04 ) 100% 91% Scheme 6 Bowman et aL8 encountered problems in their work on the synthesis of oxindoles by the TBTH-mediated cyclization of o-iodophenylacrylamides owing to the unfavourable (for cyclization) trans-amide configuration adopted by the intermedi- ate radical.Similar problems were faced by Jolly and Livinghouse' when treatment of the iodoamide (6) with TBTH under standard conditions gave only a low yield (27%) of cyclized product (7) with the major product (53%) resulting from reductive deiodination. The problem was circumvented in this case by the use of a combination of hexabutyldistannane and ethyl iodide under photolytic conditions resulting in the cyclized product (8) with a much improved yield (88%). This ingenious solution relies on the ability of ethyl iodide to quench not only the cyclized radical but also the ring-opened trans-amide radical (9) so enabling its recycling to (6). Me (7) I I I Me Me (8) (9) Three groups have independently reported on cyclizations preceded by what Curran has termed 'translocation of radical sites by intramolecular 1,5-hydrogen abstraction'.Thus Cekovic" obtained the cyclopentane (11) in 32% yield from a 'W. R. Bowman H. Heaney and B. M. Jordan Tetrahedron Lett. 1988 29 6657. R. S. Jolly and T. Livinghouse 1.Am. Chem. SOC.,1988 110 7536. Z. Cekovic and D. Ilijev Tetrahedron Lett. 1988 29 1441. 74 D. Crich modified Barton reaction involving photolysis of the nitrite ester (lo) whilst Parsons' entry into the pyrrolizidine precursor (13) was achieved (60-85%) by photolysis of the iodide (12) in the presence of TBTH." The examples (10) -+ (11) and (12)+ (13) are conceptually different in so far as in the former the initial radical provoking the 1,Shydrogen transfer is remote from the double bond required for the cyclization whilst in the latter the double bond intervenes in the reaction both as a hydrogen-abstracting vinyl radical and subsequently as a radical trap.Curran has published several examples of each type but has drawn particular attention to the use of modified protecting groups in the former type for radical generation and protection of the cyclized product as in Scheme 7.12 Bu,SnCl NaBH,CN - crCOZEt 61'/o Scheme 7 The cyclopropylmethyl/3-butenylradical rearrangement has been used as a key step in various tandem radical procedures by several groups. Thus Utim~to'~ reported on the rearrangement of butadienylcyclopropanes to alkenylcyclopentenes as illus- trated in Scheme 8. The reaction is initiated by addition of a phenylthio radical to the terminal position of the diene followed sequentially by cyclopropylmethyl ring opening 5-hexenyl ring closure and eventual p -elimination of the phenylthio group.Two groups of workers have published on an alternative procedure (Scheme 9) in which a phenylthio radical adds to a vinylcyclopropane generating after ring " D. C. Lathbury P. J. Parsons and I. Pinto J. Chem. Soc. Chem. Commun. 1988 81. D. P. Curran D. Kim H. T. Liu and W. Shen J. Am. Chem. SOC.,1988 110 5900. l3 T. Miura K. Fugami K. Oshima and K. Utimoto Tetrahedron Lett. 1988 29 1543. Reaction Mechanisms -Part (iii) Free-radical Reactions PhSH,AIBN 60 ' u L-J"c 0 Me 73O/O Scheme 8 COzMe PhSH,AIBN - VCOzMe OEt 60°C EtOv =(om OEt 79yo Scheme 9 opening a 3-butenyl radical that was quenched by addition to an alkene to give a 5-hexenyl radical which then underwent closure with expulsion of the phenylthio radi~a1.l~ The approach adopted by Motherwell" (Scheme 10) is somewhat different in so far as the fragmentation/ cyclization sequence was initiated by application of the Barton-McCombie reaction and also as the alkene introduced on cyclopropylmethyl ring opening took no further part in the sequence.Bu,SnH AlBN 80 "C 'i 71% SiMe Scheme 10 In each of the three examples listed above regioselective cleavage of the cyclopro- pyl group was crucial to the success of the reaction and whilst in the first two cases this may be explained in terms of radical stability this is not so in the third example where stereoelectronic control was invoked.Further examples of regioselective opening of cyclopropyl radicals were reported by Griller16 and Japanese workers." Turning to the related opening of oxiranylmethyl radicals Murphy'* has reported further cases in which the C-0 bond is cleaved preferentially to the C-C bond. 14 T. Miura K. Fugami K. Oshima and K. Utimoto Tetrahedron Lett. 1988 29 5135; K. S. Feldman A. L. Romanelli R. E. Ruckle and R. F. Miller J. Am. Chem. SOC.,1988 53 3300. J. D. Harling and W. B. Motherwell J. Chem. Soc. Chem. Commun. 1988 1380. 16 M. Campredon J. M. Kanabus-Kaminska and D. Griller J. Org. Chem. 1988 53 5393. 17 T. Morikawa M. Uejima and Y. Kobayashi Chem Lett. 1988 1407.J. A. Murphy C. W. Patterson and N. F. Wooster Tetrahedron Lett. 1988,29,955; J. Chem. SOC.,Chem. Commun. 1988 294; A. Johns and J. A. Murphy Tetrahedron Lerr. 1988 29 837. 76 D. Crich It is apparent that unless C-C cleavage leads to a stabilized radical (see last year’s Report) oxiranylmethyl radical cleavage takes place with scission of the C-0 bond to give 2-propenyloxyl radicals. Stork” has studied the use of ally1 radicals in cyclization reactions and found that good yields of five-membered rings can be formed (Scheme 11). f Br I 5 Jij Scheme 11 Several groups have investigated the use of acyl radicals in cyclization reactions leading to cycloalkanones. The Reporter and Boger preferred selenoesters as the precursor and noted the efficient formation of cyclohexanones by the 6-em-trig mode (Scheme 12).20 Zard on the other hand preferred S-acylxanthate esters as photolabile acyl radical precursors.21 Kagan22 has reported the isolation of hydroxy-cyclopropanes on treatment of 0-allylsalicylyl chloride with samarium( 11) iodide and suggested inter alia that the reaction might proceed by acyl radical cyclization closure of the cyclopropane and trapping of the alkoxy radical by some samarium species (Scheme 13).Blanco and Ma~s0ux-i~~ have drawn attention to the possibility of the reversibility of acyl radical cyclizations by isolating ring-opened products (17) (18) and (19) in 18,33 and 22% yield respectively from the reaction of (14) with ferric chloride. The presumed intermediates were the radical (15) the ring- opened acyl radical and the acyl chloride (16).72Yo + Scheme 12 19 G. Stork and M. E. Reynolds J. Am. Chem. SOC.,1988 110 6911. 2o D. Crich and S. M. Fortt Tetrahedron Lett. 1988 29 2585; D. L. Boger and R. J. Mathvink J. Org. Chem 1988,53 3379. 21 P. Delduc C. Tailhan and S. Z. Zard J. Cbem. SOC.,Cbem. Commun. 1988 308. 22 M. Sasaki J. Collin and H. B. Kagan Tetrahedron Lett. 1988 29 6105. 23 L. Blanco and A. Massouri Tetrahedron Lett. 1988 29 3239. Reaction Mechanisms -Part (iii) Free-radical Reactions 51% Scheme 13 Ph (16) X=C1 (17) X=OH (18) X=OEt (19) X=O c1Q Ph The use of monothioacetals or ketals in conjunction with TBTH as precursors to a-alkoxyl radicals and eventually to cyclopentanols following radical cyclization has been exploited independently by two groups (Scheme 14).24 n Bu,SnH AIBN 80 "C 60% Scheme 14 Nugent and RaJanBab~~~ have reported the generation of p-oxy radicals from epoxides on treatment with bis(cyclopentadieny1)chlorotitanium.Following cycliz- ation on to an appropriately placed double bond the organometallic reagent further served as an alkyl radical trap. Work-up with water provided alcohols (Scheme 15) and with iodine iodoalcohols. c1 c1 I OF ____ cp2i&cp2 H,O *Cp,TiC -$) THF 82Yo Scheme 15 24 V. K. Yadav and A. G. Fallis Tetrahedron Lett. 1988 29 897; T. L. Fevig R. L. Elliott and D. P. Curran J. Am. Chem Soc.1988 110 5064. 25 W. A. Nugent and T. V. RajanBabu. J. Am. Chem. SOC.,1988 110 8561. 78 D. Crich Finally in this section the cyclization of alkyl radicals on to oxime ethers was found to give good yields of N-cyclopentyl- and in some cases N-cyclohexylhy- droxylamines.26 Intermolecular Processes.-The report by Hart27 of the ability of the couple bis(trimethylstanny1) benzopinacolate (20)/ 0-benzylformaldoxime to generate alkyl radicals from halides and pseudohalides and to occasion their one-carbon homologa- tion (Scheme 16) represents a significant advance in the field of radical-mediated intermolecular carbon-carbon bond formation. In a similar vein one-carbon homologation of radicals generated by the 0-acyl thiohydroxamate route was achieved with isonitriles substituted with electron-withdrawing groups e.g.4-nitrophenylisonitrile.** OCHzPh Me,SnO OSnMe I Ph,C-CPh (20) CH,=NOCH,Ph 80°C OAc OAc Scheme 16 80% Diethyl azodicarboxylate has been reported to trap alkyl radicals generated from alkyl halides with TBTH leading after chain transfer to N-alkylhydrazinedicarboxy-late^.^^ The modest yields observed in this radical C-N bond forming process could probably be improved with the replacement of TBTH by (20). The use of organocobaloximes as precursors to alkyl radicals was again popular in 1988 the main exponents being the groups of Branchaud and Pattenden.30 The Pattenden variation of hydrocobaltation-radical coupling-dehydrocobaltation is especially interesting as very minor modifications to the experimental procedure allow the coupling of two alkenes with the controlled formation of either of two regioisomers (Scheme 17).I +ph 1” Ph Ph- CN 55% Ph Scheme 17 26 P. A. Bartlett K. L. McLaren and P. C. Ting J. Am. Chem. SOC.,1988 110 1633; K. A. Parker D. .M. Spero and J. Van Epp 1. Org. Chem 1988 53 4628. 27 D. J. Hart and F. L. Seely J. Am. Chem. SOC.,1988 110 1631. D. H. R. Barton N. Ozbalik and B. Vacher Tetrahedron 1988 44 3501. 29 M. Ohno K. Ishizaki and S. Eguchi J. Org. Chem. 1988 53 1285. 30 B. P. Branchaud M. S. Meier and Y. Choi Tetrahedron Lett. 1988 29 167; B. P. Branchaud and M. S. Meier ibid. p. 3191; H. Bhandal and G. Pattenden J. Chem. SOC.,Chem Commun. 1988 1110; J. E. Baldwin and C.S. Li ibid. p. 261. Reaction Mechanisms -Part (iii) Free-radical Reactions Other novel uses of cobaloximes have included their use in the generation of glycosyl radicals31 and their use as radical precursors for the addition of radicals to nitronate anions and pyridinium Utim~to~~ has extended his work on the assistance of various TBTH-mediated radical reactions by triethylborane (see last year's Report). Of particular note is the reaction of a-bromoketones with TBTH/Et,B resulting in the formation of a boron enolate by a radical mechanism and its in situ quenching with benzaldehyde (Scheme 18). But perhaps the observation of greatest potential importance was that the addition of Et3B enables the TBTH reduction of secondary alkyl thioesters (Barton-McCombie reaction) to be carried out efficiently at room temperature rather than the previously required minimum of 80 "C.0 OBEt2 I ~ph 74% Scheme 18 New Radical Sources.-Tris( trimethylsily1)silane (21) has been advocated34 as a convenient replacement for TBTH given the similar strength of its Si-H bond and the Bu3Sn-H bond and the comparable reactivities of the (Me3Si)3Si' and Bu3Sn' radicals towards alkyl halides. Three new sources of alkoxyl radicals -nitrate e~ters/TBTH,~' diphenylbis(tri-fluoroacetoxy)selurane (22)/iodine and an and 0-alkyl thiohydroxamates (23)37-have been reported in the course of the year. The ease of preparation of compounds (23) render them very attractive for this purpose. (Me3Si),SiH Ph,Se( OCOCF,) (21) (22) The reaction of phosphonyl chlorides with 2-mercaptopyridine N-oxide has been reported to provide the thiohydroxamic acid derivatives (24) which on photolysis with a thiol or tetrachloromethane underwent cleavage of the P-C bond by a radical 31 A.Ghosez T. Gobel and B. Giese Chem. Ber. 1988 121 1807. 32 B. P. Branchaud and G. X. Yu,Tetrahedron Lett. 1988 29 6545; B. P. Branchaud and Y. L. Choi J. Org. Chem. 1988 53 4638. 33 K. Nozaki K. Oshima and K. Utimoto Tetrahedron Lett. 1988 29 1041 6125 6127; Y. Ichinose K. Oshima and K. Utimoto Chem. Lett. 1988 1437. 34 C. Chatgilialoglu D. Griller and M. Lesage J. Org. Chem. 1988 53 3641. 35 B. Fraser-Reid G. D. Vite B. W. A. Yeung and R. Tsang Tetrahedron Lett. 1988 29 1645; G.D. Vite and B. Fraser-Reid Synth. Commun. 1988 18 1339. 36 R. L. Dorta C. G. Francisco R. Freire and E. Suarez Tetrahedron Lett. 1988 29 5429. 37 A. L. J. Beckwith and B. P. Hay J. Am. Chem. SOC.,1988 110 4415. 80 D. Crich chain mechanism; yields however were only modest even for ally1 and benzyl radicals.38 Stereochemical Aspects.-Tanne9’ has reported the use of chiral dihy-dronicotinamides for the reduction of unsymmetrical ketones. Thus the homochiral NADPH model (25) brought about reduction of phenyl trifluoromethyl ketone to the corresponding alcohol in good yield (82% ) and interesting enantiomeric excess (68%) by a chain mechanism involving SET and enantioselective hydrogen atom transfer. The synthesis of P-glycosidic linkages by stereoselective radical reactions at the anomeric centre of pyranosides has been demonstrated by two groups.40 This new chemistry differs from the previously known glycosyl radical chemistry in so far as it is a hydrogen atom that is introduced into the axial position in the stereoselective radical step rather than the more usual trapping by addition of the glycosyl radical to an alkene.The requisite 1-alkoxyglycosyl radicals may be generated by decarboxy- lation of ulosonic acids in the presence of a thiol (Scheme 19) or by the action of TBTH on a monothio-orthoester. PhCH~O~ofl} PhCHzO PhCH20 H -phCHzOh0q COZH H QReagents i b4S C1-; ii RSH hv 51%; p:ff=11:1 0 Scheme 19 2 Mechanism and Physical Rearrangements.-Radicals of the type (26) behave in substantially different ways according to the nature of the S-alkyl group.Thus in a model study for the methylmalonylSCoA to succinylSCoA rearrangment Halpern41 treated the bromide (27) with TBTH under standard conditions and obtained the expected product (28) 38 L. Z. Avila and J. W. Frost J. Am. Chem. SOC.,1988 110 7904. 39 D. D. Tanner and A. Kharrat J. Am. Chem. SOC.,1988 110 2468. 40 D. Crich and T. J. Ritchie Tetrahedron 1988,44 2319; J. Chem. Soc. Chem. Commun. 1988 1461; D. Kahne D. Yang J. J. Lim R. Miller and E. Paguaga J. Am. Chem. Soc. 1988 110 8716. 41 S. Wollowitz and J. Halpern J. Am. Chem. SOC.,1988 110 3112. Reaction Mechanisms -Part (iii) Free-radical Reactions of 1,2-thioester migration.On the other hand Tada42 isolated p -thiolactones (30) in high yield (92%) on photolysis of cobaloximes (29). Evidently 1,2-thioester migration and SH2 at sulphur are competing processes with the balance being tipped in favour of the latter by good radical leaving groups on sulphur. 0 C0,Et COlEt 0 II I I II EtSC-C-CH2Br HC-CH2-CSEt I I Me Me (27) (28) The high yield (80%) formation of the tetrahydrothiophene (32) observed on treatment of the mannitol-derived dixanthate (3 1) with TBTH has been explained in terms of the migration of a thiocarbonate moiety on to an alkyl radical followed a homolytic substitution at sulphur.43 Ph Ph The 1986 report (see Annual Reports B 1986 Volume 83) that the TBTH-promoted reductive rearrangement of the cholestanol derivative (33) to (34) proceeded without inversion of the acetoxy group oxygens has prompted further studies into 1,2-acyloxy migrations.Thus Sustmann and GieseU have looked at benzoyloxy migration in the carbohydrate field and concluded from an ‘*O labelling experiment that the migration takes place as had been previously thought with complete inversion of the ether and carbonyl oxygens via a five-membered transition state. However in a more complete study Beck~ith~~ noted that inversion of the two oxygens was not complete in the case of (33) -+ (34) and also that the rate of this particular migration was between 3 and 4 orders of magnitude faster than the analogous acyclic rearrange- ment. It was concluded that two mechanisms operate in 1,2-acyloxy migrations one 42 M.Tada M. Matsumoto and T. Nakamura Chem. Lett. 1988 199; J. Am. Chem. SOC.,1988 110,4647. 43 A. V. R. Rao K. A. Reddy M. L. Gurjar and A. C. Kunwar J. Chem. SOC.,Chem. Commun. 1988 1273; see also H. Sano T. Takeda and T. Migita Chem. Lett. 1988 119. 44 H. G. Korth R. Sustmann K. S. Groninger M. Leisung and B. Giese J. Org. Chem. 1988 53 4364. 45 A. L. J. Beckwith and P. J. Duggan J. Chem. SOC. Chem. Commun. 1988. 1000. 82 D. Crich Y (33) X=OAC; Y=p-Br (34) X=H;Y=cz-OAC (36) X = a -0OH (37) X=p-OOH involving a five-membered transition state and a second more rapid mechanism involving either a three-membered transition state or a tight ion pair. In the related area of the rearrangement of the allylic hydroperoxide (35) to (36) and (37) the Davies group conducted experiments under an atmosphere of '*OZ and found no incorporation into (36) but 80% incorporation into (37).46 It was therefore concluded that the initial rearrangement of the peroxyl radical derived from (35) to that derived from (36) takes place uia a five-membered transition state but that rearrangement of (36) to (37) requires dissociation of the intermediate peroxyl radicals.Radical Clocks and Probes.-Rate constants for the rearrangement of (38) +(39)47 and (40) +(41)48 were measured and found to be extremely rapid (1.4 x 10" s-' unspecified temperature and 1.1 x lo9s-' at 80 "C,respectively). Ph h phA I o=s---;r-o=s II 0 0 (41) 46 A. L. J.Beckwith A. G. Davies I. G. E. Davison A. Maccoll and M. H. Mruzek J. Chem. SOC.,Gem. Commun. 1988 475; D. V. Avila A. G. Davies and I. G. E. Davison J. Chem. SOC.,Perkin Trans. 2 1988 1847. 47 L. Mathew and J. Warkentin Can. J. Chem. 1988 66 11. 48 B. Vacher A. Samat A. Allouche A. Laknifli A. Baldy and M. Chanon .Tetrahedron 1988 44,2925. Reaction Mechanisms -Part (iii) Free-radical Reactions With the aid of the 0-alkyl thiohydroxamate (23; R = 4-pentenyl) Beckwith was able to estimate the rate of ring closure of the 4-pentenyloxyl radical to be 16 x lo8s-' at 80 0C.37 The controversy over the validity of cyclizable probes of the 5-hexenyl iodide variety for the elucidation of SET reaction steps continues and is summarized in two reviews published by the main protagonist^.^^ Although there are still many points of contention particularly regarding the presence or absence of impurities capable of initiating SET chain reactions and also reasons for the lack of cyclized products observed on reaction of capto-dative probe (42) with metal hydride reducing agents it is now widely agreed and appreciated by all that the simple observation of cyclic products from cyclizable radical probes especially iodides cannot be taken as evidence of an SET step.M. Newcomb and D. P. Curran Acc. Chem. Res, 1988 21 206; E. C. Ashby ibid. p. 414.

ISSN:0069-3030    

DOI:10.1039/OC9888500071

出版商:RSC    

年代:1988

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (i) Hydrocarbons By S. E. THOMAS Department of Chemistry University of Warwick Coventry CV4 7AL 1 Alkanes The alkanes are an attractive starting point for the application of molecular modelling techniques because not only do many of their properties vary in a regular manner with molecular mass but also problems associated with more polar compounds do not arise. A modelling study has been carried out on eight physical properties of seventy-four normal and branched alkanes.’ It proved possible to model most of the properties accurately with the exception of melting points which could not be modelled precisely by any of the available indices. The effect of solvent on the conformation of hydrocarbon chains has been probed using the Karplus-like response of ,.Icc to the relative disposition of two 13Catoms about a central carbon-carbon bond.* Results obtained in solvents of widely differing polarity suggest that chain conformation is remarkably insensitive to changes in solvent.The development of systems which effect selective catalytic functionalization of alkanes continues to be an area of intense research activity. Modifications to photochemical polyoxometallate methods3 and photocatalytic RhCl(CO)( PR,) for dehydrogenation of alkanes to alkenes have been reported whilst studies on alkane oxidation include a comparison of the Gif system (iron catalyst oxygen zinc carboxylic acid) with its electrochemical equivalent (the Gif-Orsay system),6 and the use of ruthenium complexes containing polypyridyl ligands to catalyse the oxidation of alkanes by alkyl hydro peroxide^.^ Photochlorination of n-alkanes adsorbed on pentasil zeolites monochlorinates terminal methyl groups more selectively than the corresponding homogeneous reaction and so provides a novel method for synthesizing terminally functionalized linear alkanes.* ’ D.E. Needham I.-C. Wei and P. G. Seybold J. Am. Chem. SOC.,1988 110 4186. * F. M. Menger and L. L. D’Angelo J. Am. Chem. SOC., 1988 110 8241. R. F. Renneke and C. L. Hill Angew. Chem. Inr. Ed. Engl 1988 27 1526. T. Sakakura T. Sodeyama Y. Tokunaga and M. Tanaka Chem. Lett 1988 263. K. Nomura and Y. Saito J. Chem. Soc. Chem. Commun. 1988 161. G. Balavoine D. H. R. Barton J. Boivin A. Gref P. Le Coupanec N.Ozbalik J. A. K. Pestana and H. Rivihre Tetrahedron 1988 44 1091. ’ T.-C. Lau C.-M. Che W.-0. Lee and C.-K. Poon J. Chem. SOC.,Chem. Commun. 1988 1406. N. J. Turro J. R. Fehlner D. P. Hessler K. M. Welsh W. Ruderman D. Firnberg and A. M. Braun J. Org. Chem. 1988 53 3731. 85 S. E. Thomas Two new methods for the reduction of alcohols to alkanes have been reported. Bu;SnH-Et3B reduces dithiocarbonates or thiocarbonates derived from secondary alcohols to the corresponding hydrocarbons under mild conditions' and acetates derived from primary secondary and tertiary alcohols are deoxygenated to hydrocarbons in high yield by p-bis( diphenylhydrosily1)benzene under homolytic conditions." 2 Alkenes Synthesis.-Di-and triquaternary alkenes have been synthesized by dehydration of secondary and tertiary neopentyl alcohols without any rearrangement occurring." For example the triquaternary alkene (1) was synthesized by addition of Bu'Li to nitrile (2) followed by hydrolysis addition of a second equivalent of Bu'Li and dehydration of the resulting alcohol.Lithium tetraalkylcerates prepared by the addition of four equivalents of alkyl-lithium to cerium trichloride add to epoxides to give alkylated alkenes. The utility of this method has been demonstrated in a short synthesis of the sesquiterpene dehydro-a-curcumene (Scheme 1).l2 43% Reagents i dirnethoxyethane-diethyl ether (2 l) -93 +-50 "C,16h Scheme 1 A mild but slow enzyme-assisted procedure for the regio- and stereo-controlled addition of perfluoroalkyl groups to alkynes has been rep~rted.'~ Thus reaction of alkynes with perfluoroalkyl iodides in the presence of several enzyme systems leads to perfluoroalkylated alkenes and perfluoroalkanoic acids (Scheme 2).An E-alkene with a chiral substituent has been synthesized in high optical purity by reaction of an alkyne with a borane bearing the required optically active sub- stituent (Scheme 3).14 K. Nozaki K. Oshirna and K. Utimoto Tetrahedron Lett. 1988,29 6125. 10 H. Sano T.Takeda and T. Migita Chem. Lett. 1988 119. C. A.Drake N. Rabjohn M.S. Tempesta and R. B. Taylor J. Org. Chem. 1988,53 4555. 12 Y. Ukaji and T. Fujisawa Tetrahedron Lett. 1988,29 5165. l3 T. Kitazurne and T. Ikeya J. Org. Chem. 1988,53 2350.14 H. C. Brown R. K. Bakshi and B. Singaram J. Am. Chem. Soc. 1988,110,1529. Aliphatic Compounds -Part (i) Hydrocarbons 87 R R = F CF, CP,. CSF,, C,F,S 24-66% 33-75% R R' = H alkyl aryl Reagents i urease/ Ni porphin or lipoxygenase/Fe porphin or catalase/ Fe protohaem H,O 9-36 days Scheme 2 72% yield 99% e.e. Reagents i NaOMe; ii Pr'C0,H Scheme 3 Addition of Grignard reagents to 5-alkyl-2,3-dihydrofurans in the presence of Ni(o) catalysts produces homoallylic alcohols (Wenkert reaction). This reactivity has been extended to 6-a1kyl-3,4-dihydro-2H-pyrans.l5 The reaction gives trisub- stituted alkenes with retention of configuration and has been applied to the synthesis of (E)-3-acetoxy-7-methylnon-6-ene, the aggregation pheromone of the square- necked grain beetle Cathartus quadricollis (Scheme 4).OAc I Reagents i EtMgBr; ii TsOH pyridine; iii MeMgBr; iv Ac20 Scheme 4 A new method for regiospecific carbon-carbon coupling of terminal alkenes based on a sulphonylation-alkylation-desulphinylationprocess has been described and applied to the conversion of (+)-limonene (3) into (E)-and (2)-a-bisabolenes (4).16This direct extension of a terminal alkene promises to be of further value in natural product synthesis. l5 P. Kocienski N. J. Dixon and S. Wadman Tetrahedron Lett. 1988 29 2353. J. E. Baldwin R. M. Adlington Y. Ichikawa and C. J. Kneale J. Chem. SOC.,Chem. Commwn. 1988,702. S. E. Thomas A review covering the conversion of enol triflates into a wide variety of alkenes by their reaction with organocopper reagents or other nucleophiles in the presence of palladium catalysts has been p~blished.’~ The Wittig reaction and related processes continue to attract a lot of attention.Further mechanistic studies have been and stereoselectivity studies have focused on Wittig reactions of allylic ylides,2’ semi-stabilized ylides,22 and ylide anions derived from semi-stabilized phosphonium ylide~.~~ Higher yielding procedures for the Wittig reaction between trifluoromethylketones and non-stabilized phosphorus ylide~,~~ and the Horner synthesis of didehydroamino acid derivatives from aldehydes and N-acyl-2-(diethoxyphosphory1)glycine esters2’ have been reported. Wittig reactions of esters thiol esters amides anhydrides and imides have been reviewed.26 To date preparation of labelled alkenes by Wittig and related reactions has been limited by scrambling and exchange processes.It has now been shown that Wittig- Horner reactions between aldehydes RCHO and phosphonates (EtO),POCH,R’ performed in 6M K2C03/ D20 give specifically deuterated alkenes RCH=CDR’ (D > 95%) in high yield.27 An ylide bearing a masked formyl group has been generated (Scheme 5).28 It cleanly reacts with aldehydes to give predominantly or exclusively (E)-vinylthiazoles which may be converted into two-carbon homologues of the original aldehydes. Two effective ketone-methylenating agents CH,(AlClMe)2 and CH2(A1ClEt) have been prepared.29 As dietherates with Et20 or THF they smoothly convert aliphatic and aromatic ketones into the corresponding alkenes with little or no concomitant alkylation or reduction.17 W. J. Scott and J. E. McMurry Acc. Chem. Rex 1988 21 47. 18 E. Vedejs C. F. Marth and R. Ruggeri J. Am. Chem. SOC.,1988 110 3940. 19 E. Vedejs and C. F. Marth J. Am. Chem. SOC.,1988 110 3948. 20 H. Yamataka K. Nagareda Y. Takai M. Sawada and T. Hanafusa 1.Org. Chem. 1988 53 3877 21 R. Tamura K. Saegusa M. Kakihana and D. Oda J. Org. Chem. 1988 53 2723. 22 A. Mylona J. Nikkokavouras and I. M. Takakis J. Org. Chem. 1988 53 3838. 23 E. G. McKenna and B. J. Walker Tetrahedron Lett. 1988 29 485. 24 F. Camps F.-J. Sanchez and A. Messeguer Synthesis 1988 823. 2s P. G. Ciattini E. Morera and G. Ortar Synthesis 1988 140.26 P. J. Murphy and J. Brennan Chem. SOC.Rev. 1988 17 1. 27 P. Seguineau and J. Villieras Tetrahedron Lett. 1988 29 477. 28 A. Dondoni G. Fantin M. Fogagnolo A Medici and P. Pedrini Tetrahedron 1988,44 2021. 29 A. M. Piotrwski D. B. Malpass M. P. Boleslawski and J. J. Eisch J. Org. Chem. 1988 53 2829. Aliphatic Compounds -Part (i) Hydrocarbons Reagents i Bu'OK; ii Mel; iii NaBH,; iv Hg2+/H20 Scheme 5 While there are many non-chiroptical methods for the assay of chiral amines alcohols and acids there are very few reliable techniques for measuring the enan- tiomeric purity of chiral alkenes. It is of note therefore that the enantiomers of alkenes (5)-( 8) are cleanly separated by capillary gas chromatography using hep- takis-(2,3,6-tri-O-n-pentyl)-P-cyclodextrin as the stationary phase,30 and that a full account of the use of optically active platinum and palladium complexes as chiral derivatizing agents for alkenes has been p~blished.~~ Reactions.-The potential energy profile for the full catalytic cycle of alkene hydroge- nation using Wilkinson's catalyst has been studied using ab initio MO methods; results indicate that the profile is smooth without any excessively high barriers or very stable intermediate^.^^ It is of note that this is the first ab initio study of the potential energy profile of a full catalytic cycle.Chiral allylic secondary alcohols have been resolved efficiently by homogeneous hydrogenation catalysed by (R)-or (S)-BINAP-Ru diacetate complexes.33 The combined effects of both intra- and intermolecular asymmetric induction give up to 76 :1 differentiation between the enantiomeric substrates.Decomposition of formic acid to hydrogen and carbon dioxide in the presence of catalytic amounts of optically active rhodium complexes has been shown to be a simple and effective alternative source of hydrogen for enantioselective hydrogenation of a$-unsaturated carboxylic Ab initio MO calculations designed to determine the transition state geometries of the reactions between halogens and ethene have been perf~rmed.~' These suggest that the transition state structure for the fluorination of ethene is four-centred whilst the transition state geometry for chlorination and bromination can be regarded as 30 J.Ehlers W. A. Konig S. Lutz G. Wenz and H. tom Diek Angew. Chem. Int. Ed. Engl. 1988 27 1556. 3' D. Parker and R. J. Taylor Tetrahedron 1988 44 2241. 32 C. Daniel N. Koga J. Han X. Y. Fu and K. Morokuma J. Am. Chem. SOC.,1988 110 3773. 33 M. Kitamura 1. Kasahara K. Manabe R. Noyori and H. Takaya J. Org. Chem. 1988 53 708. 34 H. Brunner and W. Leitner Angew. Chern. Int. Ed. Engl. 1988 27 1180. 35 S. Yamabe T. Minato and S. Inagaki J. Chem. SOC.,Chem. Commun. 1988 532. 90 S. E. Thomas a cyclic chloronium (bromonium) ion plus a chloride (bromide) ion. The calculated transition state structures agree with the observed syn-selective fluorination and anti-selective chlorination and bromination of ethene. A new catalytic process for asymmetric cis-dihydroxylation of alkenes has been reported (Scheme 6).36It is of note that unlike asymmetric epoxidations and most asymmetric hydrogenations this process does not require a directing functional group and that very small quantities of the osmium catalyst are required.dihydroquinidine esters “Ho I OH” R3 OH OH 80-95% yield “HO ’ OH” 20-88’/0 e.e. dihydroquinine esters Reagents i 0.2-0.4% OsO, acetone HzO o/ +\N’ w ‘o-Scheme 6 New methods for converting alkenes into epoxides include a sodium perbor- ate/ acetic anhydride system,37 hydrogen peroxide oxidation catalysed by a new class of quaternary ammonium tetrakis( diperoxotungsto) phosphate catalyst,38 and Bu‘OOH oxidation catalysed by a novel polystyrene-supported peptide-linked molybdenum catalyst.39 An interesting approach to the problem of preparing enan- tiomerically pure simple chiral epoxides has been reported.Thus Sharpless epoxida- tion of the alkenyl silanol (9) in the presence of (+)-diethy1 tartrate followed by protodesilylation gives (S)-styrene oxide in 85-95% enantiomeric excess.4o Ph *SiMe20H A simple direct synthesis of thiiranes from alkenes has been developed!’ Treat-ment of bis(trimethylsily1) sulphide with bromine at -78°C forms trimethylsilylsul- phenyl bromide which reacts with 1,2-disubstituted alkenes to give the correspond- ing thiiranes in moderate yield. The regioselectivity and stereoselectivity of the aziridinating agent N-acetoxyaminoquinazolone(10) has been examined.42 Aziridi- 36 E.N. Jacobsen I. Marko W. S. Mungall G. Schroder and K. B. Sharpless J. Am. Chem. SOC.,1988 110 1968. 37 G. Xie L. Xu J. Hu S. Ma W. Hou and F. Tao Tetrahedron Lett. 1988 29 2967. 38 C. Venture110 and R. D’Aloisio J. Org. Chem. 1988 53 1553. 39 Y. Okamoto and W. C. Still Tetrahedron Lett. 1988 29 971. 40 T. H. Chan L. M. Chen and D. Wang J. Chem. SOC.,Chem. Commun. 1988 1280. 41 F. Capozzi G. Capozzi and S. Menchetti Tetrahedron Lett. 1988 29 4177. 42 R. S. Atkinson and B. J. Kelly J. Chem. SOC.,Chem. Commun. 1988. 624. Aliphatic Compounds -Part (i) Hydrocarbons nation of cyclohex-2-en- 1-01 gives predominantly (95 :5) the syn-stereoisomer and aziridination of geraniol is highly selective (11 :1) for the allylic alcohol double bond.The selectivities observed are higher than those seen in corresponding reactions with peracids. This is attributed to stronger hydrogen bonding between (10) and the hydroxy group in the aziridination transition state than occurs between the peracid and the hydroxy group in the epoxidation transition state. Caesium fluoroxysulphate adds to alkenes under mild conditions to give previously unknown vicinal fluoroalkyl ~ulphates.~~ Chlorotrimethylsilane/sodium iodide in the presence of water may be used to convert alkenes into alkyl iodides under mild conditions.44 The procedure has also been used to synthesize deuterated alkyl iodides by replacing the water with D20. Benzenetellurinyl trifluoroacetate reacts with alkenes in acetonitrile in the presence of BF3 -OEt to give 2-oxazolines in good yield via amidotellurinylation of the alkene~.~~ The overall transformation of alkenes into oxazolines proceeds with Markovnikov regioselectivity and cis-stereoselectivity.Samarium diiodide has been shown to be an effective initiator for the addition of fluoroalkyl iodides to alkene~.~~ Convenient procedures for overall anti-Markovnikov hydr~iodination:~ hydro- bromination:* and hydro~hlorination~~ of alkenes have been reported. Hydrobor- ation of alkenes followed by treatment of the resulting boranes with either iodine/sodium methoxide or bramine/sodium methoxide or nitrogen trichloride gives anti-Markovnikov alkyl iodides bromides or chlorides in good yield. It has been demonstrated that rhodium( I)-catalysed and non-catalysed hydroborations may have complementary stereochemical consequence^.^^ For example hydrobor- ation of acyclic 1,l-disubstituted allylic alcohols using 9-BBN occurs with high anti-selectivity whilst Rh(PPh,),Cl-catalysed hydroboration with catecholborane takes place with high syn-selectivity (Scheme 7).Enantioselective hydroboration is mediated by homochiral rhodium( 1)-phosphine c~mplexes.~~ Whilst the reported enantiomeric excesses are moderate this new approach to asymmetric hydroboration appears to be of considerable promise. 43 N.S. Zefirov V. V. Zhdankin A. S. Koz’min A. A. Fainzilberg A. A. Gakh B. I. Ugrak and S. V. Romaniko Tetrahedron 1988 44 6505. 44 S. Irifune T. Kibayashi Y. Ishii and M. Ogawa Synthesis 1988 366.45 N. X. Hu Y. Aso T. Otsubo and F. Ogura Tetrahedron Lett. 1988 29 1049. 46 X. Lu S. Ma and J. Zhu Tetrahedron Lett. 1988 29 5129. 47 H. C. Brown M. W. Rathke M. M. Rogic and N. R. de Lue Tetrahedron 1988 44 2751. 48 H. C. Brown and C. F. Lane Tetrahedron 1988,44 2763. 49 H. C. Brown and N. R. de Lue Tetrahedron 1988,44 2785. D. A. Evans G. C. Fu and A. H. Hoveyda J. Am. Chem. SOC.,1988 110,6917. K. Burgess and M. J. Ohlmeyer J. Org. Chem. 1988 53 5178. S. E. Thomas . ... I 111 1' BunL O H 80-94% Bu nq Me J ii iii + Bunq0H 77-96% Me R = H SiBu'Me, SiBu'Ph Reagents i 9-BBN THF 25 "C;ii catecholborane cat. Rh(PPh,),Cl 25 "C; iii NaOOH Scheme 7 A chloride-free Wacker-type oxidation of terminal alkenes to methyl ketones has been de~eloped.~~ This oxidation proceeds via multi-component catalysis (Scheme 8) but the absence of cupric chloride from the oxidation relay prevents the formation of the chlorinated side products often observed in the Wacker process itself.0 II Fe(Pc) x H20 OH Fe(Pc) 402 0 Fe( Pc) = iron phthalocyanine Scheme 8 3 Polyenes Synthesis.-Thermolysis of 3,4-disubstituted 3-sulpholenes (prepared from 3-substituted 4-bromo-2-sulpholenes by nucleophilic substitution followed by isomerization) has been used to synthesize 2,3-disubstituted buta-l,3-dienes bearing chloro bromo azido trimethylsilyl phenylthio phenylsulphinyl or phenylsul- phony1 Similarly 3-cyano-3-sulpholene a stable crystalline compound has been synthesized and shown to be a good source of the unstable diene 2- cyanobuta- 1 ,3-diene.54 52 J.-E.Backvall and R. B. Hopkins Tetrahedron Lett. 1988 29 2885. 53 T.-S. Chou S.-J. Lee M.-L. Peng D.-J. Sun and S.4. P. Chou J. Org. Chem. 1988 53 3027. 54 P. G. Baraldi A. Barco S. Benetti S. Manfrdini G. P. Pollini D. Simoni and V. Zanirato Tetrahedron 1988.44 6451. Aliphatic Compounds -Part (i) Hydrocarbons Treatment of several a-allenic alcohols with methyllithium and copper iodide followed by N,N-methylphenylaminotributylphosphoniumiodide and a second organolithium reagent (Murahashi conditions) leads to 2-substituted 1,3-dienes in which the substituent is derived from the second organolithium reagent.55 2-(Phenylsulphonyl)-l,3-dienesare versatile synthons which have previously been prepared from 1,3-dienes by a 1,2-sulphonylmercuration-eliminationsequence.To avoid the use of mercury derivatives a new one-pot procedure for the transformation of 1,3-dienes into 2-(phenylsulphony1)- 1,3-dienes has now been de~eloped.~~ The reaction involves 1,2-selenosulphonation by PhS0,SePh in the presence of BF3 followed by MCPBA oxidation and gives good to excellent yields. Several palladium-mediated syntheses of 1,3-dienes have been published in 1988. It had been reported earlier that treatment of allylic acetates with triphenylphosphine and a catalytic amount of palladium acetate led to E,Z-mixtures of 1,3-dienes. Although various allylic acetates had been examined none of the substrates had a substitution pattern that would lead to 1,3-disubstituted 1,3-dienes.Examination of such substrates (11) revealed that they gave rise to stereochemically pure (E)-l,3- dialkyl- 1,3-diene~.~~ Thus the 2-alkyl substituent on the vinyl moiety appears to control the stereochemical outcome of the reaction; the nature of this control is as yet unclear. Cleavage of the .rr-allyl-palladium complex (12) to give 2,3-bis( bromomethy1)buta- 1,3-diene is more efficient with bromine than with copper( 11) bromide the reagent previously employed for this transformation. Palladium( 11) bromide used in the synthesis of (12) from allene is recovered in almost quantitative yield from the reaction.58 Allenes combine with silylated vinyl bromides in the presence of palladium(o) catalysts to give 7r-allyl-palladium complexes which can be trapped by nucleophiles to generate functionalized silylated dienes (Scheme 9).59 R2 I Br 50-75% R' = H n-heptyl R2 = H SiMe, CH,SiMe R3= H,SiMe Nu = CH(CO,Me) ,CH(C02Me)(COMe) Reagents i NaNu cat.Pdo THF or DMSO 65 "C 24 h Scheme 9 55 C. Fan and B. Cazes Tetrahedron Lett. 1988 29 1701. 56 J.-E. Backvall C. Najera and M. Yus,Tetrahedron Lett. 1988 29 1445. 57 F. M. Hauser R. Tommasi P.Hewawawam and Y.S. Rho J. Org. Chem. 1988 53 4886. 58 S. M. Ali S. Tnimoto and T. Okamoto J. Org. Chem. 1988 53 3639. 59 B. Cazes V. Colovray and J. Gore Tetrahedron Lett. 1988 29 627. S. E. Thomas Palladium-catalysed cross-coupling of (E)-1-alkenylalanes with (E)-2-bromo-vinyltrimethylsilane (performed in the presence of the 2-isomer) gives (1E,3E)-1-trimethylsilyl-1,3-dienes of high stereoisomeric purity (>99% ) (Scheme R = n-C,H, ,Bu' Reagents i cat.Pd(PPh,), THF 40 "C 16 h Scheme 10 Mono-and disubstituted penta-1,4-dienes have been synthesized from substituted (2-[ (trimethylsilyl)methyl]cyclopropyl}carbinols (13) by either treatment of the car-binol with acid or its conversion into the corresponding mesylate.61 The high trans-stereoselectivity for the alkene derived from the carbinol terminus has been exploited in a synthesis of a constituent of the pheromone emitted by the melon fly Dacus curcurbitae Coquillett. Me3Si OMe R&- - SiMe3 R R 0 R R = H,al kyl R = H,alkyl H alkyl aryl (13) (14) (15) 2-(Allyloxy)benzothiazoles react with allylic Grignard reagents in the presence of copper(1) bromide to give 1,5-dienes formed by head-to-tail coupling.If however the copper(I) bromide is complexed with the 2-(allyloxy)benzothiazoles prior to Grignard reagent addition then head-to-head coupled 1,Sdienes are generated.62 Allenic ketones give Diels-Alder adducts (14) with furan; modification of the adducts followed by regeneration of the allene moiety by thermofragmentation leads to a wide range of a-functionalized allene~.~~ Pyrolysis of propargylic derivatives (15) results in the extrusion of formaldehyde and the production of trimethylsilylal-lenes in excellent yield.64Several optically active allenes have been prepared includ-ing the enantiomers of (16) synthesized from (+)-and (-)-~amphene,~~ and (17) formed in modest optical purity (e.e.18%) by elimination of the silicon and trifluoroacetate groups from the optically active vinylsilane (18) using tris(dimethyl-amino)sulphur trimethylsilicon difluoride.66 60 B. P. Andreini A. Carpita and R. Rossi Tetrahedron Lett. 1988 29 2239. 61 S. R. Wilson and P. A. Zucker J. Org. Chern. 1988 53 4682. 62 V. Calo L. Lopez and G. Pesce J. Chem. SOC.,Perkin Trans. I 1988 1301. 63 J. L. Gras B. S. Galledou and M. Bertrand Bull. SOC.Chim. Fr. 1988 757. 64 H. Hopf and E. Naujoks Tetrahedron Lett. 1988 29 609. 65 J. MaHay M. Conrads and J. Runsink Synthesis 1988 595. 66 E.Torres G. L. Larson and G. J. McGarvey Tetrahedron Left. 1988 29 1355. Aliphatic Compounds -Part (i) Hydrocarbons 95 h It has been reported that conjugated trienes may be synthesized readily and stereoselectively by coupling 2-trialkylstannyl-3-sulpholenes(19) with vinyl iodides under palladium(0) catalysis followed by de~ulphonylation.~~ Conjugated trienes have also been prepared by a palladium-catalysed reaction between alkenes and either fumaryl chloride or (E)-5-phenylpenta-2,4-dienoyl chloride.68 Interestingly the tosylate of tropone oxime (20)undergoes a ring-opening reaction with secondary amines alkoxides and Grignard reagents to give 6-substituted (1Z,3Z,5Z) -hexa-1,3,5-trienecarbonitriles(21)in high yield.69 The Z,Z,Z-isomers are thermodynami- cally unstable and can be readily converted into more stable isomers.,OTs N II R = H,Me Tetrakis(trimethylsily1)butatriene (22) has been prepared in 41'/o yield from hexakis(trimethylsilyl)but-2-yneby flash vacuum pyrolysis at 650 0C.70 Several approaches to conjugated polyene chains have been investigated. Catalysts of the type M(CHBu')(NAr)(OBu')2 (M = Mo or W) have been shown to catalyse ring-opening metathesis polymerization of (23)in a controlled manner to give (24).7' SiMe3 .+-,- (ArN)(BU'O)~MKBul Me3Si SiMe3 F3C (22) (23) x = 3-7 (24) Treatment of (24)with pivalaldehyde gives a metal-free oligomer which on heating yields a mixture of polyenes containing 7-1 5 double bonds. These can be separated by chromatography at -40°C under a nitrogen atmosphere.Similarly ring-opening H. Takayama and T. Suzuki J. Chem. SOC., 67 Chem. Commun. 1988 1044. 68 A. Kasahara T. Izumi and N. Kudou Synthesis 1988 704. 69 T. Machiguchi T. Hasegawa M. Ohno Y. Kitahara M. Funamizu and T. Nozoe J. Chem. Soc. Chem. Commun. 1988 838. 70 H. Sakurai M. Kudo K. Sakarnoto Y. Nakadaira M. Kira and A. Sekiguchi Chem. Lett. 1988 1441. 71 K. Knoll S. A. Krouse and R. R. Schrock J. Am. Chem. SOC.,1988 110 4424. S. E. Thomas metathesis polymerization of benzvalene (25) with W(CHBu')( NAr)( OBU')~ gives polybenzvalene (26),72 which can be isomerized to conjugated polyene chains under transition metal catalysis. Addition of tungsten metathesis catalysts to 'neat' cyclo- octa-1,3,5,7-tetraene has been shown to lead to high-quality p~lyacetylene.'~ Reactions.-Treatment of buta-l,3-diene with I(py),BF in the presence of benzene or acetonitrile leads exclusively to 1,4-adducts (Scheme ll).74 It is of note that Reagents i CH,CI, C6H6 5 "C 4 h; ii CH2C12 MeCN H,O -5 "C 15 min Scheme 11 earlier reports show that treatment of buta-1,3-diene with I(py),BF in the presence of stronger nucleophiles gives 1,2-adducts.A mild method for stereo- and regioselec- tive 1,4-dialkoxylation of conjugated dienes has been de~eloped.~' The reaction is catalysed by palladium( II) uses p-benzoquinone as the oxidant and requires catalytic amounts of a strong acid. It has been demonstrated that the simple trifluorodiene (27) prepared from commercially available 4-bromo- 1,1,2- trifluorobut-1-ene can be regarded as a C4 synthon in which the fluorine at C2 is retained during the course of various electrophilic and nucleophilic transforma- tion~.~~ Ozonolysis of the sterically hindered buta-1,3-diene (28) has been studied in solution and on solid support^:'^ a range of products including (29)-(33) were obtained.1,4-Dienes cyclize to 2-methylcyclopentanones under an atmosphere of carbon monoxide and hydrogen in the presence of transition metal catalysts. The effects of altering the catalyst and varying the reaction conditions on the regio-and stereochemical outcome of this reaction have been in~estigated.'~ Electrophilic 72 T. M. Swager D. A. Dougherty and R. H. Grubbs J. Am. Chem.Soc. 1988 110 2973. 73 F. L. Klavetter and R. H. Grubbs J. Am. Chem. Soc. 1988 110 7807. 74 J. Barluenga J. M. Gonzalez P. J. Campos and G. Asensio Tetrahedron Lett. 1988 29 6497. 75 J.-E. Backvall and J. 0.Vagberg J. Org. Chem. 1988 53 5695. 76 N. Matsuo and A. S. Kende J. Org. Chem. 1988 53 2304. 77 K. Griesbaum and W. Volpp Chem. Ber. 1988 121 1795. 78 P. Eilbracht M. Acker and I. Hadrich Chem. Ber. 1988 121 579. Aliphatic Compounds -Part (i) Hydrocarbons cyclization of substituted 1,5-dienes has been re~iewed.'~ Reactions are subdivided into those catalysed by Lewis acids and those promoted by either bromonium mercurinium or phenylselenonium ions. Carboxylic acids react readily with cis-1,2-divinylcyclohexane under palladium catalysis and in the presence of oxidizing agents to give exo-cis-hydrindanes (Scheme 12).It has now been reported that the use of chiral acids in this reaction leads to modest asymmetric induction.*' H 70% Reagents i MnO, benzoquinone cat. Pd(OAc)* AcOH r.t. 42 h Scheme 12 Allene oxidation has been the subject of several reports. Addition of dimethyl-dioxirane to simple allenes gives 1,4-dioxaspiro[2.2]pentanes (34) in good yield and intermolecular nucleophilic attack proceeds regioselectively to generate a-hydroxy ketones (35).g' Similarly dimethyldioxirane oxidation of allenic alcohols (36) yields (34) (35) n = 1,2 (36) tetrahydrofuran and tetrahydropyran derivatives (37) via intramolecular nucleophilic addition to the intermediate allene diepoxide.82 Oxidation of vinyl allenes (38) with Bu'OOH and VO(acac) gives cyclopentenones (39) in 40-70% 79 N.Grionlonfoun Bull. SOC.Chim. Fr. 1988 862. 80 A. Heumann and C. Moberg J. Chem. Soc. Chem. Commun. 1988 1516. 8' J. K. Crandall and D. J. Batal J. Org. Chem. 1988 53 1338. 82 J. K. Crandall and D. J. Batal Tetrahedron Left. 1988 29 4791. S. E. Thomas n = 1,2 n = 1,2 (37) (38) (39) yield.83 This stereoselective annulation is rationalized by invoking initial hydroxy- directed allene oxide formation subsequent isomerization of the allene oxide to an oxapentadienyl cation or a vinyl cyclopropanone and finally antarafacial pericyclic ring closure. It has been reported that addition of triphenylstannane or triphenylgermane to allenes in the presence of catalytic amounts of Pd(PPh3)4 gives allylic stannanes or allylic germanes in good yield.84 Silyl-cupration of allene using (PhMe,Si),CuLi followed by treatment with iodine anomalously yields the vinyl iodide (40).85 Lithiation of (40) generates a silylated C,-nucleophile which reacts cleanly with a range of electrophiles.The utility of dimethyl allene-l,3-dicarboxylatein heterocyclic synthesis has been further demonstrated.86 It has been converted into pyridones condensed pyridones thiazopyrones thiazinones thiochromanones and thienopyridones by reaction with appropriate nucleophiles. The reactions of 1,1,4,4-tetraarylbuta-l,2,3-trieneswith elemental sulphur and selenium have been e~amined.~' Sulphurization yields novel 1,2,3,4,5-pentathiepanes (41) and selenation generates 1,2,5-triselenepanes (42).R = Ar R = Ar (41) (42) 4 Alkynes Synthesis.-A method for synthesizing the optically active acetylenic alcohol (43) has been reported;88 lithium amide-induced elimination from (44) readily prepared from L-(+)-tartaric acid gave (43) in 90% yield. 1-Alkoxyalk-1-ynes and l-alkoxyalk- 1 -yn-3-ols have been prepared from chloroacetaldehyde dialkyl a~etals.~~ The reac- tion is initiated by sodium amide and the acetylide anion produced reacts readily 83 S. J. Kim and J. K. Cha Tetrahedron Lett. 1988 29 5613. 84 Y. Ichinose K. Oshima and K. Utimoto Bull. Chem. Soc. Jpn. 1988 61 2693. 85 P. Cuadrado A. M. Gonzalez F. J. Pulido and I. Fleming Tetrahedron Lett.1988 29 1825. 86 G. J. S. Doad D. 1. Okor F. Scheinmann P. A. Bates and M. B. Hursthouse J. Chem. Soc. Perkin Trans. 1 1988 2993. 87 N. Tokitoh H. Hayakawa M. Goto and W. Ando Tetrahedron Lett. 1988 29 1935. 88 J. S. Yadav M. C. Chander and B. V. Joshi Tetrahedron Lett. 1988 29 2737. 89 W. M. Stalick R. N. Hazlett and R. E. Morris Synthesis 1988 287. Aliphatic Compounds -Part (i) Hydrocarbons with a range of alkyl halides and carbonyl compounds to give the alkyne derivatives in good yield. Dehydrobromination of (2)-2-bromovinyl silyl ethers using LDA gives trialkylsil~xyalkynes.~~ This approach provides access to the parent trialkylsily- loxyethynes for the first time. A number of acetylenic ketones have been prepared by reacting lithium acetylides with acetic anhydride N,N-dimethylacetamide or N,N-dimethylben~amide.~' Addition of alkynylzinc chlorides to acyl halides is also a practical approach to acetylenic ketones.It has been demonstrated that formyltrimethylsilane generated from (trimethylsily1)methanol by Swern oxidation reacts with lithium acetylides to give alcohols which can be oxidized readily to acetylenic acylsilanes (45).92 The first synthesis of acetylenic carboxylates has been reported.93 Reaction of PhI(OCOR)* with lithium acetylides or anion exchange of alkynylphenyliodonium tosylates gives alkynylphenyliodonium carboxylates (46) which decompose to acetylenic carboxylates and iodobenzene. 1-1odoalk-1-ynes have been synthesized by treating terminal alkynes with a sol- ution of iodine in DMF in the presence of sodium or potassium carbonate Bu",NCl and a catalytic amount of copper(1) iodide.94 A simple one-pot procedure for the preparation of primary 2-alkynamides (47) from 1-alkynyltrimethylsilanesand chlorosulphonyl isocyanate has been reported." Acetylenedicarbaldehyde has pre- viously only been isolated in the presence of formic acid.A procedure has now been reported for its isolation in pure form which involves acidolysis of the monoacetal (48) with an excess of formic acid followed by dehydration of residual formic acid with PzOs.96 0 + 0 0 Y-i OEt R-G-f R-CGCIPh R-+f SiMe3 -0COR NH2 H OEt (45) (46) (47) (48) Several approaches to enynes have been investigated. Palladium-catalysed dimerization of ethynyl-substituted mono-and disilanes produces head-to-head coupled enynes (49),97 regioselective halide substitution reactions of butatrienes (50) yield halogenoenynes (51),98 and methylation of 2-enynyl bromides (52) with MeMgI and Fe(acac) catalyst gives 2-alkyl-1-en-3-ynes (53)with net inversion of the double bond ge~metry.~' 90 R.L. Danheiser A. Nishida S. Savariar and M. P. Trova Tetrahedron Lett. 1988 29 4917. 91 H. D. Verkruijsse Y. A. Heus-Kloos and L. Brandsma J. Organomet. Chem. 1988 338 289. 92 R. J. Linderman and Y. Suhr J. Org. Chem. 1988,53 1569. 93 P. J. Stang M. Boehshar H. Wingert and T. Kitamura J. Am. Chem. SOC.,1988 110 3272. 94 T. Jeffery J. Chem. SOC.,Chem. Commun. 1988,909. 95 P. C. Bulman Page S. Rosenthal and R.V. Williams Synthesis 1988 621. 96 D. Stephan A. Gorgues A. Belyasmine and A. Le Coq J. Chem. SOC.,Chem. Commun. 1988 263. 97 M. Ishikawa J. Ohshita Y. Ito and A. Minato J. Orgnomet. Chem. 1988 346 C58. 98 C. B. Ziegler Tetrahedron Left. 1988 29 411. 99 J. A. Miller W. Leong and G. Zweifel 1. Org. Chem. 1988 53 1839. 100 S. E. Thomas R = Me,SiSi(Ph)Me, Me2PhSi MePh,Si (50) R' X = Cl,Br,I (49) (51) An enantioselective total synthesis of the enyne (54) a possible biogenetic precur- sor of a wide variety of halogenated cyclic ethers isolated from marine sources has been reported."' Asymmetry is introduced into the synthesis by the use of a Sharpless epoxidation step. A mild synthesis of 1,3-diynes from terminal alkynes which is compatible with a wide range of functional groups has been developed."' The first step of the synthesis involves a palladium(0)-catalysed coupling of terminal alkynes with cis- 1,2- dichloroethene to yield cis-chloroenynes (55); subsequent treatment of (55) with Bu,"NF provides a range of 1,3-diynes in good overall yield.Terminal arylbutadiynes (56) derived in situ from 6-arylhexa-3,5-diyn-2-01~ and base can be coupled with aryl halides under palladium catalysis to give unsymmetrical diarylbutadiynes (57).'02 R-=-? AT'-=-=-Arl -=-= -A r2 -c1 (55) (56) (57) Syntheses and properties of the medium sized carbocyclic dialkynes (58) and (59)103~104and analogues containing heteroatoms (60) and (61)'05 have been reported. Reactions.-Formation of HCN by photochemical dissociation of ammonia in the presence of ethyne has been observed.lo6 The possible role of this reaction and related photochemical processes in the formation of HCN on Jupiter is discussed.100 J. M. Palazon and V. S. Martin Tetrahedron Lett. 1988 29 681. 101 A. S. Kende and C. A. Smith J. Org. Chem. 1988 53 2655. 102 S. Adams Nye and K. T. Potts Synthesis 1988 375. 103 R. Gleiter D. Kratz and V. Schehlmann Tetrahedron Lett. 1988 29 2813. 104 R. Gleiter M. Karcher R. Jahn and H. Irngartinger Chem. Ber. 1988 121 735. 105 R. Gleiter and S. Rittinger Tetrahedron Lett. 1988 29 4529. 106 J. P. Ferris and Y. Ishikawa J. Am. Chem. Soc. 1988 110 4306. Aliphatic Compounds -Part (i) Hydrocarbons Iodine adds stereospecifically anti to alkynes on alumina to give E-dii~doalkenes."~ The reaction which is not observed in the absence of alumina is thought to occur by an ionic mechanism in contrast to the iodination of alkynes in solution where the addition is believed to occur by a free radical mechanism.The stereochemical outcome of acetoxymercuration of diphenylacetylene has been rein- vestigated and on the basis of I3C and 199Hg n.m.r. and X-ray data the product of the reaction being assigned as the trans-adduct (62).'08 This result contrasts with earlier reports on the reaction but is in agreement with the stereochemical outcome of acetoxymercuration reactions of alkylphenylalkynes and dialkylalkynes. It has been reported that P-keto sulphides (63) may be conveniently prepared by a BF3-promoted reaction of ArNHSPh with alkynes in either acetonitrile or acetic acid followed by hydrolysis of the resulting P-acetamidino- or P-acetoxy-vinyl phenyl sulphide~.'~~ Several metal-catalysed additions to alkynes have been reported.Addition of methanol to terminal alkynes under mercury( 11) chloride catalysis gives 2-methoxyalk-l-enes."o The reaction is performed in the presence of triethylamine to prevent acid-catalysed addition of methanol to the product. A full report of pal- ladium- and nickel-catalysed additions of trimethylsilyl cyanide to alkynes has been published,"' and it has been demonstrated that propyne may be added regioselec- tively to N-protected amino acids in the presence of catalytic amounts of arene- ruthenium-phosphine complexes to give isopropenyl esters in good yield."2 Photolysis of diphenyl or dimesityl diselenide with either dimethyl acetylenedicar- boxylate or methyl propiolate gave the first examples of free radical addition of diselenides to alkyne~."~ The products of the reaction between Bu"Li and di- phenylacetylene have been examined by 2D n.m.r.spectroscopy (COSY C-H shift correlation COLOC)."4 In THF the trans product (64) is obtained exclusively whilst in hexane/TMEDA (64) is accompanied by the dilithio product (65). 107 I08 109 110 111 112 113 114 S. Larson T. Lindhardt G. W. Kabalka and R. M. Pagni Tetrahedron Lett. 1988 29 35. Y. K. Grishin D. V. Bazhenov Y. A. Ustynyuk and N. S. Zefirov Tetrahedron Lett.1988 29 4631. L. Benati P. C. Montevecchi and P. Spagnolo Tetrahedron Lett. 1988 29 2381. J. Barluenga F. Aznar and M. Bayod Synthesis 1988 144. N. Chatani T. Takeyasu N. Horiuchi and T. Hanafusa J. Org. Chem. 1988 53 3539. C. Ruppin P. H. Dixneuf and S. Lecolier Tetrahedron Lett. 1988 29 5365. T. G. Back and M. V. Krishna J. Org. Chem. 1988 53 2533. W.Bauer M. Feigel G. Muller and P. von R. Schleyer J. Am. Chem. Soc. 1988 110 6033. 102 S. E. Thomas A number of reports on the oxidation of alkynes to 1,2-dicarbonyl compounds have been published. Ru04 generated by the action of NaI04 on Ru02 mediates the oxidation of disubstituted alkynes to 1,2-diketones in moderate to excellent yield. The compatibility of various functional groups with this oxidizing agent has been inve~tigated."~ Terminal alkynes may be oxidized to ketoaldehydes by the use of dilute hydrogen peroxide Na2M04 salts (M = MeV' or W"') and H~(OAC)~."~ The oxo( salen)chromium(v) complex (66) a proposed intermediate in catalytic oxygen transfer reactions has been shown to react with diphenylacetylene to give benzil."' A method for a-oxidation of alkynes to conjugated ynones using Bu'OOH in the presence of catalytic amounts of Cr03 and TsOH has been reported."' The reactions of alkynes with metal-carbene complexes continue to attract atten- tion.Cyclopentenones are obtained from the reaction between alkynes and a cyclo- propyl-methoxy chromium carbene complex (Scheme 13),* l9 and cyclopentafurans R = H alkyl aryl C0,Et 42-19% Reagents i dioxane 100 "C 4-6 h Scheme 13 are produced when alkynes are added to furan-methoxy chromium carbene com- plexes (Scheme 14).120 72% Reagents i DMF 120"C 5 h Scheme 14 115 R.Zibuck and D. Seebach Helv. Chim. Acta 1988 71 237. 116 F. P. Ballistreri S. Failla and G. A. Tomaselli J. Org. Chem. 1988 53 830. 117 B. Rihter and J. Masnovi J. Chem. SOC.,Chem. Commun. 1988 35. 118 J. Muzart and 0. Piva Tetrahedron Lett. 1988 29 2321. I19 J. W. Herndon S. U. Turner and W. F. K. Schnatter J. Am. Chem. SOC.,1988 110 3334. A. Yamashita A. Toy W. Watt and C. R. Muchmore Tetrahedron Lett. 1988 29 3403. Aliphatic Compounds -Part (i) Hydrocarbons It has been demonstrated that (Ph3P)3RhCl catalyses [2 + 2 + 21 cycloadditions between 1,6-diynes and alkynes to give polysubstituted benzene derivatives.'21 Intramolecular [2 + 2 + 21 cycloadditions are also catalysed by (Ph3P)&C1 and this reactivity has been exploited in a synthesis of calomelanolactone (Scheme 15).'22 0 Calomelanolactone Reagents i cat.(Ph,P),RhCl EtOH 25 "C 12 h Scheme 15 Chemo- and regioselective hydroboration of 2-methoxyenynes (67) with disiamyl- borane followed by oxidation of the intermediate organoborane with aqueous sodium acetate/ hydrogen peroxide produces synthetically useful methoxyenones (68) in good yield.'23 It has been shown that 1,6-enynes may be cyclized regiospecifically to methylene cyclohex-2-enes under (Ph3P)3RhCl ~atalysis.'~~ Terminal substitution on either the alkene or alkyne inhibits this reaction.Enynes and isonitriles cyciize in the presence of Ni(cod) and Bu;P to form 1-iminocyclopent-2-enes (69) which may be hydrolysed to the corresponding cyclopentenone~.'~~ 1,6- and 1,7-enynes have been used as substrates for the cyclization. 121 R. Grigg R. Scott and P. Stevenson J. Chem. Soc. Perkin Trans. 1 1988 1357. I22 S. J. Neeson and P. J. Stevenson Tetrahedron Lett. 1988 29 813. 123 G. Zweifel M. R. Najafi and S. Rajagopalan Tetrahedron Lett. 1988 29 1895. 124 R. Grigg P. Stevenson and T. Worakun Tetrahedron 1988 44 4967. I25 K. Tamao K. Kobayashi and Y. Ito J. Am. Chem. Soc. 1988 110 1286.

ISSN:0069-3030    

DOI:10.1039/OC9888500085

出版商:RSC    

年代:1988

数据来源: RSC

摘要:

5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry King's College London Strand London WC2R2LS 1 Alcohols and Ethers A wide-ranging synthesis of polyfunctional secondary alcohols depends on efficient coupling of an aldehyde and a cuprate RCu(CN)ZnI; the functional groups within the reagent may include ester nitrile enoate or amide. High yields were obtained with for example AcO(CH,),Cu(CN)ZnI and PhCHO (86%).' The absolute and relative configuration of fluorohydrins established via use of a-phenylpropionic acid as a derivatizing reagent for n.m.r. studies was supported by X-ray measure- ments.2 An article summarizing the work on generation of simple enols has been pub- li~hed.~ High selectivity has been reported for the reduction of p-hydroxyketones to anti-diols by Me4N+BH(OAc)3-.4 Controlled 'Payne-type' rearrangement of 2,3-epoxyalcohols in aprotic media has been studied and the product ratio shown to depend on the reactivity of the nucleophile; thus (1) after lithiation may by interchange afford (2) and the products (3) (4) and (5) reflect nucleophilic capture OH Nu P~CHZO+~~ PhCH20+oH PhCHzO4Nu OH Nu OH a~cordingly.~ Thus the product ratio from MeCu was significantly different to that from Ph,CuLi.This method was applied to a short synthesis of (+)-exo-brevicomin (6) in 31% overall yield. The synthesis and reactions of optically active 1.3-diols ' M.C. P. Yeh P. Knochel and L. E. Santa Tetrahedron Lett. 1988 29 3887. * P.Bravo F. Ganazzoli G.Resnati S. DeMunari and A. Albinati J. Chem. Res. (S) 1988 216. B. Capon B.-Z.Guo F. C. Kwok,A. K. Siddhanta and C. Zucco Acc. Chem. Res. 1988 21 135. D. A. Evans K. T. Chapman and E. M. Carreira J. Am. Chem. Soc. 1988 110 3560. P. C. B. Page C. M. Rayner and I. 0. Sutherland J. Chem. SOC.,Chem. Commun. 1988 356. 105 106 B. V. Smith derived from methyl 3-hydroxyglutarate have been explored particularly with respect to the synthon (7) which was converted into pure (8) (68%) by reaction with vinylmagnesium bromide.6 Easy access to t-butyl ethers and esters is achieved by reaction of Cl,C(C=NH)OBu' (from C1,CCN-ButOH) with the alcohol or acid in the presence of BF3.0Et2 .7 Some selectivity was noted for PhCH20CH2CH(OH)CH20H in which the terminal group was etherified.Reaction with acids was equally easy and afforded good yields e.g. BrCH2C02H gave 71% of ester. An alternative approach applicable to a wide range of alcohols was the use of isobutene and an Amberlyst H15 catalyst to form the t-butyl ether; this could be smoothly cleaved by Ac,O-FeCl in ether to afford the acetate. The advantage of this two-step method was that no isomeriz- ation ring closure or destruction of sensitive groups occurred; by this route (9) formed (lo) and for (1 1) -+ (12) no isomerization could be detected.' Me Et m=J(CH2)60R (9) R = But (11) R = But (10) R = Ac (12) R = AC Asymmetric synthesis of functionalized homoallylic alcohols (in both configur- ations) has employed a-sulphinylepoxides as a starting point.' High diastereoselec- tivity (90%) was noted for the synthesis of homoallylic alcohols with a syn-P-methyl group (Scheme l)." The complementary reaction of the (E)-a-chlorocrotyl boronate Reagents i RCHO CH2C12 0 "C;ii RCHO light petroleum 0 "C Scheme 1 L.Rosslein and C. Tamm Helu. Chim. Acra 1988 71 47. ' A. Armstrong I. Brackenridge R. F. W. Jackson and J. N. Kirk Tetrahedron Lett. 1988 29 2483. A. Alexakis M. Gardette and S. Colin Tetrahedron Lett. 1988 29 2951. G. Solladii C. Hamdouchi and M. Vicente Tetrahedron Lett. 1988 29 5929. LO R. W. Hoffman S. Dresely and J. W. Lanz Chem. Ber. 1988 121 1501. 107 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds (13) with 2-methylbutanal gave (14) and (15) (ca.3 1) which by reduction gave the known compounds (16) and (17) respectively. Such methods thus afford useful building blocks. qJ+ WC1 Me Me c1 Me Me * Me Me A stereoselective preparation of (E)-ally1 alcohols has been reported in which elimination from (18) by AIBN-boiling toluene is a key step." A convenient one-pot preparation of 2-substituted ally1 alcohols by transformation of an acid halide RCOCl into (19) has been reported.12 The enediol (20) was prepared in RLOH "\(""" good yield and enantiomerically pure via a boration-oxidation sequence starting from a borol-3-ene and was further transformed into a protected aldehyde (21) with a quaternary chiral centre (78%).13 Among methods which have been used in the preparation of oxiranes the following are noted.Stereospecific and efficient oxidation of alkenes by (22) (from Me2CO-K,S05) was achieved in 16 cases; for trans-2,5-dimethylhex-3-ene, compet-ing allylic oxidation lowered the yield.14 An interesting efficient and enantioselective A. Kaminura and N. Ono J. Chem. SOC.,Chem. Commun. 1988 1278. l2 J. Barluenga J. M. ConceMn J. L. Fernlndez-Simon and M. Yus J. Chem. SOC.,Chem. Commun. 1988 536. l3 G. Zweifel and T. M. Shoup J. Am. Chem. Soc. 1988 110 5578. A. L. Baumstock and P. C. Vasquez J. Org. Chem. 1988 53 3437. 108 B. V. Smith Ph .. Ph PhCOCH2Cl -VCI -H OH H H Reagents i BH,THF 1 mol % ; ii NaOH-H20 6; H Scheme 2 route to (S)-(-)-phenyloxirane is shown in Scheme 2.” Bromohydrins with base and in the presence of an optically active cobalt complex gave oxiranes of modest optical purity.16 The epoxyether (23) (R = tritylmethoxy) has been prepared in a sequence from (R)-malic acid.” Raney Ni-induced deoxygenation of tertiary alcohols in toluene shows regioselec- tivity since remote halogen for example is unaffected; neopentyl-like alcohols react normally.18 P-Hydroxyselenides with MCPBA furnished either epoxides or ketones.” With cyclic structures ring expansion occurred.A method for selective protection of 1,n-diols with preferential reaction at the secondary group is depicted in Scheme 3.20 Stereospecific 0-benzoylation of propan- 1,2-diol at C2 proceeds with inversion of configuration and was affected by dibenzoyl Reagents i (MeO),CH D-camphorsulphonic acid r.t.; ii DIBAH hexane -78 “C Scheme 3 peroxide-PPh .21 It was suggested that a 1,3,2-A 5-dioxaphospholane (24) which underwent proton-assisted ring opening to an oxyphosphonium species could account for the observed selectivities [e.g.(24) -* (25)]. A selective mono-0-benzyla- tion of a meso-divinylglycol has been used to advantage in preparation of chiral precursors of some carbohydrate derivatives.22 15 E. J. Cbrey S. Shibata and R. K.Bakshi J. Org. Chern 1988 53 2861. 16 T. Takeichi T. Takakura M. Ishimori and T. Tsuruta Bull. Chem. Soc. Jpn. 1988 61 603. 17 R. DiFabio and D. Misiti Gazz. Chim. Ital. 1988 118 209. I8 M. E. Krafft and W. J. Crooks 111 J. Org. Chem. 1988 53 432.19 S. Uemura K. Ohe and N. Sugita J. Chem. SOC.,Chem. Cornmun. 1988 111. 20 M. Takasu Y. Naruse and H. Yamamoto Tetrahedron Lett. 1988 29 1947. 21 A. M. Pautard and S. A. Evans jun. J. Org. Chem. 1988 53 2300. 22 R. R. Schmidt and K. Frische Liebigs Ann. Chem. 1988 209. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Ph3P:) OR Palladium-catalysed phenylation of allylic alcohols showed a dramatic rate enhancement in the presence of tertiary amine~.,~ Thus but-3-en-2-ol-PhI-Pd gave 97% of phenylated butan-2-ones (principally the 4-isomer). The ring opening of oxiranes by SiF4 has been examined with respect to selec- ti~ity.,~ Alkene or ether functions are unaffected and the fluorohydrin formed has fluorine at the more substituted carbon atom; from (26) the major product (78%) was (27).Anti-opening of meso-oxiranes by B-halogenodiisopinocampheylboranes F Ph/y ‘\ H’ Me OH proceeds with high e.e.; thus MeCH(OH)CH(I)Me (lR 2R) from cis-but-2-ene epoxide had 78% e.e.25 For some cyclic examples 100% e.e. was observed. Variable e.e. was observed for a number of nucleophilic ring-opening reactions in the presence of metal(1r) tartrates.26 The regio- and chemoselectivity of oxirane ring opening by Me3SiN3 in the presence of Al(OPri)3 has been examined; 2-trimethylsilyloxy derivatives are produced in a stereospecific (anti) process.*’ Alcoholysis of oxiranes catalysed by an organotin phosphate condensate gave P-alkoxyalcohols; gem-dialkyloxiranes cleaved at the tertiary C-0 bond.28 Oxiranes carrying aryl alkenyl alkynyl or trimethylsilyl groups react with titanium acetylides at the more substituted carbon to afford 2-substituted b~t-3-yn-l-ols.~~ Yields were dependent on solvent ratio of reactants and structure.‘Reactive’ titanocene deoxygenated oxiranes in a stereoselective manner; thus trans-oxiranes gave E-alkenes and cis-isomers formed Z-alkene~.~’ Phenylsulphonyloxirane (28a) is a useful synthetic equivalent for the dipolar synthon (29); ring opening and elimination from (28b) by MgBr (ether-toluene) gave (30).” il\so2ph R (28) a; R = H b; R = D allyl Me,SiMe 23 R. Benhaddou S. Czernicki and G. Ville J. Chem. SOC.,Chem. Commun. 1988 247 24 M. Shimizu and H. Yoshioka Tetrahedron Lett.1988 29 4101. 25 N. N. Joshi M. Srebnik and H. C. Brown J. Am. Chem. SOC.,1988 110,6246. 26 H. Yamashita Bull. Chem. SOC.Jpn. 1988 61 1213. 27 M. Emziane P. Lhoste and D. Sinou Synthesis 1988 541. 2a J. Otero Y. Nubo N. Tatsumi and H. Nozaki J. Org. Chem. 1988 53 275. 29 N. Krause and D. Seebach Chem. Ber. 1988 121 1315. 30 F. Schobert Angew. Chem. Int. Edn Engl, 1988,27 855. 11 -A n I-xsr 1-t. r -1 -_. 31 %I A-I. ._,--* - 110 B. K Smith Wittig rearrangement of allyloxycarbanions is of interest as a method for stereoselective C-C bond formation and two examples of the transformation (31) -+ (32) with high asymmetric induction have been described.32 2 Alkyl Halides Amongst the reagents examined for the conversion of a trialkylborane into a chloroalkane nitrogen trichloride was the best.This method permits anti-Markov- nikov hydrochlorination of alkenes via hydroboration in 66-94% yields.33 Decar- boxylative chlorination of aliphatic (and aromatic) carboxylic acids gave chloro compounds in good yield; this method is based on prior formation of benzophenone oxime esters (33) and photolytic breakdown in CC14.34 Some by-products were R C9, N=CPh2 II found but for Me(CH2)16C02H the chloroalkane was formed in 82% yield. Conver- sion of tlcohols into chloro compounds was also effected by reaction with HC1-H20- C16H33NMe3 X-(catalyst) in micellar conditions and gave for C4 to c16 80-97% of the desired product.35 A convenient one-pot reductive halogenation of carbonyl compounds has been used for aralkyl bromides and iodides.36 Some papers from H.C. Brown and co-workers have continued the investigations into hydroboration- halogenation; thus bromination in the presence of sodium methoxide is particularly. effective since all three alkyl groups are utilized and very high or quantitative yields were rep~rted.~’ The role of bromine in an inert solvent was examined and a free radical chain mechanism was suggested.38 Hydroboration-iodination sequences furnish approximately 67% of iodoalkane normally; the reaction rate is accelerated by sodium hydroxide but the yield of for example 1-iododecane is still only 60%. However with Sia2BH 95% of the iodo compound was produced. It was further established that the base-induced reaction occurs with inversion of configuration at the reaction centre.39 32 R.Bruckner and H. Priepke Angew. Chem. Inr. Edn. Engf. 1988 27 278. 33 H. C. Brown and N. R. DeLue Tetrahedron 1988,44 2875. 34 M. Hasebe and T. Tsuchiya Tetrahedron Lett. 1988 29 6278. 35 B. JurSi6 Synthesis 1988 868. 36 C. Bilger R. Royer and P. Demerseman Synthesis 1988 902. 37 H. C. Brown and C. F. Lane Tetrahedron 1988,44 2763. 38 H. C. Brown C. F. Lane and N. R. DeLue Tetrahedron 1988,44 2773. 39 H. C. Brown M. W. Rathke M. M. Rogic and N. R. DeLue Tetrahedron 1988,44 2751. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Copper(I) iodide-assisted exchange of vinyl bromides gave iodo analogues with the same isomer ratio as starting material and in 54-89% yield.40 No exchange occurred with KI in the absence of the copper(1) salt.1,l-Dibromides gave 1,l- diiodides (74% 1-4 h) and 1,2-dibromides gave low yields of diiodides (4.5 h). Longer reaction time in the latter reaction gave elimination to alkyne. HMPT and N-methylpyrrolid-2-one were more effective than diglyme or DMF. Base-promoted elimination from Sfluorononane has been reported; alkoxide gave a cis trans ratio of ca. 1:3 whereas diisopropylamide formed almost pure trans-i~omer.~' Even with Schlosser's base (LDA-KOBu') reaction was slow. The same authors report on elimination from meso-and (*)-6,7-difluorodecane. Preparation of starting materials is also reported?2 Carbonylation of Bu'Br mediated by Cp2Sm gave at -40 "C a modest yield (46%) of Bu'CH(OH)CH(OH)BU'; the intermediacy of an acyl compound (34) was presumed since heptanal trapped it to form (35)."3 Bu'CSmCp, It 0 Bu'COCH( OH)C6H,3 (34) (35) The asymmetric induction consequent upon replacement of diastereotopic bromine atoms by lithium has been probed by Hoffmann and co-workers.u As shown in Scheme 4 the diastereoisomeric ratio is high and it is presumed that the carbenoid intermediates (36) and (37) must be configurationally stable enough at low temperature to permit stereospecific trapping.By oxidation of (38) and (39) (formed in 70% yield d.s. = 93:7 respectively) it was concluded that the pro-ul-bromine45 is preferentially replaced on lithiation. Although it was not established Me3Si0 Me3SuBr Br R H R = But or Pr' (36) ii I (37)I Me3Si0 E Me3Si0 Br H Reagents i BuLi hexane -120°C; ii E = Me2C0 Me,CHCHO or HO-B 'x -120°C 0 Scheme 4 H.Suzuki,M. Aihara H. Yarnamoto Y. Takarnoto and T. Ogawa Synthesis 1988 236. 41 S. Matsubara H. Matsuda T. Harnatani. and M. Schlosser. Tetrahedron 1988. 44. 2855. 42 S. Matsubara H. Matsuda T. Harnatani and M. Schlosser Tetrahedron 1988 44 2865 2875. 43 J. Collin and H. Kagan Tetrahedron Lett. 1988 29 6097. 44 R. W. Hoffrnann M. Brewersdofi K. Ditrich M. Kriiger and R. Stunner Angew. Chem Int. Edn. Engl. 1988 27 1176. 45 D. Seebach Angew. Chern. Int. Edn. Engl. 1982 21 654. 112 B. V. Smith beyond doubt the role of the trimethylsilyloxy group in co-ordinating to the lithium atom (see Scheme 4) is believed to be crucial.Iodoalkanes in the presence of an alcohol a metal carbonyl and a platinum complex form esters in good to excellent yields.& No reaction occurred without the catalyst or light. Acid halides were produced from ButX-CO-RSO3H-CCl4 in a process believed to involve cationic intermediates (cf Koch-Haaf process).47 A very effective reducing agent for alkyl halides is tris(trimethylsilyl)silane (Me3Si)3SiH.48 A free radical pathway is suspected as reduction may be photo- initiated and inhibited by scavengers. The authors advocate its use in place of Bu3SnH and claim better ecological acceptability of silicon -could this be a 'green' reagent? A~hby~~ has replied to criticismsSo of the SET pathway in reactions of alkyl halides (and ketones) and defends his position strongly.Bromochloromethane under the influence of sonication and in the presence of lithium rapidly reacts with carbonyl groups affording high yields of ~xiranes.~~ Samarium has achieved popularity again this year and in an interesting example of use of SmI it has been shown that drastically altered stereochemistry in cleavage of (cyclic) P-halogenoethers may be realized. Thus high E selectivity was found for formation of y,8-en01s.~~ Vinyl halides with PhSeCl in MeOH gave a-alkoxyacetals presumably via addition-elimination-addition sequences; some rearrangement apparently occurred since PhCH=C( D)Br gave (40) in addition to (41).53 3 Aldehydes and Ketones This section is once again the largest in the Report and of necessity it cannot give complete literature coverage.Work reported is hopefully of general interest and not mentioned for its novelty alone. 46 T. Kondo Y. Tsuji and Y. Watanabe Tetrahedron Lett. 1988 29 3833. 47 J.-J. Brunet P. Legars Y. Peres and I. Tkatchenko Tetrahedron Lett. 1988 29 4569. 48 C. Chatgilialoglu D. Griller and M. Lesage J. Org. Chem. 1988 53 3641. 49 E. C. Ashby Acc. Chem. Res. 1988 21 414. 50 M. Newcomb et aL J. Org. Chem. 1987 52 3275; J. Am. Chem. SOC.,1987 109 1195; D. Curran Tetrahedron Lett. 1986 27 5821. 51 C. Einhorn C. Allaveno and J.-L. Luche J. Chem. Soc. Chem. Commun. 1988 333. 52 L. Crombie and L. J. Rainbow Tetrahedron Lett. 1988 29 6517. 53 M. Tiecco L. Testaferri M.Tingoli D. Chianelli and D. Bartoli Tetrahedron 1988 44,2273. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 113 Controlled potential electrolysis of Fe(CO),-RX (EtI or PhCH,Br) is a novel route to aldehydes.54 Preparation of 2,2-dialkoxyethanals (RO),CHCHO which can be tedious has been achieved in 50-70% yield by using an excess of the alcohol and sufficient catalyst. The products are useful two-carbon synthons for ketoalde- hydes oximes nitriles and amine products.55 An easy access to P-acyl- and p-arylpropanols relies on a novel silylated organotin homoenolate equivalent as an umpolung reagent (see Scheme 5).56 Direct conversion of RCHO into RCHSe and RCHS (45-85% yields) was effected by reaction with (Me,Si),Se or (Me,Si),S in the presence of a catalytic amount of BuLi in THF; R was alkyl (including But) or aryl.The selenoaldehyde was trapped with cycl~pentadiene.~~ 0 1v iv SiMe3 HCECCH,OMe Bu3Sn&OMe iii 0 SiMe3 Reagents i Bu3SnH AIYN 110 "C; ii BuLi THF -78 "C then Me3SiC1; iii RCOCI PdC12(PPh3)2 THF 65 "C; iv Bu4N F-THF 0 "C; v ArBr Pd(PPh,), 110 "C Scheme 5 H. C. Brown has continued his elegant work on the preparation of compounds with very high enantiomeric purities uia boron compound^.^^ The preparation of chiral ketones was effected by three methods (a) carbonylation (b) cyanidation and (c) iodoalkynation as shown in Scheme 6. It is notable that in the examples shown the enantiomeric purities of (42) (43) and (44) were 100 99 and 96% respectively.This must surely be one of the most versatile routes to this type of compound. The preparation of a-chiral-a'-alkynylketonesof very high e.e. starting with organyl-( 1-alkynyl)borinic esters has been rep~rted.'~ Thus (45) was obtained in 65% yield but with e.e. >99%. Aldehydes with trimethylsilyldiazomethane gave trimethylsilylketones (46) after aqueous work up; dilute hydrochloric acid gave the 54 D. Vanhoye F. Bediou A. Martreux and F. Petit Tetrahedron Lett. 1988 29 6441. S5 A. Stambouli F. Hamedi-Sangsari R. Amoroux F. Chastrette A. Blanc and G. Mattioda Bull. SOC. Chim. Fr. 1988 95. 56 J. B. Verlhac J.-P. Quintard and M. Pereyre J. Chem. Soc. Chem. Commun. 1988 503. 57 M. Segi T. Nakajima S. Sugg S. Murai I. Ryn A. Ogawa and N.Sonoda J. Am. Chem. SOC.,1988 110 1976. 58 H. C. Brown R. K. Bakshi and B. Singaram J. Am. Chem. Soc. 1988 110 1529. 59 H. C. Brown A. C. Gupta J. V. N. V. Prasad and M. Srebnik J. Org. Chem. 1988 53 1391. 114 B. V. Smith (a> iy""2 I' (44) Reagents i ,0 "C THF; ii CO 1000 p.s.i.; iii [O],pH 8; iv NaCN THF; v TFAA -78 "C; vi IC_CMe EtzO -25 "C; vii NaOMe 25 "C Scheme 6 0 y.:C C(CH2) 3 C 1 &SiMe3 R desilylated product in 43-89% yield.60 Two papers dealing with the synthesis of a-fluoroketones (and polyfluoroketones) have been published. Homochiral a-fluoroketones have been prepared from racemic a-fluorocarboxylic esters and enan- tiomerically pure sulphoxides; by this route (47) [from PhCH(F)CO,Me and the lithiated sulphoxide (48)] yielded (S)-(49) (73Y0 optically pure).61 Extension of this method to polyfluoroesters gave polyfluoroketones.62 Iodination of ketones with I,-ceric ammonium nitrate (in AcOH or MeOH) was efficient; by this method pentan-2-one gave principally the 3-iodo derivative (97% ) the remainder being the primary Ketone hydrazones via reaction of dimagnesium salts and Se,C12 gave an intermediate (tetraselenide?) which when heated in tributylamine formed a 60 T.Aoyama and T.Shiori Synthesis 1988 228. 61 P. Bravo and G. Resnati J. Chem. SOC.,Chem. Commun. 1988 218. 62 P. Bravo E. Piovosi and G. Resnati Guzz. Chim. Ztul. 1988 118 115. 63 C. A. Horiuchi and S. Kiji Chem. Lett. 1988 31. 115 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds ~elenoketone.~~ By using two equivalents of RMgX to react with the hydrazone before selenation (instead of base) a yield of 51% of Bu\C=Se was formed (rather than 28%).An approach to optically active a-unsubstituted or a-anti-substituted-/3 -hydroxy- ketones was sought via Pd-catalysed asymmetric disilylation of a,P-enones followed by oxidative cleavage of the C-Si bond. As depicted in Scheme 7 the method gave reasonable success.65 (R2) -P 'iii iv PhTR' i ii hw~ ___ 0 '"WR' Me?PhSi OL1 OH R' = R2= Me 78% e.e. Reagents i PhSiCl,SiMe,; ii MeLi PdCl,.binap; iii R'X; iv HBF4-H,02 Scheme 7 A metallation-alkylation sequence with 4H-1,3-dioxin -a new p -acyl anion equivalent -is a practicable route to a$-unsaturated aldehydes.The reagent (50) [equivalent to (51)] by alkylation gave (52) which was cleaved by methanolic HCl to give a P-hydroxyacetal; thermolysis of this (boiling toluene) gave the product.66 Three-carbon homologation of a ketone was used to prepfre a p,?-unsaturated aldehyde; acrolein with Ph3P and HBr in Pr'OH gave Ph3PCH2CH2CH0 trans- formed into (53) by HC(OPr'),. The acetal (54) [71-96% from (53) R'COR' and base] was cleaved to the product in >93% yield.67 This method is a neat exploitation of reactivity and selectivity. A variation on this phosphorane chemistry is the preparation of 4-diethylphosphonobut-2-enaland its use to prepare a conjugated aldehyde. Thus (55) protected as an imine gave with hexanal a 78% yield of deca-2,4-dienal of predominantly E,E stereochemistry.Further purification of the reaction product from 4-MeOC6H4CH0 (93% E,E-isomer) allowed a pure sample to be obtained.68 + 64 A. Ishii R. Okazaki and N. Inamoto Bull. Chem. SOC.Jpn. 1988 61 861. 65 T. Hayashi Y. Matsumoto and Y. Ito J. Am. Chem. SOC.,1988 110 5579. 66 R. L. Funk and G. L. Bolton J. Am. Chem. Soc. 1988 110 1290. 61 J. Viala and M. Santelli Synthesis 1988 395. 68 T. Rein B. Akermark and P. Helquist Acta Chem. Scand. Ser. B,1988 42 569. 116 B. V. Smith 1,l-Diorganometallics of Mg and Zn' react with Me,SnCl to accord 'mixed' reagents oxidized by air to aldehydes and ketones.69 Thus (56),after stannylation and oxidation gave (57). With formation of aryl ketones (57; RS= Ph) reaction was rapid; the generation of aldehydes was slower.It was observed that the reaction rate was enhanced by added Me,SiCl but retarded by DMF or Me$. It was possible to adapt this reaction to form aldol-like products (see Scheme 8) with reasonable selection. f" i-iii+ EttcMgBr -Et:C EtfCH OEt Hex-iv,v Hex-H i-ZnBr H Hex 0 0 88 12 Reagents i Bu'Li -78 "C; ii ZnBr,; iii C6H,,CH=CHMgBr; iv 1 eq. Me,SnCl; v O, Me3SiC1 Scheme 8 Phosphorus-containing reagents have also been used in synthesis of unsaturated ketones by chain extension. As shown in Scheme 9 good yields of (58) were obtained by either route." Typically the 2:E ratio of (58) was 3 1. Lithiated N,N-dimethyl- hydrazones derived from CU,~ -unsaturated aldehydes are alkylated to afford 0 I1 ph2py?(;l /yo R2 R' vii ii x R3 \ R' Reagents i Ph2PO-; ii HO(CH,),OH H+; iii BuLi; iv R2R3CO; v NaH; vi H30+; vii Ph3P-Me,SiCI Scheme 9 69 P.Knochel C. Xiao and M. C. P. Yeh Tetrahedron Lett. 1988 29 6697. 70 H. J. Cristau E. Torreilles and C. Barois-Gacheriau Synth. Commun. 1988 18 185. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds rearranged a-alkylated P,y-unsaturated aldehyde dimethylhydrazones. Thus from (59) and PhCH2Br there was produced (60) (63'/0).~' This approach was used in the synthesis of 2,5,9-trimethy1-2-vinyldeca-4,8-dienal(61), a sesquiterpene occurring in the intriguingly named beefsteak plant. It was further shown that dimethylhy- drazones of (2E 4E)-alkadienals underwent the corresponding rearrangement to afford a-alkylated 3 E,5Z derivatives.A stereoselective synthesis of conjugated dienones was effected by treating an alkynylketone with RuH2(PPh3)4 (with or without solvent toluene); in this way (62) was obtained in 85% yield.72 Al kylidene malonaldehydes have been obtained from (63) by treatment with RMgBr or RLi followed by hydrolysis. Simple alkyl derivatives were unstable and were trapped by cycloaddition with CH,=CHOEt; alkynyl-substituted analogues showed greater stability.73 But-2-yn-l,4-dial has been prepared but is explosive even under nitrogen.74 1,2-Diketones were prepared from alkynes by reaction with Ru02-NaI04; the terminal alkyne Me(CH,),,C_CH gave myristic acid (47Y0).~' Oxidation of a hydroxycarbonyl system by N-chlorosuccinimide-Me2S gave a range of 1,3-dicar- bonyls in good to excellent yield.76 Some limitations were noticed with for example P-hydroxyesters which gave no carbonyl-containing product.The required starting materials were prepared via the usual aldol method. Selectivity in reduction of aldehyde groups in preference to ketones was shown (>95'/0) with sodium borohydride in 30% EtOH-CH,Cl at -78 0C.77 The anti-Cram reduction of acyclic ketones has been discussed in terms of a process initiated by electron tran~fer.~' An exceptionally efficient reducing agent for prochiral ketones is diisopinocam- pheylchloroborane; reduction at -25 "C in THF is rapid and gives extremely good selectivity. This approach is recommended as superior to other methods including 71 M.Yarnashita K. Matsurniya K. Nakano and R. Suernitsu Chem. Lerr. 1988 1215. 72 D. Mo Y. Lin X. Lu and Y. Lu Tetrahedron Lett. 1988 29 1045. 73 Z. Arnold G. V. Kryshtal V. Krll D. Dvoilk and L. A. Yanovskaya Tetrahedron Lerr. 1988,29,2861. 74 D. Stephen A. Gorques A. Belyasmine and A. LeCoq. J. Chem. SOC.,Chem. Commun. 1988 263. 75 R. Zibuck and D. Seebach Hefv. Chim. Acra 1988 71 237. 76 S. Katayama K. Fukudo T. Watanabe and M. Yarnaguchi Synthesis 1988 178. 77 D. E. Ward and C. K. Wee Synrh. Commun. 1988 18 1927. 78 Y. Yarnarnoto K. Matuoka and H.Nemoto J. Am. Chem. SOC.,1988 110 4475. 118 B. V. Smith use of Alpine-b~rane.'~ Reduction was significantly better in some cases with neat reagent; thus 3,3-dimethylbutan-2-one gave a modest yield of the S-alcohol (50% ) but in high e.e.(93%).The favoured transition state for reduction was considered as boat-like (64) and the preference for S selectivity was thus rationalized. However with PhCOCMe the R-alcohol (79% e.e.) was obtained which was surprising the alternative transition state (65) should on steric grounds be less favoured. A bonus I RS RL (64) (65) from this reaction was recovery of a-pinene of ca. 100% (>99.4%) e.e.; reaction of Ipc2BC1 and PhCHO led to rapid release of 2 equivalents of the pinene. Optically active Grignard reagents (derived from naturally occurring isoprenoids) gave little or no addition but some selectivity in reduction.80 Thus the Grignard reagent from (66) with PhCOPr' gave 67% reaction and the reduction to the R-alcohol proceeded with 66% selectivity.Selective activation of one enantioface of a methyl ketone was investigated via a-bonding to a chiral metal template. Formally the reduction occurs by hydride addition and the liberated alcohol has very high e.e. For reduction of butan-2-one the highest recorded e.e. achieved was 95%;with PhCOMe e.e. >99% .81 The key intermediate [(q5-C5H5)ReNO(PPh,){ ql-Me(R)C=O}]+PF,- (68) is derived from the chiral rhenium derivative (67). 79 H. C. Brown J. Chandrasekharan and P. V. Ramachandran J. Am. Chem. SOC.,1988 110 1539. 80 M. Falarni L. Lardicci G. Uccello-Baretta and G. Giamcomelli Gazz. Chim. Ztal. 1988 118 495. 81 J. M. Fernandez K. Emerson R.D. Larsen and J. A. Gladysz J. Chem. SOC.,Chem. Cornmun. 1988 37. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Chemoselectivity in reduction and alkylation of aldehydes and ketones has been achieved via a little MADness.82 This acronym for methylaluminium bis-( 2,6-di-t- butyl-4-methylphenoxide) is not connected with the irrational; on the contrary selectivity uia complexation is a useful approach to overcoming lack of discrimina-tion by Grignard reagents or alkyllithiums as between aldehydes and ketones. MAD activates an aldehyde but not a ketone such that a nonanal-di-t-butyl ketone mixture gave only decan-2-01(62%) in the presence of MAD. Conversely the reagent Me,AIN(Me)Ph reacts with an aldehyde to form (69); the uncomplexed ketonic carbonyl is thus free to react and alkylation of a nonanal-nonan-5-one mixture gave a secondary tertiary alcohol ratio of 1:9.R'CHX I OAlRz (69) 1,2-Diketones are usually reduced by baker's yeast with low selectivity; excep- tionally 1 -phenylpropane- 1,2-dione gave pure (S)-(-) -2- hydroxy- l-phenylpropan- 1-one in good yield.83 Benzil gave racemic benzoin; modest e.e. (56%) was achieved when SmI in THF-HMPA was used and in the presence of q~inidine.~~ High stereoselectivity was observed in the Ru"B1NAP-catalysed homogeneous hydroge- nation of 1,3-diketones; e.g. MeCOCH2COMe gave anti and syn-diols (98% ratio 99 :1 e.e. >99'/0).'~ Pentan-2-one was little affected under these conditions. Reduc- tion of 2-alkyl-3-hydroxyketonesuia silyl ethers has been used as a route to anti-anti-1,3-diols; typically (70; R' = R2 = Pr') gave 73% of (71) and (72) (ratio 98:2).R3SiO R&:H-R' The Bu'Me2Si group was chosen to prevent chelation; the favoured conformer was considered to be (73).86 Two articles dealing with reviews of enantioselective alkylation of carbonyl compounds have been published.",'' A route to C-monoalkylation of p -diketones 82 K. Maruoka Y. Araki and H. Yamamoto Tetrahedron Lett. 1988 29 3101. 83 R. Chinevert and S. Thiboutot Chem. Lett. 1988 1191. 84 S. Takeuchi and Y. Ohgo Chem. Lett. 1988 403. 85 H. Kawano Y. Ishii M. Saburi and Y. Uchida J. Chem. SOC.,Chem. Commun. 1988 87. 86 R. Bloch L. Gilbert and C. Girard Tetrahedron Lett. 1988 29 1021.87 R. Noyori S. Suga K. Kawai S. Okada and M. Kitamura Pure Appl. Chem. 1985 60 1597 88 M. T. Reetz Pure Appl. Chem. 1988 60 1607. 120 B. V. Smith which avoids 0-alkylation dialkylation and cleavage reactions has been estab- li~hed.~~ Controlled electrolytic reduction of pyrrolidone in the presence of Et,N+ OTs- in DMF gave (74) which with pentane-2,4-dione gave the tetraethylammonium enolate; the latter with 1-iodohexane gave 3-hexylpentane-2,4-dione(89%). This result was contrasted with conventional alkylation (NaH-DMF then C6H131) which gave 23% of the desired product 12% of the dihexyl derivative and 3% of 0-alkylated product. For 14 examples the preferred route gave yields between 64 and 92%. Studies of the Knoevenagel reaction of ArCHO and P-ketoacids have shown that the role of catalyst (secondary or tertiary amine) is in modifying product formation and reversibility?' Effective heterogeneous catalysis of reaction between PhCHO and CNCH,CO,Et by amino groups of aminopropylsilica was reported (98% yield).No Michael addition could be detected. Pentane-2,4-dione gave a low yield of condensation product perhaps owing to its adsorption as an enol." Stereoselective aldol reaction of (R)-and (S)-2-hydroxy- 1,2,2-triphenylethyl ace- tate (75) was achieved in high optical yields (Scheme lo) and for PhCHO for example the ratio of (76):(77) in THF at -78°C (88:12) increased to 98:2 in HO MO OM HO H RU*Xh-+o<22 'Rmox;h H Ph -Reagents i 2 eq. LDA THF-Me20 -135 "C; ii MgX,; iii RCHO Scheme 10 THF-Me20 (-135°C).Hydrolysis of (76) or (77) gave P-hydroxyacids of corre-sponding optical purity." Further very detailed work on this system has sought to probe the control in additions of (R)-and (S)-(75) to chiral aldehydes.93 The general Scheme 11 predicts the outcome of the addition of enolates from (R)-and (S)-(75) to RCHO; doubly deprotonated (R)-(75) gave with (R)-(78) at -125 "C (79) and (80) (90 lo) which were cleaved in turn to (81) and (82). With (S)-(75) opposite 89 T. Shono S. Kashimura M. Sawamura and T. Soejima J. Org. Chern. 1988 53 907. 90 M. Tanaka 0.Oota H. Hiramatsu and K. Fujiwara Bull. Chern. SOC.Jpn. 1988 61 2473. 91 E. Angeletti C. Camena G. Martinetti and P. Venturello Tetrahedron Lett. 1988 29 2261.92 R. Devant U. Mahler and M. Braun Chern. Ber. 1988 121 397. 93 U. Mahler R. M. Devant and M. Braun. Chem. Ber. 1988 121 2035. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Si OBn OH OBn OH 2 L R +Mej\/CR_li' Me Me (79) 90 10 OBn OH Me&OH Me=OH + (81) (82) Reagents i (R)-(75),2 eq. LDA THF-Me,O -125 "C; ii KOH Scheme 11 selectivity was observed i.e. (79) :(80) = 5 :95. It was deduced that reagent control was dominant in the reactions studied since the controlled and predictable synthesis of anti-(81) and syn-(82) could be realized. D-Glyceraldehyde acetonide and 2-trimethylsilylthiazole react to form a 'thiazole-masked' chiral butanal; with thiazole D-erythose for example a route to (83)was available.Additionally chiral hydroxy- epoxy- and azidobutanals were prepared.94 I OCHzPh (83) 1,3-Asymrnetric induction was observed in the coupling of 2-lithio-2-( l-methylalk- 2-enyl)-1,3-dithiane with RCHO; the product ratio syn-(84):anti-(85)was a function of the aldehyde structure so whereas PhCH2CH2CH0 showed syn preference the reverse was true for MeCECCHO. Addition of BF,.OEt diminished selectivity?' A remarkably high 1,3-anti selectivity was shown in the addition of organotitanium reagents to &substituted aldehydes carrying a dithioacetal group at the a-position e.g. (86) with MeTiCI gave a 72% yield of (87) (anti:syn = 98:2)?6 Horner olefination of aldehydes with N-acyl-(2-diethoxyphosphoryl)glycine ethyl ester proved a useful route to dehydroamino acids with 2 selectivity e.g.(88) (72%) had a 2 :E ratio of 6.3 :l.97 94 A. Dondoni G. Fantin M. Fogagnolo A. Medici and P. Pedrini Synthesis 1988 685. 95 Y. Honda E. Morita K. Ohshiro G. Tsuchihashi Chem. Lett. 1988 21. 96 Y. Honda and G. Tsuchihashi Chem. Lett. 1988 1937. 97 P. G. Ciattini E. Morera and G. Ortar Synthesis 1988 140. 122 B. V.Smith High diastereo- and enantioselection was found for the addition of 2-(y-alkoxyally1)diisopinocampheylboraneto aldehydes. Lithiated ally1 methyl ether with either enantiomer of (89) followed by BF3-OEt2 gave (90) (or enantiomer). As Scheme 12 shows for EtCHO 65% yield of product was obtained with threo selectivity of 94 6 and high enantioselectivities (>go%).As a means of introducing a masked hydroxy group the methoxymethyl ether borane (91) was useful. Taken together this group of chiral (2)-alkoxyallylboranes show the highest enantio- and diastereoselection of any compounds of this type reported to date.98 )2BOMe Reagents i BuLi THF-C6H,* =78"C; ii (89),THF -78 "C; iii BF,-OEt2 Et20 -78 "C; iv EtCHO -78 "C; v H,N(CH,),OH Scheme 12 As a means of probing the intermediates and key steps in addition of allylstannanes to aldehydes spectroscopic methods were used to investigate the complexes formed. Aldehydes formed a complex with SnCl quantitatively and no free aldehyde was detected; with BF3.0Et different behaviour was observed with complexation and free species being present. Complexed MeCHO and allyltrimethylstannane showed that at -80°C both components were present at -60°C redistribution took place H.C. Brown P. K. Jadhav and K. S. Bhat J. Am. Chem. SOC.,1988 110 1535. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 123 without reaction at -20 "C the first sign of pent-4-en-2-01 formation was detected and at 0°C only this product was present. With Bu'CHO however reaction with the stannane was immediate at -80 "C. A rationale for these reactions was available on the basis of these and other experiment^.^^ Addition of tetraallylstannane to aldehydes (or reaction with an acid chloride) was smoothly effected by CsF."' Montmorillonite clay has found application as catalyst in aldol reactions of silylenol ethers with aldehydes or acetals."' The diastereoselection was sensitive to the solvent of choice but little changed by replacing A1 in the clay by Ti or H+.Addition of (92) (E :2 = 83 :17) to MezCHCHO gave a threo :erythro ratio of 72 28 (toluene -3O"C -20 "C) 74 26 (DME -30 "C -20 "C) or 46 54 (CH,Cl,). Reaction of (93) and (94) with 'Almont' clay gave (95) :(96) = 93 :7 (-65 "C),and 92 8 with 'H-mont' at -50 "C. Triethylamine proved an effective catalyst poison. The selection in aldol reactions via P-silylketones has been utilized by Enders.'" h Me3Si0 PhxCHO \ PMe3Si0 b Ph Ph+Ph Phre3 (93) (94) (95) (96) The method as outlined in Scheme 13 and with high d.e. (92-98%) and e.e. 2 98% was applied to a synthesis of sitophilure an aggregation pheromone of the rice and maize weevil.I Bu' Me Si B u' iii + R Me Reagents i Bu2BOS02CF3 PrlNEt CH2C12 -10 "C;ii RCHO -78 "C then [O],flash chromatography; iii HBF, H20 20°C Scheme 13 99 S. E. Denmark T. Wilson and T. M. Willson J. Am. Chem. Soc. 1988 110 984. 100 D. N. Harpp and M. Gingrass J. Am. Chem. SOC.,1988 110 7737. 101 M. Kawai M. Onaka and Y. Izumi Bull. Chem. Soc. Jpn. 1988 61 1237. 102 D. Enders and B. B. Lohray Angew. Chern. Inr. Edn. En& 1988. 27 581. 124 B. V; Smith Although the lithium derivative of the allenic reagent (97; M = Li) showed low regioselectivity on addition to aldehydes the titanium analogue (97; M = TiOPr;) gave much better result^."^ The products from such additions were elaborated into 2,6-dideoxyhexoses of urubino-and xylo-configuration.Titanium (or niobium) com- plexes of aldehydes block aldol-type reactions; evidence for a compound MeCl,TiOCH( R)PPh3 was obtained.lW Competitive experiments demonstrated that the heptanal heptanone reactivity ratio was 25 1 but 1 :9 in the presence of the complexing agent. Addition of diethylzinc to an aldehyde showed reasonable-to- good e.e. when conducted in the presence of a chiral tertiary-amino alcohol e.g. (98); PhCHO in the presence of (98) (20.5% e.e.) gave 96% of the s-alcohol 88% e.e.'05 Germanium enolates (from Li enolates and Me3GeX) reacted with PhCHO to give predominantly erythro-aldol products; if the co-existing lithium halide was removed before condensation then threo-product formation was favoured.lo6 This was considered to account for differences between this work and that of Stille.'" A review of proline-catalysed enantioselective aldol reactions has been pub- lished.'08 An interesting enzymatic synthesis of glycosidase inhibitors was achieved by coupling dihydroxyacetone phosphate and (R S)-(99) with aldolase; following phosphatase-mediated cleavage of the intermediates and reduction l-deoxyman- nonojirimycin (100) and 1-deoxynojirimycin ( 101) were isolated.10g Alkoxyacetylide anions react with carbonyl groups to form adducts e.g.(102) which are transformed by acid into a$-unsaturated esters (e.g. Ph2C=CHC02Me 70%).'lo An interesting account of the Bayliss-Hillman process for coupling acti- vated vinyl carbanions with aldehydes has been published.' RZ R1jG -OR3 HO (102) 10.1 R.W.Hoffrnann J. W. Lanz and R. Metternich Liebigs Ann. Chem. 1988 161. I04 T. Kauffrnann T. Abel and M. Schreer Angew. Chem. Int. Edn. Engl. 1988 27 944. I05 N. Oguni Y. Matsuda and T. Kaneko J. Am. Chem. Soc. 1988 110 7877. I06 Y. Yarnarnoto and J. Yarnada J. Chem. Soc. Chem. Commun. 1988 802. 107 J. K. Stille et a/. Tetrahedron Lett. 1983 23 627; Tetrahedron 1984 40,2329. ion C. Agarni Bull. Soc. Chim. Fr.. 1988 499. I09 R.Ziegler A. Straub and F. Effenberger Angew. Chem. Int. Edn. EngL 1988 27 716. I10 G. A. Olah A. Wu 0. Farooq and G. K. S. Prakash Synthesis 1988 537. Ill S. E. Drewes and G. H. Roos. Tetrahedron 1988 44. 4653. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Michael addition can be catalysed efficiently by montmorillonite clay and silyl ketene acetals and silyl enol ethers have been used in this way.Modest selectivity was noted for (103) and MeCH=CHCO,Me the syn :anti ratio being 27 :73 (-78 "C OSiMe3 0.5 h 84%).'I2 Enantioselective Michael addition of tin( 11) enolates to a,p-unsatur- ated ketones with chiral diamine ligands (Scheme 14) depended on activation; thus Me3SiC1 was ineffective but Me3SiOTf gave 70% yield in the displayed reaction (>95 :5 anti :syn 80%optical yield) with diamine (1O4).ll3 A similar result followed for addition of methyl dithioacetate. It was also established that a catalytic cycle could be set up with a catalytic amount of Sn( OTf),-chiral diamine complex.' l4 Addition of allyllithium reagents containing polar groups (sulphoxides phosphine oxides phosphonates) has been studied.' l5 Reagents i Sn(OTf), EtN3; ii,pNs(lO4) CH2Clz -78 "C; iii TMSOTf; 0 iv v H+ 'e Scheme 14 Enones with t-butyl hydroperoxide yield y-hydroxy derivatives.lI6 An intensive study of the silicon-directed Nazarov reaction has concentrated on the influence of substituents and the anomalous cyclization of vinyl dienyl ketones."'*"* A number of functional groups are compatible with the reaction which proceeds with good specificity e.g.(105) +40% (106) (single isomer) and 'Iz M. Kawai M. Onaka and Y. Izumi Bull. Chem. SOC.Jpn. 1988. 61 2157. 113 T. Yura N. Iwasawa and T. Mukaiyama Chem. Lett. 1988 1021. I14 T. Yura N.Iwasawa and T. Mukaiyama Chem. Lett. 1988 1025. IIS M. R. Binns R. K. Haynes A. G. Katsifis P. A. Scholer and S. C. Vonwiller J. Am. Chem. SOC.,1988 110 5411. I I6 M. R. Sabol C. Wiglesworth and D. S. Watt Synth. Commun. 1988 18 1. 117 S. E. Denmark K. L. Habermas and G. A. Hite Helu. Chim. Am 1988 71 168. IIX S. E. Denmark and G. A. Hite Helc. Chim. Acta 1988 71 195. 126 B. V. Smith 0 (107) + (108) (single isomer). The mechanism of cyclization was discussed in terms of substituent effects and stabilization of the cationic intermediates. For rearrange- ment of (109) a 1,2-cationic shift was invoked; FeC1 in CH2C12 at -10 "C gave (1lo) probably via (1 11)+(1 12). SiMe3 I SiMe3 Me3Si, i"'I Finally the preference for thioaldehydes RCHS to give endo-Diels- Alder addi- tion with cyclopentadiene has been attributed to steric effects particularly at the a-position in R.l19 4 Carboxylic Acids Esters and Lactones a-Aminoacids have been used as chiral educts in the preparation of chiral a-alkylcarboxylic acids.N-(9-Phenylfluoren-9-yl)aminoketonesgave via regioselec-tive enolization and alkylation diastereoisomeric a'-alkyl-branched a-amino-ketones. Separation gave individual diastereoisomers of >99% enantiomeric purity; deprotonation and oxidation gave the desired product in very high enantiomeric purity e.g. from L-alanine in seven steps there was obtained (R)-a-methylpentanoic acid of >99% e.e.l2' Stereoselective alkylation of chiral imide enolates has been used for a high-yielding (in both senses) process leading to a-alkylsuccinates.'21 L-Valinol was converted into (113) by metallation (Li or Na) with hexamethyl- disilazide-THF at -78 "C; alkylation (BrCH,CO,Me) and cleavage of (114) gave (115) (84% 96% e.e.).121 Asymmetric catalytic transfer hydrogenation of a$-unsaturated acids in the presence of a rhodium catalyst [from {Rh(cod)Cl} and I19 E.Vedejs. J. S. Stults and R. G. Wilde J. Am. Chem. SOC.,1988 110 5452. lZo W. D. Lube11 and H. Rapoport J. Am. Chem. SOC.,1988 110 7447. ''I A. Fade1 and J. Salaun Tetrahedron Left.. 1988. 29 6257. 127 Aliphatic Compounds -Part (ii) Other Aliphatic Cornpounds M ph2ph N PPh2 I 1-CO~BU' (116) or (117)] gave good yields. In this way itaconic acid was reduced to MeCH(C02H)CH2C02H(93% e.e.).12*A similar approach was by reduction in the presence of a chiral ferrocene-based catalyst (118) (R = Et Bu or R = c-C5HI0); thus (1 19) gave (2S,3R)-( 120) 92% e.e.123 In addition to the expected reduction incorporation of deuterium occurred at other positions and (E)-(121) gave (2S,3S)-(122) and (2S,3R)-( 123) with the relative distributions shown.Two effective methods for esters depend on bromination-oxidation (or its reverse); in the first of these (the Kiliani method 1861) methyl ethyl and isopropyl esters were prepared by brominative oxidation of a hemiacetal. The method gave poor results in attempted preparations of t-butyl esters but was successful in the presence of other functional groups. The protected (124) gave esters smoothly (Me 95%; Et 85% ;Pr' 70%) and no elimination occurred with (125).124Swern oxidation of I22 H.Brunner and W. Leitner Angew. Chem. Int. Edn. Engl.. 1988 27 1180. 12' T. Hayashi N. Kawamura. and Y. Ito. Tetrahedron Lett. 1988 29. 5969. I24 D. R. Williams F. D. Klingler E. E. Allen and F. W. Lichtenthaler Teerrahedron Lett. 1988 29 5969. I25 F. W. Lichtenthaler. P. Jarplis and K. Lorenz. Svnrhetis 1988 790. 128 B. V. Smith O/OH (126) and bromination-oxidation in methanol gave (127) (84% ).125 Amberlyst-15 is a useful catalyst for preparation of methyl esters and no racemization epimeriz- ation or ketalization was observed in appropriate examples. Remote unsaturation was compatible e.g. (128) gave 90% of the expected methyl ester and some selectivity was observed with (129) which was esterified at the acid group shown in bold type (80%).126 Ester interchange without solvent was brought about under phase-transfer catalysis Me(CH2),,C02Me exchanged with C8H,,0H in the presence of K2C03- Bu,N+ HSO (55"C) to give 97% of product ester.12' CotH A mechanistic study of the Mitsunobu reaction for synthesis of esters has been undertaken in order to clarify the role of substituents and other variables.12' Asymmetric monoesterification of malonic acids using Cinchona alkaloids has been achieved by cleavage of 2,2,5-trimethyl-5-phenyl-4,6-dioxo-1,3-dioxane (130).'29 N-Benzyl-quinidinium and -cinchonidium salts (and their epimers) with sodium alkoxides gave BnAlk+ OR- (BnAlk = benzylalkaloid cation) which for example caused formation of Ph(Me)C*(C02H)C02Me from (130) at -50 "C (73% 34% e.e.pro-R selectivity). Selective reduction of the ester function in this product gave (S)-a-methyltropic acid of modest e.e. (38%). 126 M. Petrini R. Ballini E. Marcantoni and G. Rosini Synth. Commun. 1988 18 847. I27 J. Barry G. Bram and A. Petit Tetruhedron Lerr. 1988 29 4567. I28 D. L. Hughes R. A. Reamer J. J. Bergan and E. J. J. Grabowski J. Am. Chem. SOC. 1988 110 6487. 129 J. Hiratake K. Shibata N. Baba and J. Oda Synrhesis 1988 278. 129 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Esters of 2-methyl-3-oxopropanoic acid showed variable e.e. on reduction by baker's yeast due to variation in size bulk and hydrophobicity of the alcohol rn~iety.'~' Enolates from dioxanones e.g.(131) could be decomposed to a,P-unsaturated acids or reacted with RX and the alkylated compound cleaved to a P-hydr~xyacid.'~~ A new route to (2)-a$-disubstituted acrylates has been described reduction [Ca(BH,) in MeOH-THF] of (132) to syn-(133) an$ anti-(134) (syn anti = 96:4 82% yield) folhwed by reaction of (133) with C,H5NMe BF,-Et,N then LiI gave C,H,,CH=C(Me)C02Me with 98% 2 ~electivity.'~~ For the phenyl analogue RxMe 00 OH however E selectivity was observed. Pure E-or 2-isomers of unsaturated acids have been obtained from phosphine oxide precursors Ph,P( =O)CH2R.133 A route to a$-unsaturated acids via reaction of RCHO and (135) in the presence of ZnBr gave via RCH=CHCO,SiMe, good yields (R = Me 93%) of desired A palladium-catalysed coupling of PhBr and tin-masked dienolates gave unusually y-sub~titution.'~~ OSiMe3 Me3Siy OSiMe3 (135) A flow method has been used in preparation of ethyl 2,2-difluoropent-4-enoate a useful precursor for preparation of various fluoro compound^.'^^ Rearrangement of (136) at -50 "C (BuLi in hexane-THF) gave (137) which is easily ethanolysed to the desired product.Some interesting examples of the DABCO-induced coupling of aldehydes and acrylic esters have been uncovered. Whilst a more 'normal' coupling of RCH2CH0 and CH2=CHC02R' gives acylic hydroxyenoate with PhCHzCHO I30 K. Nakamura T. Miyai K. Ushio S. Oka and A. Ohno Bull. Chem. Soc. Jpn. 1988 61. 2089.131 J. Zimmerrnann D. Seebach and T.-K. Ha Helv. Chim. Acfa 1988 71 1143. 132 M. Shimagaki M. Shiokawa K. Sugai T. Teranaka T. Nakata and T. Oishi Terrahedron Lett. 1988 29 659.. 133 D. Levin and S. Warren J. Chem. SOC.,Perkin Trans. 1 1988 1799. I34 M. Bellassoued and M. Gaudernar Tetrahedron Lerr. 1988 29 4551. 135 Y. Yarnamoto S. Hatsuya and J. Yarnada J. Chem. Soc. Chem. Commun. 1988 86. I36 M. Kolb F. Gerhart. and J.-P. Franqois Svnthesis 1988 469. 130 B. V; Smith FF FF F-pO-P-+O F (137) a [2 + 2 + 21 cycloaddition occurred as well to give (138) in addition to the 'usual' product. Aldehydoester (139) gave (140) from partial lactonization of the acyclic product; with CH2=CHC02Bu' only the cyclized product was dete~ted.'~~ Thermolysis of (141) (R = mesityl) gave a ketene (142) and thence the enolate (143) in which E-and 2-isomers are in equlibrium; 2-isomers predominate in aprotic or moderately polar s01vents.l~~ The configurational stability of enolates from @-ketocarboxylates has been investigated with respect to deprotonation under kinetic control; depending on the medium temperature and counter-ion some equilibrium was found but conditions were defined for preparation of enol ethers and esters of the desired c~nfiguration.'~' O/H-R \ RQx OR RO/c=c=o R Monoalkylmalonates condensed readily with a,@-unsaturated aldehydes forming penta-2,4-dienoic esters of predominatly E stereochemistry." Two cyclization reactions of unsaturated acid derivatives have been reported.In the first CH2=CH(CH2)3CC12C02Et formed cyclopentanes (144) (trans :cis -1:1) with RuC12(PPh3)3.'41 An 'activating device' for an acid such as CH2=CHC02H anticipates the reactivity of an acyloxyborane (the intermediate in reduction of RC02H by BH3). The formed derivative thus undergoes Diels- Alder addition acrylic acid yielding (145) (72(%0).'~~ With a chiral acid such as (146) serving as the precursor of a chiral acyloxyborane the cycloaddition product had modest e.e. (35-78% ). This is a novel and interesting approach to the construction of such systems. W. Poly D. Schomburg and H. M. R. Hoffmann J. Org. Chem. 1988 53 3701. H. Meier H. Wengenroth W. Lauer and.W. Vogt Chem. Ber. 1988 121 1643. I39 H. Meier W.Lauer and V. Franse Chem. Ber. 1988 121 1109. 140 J. Rodriguez and B. Waegell Synthesis 1988 534. 141 T. K. Hayes R. Villani and S. M. Weinreb J. Am. Chem. SOC.,1988 110 5533. I42 K. Furuta Y. Miza K. Iwanaga. and H. Yamamoto. J. Am. Chem. Soc. 1988. 110 6254. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds OH i c1 o''cozH R Enantiomerically pure (2&3 S)-and (2S,3R)-3-hydroxy-2-methylbutanoateesters have been obtained from L-or D-threonine as illustrated in Scheme 15.'43 y,6-Alkylidenedioxy-a,P -unsaturated esters undergo cleavage with LiMe,Cu (to ketones and enolates) and ultimately form P,G-dihydroxy-P,y-unsaturatedesters e.g. (147) (R' = R2 = Me R3 = Et 76'/0).'~ Me OH OR Reagents i NaN02 KBr aq.HBr -15°C; ii KOH EtOH -30°C; iii R2SO4 18-crown-6 CH2C12 20 "C; iv Me2CuLi Et20 -25 "C Scheme 15 A combination of enzymic and chemical reactions has been used to prepare each stereoisomer of methyl 6-(4-chlorophenylthio)-3,5-dihydroxyhexan0ate.'~~ An asymmetric synthesis of dimethyl (R)-4-amino-4-methylpent-2-endioates has followed a bis-lactim route with high specificity; thus addition of (148)to (149) furnished after hydrolysis of the intermediate (150)(75% ).146 Yeast-mediated Li reduction was used in an efficient synthesis of (3S,4S)-4-amino-3-hydroxypentanoic acids; (151)gave the desired product (d.e. -92%) with Hansenula anomala whereas Candida boidinii showed opposite selection in formation of the (3&4S)-isomer (d.e. 143 Y. Petit C.Sauner and M. Larchevique Synthesis 1988 538. 144 S. Takano Y. Sekiguchi and K. Ogasawara J. Chem. Soc. Chem. Commun. 1988 449. 145 M. Christen and D. H. G. Crout J. Chem. Soc. Chem. Commun. 1988 264. 146 U. Schollkopf and J. Schroder Leibigs Ann. Chem. 1988 87. 132 B. V. Smith 90%). Amazingly this reaction was run with 50 g batches of (151) to afford 35 g of product (98% d.e.).I4' P-Propiolactones with K-18-crown-6 in THF suffer C-C scission to enolates and ultimately form esters.'48 00 Ph+OMe BocNH H R1a 0 0 a$-Unsaturated esters with a carbonyl component react in the presence of SmI to form y-lactone~.'~~ It was surmised that a ketyl intermediate was involved. Chiral methyl y-oxocarboxylates with R-metal form y-lactone~.'~' Enzymatic resolution of racemic lactones (using either PPL HLE or PLE) gave products with an optical activity of 60-90%.Thus (152) gave 72% e.e. R-isomer when R = Pr and 76% e.e. for R = C7H,5.151 3-Methyl- y- butyrolactone by extrusion of CO and replacement by OH groups using Criegee's reagent yielded polypropionate 'starter' units of high enantiomeric Stabilized Wittig reagents e.g. Ph3P=CHC0,Me with unsymmetrical maleic anhydrides show Z preference in product formation particularly if an alkoxy group is present. This was interpreted as arising from interaction between the phosphorus and alkoxy oxygen acting as a Lewis base. Thus with (153) no attack occurred at the P-site and the product (154) had E 2 = 28 72.'53 0 Meoco 0 0 Long-chain hydroxy acids with lipase form lactones but the process is complicated by (po1y)lactone formation e.g.10-hydroxydecanoic acid formed di- tri- tetra- and pentalactones but no monolactone. Progress was made in elucidating the stereochemical course of dilactone formati~n.''~ Stille has used palladium-catalysed cyclization of esters with vinyl triflate and vinyl stannone groups at their termini as a route to large ring 1act0nes.l~~ 147 P. Raddatz H.-E. Radurnz G.Schneider and H. Schwartz Angew. Chem. Inr. Edn. Engl. 1988,27,425. I48 2.Jedlinski M. KowalczLk and A. Misiolek J. Chem. Soc. Chem. Commun. 1988. 1261. I49 S. Fukuzawa A. Nakanishi T. Fujinami and S. Sakai J. Chem. Soc. Perkin Trans. 1 1988 1669. I50 T. Kunz and H.-U. Reissig.Angew. Chem. Inf. Edn. Engl. 1988. 27. 268. 151 L. Blanco E. Guibk-Jampel and G. Rousseau Tetrahedron Len. 1988 29 1915. F. E. Zeigler A. Kneisley J. K. Thottathil and R. T. Wester J. Am. Chem. Soc. 1988 110 5434. I53 M. M. Kayser and L. Brean Tetrahedron Lerr. 1988 29 6203. IS4 G. Zhi-wei T. K. Ngooi A. Scilimati G. Fulling and C. .I.Sih Terrahedron Lett. 1988 29 5583. 15' J. K. Stille and M. Tanaka. J. Am. Chem. Sor. 1988 110. 3785. 133 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 5 Amines and Amides A Review of the Leuckart reaction for preparation of amines has been p~blished."~ Synthesis of secondary allylic amines in good yield and giving principally the E-isomer follows Scheme 16.'57 An efficient route to blocked allylamines relies upon 0 NR3 N R3 NHR3 Reagents i R'NH,; ii (X = C1 or Br); iii base; iv NaBH, EtOH 0 Scheme 16 Pd-catalysed coupling of an allylic acetate and NaN( BOC),; subsequent deprotec- tion gives the free amine.'58 Masked 1,3-dicarbonyl compounds have been converted into primary or secondary amine~.'~~ Tertiary amine oxides were transformed into a-functionalized t-amines; the starting material with R3SiOS02CF3 gave (1 55) R1\+ /OSiMezR4 RZ/N\ CHzR3 which by sequential treatment with a base and an electrophile yielded the product e.g.PhCH2(Me),N-0-gave PhCH2N(Me)CH2CN (40%).'60A new synthesis of imines (and thence secondary amines) resulted from reaction of R'M (a Grignard reagent or a cuprate) with an N-silyl- N-alkyl- or N-arylformamide [HCON(R2)SiMe3,etc.] to form R'CH=NR2.'6' Oxidation of amino groups e.g.PhCH,NHPh +PhCH=NPh was effected by PhIO alone or with RuC~,(PP~~)~; the ethyl ester of phenylalanine gave PhCH,CN probably via the imine.16 Coupling of R'CH=NR2 is a route to a 1,2-di-s-amine and was effected by a low valent titanium species (from TiC14-Mg-HgC12) which gave some selectivity since MeCH=NPr gave 50% of diamine with (KR):(RS) ratio 85 15. For MeCH=NCH,Ph selectivity of 90 10 was achieved and debenzylation in the formed MeCH( NHCH,Ph)CH( NHCH,Ph)Me was p0ssib1e.l~~ The preparation of N-methyl-"-( R)-methyl-1,2-diaminoethanehas been described and its use as a chiral modifying reagent for LAH reduction of prochiral ketones was studied. I56 S.Ram and R. E. Ehrenkaufer Synthesis 1988 91. I57 N. De Kimpe E. Stanoeva R.Verhe and N. Schamp Synthesis,1988 587. I SX R. D. Connell T. Rein B. Akermark and P. Helquist J. Org. Chem. 1988 53 3845. 159 J. Barluenga E. Aguilar B. Olano arid S. Fustero. 1.Org. Chem. 1988 53 1741. I60 N. Tokitoh and R.Okazaki Bull. Chem. SOC.Jpn. 1988 61 735. 161 B. L. Feringa and J. F. G. A. Jansen Synfhesis 1998 184. I62 P. Miiller and D. M. Gilabert Tetrahedron 1988 44 7171. 1h3 P. Mangeney T. Tejero. A. Alexakis. F. Grosjean and J. Normant Smhesis 1988 255. 134 B. K Smith Selectivity was moderate (PhCOPr') and the product (R)-alcohol had 59% e.e.164 An improved optical resolution of (R,R)-N,N'-1,2-diphenylethylenediamineled to an estimated 95% optical purity.An n.m.r. method was used to estimate the enantiomeric purity of a chiral aldehyde by reaction with the diamine and measure- ment of differences in 'H and I3C spectra.165 The alleged preparation of a 1-acyl-2-alkylhydrazine by reaction of a hydroxamic acid and an amine in the presence of tosyl chloride has been shown to be incorrect.'66 Lossen rearrangement occurs and the isolated product (from isocyanate and amine) is the urea. Amides are formed from nitriles on silica gel. The reaction may be slow (2-48 h) and yields are variable (35-100% ) a quantitative yield being obtained from PrCN.'67 Penicillin acylase has been shown to catalyse formation of amide bonds. The method works for a range of structural types and esters of aminoacids and di- and tri-peptides can be used as the amine component.Titanium tetrachloride-mediated addition of isocyanides to aldehydes and ketones afforded a-hydroxyamides. No selection was found for chiral is~cyanides.'~~ If a stable cation can be formed from RNC some cyanhydrin results. A 2-functionalized allylstannane reacts with 2-bromo-N-benzoylglycine methyl ester (AIBN-toluene) to give an a-alkylated aminoacid derivative (156).17' Amidoesters have been obtained uia a Kolbe reaction in which diacid hemiesters and amidoacids are co-o~idized.'~~ HN AcO,Me I COPh Alkylation of amines by aralkyl Bi"' derivatives in the presence of Cu(OAc) is moderately successful; BuNH with (PhCH,CH,),Bi gave BuNH(CH,),Ph (24% Oxidation of primary amines by NaOCl in micellar conditions gave nitriles; the reaction can be run on a 0.1 mole scale and is accelerated markedly by the micellar agent (e.g.CTAB).'73 Direct regio- and stereoselective lithiation of secondary allyl- and methallylamines proceeds cleanly; from RLNHCH2C( R2)=CH2 there was obtained I hJ M. Falorni L. Lardicci and G. Giacomelli Gazz. Chim. Ira/. 1988 118 573. I h5 P. Mangeney F. Grosjean A. Alexakis and J. F. Normant Terrahedron Lett. 1988 29 2675; P. Mangeney A. Alexakis and J. F. Normant ibid. p. 2677. 166 W. Hartmann Synthesis 1988 807 and reference cited therein. 107 K.-T. Liu M.-H. Shih H.-W. Huang and C.-J. Hu Synthesis 1988 715. I hX A. Pessina P. Liithi P. L. Luisi J. Prenosil and Y.-S. Zhang. Helo. Chim.Acra 1988 71 631.I hV D. Seebach G. Adam T. Gees M. Schiess and W. Weigand Chem. Ber. 1988 121 507. I70 J. E. Baldwin R. M. Adlington C. Lowe I. A. O'Neil G. L. Sanders C. J. Schofield and J. B. Sweeney J. Chem. SOC..Chem. Commun.. 1988. 1030. 171 M. B. Abderrahman E. Laurent and B. Marquet Bull. SOC.Chim. Fr. 1988. 571. "' D. H. R. Barton N. Ozbalik and M. Ramesh Tetrahedron Lerr. 1988 29 857. ll\ B. JurSi6. J. Chem. Rex (S). 1988. 168. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds R'NHCH,C(R2)=CH-R3 in 70-90% by reaction of the lithiated species with R3X.174 2H n.m.r. has been used to analyse the stereodynamics of N-ethyl-N-methyl-2- aminobutane in the range 100-200 6 Other Nitrogen Compounds Aldehydes with HN in the presence of an alcohol and TiC14 catalyst yield a-azidoethers.In this way C9H19CH0 gave C9H,,CH(OMe)N3 (go0/,). Pyrolysis or photolysis of such compounds gave an iminoether further transformed into a nitrile (heat) or an amide (A1203).'76 The silicon-directed Beckmann fragmentation of silylated oximes led to a nitrile and an alkene; R'C(=NOH)CH2CH2SiR3 in acid or with F- gave R'CN + C2H4. Cyclic systems behaved ~imi1arly.l~~ Silyl amines as lithium or zinc salts are oxidized by dry air (-60 to 20 "C) to form ultimately an aldehyde or ketone; probable intermediates are a nitroso compound and thence the ~xime.'~' A substantial review of the uses of nitroalkanes as synthetic equivalents of alkyl anion synthons has been p~blished.'~~ Addition of nitroalkanes to a$-unsaturated carbonyl compounds in the presence of basic Al,03 gave rise to functionalized 1,4-diketone~.'*~ Typically R'CH,NO and R2CH=CHCOR3 gave R'COCH(R2)CH2COR3 from a sequence of reactions with (i) Al,03 (ii) 30% H202-K2C03 and (iii) MeOH.Yields were 50-90%. MeNO served as a carbonyl dianion synthon since 2 moles of enone in the presence of Al,03 gave a 1,4,7- triketone. This methodology was applied to a synthesis (60%) of dihydrojasmone. Aluminium trialkyls (and then etherates) add rapidly to a,P-unsaturated nitro compounds to give 1,3-a1kylation.''' A cyclic intermediate (157) was proposed as the vehicle for transferring an alkyl group selectively. Selective hydrolysis by PLE has been used to obtain monoacetates of nitrodiols.From meso-diacetates there was obtained for example (158) in 60% yield and 90-95% e.e. Elimination of water gave nitro unsaturated esters whose addition and substitution was further studied.'" I71 J. Barluenga F. J. Fahanas F. Foubelo and M. Yus J. Chem. Soc. Chem. Commun. 1988 1135. C. T. Danehey jun. G. L. Grady P. R. Bonneau and C. H. Bushweiler J. Am. Chem. Soc. 1988 110 7269. I76 A. Hassner R. Fiaiger and A. S. Amarasekera. J. Org. Chem. 1988 53 22. I71 H. Nishiyama K. Sakuta N. Osaka H. Arai M. Matsumoto and K. Itoh Tetrahedron 1988. 44 2413. I78 H. G. Chen and P. Knochel Tetrahedron Lett. 1988 29 6701. I79 G. Rossini and R. Ballini Synthesis. 1988 833. I xn R. Ballini M. Petrini E. Marcantoni and G. Rossini Svnthesis 1988 231.1x1 A. Pecunioso and R. Menicagli 1.Org. Chem. 1988 53 45. "'M. Eherle M. Egli. and D. Seebach. Hek. Chirn. Acta. 1988. 71. 1. 136 B. V. Smith 7 Phosphorus and Sulphur Compounds This section on phosphorus compounds is shorter than usual; reference to applica- tions involving phosphorus derivatives e.g. Wittig reagents have been listed under other functional groups. A route to optically active phosphanes has been described. Sharpless oxidation of an allylic alcohol and tosylation gave (159); ring opening and displacement (LiPPh,-THF) of (159) gave potentially (160) and (161). When R = Ph only (160) was formed; with R = Pr an inseparable mixture of (160) and (161) was formed. When (160; R = Ph) was used as a chiral ligand for preparation of a rhodium catalyst asymmetric hydrogenation of a-acetamidocinnamic acid gave (It)-(-)-N-acetylphenylalanine (83 % e.e.).lg3 A new route to 1,3-diphosphabutadiene deriva- tives has been described; nucleophilic addition of a carbanion Arc=P -R to ArCEP is a key A 1,2,3-triphosphabutadienewas not produced from ArPCl and (Me3Si),P-P=C(SiMe3) or from ArP(C1)(SiMe3) and CIP=C(SiMe,),; the product was assigned the structure (162).”’ Alkenes were converted into P-chlorosulphides in a regioselective manner by reaction with either Me2SO-PhOPOC12 or Me2SO-POCI3 (-20 “C -CH,Cl,); Me(CH2)&H=CH2 gave Me( CH2)15CH( Cl)CH2SMe.‘86 Tetra-n-butylammonium oxone (from aqueous oxone and Bu,N+HSO;) is a useful and selective reagent for converting sulphide into sulphone in the presence of amino keto ester alkene and alcohol group^.'^' A review of selective dealkylation of aryl alkyl ethers and thioethers (and selenoethers) has been published.18’ The structure of the t-butylsulphinyl( pheny1)methyl carbanion in THF has been examined. It exists as two diastereoisomeric dimeric forms in the presence of an equivalent concentration of counter-cation. An excess of base causes monomer formation. The meso-form is shown as (163).lg9 Reduction of sulphoxides to thioethers has been re~iewed.”~ An unusually facile cleavage of an S-C bond in in3 H. Brunner and A. Sichender Angew. Chem. Int. Edn. Engl. 1988 27 718. A. M. Arif A. Barron A. H. Cowley and S. W. Hall 1.Chem. Soc. Chem. Commun. 1988 171. I85 R. Appel B.Niemann and M. Nieger Angew. Chem. Int. Edn. Engl. 1988 27 957. I86 H.-J. Liu and J. M. Nyangulu Tetrahedron Lett. 1988 29 5467. I 87 B. M. Trost and R. Braslau 1.Org. Chem. 1988 53 532. I88 M. Tiecco Synthesis 1988 749. 189 A. Ohno M. Higaki and S. Oka Bull. Chem. SOC.Jpn.. 1988 61 1721. 190 M. Madesclaire Tetrahedron. 1988 44 6537. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds But H h R3 But@ / ph..?5:u* Bu' sterically crowded sulphoxides occurs on attempted oxidation of ArCR' R3CH2SR2 (Ar = 1,3,5-Bu\C,H2) to afford (164) (+R2SOH).19' 2-Phenylsulphonyl-l,3-dienescan be regioselectively epoxidized at either double bond by choice of reagent MeCH=CH-C(S02Ph)=CH2 gave the 3,4-epoxide with MCPBA and the 1,2-epoxide with alkaline H202.These products were useful in regio- and stereospecific reactions with nu~leophiles.'~~ Acyclic diastereocontrol has been found in the formation and reactions of y-hydroxysulphones. The dianion of methyallyl phenyl sulphone gave on alkylation with styrene epoxide y-hydroxy- sulphone (165) (71'/0 d.e. > 99 :1). The necessary structural requirements for such selectivity were considered to be a terminal epoxide and chain branching in the sulphone and adjacent to the ~ulphone.'~~ The protonation of the dianion (166) 2-JYYR PhOzS OH during quenching was envisaged as occurring from the topside consistent with product stereochemistry; single regio- and stereoisomers were formed in coupling of Grignard reagents (catalysed by CuCN) with substitution of the sulphone.(E)-MeCH=CHCH2S02Ph was converted into (167) and then with BuMgBr- CuCN-Et20 gave (168). Double control is thus exerted first in hydroxysulphone formation and then in its substitution. Many possible transformations can thus be +H -?p+H PhOzS OTBDMS H OTBDMS 191 R. Okazaki T. Ishida and N. Inamoto 1. Chem. SOC.,Chem. Commun. 1988 40. I92 J.-E. Backvall and S. K. Juntunen 1. Org. Chem. 1988 53 2398. 193 B. M. Trost and C. A. Medic 1. Am. Chem. Soc.. 1988. 110 5216. 138 B. V. Smith envisaged based on this methodology and by taking advantage of the availability of enantiomerically pure epoxides. Chiral y-arylsulphanylbutyrolactonesundergo a stereo-controlled intramolecular ring closure to form optically pure ring-fused y-butyrolactones uia a radical or cationic pathway.194 Trost has reviewed organosulphone chemistry drawing an intriguing parallel to the chameleon !195 Perhalogenated sulphines (thione oxides) and sulphenes (thione dioxides) have been reviewed.196 Some highly efficient and selective oxidations of methyl thioether substrates by the o-hydroxylase from Pseudomonas oleovorans have been rep01ted.l~' Although MeSCH,CH,Me gave the sulphoxide with 88% e.e.MeS(CH,),CHMe gave a product of very low (2%) e.e. An interesting example of selectivity was the clean sulphoxidation of MeS(CH,),CH=CHPr (86% e.e.) with no concurrent hydroxyla- tion. A general account of such chiral sulphoxidations by biotransformations of sulphides is a~ailable.'~~ Synthetically useful extrusion reactions of organo-sulphur -selenium and -tellurium compounds have been surveyed.'99 8 Miscellaneous Three useful general reviews have been published.The characteristics of the reactions of allylsilanes and their applications to versatile synthetic equivalents has been surveyed.200A full and interesting account of organosilicon chemistry in organic synthesis provides a comprehensive coverage.*" A multi-author review of 'emerging organic reactions' has summarized much work of novelty and importance.202 194 J. P. Marino E. Laborde and R. S. Paley J. Am. Chem. SOC.,1988 110 966. 195 B. M.Trost Bull. Chem. SOC.Jpn. 1988,61 107. 196 W. Sundermeyer Synrhesis 1988 349. 197 A. G.Katopodis H. A. Smith jun. and S. W. May J. Am. Cbem. Soc. 1988 110 897. H. L. Holland Chem. Rev. 1988 88 473. I99 F. S. Guziec jun. and L. J. Sanfilippo Tetrahedron 1988 44 6241. 200 A. Hosomi Acc. Chem. Res. 1988 21 200. 201 1. Fleming (ed.) Tetrahedron 1988 44 3761. 202 Chem. Rev. 1988 86 733.

ISSN:0069-3030    

DOI:10.1039/OC9888500105

出版商:RSC    

年代:1988

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6 Alicyclic Chemistry By N. S. SlMPKlNS Department of Chemistry University of Nottingham Nottingham NG7 2RD 1 General Several reports have appeared describing ring expansion methods which give access to various ring sizes; some examples are shown in Scheme 1. Addition of doubly deprotonated phenylthionitromethane to cycloalkanones gives adducts such as (1) which are converted into the desired ring-expanded products using A1Cl3.' The method in general works satisfactorily except that cyclopentanone gives a poor yield of the initial adduct and the adducts have proved susceptible to unwanted dehydration and retro-aldol reactions. The eight-membered ring product (2) is obtained via an aldol-retro-aldol process which uses Bu'OK in DMSO at room temperature.2 Nine- and ten-membered products are obtained similarly.A less SPh (1) 92% 68Yo (2) 62% AIMeCI SiMe (4) 77% (5) trace Scheme 1 ' S. Kim and J. H. Park Chem. Lett. 1988 1323. * Z.-F. Xie H. Suemune and K. Sakai J. Chem. SOC.,Chem. Commun. 1988 612. 139 140 N. S. Simpkins familiar process involves treatment of cyclic trimethylsilylmethylaldehydes such as (3) with Lewis acids.3 In the example shown (4) is the major ring-enlarged product resulting from sequential carbon and hydrogen migrations. This reaction can be tuned to give products of type (4) or (5) with high selectivity primarily by changing the Lewis acid. A further report deals with the ring expansion method highlighted last year in which cyclic diketones are treated with ethylene glycol-BF,-OEt .4 This new variant produces cycloheptenes from suitably substituted cyclopentanones and is illustrated with a synthesis of ( * )-bulnesol (6) (Scheme 2).&-< HOCH,CH,OH BF,.OEt H HO (6) Scheme 2 Treatment of various halogenoepoxides with activated copper in THF or toluene gives the expected cycl~alkenols.~ 2 Three-membered Rings The cyclopropenone ketal (7) reacts smoothly with organocuprates to produce a cuprio-cyclopropane intermediate which can then be quenched with electrophiles to give cis-disubstituted products (e.g. Scheme 3).6 fi-fi -fi OM0 Mex (7) CuMe \ Reagents i MezCuLi EtzO-THF; ii MepSiC1 MeN qo n Me KNMe 0 Scheme 3 A number of different cuprates and electrophilic quenchers have been explored including an interesting divinylation procedure which involves in situ rearrangement to give a seuen-membered ring products.Cyclopropane products are also produced uia 1,3-elimination from y-iodo-ketones and -esters.’ Cohen has described a new K. Tanino T. Katoh and I. Kuwajima Tetrahedron Lett. 1988 29 1815 1819. M. Tanaka H.Suemune and K. Sakai Tetrahedron Lett. 1988,29 1733. ’ T.-C. Wu and R. D. Rieke Tetrahedron Lett. 1988 29 6753. E.Nakamura M. Isaka and S. Matsuzawa J. Am. Chem. SOC.,1988,110,1297. ’ M. Mori N. Kanda Y. Ban and K. Aoe J. Chem. SOC.,Chem. Commun. 1988 12. Alicyclic Chemistry variant for cyclopropanation of enones which involves conjugate addition of a suitable phenylthio-stabilized organolithium followed by internal displacement of a phenylthio group activated by copper (I) trifluoromethanesulphonate (Scheme 4).* s -,ph,j,:i"^ I cu+ &SiMe3 -18 "C SiMe3 SPh PhS SPh Scheme 4 Vinylcyclopropanes are also prepared using this method by employing suitable sulphur-stabilized allylic carbanions.Fischer carbene complexes react with both 1,3-dienes and enynes to give useful products including cyclopr~panes.~ Reaction of dibromomalonate derivatives with electron-poor olefins in the pres- ence of Bu3Sb gives cyclopropanes having three electron-withdrawing groups (Scheme 5)." The products have potential use in nucleophilic cyclopropane-opening reactions. NC ,CO,Et 88% / Scheme 5 Krief has described further studies of the little-used selenones and their derived carbanions." The cyclopropanation reaction using selenones follows along the lines of the sulphone analogue but appears somewhat more general (e.g.Scheme 6). Scheme 6 Other recent cyclopropane preparations include cyclopropylacylsilanes,'* 1-chloro-l-fluorocyclopropanes,'3and substituted cyclopropylamines prepared using a Favorskii-type pr~cedure.'~ Phase transfer conditions can be used for displacement of halogens from readily available gern-dichlorocyclopropanes.'5 T. Cohen and M. Myers J. Org. Chem. 1988 53,457; K. Ramig M. Bhupathy and T. Cohen J. Am. Chem. SOC.,1988 110 2678. P. F. Korkowski T. R. Hoye and D. B. Rydberg J. Am. Chem. SOC.,1988 110 2676; W. D. Wulff D. C. Yang and C. K. Murray ibid.p. 2653. 10 C. Chen Y.-Z. Huang and Y. Shen Tetrahedron Lett. 1988 29 1033. '' A. Krief W. Dumont and A. F. De Mahieu Tetrahedron Lett. 1988 29 3269; A. Krief W. Dumont and J. L. Laboureur ibid. p. 3265. 12 J. S. Nowick and R. L. Danheiser Tetrahedron 1988 44 4113. 13 W. R. Dolbier jun. and C. R. Burkholder Tetrahedron Lett. 1988 29 6749. 14 N. De Kimpe P. Brunet R. Verhe and N. Schamp J. Chem. SOC.,Chem. Commun. 1988 825. M. Fedorynski A. Dybowska and A. Jonczyk Synthesis 1988 549. N. S. Sirnpkins Several reports describe new preparations and reactions of unsaturated cyclopro- panes particularly alkylidenecyclopropanes. McMurry has shown that the trouble- some reactions of phosphorane (8) can be carried out efficiently using tris-[2-(2- methoxyethoxy)ethyl]amine as a phase-transfer catalyst (Scheme 7).16 The method gives vastly superior results to the standard conditions and works well even with enolizable substrates.75'/o I B n O d (Bn = benzyl) \ 83 O/o Reagents i Ph3Pd (8) N\ \OnOM,) Scheme 7 Another very general procedure which gives good results is a modification of Cohen's Peterson approach (Scheme 8).17 By refluxing the initial Peterson adduct with excess Bu'OK the need to isolate the unstable /3-silylcarbinol intermediate is avoided and better overall results are achieved. R'b:2e3 lRbY:ej 5IRK;;] -Rb R3 R2 R2 R2 OLi R2 Reagents i LDMAN -45"C THF; ii R3CHO; iii Bu'OK Scheme 8 A third very interesting route to these products involves the reaction of alkenes with 3-phenylselenoalk- 1 -enylidene carbenes (e.g.Scheme 9).'* The example shown proved particularly interesting in that rearrangement of (9) to either (10) or (11) is possible. Vinylcyclopropanes and alkylidenecyclopropanes have been utilized recently by Motherwell in studies dealing with ring opening by TolS021 and Pd"-catalysed [3 + 2]cycloadditions respectively.'' Two groups have described asymmetric routes to the vinyl cyclopropane (12) (Scheme 10). Preparation of (S) -(12) using the now familiar chiral lactams of 16 J. A. Stafford and J. E. McMurry Tetrahedron Lett. 1988 29 2531. 17 T. Cohen S.-H. Jung M. L. Romberger and D. W. McCullough Tetrahedron Lett. 1988 29 25. 16 R. T. Lewis and W. B. Motherwell J. Chem.SOC.,Chern. Commun. 1988 751. l9 R. T. Lewis W. B. Motherwell and M. Shipman J. Chern. Soc. Chern. Commun. 1988,948; M. C. M. de C. Alpoim A. D. Morris W. B. Motherwell and D. M. O'Shea Tetrahedron Lett. 1988 29 4173. A1icyclic Chemistry I-lX -4 H202 (10) X = OH H SePh (11) X = SePh Scheme 9 0 -+ $N$~~~~~-C02Me C02Me 0 0 99% d.e. J J MeOz Cqr02M e CH,(CO,Me), Bu'OCO~_/-71 COzMe Me02C4-oC02Bu' pd,(ciba);CHCI chiral catalyst (R)-(12) 70% e.e. H i ,Me Chiral catalyst = PPhz Scheme 10 Meyers gives the final product in >99% e.e. although a four-step sequence is required.20 The more direct catalytic asymmetric route using palladium so far gives only 70% e.e.2' Other chiral cyclopropanes have been synthesized using camphor-derived chiral auxiliaries,22 and also starting with a chiral oxa~olidine.~~ Finally a chiral iron acyl 20 A.I. Meyers J. L. Romine and J. A. Fleming J. Am. Chem. SOC.,1988 110 7245. 21 T. Hayashi A. Yamamoto and Y. Ito Tetrahedron Lett. 1988 29 669. 22 K. Tanaka I. Funaki A. Kaji K. Minami M. Sawada andT. Tanaka J. Am. Chem. SOC.,1988,110,7185. 23 D. J. Aitken J. Royer and H.-P. Husson Tetrahedron Lett. 1988 29. 3315. N. S. Simpkins auxiliary enables asymmetric synthesis of either cis-or trans-substituted cyclopro- panecarboxylic acids,24 whereas an alternative strategy employs tartrates as chiral starting materials2' (e.g. Scheme 11). co PPh3 yo ,PPh3 I' I i-iii iv v + -02" major diastereoisomer C02Me C02Me 1 1 Reagents i 4 eq.ZnCI,; ii 1.5 eq. Et,Zn; iii 4 eq. CH,I,; iv Br,; v HxMe Ph NH Scheme 11 3 Four-membered Rings A review dealing with the topic of cyclobutanones and cyclobutenones in nature and in synthesis has been published.26 A number of simple 1,3-disubstituted cyclo- butanes are available using a straightforward malonate alkylation pr~cedure.~' As in previous years intramolecular [2 + 2]cycloadditions have proved a popular entry to cyclobutane-containing skeletons.** Two reports indicate the utility of ring expansion of cyclopropanes as an entry to cyclobutanes (Scheme 12). The BF,.OEt,-mediated rearrangement of optically active cyclopropane (13) occurred with high stereoselectivity with the minor isomer 24 P.W. Ambler and S. G. Davies Tetrahedron Lett. 1988 29 6979 6983. 25 A. Krief W. Dumont and P. Pasau Tetrahedron Lett. 1988 29 1079; A. Krief and W. Dumont ibid. p. 1083; see also A. Krief D. Surleraux and H. Frauenrath ibid. 6157. 26 D. Bellus and B. Emst Angew. Chem. Int. Ed. Engl. 1988 27 797. 27 P. E. Pigou and C. H. Schiesser J. Org. Chem. 1988 53 3841. 28 A. G. Schultz M. Plummer A. G. Taveras and R. K. Kullnig J. Am. Chem. Soc. 1988 110 5547; A. De Mesmaeker S. J. Veenstra and B. Ernst Tetrahedron Lett. 1988 29 459; R. L. Funk P. M. Novak and M. M. Abelman ibid. p. 1493. Alicyclic Chemistry OH (13) 95 5% A Scheme 12 possibly arising from an isomer of (13) carried through from previous steps.29 The pinacol-type rearrangement of the epoxide derived from (14) occurs in situ presum-ably catalysed by m-chlorobenzoic acid.30 A selection of other substrates behave similarly and the intermediate oxaspiropentanes are isolable in certain cases.Silyloxyacetylenes have proved effective in cycloadditions with ketenes to give cyclobutenone products (e.g. Scheme 13).31Cyclobutenone products themselves can also be combined with silyloxyacetylenes in an efficient aromatic annulation pro- ~edure.~~ Addition of an organolithium to dialkyl squarates followed by acidic treatment constitutes an efficient route to substituted cyclobutenediones (Scheme 14).33 Replacement of the second R'O group with a different organolithium is also possible OSiPr; CH* P r ASi 0, I I1 85 % Scheme 13 ,"'"uo R'O (i)RLi ___,IZN-HCI Oxo (ii) H20 R CHIC12 R'O R'o OH R'O R (15) Scheme 14 29 J.Salaun and B. Karkour Tetrahedron Lett. 1988 29 1537. 30 D. W. McCullough and T. Cohen Tetrahedron Lett. 1988 29 27. 31 C. J. Kowalski and G. S. Lal J. Am. Chem. Soc. 1988 110 3693. 32 R. L. Danheiser A. Nishida S. Savariar and M.P. Trova Tetrahedron Lett. 1988 29 4917. 33 M. W. Reed D. J. Pollart S. T. Perri L. D. Foland and H. W. Moore J. Org. Chem. 1988 53 2477; L. S. Liebeskind R. W. Fengl K. R. Wirtz and T. T. Shawe ibid. p. 2482. 146 N. S. Simpkins and the intermediates (15) find an alternative application in a preparation of b~tenolides.~~ In contrast to the cyclopropanation process mentioned above,9 alkynyl chromium and tungsten carbene complexes give [2 + 2Jcycloaddition products with a range of enol ethers.35 The resulting adducts e.g.(16) appear to have some potential for cyclobutanoid synthesis (Scheme 15). OMe (16) M = Cr or W -Me H Scheme 15 In another 12 + 2]cycloaddition process cyclobutylamines are prepared following trapping of keteniminium ions with alkenes and in situ reduction using cyanoboro- h~dride.~~ Finally two groups have described syntheses of naturally occurring cyclobutane amino acids.37 4 Five-membered Rings A number of interesting and varied constructions of cyclopentanoids have appeared this year. Functionalized cyclopentenes can be prepared via base-induced ring contraction of thiocarbonyl Diels- Alder adducts (Scheme 16).38 Excellent yields are obtained although the conditions for the second step need to be tailored to each particular substrate.The method is particularly attractive in that simple dienes rather than carbonyl partners are employed in the annulation. OTBS OTBS OTBS 82'/o 92Yo Scheme 16 34 S. T. Perri L. D. Foland and H. W. Moore Tetrahedron Lett. 1988 29 3529. 35 K. L. Faron and W. D. Wulff J. Am. Chem. SOC.,1988 110 8727. 36 C. J. Urch and G. C. Walter Tetrahedron Lett. 1988 29 4309. 37 Y. Gaoni Tetrahedron Lett. 1988 29 1591; G. W. J. Fleet J. A. Seijas and M. P. Vasquez Tato Tetrahedron 1988 44,2011. 38 S. D. Larson J. Am. Chem. SOC.,1988 110 5932. AIicyclic Chemistry Me A,toluene 4-t-butylcatechol LMe (17) 81% 0 Scheme 17 Three reactions which afford cyclopentenones are outlined in Scheme 17.Forma- tion of the spirocyclic methylenecyclopentenone (17) is thought to occur uia an oxy-Cope rearrangement followed by cyclization of an enol intermediate.39 Cyclo- pentanones such as (18) are prepared stereoselectively in 40-70% yield presumably uia an allene oxide.40 The formation of (19) in large excess over its regioisomer (20) illustrates the utility of the SMe group in controlling the intermolecular Pauson reaction by ~helation.~~ Chains bearing a pendant NMe group exhibit a similar effect although oxygen groups do not work. Cyclopentenones are also available by photochemical rearrangement of quinone-derived starting materials such as ethers (21)42or ketals (22)43 (Scheme 18).0 hv hv & __* __. 0U R OMe Scheme 18 39 P. A. Jacobi L. M. Armacost J. I. Kravitz M. J. Martinelli and H. G. Selnick Tetrahedron Lett. 1988 29 6865; P. A. Jacobi L. M. Armacost J. I. Kravitz and M. J. Martinelli ibid. p. 6869; P. A. Jacobi and J. I. Kravitz ibid. p. 6873. 49 S. J. Kim and J. K. Cha Tetrahedron Lett. 1988 29 5613. 41 M. E. Krafft J. Am. Chem. Soc. 1988 110,968. 42 A. G. Taveras jun. Tetrahedron Lett. 1988 29 1103. 43 M. C. Pirrung and D. S. Nunn Tetrahedron Lett. 1988 29 163. N. S. Simpkins A cyclization/ring-contraction reaction initiated by an oxonium cation generated from an acetal allows the synthesis of cis-hydroindenes (Scheme 19).44 Similar products are also prepared using another annulation procedure (Scheme 20);45here the ketone is converted into the corresponding thermodynamic enolate which is then reacted with (23)to give an intermediate cyclopropanol that rearranges smoothly to the cyclopentanone.The yields for the first step proved somewhat disappointing and it was found to be important that R # H for the subsequent rearrangement step to give the desired cyclopentanone. Aromatic substituted cyclopentanones are also available by a method involving ring expansion starting with a substituted cyclopropyl ketone.46 a" SnCl CH,CI, -78 "C RO OR Scheme 19 OH Scheme 20 Scheme 21 shows two epoxide-based cyclizations which lead to highly functional- ized cyclopentanoid products.The first reaction is a modification of the hydrostanny- lation-cyclization procedure reported previously with the product radical opening the ep~xide.~~ The second process is also thought to be essentially a radical reaction and appears especially attractive due to its tolerance of other functionality mild reaction conditions and the fact that epoxides act as the radical initiator.48 Trost has again added significantly to the repertoire of transition metal catalysed cyclizations-Scheme 22 shows representative examples involving 1,6-diyne~,~~ dienyl allylic acetates," and enallenes." The preparation of (24) in stereoselective fashion is a particularly impressive feat. A notable feature of the method is that suitable precursors such as (25) are easily available from simple starting materials as shown- also using Pdo chemistry.44 M. Sworin and W. L. Neurnann J. Org. Chem. 1988 53 4894. 45 J. T. Carey and P. Helquist Tetrahedron Lett. 1988 29 1243. 46 B. Deb C. V. Asokan H. Ila and H. Junjappa Tetrahedron Lett. 1988 29 2111. 47 Y. Ichinose K. Oshima and K. Utimoto Chem. Lett. 1988 1437. 48 W. A. Nugent and T. V. RajanBabu J. Am. Chem. SOC.,1988 110 8561. 49 B. M. Trost and D. C. Lee J. Am. Chem. SOC.,1988 110 7255. 50 B. M. Trost and J. I. Luengo J. Am. Chem. SOC.,1988 110 8239. 51 B. M. Trost and J. M. Tour J. Am. Chem. SOC.,1988,110,5231; B. M. Trost and K. Matsuda ibid. p. 5233. Alicyclic Chemistry SnPh3 SnPh3 [Ref. 471 70% [Ref.481 Scheme 21 TBDMSO TBDMSO (dba),Pd,.CHCI Tol,P Et,SiH *< R 89% fOAc ,Pd' PhSOz (i) OC02Et Pdo -6 PhSO2 then > 00 SOzPh PhO2S SO2Ph (ii) acetylation SOzPh (25) 49% (24) 56% polymer-supported NiCIJCrCI Ed E 80'/o Scheme 22 Transition metal catalysed carbonylation-cyclization is perhaps even more syn- thetically attractive since more highly oxygenated products are produced. Two new variants which yield cyclopentenone products are highlighted in Scheme 23. In the preparation of (26) and related products two successive carbonylations occur with concomitant cyclization double-bond isomerization and ester formation.52 The E.Negishi G. Wu and J. M.Tour Tetrahedron Lett. 1988 29 6745.N. S. Simpkins n-Hex n-Hept CO(600psi.) C02Me NEt, MeOH CI,Pd(PPh,) 'T H 0 X = CI Br OAc OSO,Me efc. (26) 42-94% TBDMSO TBDMSO ArNC,Ni(cod),Bu;P Ph DMF 100°C H Ar = 2,6-dimethylphenyl (27) 83% Scheme 23 usual variety of allylic leaving groups can be usefully employed in the reaction as indicated above. The second reaction uses an aryl isocyanide in place of the more usual isoelectronic counterpart CO the products [e.g. (27)] being hydrolysable to the corresponding cyclopentenone~.~~ Enzymic methods allow the efficient enantioselective preparation of various hydroxycyclopentyl carboxylatess4 and the popular building block 4-hydroxy-2- cyclopentenyl acetate.55 Three chemical methodss6-s8 which allow the preparation of hydroxylated cyclopentanoids in high optical purity are illustrated in Scheme 24.Each of these methods is essentially a resolution and relies on the separation of diastereomeric products. 5 Six-membered Rings Treatment of suitable unsaturated substrates with I(py),BF4-HBF4 at low tem- perature results in cyclization to give six-membered ring iodides.59 A number of cyclohexane products having a 1,3-disposition of exo-cyclic alkene groups have been prepared using a palladium ene-type process (e.g. Scheme 25).60 The particular example shown is highly regio- and stereoselective with only the indicated product being obtained. Another palladium-mediated process converts a sugar-derived enol ether into the corresponding carbocycle.61 Various 2,5-cyclohexadien- 1-ones can be prepared from the corresponding dienes in higher yield than previously possible by adopting the Bu'OOH-PDC oxidation procedure used previously for allylic and benzylic oxidation (Scheme 26).62 53 K.Tarnao K. Kobayashi and Y. Ito J. Am. Chem. SOC., 1988 110 1286. 54 T. Sato H. Maeno T. Noro and F. Fujisawa Chem. Lett. 1988 1739. 55 T. Sugai and K. Mori Synthesis 1988 19; F. Theil S. Ballschuh H. Schick M. Haupt B. Hafner and S. Schwarz ibid. p. 540. 56 B. M. Eschler R.K. Haynes S. Krernmydas and D. D. Ridley J. Chem. SOC.,Chem. Commun. 1988 137. 57 E. A. Mash and S. B. Hemperly Tetrahedron Lett. 1988 29 4035. 58 F. Toda and K. Tanaka Tetrahedron Lett. 1988 29 1807. 59 J. Barluenga J. M. Gonzalez P.J. Carnpos and G. Asensio Angew. Chem. Int. Ed. Engf. 1988,27,1546. 60 W. Oppolzet R.E. Swenson and J.-M. Gaudin Tetrahedron Lett. 1988 29 5529. 6' S. Adam Tetrahedron Lett. 1988 29 6589. 62 A. G. Schultz A. G. Taveras and R. E. Harrington Tetrahedron Lett. 1988 29 3907; see also A. G. Schultz and A. G. Taveras ibid. p. 6881. Alicyclic Chemistry (ii) MCPBA Bu'O Bu'O Bu'O' 0 [Ref. 561 (and diastereomer) + '&OH HO8 &OH -+ [Ref. 571 ( -1429) recrystallize A[( -)-(29) ( -)-(28)] A vacuum ( -)(28) crystalline 100% e.e. AcO complex [Ref. 581 (28) /\/ \/\ (29) = Scheme 24 I 87% OAc Scheme 25 0 .:#' 73yo Scheme 26 N. S. Simpkins An attractive two-stage procedure converts quinones through to functionalized cyclohexenones in stereoselective fashion (Scheme 27).63Addition of the second nucleophile (either R-or H-)is controlled by the lithium alkoxide function intro- duced in the first step.The two new groups thus end up trans. The chiral monoester (30)-available in large quantities by pig-liver esterase hydro- lysis of the corresponding diester-has been effectively manipulated to give lactones (31) and (32) or their enantiomers (Scheme 28).64 The important step here is the () (ii) BrMg-=-Ph 0 63Yo MeLi TMEDA THF 0 OH 90% Scheme 27 eO2I-l -e02H ';Io -a. H C02Me ! C02Me I Me Me (31) I 1 enantiomers of (31) and (32) Scheme 28 63 M. Solomon W. C. L. Jamison M.McCormick D. Liotta D. A. Cherry J. E. Mills R. D. Shah J. D. Rodgers and C. A. Maryanoff J. Am. Chem. SOC.,1988 110 3702. 64 M. Shimada S. Kobayashi and M. Ohno Tetrahedron Lett. 1988. 29 6961. Alicyclic Chemistry alkylation of (30) [or (33)] using LDA (2.1 equivalents) and MeI which proves highly stereoselective giving essentially only the cis-isomer shown. The desired lactones are then obtained by standard chemistry. (R)-( -)-5-Trimethylsilyl-2-cyclohexenone, highlighted last year as a useful chiral synthon for cyclohexanes has been transformed into several natural products.6s As always numerous studies relating to the Diels-Alder reaction have appeared. 2-Benzoyloxynitroethylenereacts smoothly with a number of dienes to give nitro- cyclohexenes which can be reduced to the corresponding amines using LiAlH4 .66 The diene (34) gives the expected adducts in Diels-Alder reactions which can then be oxidized and treated with Bu4NF to give cyclohexadienes as products (Scheme 29).67 <SPh PhSO2-(i) 'CO,Me ABu,NF ozMe \ (ii) MCPBA SiMe3 SiMe3 (34) Scheme 29 A CONH2 (35) (36) Reagents i MeO,CCH=CHCO2Me; ii Bu,NF THF-15% H,O Scheme 30 The intriguing cyclic azadiene (35) also gives Diels-Alder adducts such as (36) which are perfectly set up to give substituted cyclohexanones (C2-C3 bond cleavage) on fluoride treatment (Scheme 30).68The reaction proved to be exo-selective and interestingly fluoride treatment of some adducts results in cleavage of the Cl-C2 bond to give substituted glutarimides.A detailed account of the asymmetric Diels- Alder reaction of @-unsaturated N-acyloxazolidinones has been published.69 Dienes bearing sulphide sulphoxide or sulphone groups are effective in Diels- Alder reaction^.^' Sulphones are useful activating groups for dienophiles as empha- 65 M. Asaoka K. Takenouchi and H. Takei Tetrahedron Lett. 1988,29,325; M. Asaoka K. Takenouchi and H. Takei Chem. Lett. 1988 1225; M. Asaoka N. Fujii and H. Takei ibid. 1655. 66 G. A. Kraus J. Thurston P. J. Thomas R. A. Jacobson and Y. Su Tetrahedron Lett. 1988 29 1879. 67 J. J. Pegram and C. B. Anderson Tetrahedron Lett. 1988 29 6719. 60 M. Rivera H. Lamy-Schelkens F. Sainte K. Mbiya and L. Ghosez Tetrahedron Lett. 1988 29 4573. 69 D.A. Evans K. T. Chapman and J. Bisaha J. Am. Chem. Soc. 1988 110 1238. 70 S.-S. P. Chou and D.-J. Sun J. Chem. SOC.,Chem. Commun. 1988 1176. N. S. Simpkins H / SO,Ph PhMe 172 “C,96h IH Ph02S 92% [Ref. 711 (OTBDMS . -. R R SOzPh PhO2S [Ref. 721 Scheme 31 sized by two recent examples of intramolecular Diels- Alder (IMDA) processes (Scheme 31).71972 Substantial interest seems to have focused on the IMDA reactions of substituted furans and some more notable example^^^-^^ are therefore highlighted in Scheme 32. These reactions illustrate the varied dienophiles and the disparate reaction conditions that have proved effective in furan Diels-Alder reactions. One other related report deals with the high-pressure induced Diels- Alder cycloadditions of butenolides using electron-rich diene~.~~ Finally Diels- Alder-type products have also been obtained in reactions involving propargyl cations78 and aryl chromium carbene complexes.79 6 Larger Rings Lee has shown that bifunctional reagents having allylsilane and acetal functions can give seven-membered ring products (Scheme 33).80 Another reaction which uses a functionalized allylsilane gives similar products via an intramolecular [3 + 41 cycloaddition process.81 Certain seven-membered rings functionalized with carboxylate groups can be prepared via a tandem a-hydroxycyclobutane rearrangement-retro-aldol cleavage process (Scheme 34).82A 71 D.Craig D. A. Fischer 0. Kemal and T. Plessner Tetrahedron Lett. 1988 29 6369.72 M. E. Jung and V. C. Truc Tetrahedron Lett. 1988 29 6059. 73 L. M. Harwood G. Jones J. Pickard R. M. Thomas and D. Watkin Tetrahedron Lett. 1988,29 5825. 74 S. G. Cauwberghs and P.J. DeClercq Tetrahedron Lett. 1988 29 6501. 75 W. H. Darlington and J. Szmuszkovicz Tetrahedron Lett. 1988 29 1883. 76 J. A. Cooper P. Cornwall C. P. Dell and D. W. Knight Tetrahedron Lett. 1988 29 2107. 77 R. M. Ortuno A. Guingant and J. d’Angelo Tetrahedron Lett. 1988 29 6989. ” P. G.Gassman and S. P. Chavan Tetrahedron Lett. 1988 29 3407. 79 A. Yamashita J. M. Timko and W. Watt Tetrahedron Lett. 1988 29 2513. 8o T. V. Lee R. J. Boucher and C. J. M. Rockell Tetrahedron Lett. 1988,29,689; T. V. Lee R. J. Boucher K. L. Ellis and K. A. Richardson ibid. p.685. R. J. Giguere S. M. Duncan J. M. Bean and L. Purvis Tetrahedron Lett. 1988 29 6071. 82 B. C. Ranu and D. C. Sarkar J. Chem. Soc. Chem. Commun. 1988 245. Alicyclic Chemistry 19 Kbar H, Pd-BaSO, ch H 9-155 I w -AO0 .H -CP 24 h 20 "C A.'U [Ref. 731 [Ref. 751 COzMe 280"C 16h ~ Scheme 32 TMSOTf-TiCI SiMe,(YoSiMe'5 H 63% [Ref. 761a H:OMe Me0 OMe H& Scheme 33 ST) * @Me HgO HBF, aq.THF n * COZH Jones reagent-GMe Me COzH Scheme 34 N. S. Simpkins fused system was also synthesized using the same method and conveniently com- bined the two rearrangements in one pot. Both tropone and 2-chlorotropone undergo nucleophilic attack at the 2-position using various nucleophiles including en01ates.~~ The products are useful in natural product synthesis especially in cycloaddition reactions highlighted in previous years.Two interesting examples of seven-membered ring formation using the divinyl- cyclopropane rearrangement are shown in Scheme 35. In the first example the highly functionalized divinylcyclopropane is produced in situ by enolization of the acidic P-keto ester function.84 Other conditions can be used to produce the opposite epimer at C4. In the preparation of (37) it is the cyclopropane group that is formed in situ -again the reaction is highly ~tereocontrolled.~~ M e 0 9 Et,N TMSCl TMSO eH Bu'0,C DMF,50 "C MeO.. -Bu'O~C OBn OBn 87% (Bn = benzyl) [Ref. 841 0 (37) 67% [Ref. 851 Scheme 35 Several other syntheses of seven-membered rings have been aimed at natural products of the guaianolide or pseudoguaianolide family (Scheme 36).86-88Both intermediates (38) and (39) are converted into known precursors of the natural product ( f )-confertin.An unsuccessful approach to the lathrane diterpenes incorporated the conversion of (40) into (41) as the key ring-forming reaction (Scheme 37).89 Similar ring-closure processes also worked on a number of simple model compounds in each case using silyl enol ethers as nucleophiles. Further details of the rearrangement of divinylcyclobutanes to cyclooctenones have been published." Intramolecular coupling reactions involving aldehydes have 83 J. H. Rigby C. H. Senanayake and S. Rege J. Org. Chem. 1988,53 4596. 84 P.A. Wender and K. Brighty Tetrahedron Lett. 1988 29 6741. 85 H. M. L. Davies C. E. M. Oldenburg M. J. McAfee J. G. Nordahl J. P. Henretta and K. R. Romines Tetrahedron Lett. 1988 29 975. 86 M. Kennedy and M. A. McKervey J. Chem. SOC. Chem. Commun. 1988 1028; H. Duddeck M. Kennedy M. A. McKervey and F. M. Twohig ibid. p. 1586. P. T. Lansbury J. P. Galbo and J. P. Springer Tetrahedron Lett. 1988 29 147. 88 M. C. Welch and T. A. Bryson Tetrahedron Lett. 1988 29 521. 89 T. F. Braish J. C. Saddler and P. L. Fuchs J. Org. Chem. 1988 53 3647. 9u S. A. Miller and R. C. Gadwood J. Org. Chem. 1988 53 2214. Alicyclic Chemistry (i)(ii) mandelate (Bu'O),AIH @Me\AcO OH (38) [Ref. 861 Bu'OK SU Go [Ref. 871 0 NaOH,H,O, TBDMSO TBDMSO (39) [Ref.881 Scheme 36 TBDMSO 0 T a - MeS-S+Me BF,-q&yMeS MeS SMe (40) (41) 77% Scheme 37 been used in assembling the cyclooctene ring present in the tricyclic framework of ophiobolins and ceroplastols (Scheme 38).91*92 The intermediate (42) was taken on to the natural products albolic acid and ceroplastol 11. Other methods for eight-membered ring formation include ring expansions using cycl~butanes,~~ and the very elegant [4 + 41 cycloaddition procedure highlighted last year.94 Finally; Marshall has further expanded his studies of cembranolide synthesis utilizing methods such as the [2,3]-Wittig ring contraction and allyltin reaction^.'^ 91 M. Rowley and Y. Kishi Tetrahedron Lett. 1988 29 4909.92 N. Kato H. Kataoka S. Ohbuchi S. Tanaka and H. Takeshita J. Chem. SOC.,Chem. Commun. 1988 354. 93 T. Fujiwara T. Ohsaka T. Inoue and T. Takeda Tetrahedron Lett. 1988 29 6283; H. Suginome M. Itoh and K. Kobayashi J. Chem. SOC.,Perkin Trans. 1 1988 491. 94 P. A. Wender N. C. Ihle and C. R. D. Correia J. Am. Chem. SOC.,1988 110 5904. 95 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1988 29 1657; J. A. Marshall and J. A. Markwalder ibid. p. 4811; J. A. Marshall E. D. Robinson and J. Lebreton ibid. p. 3547. 158 N. S. Simpkins Bu'Ph,SiO OH I? Y [Ref.91] TiCI, Zn,THF b \ \ [Ref. 921 Scheme 38 (42) 7 Bicyclics and Polycyclics Certain bridged ketones can be substituted at the bridgehead position by means of a cuprate/alkoxide mixture the reaction apparently proceeding via in situ formation of the bridgehead en one^.^^ A number of interesting hydrindanone derivatives can be prepared using a hetero- Claisen rearrangement (e.g.Scheme 39).97 Other electron-deficient allenes also participate in the reaction and the products can be further transformed e.g. (43) to (44) using HJPd followed by A1,03. An extension of previous studies has shown that Friedel-Crafts acylation of cycloalkenes can lead to useful polycyclic products.98 The polycyclization method described by Deslongchamps can be used to synthesize a steroidal skeleton in a single step (Scheme 40).99 The result is accompanied by a detailed analysis of the stereochemical aspects involved in formation of rings C and D.Another application of the rearrangement chemistry illustrated in Scheme 2 is in the preparation of spiro-fused ring systems. loo The preparation of variously sub- + =C=/SozPh-q+ Po -pdh NH SOzPh COMe COMe (44) (43) 85% Scheme 39 96 G. A. Kraus and P. Yi Synth. Commun. 1988 473. 97 A. Bosum and S. Blechert Angew. Chem. Znt. Ed. Engl. 1988 27 558. 98 A. Tubul and M. Santelli J. Chem. SOC. Chem. Commun. 1988 191. 99 J.-F. Lavallee and P. Deslongchamps Tetrahedron Lett. 1988 29 6033. I00 S. Nagumo H. Suemune and K. Sakai Tetrahedron Lett. 1988 29 6927. Alicyclic Chemistry C02Me cs,co ___, &+p CHCI C02Bu' Scheme 40 NHTs NHTs pyJ-TsNSO BF,.OEt d+Cb Me [Ref.1011 Me Me N,CHC02Et b H (45) [Ref. 1021 Me3Si02C Me (i) LDA THF Me,SiCI -78 "C (ii) PhMe reflux OSiMe (46) [Ref. 1031 Me Scheme 41 stituted decalin systems remains an important topic as indicated by chemistry highlighted in Scheme 41.'0'-'03Compounds (45) and (46) are potentially useful precursors in syntheses of compactin or mevinolin. Rearrangement of ketones bearing silylacetylenic side chains gives bicyclic products containing an allylsilane function (Scheme 42).'04 Several ketones having a methyl group in the 2-position [e.g. (47; R = Me)] give products analogous to (48). Interestingly if R = H the intermediate vinylsilane undergoes alternative rearrangement to give (49). 101 M. J. Melnick A. J. Freyer and S.M. Weinreb Tetrahedron Lett. 1988 29 3891. I02 J. P. Marino and J. K. Long J. Am. Chem. SOC.,1988 110 7916. 103 S. J. Danishefsky and J. E. Audia Tetrahedron Lett. 1988 29 1371. 104 A. S. Kende P. Hebeisen and R. C. Newbold J. Am. Chem. SOC.,1988 110 3315. N. S. Simpkins (47) Trost has described the use of vinylcyclopropanols as terminators in some remark- able cyclizations leading to polycyclic systems of several types (Scheme 43).'05 In each case products are obtained stereoselectively in high yield and without recourse to high-dilution methods. Me,SiOSO,CF H OMe 91 O/O Scheme 43 Finally two cyclization methods which utilize palladium catalysis to furnish polycyclic products from aryl (or vinyl) iodides are shown in (Scheme 44).'06*'07 8 Natural Product Synthesis Funk has applied the Claisen rearrangement-ring contraction of macrocyclic lactone (50) to prepare the tricyclic product (51) which is well suited for elaboration to ingenol (52) (Scheme 45).*08 105 B.M. Trost and D. C. Lee J. Am. Chem. SOC.,1988 110 6556. 106 M. M. Abelman and L. E. Overman J. Am. Chem. SOC.,1988 110 2328. 107 R. C. Larock H. Song B. E. Baker and W. H. Gong Tefrahedron Lett. 1988 29 2919. 108 R. L. Funk T. A. Olmstead and M. Parvez J. Am. Chem. SOC.,1988 110 3298. Alicyclic Chemistry 161 I + \ H [Ref. 1061 Et Pd(OAc) ____+ Ph,P AOP \ [Ref. 1071 Scheme 44 Scheme 45 Total syntheses of ( i)-laurenene,"' taxusin,"' ginkgolides A"' and B,'" and two independent syntheses of forskolin have been reported.' l3 Most notable this year has been the focus of synthetic attention on compounds of the esperamicin/calicheamicin family.This is hardly surprising considering their novel and challenging structural features combined with their potent biological profiles. Particularly impressive is the DNA cleavage ability of compounds such as calicheamicin yln (53),which is ascribed to the sequence of events in Scheme 46 leading to the benzenoid biradical (54). Nucleophilic addition to the Cl-C2 double bond which brings C6 and C11 closer together is thought to be R prerequisite for I09 P. A. Wender T. W. von Geldern and B. H. Levine J. Am. Chern. SOC.,1988 110 4858. 110 R. A. Holton R.R. Juo H. B. Kim A. D. Williams S. Harusawa R. E. Lowenthal and S. Yogai J. Am. Chern. SOC.,1988 110 6558. 'I' E. J. Corey and A. K. Ghosh Tetrahedron Lett. 1988 29 3205. 112 E. J. Corey M.-C. Kang M. C. Desai A. K. Ghosh and I. N. Houpis J. Am. Chern. Soc. 1988 110 649; E. J. Corey and A. V. Gavai Tetru:'tedronLett. 1988 29 3201. 113 S. Hashimoto S. Sakata M. Sonegawa and S. Ikegami J. Am. Chern. SOC.,1988 110,3670; E. J. Corey P. Da Silva Jardine and J. C. Rohloff ibid. p. 3672. 162 N. S. Simpkins 0 0 s\ SMe (54) (53) Scheme 46 the cyclization. Synthetic studies have prepared suitable model systems capable of probing this hypothesis e.g. (55),'14 (56),'15 and (57).lI6 Finally more advanced synthetic intermediates have been obtained by both Schreiber and Danishefsky e.g.(58)'" and (59).'18 0 0 Meo2c&H H H \\\ /// OTBDMS \=/ 114 K. C. Nicolaou Y. Ogawa G. Zuccarello and H. Kataoka 1.Am. Chem. SOC.,1988 110 7247; K. C. Nicolaou G. Zuccarello Y. Ogawa E. J. Schweiger and T. Kumazawa ibid. p. 4866. 115 P. Magnus R. T. Lewis and J. C. Huffman J. Am. Chem. Soc. 1988 110 6921; P. Magnus and P. A. Carter ibid. p. 1626. A. S. Kende and C. A. Smith Tetrahedron Lett. 1988 29 4217; see also P. A. Wender M. Harmata D. Jeffrey C. Mukai and J. Suffert Tetrahedron Lett. 1988 29 909. 117 S. L. Schreiber and L. L. Keissling J. Am. Chem. Soc. 1988 110 631. 118 S. J. Danishefsky N. B. Mantlo D. S. Yamashita and G. Schulte J. Am. Chem. Soc. 1988 110 6890.

ISSN:0069-3030    

DOI:10.1039/OC9888500139

出版商:RSC    

年代:1988

数据来源: RSC