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Front cover |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 005-006
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摘要:
Contemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology Dr S. E. Thomas, Imperial College of Science, Technology, and Medicine Professor E. J. Thomas, University of Manchester International Advisory Board Professor E. J. Corey, Harvard University Professor S. Hanessian, Universite' de Montrial Professor M. Julia, Universiti de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, Scripps Research Institute, La Jolla Professor R. Noyori, Nagoya University Professor L. E, Overman, University of California, Irvine Professor L.F. Tietze, University of Gottingen Contemporary Organic Synthesis is a bimonthly journal which aims to review and provide perspective in all aspects of methodology, selectivity, and efficiency in contemporary synthesis. As well as covering all the principles and methods in functional group chemistry and interconversions, organometallic chemistry and asymmetric synthesis will feature prominently, so too will modern aspects of strategy and computer aided design, biotransformations, and protecting group protocols. Special methods and techniques, such as sonochemistry, FVP, electroorganic synthesis, and supported catalysis will be included as occasional articles, and the manner in which synthesis addresses problems and provides solutions in biology, medicine, agriculture, the environment, and new materials, will also be encompassed.Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field. Although the'majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be submitted to the Senior Editor (Reviews), Books and Reviews Department, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF. Members of the Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way.All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 lHN, England. 1994 subscription rate: EC &150, USA $282, Canada .€ 169 (plus GST ), Rest of the World &16 1. Air freight and mailing in the USA by Publications Expediting Inc., 200 Meacham Avenue, Elmont 1 103; USA Postmaster, send address changes to Contemporary Organic Synthesis, Publications Expediting Inc. Second class postage is paid at Jamaica, New York 1143 1. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe.0 The Royal Society of Chemistry, 1994 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording, or otherwise, without the prior permission of the publishers. Typeset by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho LtdContemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology Dr S . E. Thomas, Imperial College of Science, Technology, and Medicine Professor E.J. Thomas, University of Manchester International Advisory Board Professor E. J. Corey, Harvard University Professor S . Hanessian, Universite' de Montrial Professor M. Julia, Universiti de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, Scripps Research Institute, La Jolla Professor R. Noyori, Nagoya University Professor L. E. Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen Contemporary Organic Synthesis is a bimonthly journal which aims to review and provide perspective in all aspects of methodology, selectivity, and efficiency in contemporary synthesis. As well as covering all the principles and methods in functional group chemistry and interconversions, organometallic chemistry and asymmetric synthesis will feature prominently, so too will modern aspects of strategy and computer aided design, biotransformations, and protecting group protocols.Special methods and techniques, such as sonochemistry, FVP, electroorganic synthesis, and supported catalysis will be included as occasional articles, and the manner in which synthesis addresses problems and provides solutions in biology, medicine, agriculture, the environment, and new materials, will also be encompassed. Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field.Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be submitted to the Senior Editor (Reviews), Books and Reviews Department, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF. Members of the Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way. All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 lHN, England. 1994 subscription rate: EC &150, USA $282, Canada S 169 (plus GST ),-Rest of the World E 16 1. Air freight and mailing in the USA by Publications Expediting Inc., 200 Meacham Avenue, Elmont 1103; USA Postmaster, send address changes to Contemporary Organic Synthesis, Publications Expediting Inc. Second class postage is paid at Jamaica, New York 1143 1. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. 0 The Royal Society of Chemistry, 1994 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording, or otherwise, without the prior permission of the publishers. Typeset by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd
ISSN:1350-4894
DOI:10.1039/CO99401FX005
出版商:RSC
年代:1994
数据来源: RSC
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Back cover |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 007-008
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摘要:
HAZARDS IN THE CHEMICAL LABORATORY Royal Society of Chemistry, Turpin Distribution Services Ltd, Blackhorse Road, Letchworth, Herts SG6 IHN, United Kingdom. CHEMISTRY Information Services II I 5th Edition ‘. . . easy to read, an excellent reference text, and a worthwhile investment .’ Journal of the American Chemical Society reviewing the 4th Edition. The new edition of this essential laboratory handbook is the ‘key’ requirement for all research, development, production, analytical and teaching laboratories worldwide. The 5th Edition provides: 0 a quick guide to the hazardous properties of 1339 substances (over 800 more than were covered in the previous edition) details of the latest UK and EC regulations an extremely useful emergency action check list - users can fill in their own key contacts for hospitals, fire etc.handy tables, symbols and statistics for ease of reference 0 a description of the American scene, including US legislation and safety practices - highlighting differences between the UWEC and USA PVC Protective Binding xx + 676 pages New features include: expanded ‘Yellow Pages’ section on hazardous substances, providing immediate information on hazardous properties, recommended control procedures and safety measures complete guide to labelling requirements to comply with EC directives and UK legislation, including the risk and safety phrases that must appear 0 chapter on electrical hazards 0 index to ‘Yellow Pages’ section, with synonyms of compounds 0 index to CAS Registry Numbers ISBN 0 85186 229 2 (1992) Price f45.00 If you have not yet ordered your copy of the NEW edition, do so now! Why take chances? Be informed and safe.5I To order, please contact: Telephone: +44 (0)462 672555 Fax: +44 (0)462 486947. 1350-4894C199411.1-9HAZARDS IN THE CHEMICAL LABORATORY Royal Society of Chemistry, Turpin Distribution Services Ltd, Blackhorse Road, Letchworth, Herts SG6 IHN, United Kingdom. CHEMISTRY Information Services II I 5th Edition ‘. . . easy to read, an excellent reference text, and a worthwhile investment .’ Journal of the American Chemical Society reviewing the 4th Edition. The new edition of this essential laboratory handbook is the ‘key’ requirement for all research, development, production, analytical and teaching laboratories worldwide. The 5th Edition provides: 0 a quick guide to the hazardous properties of 1339 substances (over 800 more than were covered in the previous edition) details of the latest UK and EC regulations an extremely useful emergency action check list - users can fill in their own key contacts for hospitals, fire etc.handy tables, symbols and statistics for ease of reference 0 a description of the American scene, including US legislation and safety practices - highlighting differences between the UWEC and USA PVC Protective Binding xx + 676 pages New features include: expanded ‘Yellow Pages’ section on hazardous substances, providing immediate information on hazardous properties, recommended control procedures and safety measures complete guide to labelling requirements to comply with EC directives and UK legislation, including the risk and safety phrases that must appear 0 chapter on electrical hazards 0 index to ‘Yellow Pages’ section, with synonyms of compounds 0 index to CAS Registry Numbers ISBN 0 85186 229 2 (1992) Price f45.00 If you have not yet ordered your copy of the NEW edition, do so now! Why take chances? Be informed and safe. 5I To order, please contact: Telephone: +44 (0)462 672555 Fax: +44 (0)462 486947. 1350-4894C199411.1-9
ISSN:1350-4894
DOI:10.1039/CO99401BX007
出版商:RSC
年代:1994
数据来源: RSC
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Catalytic applications of transition metals in organic synthesis |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 77-93
Graham J. Dawson,
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Catalytic applications of transition metals in organic synthesis GRAHAM J. DAWSON and JONATHAN M. J. WILLIAMS Department of Chemistry, Loughborough University of Technology, Loughborough, Leicestershire, LEI I 3TU, UK Reviewing the literature published between 1 July 1992 and 31 August 1993 1 2 2.1 2.2 2.3 2.4 2.5 3 3.1 3.2 3.3 3.4 4 4.1 4.2 4.3 4.4 5 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 6 6.1 6.2 7 7.1 7.2 7.3 7.4 7.5 7.6 8 9 Introduction Oxidation Oxidation of C-H bonds Dihydroxylation Epoxidation Aziridination 0 t her oxidations Hydrogenation and related processes Hydrogenation Hydroboration Hydrosilylation H y drof ormy lation Lewis acids Diels-Alder and related processes Aldol reactions Hydrocyanation and silylcyanation Other nucleophilic additions Coupling reactions Heck reactions Suzuki-type coupling Stille-type coupling Coupling reactions of other nucleophiles Carbometallation Reactions involving alkynes Hydroxycarbonylation and alkoxycarbonylation Allylic substitution Tandem and cascade processes Reactions involving metal carbenoids C y clo propanation Insertion reactions Miscellaneous Acetalization Thioether formation Conjugate addition Ring fusion and expansion Metathesis Isomerizations Conclusion References 1 Introduction This review highlights significant advances in transition metal catalysis during the period 1 July 1992 to 31 August 1993.The growing body of information in the area enables predictions to be made about the chemoselectivity and stereoselectivity of many homogeneous transition metal catalysts for particular substrates.There has been such a huge volume of publications concerned with transition metal catalysts that it is not possible to provide a comprehensive account. However, we have endeavoured to summarize current areas of interest and to provide commentary on the important advances. Only homogeneous applications have been considered for this review. 2 Oxidation 2.1 Oxidation of C-H bonds The direct oxidation of alkanes by catalysis continues to attract attention. Hirobe and co-workers have reported the oxidation of methylcyclohexane 1 into 1 -methylcyclohexanol3 using 2,6-dichloropyridine N-oxide 2 and a ruthenium porphyrin catalyst.' 1 -0 2 (0.5 mot%) nzene, r.t.. 6h 94% 3 Similarly, Murahashi and co-workers have detailed the ruthenium-catalysed a-methoxylation of tertiary amines2 and also the direct oxidation of alkanes to alcohols and ketones3 Thus, treatment of dimethylaniline 4 with 30% hydrogen peroxide solution and a ruthenium catalyst in methanol afforded the methoxymethylamine 5 .Murahashi and co-workers have also reported the oxidation of alkanes using molecular oxygen in the presence of catalytic copper salts.4 Da wson and Williams: Catalytic applications of transition metals in organic synthesis 77Me Me (DHQD),PHAL ligand. However, in the presence of I 2eq H202 a 4 the achiral catalyst quinuclidine, tetra-substituted alkenes are the most reactive category of alkene. o N \ M e RuCb.nH20 MeOH. r.t., (5 ml%T 2h u k H 2 O M e 67Yo R<R/== R- - 4 5 2.2 Dihydroxylation The asymmetric osmium-catalysed dihydroxylation of alkenes has recently been reviewed.' Crystal structures and synthetic details of the cinchona alkaloids used as ligands for this reaction have appeared? Sharpless and co-workers have demonstrated many synthetic applications of the dihydroxylation process using the commercially available AD-mix-a and AD-mix-/? reagents.[These mixtures contain K,Fe( CN),, K,CO,, K,OsO,(OH),, and either (DHQ),PHAL 6 (for AD-mix-a) or (DHQD),-PHAL 7 (for AD-&-/?).'] For example, the dihydroxylation of enol ether 8 affords a-hydroxy ketone 9,7 and the dihydroxylation of /?, y-unsaturated ester 10 affords the hydroxy lactone 1 1 .8,y 9 (97% e.e.) AD-Mk6 n 10 11 (98% e.e.) There have been numerous reports of other synthetic applications both by the group of Sharpless and by others.Fine-tuning of the ligand has been achieved to accommodate the enantioselective dihydroxylation of cis-disubstituted alkenes using the indolinyl ligand 1 2.1° Similarly, the pyrimidine ligand 13 has been used for improved enantioselectivity in asymmetric dihydroxylations of terminal alkenes.' Dh I ox 12 6 (X=DHQ) 7 (X=DHQD) Ph 13 Dihydroxylation of non-symmetrical dienes'* and rate studies on different categories of olefin have revealed a reactivity hierarchy, as illustrated in Scheme 1 .13 The anomalous position of the tetra-substituted olefin is a consequence of the steric demands of the Scheme 1 The kinetic resolution of alkenes which already contain a chirality centre has been reported using the asymmetric dihydroxylation pro~ess.'~J 2.3 Epoxidation There has been a continued interest in the development of novel catalysts for epoxidation of alkenes. Catalysts which can operate with cheap oxidants and those which can provide asymmetric induction are particularly useful.Mukaiyama and co-workers have reported the oxidation of alkenes into epoxides with molecular oxygen, catalysed by a Co" complex, using propionaldehyde diethyl acetal as the reductant,', in an extension of previous reports employing aldehydes as the reductant.17 An asymmetric variant of this process has been reported using enantiomerically pure manganese complexes to achieve up to 84% e.e. in the epoxidation of alkenes.' Enantiomerically pure ruthenium catalysts have been employed to give 50-80% e.e. in the epoxidation of styrene with iodosylbenzene, but with low yields (12-38'/0).'~ Collman and co-workers have prepared threitol-strapped manganese porphyrins which are capable of catalysing epoxidation with up to 88% e.e.,O Deng and Jacobsen have used the ( salen)MnlI1 complex 14 as a catalyst for the epoxidation of (2)-ethyl cinnamate 15 to give the product 16 with very high enantioselectivity.Treatment with ammonia afforded the ring-opened amide 17 which was readily converted into 18, the side chain of taxol.,' NaOCI, 14 (6 mI%) 4-phenylpyridine-N -oxide ph Ph=CO,Et 16 I 15 (0.25eq) 95-879h.e. 56% 18 17 H Q H 'But 14 But' 78 Contemporary Organic SynthesisAdam and Nestler have developed an interesting titanium-catalysed epoxy-hydroxylation of allylic a l ~ o h o l s . ~ ~ , ~ ~ Photo-oxygenation of the ally1 alcohol 19 affords a 90: 10 mixture of the diastereomeric hydroperoxy homoallylic alcohols 20 and 2 1.19 However, upon treatment with catalytic amounts of titanium tetraisopropoxide, the major diastereomer 20 rearranges more quickly to the epoxy diol products 22 and 23 (95 : 5) than the minor diastereomer 2 1 does to the alternative epoxy diols 24 and 25. 20 22 955 23 ?" 21 24 95:5 25 2.4 Aziridination Transition metal catalysed aziridination of alkenes has been known for several years. However, the recent demonstration of the ability of Cu' or Cu" salts to catalyse aziridination of alkenes with [ N-( p-toluenesulfonyl)imino] phenyliodinane, PhI = N T s , ~ ~ has led to reports of asymmetric variants of this reaction by the groups of Evans and Jacobsen.Evans and co-workers report the use of the bis(oxazo1ine) ligands 26 in the presence of a copper catalyst and the cinnamate 27 with PhI = NTs, to afford the aziridine 28 with excellent enantioselectivity (97% e.e.).25 Jacobsen and co-workers report that whilst salen ligands were found to afford poor results, the diimine ligand 29 was effective for providing asymmetric aziridination under conditions similar to those used by Evans. ph&co2Ph 6 mot% CuOTf, PhI=NTS. Ts I * ph&co2Ph 6 mot% CuOTf, 27 benzene,' 21 oc 28 (97%e.e. 64%) For the chromene 30, asymmetric induction in the product 3 1 was very high ( > 98°h).26 However, not all of the substrates examined by these groups gave such high levels of enantioselectivity. Furthermore, Katsuki and co-workers have reported that the use of enantiomerically pure (salen)manganese( 111) complexes for asymmetric aziridination gives moderate levels of enantioselectivity, but poor yields.27 NC 10 mol% CuOTf, PhI=NTS, CH&I2, r.t., 75% cyy NTs 30 31 (>98% e.e.) 2.5 Other oxidations Larsson and Akermark have reported a catalytic system for allylic acetoxylation. Cyclohexene 32 is oxidized to cyclohexenyl acetate 33 in the presence of catalytic palladium acetate and ferric nitrate in acetic acid under an atmosphere of oxygen.28 Pd(0AC)z (5 mop/.) L Fe(N0&9H20 (5 mot%) AcOH, 0 2 32 OAC 33 (92%) Uemura and co-workers have shown that sulfides 34 may be catalytically converted into sulfoxides 35 using titanium tetraisopropoxide in the presence of (R)-BINOL { (R)-l,l'-bi-2-naphth01].~~ In an alternative procedure, Jacobsen and co-workers have used (sa1en)manganese complexes 14 to catalyse the asymmetric oxidation of sulfides (up to 68% e.e.).30 Ti(OPh4 (10 mot%) 0 s (R)-BINOL (2OmoW) I I 5 Ar0''Me Ar' 'Me 34 H20 2 eq., Bu'OOH 2eq.toluene. r.t., 1 h 35 (up to 73% e.e.) 3 Hydrogenation and related processes This section includes recent advances in catalytic hydrogenation, hydroboration, and hydrosilylation. Additionally, hydroformylation and silylformylation are described here. 3.1 Hydrogenation Faller and Parr have demonstrated the use of chiral poisoning as a novel strategy for asymmetric ~ynthesis.~ Asymmetric rhodium-catalysed hydrogenation was chosen as the example. A mixture of [( S, S)-chiraphosRh] + and [( R, R)-chiraphosRh]+ was employed as the catalyst, and would be expected to afford racemic products in the hydrogenation of dimethylitaconate 36.However, in the presence of a chiral 'poison' 37, one enantiomer of catalyst is deactivated preferentially, and thus asymmetric induction is now observed in the product 38. Da wson and Williams: Catalytic applications of transition metals in organic synthesis 79RaOemiC LZ [(chiraphOsRh)d2*,H2 Z H NMe2 Z 38 (4me.e.) &OPPh2 MeS 36 37 Z = C02Me Phosphine-borane complexes provide a method for stabilizing phosphines to oxidation. A recent report describes the direct use of phosphine-borane complexes in asymmetric synthesis. The ( - )-DIOP-borane complex 39, upon treatment with [( COD)RhCl], and DABCO affords a catalyst which is competent for asymmetric hydrogenation reactions?* -6H3 39 Wang and Backvall have reported the ruthenium-catalysed hydrogenation of imines.Thus, the reaction between isopropanol and the imine 40 in the presence of ruthenium catalyst and base affords the amine 4 1 as the product.,, 41 (93%) 40 Whilst highly enantioselective hydrogenations of ketones and alkenes have been known for a long time, it is only recently that reports of highly enantioselective reductions of imines have been reported. Burk and Feaster have demonstrated the ability of rhodium DuPHOS complexes to catalyse the hydrogenation of N-aroylhydrazones 42 with the formation of product 43 in 72-97% e.eP4 Willoughby and Buchwald have employed enantiomerically pure titanocene complexes for the hydrogenation of imines 44 with the formation of product 45 in 53-98% e.e.35 H N/Ny I Cat; Rh(Et-DUPHOS)* b Et Ll Et‘ enantiomerically pure titanocene catalyst c P h 4 N H2 77%yield 44 H I 43 (88%e.e.) H 45 (9Phe.e.) The highly successful ruthenium-BINAP reagents introduced by Noyori and co-workers are now routinely employed for the asymmetric reduction of ketones and alkene~.,~ A recent development is the in situ formation of the catalyst.A methanolic solution of Ru( acac), and (S)-BINAP were treated with hydrogen at 1000 psi, followed by the introduction of the alkene 46. The product, ibuprofen 47 was formed with 88% e.e.37 46 47 (88%e.e.) Reagents: cat. Ru(aca& cat. (S)-BINAP, MeOH, lo00 p.s.i. H2 3.2 Hydroboration Investigations into the rhodium- and iridium-catalysed hydroboration of alkenes (Scheme 2) have been further documented, in terms of synthetic utility3* and mechani~m.~”~’ These papers effectively summarize and review the catalytic hydroboration process, and the reader is directed to these reports for further information.cat. Rho or Ir(1) kR Scheme 2 3.3 Hydrosilylation Asymmetric hydrosilylation of norbornenes4* and dihydr~furans~~ using an enantiomerically pure palladium catalyst has been reported to give hydrosilylation products of up to 96% e.e. Treatment of norbornene 48 with trichlorosilane in the presence of a palladium catalyst and the enantiomerically pure ligand 49 affords the product 50 with very high enantiocontrol. Lb 48 49 50 (up to 9 6 % ~ ) Ito and co-workers have employed an intramolecular palladium-catalysed bis-silylation of alkenes as a route to polyol ~ynthesis.4~ The reaction of the alkyne 5 1 with catalytic palladium acetate and isocyanide 52 affords the bis-silylated adduct 53 in 85% yield.Hydrogenation and oxidation leads to the formation of 1,2,4-triols 54.45 The palladium-catalysed dimerization/double silylation of 1,3-dienes under ambient conditions has been reported. The reaction of disilane 55 with diene 56 in the presence of a palladium catalyst affords the product 57 in a remarkable 85% 80 Contemporary Organic Synthesismsi.Me Ph-CEC Me3si5=u Ph 51 Ph HKoH . ._ 54 Reagents: Pd(OAc), (0.7-2 md%), Me3CCH,C(Me),NC 52(0.1-0.3equiv), toluene,ll 1 OC 2h Me,Si-SiM+ 55 56 5mt% Pd(dbah DMF r.t. 40h SiMe, Me,Si Me 57 (85%) 3.4 Hydroformylation Totland and Alper have investigated the hydroformylation of vinyl sulfones and vinyl sulfoxides catalysed by the zwitterionic rhodium compkx 58.47 The reaction of ethyl vinyl sulfone 59 with carbon monoxide and hydrogen using catalytic 58 and dppb affords exclusively the branched chain product 60 in 98% yield.CHO MeAS02Et 60 (98%) @S02Et c 59 Reagents: COW2 (600 psi), cat. dppb, CH2C12, 75 OC, Takaya and co-workers have reported an enantioselective rhodium-catalysed hydroformylation of olefins.48 Recent reports of silylformylation of aldehydes and e p o ~ i d e s ~ ~ have appeared. Wright and Cochran have shown that treatment of aldehydes 6 1 with dimethylphenylsilane in the presence of catalytic amounts of [( COD)RhCl], affords the corresponding a-silyloxy aldehydes 62 in 60-90% yield.50 OSiPhMe2 c Ar ArACHO 61 62 Reagents: Me,PhSiH, [(COD)RhClh, (0.5 mot%) CO (250psi), 23 OC, 24 h, THF 6040% 4 Lewisacids Transition metal reagents such as titanium tetrachloride have been familiar Lewis acids for a long time. However, there is a growing tendency to exploit the properties of the later transition metals as Lewis acids, since advantages in terms of catalytic turnover and ligand design may be afforded.4.1 Diels-Alder and related processes Kobayashi and co-workers have reported the use of scandium trifluoromethylsulfonate as a reusable catalyst for the Diels-Alder reaction.51 For example, the reaction of isoprene with methyl vinyl ketone afforded the Diels-Alder adduct 63 in 91% yield using scandium trifluormethylsulfonate as a catalyst.0 SC(OTf), (10 ~ o K ) L' CH2CI2 91 ,O"C, 46 13h * Other examples of transition metal catalysed Diels-Alder reactions include reactions mediated by the ruthenium catalyst 64,52 developed by Bosnich and co-workers, and the polymer-bound, iron-based Lewis acid catalyst 65.53 64 65 Evans and co-workers have prepared enantiomerically pure bis( oxazoline) ligands 66 for use in copper( 11) triflate catalysed Diels-Alder reactions.54 High levels of enantioselectivity were reported for the catalysed reaction between cyclopentadiene and oxazolidinone 67 to afford the Diels-Alder adduct 68. 68 (>98% 8.8. 98:2 endo:exo ) Reagents: 5mol% Cu(OTf)z, CH2C12, -78 "C, 18h Further advances in the use of enantiomerically pure titanium catalysts for the carbonyl-ene reaction have been described.55 Mikami and co-workers have demonstrated an asymmetric desymmetrization of 69 into 70, catalysed by a chiral titanium complex previously developed by this obtained with very high enantioselectivity and very high diastereoselectivity. Interestingly, the reaction of the silyl enol ether 7 1 with methyl glyoxylate and the same catalyst affords the ene-type product 72, rather than a Mukaiyama The product was Da wson and Williams: Catalytic applications of transition metals in organic synthesis 81aldol reaction.Furthermore, remarkably high enantioselectivity and diastereoselectivity is obtained in the aldol-like product.57 o'SiR3 (18 (BINOL)TiCI2 (10 MS ml%) 4h. -@m&le n CH&I* 0 "c -\ 0 27% SIR3 099% syn HKCOIMe 70 >99% 9.9.) OSiMe, 0 + HKC02Me 71 (5 ml%) 58% Me3SiO OH +CO2k Me 72 (982syn:anti 94:6 Z:E 99% e.e.) 4.2 Aldol reactions As well as the highly stereoselective example cited above, more conventional Mukaiyama aldol reactions have recently been reported to be catalysed by scandium trifluor~methanesulfonate,~~ ruthenium catalysts 64,59 mercuric iodide,6O the titanium and zirconium catalysts 73 and 7461 and also the unusual binuclear iron complex 75,62 which offers the possibility of bis-coordination to the carbonyl substrate.ChTi(OTf)2 73 CpzZr(0Tf)ZMF oc-,i.: ;B., oc PPh2 Ph2P' \,go u 74 75 4.3 Hydrocyanation and silylcyanation Faller has used the unusual tungsten complex 76 as a Lewis acid precursor. Upon loss of CO, a potent Lewis acid is formed, which catalyses the addition of trimethylsilyl cyanide to aldeh~des.6~ Asymmetric trimethylsilylcyanation of aldehydes has been achieved with the titanium based catalysts 77,h4 78,6s and 79.66 Inoue has exploited titanium complexes of the peptide 80 as catalysts for the asymmetric addition of hydrogen cyanide to aldeh~des.6~ In the case of a, 6-alkenyl aldehydes 81, the product cyanohydrin 82 was acetylated, treated with catalytic bis( acet0nitrile)palladium dichloride, and hydrolysed to afford the rearranged product 83.6* 79 83 09%e.e.Reagents: (i) Ti(OEt), (10 md%); (ii) A%O, C H N; (iii) 10 I ~ ~ % P ~ C I ~ ( C H ~ C N ) ~ THF;'(ii hydrolysis 4.4 Other nucleophilic additions Nuss and Rennels have employed cationic iridium and rhodium catalysts for the addition of allyltributyltin 84 to aldehydes 85 to afford the homoallylic alcohols 86.69 In the presence of enantiomerically pure catalysts, a small but promising degree of asymmetric induction was observed.m S n B u 3 / 84 + cat. Ir( CO) (PPh&J304 L 01 cat. Rh(CO)(PPh&CD4 R CH&IZ 3147% 86 R J L 05 Shibuya and co-workers have devised an enantioselective hydrophosphonylation of aldehydes 87 which uses diethylphosphonate 88 and a titanium catalyst 78 to afford a-hydroxyphosphonates 89.'O Whilst the enantioselectivities reported are modest (up to 53% e.e.), there is potential for the improvement of this process. OH O H, 7b (20mo1%) AH + 0°C 15h Etfl Ar A P(OEt)2 Ar r\ 0 87 88 89 " 82 Contemporary Organic Synthesis5 Coupling reactions This large section contains a multitude of reactions which are often identified as coupling reactions. Many of these catalysed processes involve the formation of new C-C bonds, and are therefore of great synthetic utility.Only representative examples have been chosen for this section due to the enormous amount of research activity in the area. 5.1 Heck reactions Busacca and co-workers have developed an interesting new vinylamine equivalent for use in the Heck rea~tion.~' Heck reaction between aryl iodides and the vinyloxazolone 90 affords the Heck adducts 9 1. Hydrogenation affords the corresponding phenethylamines 92. 0 P N K O pd(oAC)2 (4 k e ~ 1 H0 )=( N~HCO~, BU,NCI ArI DMF Ph 9o Ph Ph Ph /P: EtOH, HOAc H2 50 psi I\r/\/NH2 92 Another application of the Heck reaction is in the arylation of 4H- 1,3-dioxin 93.72 The arylated product 94 can be converted into cinnamaldehydes 95 upon heating ( via a retro Diels-Alder reaction).Cat. Pd(OAc)z, PPh3 0 AgS03,DMF ArI 60°C * Ar 4745% 94 93 toluene reflw 95 An interesting example of a palladium-catalysed reaction between cyclopentenylzific chloride 96 and diiodobiphenyl97 affords the cyclization product 98.73 The reaction is believed to proceed via the coupled intermediate 99, which is able to undergo an intramolecular Heck reaction. 97 McClure and Danishefsky have reported an intramolecular Heck reaction on the highly functionalized substrate 100 to afford the cyclized product 101, showing the remarkable chemoselectivity afforded by the Heck arylation reaction.74 100 cat. Pd(PPh& EtjN, MeCN 80% loh 1 101 (90%) Asymmetric Heck reactions may be achieved for certain substrates.The use of a palladium BINAP complex as a catalyst for the reaction between dihydrofuran and the alkenyl triflate 102 affords the product 103 in 62% yield and with > 96% e.e.75 ,COPE1 0 ''OTf 102 (R-BINAP)zPd (3 mot%) Proton sponge benzene 6246 1 CO2Et 06 103 (~96% e.e.) Hillers and Reiser have demonstrated that the enantioselectivity and regioselectivity of related reactions are pressure dependent.76 Ashimori and Overman have reported the asymmetric Heck cyclization of the aryl iodide 104.77 Using a palladium BINAP catalyst in the presence of a silver salt, they obtain the product 105 with up to 7 1% e.e. However, in the presence of 1 ,2,2,6,6-pentamethy1piperidine7 and the absence of silver salts, the other enantiomer of the cyclization product is obtained with 66% e.e.! 5.2 Suzuki-type coupling The coupling of boron compounds with organic halides is frequently called the Suzuki coupling.The reaction is also effective using organic triflates as one of the coupling partners.78 Soderquist and Rane have reported a synthesis of ( + )-exo-brevicomin 109 which relies upon a Suzuki coupling followed by an osmium-catalysed asymmetric dihydr~xylation.~~ Da wson and Williams: Catalytic applications of transition metals in organic synthesis 830 1 81% t 0 105 (71%e.e.) Reagents: Pd,(dba), (5 md%),R-(+)BINAP (10 mol%), 1-2eq. Ag3P04, MeCONMe2, 80 "C, 26h Coupling of the borane 106 with (E)-1-bromobut-1-ene affords the isomerically pure alkene 107.Asymmetric dihydroxylation affords the diol 108 which is readily cyclized to 109. L L 106 107 (85%) I E&D,BPHAL reductive coupling of acid chlorides 1 14 with (E)-1,2-bis( tri-n-butylstanny1)ethene 115. Thus, in order to produce these diketones, the alkene has been reduced under the reaction 112 I 110 I cat. Pd(0) F A r 111 Nicolaou and co-workers have reported an exciting example of the use of the Stille coupling for the last step in the total synthesis of the macrocycle rapamycin 1 16 from the acyclic precursor 1 17 and (E)-1,2-bis(tri-n-butylstannyl)ethene 1 15.82b This remarkable cyclization process demonstrates the chemoselectivity of reactions of this type. 5.3 Stille-type coupling Mitchell has recently reviewed the palladium-catalysed reactions of organotin compounds.81 The Stille reaction has been widely exploited recently, and only a tiny selection of such applications can be reported here.Eschavarren and co-workers have prepared 1,4-diketones 1 13 by the palladium-catalysed 114 + mMe 108 (96?/0, 95%e.e.) Whiting and co-workers have examined the reaction of the vinylborate ester 110 with aryl iodides in the presence of a palladium catalyst.80 There are two possible outcomes and either the Suzuki product 1 11 or the Heck product 112 could be obtained. The Heck product appears to be kinetically preferred, although minor changes in conditions affected the product ratio. Me., 117 t mMe Reagents: 115 (1.2eq.), Pr',EtN (1.5eq.), Pd(MeCN)&I2 (20 mol%), DMF/THF (1:1), 25 "C, 24h Moriarty and Epa have demonstrated that alkenyl iodonium salts are reactive components for the Stille coupling.83 Thus, the reaction between the iodonium salt 1 18 and tributylvinyltin 119 affords the coupled product 120 in 5 minutes at room temperature using bis( acetonitri1e)palladium dichloride as catalyst.Vedejs and co-workers have demonstrated that tin reagents 12 1 are unusually reactive in the Stille coupling, and can be used for the selective transfer of primary alkyl groups.84 84 Contemporary Organic SynthesisPh A;, Ph P s n B u , 118 Pd(MeCN)&Iz (5 d%) Ph& m + 5min r.t. 78% 120 5.4 Coupling reactions of other nucleophiles Apart from the use of boron and tin reagents for coupling reactions, other reagents can be employed, including Grignard reagents, organozincs, and other organometallic species.Snieckus and co-workers have employed nickel catalysis for the reaction between arylcarbamates or aryl triflates and Grignard are reported, including the nickel-catalysed coupling of the carbamate 122 with Grignard reagent 123 which affords the coupled product 124 in 83% yield. Many examples awmEt2 TMSCHAgCI Ni(acac)z (5 ml%) 7 EtzO, rl., 83% z - 122 Z= Et&JOC 124 Kocienski and co-workers have shown that the nickel-catalysed coupling of Grignard reagents with 5-alkyl-2,3-dihydrofrans is also effective.86 Thus, the reaction of 125 in the presence of catalytic (Ph,P),NiCl, and phenyl magnesium bromide affords homoallylic alcohol 126 as the product with 96% isomeric purity. One recent application of the cross-coupling of organozinc reagents has been reported by Negishi and co-worker~.~~ Treatment of the vinyl iodide 127 with ethylzinc bromide afforded a zinc alkoxide which could then be coupled with another alkylzinc halide using palladium catalysts to generate the product 128.4347% Me*OH R 1 27 128 Larock and co-workers have reported the coupling of aryl and vinyl halides or triflates with vinylic epoxides,88 vinylic oxetanes,89 and vinylic azetidinones.’O 5.5 Carbometallation Hoveyda and co-workers have continued a study of the zirconium-catalysed ethylmagnesation of alkenes. The reaction of ally1 alcohol 129 with four equivalents of ethylmagnesium chloride and 5 mol% of Cp,ZrCl, affords the intermediate 130, which upon treatment with oxygen affords the dioll31 with 90% d.e.” OH EtMgCl(4 eq.) Et@ Et n-nonyl Et 131 (90%d.e.70%) Conversion of the aUylic alcohol into the corresponding methyl ether affords the alternative diastereomer as the major product (78% d.e.). Furthermore, the use of enantiomerically pure zirconocene catalysts leads to highly enantioselective reactions.Y2 Knochel and co-workers have reported a novel palladium-catalysed intramolecular carbozincation of alkene~.~, The reaction of 132 with diethylzinc and 1.5 mol% of PdCl,( dppf) gives the cyclized organozinc species 133. Transmetallation with CuCN-2LiCl and trapping with benzoyl chloride affords the functionalized cyclopentane 134 in 76% yield. Ph 133 132 / (i)CuCN.PLiCI / (ii)PhCOCI Ph . .. mPh 134 (76%) 5.6 Reactions involving alkynes Ogawa, Sonoda, and co-workers have reported the palladium acetate catalysed addition of aromatic thiols 13594 and benzeneselenol 1369s to acetylenes 137 to give the products 138 and 139.In neither case was the catalyst poisoned by the reagent. 138 X = S 139 X=Se The palladium-catalysed thioboration of terminal alkynes has also been reported.Y6 Thus, treatment of pent-1-yne 140 with 9-(phenylthio)-9-BBN 141 affords the intermediate 142, which can be converted in situ, by addition of iodobenzene, into the coupled product 143 in 95% yield with 99% isomeric purity. + PhSBBN 141 /A&;: K3P04, DMF C3H7 PhS *Ph 143 (95%) Da wson and William: Catalytic applications of transition metals in organic synthesis 85Dixneuf and co-workers have investigated the stereoselective addition of carboxylic acids to alkynesg7 They have also reported that in the presence of the binuclear catalyst precursor [Ru(p-O,CH)(CO),(PPh,)],, hexyne 144 and mandelic acid 145 are converted into the 1,3-dioxolan-4-one 146.98 toluene 100 “c 144 Ph’ 145 146 (9O:lO cis.mns 86%) Kita and co-workers have shown that whilst standard catalysts for the addition of carboxylic acids to alkynes are ineffective in the case of alkoxyalkynes, catalytic amounts of [RuCl,( p-cymene)], were effective for the addition of various carboxylic acids 147 to ethoxyacetylene 148, thereby affording ethoxyvinyl ester 149.” 148 toluene 40 “C 15min 6044% 147 - 1 49 Nuss and co-workers have reported the palladium-catalysed reaction between di-iodoenyne 150 and five equivalents of the alkynyl stannane 15 1 to afford the product 152 in 32% yield, in which three new C-C bonds have been formed.I Bu3Sn+CHflTBDMS HO 161 r C H 2 0 m D M S Larock, Cacchi, and co-workers have exploited palladium catalysts for the formation of furans.lOO Reaction of the alkyne 153 with iodobenzene in the presence of a palladium catalyst directly affords the furan 154 in 57% yield. Meh, M e 2mol%Pd(PPb)4 K2CQ PhI (2 eq.) (3 eq.1 ~ Me& Me Ph 0 DMF 60 “C, 6h 153 154 (57%) Trost and Indolese have reported the novel ruthenium-catalysed addition of alkenes to alkynes.lO’ Thus, the reaction of oct-l-ene 155 and oct-l-yne 156 with a ruthenium catalyst afforded a 69% yield of the branched diene 157 and the linear diene 15 8 (157 : 158,5 : 1). Trost and co-workers have further documented the use of the ruthenium-catalysed ‘reconstitutive condensation’ of acetylenes 159 with ally1 alcohols 160 to afford the ketone 16 1.Evidence has been presented to support the proposed mechanism for the catalytic cycle.102 Applications to the functionalization of steroidal side chains have been reported. lo3 155 CpRu(C0O)CI (5 ml%) DMFH20 (3:l) 100°C. 2h, 69% I 157 5:l 158 doH cat. CpRu(PPh&CI NHQF6 100 “c neat R E + 159 160 161 5.7 Hydroxycarbonylation and alkoxycarbonylation An interesting approach to a-amino perfluoroalkanoic acids has been designed by Uneyama and co-workers. lo4 Palladium-catalysed carbonylation of the imidoyl iodide 162 in the presence of benzyl alcohol affords the corresponding a-imino ester 163, with further transformation giving the a-amino acid 164.163 164 Reagents: CO(latm), Pdp(dba)3CHC13, PhCH20H, K2C03, toluene Ali and Alper have reported a highly regioselective catalytic process for the hydrocarboxylation of methylenecy~loalkanes.~~~ The reaction of methylenecyclohexane 165 with two equivalents of formic acid in the presence of catalytic amounts of 1,4-bis( dipheny1phosphino)butane and palladium acetate under 6.8 atmospheres of carbon monoxide afforded the product 166 in 94% yield. The choice of ligand was crucial for high yields of product. Pd(0Ac)z (2 mol%) dppb (4 mol%) HC02H. 6.8 afrn CO DME 150 “c 1 65 166 (94%) 86 Contemporary Organic SynthesisAlkoxycarbonylation can be achieved using chloroformates as the coupling partner. We are reminded of this in the conversion of the stannylfuran 167 into the corresponding ester 168, which occurs upon treatment with chloroformate 169 under palladium catalysis.lo6 Wang and Alper have reported an unusual rearrangement reaction to afford lactam products.lo7 Treatment of the ketone 170 with catalytic amounts of Co,(CO), and Ru,(CO),, affords the rearranged product 17 1 in 72% yield. 170 171 (72%) O'Connor and Ma have described a useful method for the metal-catalysed decarbonylation of aldehydes 172 into alkanes 173 at room temperature.los The method relies upon the presence of stoichiometric amounts of diphenylphosphoryl azide 174, which prevents the rhodium catalyst from forming inactive carbonyl complexes. 0 phoxF, -t- RCH2CHO cat. Rh(PPh3)CI RCH3 THF r.t. 90-9996 173 PhO' N3 172 1 74 (slow addition) 5.8 Allylic substitution The majority of research in the area of catalysed allylic substitutions is currently centred around palladium catalysis, and has recently been reviewed.loY has been used for the selective 1,4-opening of vinyl epoxides.O Trimethylsilyl cyanide successfully delivers cyanide as a nucleophile in palladium-catalysed allylic substitution.' Tamaru and co-workers have employed cyclic carbonates 175 as substrates.' By using isocyanates as the incoming nucleophiles, a highly regioselective amination occurs by pre-coordination of the nucleophile to give the product 176. For other nucleophiles, the regiochemistry would be expected to involve nucleophilic addition to the less sterically encumbered allyl terminus. ' The use of triphenylsilanol as an oxygen nucleophile Pd(PPh&(2fn01%) TsNCO dbxane 'yo f75 r.t.l l h 0 176 (80%) Palladium-catalysed azidation of 1-alkenylcyclopropyl tosylate 177 affords the azide substituted product 178 with the indicated regiochemistry.' l4 Functional group manipulation affords 2,3-methanoamino acid 179. 177 M-F 79% 178 1 79 Genet and co-workers have reported the use of N, 0-bis-t-Boc protected hydroxylamine 180 as a nucleophile for palladium-catalysed allylic substitution.115 Thus the allyl carbonate 181 is converted into the substitution product 182, which is further transformed into ( + )- N6-hydroxylysine 183. HNZBoc OBoc 180 183 The use of palladium acetate or palladium acetylacetonoate in combination with tributyl phosphine has been recommended as a particularly active catalyst,l16 and has been used in the introduction of exocyclic methylene groups.For example, myrtenyl formate 184 selectively affords /3-pinene 185 upon treatment with this catalyst.li7 (OCHO II 184 i as Three groups have reported the use of the ligand 186 for enantioselective palladium-catalysed allylic substitution.' l8-I2O This ligand provides higher enantioselectivities than previous ligands for some reactions. For example, the reaction of allyl acetate 187 with dimethylmalonate affords the allylic substitution product 188 with up to 99% e.e. These, and related ligands appear to rely upon a disparity in the electronic/steric properties of the two donor atoms.12 palladium-catalysed allylic substitution in the synthesis of aminocyclopentitol glycosidase inhibitors.22 They are pursuing asymmetric variants of these syntheses Trost and Van Vranken report the use of Dawson and Williams: Catalytic applications of transition metals in organic synthesis 87188 (up to 99% 8.8. up to 99%) Reagents: [Pd(q3-C3H&q2 (1 mol%). KOAc,BSA (2 mdo/), H2C(C02Me)2. CH2Clp. 23 "C using highly effective ligands exemplified by structures 189 and 190.'23J24 190 Backvall's group has demonstrated the synthetic power of the palladium-catalysed 1,4-0xidation of conjugated dienes, a reaction which also proceeds via n-allylpalladium intermediates.' 25 A recent development has been the use of tethered nucleophiles which are able to add to both ends of the diene. For example, the reaction of the dienamide 191 with catalytic palladium acetate and excess cupric chloride using oxygen as the primary oxidant afforded the pyrrolizidinone 192 in 90% yield.191 192 3 5.9 Tandem and cascade processes There are a growing number of tandem and cascade processes being reported wherein the catalyst triggers a series of reactions on one molecule. The various components of these reactions are familiar catalytic reactions, such as those that we have seen in the preceding sections. Grigg's research group has accessed various polycyclic structures by identlfylng various 'starter components' for catalytic cascade reactions. For example, the reaction of benzylic bromide 193 with norbornene 194 affords the cyclized product 195.12'j Intermediate palladium alkyl species can also be trapped by hydride ion capture127 or cyanide ion capture.28 have both reported palladium-catalysed tandem reactions as an entry into vitamin D derivatives. Thus, Nuss and co-workers have shown that the palladium-catalysed reaction between the vinyl bromide 196 and the vinyl stannane 197 afforded the cyclized and coupled product 198, which is in equilibrium with 199 via a [l, 71 H shift. The research groups of Nuss129 and 195 Z:E 2:l Reagents: Pd(OAc), (10 md%), PPhs(20 moWo), 2eq. K2C03, EtNCI (leq.), CsHs, 80 "C, 18h. 6 Reactions involving metal carbenoids Whilst many transition metals are believed to catalyse reactions which proceed via intermediate carbenes or carbenoids, the majority of work has been centred around rhodium- and copper-catalysed reactions. The behaviour and chemoselectivity of these carbenoids are becoming more well under~tood.'~~ There are increasingly complex cascade reactions which begin with metal carbenoids and lead to polycyclic products.' 32 6.1 Cyclopropanation Katsuki and co-workers have reported the use of bipyridine ligands for copper-catalysed asymmetric cyclopropanation.33, 34 Cyclopropanation of styrene 200 with t-butyl diazoacetate 201 in the presence of catalytic copper triflate and the ligand 202 afforded the trans cyclopropane 203 selectivity with 92% e.e. 203 (86:14 trans:cis 92Vl.0. 75%) N2CHC02But 0 9 SiM% Me&I 201 2Q2 Enantioselective intramolecular cyclopropanations have also been reported with enantiomerically pure copper*35 and rhodium136 catalysts. Enantiomerically pure polyethylene-bound rhodium( 11) complexes have also been developed, and are especially efficient for enantioselective intramolecular cyclopr~panations.~ 37 8 8 Contemporary Organic SynthesisNot all metal-catalysed cyclopropanation reactions proceed via carbenes.Murai and co-workers have reported the palladium-catalysed reaction of ketone a-carbonates 204 with norbornenes 205 to afford cyclopropane products 206.138 The reaction is believed to proceed via an oxa-n-allylpalladium intermediate rather than via a palladium carbene. 0 Me I1 204 0 Pd(PPh,)4(10mol%) + toluene, reflux 144h * 205 74% V 206 6.2 Insertion reactions Clark has shown that Cu( acac), is superior to Rh,(OAc), for the conversion of 207 into 208.13' The mechanism is suggested to occur through a metal bound oxonium ylide 209, since variation in the catalyst results in differing levels of diastereoselectivity in the product. Reactions involving the corresponding ammonium ylide have been reported by West and Naidu.140 Thus cyclization of 2 10 in the presence of catalytic rhodium(I1) acetate affords the intermediate 2 11, which undergoes a Stevens [ 1,2] shift to afford the piperidine 2 12 in 99% yield.Alternative C-H insertion reactions were not observed. P h , , r 4 210 N2 R~AOAC)~ (3 ml%) CHSl2, r.t. I 21 1 Me 212 Padwa and Kinder have reported the rhodium(~r) acetate catalysed formation of substituted fur an^.'^^ Treatment of the diazo precursor 2 13 affords the bicyclized product 2 14 in 76% yield. A range of similar cyclizations were also reported. Padwa's group has continued its investigations into tandem rhodium- catalysed cyclization/ 1,3-dipolar cycloaddition processes.142 In particular, an intramolecular system 2 15 has been reported to proceed via the intermediate 2 16 to afford the tetracyclic product 2 17 in 88% yield.143 213 21 4 - N2 21 5 cat.Rh2(OAc)4 benzene reflux I hgMe __c @Me H 217 (88%) 21 6 Moody and co-workers have reported the benefits of using rhodium( 11) trifluoroacetamide as a catalyst for O-H insertion rea~ti0ns.l~~ The diazobisphosphonate 2 18 afforded none of the desired O-H insertion product 2 19 in the presence of rhodium( 11) acetate. However, the use of rhodium( 11) trifluoroacetamide as the catalyst afforded an 8 1'/0 yield of product 2 19. 0 0 21 9 21 8 7 Miscellaneous This last section contains a pot-pourri of interesting reactions which do not readily fall into one of the major categories.In some cases, the difficulty of categorization is a reflection of the novelty of the reaction concerned. 7.1 Acetalization A diastereoselective palladium-catalysed acetalization of alkenes has been reported.145 The greatest diastereoselectivity was observed with the t-butyl substituted oxazolidinone 220. Treatment of 220 with methanol, palladium chloride catalyst, and stoichiometric cuprous chloride under an atmosphere of oxygen afforded the product 22 1 with 95% d.e. Da wson and Williams: Catalytic applications of transition metals in organic synthesis 89220 221 (89% 95% d-e.) 231 230 " 7.2 Thioether formation Bulman Page and co-workers have reported an unusual reaction involving the platinum-catalysed formation of thioethers from thiols and akyl halides.'46 For example, treatment of butane thiol, iodobutane, and sodium carbonate with a platinum catalyst affords dibutylsulfide 2 2 2 in 80% yield.BuSBu 222 BUSH (dpprn)PtCI, (5ml%) + Bul Na@3 80% - 7.3 Conjugate addition Tanaka and co-workers have developed the use of the ligand 223 for catalytic enantioselective conjugate addition. The reaction of 224 with methyllithium in the presence of 0.36 equivalents of the ligand 223 and 0.33 equivalents of copper iodide and 0.33 equivalents of THF afford the conjugate addition product, muscone 225 with 99% e.e.147 Such high levels of enantioselectivity hold great promise for reactions involving less catalyst. 225 (99% e.e.) 224 Ito and co-workers have employed the trans chelating ligand 226 for a rhodium-catalysed addition of a-cyan0 carboxylates to Michael acceptors.Thus the reaction between 227 and 228 in the presence of catalytic amounts of RhH(CO)(PPh,), and ligand 226 affords the addition product 229 with 87% e.e.148 H cat. RhH(CO)(PPh3)3 227 Nc$ OP+ Me 228 g e - Me' PPh2 226 H q O P 4 Me' CN 229 (88% 87% e.e.) 7.4 Ring fusion and expansion Huffman and Liebeskind have designed a novel intramolecular carbocyclic ring-fusion process.149 Treatment of 4-cyclopropyl-2-cyclobutenone 230 with 5 mol% RhCl(PPh,), affords the cycloheptadienone 231 in 84% yield. Iwasawa and Matsuo have reported the ring expansion of 1 -alkynylcyclopropanols 232 into cyclopentenones 233 on treatment with 10 molo/o Co,(CO), followed by 20 mol% P(OPh),.lS0 HOf' 232 R b 233 7.5 Metathesis The catalytic ring-closing of dienes has been pursued by Fu and Grubbs.lS1 For example, the reaction of the diene 234 in the presence of the catalyst 235 affords an 85% yield of pyrroline 236.235 benzene, 20 "C. 3h Me Me 234 236 7.6 Isomerizations It is well known that transition metals are able to isomerize alkenes. Particularly useful are the isomerizations of allyl a l ~ o h o l s ~ ~ ~ J ~ ~ and allyl amines, as these next examples illustrate. Mothenvell and Sandham have demonstrated the nickel-catalysed transformation of allylic alkoxides 237 into enolates, and their use in an aldol reaction with benzaldehyde to afford the aldol products 238 and 239.154 Ph 237 (i) cat. [Rh(dppe)lClO, or cat. 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ISSN:1350-4894
DOI:10.1039/CO9940100077
出版商:RSC
年代:1994
数据来源: RSC
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Saturated nitrogen heterocycles |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 95-111
John Steele,
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摘要:
Saturated nitrogen heterocycles Bn02C SO~CIZ TrNH-*.R OH JOHN STEELE m z e r Central Research, Sandwich, Kent CT13 9NJ, UK Tr Reviewing the literature published between January 1992 and May 1993 1 1.1 1.2 2 2.1 2.2 2.3 3 3.1 3.2 3.3 3.4 3.5 3.6 4 4.1 4.2 4.3 5 6 Three- and four-membered rings A zirid ine s Azetidines Five-membered rings with one nitrogen atom Pyrrolidines Pyrrolidinones Pyrrolizidines and related compounds Six-membered rings with one nitrogen atom Piperidines Tetrahydroisoquinolines and related compounds Indolizidines Quinolizidines Aza Diels-Alder reactions Piperidinones Rings with two or more nitrogen atoms Five-membered rings Six-membered rings Seven-membered rings Seven-, eight-, and nine-membered rings References 1 Three- and four-membered rings 1.1 Aziridines A useful new aziridination of alkenes has appeared.Thus, the N-arylhydroxamic acid 2 reacts efficiently with electron-deficient alkenes 1 to generate the functionalized aziridines 3. The mechanism of the transformation has not been fully resolved. 1 (EWG = Electron Withdrawing Group) 3 Two separate reports have described the utility of Payne-like rearrangements of aminomethyl oxiranes for aziridine synthesis. In the first of these,* the epoxide 5, prepared by straightforward mCPBA oxidation of the allylsulfonamide 4, rearranges in aqueous sodium hydroxide to afford the tosyl aziridine 6. Predictably, no product from the alternative 4-endo-tet cyclization mode is observed. In the second report, Vaultier and co-workers3 describe the trimethylaluminium-mediated rearrangement of the N-unsubstituted epoxy amines 7 into the aziridinemethanols 8 in good yield.3 An alanate complex is a proposed intermediate.4 5 6 (i) BuLi, AIMe3 R W N H Z PhMe, -80 "C c OH 0 (ii) NaF, H f l 7 8 The synthesis of homochiral aziridines has featured prominently in several publications. Thus, Berry and Craig have highlighted a simple but nonetheless effective reduction/ring closure sequence for conversion of the a-amino acids 9 into the chiral monosubstituted aziridines Yields are generally excellent. Continuing the 'chiral pool' theme, the trityl serine and threonine esters 11 [R = H, Me] are converted into the cyclic sulfamidates 12 using sulfuryl chloride and triethylamine. The sulfamidates 12 are inherently unstable and rearrange in situ to give the chiral aziridines 13.5 (i) LiAIH4 or BH, (ii) TsCI.DMAP N CHzCIz Ts NHTs 9 10 I- 1 L J 11 13 12 Finally, Fujisawa and his group6 have described remarkable metal-dependent diastereoselectivity in the condensation reactions of the chloroketene acetals 15 with the chiral imine 14. The lithium enolate 15, M = Li affords only the 2R, 3 s aziridine 16, whilst metal exchange to a zinc enolate 15, M = ZnCl generates only the 2S, 3 R isomer 17. Steele: Saturated nitrogen heterocycles 95F O B " ' " 15 B''osw R* (K Bub& 8w' R* N THF. -78 "c N H 14 I I A1 Ar 16 17 M = Li M = ZnCl Molina et al. have achieved a short and regioselective entry into the fused azirino[ 1,2-a]indole ring system 22 (Scheme 1).7 The method relies on generation of the intermediate iminophosporanes 19 from appropriate azide precursors 18, followed by cyclization to the betaines 20 which then rearrange to 2 1.Cyclization of 2 1 and concomitant elimination of phosphine oxide finally produces 22 in 45-95% yield. r 1 18 L 19 J \ R' R' "h- - Ph3PO 22 R2&06Ph3 1 21 Scheme 1 1.2 Azetidines Developments in the synthesis of /3-lactams will be reviewed in a separate article in this Journal. Toda and co-workers8 have exploited the efficient aminolysis of the epibromohydrin derivatives 23 to prepare homochiral3-hydroxyazetidines like 24. RNH, R' P h L 0 MeOH, 20 "C - 23 24 The benzhydryl azetidine-2-carboxylate 27 is a key intermediate in the synthesis of the oxazaborolidine catalyst 28 and, in a new twist to some standard chemistry, this intermediate has been prepared by bis-alkylation of benzhydrylamine 26 with the dibromobutyrate 25 under microwave irradiation." The use of microwaves shortened the reaction time from 24 hours to 15 minutes and enhanced the yield considerably.Ph Ph 26 Br+fco2Bn Br MeCN )-w hv, Microwave H 28 2 Five-membered rings with one nitrogen atom 2.1 Pyrrolidines The intramolecular addition of nitrogen to double and triple bonds continues to extend the scope of available pyrrolidine syntheses. As part of a chirospecific synthesis of pyrrolizidines, Takahata and Momoselo have exploited a selective amidomecuration of the terminal alkene in 29 to generate the trans-2,5-disubstituted species 30. Demercuration then affords the prolinol3 1. Cbz 29 30 n 31 By contrast, butyllithium-mediated cyclization of the secondary amines 32 is remarkably selective in favour of the cis-2,5-disubstituted pyrrolidine products 33.l' The reaction proceeds optimally in the presence of only a catalytic amount of alkyllithium.BuLi -78 "C Me 32 33 The intramolecular addition of azide to double bonds is a well established route to pyrrolidines, and Pearson et al. have now used the procedure in a concise synthesis of racemic y-lycorane 36.'* Thus, thermolysis of the azide 34 first generated the transient iminium ion 35 which was reduced selectively in situ to generate lycorane 36 (Scheme 2). 96 Contemporary Organic Synthesisr 1 (i) Cpgr(1-butene) 47 (ii) CO (iii) HCI N3 R 0 I CI 34 35 n 36 Scheme 2 With suitable catalysis, amines will also add readily to sp-centres.Livinghouse and his colleagues have described the titanium-catalysed cyclization of the acetylenic amine 37 via a formal [2 + 21 cycloaddition of a metalloimine complex, generating the intermediate metallacycle 38. Aqueous hydrolysis of 38 then liberates the A'-pyrroline 39 in excellent yield.I3 37 38 39 Moving from N-C to C-C bond forming reactions, Livinghouse et al. have also prepared more-functionalized pyrrolines using the cyclization of acyliminium ions. Thus, the 2,3-diacyl derivatives 41 are assembled in good yield by a one-pot ac ylation/silver-mediated c yclization of the isonitriles 40.14 H- -tt- - R' (ii) AgBF,, -78 "C " 1 R' +!\ "/y2 0 1C 41 40 The enyne 42 reacts with Fischer carbene complexes like 43, in the presence of the iron catalyst 44, to generate the unusual bicyclic pyrrolidine 45.15 The reaction is assumed to proceed via two intermediate chromacyclobutanes. In a structurally related enyne cyclization, Mori and co-workers have shown that perhydroindole derivatives like 4 8 can be constructed, albeit in modest yields, by a reductive coupling of the silyl acetylene 46 promoted by the zirconium complex 47.16 The product 48, R = Bn was then used in a formal synthesis of dendrobine.OEt Me (i) (C0)5Cr=( 43 (ii) [FeCI,][Fe(DMF)3C12] 44 Ts Ts 42 45 O L SiMe3 46 48 Several research groups have published details of new dipolar cycloaddition routes to pyrrolidines or embellishments of existing methods. Takano and his group17 report that deprotonation of the C2 symmetric N-oxide 49 produces the dipolar species 50 which presumably equilibrates to the isomer 5 1 before undergoing an intramolecular cycloaddition to afford the tricyclic pyrrolizidine-like structure 52 (Scheme 3).50 52 L 51 Scheme 3 This represents the first disclosure of an intramolecular 1,3-dipolar cycloaddition of a non-stabilized ylide generated from an amine oxide. At the other thermal extreme, Heathcock et al. have used flash vacuum pyrolysis to accelerate the intramolecular cycloaddition reactions of stabilized ylides with unactivated dipolarophiles.18 Thus the aziridine 53 is converted into the functionalized bicyclic system 54 by brief heating at 350°C. Finally, Jung and his collaborators have exploited the 3-hydroxypyridinium salt 55 as a useful ylide precursor. Treatment of 55 with acrylonitrile 56 and triethylamine affords a roughly equal mixture of the diastereoisomeric azabicyclo[3.2.l]octenones 57 and 58.The latter isomer, 58, is an intermediate in the authors' synthesis of Bao Gong Teng A, a natural antiglaucoma agent." FVP 350 "C. 0.02 Torr w - R H 53 54 0 0 . ._ 57 58 1:1.5 55 Steele: Saturated nitrogen heterocycles 97The synthesis of substituted prolines is a well represented area, and two related dipolar cycloaddition approaches are particularly worthy of note. Williams et al. have established the diphenylmorpholinone 59 as a valuable cycloaddition template. Reaction of 59 with an aldehyde generates a transient, stablized ylide 60 which is trapped in situ by, for example, dimethyl maleate 61 to afford the bicyclic adduct 62 (Scheme 4).The chiral auxiliary is then discarded by hydrogenation to give the tetrasubstituted pyrrolidine 6 3 .20 Bu3SnH p h F o RCHO ~ H N A 0 PTSA. PhH AlBN 59 H Me02C' R--c7--cozH 'C0,Me 63 Scheme 4 HdPd-C 60 THF I 61 t 62 Harwood and Lilley have shown that the intramolecular variant of this cycloaddition sequence proceeds in high yield and with excellent diastereoselectivity, notably with unactivated akenes as dipolarophiles.21 Thus, the phenylmorpholinone 65 and 5-hexenal64 afford the tricyclic pyrrolidine 66 in boiling benzene, and hydrogenation then liberates the bicyclic proline analogue 67. 65 66 HdPd(OH), cat. TFA H 1 *C02H H 67 As part of a synthetic approach to the hydroindole core of Stemona alkaloids, Wipf and Kim have demonstrated an effective oxidative cyclization of tyrosine 68 by iodobenzene diacetate to yield the bicyclic enone 69.** In the absence of sodium bicarbonate only ips0 spirolactonization is observed.H OH .. 68 69 R = Cbz or Boc Radical cyclizations have also provided new entries to substituted prolines. The thioaminals 70 serve as precursors for carbon-centred glycine radicals, and their treatment with tributylstannane affords a mixture of the five- and six-membered products, 71 and 72.23 t '$CO,Me + 'D CO,Me C0,Et CO, Et 71 72 (2:l) The transformation is reasonably tolerant of substituents although yields are variable. The homochiral4-exomethyleneproline 74 has been prepared by a tributylstannane-promoted 5-exo-dig cyclization of the acetylene 73.24 The neuroexcitatory prolinoid kainic acid and its congeners have attracted continued synthetic attention.Thus, Knight and his co-workers have employed a particularly elegant transannular ester-enolate Claisen rearrangement reaction as part of their total synthesis of ( - )-a-kainic acid.*5 Deprotonation of the nine-membered azalactone 75, by LDA, followed by warming effects rearrangement via a boat-like transition state leading to the key functionalized pyrrolidine 76. I S02Ph 73 0 I kO,Ph 74 I C02Et 75 I COzEt 76 Baldwin et al. have shown that samarium iodide cyclizes the alkene substituted aminoaldehydes 77 to diastereoisomeric mixtures of the kainoid precursors 78;26 an N-acyl substituent is apparently essential for the transformation to proceed. 98 Contemporary Organic SynthesisSml, THWHMPA D R'O 77 78 Finally, Takano and colleagues have developed conditions for the intramolecular Pauson-Khand cyclization of the dicobalt carbonyl protected acetylene 79.The bicyclic enone product 80 is a key intermediate in the authors' enantiospecific synthesis of ( - )-kainic acid.27 I C02Me 79 Me' + CH2C12 0 "C OR XOB" I C02Me 80 2.2 Pyrrolidinones The intramolecular addition of amide nitrogen centres to unsaturated bonds is a popular route to y-lactams. Knapp et al. have extended their earlier work in this area by developing an efficient, stereoselective iodolactamization of the primary amide 8 1 affording the hydroxypyrrolidinone 82 after removal of the transient protecting group.28 0 9 * (i) Me3SiOTf (3 equiv.) Et3N HO (iii) aq. Na2S03 81 1 82 Although amide bond formation per se is outside the remit of this review, several noteworthy y-lactam syntheses are appropriately included.A simple asymmetric synthesis of 5-substituted 2-pyrrolidinones which relies on the chiral auxiliary phenylglycinol84 has been reported by Meyers et al. (Scheme 5). R fO" Ph"NH, 04 PhMe, reflux 83 Pti 0 85 I TiCI. H O T N ? Li, NH3 EtOH 0 Ph 0 Condensation of 84 with y-ketoacids 83 yields the bicyclic aminals 85. Stereoselective reduction of 85 with alane or triethylsilane/Lewis acid next generates the substituted lactams 86. Removal of the residual auxiliary, liberating the 5-substituted pyrrolidinones 87 is then achieved by a dissolving metal reduction.29 Schollkopf has described a synthesis of the novel 5-phosphonate 90 in the course of studies on phosphonoproline analogues.A Michael addition of the chiral metallated imine 88 to methyl acrylate 89 gives the homochiral lactam 90 after hydrolytic work-up. Zinc appears to be essential since the reaction fails when a lithiated imine is employed.30 a0 The use of transition metals is affording some effective new syntheses in this area. Thus, the chiral rhodium catalyst Rh,( 4S-MEOX), 92 almost quantitatively converts the diazoamide 9 1 into the lactam 93 with a moderately good e.e. (78%). The authors also describe several related catalysts which give varying amounts of azetidine by-prod~cts.~~ I 1 93 N2 91 r Many radical-based approaches to polyhalogenated pyrrolidinones have appeared in recent years, and three recent reports add to this list.Itoh and co-workers3* have reported that N-ally1 trichloroacetamides such as 95, which are readily prepared from the appropriate ally1 alcohols 94 by an Overman-type [ 3,3]-sigmatropic rearrangement, are converted into the pyrrolidinones 96 in good yield under ruthenium catalysis. (11)14U 'G 95 JV 87 86 Scheme 5 96 Steele: Saturated nitrogen heterocycles 99Jones and Storey have assembled the oxindoles 98 by a tin-mediated radical cyclization of the bromoanilide 97 although, in some cases, small amounts of corresponding dihydroquinolone products were formed by the alternative 6-endo cy~lization.~~ No competitive addition to the isolated ally1 double bond in 97 was obseved. Finally, Ikeda and his colleagues have documented the radical cyclization of N-vinyl chloroacetamides such as 99, affording the bicyclic pyrrolidinone 100.This chemistry has then been extended to a useful synthesis of perhydr~erythrinane.~~ Bu3SnH PhMe reflux I I 97 98 Bu3SnH AIBN PhMe, reflux A Me Me 99 100 Two interesting pericyclic approaches to pyrrolidinones have emerged recently. In the first, the pyrrolo[3,4-b]pyrrolidinone 103 is assembled quickly and efficiently by a thermal intramolecular Diels-Alder reaction of the acetylenic imidazole 10 1. The presumed intermediate adduct 102 is not observed and almost certainly extrudes HCN in sit^.^^ In the second report, the homochiral aminoacrylamide 104 undergoes an asymmetric intramolecular ene reaction on heating at 150°C. Hydrolysis of the separated diastereoisomeric products then gives the enantiomeric spiropyrrolidinones 105 and 106 in a ratio of 77 : 2 3 , corresponding to 52% e.e.for the ene reaction.36 101 102 R 104 (iii) AcOH 1 (i) A, 150 "C neat (ii) Separate diastereomers Ring expansion reactions are frequently serendipitous discoveries, and Black and his co-workers have now described such an expansion of P-lactams which may have considerable synthetic scope. The reaction of chlorosulfonyl isocyanate (CSI) with simple 1,l-disubstituted alkenes 107, bearing at least one allylic proton is presumed to generate the classical P-lactam intermediates 108. On heating the reaction mixture, however, only the sulfonyl pyrrolidinones 109 are isolated, in 60-70% yield.37 L 108 109 In an unrelated ring expansion, the N-phenylazetidinone 1 10 is converted stereospecifically into the iminopyrrolidinone 11 1 on treatment with cyanotrimethylsilane and aluminium chloride .tt-8 Ph AICl3, Me3SiCN PhH * {<+. MeH NH Me H 110 111 Smith and Hirschmann have described a short synthesis of the homochiral3-pyrrolidinones 114 which are readily assembled into oligomeric P-strand pep ti do mimetic^.^^ The synthesis of 114 relies on imine formation between the aldehyde 112 and the unnatural amino acids 1 13, followed by KHMDS-induced cyclization. Bn 113 NHBM PhMe - O H C d C O , M e (ii) KHMDS THF 112 H 114 2.3 Pyrrolizidines and related compounds A new route to pyrrolizidine alkaloids, developed by Anderson and Ba~kvall,~~ relies on a palladium catalysed tandem cyclization of the dienyl amide 1 15 generating the bicyclic lactam 116 which was then converted into ( k )-heliotridane 1 17. Me I I1 0 115 117 II 0 116 An intramolecular amidocarbonylation of the pyrrolidinone 1 18 proceeds under rhodium catalysis 105 ?7:23 106 and very high pressures of carbon monoxide and 100 Contemporary Organic Synthesishydrogen ( > 100 atmospheres) to give the aminall19 as a 2 : 1 mixture of isomers. The isomers of 119 were then transformed into isoretronecanol and trachelantha~nidine.~~ 1:l CO/H, 16OOpsi f OTBS HCiOEt)3 .HRh(CO)(PPh& 0 OEt 118 119 Significant developments in radical-mediated ring closure reactions have emerged. Bowman and his c o - ~ o r k e r s ~ ~ have prepared the tetracyclic pyrrolizidine analogue 124 from the bicyclic sulfenamide 120 (Scheme 6). The reaction proceeds by generation of the aminyl radical intermediate 12 1 which then undergoes tandem cyclizations via 122 and 123 before abstracting hydride and regenerating the catalytic tin radical.SPh 120 121 / 124 Scheme 6 123 The a-amino radical generated by photolysis of 125 in the presence of 1,4-dicyanonaphthalene 126 as an electron-transfer agent cyclizes stereoselectively to afford the pyrrolizidine 127. Less than 3% of the a-methyl isomer is produced during the ring closure.43 hv, >280 nM * NC 127 125 @ , pi*" ~ 3 % a-Me isomer NC 126 In a reaction analogous to the formation of the pyrrolidinone 96, the vinyl pyrrolidine 129, which is readily available from cbz-proline 128, is shown to cyclize under copper ( I ) catalysis to generate the trichlorolactam 130 in 93% ~ield.4~ Dechlorination 6 steps cN?;C*.H--- Cbz 128 129 CUCl MeCN 150 "C ____c H CC' and amide reduction then completes a synthesis of pseudoheliotridane. In the last radical cyclization example, the tin mediated cyclization of thioacetall31 provides a 1 : 1 mixture of the bicyclic lactams 132 and 133; the mixture has then been used to complete a synthesis of racemic ~upinidine.~~ 0 131 Bu3SnH AIBn (SiMe3 1 Bu3SnYiMe3 0 0 132 (28%) 133 (29%) Finally, Hassner and his co-workers have described the intramolecular oxime-olefin cycloaddition reaction of the prohe-derived vinyl pyrrolidine 134 to afford the tricyclic adduct 135.46 Despite the need to heat the oxime neat at 180°C for 15 hours, the product 135 is isolated in 56% yield, and has also been converted into supinidine. 134 180 "C neat 15h 135 3 Six-membered rings with one nitrogen atom 3.1 Piperidines An excellent review of synthetic approaches to the Daphniphyllum alkaloids has appeared.47 Amongst a wealth of chemistry, the review contains a valuable summary of fused piperidine ring constructions.Returning to the theme of nitrogen addition to unsaturated bonds, Weinreb et al. have described a regioselective synthesis of the piperidine 137 by palladium-mediated sequential cyclizations of the aminodiene 1 36.48 The azidoboronates 138, prepared via hydroboration of a suitable alkene with HBC1, and an alcohol, are readily cyclized by treatment with boron trichloride to give the intermediate dichloroboranes 139. Basic hydrolysis efficiently liberates the bicyclic perhydroquinolines 1 40.49 Me 136 130 138 137 140 BClz 139 Steele: Saturated nitrogen heterocycles 101Overman and his colleagues have extended their existing work on the Mannich-like intramolecular addition reactions of alkynes to imines by demonstrating that the imines 142, prepared by condensation of the amines 14 1 with a range of aldehydes, readily undergo an iodide-promoted cyclization to form the alkylidenepiperidines 143.s0 L 143 141 142 Angle and his group have published more details of their elegant, stereoselective pipecolic acid synthesis.Conversion of the oxazinones 144 into their corresponding TIPS ketene acetals facilitates a conformationally restricted Claisen rearrangement which proceeds by a boat-like transition state to generate the pipecolic acids 145.51 The procedure has also been applied to the synthesis of enantiomerically pure piperidine derivatives.Angle has also described an unrelated synthesis of piperidines which relies on silver oxide oxidation of the phenol 146 to the quinonoid species 147. Addition of zinc chloride then catalyses cyclization of the enecarbamate 147, generating the intermediate 148 which can be isolated as a mixture of 149 and 150 in which the new enecarbamate 149 predominates (Scheme 7).s2 manzamines, Marko and his group have detailed a remarkable anionic cyclization of the indole 15 1 to give the tetracyclic system 152. Overall, the transformation is the equivalent of an indole-based IMDA reaction. The authors suggest a plausible mechanism involving kinetic addition of the indolyl anion to the dienoate followed by a fast, intramolecular Mannich reaction.53 Finally, as part of a synthetic approach to OH 0 Cbz 146 Scheme 7 Cbz 147 CO,R H C02R 151 152 3.2 Tetrahydroisoquinolines and related compounds Two similar reports of the utility of intramolecular Pummerer reactions in the synthesis of tetrahydroisoquinolines have appeared.In the first, by Craig and co-worker~,~~ treatment of the p-aminosulfoxides 153 with TMS triflate generates the presumed thionium ion intermediates 154 which then cyclize to generate moderate yields of the tetrahydroisoquinolines 155. Takano has described essentially the same cyclization of 156 to 157 catalyzed by TFAA.55 ?- TSN/\/SPh Me,SiOTf R15Q * R2 153 L 154 1 155 156 157 The venerable Pictet-Spengler reaction continues to show new facets. As part of a synthetic approach to tetracyclic eudistomins, a stereoselective synthesis of the tetrahydro-P-carbolines 159 has been achieved by reduction of the esters 158 followed by in situ cyclization of the resulting aldehydes with TFA.56 OH Cbz 148 150 (5%) 102 Contemporary Organic SynthesisR (ii) TFA R' .-H ) -70 "C S Me Me 159 158 165 Photolysis of the tryptamine analogues 160 in the presence of TMSCN and 9,lO-dicyanoanthracene 162 as a photosensitizer produces the tetracyclic indoloquinolizidines 16 1 after acidification. The reaction proceeds by cyanation to generate intermediate a-aminonitriles which afford Pictet-Spender products on treatment with acid.57 h3 160 r YN 1 IDCA=QJp] CN 162 A 3 161 Appropriately substituted tryptophan derivatives can give excellent stereoselectivity in cyclocondensations with aldehydes.Thus the N-benzhydryl tryptophan isopropyl ester 163 condenses with aldehydes to generate the trans tetrahydro-p-carbolines 164 excl~sively.~~ 163 R 164 Tietze and Wichmann have established a short and neat entry to corynanthe type alkaloids which relies on tandem Pictet-Spengler and intramolecular Michael reactions (Scheme 8).59 Thus, treatment of the amino triene 165 with TFA generates the intitial cyclization product 166 which is not isolated. Exposure of 166 to tin tetrachloride then mediates a stereoselective Michael reaction producing the tetracyclic amine 167. Interestingly, no single Bronsted or Lewis acid alone could be found to achieve both cyclizations.Two somewhat unusual tetrahydroisoquinoline syntheses have been published. Kihara and co-workers60,h have reported the lithiation and cyclization of 168 to generate the carbinoll69 on exposure to butyllithium (a so-called intramolecular Barbier reaction). Lastly, MaryanofF2 has shown that reaction of the formyltryptamine 170 with paraformaldehyde generates a formyliminium ion which then cyclizes spontaneously to the formamide Scheme 8 17 1. The reaction has not been extended to aldehydes other than formaldehyde. 168 1 69 (CH20)" TFA, refiw 'CHO 170 171 3.3 Indolizidines A comprehensive, 94-reference, review of synthetic approaches to castanospermine, its stereoisomers and analogues has a~peared."~ The total syntheses of several complex indolizidines have recently been described.A pivotal step in the construction of the dendrobatid alkaloid ( + )-allopumiliotoxin 339A by Overmad4 is the generation and cyclization of an iminium ion from 172 leading to the vinyl iodide 173. In a second synthesis of allopumiliotoxin 339A, the vinyl iodide 174 is converted into an organochromium intermediate by Nozaki chemistry. The subsequent cyclization gives the advanced intermediate 1 75.65 Me-'T/ acetone-Hfl OBn Me OBn 1 172 173 crc12 cat. NiC12, DMF 20 "C 174 175 Steele: Saturated nitrogen heterocycles 103The elegant synthesis of indolizomycin by Danishefsky et aZ.66 achieves the requisite pendant functionality by assembling and then fragmenting an indolizidine-like core unit (Scheme 9). Thus, the dihydropyridone 176 is ring enlarged to first give the azonine 177.After further modification to 178, deprotection of the ring nitrogen initiates a spontaneous transannular cyclization affording indolizomycin 179. 1 176 1302C > / lT7 / 1 - R02C -?- Me Me 1 78 179 Scheme 9 An enantioselective synthesis of ( - )-slaframine 18 1 exploits a chemoselective hydrogenation of the azide 180 followed by tandem cyclization of the resulting amine. Acetylation and deprotection then liberate the alkaloid 18 1 .67 0 (1) HI, Pd-C A H I (ii) K&03 Ac I 1 CbZ N3 180 181 Oxidation of the homochiral hydroxamic acid 182 transiently generates the acylnitrosodiene 183 which then undergoes an IMDA cyclization, affording the key adduct 184 as a mixture of diastereomers (Scheme These intermediates 184 have been used as Me 1 182 185 Scheme 10 183 1 common precursors for several of the gephyrotoxin , alkaloids including 209B 185.Wasserman et ~ 1 . ~ ' have shown that the vicinal tricarbonyl derivative 186 is converted via the acyliminium ion 187 into the bicyclic amine 188 simply by the action of silica gel. 186 L 187 J $W0 C02But 188 3.4 Quinolizidines A useful aza-annulation has been devised as the key component of a stereocontrolled route to lupinine 19 1. Reaction of the B-aminocrotonate 189 with acryloyl chloride generates only the lactam 190 in 80% yield.70 Two related cyclizations of acyliminium ions derived from hemi-aminals have been used to assemble quinolizidines. In the first,71 exposure of the hemi-aminall9 2 to TFA promotes iminium ion formation and interception by the pendant allylsilane then affords the isomeric bicyclic lactams 193.The second report uses identical conditions, but an acetylenic terminator rather than an allyl~ilane;~~ thus 194 affords the lactams 195 C02Et 189 OH O Me 192 194 1 90 I 191 H qqy 0 Me [P:u = 7:3] 1 93 0 195 104 Contemporary Organic Synthesis3.5 Aza Diels-Alder reactions The synthesis of six-membered rings containing nitrogen has fuelled continued interest in aza-variants of [4 + 21 cycloadditions, with the majority of recent developments in the azadienophile domain. Abraham and Stella73 have achieved near total diastereocontrol in the cycloaddition of the homochiral imine 196 with, for example, cyclopentadiene 197 to afford the adduct 198. A critical development is the use of a catalytic mixture of TF’A and BF, to optimize the process.203 g;B - OAr 204 ,C02Me II TI p;u” +a- Cti+lz I Y .. \ C’ 196 198 197 Me ‘A-BF3 _I_) . . ^. Diethylaluminium chloride has been established as an excellent catalyst for the cycloaddition reactions of a-alkoxyimines such as 199.74 Diastereoselectivity in the reaction of 199 with the diene 200, to afford the lactams 201, varies from moderate to very good. I 200 OBn 199 dBn 201 Variation of the diene substitution can result in a complete reversal of the cycloaddition regiochemistry. In contrast to the previous example, the imine 202 reacts with the dienes 203 to provide the 4-pyridone derivatives 205. Use of the BINAP-based boronate 204 results in up to 90% e.e.75t76 OMe T O s i M e 3 ZnCI, 207 II + Me3Si0Y N/Bn 2 Ph Ph H** &jR Bn 205 Waldmann and his co-workers have demonstrated some useful levels of diastereocontrol in the zinc chloride catalysed reaction of the tryptophan-based imines 206 with Danishefsky’s diene 207.77 The dihydropyridones 208 are isolated typically as ca.3 : 1 mixtures. The actual mechanism of this, and related cycloadditions, is the subject of a study by the same research OMe 0 207 206 208 [p:0l-3:1] The imines 209 react with the diene 207 as in the previous example, to give the dihydropyridones 2 10 together with a trace impurity 2 1 1 arising from residual nucleophile incorporation. The authors have detected no intermediates akin to 2 12 which would be consistent with a concerted [4 + 21 cycloaddition. However, the observation of 2 1 1 is circumstantial evidence for a tandem Mannich-Michael sequence via intermediates such as 2 13 (Scheme 1 1).0 0 OSiMe3 via lR’$OMe 21 2 Scheme 11 Steele: Saturated nitrogen heterocycles or I C’ 21 0 21 1 (trace only) 21 3 1053.6 Piperidinones Alper and his group7' have continued their explorations of carbonylative ring expansion reactions by demonstrating an efficient, cobalt-mediated conversion of the pyrrolidines 2 14 into the &lactams 2 15. The reaction is regioselective in that only the more substituted ring carbon migrates to CO. Although the Diels-Alder reaction primarily assembles C-C bonds, a corollary may be the generation of new heterocycles, and two research groups have recently used this protocol to advantage in alkaloid synthesis. Firstly, Yamaguchi and his co-workerss4 have achieved a quick entry to the yohimbane system which relies on nucleophilic addition of the dienylstannane 227 to a suitable cyclic imine 226 followed by in situ acylation with acryloyl chloride 228 to yield the bicycloannulated product 230.The triene intermediates 229 are not observed (Scheme 12). In the second report, by Leonard and his transiently the amidotriene 232 which rapidly cyclizes to generate the bicyclic amide 233. thermolysis of the sulfolene 231 liberates f+ 21 4 A' 21 5 The alkenamides 2 16 react with aryl aldehydes 2 17 typically in hot polyphosphoric acid to afford the unsaturated lactams 218 in good yield and with useful levels of diastereoselectivity in the C-C bond forming process.*" Momose and his colleagues* have disclosed that thioimidates 220, prepared from the unsaturated thioamides 2 19, undergo an efficient iodolactamization to provide the functionalized 2-piperidinones 22 1.0 0 Ar PPA or PPE 60 "C A4 21 7 21 6 + 21 8 Bn 21 9 Bn 220 22 1 The hydration-cyclization of y-ketonitriles such as 222 under ruthenium hydride catalysis generates the ene-lactams 223 in high yield, and Murahashi et aLS2 have applied this procedure to a relatively short synthesis of ( - )-pumiliotoxin C. Radical-initiated carbon-carbon bond formation is now almost ubiquitous in heterocyclic synthesis, and Gennari et a1.*3 have described an enantioselective synthesis of the tricyclic lactams 225 by a tin hydride facilitated cyclization of the aryl bromide 224. 0 R u H ~ ( P ~ ~ P ) ~ Cat.R' R' VCN H20 + 222 $?SPh Br I k' 223 Bu3SnH Alan - R m N R x - 229 L Scheme 12 231 PhMe reflux - 0 (..$ NMe2 ' 232 - v 230 -3 0 NMf+ 233 A useful Stevens [ 1,2]-shift route to 3-piperidinones has emerged. Thus, West et aZ.86 report that exposure of the aminopropyl diazoketones 234 to standard rhodium carbenoid conditions affords the cyclic aminoketones 236, presumably by a [ 1,2]-alkyl shift of the intermediate ylides 235. Using a similar protocol, the 5-oxopipecolic acids 238 have been assembled by a rhodium-mediated insertion of the carbenoid derived from the diazoketone 237.s7 r 1 kbz 237 Cbz 238 106 224 225 [P:a = 851 51 Contemporary Organic SynthesisLastly, reaction of the azapropenylium salts 239 with the enamine 240 generates the bicyclic imines 241, which are readily hydrolysed to the azabicyclo[3.2.l]octenones 242 (Scheme 13).88 R’ OEt EtO MRZ B Fq- 239 + 6 240 242 Scheme 13 4 Rings with two or more nitrogen atoms 4.1 Five-membered rings Treatment of the a-bromoacyl phenylhydrazones 243 with tributylstannane generates the radical intermediate 244 which then cyclizes to give the pyrazolidinones 245 rather than the anticipated diazetidinone 4-exo-trig products.89 As part of a new BugSnH I Me\! 243 244 synthesis of a-amino acids (Scheme 14), the chiral amidal246 has been converted into the organomercurial imidazolidinone 247.This versatile intermediate can then either be demetallated reductively, affording 249, or oxygenated, generating the alcohol 248.’O Baldwin and his co-workers have synthesized the conformationally restricted, bicyclic y-lactam dipeptide analogue 2 5 1, utilizing as the key transformation a cyclization of the acyliminium ion derived from the hemi-aminal 250.91 ‘!Cbz 247 n 246 Me TogoH NvNCbz 248 249 Scheme 14 CbzHN ph$pH cat.TFA 5;fk ~ C02Bn 250 25 1 4.2 Six-membered rings An efficient synthesis of both enantiomers of piperazic acid, a constituent of the anti-tumour antibiotic azinothricin, has been reported.92 The lithium enolate of the bromovaleryl carboximide 252 adds to the azodicarboxylate 253 giving direct access to the piperazine 254.Hydrolysis of 254 with lithium hydroxide then liberates bis-Boc (3 R )-piperazic acid 255. A further example of nucleophilic amide additions to acyliminium ions is provided by Wasserman and co-~orkers’~ as part of a synthetic route to azadethiacephams. The hemi-aminal256 liberates the iminium ion 257 on heating with pyridinium tosylate and subsequent cyclization then provides the bicyclic amidal258.0 LDA BU‘O~C-N=N -CO~BU’ * 253 252 r 256 Boc 254 LiOH THF J H*O Ho2cn BocO ‘y Boc 255 1 L 257 C0,Me I 0 258 In the course of an impressive enantioselective synthesis of ( - )-decarbamoylsaxitoxin, Hong and KishP4 have developed a remarkable trimolecular cyclization of the /I-amino unsaturated ester of the aminocrotonate 259, R-glyceraldehyde acetonide 26 1 and silicon tetraisothiocyanate 260 affording the cyclic thiourea 264 in 72% yield, Scheme 15. The reaction presumably proceeds by formation of the thiourea 262 which next undergoes a [ 3,3] cyclization, generating the zwitterion 263.A proton shift then gives 264. Steele: Saturated nitrogen heterocycles 107Me02C (SCN)3SiN=C= S 260 M e t o d Me O? H N k l 259 OHC 261 1 I 264 263 Scheme 15 Miknis and William~'~ have shown that reaction of the benzofuran 265 with N-bromosuccinimide generates stereoselectively the spirodiketopiperazine 266, an intermediate in the authors' completed synthesis of the fungal metabolite aspirochlorine. NR7 NH.OMe CI 0 266 4.3 Seven-membered rings As part of a programme to prepare analogues of the anti-HIV- 1 agent TIBO, Parker and Coburng6 have reported a regioselective synthesis of the benzodiazepines 268 by cyclization of the difluoronitrobenzenes 267. No attack at the para-fluoro position is observed. 02y *2N H K2C03 140 "C &>--Me N R H DMF R F F 268 267 5 Seven-, eight-, and nine-membered rings Two new azepane syntheses rely on photocyclization reactions.Thus, Piva and co-~orkers'~ have shown that photolysis of the vinylogous ketoamide 269 at 366 nm affords the tricyclic [2 + 21 cycloaddition product 270. In a study of intramolecular stilbene amine photoadditions, Lewis and Reddyg8 have demonstrated that the substrates 271 show a clear preference for seven-membered rings formation regardless of amine side chain length. Thus photolysis at 300 nm leads to either 272 or 273 with no formation of six- or eight-membered by-products (Scheme 16). 0 0 I f Ph 270 272 271 (n = 1 or2) Scheme 16 e N M e \ 273 Hydrogen chloride effects the cyclization of the keto-aminal274 via an intermediate iminium ion, to provide the azepane 275 as a mixture of isomers.Yg The product 275 has then been used to complete a Synthesis of ( + )-anatoxin a.274 V 275 Garner and his grouploo have used a 173-dipolar cycloaddition reaction between the acryloyl sultam 277 and a dipole generated by photolysis of the aziridinylimide 276 to provide the adduct 278 in good yield. This chemistry forms the basis of an asymmetric synthesis of ( - )-quinocarcin. OfloMe hv, 254 nm 276 dioxan 278 Overman et al. have established a useful, general route to medium-ring nitrogen heterocycles based on an iodide-promoted Mannich cyclization of alkynylamines such as 279.Io' The product 108 Contemporary Organic Synthesisdistribution favours the azepanes 280 over azocanes 28 1. A general route to monocyclic medium-ring lactams has been reported by Holmes and co-workers.lo2 The method relies on a Claisen rearrangement of the ketene aminals 282, which are generated in situ by selenoxide elimination, to afford the lactams 283. Yields are generally high for the assembly of seven-, eight-, and nine-membered rings.7" Bn 0 R (CH20)n Bu4NI ~ GR + (JJ, camphor sulonic acid I 279 I 280 281 Major Minor II. A PhMe or mxylene Cb! 0 _ _ _ 283 282 ( n = 0,1,2) The reaction of optically active p-ketoesters such as 284 with hydrazoic acid and a Lewis acid generates the tetrazoloazocanes 285 via the Schmidt rearrange- ment.lo3 The products 285 are then readily reduced by LAH to the homochiral azocane carbinols 286. C02Me R HN3, BFfOEt2 OH OR 284 285 286 As a key step in the synthesis of the fungal metabolite FR-900482, the lactone 287 was reduced to an intermediate aldehyde followed by a novel macrocyclic reductive alkylation to provide the benzazocane 2 88 .Io4 OAr 287 H 288 Finally, Moody and his grouplo5 have published full details of their synthesis of ( - )-indolactam V.In the course of this work, the authors describe photocyclizations of the tryptophan-derived amide 289. Photolysis in dry acetonitrile affords only the eight-membered lactam 290 but, in the presence of trace amounts of water, the major reaction product is the lactone 291. 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ISSN:1350-4894
DOI:10.1039/CO9940100095
出版商:RSC
年代:1994
数据来源: RSC
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5. |
Organic halides |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 113-124
P. L. Spargo,
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摘要:
Organic halides P.L. SPARGO Process R&D Department, Pfizer Central Research, Sandwich, Kent, CT13 9NJ, UK Reviewing the literature published between 1 July 1992 and 30 June 1993 1 2 2.1 2.2 2.3 3 3.1 3.2 3.3 3.4 4 4.1 4.2 5 6 7 8 9 9.1 9.2 9.3 10 Introduction Alkyl halides By halogenation of alkanes By nucleophilic substitution By other methods Vinyl halides From alkynes From other vinyl derivatives By C=C bond formation By other methods Aryl halides By electrophilic halogenation By nucleophilic substitution Alkynyl halides 1,l -Dihalo compounds 1,l -Halohydrins and related compounds 1,2-Dihalo compounds 1,2-Halohydrins and related compounds By addition to alkenes By epoxide opening With C-C bond formation References 1 Introduction The huge synthetic potential of organic halides puts them in a unique position within organic chemistry.Whether through palladium catalysis, by halogen-metal exchange, by conversion into radicals, or by good old-fashioned nucleophilic substitution, organic halides play a key role in much of contemporary organic synthesis. This coverage does not attempt to be fully comprehensive, but it is hoped that the chemistry selected for presentation is that which will be of particular utility or interest to the practising synthetic organic chemist. The area of perfluoroalkyl chemistry1y2 will not be discussed, as it will be reviewed in this journal at a future date. No general reviews on the preparation of organic halides appeared during the review period, but some reviews specifically concerning fluorination were 2 Alkyl halides 2.1 By halogenation of alkanes The direct halogenation of unactivated alkanes using 'Gif-type' chemistry has continued to be developed in the research group of Barton,"-9 but the lack of substrate functional group requirement for this chemistry does rather restrict its use to highly symmetrical systems such as cycloalkanes (Scheme l).9 LiX or NaX pyridinalAcOH BU'OOWF~(NO~)~ X = CI, Br 0 Scheme 1 A review on this and related chemistry has been published.* Breslow's template-directed radical functionalization of apparently unactivated positions of steroids continues to prove synthetically useful, giving regioselectively chlorinated derivatives in impressively high yields (Scheme 2).1° Alkyl chlorides can also be prepared by hydrochlorination of alkenes with thionyl chloride in a surface-mediated reaction on silica.' Scheme 2 a-Halogenations of ketals and acetals have been described by a number of research groups, using MnO,, TMSCl;I2 Br,, ROH;13 and Br,, CC14;14 the latter being part of a detailed study of the stereochemistry of spiro-ketal brominations and their subsequent elimination products.Halogenation by quenching of organometallic has shown occasional utility,16 and can be achieved with one of the latest additions to the battery of elec tro philic flu0 rina ting agents , the N-fluoro-DABCO derivative l , I 7 which has been named a 'Selectfluor' reagent (Scheme 3). It is a virtually non-hygroscopic, high-melting solid with considerable synthetic potential, as will be seen in later sections of this review.species with elemental halogen ( i.e. RLi + F2 -. RF lS ) Spargo: Organic halides 113KJ I + (EF4-)2 F 1 RM - RF M = MgBr, Na, K; R = alkyl. aryl Scheme 3 The most frequently halogenated sp3 carbon atoms are of course those stabilized by an adjacent carbonyl group, and a number of examples of this chemistry can be found in the literature under review, including lactams (TMSI, I, (or Br,), Et3N;I8 LDA then ClSO,Ph"), a-thiolactams (by electrochemical means20v21), malonate derivatives (CCl,, TBAF;,, Selectfluor reagents;" I,, K2C03, Phase transfer catalysis23), ketoesters (TMSC1, Selectfluor reagents' 7), and sensitive 2-fury1 ketones.25 An interesting new method for the preparation of a-chloroamides is outlined in Scheme 4.26 Use of only one equivalent of triethylamine allows the reaction to stop at the N-mesyloxyamide intermediate 2.Treatment of 2 with LiBr and Et3N then gives the a-bromoamide. Note, however, that a conjugating group at C-2 is essential for 0 OH Scheme 4 this reaction to proceed. 2 LiBr Asymmetric fluorination of enolates has been described using the Davis N-fluoro-camphorsultam derivative 3 (Scheme 5),27 while asymmetric bromination28 and iodination29 of enolates have been achieved using covalently bound chiral auxiliaries (Schemes 6 and 7). NaHMDS V dMe 0 575% 8.8. &Cl -40% SO: 'F 3 Scheme 5 >99% d.e. Scheme 6 0 ; 0 ' \OMe \OMe ~ 8 9 : 11 Scheme 7 a-Fluorocarboxylic acids of up to 90% e.e. have been prepared by asymmetric hydrogenation of a-fluoroacrylates (Scheme 8).30 Lastly, a completely novel approach to enantiometrically pure a-fluoroketones has been developed which uses a Sharpless asymmetric epoxidation as the original source of chirality (Scheme 9).31 H2(540 atm.) RJco2H Ru-(R)-BINAP MeOH RJC02H 100% 56-90% e.8.Scheme 8 A Scheme 9 i 9647% e.e. 2.2 By nucleophilic substitution The Finkelstein reaction between alkyl halides and aqueous HC1, HBr, or HI has been shown to be strongly accelerated under phase transfer catal~sis,~, whle a new method for the conversion of alkyl chlorides or bromides into fluorides (PbF,, NaBr, MeCN) has been reported, although this is restricted to benzylic systems nucleophilic substitution a mild, cheap, and apparently general method for converting alkyl tosylamines to alkyl halides has been described (Scheme 1 O).34 When the chloride is desired, this is a one-pot procedure.However, the bromide and iodide can also be prepared in high yield by isolation of the intermediate tosylhydrazine 4 followed by treatment with bromine or iodine. . While not strictly a -r_ KOH IS NH,CI or I2 or Br, NH&I I A r w N H T ~ - Ar-"NH2 A,/\/' base 4 Scheme 10 X = CI, Br, I The most common precursors to alkyl halides are, of course, alcohols. Selective halogenations of primary alcohols in the presence of secondary ones have been studied in detail, chlorination being achieved with the Vilsmeier-Haack reagent 5 in DMF (Scheme 1 1),35 and bromination with HBr in acetic acid.36 +cI- MeA= CHCl 5 "+OH OH OH 77% DMF OH OH (isolated as the triacetate) Scheme 11 1 14 Contemporary Organic SynthesisThe patent literature contains a report of a phosphine oxide mediated conversion of alcohols into alkyl chlorides with phosgene.37 This is complemented by a report on the use of triphosgene and PPh, which has been shown to give excellent yields of alkyl chlorides from a wide range of alcohols.38 The triphenylphosphine-bromine adduct PPh,Br, continues to find use, particularly when sensitive functionality is also present in the starting alcohol,39 and the combination of NBS and PPh, at low temperature has been shown to effect the previously difficult transformation shown in Scheme 12 .40 Scheme 12 For less sensitive systems, a high-yielding and economical large-scale preparation of bromides from alcohols with inversion of configuration has been described, using the simple reagent combination of SOCl,, pyridine, and HBr( 8): A reagent originally devised for the conversion of nucleoside phosphates to phosphorochloridates, [tris( 2,4,6-tribromophenoxy) dichlorophosphorane/pyridine] 6, has been shown to convert primary alcohols to alkyl chlorides in high yield (Scheme 1 3),42 while one of the other halogenation reagents used in nucleoside chemistry (methyl-triphenoxyphosphonium iodide and HMPA ) has proved useful in simple aliphatic chemistry where more traditional procedures failed.43 Alkyl iodides can also be prepared from carboxylic acids, aldehydes, ketones, and alcohols by treatment with BHI,.Me,NPh (prepared by treating borane-dimethylaniline complex with This reagent system effects the necessary reduction( s) before iodination occurs.How 6BZ R = 3-N-benzoylthymine Scheme 13 OBz 2.3 By other methods 'Texan sunshine' has entered the field of 'not-universally-available' reagents for the photochemical halodecarboxylation of carboxylic acids via their thiopyridyl hydroxamate derivatives (Scheme 14).45 Fortunately, other sources of light are also suitable, and a report of an application of this procedure in Europe has already appeared.46 The old-fashioned Hunsdiecker reaction nevertheless still finds its ad~ocates.4~ Bromomethylation of polymethylated benzenes (CH,O, HBr, AcOH) can be controlled to give mono-, di-, or tri-bromomethylated products in high yields,48 while aromatic chloromethylation can be achieved with MOM chloride at low temperat~re.~~ 1,l -Dihalocyclopropanes are a useful source of monohalocyclopropanes either by classical reduction (Raney Ni, NH,NH,, KOH),50 or by monometallation and quenching with e l e ~ t r o p h i l e s .~ ~ ~ ~ ~ Meanwhile, copper-catalysed oxidative cleavage of 1,2-~yclohexanediones in the presence of halides has been shown to give the open chain 2-halo diacids (Scheme 1 5).53 @ H02C L C 0 2 H aq. MeOH 7446% X = CI, Br, I Scheme 15 A number of examples of radical atom transfer additions of geminal-polyhaloalkanes to olefins, both inter-54 and intra-m~lecular~~-~~ have been reported. This is illustrated by one example59 (Scheme 16) which is particularly interesting since it allows the preparation of often-difficult eight- and nine-membered ring lactones in high yield. CuCI. 2, P'-bipyridyl 92% 0 0 Scheme 16 Other potentially useful transformations resulting in alkyl halides are illustrated in Schemes 1 760 and 18.6' Also noteworthy is a paper describing efficient procedures for the synthesis of tertiary alkyl fluorides by successive introduction of three different alkyl groups onto a fluorine-bearing prototertiary carbon fragment.6 0 96% Scheme 17 Scheme 18 R' or R2 = silyt 3 Vinyl halides 3.1 From alkynes a-Iodoacrylates have been prepared by a one-pot hydrostannylation-iododestannylation procedure s Scheme 14 Spargo: Organic halides 115(Scheme 19).63 Generally, separable mixtures of E and 2 isomers were obtained, although in one case (R' = Ph, R2 =Me) > 99% 2-isomer was obtained.R'-R2 cat. PdBr$MeCN), 5548% I COR~ Scheme 24 R ' a 3745% - CoR2 ---- R i d C O R 2 + R ' d I Z E (i) M%"3 eq), CP2~12(0.2 eq) R' = n-C5Hlr, Ph R2 = Me, Ph W U .5 eq) (i9 4 Me I3-z Reagents: (i) Bu3SnH, Pd(PPh3),; (ii) 12; (iii) aq. KF, Et20 6249% Scheme 25 Scheme 19 The addition of halides to a chiral a,B-acetylenic R = P d 0 sulfoxide has also been reported to give the 2-B-halovinylsulfoxides without affecting the configuration of the chiral centre (Scheme 20).64 dibenzoyl peroxide 3344% R3 0 R4 7 Scheme 26 Scheme 20 X = CI, Br, I 3.2 From other vinyl derivatives In related chemistry, E-B-iodpvinylsulfones, prepared by photochemical addition of sodium benzenesulfonate and iodine to an alkyne, have been used in isoxazole synthesis (Scheme 2 1):' stmanes have proved to be a of vinyl fluorides (Scheme 27), by treatment with caesium fluoroVsulfate (CsS04F );71 XeF2, A@F6;72 Or the Selectfluor reagent 1 .73 Meanwhile, vinyl phosphates have been shown to be useful precursors to vinyl iodides (Scheme 28).74 PhS02Na 3848% I RCONH\\ - RCONH S02Ph 12.hv 'F +' =- R 2 q R 4 R3 Scheme 21 Formal addition of HCl or HBr to unactivated terminal alkynes to yield E-vinyl halides can be achieved in high yield by regio- and stereo-selective hydroboration followed by treatment with copper( 11) halide (Scheme 22)F6 By starting with a haloalkyne, hydroboration followed by protonolysis leads to 2-vinyl halides (Scheme 23).67 r 1 L J X = CI, Br 7049% overall Scheme 22 1 Scheme 23 J quant. Scheme 27 A2 Scheme 28 Another approach to vinyl iodides uses highly active, zero-valent copper to generate a vinyl cuprate which can be quenched with iodine (Scheme 29).75 In related work, halogen-metal exchange on 1,l -dibromoalkenes has been shown to occur stereoselectively at the sterically more hindered bromine position, thus facilitating the stereospecific synthesis of substituted vinyl bromides (Scheme 30).76377 (i) 'Highly Actiie A novel palladium-catalysed addition of ally1 bromide to alkynes has been described (Scheme 24),68 while the Negishi carboalumination of alkynes has &want Copper 1 JJ", &Cl (ii) PhcHo (I@ I 2 been shown to be accelerated by the addition of 1.5 69% Scheme 29 equivalents of water, thus improving access to unactivated vinyl iodides (Scheme 25):' E-iodoalkylidene lactones 7 in good yield Br >=\, (ii) E * E R atom-transfer reaction has been shown to give the (Scheme 26).70 Scheme 30 (i) R'U or R 1 ~ n L l L Brh Turning to intramolecular reactions, a radical Br 2448% 116 Contemporary Organic Synthesisa-Halogenation of a,/?-unsaturated carbonyl compounds continues to be popular, and recent examples of this approach include the 3-iodination of flavones, thioflavones, and chromones with I,/CAN,7s a-chlorination of enones with HCl-mCPBA in DMF,79 and halogenation of 1,4-benzoquinones with CuCl, or CuBr, adsorbed on alumina, to give mono-, di-, tri-, and tetra-haloquinones, depending on the substrate and reaction conditions.80 Bromination-dehydrobromination of 3-silylacrolein 8 (Scheme 3 1)81 gives a mixture of geometric isomers, but equilibration under the reaction conditions gives predominantly the 2-isomer 9, a compound which has great synthetic potential.RCHO 6747% R X w X - CI, Br. 1 Scheme 35 An interesting Wittig synthesis of a-chloro-a, /?-unsaturated esters has also been reported (Scheme 36),g8 while Reformatsky-type chemistry can yield similar products (Scheme 37).@) Unfortunately, the latter cannot be extended to a-bromoenones, since reductive debromination of the CHO bromohydrin intermediate also occurs. L NaOH CI Me3si SiMe3 8 9’ Z E 75% Scheme 31 Scheme 36 8-Bromination of a dienone has also been reported, utilizing an ethoxycarbonylhydrazone derivative 10 (Scheme 32),82 while conditions for the selective conversion of a-methyl styrenes into the useful synthon 11 (Scheme 33) have also been optimized.83 Allenes have also proved to be useful precursors to vinyl iodides, by treatment with iodine (followed by further reaction of the resulting 2-iodoallyl i ~ d i d e ) ~ ~ , ~ ~ or by N-iodosuccinimide treatment in the presence of an internal nucleophile (Scheme 34).86 R’ R1 N 93% EtOSC’ ‘N 10 Scheme 32 Ar NBS +,Br 61 % Br PhCl A 11 Scheme 33 NBS Br 0 (i) Zn.CuBr Et&K;I - A r q R (ii) MsCI. Etd, CI ArCHO + Br+R CI DBU 93% Scheme 37 Related a-fluoro- a , /?-unsaturated carbonyl compounds can be accessed by related chemistry using palladium catalysis (Scheme 38).90 Lastly, a Knoevenagel-type condensation between aldehydes and bromonitromethane has been reported (Scheme 39):’ but the risk of explosion associated with this procedure may limit its use. 0 0 Scheme 38 Br\,N4 (2eq.I A r y N o 2 Br Bu”ds 6049% ACHO Scheme 39 NIS bpi 3.4 By othermethods 95% c A novel approach to a-fluoro- a , /?-unsaturated Scheme 34 >%Yo cis carbonyl compounds via geminal fluoro-selenation followed by oxidative selenoxide elimination is depicted in Scheme 40.”, Sulfoxide elimination from a-fluoro- a-sulfoxido carbonyl compounds has also been used to generate vinyl halidesj3 3.3 By C=C bond formation A general method for the preparation of 2-vinyl (Scheme 35).87 The yields and stereoselectivities are halides by Wittig chemistry has been described R1%Z PhSeF_ [ R’v;p] Hf12t R1%F high, and chlorides, bromides, and iodides can all be R2 prepared this way.Note, however, that yields and 51-85% stereoselectivities were much lower when vinyl fluorides were prepared in this way.R1 = Alkyl, alkoxy Scheme 40 Spargo: Organic halides 1174 Aryl halides 4.1 By electrophilic halogenation The search for selective electrophilic aromatic halogenation procedures has continued unrelentlessly, and has yielded some useful results. Regioselective monobromination of anilines has been achieved with pyridinium hydrobromide perbromide in THF, giving minimal polybromination, and predominantly para-selectivity (75-95% yields).', The use of molecular bromine with a catalytic tetraethylammonium chloride (0.1 equivalents) and methanol (0.5 equivalents) system has also given high para-regioselectivity in the bromination of aniline~.~~ In addition, it has been shown that heating an isomeric mixture obtained by the bromination of aniline with a deficiency of bromine in the presence of HBr leads to isomerization, giving 4-bromoaniline as essentially the only product.96 paraselective monoiodination of aniline derivatives has been achieved with iodine and silver sulfate in generally excellent yields.97 Under these conditions, aniline itself gave only 46% yield, while acetanilide gave 9 1%.Interestingly, these conditions also work for nitroanilines. The preparation of 2,6-dichloroanilines via 2,4,6 trichlorination followed by regioselective hydrogenolysis of the 4-chloro group has also been described (Scheme 4 1 ).y8 CI Scheme 41 High-yielding 2,4,6-tribromination of anilines and phenols can be readily achieved using bis (dimethylacetamide) hydrotribromide,99 while selective ortho-bromhation of phenols has been effected by the inclusion of diisopropylamine or dibutylamine in a reaction mixture containing the arene and N-bromosuccinimide.loO The effective halogenating agent is believed to be the N-bromoamine.The ortho-selectivity of ferric chloride catalysed chlorination of toluene has also been shown to be enhanced by using alcohols as co-catalysts.'O' Electrophilic halogenation procedures of fairly broad scope (with respect to substrate) and generally high yield include the use of N-chloro- or N-bromo-succinimide with catalytic perchloric acid,lo2 hexamethylenetetramine hydr~tribromide,'~~ N-bromo- or N-chloro-saccharin with pyridinium poly( hydrogen fluoride),lo4 and bis( pyridine )iodine monofluoroborate ( IPy2BF4) with HBF, .105J06 The latter reagent system can also be used to controllably generate polyiodinated corn pound^.'^^ Substitution of the HBF, with trifluoromethane sulfonic acid also allows deactivated arenes to be effectively iodinated with IF'y2BF4 .lo6 Indeed, triflic acid also facilitates iodination of deactivated arenes with N-iodosuccinimide (Scheme 42).lo8 It is believed that the active agent is 'superelectrophilic' iodine( I) triflate 12 which is generated in situ.+OH CF3SO3- 1 12 Scheme 42 A novel bromination procedure which is only suitable for use on deactivated arenes uses BrF, and Br2.109 This avoids problems associated with the use of BrF, and it is also interesting to note that until now BrF, has only been used as a fluorinating agent. Meanwhile, an aqueous medium (NaOH) has been used for the N-bromosuccinimide- or dibromodimethylhydantoin-mediated bromination of substituted benzoic acids.' Hypervalent iodine reagents are beginning to find use in the catalysis of electrophilic halogenations.In particular, PhI( OH) OTs (Koser's reagent) has been found effective for halogenation of polyalkylbenzenes with N-iodo- and N-bromo-succinimide.' previously mentioned 'Selectfluor' reagent 1 (Scheme 3) shows poor regioselectivity, although this reagent does show potential for the synthesis of aryl fluorides by reaction with aryl Grignard species. Regiospecific preparation of aryl halides can also be achieved by halodesilylation of aryltrimethylsilanes. A review on this and related chemistry has been published,' l2 while the specific case of iodination of arylsilanes with IC1 and silver salts has been studied in some detail.]l3 Aryl boronates can be converted to aryl fluorides in moderate yields by treatment with caesium fluoroxysulfate (CsS0,F ),' while the quenching of certain arylmanganese species with NBS or NIS has also shown some synthetic utility.' l 5 Fluorination of toluene or xylenes with the 4.2 By nucleophilic substitution Heteroaromatic chlorides such as 2-chloro-pyridines and pyrimidines and 2,4-dinitrochlorobenzene undergo counter-thermodynamic halogen-exchange fluorination on treatment with HF or HF-pyridine or HF-collidine.' l6 Similar results are achieved with tetrabutylphosphonium hydrogendifluoride (BuI;P+HF; ),l' by an extension of a previously described method for fluorination of heat- or base-sensitive substrates in non-polar solvents.' l8 Proton sponge hydrofluoride also acts as a useful source of fluoride ion, it being soluble in acetonitrile.This is especially useful for the nucleophilic substitution of heteroaryl chlorides, since the by-product proton sponge hydrochloride is insoluble, allowing ready recovery of the base.' lY The use of caesium fluoride for related halogen exchange fluorination has been recently highlighted.12" Meanwhile, treatment of aryl diazonium salts with BF, under photochemical or thermal conditions has been shown to be another effective approach to aryl fluorides.121 In addition, new conditions for fluoro-denitration of nitroarenes have also been reported, using dry tetramethylammonium fluoride in DMS0.122 Finally, aryl iodides can be readily 118 Contemporary Organic Synthesisconverted via the iodylarene intermediate 13 into the corresponding aryl chlorides by treatment with hypochlorite under phase transfer conditions (Scheme 43).123 The explosive nature of iodylarenes may limit the use of this protocol.- ArCl NaOCl Bu4NHS04 - 13 41-100% Scheme 43 5 Alkynyl halides While not a particularly active area, three groups have made noteworthy contributions. Firstly, bromination of terminal alkynes in a novel triphase brominating-oxidizing system (NaBr, NaOCl, Bu,NHSO,) has been shown to give alkynyl bromides (in stark contrast to the use of Bu,NBr,, which gives 1,l -dibr~moalkenes).'~~ Secondly, further developments in the elimination of HCl from 1,l -dichloroalkenes have been described (Scheme 44),125 and thirdly, rearrangement of the hypervalent iodine species 14 under basic conditions gives the alkynyl bromide (or chloride) (Scheme 45).'26 /=("I KOH.Miquat 336 c R-CEC-CI 90% R CI 60-8096 Scheme 44 R-CEC-X R X%Iph q. MeOH, cH&i2) X = Br, 98% N a H q 14 X = CI, 52% Scheme 45 6 1,l -Dihalo compounds A variety of methods for the preparation of geminal dihalo compounds have been described in the period under review. 1,l-Difluorides are readily obtained from aldehydes by initial conversion to the geminal-bis-triflate followed by treatment with Bu,NSnPh,F, (Scheme 46).127 This reagent is non-hygroscopic, non-toxic, easy to handle, and requires relatively mild conditions compared to many other fluorinating agents. Complementary to this is a CBr,F,/Zn reagent system which allows access to geminal difluorides from ketones, and indeed fails when applied to aliphatic aldehydes.' 28 48),133 by 2 + 2 cycloaddition of dichloroketene with alkenes,l 34 and by controlled reduction of 1,1,1 -trichloroalkanes.' 35 A r h C ' BnNM%IC14(2 eq.) A AcOH.70"C Ic CI Ar 77-96% Scheme 47 MeC OMe NIS or NBS cat.PTSA PhCECH MeOtl 7&93% Scheme 48 A variety of examples of geminal-dihalocyclopropane formation by base-induced carbenoid addition of either CH,Br, 36 or CHBr3,137 or CHC13138 to alkenes have also been described. Various bromo-propargylic alcohols have been converted via a rearrangement reaction into l-bromo-l-iodoalkenes,13Y~140 and an example140 is illustrated in Scheme 49. The high level of functionality in these products suggests that they could be useful synthetic precursors.OH I Iz , PhI(0H)OTs OH'\ 96% Pti '= Br Scheme 49 Other ketone derivatives which have been successfully converted into geminal dihalides include oximes (Cl,, BF,.OEt,),' 2Y~130 1,l -nitrosohalides (HX, CH,Cl,; X = F, C1, Br)I3O and thioketals (electrochemical anodic desulfurization/Et,N. 3HF ).131 a-Dihalocarbonyl compounds have been derived from ketones (Scheme 47)13, and alkynes (Scheme A1 Br 7 1,l-Halohydrins and related compounds The most common occurrence of 1,l-halohydrins in organic chemistry is, of course, in carbohydrate systems. Two selected examples which would appear to have general synthetic applicability include the reaction of aldoses with (PhO),P, Br,, and pyridine to give the a-bromo anomer (Scheme 5O),l4l and the conversion of a-bromoglycosides into the corresponding p-fluoro anomers by treatment with triethylamine trishydrofluoride (Scheme 5 1).14* AcO \ AcO \ U.Scheme 50 RCHo 6245% * Scheme 46 Scheme 51 8 1,2-Dihalo compounds The addition of bromine or bromine plus nucleophile across a double bond continues to fascinate the physical chemist, with a number of detailed mechanistic studies being p ~ b l i s h e d . ' ~ ~ - ' ~ ~ Of greater Spargo: Organic halides 119interest to the synthetic chemist, are the previously-mentioned Selectfluor reagents ( 1, Scheme 3) which, when combined with HF-pyridine, give 1,2-difluoroalkanes from alkenes.17 For mixed 1,2-dihalides, N-bromo- (or N-iodo-) succinimide or dibromodimethylhydantoin in combination with either Bu,PH,F,'~~ or Bu,NH,F~'~~ have been found to be effective.Finally, alkene iodofluorination using I, and AgF has proved beneficial in the synthesis of fluorinated nucleoside derivatives.' 48 9 1,2-Halohydrins and related compounds 9.1 By addition to alkenes Semi-empirical molecular orbital calculations have indicated that bromonium ions may not, after all, be intermediates in the intramolecular bromoetherification of alkenes (or indeed intermolecular bromohydrin reactions), but instead a rather weak alkene-Br+ n-~ornplex.'~~ Whatever the true detail of the reaction mechanism, this type of chemistry continues to be a rich source of diverse functionality. For example, the Selectfluor reagents ( 1, Scheme 3) previously described in this review can also be used to generate a range of fluorohydrin derivatives, specifically ethers, esters, and fluorohydrins themselves.' Additionally, t-butyl ethers of fluorohydrins have been prepared by reaction of alkenes with B U ~ O F .' ~ ~ Intramolecular iodoetherification can be controlled to give anti-2,5-disubstituted tetrahydrofurans (Scheme 52).151 \ R 1' 1 Scheme 52 Classical iodohydrin formation has found continued use in carbohydrate ~ h e m i s t r y , l ~ ~ J ~ ~ while a less common mode of alkene functionalization, in which a molecule of ethylene oxide becomes incorporated into the product, has also been described (Scheme 53).15, Potassium monoperoxysulfate ('Oxone@') continues to find applications in many areas of organic chemistry, and alkene oxidation is no exception.Specifically, treatment of an alkene with oxone in acidic DMF gives halohydrin formate esters (Scheme 54).155 X = Br, CI Scheme 53 0 aq. HCI, DMF 85% Scheme 54 Another area of fruitful research has been that of halolactonization. The formation of simple fo~r-rnernbered'~~ and seven- to eleven-membered rings 57 by bromo and iodolactonization respectively have been studied, while much of the other literature in the field concentrates on five- and six-membered ring formation (including cyclic carbonateP and carbamates' 59) with particular emphasis on diastereoselectivity. Space precludes detailed discussion of much of this chemistry,160J61 but three examples of particular interest are illustrated in Schemes 55,56, and 57. In the first (Scheme 55),158 IBr is found to give much greater levels of diastereoselectivity than I,, while in the second (Scheme 56),16, a polymer-supported chiral auxiliary is used to induce asymmetry (although the stereoinduction was not spectacular). The third example (Scheme 57)'63 makes use of a chiral Lewis acid as the source of asymmetry.0 0 0 >20 : 1 Scheme 55 0-Resin -!L aq. THF 40% I 30% 0.0. Scheme 56 65% 0.0 Scheme 57 Other heteroatoms which have been added across alkenes concomitantly with a halide include sulfur, 164,165 selenium,166J67 and nitrogen, 168, 169 but these will not be discussed further in this review. 9.2 By epoxide opening This is perhaps the most widely-studied approach to 1,2-halohydrins, in which stereo- and regio-selectivity are of course the major issues. In the case of epoxides derived from terminal alkenes, a detailed study of the effect of varying the Lewis acid has been performed.170 It was shown that strong Lewis acids, e.g.TiC1, or TBr,, give the 2-halogenoprimary alcohol 15 (Scheme 58), while Lewis bases such as TiBr,(NEt,), give the regioisomeric secondary alcohol 16. The synthetic importance of this work is underlined by the fact that reagents and conditions have been found which enable either regioisomer to be prepared in high yield with about 95% regioselectivity. 120 Contemporary Organic Synthesis15 16 Scheme 58 Halogenative ring-opening of 2,3-epoxy alcohols (i.e, epoxides derived from allylic alcohols) gives a variety of regio- and stereo-isomers with the selectivity strongly dependent on the substrate and reaction condition^.'^^-'^^.Regioselective epoxide opening has been used to prepare enantiomerically pure 1,2-dibromo-3-chloropropane 17 from enantiomerically pure epichlorohydrin (Scheme 59).'74 t B r L C l 17 Scheme 59 In certain cases, the regioselectivity of epoxide opening can be switched by judicious choice of reagents (Scheme 60).175 Aryl ethers of 1,2-chlorohydrins can be prepared directly from epoxides as long as the aryl group is electron-deficient (Scheme 6 further versatility is added to the epoxide reaction manifold by the use of Swern conditions for direct oxidative conversion of epoxides to a-chloroketones in good yields.' 77 It is also perhaps worth mentioning that there are sometimes cases where it is more practical to prepare a 1,2-halohydrin by regioselective hydrolysis of a 1,2-dihalide.l 78 while 0 Ph v 0 PhH, A PhCOCI, PPh3 0 OCOPh 1 0 CI 6CO Ph Cl with SnCh 99:l (58% yield) with Bu2SnC12 13:87 (80% yield) Scheme 60 HetCl cat.DTMAC, A -93% HetO Het = electrondeficient aromatic DTMAC = dodecyltrirnethylammonium chloride Scheme 61 9.3 With C-C bond formation Two examples suffice to illustrate this approach. The first, an apparently general method for a-fluoro-b-hydroxyester synthesis, uses Refomatsky-type chemistry (with or without CeCl, catalysis) (Scheme 62),179 while the second (Scheme 63)lS0 uses an asymmetric boron ligand for the aldol condensation of an a-bromoacetate residue, The latter example has been described previously in the literature, but the reference cited herein includes key experimental improvements for larger scale work.C02Et 0 zn DMA -5% F F DMA = N, Ndirnethylacetamide Scheme 62 Scheme 63 10 References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 H. Uno and H. Suzukib, Synlett, 1993,9 1. M.A. McClinton and D.A. McClinton, Tetrahedron, 1992,48,6555. O.A. Mascaretti, Aldrichim. Acta, 1992,26,47. M.J. Silvester, Chem. Br., 1993,215. W.B. Mothenvell, Aldrichim. Acta, 1992,25,71. D.H.R. Barton, E. Csuhai, and D. Doller, Tetrahedron Lett., 1992,33,3413. D.H.R. Barton, E. Csuhai, and D. Doller, Tetrahedron, 1992,48,9195. D.H.R. Barton and D. Doller, Acc. Chem. 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Chern., 1993,58,3194. 109 S. Rozen and 0. Lerman, J. Org. Chem., 1993,58,239. 110 J. Auerbach, S.A. Weissman, T.J. Blacklock, M.R. 3072. 779. Angeles, and K. Hoogstein, Tetrahedron Lett., 1993, 34,931. 11 1 P. Bovonsombat and E. McNelis, Synthesis, 1993,237. 1 12 B. Bennetau and J. Dunogues, Synlett, 1993,17 1. 113 L.A. Jacob, B.-L. Chen, and D. Stec, Synthesis, 1993, 611. 114 L.J. Diorazio, D.A. Widdowson, and J.M. Clough, Tetrahedron, 1992,48,8073. 115 R.C. Cambie, M.R. Metzler, C.E.F. Rickard, P.S. Rutledge, and P.D. Woodgate, J. Organornet. Chem., 1992,431,177. 1 16 T. Fukuhara and N. Yoneda, Chem. Lett., 1993,509. 1 17 Y. Uchibori, M. Umeno, and H. Yoshioka, Heterocycles, 118 Y. Uchibori, M. Umeno, H. Seto, Z. Qian, and 119 R.D. Chambers, T.F.Holmes, S.R. Korn, and 1992,34,1507. H. Yoshioka, Synlett, 1992,345. G. Sandford, J. Chem. SOC., Chem. Commun., 1993, 855. 120 H.Hofmann, Spec. Chem., 1993,13,59. 121 K. Shinhama, S. Aki, T. Furuta, and J. Minamikawa, Synth. Commun., 1993,23, 1577. 122 N. Boechat and J.H. Clark, J. Chem. SOC., Chem. Commun., 1993,92 1. 123 T.O. Bayraktaroglu, M.A. Gooding, S.F. Khatib, H. Lee, M. Kourouma, and R.G. Landolt, J. Org. Chem., 1993, 58,1264. 124 J.Correia, J. Org. Chern., 1992,57,4555. 125 P. Vinczer, S. Sztruhar, L. Novak, and C. Szantay, Org. 126 M. Ochiai, K. Uemura, and Y. Masaki, J. Am. Chem. Prep. Proc. Int., 1992,24,540. SOC., 1993,115,2528. 127 A. Garcia Martinez, J.O. Barcina, A.Z. Rhys, and L.R. Subramanian, Tetrahedron Lett., 1992,33,7787. 128 C.-M. Hu, F.-L.Quing, and C.-X. Shen, J. Chem. Soc., Perkin Trans. 1,1993,335. 129 M. Tordeaux, K. Boumizane, and C. Wakselman, J. Org. Chem., 1993,58,1939. 130 Rhone Poulenc Chim., French Patent, FR-2672284 13 1 T. Yoshiyama and T. Fuchigami, Chem. Lett., 1992, 132 T. Kakinami, Y. Urabe, I. Hermawan, H. Yamanishi, (92-325965). 1995. T. Okamoto, and S. Kajigaeshi, Bull. Chem. SOC. Jpn., 1992,65,2549. 1992,33,4123. 133 P. Bovonsombat and E. 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Lauterbach, Heterocycles, 1993, 16 1 W. Pinyarat and K. Mod, Biosci, Biotech. Biochem, JP-4089434 (92-147549). 1992,22,2521. 141 1. 4. Tetrahedron Lett., 1992,33,6439. Tetrahedron Lett., 1992,33,4257. 35,627. Spargo: Organic halides 1231993,57,419. 162 H.-S. Moon, N.E. Schore, and M.J. Kurth, J. Org. Chem., 1992,57,6088. 163 0. Kitagawa, T. Hanano, K. Tanabe, M. Shiro, and T. Taguchi, J. Chem. SOC., Chem. Commun., 1992, 1005. 164 X.-F. Ren and E, Turos, Tetrahedron Lett., 1993,34, 1575. 165 L. Benati and P.C. Montevecchi, Tetrahedron, 1993,49, 5365. 166 Y. Takanohashi, N. Tabata, T. Tanase, and S. Akabori, J. Chem. SOC., Perkin Trans. 1,1993,813. 167 S.A. Lermontov, S.I. Zavorin, A.N.Pushin, A.N. Chekhlov, N.S. Zefirov, and P.J. Stang, Tetrahedron Lett., 1993,34,703. 168 EE. McDonald and S.J. Danishefsky, J. 0%. Chern., 1992,57,7001. 169 U.LunungandA.Kirsch, Chem. Ber., 1993,126,1171. 170 J.J. Eisch, Z.-R. Liu, X. Ma, and G.-X. Zheng, J. 0%. Chem., 1992,57,5140. 171 C. Bonini, C. Giuliano, G. Righi, and L. Rossi, Synth. 172 C. Bonini, C. Giuliano, G. Righl, and L. Rossi, 173 P. Bovicelli, P. Lupattelli, and M.T. Bersani, Tetrahedron 174 S.A. Kouzi and S.D. Nelson, J. Org. Chem., 1993,58, 175 I. Shibata, N. Yoshimura, and H. Matsuda, Tetrahedron 176 R.-H. Jin and T. Nishikubo, Synthesis, 1993,28. 177 S. Raina, D. Bhuniya, and V.K. Singh, Tetrahedron Lett., 178 S.S. Bhosale, P.L. Joshi, and A.S. Rao, Org. Prep. Proc. 179 Y. Shen and M. Qi, J. Chem. Rex (S), 1993,222. 180 E.J. Corey, D.-H. Lee, and S. Choi, Tetrahedron Lett., Commun., 1992,22,1863. Tetrahedron Lett., 1992,33,7429. Lett., 1992,33,6181. 771. Lett., 1992,33,7149. 1992,33,6021. Znt., 1992,24,695. 1992,33,6735. 124 Contemporary Organic Synthesis
ISSN:1350-4894
DOI:10.1039/CO9940100113
出版商:RSC
年代:1994
数据来源: RSC
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Stoichiometric applications of organotransition metal complexes in organic synthesis |
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Contemporary Organic Synthesis,
Volume 1,
Issue 2,
1994,
Page 125-143
Julian Blagg,
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摘要:
Stoichiometric applications of organotransition metal complexes in organic synthesis JULIAN BLAGG Pfizer Central Research, Sandwich, Kent, CT13 9NJ, UK Reviewing the literature from 1 July 1992 to 3 1 August 1993 1 2 2.1 2.2 2.3 2 -4 2.5 3 4 4.1 4.1.1 4.1.2 4.2 4.2.1 4.2.2 4.3 4.3.1 4.3.2 4.4 4.5 4.5.1 4.5.2 5 5.1 5.2 5.3 5.4 5.5 6 Introduction Transition metal alkyl, allyl, alkenyl, alkynyl, and acyl complexes in organic synthesis Hydrozirconation methodology Ally1 zirconium species Zirconacycles in synthesis Alkyl, allyl, alkenyl, and alkynyl chromium species in synthesis Acyl transition metal complexes in synthesis Transition metal carbene complexes in synthesis r] 2- r] 6-Complexes in organic synthesis r] 2-Complexes in organic synthesis q 2-Alkyne dicobalt hexacarbonyl complexes r] 2-Complexes of zirconocene r] 3-Complexes in organic synthesis r] 3-Complexes of iron tetracarbonyl q 3-Allyl molybdenum complexes in organic synthesis q4-Complexes of iron tricarbonyl in organic synthesis Acyclic complexes Cyclic systems r] 5-Cyclohexadienyl iron tricarbonyl cations in synthesis r]6-Complexes in organic synthesis $-Arene chromium tricarbonyl complexes in organic synthesis y6-Arene manganese tricarbonyl cations in organic synthesis Transition metal mediated cycloadditions in organic synthesis The Pauson-Khand and related cycloadditions Titanium- and zirconium-mediated cycloadditions Cobalt-mediated cyclotrimerizations Higher order [6n + 4n] and [6n + 2n] c ycloadditions Rhenium-promoted cycloadditions References 1 Introduction This review covers the literature from 1 July 1992 to 31 August 1993 and is a selective account of recent developments in the applications of stoichiometric organotransition metal chemistry to organic synthesis.Particular attention has been given to work of general applicability to the practising synthetic organic chemist and to reactions which lead efficiently to otherwise elusive structural entities. Areas which have seen particularly notable advances in their synthetic applicability in the period covered include hydrozirconation reactions, the use of carbene complexes in organic synthesis, and transition metal mediated cycloadditions. Relevant reviews published during the period are cited in the text. 2 Transition metal alkyl, allyl, alkenyl, alkynyl, and acyl complexes in organic synthesis 2.1 Hydrozirconation methodology The utility of the classical hydrozirconation reaction originally developed by Schwartz' has been considerably expanded over the past year with much of the work having general applicability in organic synthesis.For example, regioselective hydrozirconations of alkenes followed by transmetallation of the resulting alkylzirconate 1 (Scheme 1 ) with catalytic CuCN ( 1 Omol%) gives alkyl cuprates which can subsequently be used in coupling reactions with allylic chlorides, bromides, or phosphonates. For unsymmetrically substituted allylic systems the predominant mode of attack is S,2'. Unfortunately, couplings with monosubstituted epoxides, allylic acetates, and aryl or alkenyl halides were unsuccessful.2 Transmetallation of alkyl and alkenyl zirconates with CuBr.SMe, ( 5 - 10mol%) in the presence of an acid chloride gives ketones in a one-pot reaction.In the absence of a copper catalyst this reaction is very slow for alkylzirconates and fails for alkenyl zirconates (Scheme 1).3 An alternative approach to enhancing the reactivity of alkyl and alkenyl zirconates avoids transmetallation but uses a catalytic amount of AgClO, (0.1-5mol%) to generate the cationic species 2; reactions with aldehydes lead to a highly efficient C-C bond forming process (Scheme 2).4 Epoxides have been shown to react in a similar manner via in situ generation of an activated aldehyde. the presence of catalytic AgClO, has been applied to the highly E-selective synthesis of terminal 1,3-dienes via three-carbon homologation of an aldehyde The Grignard-like reactivity of alkenyl zirconates in Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 125r 1 J 1 10 mol % CuCN w c l 1 90% OTBDMS OTBDMS - 6;, (i) Cp&(H)CI, THF, 40°C (ii) 9'' , CuBr.SMe,(cat.) 0 6 0 5290 trans : cis ( 8 : 1) i- OTBDMS 4r 0 Scheme 1 Ph JH Ph &Bu * 90% Scheme 2 H-OEt 3 Cp,Zr(H)CI CH$I2,I0 min: (ii) H30+ (Scheme 3): Moreover, hydrozirconation of ethoxyethyne 3 or (2)- 1 -methoxy-but- 1-en-3-yne 4 followed by AgC10, catalysed reaction with aldehydes gives an efficient two-and-four-carbon homologation protocol respectively, leading to conjugated polyenals (Scheme 3).7 hydrozirconation of the allenyl stannane 5 to give the allylzirconate 6 which undergoes smooth reaction with aldehydes and ketones in the absence of any catalyst.Subsequent F,B .OEt, catalysed p-elimination affords an alternative approach to terminal E-dienes (Scheme 4).8 An interesting aspect of this chemistry is the 92% E : Z = 96 : 4 L J Scheme 4 Hydrozirconation products from acyclic alkenesy or a1kynesl0 have also been shown to be useful precursors to alkyl or alkenyl boranes respectively via transmetallation with BCl,, BBr,, or chlorocatecholborane. Hydrozirconations of various vinyl-9-BBN derivatives give 1 , 1 -dimetalloalkanes 7; the C-Zr bond can be selectively cleaved with bromine to give a-bromoboranes (Scheme 5).11 highly efficient synthesis of 2-alkenyl stannanes via the 1,l-dimetallic species 8. The dimetallic intermediates 8 offer the potential for regioselective Hydrozirconation of alkynyl stannanes gives a nC1 ,,H2,CH0 r.t, 1 h, then refludl h 82% E :Z = 97:3 rCHO 03% CHO U 126 4 (ii) H,O+ ao% Scheme 3 Contemporary Organic Synthesisfunctionalization using the differences in reactivity between alkenyl stannanes and alkenylzirconates (Scheme 5).12 r 1 Cp2Zr( H)CI THF, r.t.- Me-SnBu, Scheme 5 -sot Br2 I B u y Br 97% H Me HH SnBu, A novel synthesis of a,b-unsaturated esters has been developed via reductive deoxygenation of P-ketoesters. Generation of the zirconium enolate 9 followed by hydrozirconation and /3-elimination gives the corresponding a, /3-unsaturated ester (Scheme 6).', The extension of this work to amide and lactam deoxygenation is of particular synthetic utility (Scheme 6).14 L J 9 /\/CO2Et Ph \ i oZcp2H 1 ( i ) KH, THF, 0°C dNHph (ii) Cp&(H)CI, - 20°C -+ phANJPh 78% Scheme 6 An alternative method for the generation of alkenyl zirconates involves zirconium-mediated carboalumination of alkynes.I5 A recent paper reports a significant increase in the rate of carboalumination in the presence of water, such that reaction can be achieved at - 23"C.16 2.2 Ally1 zirconium species The generation of allyl zirconium species via P-elimination of the alkoxy group from the zirconocene complexes of a, p-unsaturated acetals 10 has recently been developed (Scheme 7).17 The allyl zirconium intermediates react in a diastereoselective manner with a variety of aldehydes and ketones to give predominantly syn or anti 1,2-dioxygenated species in the presence or absence of a Lewis acid respectively.Although allyl zirconium species do not react with alkynes, the allylation of alkynes can be achieved via reaction of zirconocene-alkyne complexes 1 1 (prepared from the corresponding alkyne and Cp,ZrBu;) with an appropriate allylic ether. The reaction is highly regioselective with C-C bond formation occurring only at the y-position of the allylic ether. P-Elimination of the alkoxy substituent in the zirconacycle intermediate 12 is postulated to account Lc eme for the formation of the 1,4-diene products (q h P-Elimination of an alkoxy group in the zirconocene complex of an allylic ether also results in a mild, efficient deprotection method for allyl ethers (Scheme 7)." 7 ) . ' 8 2.3 Zirconacycles in synthesis The use of zirconacyclopentenes in synthesis continues to increase; the last year has seen important developments in the methodology of zirconacycle formation and subsequent trapping.A more facile route to these complexes which avoids the use of PMe, or hydrozirconation has been reported via reaction of diethylzirconocene and an alkyne. Subsequent Cb-Cp' bond cleavage, with extrusion of ethylene, provides a convenient source of Cp,Zr-alkyne complexes which can be trapped by a variety of unsaturated functional groups (Scheme 8).20 Although the former protocol is limited to the use of diethylzirconocene it has recently been shown that more general pair-selective couplings of alkynes and alkenes can be achieved if excess alkene is present.2' functionalization of the C-Zr bonds of zirconacyclopentenes and zirconacyclopentanes have also been introduced in the last year and these greatly increase the synthetic potential of zirconium-mediated coupling reactions.For example, protonation of zirconacyclopentenes 13 occurs regioselectively at the alkylcarbon-zirconium bond2* whilst the corresponding symmetrical zirconac yclopentane 1 4 undergoes selective monoprotonation, allowing halogenation of the remaining alkyl-zirconium bond (Scheme 9).23 Important methods for the regioselective Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 1271 OEt I -1 10 OH 1 0 Et I OEt ChZr/\=/ SYn No Lewis Acid 14 1.m F3B.OEtZ n (i)cpgBuT (?H MF, - 78 “C + r.t.* p h j \ 97% PhA (ii)iN HCI Scheme 7 F? 1 R3CN R3CH0 Scheme 8 2.4 Alkyl, allyl, alkenyl, and alkynyl chromium species in synthesis The use of organochromium reagents in organic synthesis has been rapidly increasing over the past decade; of particular note is the increased use of allyl, alkenyl, and alkynyl chromium reagents in C-C bond forming reactions.24 The period under review witnessed some useful extensions of the methodology, particularly in the field of y-substituted allyl chromium reagents.The first silyl substituted allyl chromium reagents have been shown to react with aldehydes in a 1 OCH0 anti 86 59%yield 23 85%yield 12 Ph - H + Me3SiYbx 1.5 eq. 13 81 % ’ Ph CkZr y I OMe 1.2 eq. 12 (single isomer) 78% 14 L J Br% 88% Scheme 9 highly regio- and diastereoselective manner to give anti B-hydroxysilanes 15 (Scheme 1 O).25 Although this class of reaction is normally highly diastereoselective regardless of the stereochemistry of the starting allylic halide, it has now been demonstrated that y, y-disubstituted allylic phosphonates 16 react with CrC1, and aldehydes without equilibration of the allyl chromium intermediate (Scheme 1 O).26 128 Contemporary Organic SynthesisM e 3 S i v B r + Me3si'(\\ br CrCI2, PhCHO THF, r.t, 2h I &Me, 15 (69%) * w n h e x P r ~ O P ( O ) ( O e ) , n-hexCHO.XrC12 LiI(O.2eq) Bu DMA 25 "C, S12h Bd Pr 16 Bu,p,0P(0)(OEt)2 n-hexCHO, LiI(0.2eq) XCIL +nhex Pr DMA25"C, 3-12h pi B' a : M A B r . CrCI,, F3B.0Et2, THh N * .N (ii) NaSO3, H20 Ph 65% PhKH 17 Scheme 10 The highly stereoselective reaction of y-substituted allyl chromium reagents with aldehydes in an intramolecular sense has recently been utilized as a key step in the total synthesis of Acer~solide.~~ A new development is the reaction of allyl chromium species with activated aldimines 17 to give homoallylic amines (Scheme 1 O).28 The reaction of propargylic chromium species with aldehydes2' has been extended to functionalized propargylic reagents, This work exemplifies the selectivity of formation of the chromium( 111) intermediate since ester, cyano, or chloro groups do not interfere (Scheme 1 I).," The intramolecular cyclization of alkynyl iodides onto aldehydes mediated by CrCl,/NiCl, has continued to be applied to organic synthesis; two elegant examples of this approach are the total synthesis of the macrocycle taxamycin31 and the oxabicyclo [ 7.2.13 enediyne moiety from a sensitive furanoside precursor.32 Scheme 11 The use of a gem-dichromium reagent derived from Bu,SnCHBr2 with aldehydes has been demonstrated to give E-vinyl stannanes (Scheme 1 2).33 This procedure is complementary to the 2-vinyl stannane synthesis reported by Lipshutz (Scheme 5).12 SnBu3 ocHo CrCI, Bu3SnCHBr,LiI DMF, THF, 25°C 62% Scheme 12 2.5 Acyl transition metal complexes in synthesis Applications of stoichiometric transition metal-acyl complexes have largely involved exploitation of the stereochemical control exerted by the chiral auxiliary CpFe( CO)PPh,. Highlights include the asymmetric synthesis of ( - )-Actinonin and ( - )-epi-A~tinonin,,~ (3R,4S)-Stati11e,~~ as well as the synthesis of S-( - )-methyl tropinate 19 via a novel benzyne-mediated arylation of the homochiral complex 18 (Scheme 1 3).36 (iii) MeOH 18 ( i ) Bu"U (ii) PhAO*CI 1 19 (44% overall) Scheme 13 A series of homochiral organometallic NADH mimics which exert their stereocontrol via attachment of the chiral auxiliary CpFe(CO)PPh, to the C-3 carbonyl of the 1,4-dihydronicotinoyl moiety have been investigated.These complexes stereoselectively reduce ethyl benzoylformate with high enantiomeric excess.37 3 Transition metal carbene complexes in synthesis The period under review witnessed interesting extensions of the use of chromium, molybdenum, and tungsten carbene complexes in organic synthesis. Particular highlights include a novel dipeptide synthesis and the intramolecular trapping of carbenes in a variety of ring-forming reactions of potential synthetic interest.been coupled with subsequent intramolecular nucleophilic substitution of the intermediate ( q6-arene)Cr( CO), complexes. This tandem reaction sequence involves a crucial in situ protection of the phenol generated in the first step and can provide a novel entry into tetracyclic systems (Scheme 14).38 The classical reactivity of Fischer carbenes has now Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 129Scheme 14 77% X (? 12e.q LDA, -78 "c to 0 "c (11) 7 8.q I*, 0 "C to r.t. OTI PS OMe SPh OMe 85% The classical reaction of vinyl chromium carbene complexes with alkynes depicted in Scheme 14 has been shown to proceed with improved rate under milder conditions using dry state absorption conditions first applied to the Pauson-Khand cyclization. Promotion of ligand exchange in the intermediate carbene complexes via donor centres on the solid support is believed to accelerate the reaction.39 undergo exclusive 1,4-addition to enones; indeed, chiral carbene complexes give good diastereoselectivities in their Michael additions.These reactions display the highest facial selectivity observed in enolate-type additions to enones; they proceed via a kinetically controlled process and readily yield the free organic product via oxidation (Scheme 1 5).40 Anions of aminocarbenes 20 have been shown to 20 95% e.8. 51% yield Scheme 15 In contrast to classical metalloenolates the delocalized aminocarbene anion is a soft nucleophile.The carbene functionality also significantly modifies the reactivity of the dienophile in Diels-Alder reactions; for example, the alkyne complex 2 1 undergoes a facile cycloaddition with cyclopentadiene in contrast to the free propriolic amides which do not react (Scheme 16).41 Similar effects are seen in the intramolecular Diels-Alder reaction; the carbene moiety acts as an internal Lewis acid, giving rise to higher endolexo selectivities and shorter reaction times (Scheme 1 intramolecular alkyne trapping of Fischer carbenes has also been reported, leading to a novel synthesis of functionalized quinones under photochemical condition^.^^ Intramolecular trapping of a carbene with The use of a silicon tether to promote the N 21 81 % end0 X = W(CO), 80 "C, 6h 88% >98 x=o 150 "C, 24h 65% 60 x=o EtAICI,, 23 "C, 36h 60% 100 Scheme 16 a pendant alkyne generates a second carbene species which, in the presence of an internal alkene trap, gives rise to a novel, tandem ring-forming process (Scheme 1 7).44 Scheme 17 A number of publications have appeared on intermolecular ring-forming reactions from carbene complexes, in particular leading to five- or seven-membered rings. Herndon has demonstrated an interesting divergence of reactivity between cyclopropylcarbene-chromium complexes 22 and their molybdenum and tungsten analogues. The former, on trapping with alkynes, give predominantly five-membered ring products whilst the molybdenum and tungsten analogues give seven-membered rings (Scheme 1 8)?5 A similar difference in reaction pathway is found in the reaction of simple alkyl carbene complexes with alkynes; the chromium derivatives yield cyclopentenones whilst the molybdenum and tungsten analogues yield 1,3-diene~.~~ Seven-membered rings can be formed from vinyl chromium carbenes, however, via an interesting Cope rearrangement on the initially formed cyclopropane 23 (Scheme 19).47 The potential for stereocontrol of this process has been exploited by Barluenga via use of a chiral2-amino-buta- 1 ,3-diene.48 A novel entry into y-lactones has been reported via C-H insertion of an in situ generated non-heteroatom stabilized carbene complex 24 (Scheme 20).Using this methodology, Eldanolide was prepared in 50% overall yield with high trans-stereoselectivity (Scheme 20).49 One of the highlights of chromium carbene chemistry has been the photolytic coupling of chromium aminocarbene complexes to give a 130 Contemporary Organic SynthesisD4cr(c0)5 OMe =!(OM= w e (1) 22 0 0 THF. CO, 80 "C, 3d (ii) aq.HCI - + Ph Me0 Ph 78% (85:15,tramciS) 2% p(M0(c0)5 PhCZCPh Ph THF, 65 "c, 2h OMe OMe 52% Scheme 18 qH,OMe h + H + Me-,+ Ph MeCN 25"C,2h I r OMe L 23 3rd. HCI, THF, 25 "C, 2h I Me 82% Scheme 19 stereoselective peptide synthesis via chiral ketene complexes (Scheme 2 1).50 The intramolecular trapping of similar chiral aminoketene complexes facilitated a new synthesis of arylglycine~.~~ The photolysis of optically active aminocarbene chromium complexes 25 with N-protected imidazolines has also been shown to give a-amino protected azapenems 26 with high diastereoselectivity (Scheme 2 1).52 Recently, Petasis has reported a new convenient method for the methylenation and benzylidenation of 24 Ph Go 50% trans:ciS Eldanolide 24:l Scheme 20 \ C02Bu' hv, THF I 77% (93:7 d.e.) Scheme 21 26 (>97% d.e.) Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 131aldehydes, ketones, esters, lactones, and amides via dimethyl- and dibenzyl-titanocene derivatives respectively.He has extended this methodology to the synthesis of vinylsilanes and vinylcy~lopropanes.~ However, these reactions require rather high temperatures and give a low Z/E selectivity. Grubbs has recently reported the new carbene species 2 7 which selectively reacts with the alkene of an olefinic ketone to form a new alkylidene complex via olefin metathesis; subsequent intramolecular carbonyl olefination leads to cycloalkenes (Scheme 22).54 This strategy is effective for the synthesis of five-, six-, and seven-membered rings; the more reactive tungsten analogue of 27 allows the formation of cyclic enol ethers from acyclic olefinic esters.Q benzene, 20 "C, 30 min. 27 Scheme 22 4 qz- q6-Complexes in organic synthesis 4.1 rf-Complexes in organic synthesis 4.1.1 qz-Alkyne dicobalt hexacarbonyl complexes The Nicholas reaction of dicobalt hexacarbonyl stabilized propargyl cations with nucleophiles has been widely used in organic synthesis, in particular to avoid the allenic by-products associated with classical propargylation reagents. Few examples of reactions with nitrogen nucleophiles have been published; however, Roth has now demonstrated the facile reaction of a range of cobalt-stabilized propargylic cations with primary and secondary amines, although a mixture of mono and bis propargylated products may be obtained from reactive primary a m i n e ~ .~ ~ An efficient C-3-propargylation of indoles has also been reported via reaction with cobalt-stabilized propargylic cations; no products from attack at the indole nitrogen or other aromatic positions were detected.56 A novel diastereoselective propargylation reagent has been reported by Nicholas in which replacement of one of the CO ligands on cobalt with the n-acceptor ligand tris( 1,1,1,3,3,3-hexafluoroisopropyl)phosphite gives a more electrophilic chiral complex 28, capable of stereocontrolled reaction with carbon nucleophiles.The complexes 28 are formed as easily separable diastereoisomers from chiral alcohol precursors; reaction of a single diastereoisomer with silyl enol ethers proceeds with complete retention of configuration at the propargylic carbon atom (Scheme 23).57 Propargylic cations are presumably implicated in the a to B epimerization of C-1-alkynyl substituted pyranose derivatives 29 via their dicobalt hexacarbonyl derivatives (Scheme 23). OH H,+<-Ph H Acol Scheme 23 This acid-mediated transformation was also examined using 2-substituted A3.4 substrates. The even higher a$ ratios observed with these substrates was attributed to the unfavourable interaction of the bulky coordinated alkyne with the pyranose 2-substituent in the a - a n ~ r n e r .~ ~ observed in the additions of nucleophiles to complexes of propynal with hexacarbonyldicobalt 30; addition of 0-silylketene- 0,s-acetals gives rise to a highly syn selective aldol reaction which complements the corresponding anti selective aldol reactions of uncomplexed propynal3 1 (Scheme 24). This methodology has been applied to the synthesis of p-lactamss9 and the antibiotic Blastmych60 A high degree of stereocontrol has also been H OTMS HSBut Me TMS-CHO + TiCi4 Me I 31 TMS antisyn (95:5) I 30 (i) TIC14 (ii) CAN 1 TMS syn :anti(>98:<2) Scheme 24 132 Contemporary Organic Synthesis4.1.2 q*-Complexes of zirconocene q 2-Complexes of imines have been widely used as a means of functionalizing the a-position of amines; this process has been carried out in a highly enantioselectve manner through the use of a chiral zirconium reagent to give homochiral allylic aminese6 Taguchi has adopted an alternative approach via attachment of a chiral group onto the nitrogen of the precursor aldimine 32 (Scheme 25).Although a degree of stereocontrol could be observed in the formation and trapping of the q *-imine complexes, the reactions were highly temperature dependent.62 The activation of positions a to nitrogen in an aromatic system has been extended from pyridines to pyrazines by Jordan. The q 2-pyrazine complexes are formed from the cationic complex Cp,Zr(CH,)(THF )+ 33 via a C-H activation/CH, elimination sequence (Scheme 25).6, 4.2 q3-Complexes in organic synthesis 4.2.1 q3-Complexes of iron tetracarbonyl The regio- and stereo-selective substitution of an allylic leaving group is commonly achieved via n-ally1 palladium intermediates in a catalytic manner; however, the more electrophilic n-ally1 complexes of iron tetracarbonyl react with a wider range of nucleophiles in a similar but stoichiometric manner. The high degree of stereocontrol associated with reactions via cyclic q 3-iron intermediates is exemplified by the synthesis of C-5 substituted pyrrolidinones 34 (Scheme 26).63 Complexation of the homochiral pyrrolidinone 35 gave a mixture of cis and trans q 2-complexes 36 which could be separated.Lewis acid catalysed reaction with allylsilanes occurred via the corresponding q 3-complexes with predominant inversion or retention respectively.Acyclic stereocontrol has also been achieved in the reaction of nitrogen nucleophiles with (E)-( 4s)-( - )-benzyloxypent-2-enoic ethyl ester 37 via formation of the intermediate n-ally1 complex 38 and regioselective y-attack on the face of the complex away from the bulky metal moiety (Scheme 26).6, The Lewis acid catalysed reactions of nucleophiles with iron tetracarbonyl complexes of y-benzyloxy- a, B-unsaturated ketones 39 also proceeds, to give exclusively the y-substitution products, with retention of double-bond configuration (Scheme 26).65 n-Ally1 palladium complexes can undergo facile synlanti isomerization to the favoured anti isomer; however, the corresponding iron tetracarbonyl systems appear stable to isomerization; for example, E or 2 vinyl silanes may be prepared via regioselective y-attack on the stereochemically defined silyl substituted syn and anti n-ally1 complexes 40 and 4 1 respectively (Scheme 27).66 4.2.2 q3-Allyl molybdenum complexes in organic synthesis The reactions of aldehydes with allyl molybdenum complexes occurs with high stereoselectivity; however, to date, the ready availablility of homochiral allyl boron and allyl titanium reagents has led to their preferential use in synthesis.Faller has now reported the resolution of q ,-2-methallyl molybdenum complexes via the covalent attachment of a camphorsulfonate ligand to the metal. Although this procedure does not yield the homochiral parent q 3-allyl complex, the 2-methallyl complex 42 is 32 (9 C@BU~" (ii) PhCHO, THF Temp.0 "C 94 6 Reflux 5 95 Scheme 25 Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 133Cis: t m n ~ = 3:l 37 (>95% e.e.) 0 1 53% 55% 8.8. 51% >95% 8.8. 0 91% (97% e.e.) 39 Scheme 26 01 % L J E -only (9 (ii) F3B.OEt2, 6"" CH&12 e S i M e 3 (iii) air 41 OAc 54% 0 SiMe, (i) FaB.OEt2, CH&12 (ii) $ISiMe3 P? 61 % U (iii) air 40 Scheme 27 accessible and reacts with aldehydes to give enantiopure allylic alcohols (Scheme 28).67 Cyclic q 3-allylmolybdenum complexes have been used in the enantiospecific synthesis of pyranose derivatives; reaction of the readily available lactone complex 43 (Scheme 28) with Et,O+PF; generates the air-stable cationic complex 44 which can be reacted with nucleophiles in a highly regio- and stereo-specific manner.The incoming nucleophile approaches the ally1 moiety away from the metal, to generate the trans isomer 45. Reformation of the cationic complex and hydride addition gave the corresponding cis isomer 46. Stereospecific synthesis of gem-disubstituted pyranose derivatives may also be achieved via this methodology.68 4.3 q4-Complexes of iron tricarbonyl in organic synthesis 4.3.1 Acyclic complexes The iron tricarbonyl moiety has been widely used as a stereocontrol element in the diastereoselective generation of chiral centres adjacent to a conjugated diene, generally via nucleophilic attack on a pentadienyl cation or on an adjacent carbonyl group. Methodology exists for preparing homochiral diene iron tetracarbonyl complexes either via classical resolution69 or enzymatic kinetic resolution70 and these techniques have been expanded upon in the last year.71 The utility of homochiral q 4-diene iron tricarbonyl complexes in synthesis is exemplified by the recent synthesis of hydroxylated eicosatetraenoic acids by Lellouche and Gree.The key step involves diastereoselective dihydroxylation of the alkene adjacent to the complexed diene moiety of 47 (Scheme 29).72 The diastereoselective alkylation of carbanions generated a- to the complexed dienyl moiety of racemic tricarbonyl( methyl-hexa- 3,5-dienoate) iron 134 Contemporary Organic SynthesisPhCHO, MeOH, CWI3 c Ph lW!, l l h S ON- - -Mo c" v Me 42 >98% e.8. @ I 43 Et30* PFs- I 45 (i) Ph&'PFe- (ii) Na BH4 1 Q I 44 H 46 Scheme 28 has also been reported.73 Application of the resolution procedures discussed above should permit the use of this methodology in homochiral synthesis.iron tricarbonyl have been extended to the corresponding a, B-unsaturated acyl silanes (Scheme 29).74 Reaction with alkyllithiums generates 174-dicarbonyl products 48, in accord with the chemistry of other q4-ct, P-unsaturated ketone complexes of iron tricarbonyl. The q4 complexes of a, B-unsaturated ketones with 4.3.2 Cyclic systems The regio- and stereo-selective functionalization of cycloheptadienones, cycloheptatrienones, and cyclooctadiene via their q 4-iron tricarbonyl-type complexes has resulted in some particularly useful applications to organic synthesis in the past year. For example, ( q4-tropone)Fe(CO), 49 can be stereoselectively reduced to the protected alcohol 50; subsequent osmylation gives the single triol derivative 5 1 , a key precursor for the synthesis of heptitol derivatives (Scheme 30).75 The corresponding cycloheptadienone complex 52 has been prepared via > C02Me 0 P h d S i B u ' M e , Et20,35 "C, 14h : kiBu'Me, 94% k 3 3 SiBu'Me, 0 48 Scheme 29 highly regio- and stereo-selective iron tricarbonyl directed hydroboration of the q4-triene complex 53 followed by oxidation (Scheme 30).Double hydroxylation of 52 is accomplished via sequential treatment with KHMDS and the Davis oxaziridine reagent; alcohol protection and reduction of the central carbonyl moiety then affords the protected triol 54 with three contiguous chiral centres. Dimethylation of 52 followed by reduction of the central carbonyl gives the alcohol 55.This material is a key precursor for the synthesis of the C-10 to C-13 portion of Calyculin A and the C- 19 to C-25 subunit of Swinholide A (Scheme 30).7h It should be noted that in the cycloheptadiene work, one of the ligands on the iron has been replaced with triphenylphosphite, a poorer n-acceptor which reduces competing reactions on the CO ligands. This strategy has been crucial in controlling the chemistry of the corresponding cyclooctadiene derived complexes where replacement of one CO by PPh, gives the versatile key intermediate 56 (Scheme 30), which can be functionalized either by hydroboration of the uncomplexed alkene, nucleophilic attack on the q "dienyl complex, or Friedel-Crafts type alkylati~n.~~ 4.4 q5-Cyclohexadienyl iron tricarbonyl cations in synthesis Nucleophilic attack onto q s-cyclohexadienyl tricarbonyl iron cations is well researched and occurs exclusively at the termini of the n-system on the face Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 135(I) NaBH&eCI3 0 (ii) TBDMSOTf, CH$12 - pyridine 49 Fe(CO), osmylatbn D O T B D M S 6 OTBDMS H Hd OH 50 51 53 Fe(C0)2PPh3 0 56 Scheme 30 \\ 0 0 PhCH'-NSOPh Fe(CO),P(OPh), Fe(CO),P(OPh), (i) Et~SiOTf,2,6-lutiiine - &SiEt3 Et3Si OH Q--OH (ii) LBH4 OH 0 54 away from the metal moiety.The application of this type of methodology to the synthesis of alkaloid skeletons has recently been reviewed,78 although McKillop and Stephenson subsequently published a synthesis of tetrahydrophenanthrene derivatives 58 via cuprate attack onto the 7 5-cyclohexadienyl cation 57 followed by regeneration of the cationic system and spontaneous intramolecular ring closure (Scheme 3 1).79 Other applications of nucleophilic attack onto 7 5-cyclohexadienyl cations have been numerous in the past year; highlights include nucleophilic attack by serine derived zinc/copper reagents in the synthesis of a-substituted amino acids 59 (Scheme 31)80 and nucleophilic attack by alkynyl cuprates to give the substituted cyclohexenone 60 (Scheme 3 1).81 iron cationic complexes have been generated in The corresponding acyclic q 5-dienyl tricarbonyl enantiomerically pure form by Donaldson, and applied to the enantioselective synthesis of 5-hydroxyeicosatetraenoic acid methyl ester.A key step involved the reaction of the homochiral cation complex 6 1 with a cuprate to give the dienediynoate 62 (Scheme 32).82 The ester was subsequently reduced to the aldehyde which was subjected to a second stereocontrolled nucleophilic attack to introduce the chiral centre a-to the diene as required in the natural product. 4.5 $-Complexes in organic synthesis 4.5.1 q66-Arene chromium tricarbonyl complexes in organic synthesis The preparation of simple enantiomerically pure q6-arene chromium tricarbonyl complexes as synthons 57 58 k02Bn MeCN NHBoC .. .. I-... .b I- L- 68% 136 Contemporary Organic Synthesishas been well studied in recent years; the best methods involve resolution of o-substituted benzaldehyde chromium tricarbonyl complexes via the formation of diastereomeric derivative^.^^ A potentially exciting new approach involves the catalytic asymmetric induction of planar chirality in g6-( 1,2-dichlorobenzene)Cr(CO), 63, via palladium-catalysed cross coupling with a vinyl metal species in the presence of a chiral ligand on palladium, although the enantioselectivities to date have been low (Scheme 33).84 Applications of such enantiomerically pure complexes to organic synthesis include the diastereoselective 1,4-additions of cuprates to o-substituted E-enone complexes 64 (Scheme 33)85 and diastereoselective aldol reactions on the complexed acetophenone 65 (Scheme 33).86 S-t-butylbenzyloxyethanethiolate 66 to the enantiomerically pure aldehyde 67 has been used to give the anti aldol product in a highly stereoselective reaction (Scheme 34).87 Stereoselective benzylic alkylation of enantiomerically pure complexes 68 has also been demonstrated (Scheme 34).88 The susceptibility of arene chromium tricarbonyl complexes to nucleophilic attack on the 7 6-arene ligand has continued to be exploited.Kundig has extended the previously published tandem nucleophilic addition acyl transfer methodology to homochiral oxazolidinone substituted arene ligands The nucleophilic addition of the titanium enolate of d H anti SYn 95 : 5 (i) Bu'Li, THF (iii) MeI, THF (iii) hv,Op,Et@ qoMe dr(co>, OMe OMe Scheme 34 69; two new chiral centres are generated on a highly functionalized six-membered ring (Scheme 35).*' Semmelhack, both of which involve the nucleophilic Two total syntheses have recently been described by PFS CuBr.Me# EtS:THF(4:1). -45 "c 64% Me02C 61 62 Scheme 32 64 diastereorner 92:8 ratio Scheme 33 Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 137(i) MeLi, THF (iii) NaWMeIIHMPA (U) MI, MecNlco w (ill) NH4PFs Y (ii) NBSnt@ (31) 0.25N HCI (iv) benylchloroformate. NaHC03, r.t.. 1 t 58% Bu' l-3' 0YN (98% d.e.) 69 Scheme 35 attack of a stabilized carbanion on an ( v6-indole)Cr(CO), moiety as the key step. In the total synthesis of Clavucipitic acid an a-amido carbanion is used in the key step of a stereoselective, intramolecular attack on the indole C-4 position of 70;90 whilst in a formal total synthesis of Telocidin A the nucleophile is an a-cyano stabilized carbanion which attacks the indole C-7 position of 7 1, the alternative C-4 position being blocked (Scheme 34).91 (i) LDA, -78 OC to- (11) 12, - 78 % to r l .(CO),Cr Ph-& bh 70 + ,Si. .0 ' Y H ' dN-jH Ph I 1 Scheme 36 4.5.2 q6-Arene manganese tricarbonyl cations in organic synthesis q 6-Arene manganese tricarbonyl cations have been less thoroughly investigated than their neutral chromium tricarbonyl counterparts; however, their cationic nature renders them more reactive to nucleophilic attack on the coordinated arene. Grignard reagentsY9* enolate anions, and malonate anions have all been shown to add in an efficient manner; moreover, improved preparative procedures for cationic arene manganese tricarbonyl complexes make their use in organic synthesis more a~pealing."~ Pearson has used this methodology in an extension of his previous worky4 to prepare the diaryl ether subunit of Ristocetin A.The key step involves the nucleophilic attack of the protected aryl glycine phenoxide anion 72 onto the arene manganese tricarbonyl cation 73 to generate a highly functionalized diaryl ether which is then subjected to a second nucleophilic attack by the Schollkopf glycine enolate equivalent to give, after deprotection, the target compound 74 (Scheme 37).g5 H Meo&+NHBoc OMe 74 Scheme 37 5 Transition metal mediated cycloadditions in organic synthesis 5.1 The Pauson-Khand and related cycloadditions There have been significant improvements in the Pauson-Khand reaction in the last few years; in particular, the use of amine N-oxides or phosphine oxides to generate a free coordination site on the cobalt moietyg6 and the use of dry state absorption conditionsg7 or sonicationg8 to lower the reaction times and temperatures.The use of DMSO in dichloromethane (or benzene) has also been shown to promote the Pauson-Khand reaction." The use of pendant coordinating ligands to accelerate the intramolecular reaction has been explored; for example, pendant sulfides capable of liberating a free coordination site on the cobalt allow high conversions after 15 minutes at 71°C.100 Recently, the scope of the reaction has also been extended with the finding that electron-deficient alkenes and alkynes can participate. For example, cyclization of the conjugated alkynoates 75 can be achieved using the mild amine N-oxide mediated conditions, although the alkyne must bear a terminal substituent for good yields (methyl or phenyl for example) (Scheme 38).lo1 1,6-Enynes 76 undergo cycloaddition in acetonitrile at 75°C despite the electron-deficient alkyne moiety; the choice of solvent and the beneficial effect of a gem-dialkyl substituent in the ring-closure contributes to the success of this process (Scheme 38).lo2 The classical intramolecular Pauson-Khand cycloaddition of N-protected propargylamines usually gives unsaturated products i.e. 3-azabicyclo [3,3,0]oct- 1 -ene-7-ones.However, performing the reaction under the dry state absorption 1 3 8 Contemporary Organic Synthesis75 76 Scheme 38 conditions vide supra in an inert atmosphere gives exclusively the saturated bicyclic system 7 7 (Scheme 39).'03 77 Scheme 39 Several applications of the classical Pauson-Khand reaction to total synthesis have been reported in the last year, including the preparation of pentalenone,lo4 whilst the milder amine N-oxide promoted cycloadditions have been used in the total synthesis of Loganinlo5 and ( - )-Kainic acid.'06 A combination of the ability of cobalt complexed alkynes to stabilize a propargylic cation and then to promote a cycloaddition has been used before as a strategy in total synthesis.'07 A new version of this approach involves the electrophilic addition of an a, P-unsaturated carbonyl compound to a cobalt complexed conjugated enyne to give the Pauson-Khand precursor 78; after reduction of the a, P-unsaturated ketone to an allylic alcohol, this then cyclizes to afford the highly functionalized bicyclic system 79.A range of tri- and tetra-cyclic skeletons were prepared using this powerful methodology (Scheme 40).'08 c02(c0)6 H c02(c0)6 I (i) [ &i+BF4-] I-+ OMe M e \ c (ii) MeOH 78 (I) MeMgI (ii) [2+2+1] 1 Me OHMe 79 Scheme 40 The Pauson-Khand type cyclization reaction has also been achieved with Mo( CO), in the presence of DMS0,1°9 W(CO),THF,llo Ni(CO),,"' and Fe( CO),.' * A potentially useful iron-mediated carbonylative cycloaddition of 1,1,3 trisubstituted conjugated dienes 80 has also been reported (Scheme 4 l).' l 3 ( R)-(+)-PUIWOIW 80 AIBr3Fe(C0)5 CO. CH&IZ, 20 "C I = H" so Scheme 41 5.2 Titanium- and zirconium-mediated cycloadditions The well known reductive cyclization of enynes mediated by zirconium or titanium metallacycle formation has continued to be applied to organic synthesis.The lower oxophilicity of titanium versus zirconium allows a wider functional group tolerance in this type of reaction. Advances have been made in methods for functionalization of the intermediate metallacycles (see also section 1.3); for example, trapping of metallacycle 81 with an isocyanide allows the introduction of an exocyclic nitrogen (Scheme 42),' l 4 and whilst one further C-C bond forming step has been incorporated by interception of the 11 2-imine complex 82 from isocyanide trapping of the intermediate zirconacycle formed from c ycloaddition of the diallyl species 83 (Scheme 42).'15 zirconium-mediated carbonylative cyclization strategy is the recently published synthesis of Dendrobine by Mori in which the key step involves a regio- and stereo-controlled construction of the tricyclic Dendrobine skeleton 85 in a single step from an enantiomerically pure carvone derivative 84 (Scheme 43).lI6 Stille has recently published a carbocycle-forming reaction which occurs via intramolecular insertion of alkynes into Ti-C bonds (Scheme 44),ll7 This type of reaction has previously been accomplished with alkyl magnesiums and alkyl lithiums.The advantage of the titanium species is their relative stability towards hydrolysis and air oxidation. The reactions proceed in high yield under Lewis acid catalysis. A particularly elegant application of the 5.3 Cobalt-mediated cyclotrimerizations The formation of aromatic rings via cobalt-mediated [ 2 + 2 + 21 cycloadditions has continued to be applied Blagg: Stoichiometric applications of organotransition metal complexes in organic synthesis 13981 BU'NC I C C O z M e (9 C@G12,2~q BU"Li,THF - 78 "C (10 PrC=CPr,PhNC,THF,20 "C B"o< 63 Y B"*%ZP2 [ I (i) 67 "C, 3h (ii) MeOH, H$ Y H Pr 68% (55:45 mix d diastereomers) Scheme 42 0.84 Scheme 43 85 Scheme 44 Scheme 45 Several synthetically useful variants of this strategy have been reported over the past year, including reactions of coordinated cycloheptatrienes 86 with isocyanates (Scheme 46)121 and the reaction of coordinated N-carboxyazepines 87 with 4x and 2x systems (Scheme 46).12* The intramolecular versions of these reactions have also been reported123 and, more sigmficantly, a catalytic version.24 in synthesis;' l8 a particularly interesting report C0,Me c02w 1 concerned the use of supercritical water (374°C) to promote the cyclotrimerization of alkenes.' l 9 A recent approach to the synthesis of the alkaloid Lycorane (Scheme 45) illustrates the rapid construction of polycyclic systems via the cobalt-mediated [ 2 + 2 + 21 cyclization strategy. 2o Scheme 46 0 88% - HeFHo2Et \ / tw. pyrex, P C o g t - 'Cr(C0)3 87 5.4 Higher order [6n + 4n] and (6n + 2 4 cycloadditions 5.5 Rhenium-promoted cycloadditions A relatively new development in metal promoted cycloaddition chemistry is the use of chromium tricarbonyl coordinated trienes in higher order [6x + 4x1 and [6x + 2x1 cycloaddition reactions. 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ISSN:1350-4894
DOI:10.1039/CO9940100125
出版商:RSC
年代:1994
数据来源: RSC
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