摘要:

~~ Contemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, and Medicine Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology 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, Universite' de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R. Noyori, Nagoya University Professor L.E. Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla 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 Dr S. R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK.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. 1996 subscription rates: EEA f185, USA $350, Canada 2190 (plus GST), Rest of the World X190. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Second class postage is paid at Rahway, NJ.USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. (3 The Royal Society of chemistry, 1997 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 in Great Britain by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd VContemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P.D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, and Medicine Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology Professor E. J. Thomas, University of Manchester International Advisory Board Professor E. J. Corey, Haward University Professor S. Hanessian, Universiti! de Montre'al Professor M. Julia, Universite' de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R. Noyori, Nagoya University Professor L. E. Overman, University of California, Iwine Professor L.F. Tietze, University of Gottingen California at San Diego, La Jolla 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 Dr S. R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK. 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. 1996 subscription rates: EEA f185, USA $350, Canada f190 (plus GST), Rest of the World f190. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Second class postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. Q The Royal Society of Chemistry, 1996 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 in Great Britain by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd

ISSN:1350-4894    

DOI:10.1039/CO99603FX001

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

280 H. Tani, S. Irie, K. Masumoto and N. Ono, Hetero- 281 S. Dhanalekshmi, C. S. Venkatachalam and K. K. cycles, 1993, 36, 1783. Balasubramian, J. Chem. SOC., Chem. Commun., 1994, 511. Chem. Soc., 1994, 116,6713. 1993,36, 1795. J. Chem. SOC., Perkin Fans. 1, 1995, 2855. 1994,352299. Chem., 1992,45, 1639. 282 W. Adam, M. Ahnveiler and D. Reinhardt, J. Am. 283 B. Alcaide, C. Biurran and J. Plumet, Heterocycles, 284 M. A. Brimble, S. J. Phythian and H. Prabaharan, 285 D. G. Barrett and S.H. Gellman, Tetrahedron Lett., 286 D. B. Clarke, J. R. Guild and R. T. Weavers, Aust. J. Williams: The synthesis of carbocyclic aromatic systems 287 H. R. Sonawane, S. N. Bellur and S. G. Sudrik, Ind. J. 288 E. V. Dehmlow and C. Bollmann, Tetrahedron, 1995, 289 G. P. Shkil and R. S. Sagitullin, Tetrahedron Lett., 290 H.A. Etman, Ind. J. Chem., Sect. B, 1995,34, 285. 291 T. Nakazawa, M. Ishihara, M. Jiguji, M. Yamaguici, Y. Sugihara and I. Murata, Tetrahedron Lett., 1992, 33, 6487. 292 H. Nishino, S. Kajikawa, Y. Hamada and K. Kuro- sawa, Tetrahedron Lett., 1995, 36, 5753. 293 R. F. C. Brown, F. W. Eastwood and J. M. Horvath, Aust. J. Chem., 1995, 48, 1055. Chem., Sect. B, 1992, 31, 606. 51, 3755. 1994,35, 2075. 567280 H. Tani, S. Irie, K. Masumoto and N. Ono, Hetero- 281 S. Dhanalekshmi, C. S. Venkatachalam and K. K. cycles, 1993, 36, 1783. Balasubramian, J. Chem. SOC., Chem. Commun., 1994, 511. Chem. Soc., 1994, 116,6713. 1993,36, 1795. J. Chem. SOC., Perkin Fans. 1, 1995, 2855. 1994,352299. Chem., 1992,45, 1639. 282 W. Adam, M. Ahnveiler and D. Reinhardt, J. Am. 283 B. Alcaide, C. Biurran and J. Plumet, Heterocycles, 284 M. A. Brimble, S. J. Phythian and H. Prabaharan, 285 D. G. Barrett and S.H. Gellman, Tetrahedron Lett., 286 D. B. Clarke, J. R. Guild and R. T. Weavers, Aust. J. Williams: The synthesis of carbocyclic aromatic systems 287 H. R. Sonawane, S. N. Bellur and S. G. Sudrik, Ind. J. 288 E. V. Dehmlow and C. Bollmann, Tetrahedron, 1995, 289 G. P. Shkil and R. S. Sagitullin, Tetrahedron Lett., 290 H. A. Etman, Ind. J. Chem., Sect. B, 1995,34, 285. 291 T. Nakazawa, M. Ishihara, M. Jiguji, M. Yamaguici, Y. Sugihara and I. Murata, Tetrahedron Lett., 1992, 33, 6487. 292 H. Nishino, S. Kajikawa, Y. Hamada and K. Kuro- sawa, Tetrahedron Lett., 1995, 36, 5753. 293 R. F. C. Brown, F. W. Eastwood and J. M. Horvath, Aust. J. Chem., 1995, 48, 1055. Chem., Sect. B, 1992, 31, 606. 51, 3755. 1994,35, 2075. 567

ISSN:1350-4894    

DOI:10.1039/CO99603BX003

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

~~ Saturated and partially unsaturated carbocycles CHRISTOPHER D. J. BODEN and GERALD PATTENDEN Department of Chemistry, Nottingham University, University Park, Nottingham NG 7 2RD, UK Reviewing the literature published between January 1994 and April 1995 Continuing the coverage in Contemporary Organic Synthesis, 1994, 1, 433 1 1.1 1.1.1 1.1.2 1.2 1.3 1.4 2 2.1 2.2 2.3 3 3.1 3.1.1 3.1.2 3.1.3 3.1.4 3.2 3.3 3.4 3.5 3.6 4 4.1 4.2 4.3 4.4 4.5 5 6 7 8 9 Three-membered rings Metal carbenoid-based methods From dihaloalkanes From diazocarbonyl compounds Free radical methods Ylide-based methods Other routes to three-membered rings Four-membered rings Photochemical met hods Other routes to four-membered rings Cyclobutenes Five-membered rings Transition metal-based methods Cobalt Palladium and nickel Zirconium Other transition metals Free radical-based methods Cationic methods Anionic methods Other routes to five-membered rings Polyquinanes and 'cascade' polycyclisations Six-membered rings Diels-Alder reactions Other cycloaddition routes Free radical cyclisations Electrophilic polyene cyclisations Other routes to six-membered rings Seven-membered rings Eight-membered rings Nine-membered and larger rings General carbocycle synthesis References 1 Three-membered rings 1.1 Metal carbenoid-based methods 1.1.1 From dihaloalkanes The familiar zinc carbenoid-based Simmons-Smith cyclopropanation remains a popular method for the formation of three-membered rings, allowing as it does the induction of chirality through transition state interactions with chelating heteroatoms (usually oxygen).Allylic alcohols such as 1 are the most commonly used starting materials, and a number of new chiral auxiliaries and/or catalysts have been developed to facilitate their asymmetric cyclopropanation. The most notable examples are the tartrate-derived dioxaborolane ligands 3 and 4 reported by Charette et al. prior to treatment with the conventional Simmons- Smith reagent (Zn/CH21,), give the corresponding cyclopropyl methanols 2 with excellent yields and enantiomeric excesses. Care is, however, required for the safe use of this method.2 The method has also been used by Zercher et al.3 and by Barrett et al. for the preparation of vicinal cyclopropanes; for example the conversion of the diene 5 into either 6 or 7, in which it was found to be markedly superior to other method^.^ which, when added to 1 R t q o H ii. i.Zn(CH& 3, CH2CI2 (2.2 q.) RJ+oH R3 R3 CH&I, 25 "C, 2 h 1 2 280% yield 9144% 88 Me,NOCh CONMe, Me2NOC,,dCONMe2 O?/O o.B/o I Bu Bu 3 4 HO 5 \\i. 3; ii. Zn(CH2Q2 OH 1. 4;ii. Zn(CH,Q2 Hov -.: \' \ 6 \ H O m o H 7 A more conventional approach to such vicinal cyclopropanes (which form part of the natural product FR-900848) has been reported by Armstrong et al.' In a similar vein Denmark et al. have studied the use of auxiliaries derived from the chiral diamines 8 and 9,6,7 obtaining moderate to Boden and Pattenden: Saturated and partially unsaturated carbocycles 1910 good enantiomeric excesses. The new acetal-type auxiliary 10 derived from fructose has been described for the cyclopropanation of 2-alkenal~.~ An unusual route into terpenoid-derived bicyclo[4.1.0] systems such as carene 12 from acyclic terpenoid enals, e.g.citral 11, has been described by Motherwell et aL9 The outcome appears to be independent of the alkene geometry in the substrate. Lautens has studied the samarium-based cyclopropanation of a range of mono- and bi- metallic alkenols 13, with the syn cyclopropanes 14 being obtained in very good yields and with high diastereoselectivity." The same procedure was also applied" to the regioselective cyclopropanation of a-allenyl alcohols 15, giving the synthetically useful cyclopropylmethylenes 16. It is noteworthy that in the latter case conventional zinc carbenoid methods completely failed to give the required chemoselectivity .0 CISiMe2(CH2)&Me2CI --H singleisom 11 12 13 14 R' = alkyl; R2, R3 = H, alkyl, TMS, BuoSn OH 15 R' = alkyl; R2 = H, alkyl, Me0 OH 16 1.1.2 From diazocarbonyl compounds The other classical method for effecting metal- carbenoid mediated cyclopropanations - treatment of alkenes with diazocarbonyl compounds in the presence of a metal catalyst - has also received considerable attention recently. Nishiyama has reported the use of the chiral ruthenium bis(oxazoliny1)pyridine catalyst 17 for the asymmetric cyclopropanation of terminal alkenes.12 In a similar vein, Kanemasa et al. have described a 1,2-diamine-Cu( 11) triflate complex derived from 18, which is applicable to the cyclopropanation of disubstituted alkenes as well;13 diastereoisomeric and enantiomeric excesses are only moderate however.Finally, Martin and co-workers have studied the intramolecular cyclopropanation reactions of secondary allylic diazoacetates 20 using the rhodium catalyst 19; good to excellent degrees of endo- selectivity were achieved.I4 17 18 P A R 3 20 endo 21 Me0& -b 19 1.2 Free radical methods ex0 22 4 Free radical methods are not commonly used for cyclopropane ring synthesis, since 3-exo-trig closures to give cyclopropylmethyl radicals are readily reversible, with the equilibrium favouring the open- chain form. However, if the product radical is either trapped out, or is sufficiently stable to allow reduction to be competitive with ring opening, cyclopropane products can be obtained. An example of the former has been reported by Gravel, where dienes such as 23 may be cyclised to give the intermediate 24, which immediately eliminates phenylthiyl radical to give the bicycl0[3.l.O]hexane 25.15 A more unusual example has been described by Malacria, where the enyne 26 undergoes sequential 5-exo-dig, 6-exo-trig and 3-exo-trig cyclisations to give an allylic radical, which proves to be more stable than the open chain form resulting from the first two cyclisations.'6 Final hydrogen abstraction from the tin hydride then leads to the tricycle 27.20 Contemporary Organic Synthesis1.4 Other routes to three-membered rings Fused cyclobutane ring systems such as 31 have been transformed cleanly and efficiently into the fused cyclopropanes 32.19 Two research groups have Me02C C02Me c y c ~ ~ ~ e o & c o w reported new approaches to various cyclopropyl amino acids.Cativiela et al. have followed the most straightforward of these, by treating a$-didehydro- amino acid derivatives such as 33 with either diazoalkanes or sulfonium ylides, to give the protected amino acids 34.*' In contrast, de Meijere and co-worker have reported the use of three carbon synthons such as 36 as Michael acceptors in a synthesis of the cyclopropyl-substituted protected amino acids 37.2' phsk sexetrig. (Bu$n)* then r% Sexetrig 23 24 l- Me02C '6 CO*e I EuSnH. AIEN. PhH, 80 'c. 16 h 25 Stwedig, Bexetrig, then Sexetrig. folkwed by hydrogen abstraction Me0& C02Me xq 0 0 U 26 27 1.3 Wide-based methods An unusual method for the synthesis of cyclo- propanes, based on organotellurium chemistry, has been described by Huang et al., wherein chalcones 28 are reacted with the reagent 29 in the presence of an inorganic base, giving the cyclopropanes 30.'7 Also, the familiar dimethylsulfoxonium methylide cyclopropanation of chalcone has now been carried out in the solid state." 6545% yield cs2c03 Ar.vinyl trans :cis 210:l Ar. PhCO always trans 1 31 32 CH2N2. 0 'c. 5 h 33 xn6 34 (=cp' I. BuLi. THF,-78 'c, 1 h ii. 36, -78 'c, 1-1 5 h 63-81s >959cde c02eu' 2 Four-membered rings 2.1 Photochemical methods The elaboration of cyclobutanes by photocyclo- additions between alkene bonds remains one of the most engaging and enduring reactions in modern synthesis. Houk et a1.22 have used ab initio theory to study the regioselectivity of intermolecular photo- cycloadditions of triplet cyclohexenones to alkenes; and Becker et a1.23724 have provided further results of their extensive studies of the regio- and stereo- chemical outcomes of intramolecular [2 + 21 photocycloadditions involving various alkene substituted cyclo-Zalkenones. A silicon-tethered variant of the intramolecular [2 + 21 photocyclo- addition process has been described.25 Meyers et al.,26 together with Koga et al. ,27 have demonstrated the power of intramolecular [2 + 21 photocyclo- additions involving chiral starting materials (38 and 40) in the target synthesis of natural products, viz lintenone A 39 and stoechospermol B 41 respectively. Boden and Pattenden: Saturated and partially unsaturated carbocycles 2138 95% 39 Qp - 0 OTBS 0 H H OTBS 40 41 2.2 Other routes to four-membered rings The procedure whereby cyclobutanones can be prepared through an intramolecular [2 + 21 cycloaddition between an in situ generated a$-unsaturated ketene and a C=C bond, has now been ~ t i l i s e d ~ ~ , ~ ~ in a stereoselective synthesis of the pheromone grandisol42 (Scheme l).30 iii I 42 Reagents: i.A@. CH,CQK. 4 S. NHfiH, then (EtOCH&3i2)20, then SOCIS v. LWHAtfl KOH, II. RUCI-104; iv. Me8K=H&lgCI, Scheme 1 43 Some interesting alkenylidene cyclobutanes have been synthesised by cyclisations of acetylenic alkyllithiums (formed by lithium-iodine exchange) bearing a prop-2-ynylic leaving group, viz 44-+45,32 and Ihara et a1.33 have described a neat synthesis of fused four-membered rings from cyclopropyl ketones on treatment with TMS-iodide, i.e.46-+47. Me0 Bu'Li,-78 "C 44 45 46 2.3 Cyclobutenes Cyclobutenes are useful intermediates in synthesis; for example, they undergo facile electrocyclic ring opening to functionalised 1,3-dienes. 3,3-Dimethoxycyclobutenes 49 are now easily prepared from the [2 + 21 cycloaddition of 1,l-dimethoxyalkenes 48 to electron-poor alkynes in anhydrous chloroform at low temperature, e.g. 18 0C.34 Other substituted cyclobutenes, e.g. 51 can be produced from Lewis acid catalysed reactions between allylsilanes and acetylenes, viz 50-+51.35 COPh CHCI,, 18 "C M . & ) y P h COPh MeoToMe + 111 98% In a demonstration of the scope for the reported selenium-directed, stereoselective [2 + 21 cyclo- addition of silyl vinyl selenides to enones, Yamazaki et aL3' have described a concise synthesis of fragenol COPh 43, which is a constituent of Artemisia fiagrans willd.40 49 22 Contemporay Oiganic Synthesis51 3 Five-membered rings 3.1 lkansition metal-based methods 3.1.1 Cobalt The familiar Pauson-Khand reaction (henceforth 'PKR') has once again been the subject of considerable interest. Perhaps the most notable achievement has been the discovery by Jeong, Chung and co-workers of the first reasonably general catalytic version of the reaction.36 The method is effective for both the intermolecular (52+53) and the intramolecular (54-55) reaction; the same authors have reported an alternative method for the latter based on the use of phosphite co-ligand~.~' R' H 19 (1 ,S-Ood)Co( ind), 1-5 md% CO (15 atrn), DME, 100 "C, 40 h 9x0 only 82%7% h R2 52 53 R', R2 = alkyl, Ph, H (1,s-cod)Co(ind), 2 mol% 92% 54 55 Another interesting development has been the observation by Schore et al.of reversed (endo) selectivity in the PKR of the dienyne 56;38 this clearly indicates that the normal ex0 preference of the intramolecular reaction can be reversed in certain situations. Progress has also been made in the field of chiral auxiliaries, with Greene and Pericas describing the use of a camphor-derived auxiliary to control diastereoselectivity in the PKR of 57; the conversion of the product 58 into the useful chiral cyclopentenone 59 is also described.39 De Meijere et al. have synthesised a range of spiro(cyclopropy1)cyclopentenones such as 61 by using met hylenecyclopropanes 60 as the alkene c o m p ~ n e n t ~ ~ ' ~ ' - a reasonable (6.5: 1) ratio of diastereoisomers was obtained by the use of the appropriate chiral dioxolane auxiliary. In a similar vein a-methylene cyclopentenones 63 have been prepared by carrying out the PKR with allene intermediates such as 62.42 In this case the substitution of molybdenum for cobalt was required in order to effect reaction.Finally, syntheses of ( + )-kainic acid,43 (+)-ta~lorione~~ and a model for xest~bergsterol~~ have been published using the PKR in key steps. One other novel use of cobalt catalysis is in the cycloisornerisation of &'-acetylenic P'-alkyl b-ketoesters such as 64 to methylenecyclopentanes 65.46 i. C02(C0)8 ii. TMANO, 0,25 "C. 16 h 1 76% 46Hll 61 MO(CO)~, DMSO, PhMe, 100 "C 68% 62 - wpo+wo I.C02(CO),, CH&12 ii. NMO, 02.25 'C, 3 h 55%, I : H ' : h I 1 1 1 I * 56 3: 1 (COh (COh & b where R*=& SMe co co 57 58 59 i. NMO, 25 "c, CH2CI2 R'O '*'flfH ii. norbornadiene, -20 OCd SiMe, 63 Boden and Pattenden: Saturated and partially unsaturated carbocycles 233.1.2 Palladium and nickel The use of methylenecyclopropanes in Pd-catalysed [3 + 21 cycloadditions to alkynes has been explored by Motherwell et aL4’ and by Lautens et aLa Lautens et al. have also shown that the process (e.g. 66+67) proceeds with overall retention of stereochemistry at the cyclopropane chiral centre. Mandai and co- workers have devised an interesting route from /I-alkynyl carbonates such as 68 to the cyclic products 69; the reaction is believed to proceed via a 1,l-dicarboethoxyallene intermediate, which undergoes an intramolecular ene reaction to give the observed HO 10 mol% Pd@ao 40 md% (P+O)3p, @o PhMe.reflux. 3 h. 85% H ( 5 6 h 1 i=6H 11 66 67 68 Pd(OAc)2 (5 m) I dppp (5 d 9 L ) PhM&hOH. 4 h, 799c I 6Q Liebeskind et al. have reported a convenient approach to cyclopentenones such as 71 by the Pd-Hg mediated ring expansion of alkynyl cyclo- butenols such as 70.50 The method can also be used to make cyclopent-4-ene-l,3-diones, as can the treatment of 1-hydroxy-1-alkynyl cyclobutenols with Fischer ~arbenes.~~ In another related use of ring expansion Fukumoto et al. have developed a novel approach to tetrahydro-indanones 73 by treating vinylcyclobutanols such as 72 with catalytic Pd(1r); the alkyl palladium species formed by ring expansion inserts in situ into the pendant alkene.52,53 The work of Trost et al. towards ‘atom economical’ cyclisations continues; a Pd catalyst for the cycloisomerisation of 1,6- or 1,7-enynes to di- alkylidene cyclopentanes or cyclohexanes (which can 70 y y Bu Me0 81% 71 qL TBSO 72 P ~ C I ~ ( M O C N ) ~ DME.reflux, 18 h 28% I TBSO 9 73 then be used as dienes in similarly economical Diels-Alder cycloadditions) has been De Meijere and co-workers have reported a similar method, whereby the cycloisomerisation step is replaced with a Heck rea~tion.~’ Finally, two interesting uses of nickel catalysis have been reported. In the first of these Ryu, Sonoda and others have described a relatively mild method for carrying out a vinylcyclopropyl ether to cyclopentanone enol ether rearrangement, viz 74475, based on the use of a Zn-Ni catalyst.56 In the second, Mori et al.have published details of a novel cyclisation of n-ally1 nickel complexes, derived from 1,3-dienes, onto pendant carbonyl groups; the method is also applicable to six- and seven- membered rings.57 TBSO TBSY (PPh,),NiCI, (5 moffi), zn (10 moffi) PhMe, refkm, 2 d 74 84% 75 3.1.3 Zirconium The Zr-mediated intramolecular cyclisation of 1,6-dienes or enynes 76 is a well-established method of forming cyclopentanes, and proceeds by way of intermediate zirconabicycles 77. Whitby et al. have shown that the conversion of 77 into amino bicyclo[3.3.0]octanes 78 is possible by treatment with 24 Contemporary Organic Synthesis76 isonitriles, followed by heating and then quenching, either with methanol or an alkyne (the latter giving a vinyl amine A number of researchers have published studies of regio- and stereo-control in the initial cyclisation step,"-" of which Negishi's is perhaps the most interesting.62 Finally, the method has been used as the key step in a formal total synthesis of ( -)-dendr~bine.~"~ 3.1.4 Other transition metals Normant and Marek have published a general study of intramolecular carbometallations of organozinc reagents derived from 6-halo-l-alkenes, and observed exclusively 5-exo-trig cyclisation in all cases studied.65 This is a potentially powerful method, in that it tolerates quite reactive functional groups (e.g.esters). The RZn species is also easily prepared and, unlike in radical reactions, the product can be trapped intermolecularly using a wide range of electrophiles.The same authors have also published a novel route to alkynyl exo-methylene cyclo- pentanes 80, based on the 3-metallation of 3-methoxy-l,7-diynes 79.66 In related work the MeO 79 -70 "C + 20 OC L -I I E+ + Me3Si ,, E &rSiMe3 80 equivalent metallo-ene reaction has also been performed, by carrying out the metallation- transmetallation procedure on a 1,6-en~ne.~~ Oppolzer et al. have described a similar reaction, using a Pd-Zn system to effect the conversion of 81 into 82, as predominantly the cis isomer.68 i. 5 m1Y0 Pd(PPh&, p m z s ~ , , Ph02S ii. E', where E = H, I 4 eq. ZnEt, Etfl, reflux -. ... 45-6046, >91 de 81 82 In another variation on metal-catalysed enyne cyclisation, Murai et al.have demonstrated that the isomerisation of 1,6-enynes 83 to vinyl cyclo- pentenes 84 (usually achieved using Pd catalysis - see Section 3.6 for examples) can be effected using a ruthenium catalyst.69 This approach has the advantage over Pd-based methods in that terminal alkynes can be used without formation of undesirable isomers; it can also be applied to 1,7-enynes. Finally, a new variant on the cyclisation of 1,6-diynes has been reported by Ojima et al., based on silylformylation.70 4 md% RuC12(CO&, PhMe, CO, 80 "C Kw. TBsb 83 lBsd 04 3.2 Free radical-based methods Work by Singleton and collaborators has shown that the synthesis of methylenecyclopentanes, starting from methylenecyclopropanes, can be carried out by using a radical-mediated [3 + 21 cyclisation ~trategy.~' The method is illustrated by the conversion of 85 into the diquinane 86,72 and can also be applied to intermolecular cycloaddition~.~~ SiMe3 I MenSi Me3SnSnMe3.hv. PhH 77% 85 86 COzEt Snider has utilised the Mn-based oxidative radical fragmentation of alkynyl cyclobutanols 87 (cf the Pd/Hg method in Section 3.1.2) in a total synthesis of ( -)-methyl cantabradienate 88.74 Shirahama and Matsuda have described a completely diastereo- selective route to 2-vinylcyclopentaols 90, based on the trapping of ketyl radicals formed by samarium( 11) iodide reduction of carbonyl compounds such as 89.75 Molander et al. have published a related study on the 5-exo and 6-ex0 cyclisations of similarly-obtained ketyl radical^,'^ and Fallis et al.have studied the intramolecular trapping of samarium-generated radicals with hydrazone acceptors.77 Boden and Pattenden: Saturated and partially unsaturated carbocycles 2587 Smi,. THF-HMPA. -78 "c 789'0 f , steps 89 90 The concurrent use of radical methods and Lewis acid chelation of chiral ester auxiliaries has been deployed by Nishida et al. for the asymmetric synthesis of 3-alkylcyclopentenes 92 starting from cu-haloalkenyl acrylates 91.78 The reaction gives good enantiomeric excesses and can also be used with dibromoolefins. 91 MAD. BuoSnH, EtoB, PhMe, -98 "c, 2 h 90% yield, 88% ee I wco2"' 92 Hydrogen atom transfer reactions are an increasingly important facet to radical cyclisation chemistry, and Malacria has reported an interesting example (Scheme 2).79 In a similar vein, Parsons and Caddick have described a synthesis of spiro-fused cyclopentanones based on 1,5-abstraction from an allylic centre.*' Finally, radical spirocyclisation has been used by Clive et al. in a total synthesis of (k)-fredericamycin A," and the same authors have described a route to the triquinane ( f )-cerato- picanol using a radical derived from an epoxide." 3.3 Cationic methods The conversion of ketones (or their ketals) into cyclopentane 1,3-diones (e.g.93 +94) by reaction with 1,2-bis(trimethylsilyloxy)cyclobutene is a well- established tactic in total synthesis. Burnell and co- workers have reported a method for carrying out this transformation in a single step, using an excess of boron trifluoride etherate,83 and have used the method in a new total synthesis of (&)-penta- 1enene.84 Furthermore, Curran et al.have extended the process to include a subsequent 5-exo cyclisation onto a pendant alkene or alkyne, giving a diquinane such as 95 (Scheme 3)."@ The use of Q4 -1 95 Scheme 3 96 164% 97 Scheme 2 26 Contemporary Organic Synthesis1,2-bis(trimethylsilyloxy)cyclopentenes instead gives a bicyclo[4.3.0]nonane product 97, by way of the 1,3-dione 96. for cationic cyclisations remains the ally1 or propargyl silane. Amberlyst-15 has been shown to be a simple and effective catalyst for such reactions.*' Weinreb et al. have reported a fascinating synthesis of the natural product papuamine, featuring as a key step a Lewis acid- catalysed imino-ene reaction onto an allenylsilane (98-+99).88 Such catalysis has also been used effectively in a more straightforward Alder-ene approach to vinyl cy~1opentanes.*~~~~ Nagao and co- workers have developed a new geminal spiro-endo mode of cyclisation of allenyl ketones, which is illustrated for dimethoxyaryl cases by loo+ 101.91-93 One of the most widely used terminating groups @ p S i M e 2 P h 98 SnCI,.PhH, 25 "C 281% 1 H H, A N C H 2 P h 'SiMe2Ph 99 OMe loo BF@Et2,-78 "C to-10 "C, CH2CIZ 8096 I YMe./,O 0 m 101 3.4 Anionic methods Cooke et al. have extended their work on halogen- metal exchange as an initiator of sequential Michael additions to the formation of bicyclic [4.3.0] and [3.3.0] In related work, Ovaska, Bailey and co-workers have devised a synthesis of 1,3-bis- exocyclic dienes 103, based on 5-exo-dig cyclisation of vinyllithiums onto alkynes such as 102.96 As with the Pd-catalysed work of T r o ~ t , ~ ~ the diene products can be reacted in situ with a suitable dienophile, making for a one-pot synthesis of bicyclo[4.3.0]- nonenes. 1 02 i.2.0 eq. Bu'Li, Et20, pentane. -100 "C ii. MeOH, 0 "C I 103 944b single isomer Padwa et al. have published a convenient route to bicyclo[3.3.0]octenes 104, based on an anionic [3 + 21 cycloaddition The same authors have published a route to arylcyclopentones from diazoacet~phenones,~~ and Asaoka et al. have described a convenient and enantioselective route to a capnellene fragment, based on silyl-directed cyclopentanone enolate alkylation." 2-sulfonyl cyclopentenones 106, via a tandem Michael addition-carbene insertion methodology starting from y-ketoethynyl phenyl iodonium triflates 105.1"03'01 Finally, Stang et al.have reported a novel route to 0 S02Ph 1 NaH S02Ph I 0 104 + 105 MePhSOfla, CH2CI2, 20 "C 75% I 0 106 3.5 Other routes to five-membered rings Thermal Wolff rearrangement of the 1,2-bis(diazo- ketone) 107 has been used by Nakatani and co-workers as the basis of a synthesis of trans- hydro-1H-2-inden-1-one 108. Io2 Boden and Pattenden: Saturated and partially unsaturated carbocycles 271 07 108 3.6 Polyquinanes and 'cascade' polycyclisations The methods of five-membered ring synthesis detailed so far have all dealt primarily with the formation of single ring. However, the trend in modern organic synthesis is increasingly towards the formation of two or more rings in the same step, whether by conventional means (e.g.rearrange- ments) or by the increasingly popular 'tandem' or 'cascade' processes, wherein the product from the first cyclisation initiates further ring closures. Five membered rings are well suited to the latter, as 5-ex0 cyclisations are usually preferred to 6-endo, and 5-endo to 4-ex0, especially in free radical processes, making polyquinane constructions a favourable option. One of the most useful and rapid rearrangement- based methods is the conversion of squarate esters 109 to diquinanes 112 by sequential treatment with suitable anions. Paquette and co-workers have shown that by using an acetylide as the second anionic component, the regiochemistry of the aldol reaction (110+111) can be c ~ n t r ~ l l e d ' ~ " " ~ ~ (Scheme 4; compare this with the work of Hirama et al.described in Section 7, i.e. 212-+213). Rawal et al. have developed a fragmentation route to diquinanes based on the photocycloadducts 113, which are readily obtainable by a photo- cyclisation of norbornene derivative^.'^^ The radical Proi pro&oo 109 i. "-0 ii. LiECMe Pro' prois 0 110 PSO @ PSO OH 112 Scheme 4 28 Contemporary Organic Synthesis 111 LDBB = Li+ 114 formed on the diquinane skeleton arising from the initial fragmentation can be trapped with a pendant alkene, allowing the triquinane skeleton 114 to be prepared. lo6 The Heck reaction is a well-established staple of carbocycle synthesis.lo7 Weinreb et al. have assessed the possibility of carrying out the reaction on a substrate such as 115 which gives rise to a 71-ally1 Pd complex 116, which can then be displaced with a soft carbanion.'os The results confirm that the reaction is possible, but is reduced somewhat in value by the usual problems of a:y selectivity, giving a mixture of 117 and 118.Palladium also features in a fascinating extension to Trost's work of enyne cycloisomerisation; Trost et al. have developed a catalyst which allows direct conversion of 1,6-enynes 119 into tricycles 121, by reaction with 1,3-dienes or 1,3-enynes such as 120 (Scheme 5).'09 The most common ways of effecting 'cascade' reactions involve either free radical intermediates or palladium catalysis. The single exception to appear recently is the use by Negishi et al. of an aluminium-titanium reagent to effect the tricyclisation of a triene; selectivity is lacking in this process, however.'" Of the Pd-catalysed methods 7 C 0 2 M e C02Me 115 Pd(OAc), P(eTd)a Bu,NCI, NaH, DMF I C0,Me 116 117 118r I cHFB 120 E"" H w2c>cf7H Meo2c 6 121 EHFB 1 L Scheme 5 KH.THF. 25 "C 5 m ~ l % Pd(0AC)z 10 mow dppe 0 - capnelkne # * Ql 5% + Scheme 6 the most notable work has been that of Balme and co-workers (Scheme 6) which has been used in a total synthesis of (+)-capnellene and, like the work of Weinreb et al. cited above, involves the trapping of a Heck reaction product.1"311Z Oppolzer has also made a recent contribution to this field.'I3 Of radical cascade methods the work of Pattenden and co-workers is notable. Thus, the 5,7,5-tricycle 123 has been assembled by a macrocyclisation- transannulation approach, starting from the triene 122 (Scheme 7)."4,115 Kilburn et al.have also made contributions to this 4 Six-membered rings 4.1 Diels-Alder reactions The scope for the intramolecular variant of the Diels-Alder reaction in difficult ring constructions has been further illustrated in Jackson and Shea's synthesis of the highly functionalised taxane intermediate 125 from 124,"' and in the elaboration of the steroid-taxane hybrid 126, described by Danishefsky et al. In another neat approach to the taxane ring system Winkler et al. have used a combination of inter- and intra-molecular Diels- Alder reactions, vis 127+128 and 1284129, from readily available precursors; this very direct two step synthesis produces 129 in 50% overall yield and with excellent stereocontrol.Spino et al. have published similar sequential inter- and intramolecular Diels-Alder reactions in their approaches to perhydrophenanthrenes, viz 130+132 via 131,'217122 and to the quassinoids."' De Clerq and his collaborators have extended their elegant studies on the scope of the intra- Bu3SnH, AIBN, PhH 55% H G 122 123 13-endo 1 [v - 0 Scheme 7 Boden and Pattenden: Saturated and partially unsaturated carbocycles 29&& 0 0 PhMe,A 124 125 M e G PhMe, 180 "C 126 130 Ideps 132 127 TQ3 H O 129 molecular Diels-Alder reaction with furan-dienes, and described a total synthesis of gibberellins Al and A3, based on the cycloaddition 1334134 as a key step.124 Lithium perchlorate in diethyl ether has been shown to have a profound effect on the reaction rates of many Diels-Alder reaction^.'^' Now Grieco et aZ.have shown that catalytic camphorsulfonic acid in 5.0 M lithium perchlorate-diethyl ether solution promotes Diels-Alder reactions of conformationally restricted substrates with concomitant migration of the diene moiety prior to cycloaddition, viz 135-+137 via 136.'26 In a detailed investigation Gorman and Gassman'*' have studied the influence of alkyl substitution on the ionic intermolecular Diels-Alder reactions of a wide range of methyl analogues of 3E,8E-1,3,8,10-undecatetraenes; this paper is well worth reading in detail. The transannular Diels-Alder reaction of the triene 138 produces the trans-anti-cis tricyclic COzMe 133 # bOzMe 134 135 136 e 137 0 lactone 139 as a single cycloadduct in 63% yield;'28 and Takahashi et have extended their investi- gation of this approach to polycycle constructions by carrying out detailed studies of the transannular Diels-Alder reactions of the trienones 140. 30 Contemporaly Organic Synthesis25 "C - CF,SO#I,A,,NS02CF, ArxA' I 138 139 98% yield, 93% ee H eR=H; bR=OH 140 Catalytic enantioselective Diels-Alder reactions are very much in vogue these days.Thus Corey et al. have described further aspects of their oxazaboro- lidine-catalysed reaction^,'^' and also the first example of an enantioselective catalytic Diels-Alder reaction of an achiral C2,-symmetric dienophile and an achiral diene, i.e. 141 + 142-+143.13' The applications of q4-diene iron tricarbonyl complexes132 and of a chiral scandium enantioselective Diels-Alder reactions have also been described.in MeO 1 + (Nb 0 141 142 143 4.2 Other cycloaddition routes Allenes have been used as new partners in intra- molecular cobalt-mediated [2 + 2 + 21 cycloaddition reactions for the first time, leading to facile syntheses of polycycles after decomplexation, e.g. 144+145.'34 Padwa et al. have shown that dipolar cycloaddition reactions using carbonyl ylides can be used as key steps in the construction of the illudin, ptaquilosin and pterosin families of sesquiterpenes, e.g. 146-+147.1353'36 A new sequential carbonyl ene cyclisation/cyclo- addition of trifluoromethyl ketones catalysed by Lewis acids has been applied to the synthesis of polycycles, viz 148-+ 149.'37 White and So~ners'~* have published full details of their approach to the 144 C~CO(CO)~, xylenes - A, hv, 5 h 145 SiOp 4 N2 146 HO-- 9$& \ opJ& 0 illudm M 147 EtAIC12,O "C C 3 1 ratio d I4Bepimer F3C 0 148 F3d q9 OH 149 + F3C VHJ OH stemodane nucleus based on a hydroxy-directed intramolecular ene reaction.4.3 Free radical cyclisations A number of interesting 6-endo cyclisations leading to six-membered annulated ring systems have been published in recent years. Thus Parker and F o k a ~ ' ~ ~ , ' ~ ' have used this tactic in their approach to the morphine ring system, e.g. 150+151, and Ghatak et al. 14' have synthesised a range of linearly condensed hydroaromatic carbocyclic systems, e.g. 153 from 152 through 6-endo-trig closures. Now Marco-Contelles and c011eagues'~~ have shown that cyclitols of constitution 155 containing a trans 1,3-dioxolane moiety can be produced from Boden and Pattenden: Saturated and partially unsaturated carbocycles 31Me0 BuSnH - 0 150 151 152 153 OAC OAc 154 155 5-hexenyl radicals derived from 154 by way of a facile 6-endo-dig cyclisat ion.hexenones containing pendant aldehyde functionality leads to a neat synthesis of directed aldols by way of allylic O-stannylketyl intermediates, e.g. 156+157.'43 Some novel cyclobutanone-based tandem free radical rearrangements,la and cyclisations involving methylenecyclopropane derivatives,'457146 have been used to access certain mono- and bi-cyclic cyclohexanes. The addition of Bu3SnH-AIBN to cyclo- 15s 1 H 157 Tandem radical-mediated cyclisations have also been used with silicon tethered precursors, e.g.158, to access intermediates 159 containing the steroid ske1et0n.l~' Treatment of appropriately substituted polyene phenylselenyl esters, e.g. 160 and 162, with Bu3SnH-AIBN has been shown to lead to linear and angular six-ring fused carbocycles (such as 163 and the steroidal ring system 161), via consecutive 6-endo-trig mode cyclisations starting from the corresponding polyolefin acyl radical intermediate^.'^^ 4.4 Electrophilic polyene cyclisations The elaboration of polycycles based on cyclisations of polyolefinic substrates in the presence of electro- &:. \ 158 L Bu&H Y. CH3MgBr 1 QpP Sie3 159 160 0 B@nH AlBN 1 0 1 62 Bu3SnH AlBN 1 163 philic reagents, pioneered by W. S. Johnson, has provided organic chemistry with one of its major and enduring synthetic methods.Now Fish and Johnson have described further ramifications of this strategy in synthesis, reporting the first examples of non-enzymatic biomimetic polyene pentacyclisa- tions, viz 164+165,149 and a total synthesis of sophoradiol 166 using the tetramethylallyl cation as a surrogate for the epoxide function as an initiator of the polyene cycli~ation.'~~ The same research group has also described the use of the allylsilane group as an internal terminator group in polyene 32 Contemporary Organic Synthesis1% CFSCO~H, CH&12 -78 "C, 31% I x t x HO q(j@ - . 1 66 cyclisations, 15* and studies towards the oleanes based on similar polyene cyclisations P-alkynyl involving silane precursors. 152 Finally, in the first demonstration of a carbo- cation-olefin cyclisation route to the lanasterol series, Corey et al.153 have described the silicon- assisted double cyclisation 167+168. 4.5 Other routes to six-membered rings Palladium-catalysed cyclisations remain popular in approaches to six-membered carbocycles. Thus Tietze and S ~ h i m p f ' ~ ~ and Terakado et al. 155 have . 167 i. MeAIC12, -78 "C ii. AcCI, pyr, DMAP I 168 both highlighted the control that can be exercised by the allylsilane moiety in intramolecular Heck reactions, e.g. 169-170, and Hatakeyama et al. (cf work by M ~ r i a r t y ) ' ~ ~ have outlined an efficient route to the A-ring synthon 173 for la,25-dihydroxy- vitamin D3 based on the same Heck reaction, viz 171 -172. Pd catalysis (S )-BINAP 169 170 171 172 POPh, TBSO'* &TBS 173 An unusual sequence of ring-closure metathesis reactions from acyclic dienynes, catalysed by the ruthenium carbene complex 174 has been used by Grubbs et al.'" to produce fused bicyclic rings, including the 6,6-fused system 175. The first examples of tandem Cope-Cope rearrangements have now been identified, e.g. 176-+178 via 177,'59 and a range of new tandem anion-induced reactions involving the Michael reaction and the Claisen condensation,'60 the aldol reaction16' and or-alkylation,'62 have been described. 175 I 176 - 177 cope-2 1 1 78 Boden and Pattenden: Saturated and partially unsaturated carbocycles 33Ally1 and vinyl silanes have featured prominently in a range of recently described cationic six-ring cycli~ations.'~"~" Perhaps one of the most impressive examples of a vinyl silane-mediated cationic cyclisation is the synthesis of the tricyclic inter- mediate 180 from 179 described by Burke et their approach to an enantioselective synthesis of nagilactone F 181.in 0 U CH&12, -78 "C 181 5 Seven-membered rings Perhaps the most common approaches to seven- membered ring constructions are those utilising ring expansions, which are typically carried out by fragmentation reactions. Thus, Dowd and co- workers have devised a neat synthesis of fused cycloheptanones such as 183 based on radical fragmentation of the alkoxyl radicals derived from cyclobutanones such as 182.'66 Several strategies for forming the substrates have been devised.'66-'68 The same research group has also reported an unusual rearrangement of cyclobutanones 184 to give tricycles 185. ' 69 183 184 185 Radical fragmentations of cyclobutanes have also been used by Lange and co-worker, as the basis for the synthesis of 7 5 , 7,6-, 8,s- and 8,6-fused bicyclic~.'~~ Either tin hydride- or samarium- mediated reductions can be used,'71 and the method has been used in a total synthesis of alismol 186.17* Ranu has examined similar radical fragmenta- t i o n ~ .' ~ ~ A thermal diradical fragmentation has been reported by Little and where the diradical formed from 187 is converted into 188, presumably via an hydrogen atom-transfer step. I. Me&O,H+ ii. MeMgBr, CeCl, H \\ 186 -OH I CO,Me PhMe, reflux. 73% slow additionc sMe 1 87 188 Lautens et al. have devised a new route to the 7,s-systems 190, based on intramolecular ring opening of adducts 189 derived from [4 + 31 cycloadditions to f~rans."~ A similar cycloaddition has been used by Harmata and colleagues in a model study for the synthesis of the ingenane carbon skeleton;'76 and an alternative approach to ingenanes has been described by Winkler, Blumberg and co-workers, based on intramolecular [2 + 21 cycloaddition of 191 to give 192, followed by ring opening under basic conditions to give the tricycle 193.'77 Similarly, Tochtermann et al.have reported a route to the tremulane carbon skeleton based on alkaline rearrangement of oxepine~.'~~ McMills et al. have described an approach to tigliane diterpenes, based on cyclisation of the oxonium ylide 195 derived from the diazocarbonyl 34 Contemporary Organic SynthesisSnBu, 0 (0% 189 0' Mdi.M F , -78 OC W 5 % / R = H. Me, f3n. TBS 190 191 Me6 1 92 C02H 193 0 195 196 precursor 194, to give the 5,7,6-tricycle 196.179 Finally, two research groups have published studies of cationic cyclisations leading to seven-membered rings: Angle et al. have utilised cations derived from p-quinonemethides,'" and Majetich et al. have further developed their work on the addition of electron rich aryl systems (in this case furans) to conjugated dienones.'" 6 Eight-membered rings Radical cyclisations are generally not used for eight- membered ring synthesis, owing to the slowness of the ring closure relative to common side reactions. However, Molander and co-worker have shown that ketyl radicals deriving from SmI, reduction of ketones can be rendered highly persistent by carry- ing out the formation under certain conditions.'82 Thus the radical 8-endo cyclisation of 197 to 198 is rendered feasible.O R Me 197 Sml,. Bu'OH. THF, HMPA 4943% 3-30:l de. R - Me. Ph. Pr' I W 198 Another unusual approach to eight-membered rings has been described by Grubbs et al., who use Ru-catalysed olefin metathesis to effect the conversion of 1,9-dienes into fused cyclo-octenes, e.g. 199+200, using complex 201 as the catalyst.'*' cyclooctanes is the use of Ni-catalysed [4+4] cycloaddition of butadienes. In a related process, Harmata et al. have shown that cationic [4+3] cycloadditions can be used in similar fashion, e.g. by conversion of furan-cyclopentanones 202 into the doubly bridged cyclo-octene 2O3.ls4 Several researchers have used more standard methods to make eight-ring containing natural products, and of these the most interesting is perhaps Schreiber's use of the Nicholas reaction in the synthesis of ( + )-epoxydi~tyrnene.'~~ Other examples include the use of the C1aisenlE6 and ~xy-Cope"~ rearrange- ments to effect ring expansion, and the use of sulfone-stabilised carbanion additions to esters.188 One of the most widely-used routes to 5 mol% 201.PhH. 25 "c. 4 h 75% 199 200 .Ph CI. FHPh crqu- PCY3 201 Boden and Pattenden: Saturated and partially unsaturated carbocycles 35203 [a] /55% Interest in the much-studied taxane 6,8,6-fused tricyclic carbon skeleton has remained high,lg9 culminating in two total syntheses of the valuable anticancer agent Taxol@ 204.'90-'95 Both of the synthetic approaches taken are interesting from the point of view of eight-membered ring synthesis, as is the work of Kuwajima et al.on the synthesis of taxinine derivatives such as 206.196 In the latter work intermediates such as 205 were cyclised in a facile and diastereoselective manner by the use of an appropriate Lewis acid catalyst. In similar work, Swindell et al. have reported a synthesis of the eight- membered ring in the taxanes by Ti-mediated pinacol closure,'97 and Romero et al. have utilised an intramolecular aldol c~ndensation.'~~ Paquette et al. have published more work based on the use of oxy-Cope rearrangements to give the eight-membered ring,'99 as have Martin et aL2" Finally Kanematsu and co-workers have devised a novel route to the taxane carbon skeleton, making use of a tandem [2 + 2]-cycloaddition-[3,3]-sigma- tropic shift process for the conversion of 207 into 209, via the allenyl intermediate 208.20' OAC Ph 204 OTIPS HO:@ CH(OMe)2 Me 4 5 SnC14'CHzC'2 7796, "C, single 330 min M& c H o g r e Me0 isomer o& L O 208 209 7 Nine-membered and larger rings Melikyan et al.have described an interesting variation on the well-known Nicholas reaction, which allows the cobalt-complexed 1,5alkadiynes 210 to be cyclised via P-alkynyl radical inter- mediates.202 Subsequent oxidative decomplexation then gives the cyclic alkadiynes 211. Hirama et al. have reported a remarkable synthesis of the highly strained nine-membered ring 213 (which rearranges on warming to give the diquinane 214) by intramolecular acetylide addition in the m-alkadiynal 212.*03 In related studies, the synthesis of enediyne antibiotics remains an active field, with several research groups reporting new result^.^^-^^^ investigated by a number of research groups.McMurry and Siemers have reported a total The synthesis of medium ring dienes has also been i. HBF, 21 0 ii. Zn co2(co)6 ?02(c0)6 p: / 21 1 205 206 36 Contemporary Organic Synthesis?% 21 3 26Y 21 4 synthesis of periplanone based on intramolecular low-valent titanium coupling of aldehyde and alkenone moieties;208 and Hodgson et al. have described a route into the germancranes, based on a Pd-catalysed vinyl halide-vinyl stannane coupling to the corresponding 1,3-diene.2w Allyl-ally1 cyclisation has also been reported by Takayanagi et al., as part of a total synthesis of the cembranoid sarcophytol A,210 and by Williams and Coleman as part of a synthesis of neodolabellenol.211 As with eight-membered rings, ring expansion remains a popular method for the formation of medium rings.The most notable innovation has been the use by Suarez et al. of a tandem alkoxyl radical fragmentation-cyclopropylcarbinyl A c o ' - w OH 21 5 I DIB+ (2.51.5). 40 'c Ar, 90 min, 50% I C8H17 ACOI I 4 0 21 6 DIE = (diacetoxyiodo)benzene rearrangement strategy to enable the conversion of decalins such as 215 into the corresponding eleven- membered cyclic ketones such as 216.212,213 The oxy- Cope rearrangement has also been used as the basis of a route to the dolabellane carbon 8 General carbocycle synthesis Although no reviews directly concerned exclusively with carbocycle synthesis have been published, a number of reviews offering partial coverage have appeared.These include reviews of the Heck reaction,lo7 particularly in its asymmetric and a review of synthetic routes to vitamin D.217 9 References 1 A. B. Charette and H. Justeau, J. Am. Chem. SOC., 1994,116,2651. 2 A. B. Charette, S. Prescott and S. Brochu, J. 0%. Chem., 1995,60, 1081. 3 C. R. Theberge and C. K. a r c h e r , Tetrahedron Lett., 1994,35,9181. 4 A. G. M. Barrett, W. W. Doubleday, K. Kasdorf, G. F. Tustin, A. J. P. White and D. J. Williams, J. Chem. SOC., Chem. Commun., 1995,407. 5 R. W. Armstrong and K. W. Maurer, Tetrahedron Lett., 1995, 36, 357. 6 S. E. Denmark, B.L. Christenson, D. M. Coe and S. P. O'Connor, Tetrahedron Lett., 1995,36, 2215. 7 S. E. Denmark, B. L. Christenson and S. P. O'Connor, Tetrahedron Lett., 1995,36, 2219. 8 J. Kang, G. J. Lim, S. K. Yoon and M. Y. Kim, J. Org. Chem., 1995,60,564. 9 W. B. Motherwell and L. R. Roberts, Tetrahedron Lett., 1995,36, 1121. 10 M. Lautens and P. H. M. Delanghe, J. 0%. Chem., 1995,60,2474. 11 M. Lautens and P. H. M. Delanghe, J. Am. Chem. SOC., 1994, 116, 8526. 12 H. Nishiyama, Y. Itoh, H. Matsumoto, S.-B. Park and K. Itoh, J. Am. Chem. SOC., 1994, 116, 2223. 13 S. Kanemasa, S. Hamura, E. Harada and H. Yamamoto, Tetrahedron Lett., 1994,35, 7985. 14 S. F. Martin, M. R. Spaller, S. Liras and B. Hartmann, J. Am. Chem. SOC., 1994,116,4493. 15 R. C. Denis and D. Gravel, Tetrahedron Lett., 1994, 35, 4531.16 M. Journet and M. Malacria, J. 0%. Chem., 1994,59, 718. 17 Y.-Z. Huang, Y. Tang, Z.-L. Zhou, W. Xia and L.-P. Shi, J. Chem. SOC., Perkin Trans. I , 1994, 893. 18 F. Toda and N. Imai, J. Chem. SOC., Perkin Trans. I , 1994,2673. 19 M. Ihara, T. Taniguchi, Y. Tokunaga and K. Fukumoto, J. 0%. Chem., 1994,59, 8092. 20 C. Cativiela, M. D. Diaz-de-Villegas and A. I. JimCnez, Tetrahedron, 1994, 50,9157. 21 J. Zindel and A. de Meijere, Synthesis, 1994, 190. 22 J. L. Broeker, J. E. Eksterowicz, A. J. Belk and K. N. 23 D. Becker, N. Morlender and N. Haddad, Tetrahedron 24 D. Becker and N. Klimovich, Tetrahedron Lett., 1994, 25 M. T. Crimmins and L. E. Guise, Tetrahedron Lett., Houk, J. Am. Chem. SOC., 1995,117,1847. Lett., 1995,36, 1921. 35, 261.1994,35, 1657. Boden and Pattenden: Saturated and partially unsaturated carbocycles 3726 J. E. Resek and A. I. Meyers, Synlett, 1995, 145. 27 M. Tanaka, K. Tomioka and K. Koga, Tetrahedron, 28 E. Marotta, I. Pagani, P. Righi and G. Rosini, 29 E. Marotta, M. Medici, P. Righi and G. Rosini, J. 0%. 30 G. Confalonieri, E. Marotta, F. Rama, P. Righi, 1994,50, 12829. Tetrahedron, 1994, 50, 7645. Chem., 1994, 59,7529. G. Rosini, R. Serra and F. Venturelli, Tetrahedron, 1994,50,3235. 31 S. Yamazaki, H. Fujitsuka, F. Takara and T. Inoue, J. Chem. SOC., Perkin Trans. I, 1994, 695. 32 W. F. Bailey and P. H. Aspris, J. 0%. Chem., 1995, 60, 754. 33 M. Ihara, T. Taniguchi and K. Fukumoto, Tetrahedron Lett., 1994, 35, 1901. 34 M. L. Graziano, M. R. Iesce and F. Cermola, Synthesis, 1994, 149.35 H. Monti, G. Audran, J. P. Monti and G. Uandri, Synlett, 1994, 403. 36 B. Y. Lee, Y. K. Chung, N. Jeong, Y. Lee and S. H. Hwang, J. Am. Chem. SOC., 1994, 116,8793. 37 N. Jeong, S. H. Hwang, Y. Lee and Y. K. Chung, J. Am. Chem. SOC., 1994,116,3159. 38 J. A. Casalnuovo, R. W. Scott, E. A. Harwood and N. E. Schore, Tetrahedron Lett., 1994, 35, 1153. 39 X. Verdaguer, A. Moyano, M. A. Perichs, A. Riera, V. Bernardes, A. E. Greene, A. Alvarez-Larena and J. F. Piniella, J. Am. Chem. SOC., 1994, 116, 2153. Tetrahedron Lett., 1994, 35, 3517. Tetrahedron Lett., 1994, 35, 3521. Tetrahedron Lett., 1995, 36, 2407. 40 A. Stolle, H. Becker, J. Salaun and A. de Meijere, 41 A. Stolle, H. Becker, J. Salaiin and A. de Meijere, 42 J. L. Kent, H. Wan and K.M. Brummond, 43 S. Yo0 and S. H. Lee, J. 0%. Chem., 1994,59,6968. 44 C. Johnstone, W. J. Kerr and U. Lange, J. Chem. SOC., Chem. Commun., 1995,457. 45 M. E. Krafft and X. Chirico, Tetrahedron Lett., 1994, 35, 4511. 46 P. Cruciani, C. Aubert and M. Malacria, Tetrahedron Lett., 1994,35, 6677. 47 H. Corlay, R. T. Lewis, W. B. Motherwell and M. Shipman, Tetrahedron, 1995, 51, 3303. 48 M. Lautens, Y. Ren and P. H. M. Delanghe, J. Am. Chem. SOC., 1994, 116,8821. 49 T. Mandai, Y. Tsujiguchi, J. Tsuji and S. Saito, Tetrahedron Lett., 1994, 35, 5701. 50 L. S. Liebeskind and A. Bombrun, J. 0%. Chem., 1994,59, 1149. 51 M. Zora and J. W. Herndon, J. 0%. Chem., 1994,59, 699. 52 H. Nemoto, M. Shiraki and K. Fukumoto, Synlett, 1994,599. 53 H. Nemoto, M. Shiraki and K. Fukumoto, Tetrahedron, 1994, 50, 10391.54 B. M. Trost, G. J. Tanoury, M. Lautens, G. Chan and D. T. MacPherson, J. Am. Chem. SOC., 1994,116, 4255. 55 F. E. Meyer, K. H. Ang, A. G. Steinig and A. de Meijere, Synlett, 1994, 191. 56 I. Ryu, K. Ikura, Y. Tamura, J. Maenaka, A. Ogawa and N. Sonoda, Synlett, 1994,941. 57 Y. Sato, M. Takimoto, K. Hayashi, T. Katsuhara, K. Takagi and M. Mori, J. Am. Chem. SOC., 1994, 116, 9771. Tetrahedron Lett., 1994, 35, 1445. Tetrahedron, 1995, 51, 4421. 58 J. M. Davis, R. J. Whitby and A. Jaxa-Chamiec, 59 B. L. Pagenkopf, E. C. Lund and T. Livinghouse, 60 D. F. Taber and J. P. Louey, Tetrahedron, 1995,51, 61 E. I. Negishi, J. P. Maye and D. Choueiry, 62 E. I. Negishi, D. Choueiry, T. B. Nguyen and D. R. 4495. Tetrahedron, 1995,51,4447. Swanson, J.Am. Chem. SOC., 1994,116,9751. K. Okamura and T. Date, J. OR. Chem., 1994, 59, 5633. Tetrahedron, 1995, 51,4439. Normant, Tetrahedron, 1994,50, 11 665. Tetrahedron Lett., 1994,35, 5645. Normant, J. 0%. Chem., 1995,60,863. 35, 7939. J. Am. Chem. SOC., 1994, 116,6049. P. Banerji, J. 0%. Chem., 1994, 59, 7594. 59, 2020. 1994,35, 689. Synlett, 1994, 273. 5419. Shirahama, J. 0%. Chem., 1994, 59, 5111. 60, 872. 1994, 116, 7447. E. Yanaginuma, 0. Yonemitsu, A. Nishida and N. Kawahara, Tetrahedron Lett., 1995, 36, 269. 79 S. Bogen, M. Journet and M. Malacria, Synlett, 1994, 958. 80 P. J. Parsons and S. Caddick, Tetrahedron, 1994, 50, 13 523. 81 D. J. Clive, Y. Tao, A. Khodabocus, Y. J. Wu, A. G. Angoh, S. M. Bennett, C. N. Boddy, L. Bordeleau, D. Kellner, G. Kleiner, D.S. Middleton, C. J. Nichols, S. R. Richardson and P. G. Vernon, J. Am. Chem. SOC., 1994, 116, 11 275. 82 D. L. J. Clive and S. R. Magnuson, Tetrahedron Lett., 1995, 36, 15. 83 T. J. Jenkins and D. J. Burnell, J. Org. Chem., 1994, 59, 1485. 84 Y. J. Wu, Y. Y. Zhu and D. J. Burnell, J. Org. Chem., 1994, 59, 104. 85 A. Balong and D. P. Curran, J. 0%. Chem., 1995, 60, 337. 86 A. Balong, S. J. Geib and D. P. Curran, J. 0%. Chem., 1995, 60, 345. 87 D. Schinzer and K. Ringe, Synlett, 1994,463. 88 R. M. Borzilleri, S. M. Weinreb and M. Parvez, 89 T. K. Sarkar, B. K. Ghorai, S. K. Nandy and 90 T. K. Sarkar, B. K. Ghoral and A. Banerji, 91 Y. Nagao, W. S. Lee, I. Y. Jeong and M. Shiro, 92 Y. Nagao, W. S. Lee and K. Kim, Chem. Lett., 1994, 63 N. Uesaka, R. Saitoh, M.Mori, M. Shibap-. II- n 64 F. Saitoh, M. Mori, K. Okamura and T. Date, 65 C. Meyer, I. Marek, G. Courtemanche and J. F. 66 C. Meyer, I. Marek, J. F. Normant and N. Platzer, 67 C. Meyer, I. Marek, G. Courtemanche and J. F. 68 W. Oppolzer and F. Schroder, Tetrahedron Lett., 1994, 69 N. Chatani, T. Morimoto, T. Muto and S. Murai, 70 I. Ojima, D. A. Fracchiolla, R. J. Donovan and 71 C. C. Huval and D. A. Singleton, J. 0%. Chem., 1994, 72 C. C. Huval and D. A. Singleton, Tetrahedron Lett., 73 C. C. Huval, K. M. Church and D. A. Singleton, 74 N. H. Vo and B. B. Snider, J. 0%. Chem., 1994,59, 75 T. Kan, S. Nara, S. Ito, F. Matsuda and H. 76 G. A. Molander and J. A. McKie, J. 0%. Chem., 1995, 77 C. F. Sturino and A. G. Fallis, J. Am. Chem. SOC., 78 M. Nishida, H. Hayashi, Y.Yamaura, J. Am. Chem. SOC., 1994, 116,9789. B. Mukherjee, Tetrahedron Lett., 1994,35, 6903. Tetrahedron Lett., 1994, 35, 6907. Tetruhedron Lett., 1995, 36, 2799. 389. 38 Contemporary Organic Synthesis93 Y. Nagao, W. S. Lee, Y. Komaki, S. Sano and 94 M. P. Cooke Jr and D. Gopal, Tetrahedron Lett., 1994, 95 M. P. Cooke Jr and D. Gopal, J. Org. Chem., 1994, 96 T. V. Ovaska, R. R. Warren, C. E. Lewis, M. Shiro, Chem. Lett., 1994, 597. 35, 2837. 59, 260. N. Wachter-Jurcsak and W. F. Bailey, J. 0%. Chem., 1994,59,5868. 97 A. Padwa, S. H. Watterson and Z. Ni, J. 0%. Chem., 1994,59,3256. 98 A. Padwa, J. M. Kassir, M. A. Semones and M. D. Weingarten, J. 0%. Chem., 1995, 60, 53. 99 M. Asaoka, K. Obuchi and H. Takei, Tetrahedron, 1994, 50, 655. 100 B. L. Williamson, R.R. Tykwinski and P. J. Stang, J. Am. Chem. SOC., 1994, 116,93. 101 R. R. Tykwinski, P. J. Stang and N. E. Perksy, Tetrahedron Lett., 1994,35, 23. 102 K. Nakatani, K. Takada and S. Isoe, J. 0%. Chem., 1995,60,2466. 103 T. Morwick, J. Doyon and L. A. Paquette, Tetrahedron Lett., 1995, 36, 2369. 104 L. A. Paquette and T. Morwick, J. Am. Chem. SOC., 1995,117, 1451. 105 V. H. Rawal, C. Dufour and S. Iwasa, Tetrahedron Lett., 1995, 36, 19. 106 V. H. Rawal and C. Dufour, J. Am. Chem. SOC., 1994, 116,2613. 107 A. de Meijere and F. E. Meyer,Angew. Chem., Int. Ed. Engl., 1994, 33, 2379. 108 C. S. Nylund, J. M. Klopp and S. M. Weinreb, Tetrahedron Lett,, 1994, 35, 4287. 109 B. M. Trost and A. S. K. Hashmi, J. Am. Chem. SOC., 1994, 116, 2183. 110 E. I. Negishi, M.D. Jensen, D. Y. Kondakov and S. Wang, J. Am. Chem. SOC., 1994,116,8404. 111 G. Balme and D. Bouyssi, Tetrahedron, 1994, 50,403. 112 P. Vittoz, D. Bouyssi, C. Traversa, J. GorC and G. Balme, Tetrahedron Lett., 1994, 35, 1871. 113 W. Oppolzer and C. Robyr, Tetrahedron, 1994,50, 415. 114 M. J. Begley, G. Pattenden, A. J. Smithies and D. S. Walter, Tetrahedron Lett., 1994, 35, 2417. 115 G. Pattenden, A. J. Smithies and D. S. Walter, Tetrahedron Lett., 1994,35, 2413. 116 M. Santagostino and J. D. Kilburn, Tetrahedron Lett., 1995,36, 1365. 117 M. Santagostino and J. D. Kilburn, Tetrahedron Lett., 1994,35, 8863. 118 R. W. Jackson and K. J. Shea, Tetrahedron Lett., 1994, 35, 1317. 119 T. K. Park, I. J. Kim, S. J. Danieshefsky and S. de Gala, Tetrahedron Lett., 1995, 36, 1019.120 J. D. Winkler, H. S. Kim and S. Kim, Tetrahedron Lett,, 1995,36, 687. 121 C. Spino and J. Crawford, Tetrahedron Lett., 1994, 35, 5559. 122 C. Spino, J. Crawford and J. Bishop, J. 0%. Chem., 1995, 60,844. 123 C. Spino and N. Tu, Tetrahedron Lett., 1994, 35, 3683. 124 F. Nuyttens, J. Hoflack, G. Appendino and P. J. De Clerq, Synlett, 1995, 105. 125 P. A. Grieco, S. T. Handy and J. P. Beck, Tetrahedron Lett., 1994, 35, 2663. 126 P. A. Grieco, J. P. Beck, S. T. Handy, N. Saito and J. F. Daeuble, Tetrahedron Lett., 1994, 35, 6783. 127 D. B. Gorman and P. G. Gassman, J. 0%. Chem., 1995, 60, 977. 128 S. H. Jung, Y. S. Lee, H. Park and D. S. Kwon, Tetrahedron Lett., 1995, 36, 1051. 129 Y. Sakamoto, H. Yamada and T. Takahashi, Synlett, 1995, 231. 130 E. J. Corey, A.Guzman-Perez and T. P. Loh, J. Am. Chem. SOC., 1994, 116, 3611. 131 E. J. Corey, S. Sarshar and D. H. Lee, J. Am. Chem. SOC., 1994, 116, 12089. 132 W. R. Roush and C. K. Wada, J. Am. Chem. SOC., 1994,116,2151. 133 S. Kobayashi, M. Araki and I. Hachiya, J. 0%. Chem., 1994,59,3758. 134 C. Aubert, D. Llerena and M. Malacria, Tetrahedron Lett., 1994,35, 2341. 135 A. Padwa, V. P. Sandanayaka and E. A. Curtis, J. Am. Chem. SOC., 1994, 116,2667. 136 E. A. Curtis, V. P. Sandanayaka and A. Padwa, Tetrahedron Lett., 1995,36, 1989. 137 A. Abouabdellah and D. Bonnet-Delpon, Tetrahedron, 1994,50, 11 921. 138 J. D. White and T. C. Somers, J. Am. Chem. SOC., 1994,116,9912. 139 K. A. Parker and D. Fokas, J. 0%. Chem., 1994,59, 3927. 140 K. A. Parker and D. Fokas, J. 0%. Chem., 1994,59, 3933.141 S. Pal, J. K. Mukhopadhyaya and U. R. Ghatak, J. 0%. Chem., 1994,59,2687. 142 J. Marco-Contelles, M. BernabC, D. Ayala and B. Sinchez, J. Oe. Chem., 1994,59, 1234. 143 E. J. Enholm, Y. Xie and K. A. Abboud, J. 0%. Chem., 1995,60, 11 12. 144 P. Dowd, W. Zhang and K. Mahmood, Tetrahedron, 1995, 51, 39. 145 C. Destabel, J. D. Kilburn and J. Knight, Tetrahedron, 1994,50,11267. 146 C. Destabel, J. D. Kilburn and J. Knight, Tetrahedron, 1994,50, 11 289. 147 S. Wu, M. Journet and M. Malacria, Tetrahedron Lett., 1994,35,8601. 148 L. Chen, G. B. Gill and G. Pattenden, Tetrahedron Lett., 1994,35, 2593. 149 P. V. Fish and W. S. Johnson, J. 08. Chem., 1994, 59, 2324. 150 P. V. Fish and W. S. Johnson, Tetrahedron Lett., 1994, 35, 1469. 151 P. V. Fish, Tetrahedron Lett., 1994,35, 7181.152 G. S. Jones, Tetrahedron Lett., 1994,35, 9685. 153 E. J. Corey, J. Lee and D. R. Liu, Tetrahedron Lett., 154 L. F. Tietze and R. Schimpf,Angew. Chem., Int. Ed. 155 M. Terakado, M. Miyazawa and K. Yamamoto, 156 S. Hatakeyama, H. Irie, T. Shintani, Y. Noguchi, 1994,35,9149. Engl., 1994,33, 1089. Synlett, 1994, 134. H. Yamada and M. Nishizawa, Tetrahedron, 1994, 50, 13 369. Tetrahedron Lett., 1995, 36, 51. Chem. SOC., 1994, 116, 10801. 1994,116, 1776. 59, 6710. Tetrahedron, 1994, 50, 906 1. 1995,369. 157 R. M. Moriarty, J. Kim and H. Brumer 111, 158 S. H. Kim, N. Bowden and R. H. Grubbs, J. Am. 159 R. Guevel and L. A. Paquette, J. Am. Chem. SOC., 160 0. Z. Pereira and T. H. Chan, J. 0%. Chem., 1994, 161 B. Ye, L. X. Qiao, Y. B. Zhang and Y.L. Wu, 162 D. Enders, J. Wiedermann and W. Bettray, Synlett, Boden and Pattenden: Saturated and partially unsaturated carbocycles 39163 S. V. Ley and C. Kouklovsky, Tetrahedron, 1994,50, 835. 164 T. Tokoroyama, M. Kato, T. Aoto, T. Hattori, H. Iio and Y. Odagaki, Tetrahedron Lett., 1994,35,8247. 165 S. D. Burke, M. E. Kort, S. M. S. Strickland, H. M. Organ and L. A. Silks 111, Tetrahedron Lett., 1994,35, 1503. Tetrahedron Lett., 1994,35, 3865. Tetrahedron, 1994,50, 12579. Tetrahedron Lett., 1995,36, 2729. 5161. 2183. 35, 6607. 35, 8513. Trans. 1, 1994, 921. 1994, 116,5487. 1995,117, 1954. Tetrahedron Lett., 1995,36, 1397. Kazanietz and P. M. Blumberg, J. 0%. Chem., 1995, 60, 1381. 178 T. Habeck, C. Wolff and W. Tochtermann, Tetrahedron Lett., 1995,36, 2041.179 M. C. McMills, L. Zhuang, D. L. Wright and W. Watt, Tetrahedron Lett., 1994, 35, 8311. 180 S. R. Angle and M. A. Hossain, Tetrahedron Lett., 1994,35,4519. 181 G. Majetich, Y. Zhang and S. Liu, Tetrahedron Lett., 1994,35,4887. 182 G. A. Molander and J. A. McKie, J. 0%. Chem., 1994, 59, 3186. 183 S. J. Miller, S. H. Kim, Z. R. Chen and R. H. Grubbs, J. Am. Chem. SOC., 1995,117,2108. 184 M. Harmata, S. Elahmad and C. L. Barnes, J. 0%. Chem., 1994,59, 1241. 185 T. F. Jamison, S. Shambayati, W. E. Crowe and S. L. Schreiber, J. Am. Chem. SOC., 1994, 116,5505. 186 L. A. Paquette, T. Z. Wang and E. Pinard, J. Am. Chem. SOC., 1995, 117, 1455. 187 L. A. Paquette, D. Koh, X. Wang and J. C. Prodger, Tetrahedron Lett., 1995,36, 673. 188 E. L. Grimm, S. kvac and M.L. Coutu, Tetrahedron Lett., 1994,35, 5369. 189 K. C. Nicolaou, W. M. Dai and R. K. Guy, Angew Chem., Int. Ed. Engl., 1994, 33, 15. 190 K. C. Nicolaou, P. G. Nantermet, H. Ueno, R. K. Guy, E. A. Couladouros and E. J. Sorensen, J. Am. Chem. SOC., 1995, 117,624. Sorensen, C. F. Claiborne, R. K. Guy, C. K. Hwang, M. Nakada and P. G. Nantermet, J. Am. Chem. SOC., 1995, 117,634. 166 W. Zhang, Y. Hua, G. Hoge and P. Dowd, 167 W. Zhang, Y. Hua, S. J. Geib, G. Hoge and P. Dowd, 168 W. Zhang, M. R. Collins, K. Mahmood and P. Dowd, 169 W. Zhang and P. Dowd, Tetrahedron Lett., 1994,35, 170 G. L. Lange and C. Gottardo, J. 0%. Chem., 1995,60, 171 G. L. Lange and C. Gottardo, Tetrahedron Lett., 1994, 172 G. L. Lange and C. Gottardo, Tetrahedron Lett., 1994, 173 B. C. Ranu and A. R. Das, J. Chem. SOC., Perkin 174 C. F. Billera and R. D. Little, J. Am. Chem. SOC., 175 M. Lautens and S. Kumanovic, J. Am. Chem. Soc., 176 M. Harmata, S. Elahmad and C. L. Barnes, 177 J. D. Winkler, B. C. Hong, A. Bahador, M. G. 191 K. C. Nicolaou, J. J. Liu, Z. Yang, H. Ueno, E. J. 192 K. C. Nicolaou, Z. Yang, J. J. Liu, P. G. Nantermet, C. F. Claiborne, J. Renaud, R. K. Guy and K. Shibayama, J. Am. Chem. SOC., 1995,117,645. 193 K. C. Nicolaou, H. Ueno, J. J. Liu, P. G. Nantermet, Z. Yang, J. Renaud, K. Paulvannan and R. Chadha, J. Am. Chem. SOC., 1995,117,653. 194 R. A. Holton, C. Somoza, H. B. Kim, F. Liang, R. J. Biediger, P. D. Boatman, M. Shindo, C. C. Smith, S. Kim, H. Nazidadeh, Y. Suzuki, C. Tao, P. Vu, S. Tang, P. Zhang, K. K. Murthi, L. N. Gentile and J. H. Liu, J. Am. Chem. SOC., 1994,116, 1597. 195 R. A. Holton, C. Somoza, H. B. Kim, F. Liang, R. J. Biediger, P. D. Boatman, M. Shindo, C. C. Smith, S. Kim, H. Nazidadeh, Y. Suzuki, C. Tao, P. Vu, S. Tang, P. Zhang, K. K. Murthi, L. N. Gentile and J. H. Liu, J. Am. Chem. SOC., 1994, 116, 1599. 196 M. Seto, K. Morihira, Y. Horiguchi and I. Kuwajima, J. 0%. Chem., 1994,59, 3165. 197 C. S. Swindell, W. Fan and P. G. Klimko, Tetrahedron Lett., 1994,35, 4959. 198 M. A. Romero, R. P. Franco, R. Cruz-Almanza and F. Padilla, Tetrahedron Lett., 1994,35, 3255. 199 S. W. Elmore and L. A. Paquette, J. 0%. Chem., 1995,60,889. 200 S. F. Martin, J. M. Assercq, R. E. Austin, A. P. Dantanarayana, J. R. Fishpaugh, C. Gluchowski, D. E. Guinn, M. Hartmann, T. Tanaka, R. Wagner and J. B. White, Tetrahedron, 1995,51, 3455. 201 S. K. Yeo, N. Hatae, M. Seki and M. Kanematsu, Tetrahedron, 1995,51,3499. 202 G. G. Melikyan, R. C. Combs, J. Lamirand, M. Khan and K. M. Nicholas, Tetrahedron Lett., 1994,35, 363. 203 K. I. Iida and M. Hirama, J. Am. Chem. SOC., 1994, 116, 10310. 204 A. G. Myers, M. E. Fraley and N. J. Tom, J. Am. Chem. SOC., 1994,116, 11 556. 205 T. Brandstetter and M. E. Maier, Tetrahedron, 1994, 50, 1435. 206 T. Nishikawa, S. Shibuya and M. Isobe, Synlett, 1994, 482. 207 J. F. Kadow, D. J. Cook, T. W. Doyle, D. R. Langley, K. H. Pham, D. M. Vyas and M. D. Wittman, Tetrahedron, 1994,50, 1519. 1994,35,4505. Synlett, 1995, 267 Chem., 1994,59,2700. 1995, 36, 35. Lett., 1994,35, 5509. J. 0%. Chem., 1994,59,4393. Tetrahedron Lett., 1994,35, 2761. 208 J. E. McMurry and N. 0. Siemers, Tetrahedron Lett., 209 D. M. Hodgson, L. T. Boulton and G. N. Maw, 210 H. Takayanagi, Y. Kitano and Y. Morinaka, J. OR. 211 D. R. Williams and P. J. Coleman, Tetrahedron Lett., 212 A. Botom, C. Betancor and E. Suiirez, Tetrahedron 213 A. Boto, C. Betancor, T. PrangC and E. Suiirez, 214 G. Mehta, S. R. Karra and N. Krishnamurthy, 215 L. E. Overman, Pure Appl. Chem., 1994,66, 1423. 216 M. Shibasaki and M. Sodeoka, J. Syn. 0%. Chem. 217 H. Y. Dai and G. H. Posner, Synthesis, 1994, 1383. Jpn., 1994, 52, 956. 40 Contemporary Organic Synthesis

ISSN:1350-4894    

DOI:10.1039/CO9960300019

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

ISSN 1350-4894 COGSE6 3 1-1-1-54 (1996) ~~~~~~ ~ ~ Contemporary Organic Synthesis A journal of current developments in Organic Synthesis V O L U M E 3 INDEXES CONTENTS ... 111 Contents of volume 3 iv Contributors to volume 3 V Journal details 1-1 Index of authors cited 1-29 Subject index Notice to librarians: Journal binding Preliminary pages iii-vi are designed to be bound at the beginning of volume 3, and the Indexes bound at the end, 1ISSN 1350-4894 COGSE6 3 1-1-1-54 (1996) ~~~~~~ ~ ~ Contemporary Organic Synthesis A journal of current developments in Organic Synthesis V O L U M E 3 INDEXES CONTENTS ... 111 Contents of volume 3 iv Contributors to volume 3 V Journal details 1-1 Index of authors cited 1-29 Subject index Notice to librarians: Journal binding Preliminary pages iii-vi are designed to be bound at the beginning of volume 3, and the Indexes bound at the end, 1ISSN 1350-4894 COGSE6 3 1-568, 1-1-1-54 (1996) Contemporary Organic Synthesis A journal of current developments in Organic Synthesis V O L U M E 3 CONTENTS 1 19 41 65 93 125 133 151 173 201 229 243 259 277 295 Stoichiometric applications of organotransition metal complexes in organic synthesis Timothy J.Donohoe Reviewing the literature published between 1 September 1994 and 30 April 1995 Saturated and partially unsaturated carbocycles Gerald Pattenden Reviewing the literature published between January 1994 and April 1995 The enediyne and dienediyne based antitumour antibiotics. Methodology and strategies for total synthesis and construction of bioactive analogues.Part 1 Hem6 Lhermitte and David S. Grierson Reviewing the literature published up to 15 October 1995 Alcohols, ethers and phenols C. S. Hau, Ashley N. Jarvis and Joseph B. Sweeney Reviewing the literature published between August 1993 and February I994 The enediyne and dienediyne based antitumour antibiotics. Methodology and strategies for total synthesis and construction of bioactive analogues. Part 2 Hem6 Lhermitte and David S. Grierson Reviewing the literature published up to 15 November I995 The discovery of fluconazole Reviewing the literature published up to December 1994 Organic halides Stephen I? Marsden Reviewing the literature published between 1 July 1993 and 30 June 1995 Aldehydes and ketones Patrick G. Steel Reviewing the literature published between October 1994 and September I993 Recent developments in chemical oligosaccharide synthesis Geert- Jan Boons Reviewing the literature published up to October 1995 Main group organometallics in synthesis Martin Wills Reviewing the literature published between January 1994 and June I995 Saturated oxygen heterocycles Reviewing the literature published between October 1994 and September I995 Carboxylic acids and esters Tammy Ladduwahetty Reviewing the literature published between 1 August 1994 and 31 July 1995 Saturated nitrogen heterocycles Timothy Harrison Reviewing the literature published in 1995 Catalytic applications of transition metals in organic synthesis Graham J.Dawson, Justin F. Bower and Jonathan M. J. Williams Reviewing the literature published between I September 1994 and 31 October 1995 Saturated and unsaturated lactones Ian Collins Reviewing the literature published between 1 August 1994 and 31 October 1995 Christopher D.J. Boden and Ken Richardson Christopher J. Burns and Donald S. Middleton ... 111323 345 373 397 433 447 473 499 535 I- 1 1-29 Amines and amides Michael North Reviewing the literature published in 1995 Synthetic approaches to rapamycin Mark C. Norley Reviewing the literature published up to August I995 Synthetic applications of flash vacuum pyrolysis Hamish McNab Reviewing the literature published between 1990 and 1995 Protecting groups Krzysztof Jarowicki and Philip Kocienski Reviewing the literature published in 1995 The synthesis of quinones Peter T. Gallagher Reviewing the literature published between 1 January 1991 and 31 December 1995 The intramolecular Heck reaction Richard J.Middleton Reviewing the literature published up to the end of 1995 Saturated and partially unsaturated carbocycles Kevin I. Booker-Milburn and Andrew Sharpe Reviewing the literature published between May 1995 and April 1996 Synthesis of thiols, selenols, sulfides, selenides, sulfoxides, selenoxides, sulfones and selenones Christopher M. Rayner Reviewing the literature published between March 1995 and May 1996 The synthesis of carbocyclic aromatic systems Andrew C. Williams Reviewing the literature published between Janualy 1992 and December 1995 Susan E. Gibson (nee Thomas) and Index of authors cited Subject index Contributors to Volume 3 Boden, Christopher D.J., 19 Booker-Milburn, Kevin I., 473 Boons, Geert-Jan, 173 Bower, Justin F., 277 Burns, Christopher J., 229 Collins, Ian, 295 Dawson, Graham J., 277 Donohoe, Timothy J., 1 Gallagher, Peter T., 433 Gibson (nee Thomas), Susan E., 447 Grierson, David S., 41, 93 Harrison, Timothy, 259 Hau, C. S., 65 Jarowicki, Krzysztof, 397 Jarvis, Ashley N., 65 Kocienski, Philip, 397 Ladduwahetty, Tammy, 243 Lhermitte, Heme, 41, 93 Marsden, Stephen P., 133 McNab, Hamish, 373 Middleton, Donald S., 229 Middleton, Richard J., 447 Norley, Mark C., 345 North, Michael C., 323 Pattenden, Gerald, 19 Rayner, Christopher M., 499 Richardson, Ken, 125 Sharpe, Andrew, 473 Steel, Patrick G., 151 Sweeney, Joseph B., 65 Williams, Jonathan M. J., 277 Williams, Andrew C., 535 Wills, Martin, 201 iv~~ Contemporary Organic Synthesis Editorial Board Professor G.Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, and Medicine Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology 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, Universite' de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R.Noyori, Nagoya University Professor L. E. Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla 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 Dr S. R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK. 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. 1996 subscription rates: EEA f185, USA $350, Canada 2190 (plus GST), Rest of the World X190. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices.Second class postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. (3 The Royal Society of chemistry, 1997 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 in Great Britain by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd V~~ Contemporary Organic Synthesis Editorial Board Professor G.Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, and Medicine Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology 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, Universite' de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R. Noyori, Nagoya University Professor L. E.Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla 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 Dr S. R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK.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. 1996 subscription rates: EEA f185, USA $350, Canada 2190 (plus GST), Rest of the World X190. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Second class postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. (3 The Royal Society of chemistry, 1997 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 in Great Britain by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd V

ISSN:1350-4894    

DOI:10.1039/CO99603FP025

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Contemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, and Medicine Professor P. J. Kocienski, University of Southampton Professor C. J. Moody, Loughborough University of Technology Professor E. J. Thomas, University of Manchester International Advisory Board PrGfessor E. J. Corey, Harvard University Professor S. Hanessian, Universiti de Montrial Professor M. Julia, Universiti de Paris X I (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R. Noyori, Nagoya University Professor L.E. Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla 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 Dr Sheila R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK.Deputy Editor: Nicole Brooks. Production Editor: Nicola Coward. Technical Editor: Tony Breen. Tel +44 (0) 1223 420066 Fax +44 (0) 1223 420247 E-mail rscl@rsc.org RSC Server http://chemistry.rsc.org/rsc/ 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. 1996 subscription rates: EEA f185, USA $350, Canada El90 ‘(plus GST), Rest of the World f190. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December.Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Periodicals postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. 0 The Royal Society of Chemistry, 1996. 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 in Great Britain by Unicus Graphics Ltd, Horsham, West Sussex Printed in Great Britain by Whitstable Litho Ltd, Whitstable, KentContemporary Organic Synthesis Editorial Board Professor P.J. Kocienski (Chairman), University of Glasgow Professor P. D. Bailey, Heriot- Watt University Dr S . E. Gibson (nee Thomas), Imperial College of Science, TechnoloD, and Medicine Professor R. F. W. Jackson, University of Newcastle Professor C. J. Moody, University of Exeter Professor G. Pattenden, FRS, University of Nottingham Professor R. J. K. Taylor, University of York International Advisory Board Professor E. J. Corey, Haward University Professor S . Hanessian, Universitk de Montreal Professor M. Julia, Universite de Paris X I (Paris-Sud) Professor P.D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R. Noyori, Nagoya University Professor L. E. Overman, University of California, Iwine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla 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 Dr Sheila R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry: Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK. Deputy Editor: Dr Roxane Owen. Production Editor: Nicola Coward. Technical Editor: Dr Helen Saxton. Tel +44 (0) 1223 420066 Fax +44 (0) 1223 420247 E-mail perkin@rsc.org RSC Server http://chemistry.rsc.orglrsc/ 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.1997 annual subscription rate: f199.00; US$358.00. Customers in Canada will be charged the sterling price plus a surcharge to cover GST. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Periodicals postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. The Royal Society of Chemistry, 1997. 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 in Great Britain by Unicus Graphics Ltd, Horsham, West Sussex Printed in Great Britain by Whitstable Litho Ltd, Whitstable, Kent

ISSN:1350-4894    

DOI:10.1039/CO99603FX029

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

280 H. Tani, S. Irie, K. Masumoto and N. Ono, Hetero- 281 S. Dhanalekshmi, C. S. Venkatachalam and K. K. cycles, 1993, 36, 1783. Balasubramian, J. Chem. SOC., Chem. Commun., 1994, 511. Chem. Soc., 1994, 116,6713. 1993,36, 1795. J. Chem. SOC., Perkin Fans. 1, 1995, 2855. 1994,352299. Chem., 1992,45, 1639. 282 W. Adam, M. Ahnveiler and D. Reinhardt, J. Am. 283 B. Alcaide, C. Biurran and J. Plumet, Heterocycles, 284 M. A. Brimble, S. J. Phythian and H. Prabaharan, 285 D. G. Barrett and S.H. Gellman, Tetrahedron Lett., 286 D. B. Clarke, J. R. Guild and R. T. Weavers, Aust. J. Williams: The synthesis of carbocyclic aromatic systems 287 H. R. Sonawane, S. N. Bellur and S. G. Sudrik, Ind. J. 288 E. V. Dehmlow and C. Bollmann, Tetrahedron, 1995, 289 G. P. Shkil and R. S. Sagitullin, Tetrahedron Lett., 290 H.A. Etman, Ind. J. Chem., Sect. B, 1995,34, 285. 291 T. Nakazawa, M. Ishihara, M. Jiguji, M. Yamaguici, Y. Sugihara and I. Murata, Tetrahedron Lett., 1992, 33, 6487. 292 H. Nishino, S. Kajikawa, Y. Hamada and K. Kuro- sawa, Tetrahedron Lett., 1995, 36, 5753. 293 R. F. C. Brown, F. W. Eastwood and J. M. Horvath, Aust. J. Chem., 1995, 48, 1055. Chem., Sect. B, 1992, 31, 606. 51, 3755. 1994,35, 2075. 567280 H. Tani, S. Irie, K. Masumoto and N. Ono, Hetero- 281 S. Dhanalekshmi, C. S. Venkatachalam and K. K. cycles, 1993, 36, 1783. Balasubramian, J. Chem. SOC., Chem. Commun., 1994, 511. Chem. Soc., 1994, 116,6713. 1993,36, 1795. J. Chem. SOC., Perkin Fans. 1, 1995, 2855. 1994,352299. Chem., 1992,45, 1639. 282 W. Adam, M. Ahnveiler and D. Reinhardt, J. Am. 283 B. Alcaide, C. Biurran and J. Plumet, Heterocycles, 284 M. A. Brimble, S. J. Phythian and H. Prabaharan, 285 D. G. Barrett and S.H. Gellman, Tetrahedron Lett., 286 D. B. Clarke, J. R. Guild and R. T. Weavers, Aust. J. Williams: The synthesis of carbocyclic aromatic systems 287 H. R. Sonawane, S. N. Bellur and S. G. Sudrik, Ind. J. 288 E. V. Dehmlow and C. Bollmann, Tetrahedron, 1995, 289 G. P. Shkil and R. S. Sagitullin, Tetrahedron Lett., 290 H. A. Etman, Ind. J. Chem., Sect. B, 1995,34, 285. 291 T. Nakazawa, M. Ishihara, M. Jiguji, M. Yamaguici, Y. Sugihara and I. Murata, Tetrahedron Lett., 1992, 33, 6487. 292 H. Nishino, S. Kajikawa, Y. Hamada and K. Kuro- sawa, Tetrahedron Lett., 1995, 36, 5753. 293 R. F. C. Brown, F. W. Eastwood and J. M. Horvath, Aust. J. Chem., 1995, 48, 1055. Chem., Sect. B, 1992, 31, 606. 51, 3755. 1994,35, 2075. 567

ISSN:1350-4894    

DOI:10.1039/CO99603BX031

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

~~ The enediyne and dienediyne based antitumour antibiotics. Methodology and strategies for total synthesis and construction of bioactive analogues. Part 1 HERVE LHERMITTE AND DAVID s. GRIERSON* Institut de Chimie des Substances Naturelles, F-91198 Gij-sur-Yvette, France Reviewing the literature published up to 15 October 1995 1 Introduction 2 3 4 Simple yne-ene-allenes and yne-ene-cumulenes 5 Ten-membered ring and higher neocarzinostatin chromophore analogues 6 Conclusion 7 References and notes Enediyne construction and simple monocyclic and bicyclic enediynes Monocyclic and bicyclic enediynes with novel activating devices 1 Introduction In a key contribution to the study of aromatic systems and aromaticity, Bergman and collaborators carried out experiments nearly twenty-five years ago to define the physical existance, structure, bonding properties and reactivity of 1,4-dehydrobenzene 2.' In one particularly elegant experiment the scrambling of the deuterium label in the acyclic enediyne 1 (R = D) provided convincing evidence for the intermediacy of phenylene diradical2 (Scheme 1).This result, further, offered a coherent mechanistic rationale for a number of unexpected transformations, including the tendency of molecules such as the dehydro-azulene 3 and the 1,5-dehydro[ lolannulene 4 to undergo rapid cycloaromatization.27' As important as these studies remain today from a fundamental point of view, the human spirit was a long way at that time from imagining the creative way in which nature has for eons enabled microorganisms to employ this same process in a controlled and lethal manner to assure their proper defence.However, our awareness of this situation changed in the mid 1980s with the structure elucidation of the complex and extraordinary novel antibiotics calicheamicin 5,4 esperamicin 65 and the neocarzinostatin chromophore 9,6 the first three members of a family 3 + r 1 4 & Scheme 1 of naturally occurring and highly potent cytotoxic agents. The most notable features in the common core structure of ( -)-calicheamicin yI1 and (-)-esperamicin Al (Scheme 2) are the presence of a contiguous yne-ene-yne (or 'enediyne') system incorporated into a bicyclo[7.3.l]tridecane framework, an allylic trisulfide unit, and an enone system in which the double bond occupies the bridgehead position.Chemical and biochemical investigations have shown that these entities react in concert to generate the highly reactive 1,4-phenylene diradical intermediate 8 which cause cell destruction through single and double strand Lhemitte and Grierson: Enediyne based antitumour antibiotics. Part 1 41lHfio MesSS MeO 0 Me 5 calicheamicin-yl* R' = H, R2 = Et, R3 = I 1. S 3 M d - ii. Michael addition 7 Scheme 2 Me 8 A? cleavage of duplex DNA.7-9 This is brought about by an unprecedented multistep mechanism involving the aryl oligosaccharide mediated association of the antibiotic with its intracellular target, cleavage (reduction) of the trisulfide bond, and Michael addition of the resulting thiolate anion to the enone double bond to produce the highly strained intermediate 7 lacking the crucial C-9,lO bridgehead double bond.This latter structural modification activates, or unlocks, the molecule with respect to spontaneous Bergman type cycloaromatization to diradical 8. The neocarzinostatin chromophore 9, a very heat-, light- and pH-sensitive 9-membered bicyclic dienediyne, exists in nature in association with an apoprotein." With the knowledge that 9 is activated towards DNA cleavage through reaction with thiols,*-" Myers proposed a mechanism whereby thiol addition at C-12 initiates epoxide ring opening and formation of the yne-ene-cumulene 10 (Scheme 3).11 This strained and very highly reactive intermediate then undergoes a cycloaromatization reaction, analogous to that for the enediynes, giving the diradical 11 which cleaves DNA through hydrogen atom abstraction.In an elegant series of NMR experiments Myers both confirmed the formation of the thioglycolate derivative of 10, measured its stability (ti = 2 h at -38 "C), and deduced the absolute stereochemistry of 9.l27I3 Recently, it has been shown that the alternative pathway, leading to the diradical 13 or its zwitterionic resonance form 14 via cumulene 12, is also operative in aqueous buffered ~olution.'~ In 1990, Konishi and Clardy reported the structure of another enediyne antibiotic, Ar 11 10 12 neocarzinostatin 9 . 13 t L Scheme 3 42 Contemporary Organic Synthesis(+)-dynemicin A 15 (Scheme 4).lS This unique hybrid molecule is essentially composed from an enediyne core as found in calicheamicin/ esperamicin, and an anthraquinone unit typical of the anthracyclines which can associate with DNA through inter~alation.~~~””’” Between these two halves of the molecule is an angular epoxide function which acts as the triggering device.Bioreduction of the paraquinone system of 15 giving 16 activates the molecule toward epoxide opening according to pathway B, or through participation of the electrons on nitrogen (pathway A). As discussed further on, the latter mechanism has, in particular, been exploited to activate simplified analogues of dynemicin A. Reaction of either intermediate with the OH- (Nu-) ion giving 17 alters the shape and strain energy of the D/E rings promoting spontaneous Bergman cyclization to diradical 18. The highly strained nature of dynemicin A is readily apparent from the X-ray crystal structure of its triacetate derivative.” In this molecule the alkyne substituents are bent by up to 20” from linearity, and the distance between the tyo acetylene terminal carbons 23 an< 28 is 3.54 A, i.e.considerably less than the 4.17 A separation observed between the same carbons in 1. Over the past three or four years three new molecules have been added to the list of enediyne based antitumor agents. These include kedarcidin 1918 and C-1027 2OI9 which both possess an enediyne unit within a 9-membered bicyclic framework related to the neocarzinostatin chomophore (Scheme 5). Certain elements are still undetermined concerning the structure of the third and extremely labile molecule named maduropeptin.” However, from the structure of the artifact 21, one perceives a new mechanism of activation involving SN2’ displacement of X- and generation of the central enediyne double bond in 22.discovering new anticancer agents based upon the novel structure and mechanism of action of the enediyne-dienediyne antibiotics, intense efforts have been made to both achieve their total synthesis, and to access simpler and more stable biologically active analogues. Work toward both goals has necessitated the development of new synthetic methodology for the efficient construction of the enynes and enediynes, and for the incorporation of these entities into strained mono- and polycyclic structures under conditions where adventitious cycloaromatization, and/or other undesired rearrangements are avoided. It has similarly required the invention of novel triggering devices, and experiments to establish the different factors which permit Bergman and Myers type electrocyclization of enediyne, yne-ene-allene and yne-ene-cumulene systems to occur at physiological temperatures.These, and many other challenging aspects of the chemistry in this field, are described in this two-part review. In Part 1, synthetic approaches, and the reactivity of simple enediynes and neocarzinostatin analogues are described. In Part 2,20a the discussion In view of the large possibilities of designing and OH 0 OH (+)-dynemicin A 15 IEE OH OH OH 16 C02H OH OH OH OMe OH OH OH OH OH OH 17 Bergman cyclization I COPH OMe OH OH OH 18 Scheme 4 Lhermitte and Grierson: Enediyne based antiturnour antibiotics.Part I 43Me' kedarcidin 19 o \ A0 NH2 C-1027 20 maduropeptin 21 (major artifact) I I h;le Scheme 5 centres more specifically upon the strategies developed for the total synthesis of the neocarzinostatin chromophore, calicheamicin yl', esperamicin Al and dynemicin A. Several earlier reviews have appeared treating the chemistry and/or biological properties of the enediyne-diendiyne antibiotic^.^*^'^'-^* 2 Enediyne construction and simple monocyclic and bicyclic enediynes The seminal investigations by Bergman on the cycloaromatization of simple acyclic enediynes demonstrated that heating to approximately 200 "C is required in order to surmount the activation barrier (AEact = 28-32 kcal mol-') to transformation of 1 to the 174-phenylene diradical 2.1,26,27 In contrast, calicheamicin, dynemicin A and the other enediynes undergo almost instantaneous ambient temperature cycloaromatization upon activation, indicating that incorporation of the enediyne system into a cyclic structure lowers A&,, significantly (21-24 kcal mol-' range).To systematically examine the influence of ring size, and hence the distance rc,d between the acetylene terminal carbon atoms, on cycloaromatization rates, Nicolaou devised a route to the monocyclic enediynes 25 (n = 2-8) starting from the appropriate dibromides 23-28-30 In this approach the key step was the Ramberg-Backlund ring contraction of the sulfone intermediates 24 (Scheme 6).31 These studies showed that for the 10-membered all carbon monocyclic Fnediyne 25 (n = 2), rc,d falls in the range (3.20-3.30 A; MMX calculations) where Bergman cyclization can occur at an appreciable rate at 37 "C (flI2 = 11.8 h).Interestingly, attempts to prepare the 9-membered enediyne 25 (rz = 1) by this route resulted in formation of enediyne 27, presumably by a Cope type rearrangement of 26 and SOz extrusion. Magnus and Snyder further showed that for more highly functionalized cyclic enediynes, AEact is primarily determined by factors influencing the strain energy (i) of the ground state structure and (ii) at the transition state for the cycloaromatization r e a ~ t i o n . ~ ~ , ~ ~ 27 26 Schema 6 44 Contemporary Organic SynthesisOf major impact to all subsequent syntheses of the enediyne and neocarzinostatin type systems has been the existence of modern palladium(0) based coupling methodology permitting assembly of the key ene-yne motif from a wide variety of olefin and acetylene precursors under operationally simple, exceptionally mild, and high yielding conditions.The generality of this approach is nicely illustrated by the construction of the parent 3-ene-1,5-diyne 1 (R = TMS) by V ~ l l h a r d t , ~ ~ ~ ~ ~ and the stable 12-membered ring lactone 30 by Linstrumelle (Scheme 7).35736 In this latter synthesis, described two years prior to the discovery of calicheamicid esperamicin, the species produced by oxidative addition of cis-dichloroethene 28 to Pd(0) reacts with an in situ generated copper acetylide intermediate, and the resulting vinyl-alkynyl palladium derivative undergoes a reductive elimination to liberate the ene-yne product 29 and the Pd(0) catalyst.Various amine bases (Et2NH, Et3N, PriNH2, BuNH2) can be employed in this (Ph3P)4Pdo can be replaced by (Ph3P)2PdC12 when a slight excess of the acetylene component is used to effect reduction of Pd(11).'~ Vinyl and alkynyl tin, zinc and boron reagents can also be employed in these palladium co~plings."~-~* Recently it has been shown that Pd(0) coupling of terminal acetylenes with vinyl bromides, iodides and triflates does not require added CuI when pyrrolidine or piperidine is used as the and, as described by Sonogashira, I"" Pdo-CuI - To" 30 Scheme 7 Following the Linstrumelle strategy the more strained 10-membered monocyclic enediyne 31 has been prepared,@ and by replacing cis-dichloroethene by o-dibromobenzene the related benzodiyne 32 was also These compounds undergo Bergman cyclization at temperatures higher than the parent enediyne 25 (n = 2).Pdo-CuI mediated coupling of aryl iodides with enediyne 1 (R = H) is similarly efficient, and has been used to prepare the novel crown ether 33.46 The reaction threshold for this molecule is apparently lower than for 1 (R = H). However, the 2: 1 sandwich complex with the K+ ion is less reactive. In the search for new enediyne systems which can intercalate with DNA, the acyclic benzodiyne 35 was constructed from the naphthalimide derivative 34 through reaction with two molecules of trimethylsilyl acetylene.47 31 32 : N T 0 &$ CI I 33 i. TMS Pdo-CuI Ill 3s 34 Beau and co-workers have demonstrated the power of the Nozaki-Kishi reaction (CrC12-NiC12) between an acetylenyl iodide and an aldehyde to effect ring closure of 36 to the 10-membered enediyne 37 bearing a prop-2-ynylic alcohol substituent (Scheme 8).48v49 This reaction is similarly a key step in the conceptually interesting synthesis by Fallis of the 'taxamycin' 38 (an enediyne-taxol hybrid):' and the equally novel enediyne-estradiol hybrid 39 by De Clercq." Boger et al.on the other hand, found that the benzodiyne 40 undergoes ring closure to 41 on treatment with lithium amide base, albeit in modest yield (21%).52 This compound was coupled to CDP13, a synthetic non-covalent DNA minor groove binder, and the resulting conjugate 42 was shown to display potent capacity to interact with and cleave supercoiled DNA. has also been used by Nicolaou to effect ring A samarium iodide induced Pinacol type reaction Lhermitte and Grierson: Enediyne based antiturnour antibiotics.Part 1 4560% \OH 36 38 TWO 39 Scheme 0 40 closure of the readily accessible dialdehyde 43 to the 10-membered enediyne 44 (42%) (Scheme 9).53 Working along different lines, Magriotis et al. plan to exploit the facility with which the enediyne antibiotics undergo cycloaromatization to promote tandem Ireland-Claisen rearrangement-Bergman cyclization of the 14-membered lactone 48 to tetrahydronaphthalene systems (Scheme The 43 Scheme 9 Sm12 42% + i. ZnCI? 'Cu(CN)Li '2 44 co&le '- Ro+:ms 47 PdO-CuI ii. desilylation iii. hydrolysis iv. DCC-PPTS 48 Scheme 10 enyne intermediate 46 was prepared by reaction of a stannyl vinyl cuprate with iodoacetylene 45 in the presence of ZnC12, followed by iododestannylation.Subsequent Pdo-CuI mediated coupling of 46 with the acetylene derivative 47 and macrocyclization gave 48. Note the compatibility of this palladium coupling reaction with the presence of the vinyl sulfide unit in the acetylene derivative 47. With the idea of ring contracting larger stable cyclic enediynes to more reactive 10-membered monocyclic forms, Maier and Brandstetter devised a route to compound 51 (Scheme ll).55 The acyclic enediyne intermediate 49 was again obtained in two steps from cis-dichloroethene 28. The key cyclization of 50 was achieved via a Nicholas reaction.56 Under these conditions (Tic&, DABCO) a carbocation species is generated adjacent to the dicobalt hexacarbonyl complexed triple bond which reacts with the electron rich enol ether system at the other extremity of the chain.This ring closure strategy was first introduced to the enediyne field by Magnus and co-workers as part of a systematic study to prepare bicyclic enediynes which have different ring sizes and substituent patterns (Scheme 12).57 As illustrated by the preparation of enediyne 53, the interest in this approach resides in the fact that, compared to the ~ 46 Contemporary Organic Synthesisparent linear enediyne system, the alignment of the reacting centres in the cobalt complex are optimized, and the distance between them is significantly less. This results from the altered 145" bond angles in the masked (complexed) triple bond.In addition, cobalt complexation stabilizes the derived bicyclic product 52, facilitating its isolation and handling. Indeed, on decomplexation of 52 enediyne 53 was observed to cycloaromatize spontaneously. In contrast, the isomeric bicyclic enediyne 54, described in further detail in Scheme 18 of Part 2 of this review,20a was found to be stable. Using Magnus's methodology, compound 58 and yne-ene-allene 59 were prepared by Maier from 5-cycloheptenone 55 (Scheme 13).58 Enediyne 58 cycloaromatizes spontaneously. However, it is remarkable that the yne-ene-allene product 59 - issuing from the cyclization of 56, dyotopic rearrangement of 57 and decomplexation - is stable. completed the synthesis of a 11-membered enediyne possessing a 1,3-trans bicyclic ring junction (Scheme 14).59,60 To obtain ketone 62 the acetylenyl cuprate reagent 61 was added to the cyclohexadienyl iron Schinzer and Kabbara were the first to have i.CO*(CO)& 80% ii. Swern oxidation iii. TBSOTI 1 qTBS 50 TMs\, (4" 0 Q -c Scheme 11 55 i. Ll- li. 28, Pdo-CuI Ui. TBSCI k. - Pdo-Cul OMe 0 i. COdCO), 829L ii. TBSOTf I c i. ii. 56 I 'b' 1. TiCI,, DABCO ii. CAN 1.- 1 TBSO TBSO %> 53 54 59 Scheme 13 Scheme 12 47 Lhermitte and Grierson: Enediyne based antitumour antibiotics. Part 165 Scheme 14 64 complex 60 (98% yield), followed by desilylation and oxidative demetallation. Lewis acid promoted Sakurai of 62 with ally1 silane 63 then proceeded regio- and stereospecifically to produce compound 64. The intramolecular Pdo-CuI coupling of the acetal derived from 64 to give enediyne 65 is remarkable, despite the only moderate yield observed.Mikami has explored a novel approach involving an ene reaction to create the crucial bond between the enediyne containing chain and the 6-membered ring 'platform' component of the calicheamicin/ esperamicin core ~tructure.6~ This involved conversion of the readily accessible alkynyl aldehyde intermediate 66 to the 11-membered bicycle 67 (Scheme 15). A subsequent Nicolaou type r S. I I I I 1 6s 200%,30min PhMe 67 L Scheme 15 Ramberg-Backland ring contraction step could then be exploited to introduce the central double bond. However, at present, the thermal conditions employed (200 "C, 30 min) effect dehydration of the desired product to the enediyne containing compound 68. dynemicin analogue 72 in which the enediyne unit is built across a tetrahydropyridine backbone (Scheme 16)." Thus, reaction of pyridine 69 with ethylchloroformate and ethynylmagnesium bromide (Yamaguchi condition^^^) led to formation of the 1,Zaddition product 70 which was elaborated to the A3.4-piperideine aldehyde 71 (and its A495 isomer; 2: 1 mixture).Reaction of 71 with LHMDS/CeC13 at low temperature produced compound 72 in 35% yield. Brana and co-workers prepared the novel UHMDS -33 I' 35% 72 71 Scheme 16 3 Monocyclic and bicyclic enediynes with novel activating devices Several concepts have been evaluated which have potential application for the in vivo transformation of stable or latent enediyne systems to more reactive forms. One interesting strategy, which in a sense was a prelude to the discovery of mauduropeptin 21, involves introduction of the central enediyne double bond as the triggering step toward cycloaromatization. For instance, Myers and Dragovich envisaged that, by analogy to dynemicin A, bioreduction of anthraquinone 77 would lead to loss of the succinate residue and formation of the 10-membered enediyne 78 (Scheme 17).66 Key synthetic operations in the preparation of 77 include the modified Pedersen pinacolic to convert dialdehyde 73 to a mixture of cis and trans diols 74 (4:l; 40%), and reaction of the derived ketone 75 with the anthracenyllithium reagent 76. Reductive activation of 77 with a flavin-based enzyme system at pH 8.0 proceeded rapidly to give enediyne 78 (75%), which slowly cycloaromatizes at 37 "C in the presence of cyclohexadiene (CHD) (tj = 2 d).48 Contemporary Organic Synthesisd ?3 0' 40% 74 X = H, OH 75X=O J 76 Dess-Martln 1 0 OMe I. Tf,0.2.&lut#Ine 1 li. 8uccI;;hydrlde Q OMe 70 Scheme 17 Taking advantage of the slower cycloaromatiza- tion rate of benzodiynes compared to enediynes, Nicolaou and Semmelhack have independently studied the differential reactivity of hydroquinone based diynes and their corresponding quinone forms ( c j 79 and 80; Scheme 18).68-70 OPiv 0 ?H 79 80 PMP 81 82 PMP = pmethoxyphenyl Scheme 18 Maier has also shown that the enediyne double bond can be introduced via benzylic oxidation in bicyclic 1,5-diyne systems functionalized at the 3 position by a p-methoxyphenyl substituent (81 4 2 ; Scheme 18).71 bicyclic core structure of calicheamicin/esperamicin, Grierson and co-workers constructed the unstrained 13-membered macrocyclic ether 84 by cyclization of 83, and studied its 2,3-Wittig rearrangement to 85 under basic conditions (Scheme 19).72,73 As anticipated from the calculated rc,d distance (3.20 A; MMX calculations) and observations by Magnus on In the course of work on an approach to the 77 the related compound 53, the in situ generated enediyne 86 underwent spontaneous Bergman cycloaromatization. Interestingly, this was accompanied by a 1,5-hydrogen translocation to give the more stable diradical 87, which evolved to a number of products. A similar radical translocation was observed earlier by Wender during studies on neocarzinostatin chromophore analogues.74 Such studies may have relevance to internal radical quenching reactions suspected to occur on cycloaromatization of neocarzinostatin 9 and esperamicin 6.Other strategies through which the central double bond of the enediyne system is generated include the Norrish type I1 photochemical fragmentation of aromatic ketone 88,75 and the Diels-Alder reaction of dienediynes 89.76 Semmelhack has similarly devised methodology for introduction of this double bond based upon the Corey-Winter reaction of thionocarbonate 91 (Scheme 20).77 Note also that the two acetylene functions in 91 were elaborated by reaction of the chlorohydrin derivative 90 with excess LDA. Interestingly, the conjugate 92, formed by joining 37 to a truncated netropsin derivative via a four carbon (crotonate) tether, is 2000 times more effective as a DNA cleaving agent than 37 itself.78 Glycoside bond cleavage, which would convert the sugar derived enediyne 98 to the 10-membered monocycle 99, has also been envisaged as a triggering mechanism for cycloaromatization (Scheme 21).79 To access this bicyclic acetal the ketone 93 (obtained from D-xylose) was reacted with lithium trimethylsilylacetylide in the presence of CeC1,. This preferentially gave the P-substituted product 94, which was converted in three steps to alcohol 95.Attempts to achieve ring closure of aldehyde 96 under strongly basic conditions failed. However, compound 98 was obtained from the corresponding iodoalkyne intermediate 97 under Nozaki-Kishi conditions (CrCl,-NiCl,; 26%).49 Lhermitte and Grierson: Enediyne based antiturnour antibiotics. Part 1 49";o- N \ Et20,O "C 84% (Br K p ___I) hv.PhH pyrex 87% Ph * + Ph L 83 68 TBSO NaH, THF. H& (trace) 1 .OTBS ACi Nio(cat.) * 89 LiTMP 2J-W~i R'O-' rearrangement I 6TBS 84 PhMe, A 1 0 R O K R 0 \\ DBU,CHD r 1 1 Meo" 8 I 6TBS OH MeO' L 86 91 I I 90 OH Products - 37 L A N ? NH2 i d 0 oJ$*o \ q Scheme 19 \ Similarly it was conceived that enol ether hydrolysis of the benzodiyne 103 would give a monocyclic enediyne susceptible to undergo the involved condensation of the ketone 100 (prepared in two steps from 1-tert-butylthio-D-xylopyranoside) with the acetylenyl cerium(m) reagent 101, followed by elaboration of aldehyde 102 and chromium mediated ring closure (95% yield!). an alternative means to destroy the bridgehead double bond in the bicyclic calicheamicid esperamicin system (Scheme 23).81 To obtain analogue 108 the aldehyde 104 was converted to Bergman reaction (Scheme 22).80 Preparation of 103 \ 92 Scheme 20 Enol ether hydrolysis has also been exploited as acetylene 105 by reaction wth ( Me0)2POCHN2,82 and from-there to enediyne 106 by coupling with l-chloro-4-trimethylsilyl-(Z)-but-l-en-3-yne.3s Final cyclization was achieved by treatment of 107 with LiHMDS.The hydrolysis product, ketone 109, is 50 Contemporary Organic SynthesisOMe 98 R = H 97 R = I t H O q o M e OMe 98 Scheme 21 OMe 95 R = H , I 1 J 99 stable enough to be isolated (compare with 53), but does cycloaromatize fairly rapidly [t+ = 35-53 min (R = H, TBS) at 37 "C]. 4 Simple yne-ene-allenes and yne-ene-cumulenes A clear demonstration of the much greater propensity of yne-ene-allenes and yne-ene- cumulenes to cycloaromatize to diradical intermediates compared to enediynes was provided by the simple experiment wherein the 10-membered sulfone 110 was either heated in the presence of cyclohexadiene as the only additive, or treated at room temperature with triethylamine base (Scheme 24).Under the first set of conditions Bergman cyclization occurred progressively (80 "C, 18 h). However, in the presence of Et3N a very rapid cycloaromatization reaction ( < 1 min) was observed via the yne-ene-allene intermediate 11 1 generated by proton rearrangement.83,.84 Koga et al. have attributed the difference in reactivity of these two conjugated systems to less favourable orbital interactions created during enediyne electrocy~lization."~~~ A decrease in the rc,d distance between the reacting centres in yne-ene- allene systems compared to enediynes most probably also contributes to their higher reactivity.In any event, containment of yne-ene-cumulenes in strained rings is not an obligatory requirement for 0 W S B U t O k o 100 OMe i . TBAF Iii. 1,. T i n e OMe 102 Scheme 22 LDA c-- H&O 80% CrClr NiCI, 95% - 1. m CPBA il. BuU OMe 103 these systems to undergo Myers type cycloaromatization at ambient temperatures. For instance, the unstrained acyclic yne-ene-allenes 114 and 115 both cycloaromatize smoothly at 37 "C (t+ = 1.5 to 8 h) and effect cleavage of supercoiled DNA. These compounds were prepared by [2,3]-sigmatropic rearrangement of the in situ formed phosphinite derivatives of enediyne 112 and prop-2-ynylic alcohol 113, respectively (Scheme 25).86-88 As illustrated by the reactivity of 116, substituents on the terminal acetylene carbon C-1 have a considerable influence on the mode of cycloaromatization; i.e. in the presence of cyclohexadiene (CHD) 116 (R = H) cycloaromatizes in the Myers mode (c,-c6 bond formation) to produce 118, whereas 116 (R = tolyl) reacts to give 117 as a consequence of c2-c6 bond formation.89 This may be due to steric hindrance, and/or ground state stabilization of the acetylene moiety.In a more sophisticated experiment compound 119 was constructed, and shown to undergo an intramolecular SN2' reaction giving 120 directly (75% yield) (Scheme 26).90 Lhermitte and Grierson: Enediyne based antitumour antibiotics.Part 1 51108 1 07 109 Scheme 23 Ph2P+ 112 R=H - R=PPh2 0 PhpCl 114 117 (76%) I Scheme 25 110 111 Scheme 24 The parent unsu bs ti tu t ed (2)- 1,2,4- hept a t rien- 6-yne system 124 has been synthesized by either Zn-Cu reduction of mesylate 121,86 or via a sigmatropic rearrangement initiated by oxidation of prop-2-ynylic hydrazine 122 to the unstable diazene 123 at 0 "C (Scheme 27).9',92 Interestingly, these unsubstituted yne-ene-allenes cycloaromatize relatively slowly (ti x 24 h). NMR evidence suggests that this may result from a preference for them to adopt the less hindered s-trans conformation. Saito and co-workers made use of their experience on the [2,3]-sigmatropic rearrangement of prop-2-ynylic phosphinites to prepare phosphine oxide 125 and react it with aldehyde 126 (Scheme 28)?3 This permitted them to construct the acyclic yne-ene-cumulene derivative 127 related to the thiol addition product 10 of the neocarzinostatin chromophore.Alternatively, Wang showed that mesylate 129, obtained by reaction of 126 with lithium acetylide 128, undergoes very mild conversion to 127 on treatment with TBAF.94795 Like the above acyclic allenes this compound could be isolated by flash column chromatography or HPLC and characterized. 115 cy / : ""P(O)Ph2 6 H 118 (57%) Bu'Li R' = Br R' = CHO DMF; -120 % 71% 119 Scheme 26 52 Contemporary Organic SynthesisTwo strategies for the preparation of acyclic yne- ene-ketene analogs of cumulene 10 have also been reported.On the one hand, ketene 131, which cycloaromatizes spontaneously, was generated by heating or photolysing (254 nm) diazoketone 130 (Scheme 29).% In the second study, Moore et al. showed that cyclobutenone 132 fragments on mild heating (CH,CN; 82 "C) to the ketene 133.97 Cyclization of this intermediate to a diradical 122 X = NHNH, 123 zn-cu. 0 'c [2 31 I s-trans 124 S-Ck 124 Scheme 27 Me HO-* Me K O 9-" COzEt 1 30 r Scheme 29 Scheme 28 Lhemitte and Grierson: Enediyne based antitumour antibiotics. Part 1 131 Ph I - Meoxf R 132 1 33 0 TBAF 54% 127 / TMS RO 53'NU-DNA 134 135 R 'R 137 136 Scheme 30 ii.pHa7 1 lHzO DNA cleavage accounts at least partially for the capacity of this intermediate to cleave DNA. sulfones, Nicolaou has suggested that Myers cycloaromatization is not the only route through which these systems can potentially cut DNA (Scheme 30).98 Indeed, on pH dependent conversion of 134 to the corresponding bis(al1enic) sulfone 135, further reaction can occur giving the diradical 136 (pathway A), or through direct reaction with a DNA-nucleophile to give adduct 137 (pathway B).Studies of the reactivity of a series of mono and bis(prop-2-ynylic) sulfones, as well as the novel crown ethers 138 and 139 and compounds 140, has provided convincing evidence for the polar reaction pathway in DNA cleavage (note 138-+141).99-'02 Similarly, it was observed that the 10-membered ring sulfide 143, obtained by dehydration of 142, is converted to the conjugated allene 144 in a basic medium. This intermediate reacts via both polar and radical mechanisms (Scheme 31).Io3 Attachment of aromatic ester residues to these monocycles increased their ability to interact with DNA through intercalation.Somewhat of a surprise, oxidation of sulfide 145 with m-CPBA led to formation of the enyne-allene sulfone 146 as a stable compound.'04 Cycloaromatization of the allene-cumulene 147 Returning to the reactivity of bis(prop-2-ynylic) 0 generated by elimination of HOR from 146 was also split between polar and radical pathways. The Pd(0) coupling and ring closure technology developed during the study of enediyne-dienediyne systems was brought to bear by Myers to construct the fully conjugated 'aromatic' 1,6-didehydro- [lolannulene 151 (Scheme 32).'05 This was achieved by coupling vinyl iodide 148 with a but-3-ynylic alcohol derivative (79%), followed by Wittig olefination, and ring closure of 149 under Nozaki- Kishi conditions to the alcohol 150.Subsequent triflate elimination to give 151 had to be conducted at -90 "C! The half-life for cyclization of 151 at -51 "C is z 25 min, making this the most rapid diradical-forming cycloaroma t iza t ion yet recorded (c.5 10+11; t+ = 2 h at -38 "C). then went on to incorporate the 1,6-didehydro- In a synthetically economic and astute way Myers 138 OMe OMe 141 139 I o=s=o 140n =13,X=CH,N OH [lolannulene system in latent form into the neocarzinostatin analogue 155 (Scheme 33).'06 Compound 155 was prepared starting by reaction of enantiomerically pure 152 with allenylmagnesium 54 Contemporary Organic Synthesis143 R2=H R2 = OCOAr J 144 H+ radical route / k Sm 0 S * H 145 Scheme 31 147 bromide, followed by stannylation of acetylene 153.This product was dimerized under Pd(0) conditions, affording the C2-symmetric alcohol 154 in 34% yield. Mesylation of 154 gave the target molecule 155, which proved to be stable with respect to column purification. However, treatment of this compound with methyl thioglycolate and Et,N led to 148 i.BuUTh4S = (4.3: 1 z : E ) 71% B ii. c&co2H iii. EbN*HF v. Dess-Martin iv. NIS, &NO3 b R 150 151 (stored at 430 "C) Scheme 32 149 152 zl 153 R = H R = SnBuo Scheme 33 Lhermitte and Grierson: Enediyne based antiturnour antibiotics. Part I HSAC02Me EtsN.12 h. 23 "c - TBSO" 154 x 0-0 41% ii. (Ms)&. 70% 1 55cycloaromatized products whose formation may 1.CBr4. P(Phh ii. BuU iii C w e c 37, Suffert showed that upon EtS- addition the -JmS TBSO 83% imply 156 as an intermediate. Applying techniques described later in Scheme benzodienediyne 157 rearranges to a didehydro- [ lolannulene. This intermediate cycloaromatized CHO 159 spontaneously to 158 (Scheme 34)’” in an analogous fashion to the Saito pathwayI4 for the neocarzinostatin chromophore. cow kSA r Ets> SEt 157 € b P / * 156 diradii - 158 Scheme 34 The simple monocycle 163 (Scheme 35) was designed by Toshima et aZ. to undergo cycloaromatization through thiol-acetate addition elimination in a manner closely analogous to neocarzinostatin 9.1m In four steps, D-xylitol was converted to the dialdehyde 159. According to the Corey-Fuchs procedure’0g this compound was elaborated to the diester 160, and from there to the keto-aldehyde 161.An intramolecular Aldol reaction then gave 162, whose conversion to 163 could not be achieved directly under Wittig conditions. neocarzinostatin chromophore skeleton, Wender and Tebbe designed the monocyclic E-configured dienediynes 165 which react as Michael acceptors in the presence of thiols (Scheme 36).74.”0.”’ Although MsOH elimination from 164 produces the less hindered thermodynamic product, the reactive s-cis In conjunction with their pioneering work on the L DIBAL ii. MeMgBr In. De6bMattIn 1 O/ OTBS Scheme 35 conformation can easily be adopted in the tetraene 166. A thorough study of the Myers type cycloaromatization chemistry of 165 was made, which both demonstrated that 166 cyclizes spontaneously and also brought to light an internal radical quenching process involving 1,5-hydrogen transfer (167 + 168).Suffert and Terashima have further defined methodology for stereospecific construction of monocyclic 2- and E-dienediynes from 2- and E- monoenol triflate and dienol triflate precursors (Scheme 37).11271’3 The essential challenge in their work was to establish conditions for controlled preparation of compounds 170 and 171, as well as 172 and 173, from 2-formylcyclopentanone 169. It was found that the 2-enol form of 169 reacts with triflic anhydride and amine base to give the E- configured monoenol triflate 170, whereas reaction of the lithium enolate of 169 with the same reagent gives the 2-monoenol triflate 171. Alternatively, partial conversion of 170 to 171 could be achieved photochemically (254 nm).Similarly, 2-formylcyclopentanone was converted directly to the E-dienol ditriflate 172 (63-71%), and compound 171 was converted to 173 in 47% yield through treatment with LHMDS and PhNTf,. It is interesting that reaction of the lithium enolate of 169 with PhNTf, led to the E- rather than the Z - monoenol triflate, and that there is a-loss of 56 Contemporary Organic SynthesisOTf 3 1 % fi 1 :12 1 y N 9 172 169 0 hv & 0 - LIHMDS PhNTf, JOT, - 4% 254 nm 170 171 173 4 0 165 1 HS-COfle s-co2Me SAC02Me &OTI R1-Z PdO-CuI c gfR' 166 (4: 1 to 12: 1 ratio) 173 I R2-= PdO-CuI r C02Me Me0 I 1 R' \ S*H produds PdO-CuI I C02Me TI 0, TfO, 168 172 Scheme 36 Scheme 37 stereochemistry on treatment of monoenol triflate 171 with Tf20 (171-172).The subsequent Pdo-CuI bis-coupling of dienol ditriflates 172 and 173 with >2 equivalents of diversely substituted terminal acetylenes provided open chain E- and 2-dienediyne systems respectively with common acetylene functions [Z- series: 36-73% yields; E-series: 79-98% yields]. However, sequential addition of two different acetylene units can also be accomplished. As one might expect, for 2-compound 173 there is preferential reaction at the more accessible exocyclic enol triflate function (4:l to 12:l). However, for 22-172 it is the endocyclic position which is substituted first (3:l to 8:l). In this latter instance, the order of introduction of two different acetylene units can be inversed by first coupling with monotriflate 170.A strategy based upon a Pd(0) catalysed insertion-cross coupling sequence has been developed which permits both creation of the cyclopentene ring from an acyclic precursor and introduction of an acetylene appendage with control of the exocyclic C,-& olefin geometry (Scheme 38).'14-"' In the experiment, Pd(0) reacts with dibromo (or diiodo) 174 via n-complexation and selective oxidative addition to the more hindered proximal 2-1-Br bond to give the critical Pd-C a-bonded species 175. In a solvent dependant reaction, this intermediate then undergoes rapid carbometallation of the precoordinated alkyne, resulting in formation of the 2-vinyl organometallic 57 Lhermitte and Grierson: Enediyne based antitumour antibiotics. Part 1ii. BnCl -1 R'=H,Bn 174 - I 175 R'O 176 - 177 Scheme 38 176.Reaction of 176 with the stannylacetylene reagent present in the medium gives the product diene-yne 177. The presence of the vinyl bromide functionality can subsequently serve for introduction of a second acetylene unit. In another Pdo-CuI based approach, reaction of the in situ generated organocopper species 179 with the a-ethynylpalladium species 180 produces the Z - ene-yne product 181 (Scheme 39).'16 This is achieved by slow addition of iodide 180 to a solution of the preformed potassium enolate 178 in the presence of (Ph3P)4Pd and CuI. 178 179 180 181 Scheme 39 Ziegler has shown that the cyclopentenynes such as 185 can be constructed by Bu3SnH induced radical cyclization of either bromo[3]cumulene 182 or the bromoenyne precursor 183, since both systems produce the same delocalized radical intermediate 184 (Scheme 40)."' + ph3p3Br Br- LIHMDS.-70 'C I 182 Bu3SnH AIBN. 80 'C 20 min 1 L 184 \ Bu3SnH AIBN. 80 % 20 min 1 184 I Scheme 40 58 Contemporary Organic Synthesisi. H202 NaOH. H& 1 ii. B u ~ ~ P A OH R * g 9 B r 0 186 R=H 191 R=OTBS \ OTBS 189 iv. BuLi. Bu&nCI R = H 187 R=OTBS R = CH2CH20TES 1 i.i'+L$ R = CH~CO~BU oxidation - OTBS from 193 - OTBS I U 194 195 Scheme 41 5 Ten-membered ring and higher neocarzinostatin chromophore analogues Calculations made by Hirama and collaborators suggest that 10-membered neocarzinostatin chromophore analogues should be more stable than 9 due to reduced ring strain, but at the same time retain the capacity to undergo Myers type cycloaromatization to a diradical intermediate (small difference in the rc,d distance).They thus prepared the conjugated ketone 190 from 2-bromocyclopent-2-enone 186 (Scheme 41) via reaction of the Grignard reagent derived from intermediate 187 with aldehyde 188, followed by Pd(0) catalysed ring closure of the stannane 189 (72%) and Swern ~xidation."**"~ By the same route compound 192 (R = OH, OCOAr) was prepared from monochiral ketone 191.I2O This 10-membered dienediyne ketone cleaves supercoiled DNA with a very marked selectivity for purine bases (G >A). Incorporation of an internal thiol triggering device '0 0 I90 R = H 192 R=OH as in 194 was also achieved starting from the readily available ketone 193.I2l As expected, methanolysis of thioacetate 194 at room temperature resulted in spontaneous thiol addition and Myers type cycloaromatization. Finally, the conjugate 195 was prepared which displayed potent DNA cleaving capacity.122 Krebs et al.have also constructed the cross- conjugated 10-membered dienediyne ketone 198 from acetylene 196 (Scheme 42).'23 The key step in their approach is the Noyori type intramolecular aldol reaction between the acetal and silyl enol ether moieties in the intermediate generated from 197. More recently, Ueda has also described the elaboration of 199 to the isomeric ketone 200, in which a phenyl group replaces the double bond o! to the carbonyl fun~ti0n.I~~ stereoselective introduction of acetylene containing side chains onto 2-formylcyclopentanone derived enol triflates (Scheme 37), Terashima has described In an extension of work on the regio- and Lhermitte and Grierson: Enediyne based antitumour antibiotics.Part 1 59196 R' = MEM, f? = CH(0Et)z 199 R' = THP, f?= TMS 197 lmgn 1. Cr-Ni 1 98 QTp MPO - 0 200 Scheme 42 PivO O f - # PivO **OH Me0 OH the preparation of the two chiral acetylene derivatives 201 and 202, and their coupling to enol triflate 203 (Schemes 43 and 44).1137'25 Further conversion of compound 204 to epoxide 206 provided the possibility of obtaining the 10-membered bicycle 207. However, the 9-membered neocarzinostatin analogue 209 was not accessible from the corresponding epoxide prepared from 205. Similar efforts to prepare this compound by intramolecular acetylide condensation in 208 were also unsuccessful.Interestingly, attempted assembly of the novel 10-membered 1,3-dioxolane 211 through intramolecular transketalization of the polyhydroxylated intermediate 210 led instead to formation of the ll-membered bicycle 212. 6 Conclusion Much of the methodology used to access both the neocarzinostatin analogues and the enediyne systems described so far has either been applied to, or been developed during, efforts to achieve the x:ho HO OH 204 I Q HO'* COpEt 201 202 I 203 I PdO-CuI Scheme 43 60 Contemporary Organic Synthesis 1 206 207 %o 0-.$ OH 209 R=Me 208 R=TBS Scheme 44 21 2total synthesis of the three major enediyne- dienediyne antibiotics: the neocarzinost at in chromophore 9, calicheamicin yl' S/esperamicin A, 6 and dynemicin A 15. The outstanding achievements in this direction are analysed in Part 2 of this review, which will appear in the next issue of Contemporary Organic Synthesis (H.Lhermitte and D. S. Grierson, Contemp. 0%. Synth., 1996, 3, 93). 7 References and notes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 R. R. Jones and R. G. Bergman, J. Am. Chem. SOC., 1972,94,660; R. G. Bergman, Acc. Chem. Res., 1973, 6, 25; T. P. Lockhart, P. B. Comita and R. G. Bergman, J. Am. Chem. SOC., 1981,103,4082; T. P. Lockhart and R. G. Bergman, J. Am. Chem. SOC., 1981, 103,4091. J. Mayer and F. Sondheimer, J. Am. Chem. Soc., 1966,88,602 and 603. N. Darby, C. U. Kim, J. A. Salaiin, K. W. Shelton, S. Takada and S. Masamune, J. Chem. SOC., Chem. Commun., 1971, 1516. M. D. Lee, T. S. Dunne, M. M. Siegel, C. C. Chang, G.0. Morton and D. B. Borders, J. Am. Chem. SOC., 1987,109,3464; M. D. Lee, T. S. Dunne, C. C. Chang, G. A. Ellestad, M. M. Siegel, G. 0. Morton, W. J. McGahren and D. B. Borders, J. Am. Chem. SOC., 1987, 109, 3466. J. Golik, J. Clardy, G. Dubay, G. Groenewold, H. Kawaguchi, M. Konishi, B. Krishnan, H. Ohkuma, K.-I. Saitoh and T. W. Doyle, J. Am. Chem. Soc., 1987, 109, 3461; J. Golik, G. Dubay, G. Groenewold, H. Kawaguchi, M. Konishi, B. Krishnan, H. Ohkuma, K.-I. Saitoh and T. W. Doyle, J. Am. Chem. SOC., 1987, 109,3462. N. Ishida, K. Miyazaki, K. Kumagai and M. Rikimaru, J. Antibiot., 1965, 18, 68; K. Edo, M. Mizugaki, Y. Koide, H. Seto, K. Furihata, N. Otake and N. Ishida, Tetrahedron Lett., 1985, 26, 331. M. D. Lee, G. A. Ellestad and D. B. Borders, Acc.Chem. Res., 1991,24 235. G. Pratviel, J. Bernadou and B. Meunier, Angew. Chem., Int. Ed. Engl., 1995,34, 746, and references cited therein. Enediyne Antibiotics as Antitumor Agents, ed. D. B. Broders and T. W. Doyle, Dekker, 1994. L. H. Goldberg, Acc. Chem. Res., 1991, 24, 191. A. G. Myers, Tetrahedron Lett., 1987, 28, 4493. A. G. Myers and P. J. Proteau, J. Am. Chem. SOC., 1989, 111, 1146. A. G. Myers, P. J. Proteau and T. M. Handel, J. Am. Chem. SOC., 1988,110, 7212. H. Sugiyama, K. Yamashita, M. Nishi and I. Saito, Tetrahedron Lett., 1992, 33, 515; for model studies of this cycloaromatization pathway, see: references 107 and 119. M. Konishi, H. Ohkuma, T. Tsuno, T. Oki, G. D. Van Duyne and J. Clardy, J. Am. Chem. SOC., 1990,112, 3715. D. R. Langley, T. W. Doyle and D.L. Bevridge, J. Am. Chem. SOC., 1991, 113,4395. P. A. Wender, R. C. Kelly, S. Beckham and B. L. Miller, Proc. Natl. Acad. Sci. USA, 1991, 88, 8835. J. E. Leet, D. R. Schroeder, F. J. Hofstead, J. Golik, K. L. Colson, S. Huang, S. E. Klohr, T. W. Doyle and J. A. Matson, J. Am. Chem. SOC., 1992, 114,4976; J. E. Leet, D. R. Schroeder, D. R. Langley, K. L. Colson, S. Huang, S. E. Klohr, M. S. Lee, J. Golik, 19 20 S. J. Hofsted, T. W. Doyle and J. A. Matson, J. Am. Chem. SOC., 1993,115,8432; N. Zein, A. M. Casazza, T. W. Doyle, J. E. Leet, D. R. Schroeder, W. Solomon and S. G. Nadler, Proc. Natl. Acad. Sci. USA, 1993, 90,2822; N . Zein, A. M. Casazza, T. W. Doyle, J. E. Leet, D. R. Schroeder, W. Solomon and S. G. Nadler, Proc. Natl. Acad. Sci. USA, 1993,90, 8009; M.Hornyak, 1. F. Pelyvas and F. J. Sztaricskan, Tetrahedron Lett., 1993,34, 4087; T. Vuljanic, J. Kihlberg and P. Somfai, Tetrahedron Lett., 1994,35, 6937. T. Otani, Y. Minami, K. Yoshida, R. Azuma and M. Saeki, Tetrahedron Lett., 1993, 34, 2633; K.-I. Yoshida, Y. Minami, R. Azuma, K. Saeki and T. Otani, Tetrahedron Lett., 1993,34, 2637; K.-I. Iida, T. Ishii, M. Hirama, T. Otani, Y. Minami and K.-I. Yoshida, Tetrahedron Lett., 1993,34,4079; Y. Sugiura and T. Matsumoto, Biochemistry, 1993,32,2637; T. Matsmato, Y. Okuno and Y. Sugiura, Biochem. Biophys. Res. Commun., 1993, 195,659; Y. Okuno, M. Otsuka and Y. Sgiura, J. Med. Chem. 1994,37,2266. D. R. Schroeder, K. L. Colson, S. E. Klohr, N. Zein, D. R. Langley, M. S. Lee, J. A. Matson and T. W. Doyle, J. Am. Chem.SOC., 1994, 116, 9351. 20a For Part 2 of this review, see H. Lhermitte and D. S. 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Grierson, Contemp. 0%. Synth., 1996, 3, 93. K. C. Nicolaou and W.-M. Dai, Angew. Chem., Int. Ed. Engl., 1991,30, 1387. T. Skrydstrup, H. Audrain, G. Ulibarri and D. S. Grierson, in Recent Progress in the Chemical Synthesis of Antibiotics, ed. G. Luckacs, Springer-Verlag, 1993, M. Hirama, in Recent Progress in the Chemical Synthesis of Antibiotics, ed. G. Luckacs, Springer- Verlag, 1993, vol. 2, pp. 293-329. J. A. Murphy and J. Griffiths, Nut. Prod. Rep., 1993, 10, 551. M. E. Maier, Synlett., 1995, 13. For a revised determination of AE,,, for the conversion of 1 to 2, as well as an alternate view on the mechanism and factors governing cycloaromatization rates, see: R.Lindh and B. J. Persson, J. Am. Chem. SOC., 1994,116,4963; R. Lindh, T. J. Lee, A. Bernhardsson, B. J. Persson and G. Karlstrom, J. Am. Chem. SOC., 1995,117, 7186; E. Kraka and D. Cremer, J. Am. Chem. SOC., 1994,116, 4929; J. Wisniewski Grissom, T. L. Calkins, H. A. McMillen and Y. Jiang, J. 0%. Chem., 1994, 59, 5833. For examples of inter- and intramolecular capture of diradical intermediates related to 1 and 2, see: J. Wisniewski Grissom, D. Klingberg, S. Meyenburg and B. L. Stallman, J. 0%. Chem., 1994,59,5833, and references sited therein. K. C. Nicolaou, G. Zuccarello, Y. Ogawa, E. J. Schweiger and T. Kumazawa, J. Am. Chem. SOC., 1988,110,4866. K. C. Nicolaou, Y. Ogawa, G. Zuccarello and H. Kataoka, J. Am. Chem. SOC., 1988,110,7247.K. C. Nicolaou, G. Zuccarello, C. Riemer, V. A. Estevez and W.-M. Dai, J. Am. Chem. SOC., 1992,114, 7360. L. A. Paquette, 0%. Reactions, 1977,25, 1. J. P. Snyder, J. Am. Chem. SOC., 1989,111,7630; J. P. Snyder, J. Am. Chem. SOC., 1990,112,5367; P. Magnus, S. Fortt, T. Pitterna and J. P. Snyder, J. Am. Chem. SOC., 1990,112,4986. K. P. C. Vollhardt and L. S. Winn, Tetrahedron Lett., 1985, 26, 709. S. J. Danishefsky, D. S. Yamashita and N. B. Mantlo, Tetrahedron Lett., 1988,37, 4681. VO~. 2, pp. 213-292. Lhemzitte and Grierson: Enediyne based antitumour antibiotics. Part I 6335 D. Guillerm and G. Linstrumelle, Tetrahedron Lett., 36 See also: V. Ratovelomanana and G. Linstrumelle, 1985,26,3811. Tetrahedron Lett., 1982, 22, 315; V. Ratovelomanana and G. Linstrumelle, Tetrahedron Lett., 1984, 25, 6001; D.Guillerm and G. Linstrumelle, Tetrahedron Lett., 1986,27,5857; M. Alami, B. Crousse and G. Linstrumelle, Tetrahedron Lett., 1995,36, 3687. 37 D. Chemin and G. Linstrumelle, Tetrahedron, 1994, 50, 5335. 38 K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975, 4467. 39 Z. Wang and K. K. Wang, J. 0%. Chem., 1994,59, 4738; K. K. Wang and 2. Wang, Tetrahedron Lett., 1994,35, 1829. 40 J. K. Stille and J. H. Simpson, J. Am. Chem. SOC., 1987, 109, 2138; N. Chatani, N. Amishiro and S. Murai, J. Am. Chem. SOC., 1991,113,7778. 41 E.-I. Negishi, T. Yoshida, A. Abramovich, G. Lew and R. H. Williams, Tetrahedron, 1993, 47, 343; I. Rivera and J. A. Sonderquist, Tetrahedron Lett., 1991, 32, 2311. see: J. Ohshita, K.Furumori, A. Matsuguchi and M. Ishikawa, J. 0%. Chem., 1990,55, 3277; I. P. Kovalev, K. V. Evdakov, Y. A. Strelenko, M. G. Vinogradov and G. I. Nikishin, J. OGanomet. Chem., 1990, 386, 139. Lett., 1993,34, 6403. M. Kido, Tetrahedron Lett., 1991, 32, 4363. 42 For alternate Rh(r) catalysed coupling procedures, 43 M. Alami, F. Ferri and G. Linstrumelle, Tetrahedron 44 Y. Sakai, E. Nishiwaki, K. Shishido, M. Shibuya and 45 R. Singh and G. Just, Tetrahedron Lett., 1990, 31, 185. 46 B. Konig and H. Riitters, Tetrahedron Lett., 1994,35, 3501. 47 M. F. Brana, M. Moran, M. J. P. de Vega, I. Pita- Romero and N. Walker, Tetrahedron, 1995, 51,9127. 48 C. CrCvisy and J.-M. Beau, Tetrahedron Lett., 1991,32, 3171. 49 K. Takai, T. Kuroda, S. Nakatukasa, K. Oshima and H. Nozaki, Tetrahedron Lett., 1985, 26, 5585; T.D. Aicher and Y. Kishi, Tetrahedron Lett., 1987, 28, 3463. 50 Y.-F. Lu, C. W. Harwig and A. G. Fallis, J. 0%. Chem., 1993,58,4202. 51 J. Wang and P. J. De Clercq, Angew. Chem., Int. Ed. Engl., 1995, 34, 1749. 52 D. L. Boger and J. Zhou, J. 0%. Chem., 1993,58, 3018. 53 K. C. Nicolaou, E. J. Sorensen, R. Discordia, C.-K. Hwang, R. E. Minto, K. N. Bharucha and R. G. Bergman, Angew. Chem., Int. Ed. Engl., 1992,31, 1044. 54 P. A. Magriotis and K. D. Kim, J. Am. Chem. SOC., 1993, 115, 2972; P. A. Magriotis, M. E. Scott and K. D. Kim, Tetrahedron Lett., 1991,32, 6085; P. A. Magriotis, T. J. Doyle and K. D. Kim, Tetrahedron Lett., 1990, 31, 2541. 55 M. E. Maier and T. Brandstetter, Liebigs Ann. Chem., 1993, 1009. 56 K. M. Nicholas,Acc.Chem. Res., 1987, 20, 207. 57 P. Magnus, P. Carter, J. Elliott, R. Lewis, J. Harling, T. Pitterna, W. E. Bauta and S. Fortt, J. Am. Chem. SOC., 1992, 114,2544; P. Magnus, R. T. Lewis and J. C. Huffman, J. Am. Chem. SOC., 1988, 110,6921; P. Magnus and P. A. Carter, J..Am. Chem. SOC., 1988, 110, 1626. 58 M. E. Maier and D. Langenbacher, Synlett, 1994, 713. 59 D. Schinzer and J. Kabbara, Synlett, 1992, 766. 60 J. Kabbara, C . Hoffmann and D. Schinzer, Synthesis, 1995, 299. 61 A. Hosomi, A. Shirahata and H. Sakurai, Tetrahedron Lett., 1978, 3043. 62 For ring closure to a neocarzinostatin analogue under Sakurai conditions, see also: J. Suffert, Tetrahedron Lett., 1990,31, 7437. 63 K. Mikami, H. Matsueda and T. Nakai, Tetrahedron Lett., 1993, 34, 3571. 64 M. F. Brana, M.Moran. M. J. P. de Vega and I. Pita- Romero, Tetrahedron Lett., 1994,35, 8655. 65 R. Yamaguchi, Y. Nakazono and M. Kawanishi, Tetrahedron Lett., 1983, 24, 1801. 66 A. G. Myers and P. S. Dragovich, J. Am. Chem. SOC., 1992, 114, 5859. 67 A. S. Raw and S. F. Pedersen, J. 0%. Chem., 1991,56, 830. 68 K. C. Nicolaou, A. Liu, Z. Zeng and S. McComb, J. Am. Chem. SOC., 1992,114,9279. 69 M. F. Semmelhack, T. Neu and F. Foubelo, Tetrahedron Lett., 1992,33, 3277. 70 P. J. Boniface, R. C. Cambie, C. Higgs, P. S. Rutledge and P. D. Woodgate, Aust. J. Chem., 1995, 48, 1089. 71 M. E. Maier and B. Greiner, Liebigs Ann. Chem., 1992, 855; M. E. Maier and T. Brandstetter, Tetrahedron Lett., 1991, 32, 3679. 72 T. Skrydstrup, H. Audrain, G. Ulibarri and D. S. Grierson, Tetrahedron Lett., 1992,33 4563; H.Audrain, T. Skrydstrup, G. Ulibarri and D. S. Grierson, Synlett, 1993, 20; H. Audrain, T. Skrydstrup, G. Ulibarri, C. Riche, A. Chiaroni and D. S. Grierson, Tetrahedron, 1994, 50, 1469. Y. Naoe, Tetrahedron Lett., 1995,36, 897; R. S. Huber and G. B. Jones, Tetrahedron Lett., 1994,35, 2655; see also reference 51. 74 P. A. Wender and M. J. Tebbe, Tetrahedron Lett., 1991,32,4863; P. A. Wender and M. J. Tebbe, Tetrahedron, 1994, 50, 1419; and references therein pertaining to radical translocations. 75 J. M. Nuss and M. M. Murphy, Tetrahedron Lett., 1994, 35, 37. 76 H. Hopf and M. Theurig, Angew. Chem., Int. Ed. Engl., 1994, 33, 1099. 77 M. F. Semmelhack and J. J. Gallagher, Tetrahedron Lett., 1993, 34, 4121. 78 M. F. Semmelhack, J. J. Gallagher, W.-d.Ding, G. Krishnamurphy and G. A. Ellestad, J. 0%. Chem., 1994,59,4357. 79 M. E. Maier and T. Brandstetter, Tetrahedron Lett., 1992,33, 7511; T. Brandstetter and M. E. Maier, Tetrahedron, 1994,50, 1435. 80 I. Dancy, T. Skrydstrup, C. CrCvisy and J.-M. Beau, J. Chem. SOC., Chem. Commun., 1995, 799. 81 M. F. Semmelhack, J. J. Gallagher, T. Minami and T. Date, J. Am. Chem. SOC., 1993, 115, 11 618. 82 J. Gilbert and U. Weirasooriya, J. 0%. Chem., 1979, 44,4997. 83 Y. Sakai, Y. Bando, K. Shishido and M. Shibuya, Tetrahedron Lett,, 1992, 33, 957. 84 For the corresponding example in the acyclic series, see: M.-J. Wu, C.-F. Lin, J.-S. Wu and H.-T. Chen, Tetrahedron Lett., 1994, 35, 1879. 85 N. Koga and K. Morokuma, J. Am. Chem. SOC., 1991, 113, 1907. 86 R. Nagata, H.Yamanaka, E. Murahashi and I. Saito, Tetrahedron Lett., 1990, 31, 2907. 87 R. Nagata, H. Yamanaka, E. Okasaki and I. Saito, Tetrahedron Lett., 1989, 30, 4995. 88 K. C. Nicolaou, P. Maligres, J. Shin, E. de Leon and D. Rideout, J. Am. Chem. SOC., 1990,112, 7825. 89 M. Schmittel, M. Strittmatter and S. Kiau, 73 For related examples, see: M. Shibuya, Y. Sakai and 62 Contemporary Organic SynthesisTetrahedron Lett., 1995,36,4975; see also reference 111. 1989,111,9130. Chem. SOC., 1989, 111,8057; A. G. Myers, N. S. Finney and E. Y. Kuo, Tetrahedron Lett., 1989, 30, 5747. 92 Y. W. Andemichael, Y. G. Gu and K. K. Wang, J. 0%. Chem., 1992, 57, 794. 93 I. Saito, K. Yamaguchi, R. Nagata and E. Murahashi, Tetrahedron Lett., 1990, 31, 7469. 94 K. K. Wang, B. Liu and Y.-d.Lu, Tetrahedron Lett., 1995, 36, 3785; K. K. Wang, B. Liu and Y.-d. Lu, J. 0%. Chem., 1995,60, 1885. SOC., Chem. Commun., 1994,2121; H. F. Chow, X.-P. Cao and M.-K. Leung, J. Chem. SOC., Perkin Trans. 1, 1995, 193. 96 K. Nakatani, S. Isoe, S. Maekawa and I. Saito, Tetrahedron Lett., 1994, 35, 605. 97 J. E. Ezcurra, C. Pham and H. W. Moore, J. 0%. Chem., 1992, 57, 4787; R. W. Sullivan, V. M. Coghlan, S. A. Munk, M. W. Reed and H. W. Moore, J. 0%. Chem., 1994,59, 2276. Zuccarello, E. J. Schweiger, K. Toshima and S. Wendeborn, Angew. Chem., Int. Ed. Engl. , 1989,28, 1272. Isshiki, N. Zein and G. A. Ellestad,Angew. Chem., Int. Ed. Engl., 1991, 30, 418. 90 A. G. Myers and P. S. Dragovich, J. Am. Chem. SOC., 91 A. G. Myers, E. Y. Kuo and N. S. Finney, J. Am.95 H. F. Chow, X.-P. Cao and M.-K. Leung, J. Chem. 98 K. C. Nicolaou, G. Skokotas, P. Maligres, G. 99 K. C. Nicolaou, S. Wendeborn, P. Maligres, K. 100 S. M. Kerwin, Tetrahedron Lett., 1994, 35, 1023. 101 G. Xie, A. R. Morgan and J. W. Lown, Biooq. Med. Chem. Lett., 1993,3, 1565; R. Gupta, G. Xie and J. W. Lown, Gene, 1994, 149, 81. 102 W.-M. Dai and K. C. Fong, Tetrahedron Lett., 1995, 36, 5613. 103 K. Toshima, K. Ohta, A. Ohashi, T. Nakamura, M. Nakata, K. Tatsuta and S. Matsumura, J. Am. Chem. SOC., 1995, 117,4822; K. Toshima, K. Ohta, T. Ohtake and K. Tatsuta, Tetrahedron Lett., 1991,32, 391; K. Toshima, K. Ohta, T. Ohtake and K. Tatsuta, J. Chem. SOC., Chem. Commun., 1991,694; K. Toshima, K. Ohta, A. Ohashi, A. Ohtsuka, M. Nakata and K. Tatsuta, J. Chem. SOC., Chem. Commun., 1992, 1306.104 K. Toshima, K. Ohta, A. Ohtsuka, S. Matsumura and M. Nakata, J. Chem. SOC., Chem. Commun., 1993,1406. 105 A. G. Myers and N. S. Finney, J. Am. Chem. SOC., 1992, 114, 10 986. 106 A. G. Myers and P. S. Dragovich, J. Am. Chem. SOC., 1993, 115,7021. 107 J. Suffert and R. Bruckner, Synlett, 1994, 51; see also: M. Eckhardt, R. Brukner and J. Suffert, Tetrahedron Lett., 1995, 36, 5167. 108 K. Toshima, K. Yanagawa, K. Ohta, T. Kano and M. Nakata, Tetrahedron Lett., 1994,35, 1573. 109 E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 1972, 3769. 110 For another example of the vinylogous SN2’ mechanism, see: K. Fujiwara, H. Sakai and M. Hirama, J. 0%. Chem., 1991,56,1688. 11 1 For another example of the vinylogous SN2’ mechanism, see also: S. W. Scheuplein, R. Machinek, J. Suffert and R. Bruckner, Tetrahedron Lett., 1993, 34, 6549. Tetrahedron Lett., 1991, 32, 1449; J. Suffert and R. Bruckner, Tetrahedron Lett., 1991, 32, 1453; S. W. Scheuplein, K. Harms, R. Bruckner and J. Suffert, Chem. Bel: 1992, 125, 271; J. Suffert, A, Eggers, S. W. Scheuplein and R. Bruckner, Tetrahedron Lett., 1993, 34, 4177; M. Moniatte, M. Eckhardt, K. Brickmann, R. Bruckner and J. Suffert, Tetrahedron Lett., 1994, 35, 1965. 113 K. Nakatani, K. Arai, K. Yamada and S. Terashima, Tetrahedron Lett., 1991,32, 3405; K. Nakatani, K. Arai, K. Yamada and S. Terashima, Tetrahedron, 1992,48,3045. 114 J. M. Nuss, B. H. Levine, R. A. Rennels and M. M. Heravi, Tetrahedron Lett., 1991, 32, 5243; J. M. Nuss, R. A. Rennels and B. H. Levine,J. Am. Chem. SOC., 1993, 115,6991. 115 S. Torii, H. Okumoto and A. Nishimura, Tetrahedron Lett., 1991,32, 4167; S. Torii, H. Okumoto, T. Tadokoro, A. Nishimura and Md. A. Rashid, Tetrahedron Lett., 1993, 34, 2139. 1991,32, 6541. 112 R. Bruckner, S. W. Scheuplein and J. Suffert, 116 D. Bouyssi, G. Balme and J. Gore, Tetrahedron Lett., 117 C. B. Ziegler Jr, J. 0%. Chem., 1990,55,2983. 118 M. Hirama, K. Fujiwara, K. Shigematsu and Y. Fukazawa, J. Am. Chem. SOC., 1989, 111,4120. 119 In a similar way, the isomeric bicyclic compound, wherein the position of the keto function and the geminal dimethyl group are inversed, was prepared: K. Fujiwara, A. Kurisaki and M. Hirama, Tetrahedron Lett., 1990, 31, 4329. 120 M. Hirama, T. Gomibuchi, K. Fujiwara, Y. Sugiura and M. Uesugi, J. Am. Chem. SOC., 1991,113,9851; S. Kawata, T. Oishi and M, Hirama, Tetrahedron Lett., 1994,35,4595. 1991,651. M. Uesugi and Y. Sugiura, Tetrahedron Lett., 1993, 34, 669. 1990,31,6625. analogue, see: Y. Matsumoto, Y. Kuwatani and 1. Ueda, Tetrahedron Lett. , 1995, 36, 3197. 125 K. Nakatani, K. Arai and S. Terashima, J. Chem. SOC., Chem. Commun., 1992, 289; K. Nakatani, K. Arai, N. Hirayama, F. Matsuda and S. Terashima, Tetrahedron Lett., 1990, 31, 2323; K. Nakatani, K. Arai, N. Hirayama, F. Matsuda and S. Terashima, Tetrahedron, 1992, 48, 633; K. Nakatani, K. Arai and S. Terashima, Tetrahedron, 1993,49, 1901. 121 M. Hirama, M. Tokuda and K. Fujiwara, Synlett, 122 M. Tokuda, K. Fujiwara, T. Gomibuch, M. Hirama, 123 T. Wehlage, A. Krebs and T. Link, Tetrahedron Lett., 124 For the preparation of the corresponding benzo- Lhemzitte and Grierson: Enediyne based antiturnour antibiotics. Part 1 63

ISSN:1350-4894    

DOI:10.1039/CO9960300041

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Alcohols, ethers and phenols C. S. HAU, ASHLEY N. JARVIS and JOSEPH B. SWEENEYS School of Chemistiy, University of Bristol, Cantock's Close, Bristol BS8 1 TS, UK *Present address: Department of Chemistry, University of Reading, Reviewing the literature published between August 1993 and February 1995 Continuing the coverage in Contemporary Organic Synthesis 1994, 1, 243 1 1.1 1.1.1 1.1.2 1.2 1.3 1.4 1.5 2 3 Preparation of alcohols From carbonyl compounds Via carbon-carbon bond-forming reactions Alcohol synthesis by reductive addition to carbonyl compounds Oxidative methods for alcohol synthesis Alcohol synthesis from epoxides Alcohol synthesis via biotransformations Miscellaneous methods for alcohol synthesis Preparation of ethers and phenols References 1 Preparation of alcohols 1.1 From carbonyl compounds Evans, Dart and Duffy have examined the origins of 1,3-asymmetric induction in two well-known and much-utilised reactions of carbonyl compounds: hydride addition' and Mukaiyama-type aldol reactions2 As a result of these authors' experiments analysing the effects of acyl substituents (RAC), P-substituents (R,) and the steric demand of reducing agent, they have concluded that a revision of the original 'polar Cram model'3 is necessary to account for syn-selectivity in non chelation- controlled reactions. Transition states (TS) A and B are proposed as those responsible for the observed stereoinductive effects, with A generally favoured in hydride reduction except when R, is sterically demanding, in which case B may be preferred.In the case of Mukaiyama aldol reactions, TS B is generally preferred, because there is no acyl substituent (i.e.RAC = H) and TS B minimises the non-bonded interaction shown in Scheme 1. PO Box 224, whiteknights, Reading RG6 2AD, UK 1.1.1 Via carbon-carbon bond-forming reactions 3-Zircona-1 -cyclopentenes and zirconacyclopentanes react with aldehydes to give oxazirconocycles 1 which may be protiolysed to (E)-pent-l-en-5-ols 2 or converted via reaction with elemental iodine to the corresponding 1-iodo analogues 3 (Scheme 2).4 In a similar vein, Whitby and co-workers' contributions to organozirconium chemistry continue: zircona- cyclopentanes 4 undergo sequential insertion reaction with a-lithioallychloride (to give $-ally complex 5 ) and aldehydes or ketones to give (after protonation) (E)-5-cyclopentylpent-3-en-l-q 01s 6 in good yield (Scheme 3).5 Where stereoisomers are produced, diastereoselectivities are low.C6H13 HO '3" Ph I bh 1 1 l2 w H13 Ph 3 65% yield 'Ph Scheme 1 Scheme 2 Hau, Jawis and Sweeney: Alcohols, ethers and phenols 65H*- % 75% yield E :Z = >98:2 4 5 I 0 'OH 6 R' R2 YieM of 6 ("lo) H Ph 90 H 2,4-di-M&Ph 60 H P i 90 H P f 95 M e Me 54 Ph Ph 57 --(CH2)5- 56 Scheme 3 Hydrozirconat ion of 1,l -dimet hylpropa- 1,2-diene gives chlorodicyclopentadienylprenylzirconium 7 which allylates aldehydes and ketones in good yield with high anti:syn selectivity and with allylic rearrangement (Scheme 4).6 The reaction may be applied to a range of other allenes. Enol(oxysilacyc1obutanes) 8, prepared from dichlorosilacyclobutanes7 undergo highly diastereoselective and uncatalysed aldol addition reactions with aldehydes' (Scheme 5).However, only predominantly (E)-enols undergo diastereoselective aldol reaction. The reaction is proposed to proceed via the ubiquitous six- membered transition state. A new catalyst for asymmetric Mukaiyama aldol reactions has been reported.' Thus, catalyst 9'' effects highly enantioselective acetate aldol addition reactions (Scheme 6). The aldol reactions of the lithium enolates of chiral NJV-dialkyl-a-aminomethylketones 10 are enantioselective," due (it is proposed) to the boat- like chelate formed by the neighbouring amine (Scheme 7). This proposal is necessary because methylketone-derived lithium enolates usually react with poor enantioselectivity.Ph 7 OH R Yield (%) anti :syn C5H11 79 96:4 C3H7 82 9o:lO Ph 95 955 77 99:l 88 99:l Scheme 4 Bu'O.7 Zi RCH0,ZO"C * M e O v R + M e O v R >= HFrrHF Me0 8 E:Z in8 R Solvent Yield (Yo) syn :anti 0:lOO Ph CDC13 80 4258 95:5 Ph CDCl3 94 955 93:7 89:11 phd CDC13 95 89:ll C5Hll CDCl3 91 93:7 89: 1 1 CGH11 CDC13 85 >99:1 Scheme 5 The Baylis-Hillman-like aldol condensation of a-allenic esters with aldehydes allows (inter aka) direct preparation of enynes (Scheme 8).12 Microwave irradiation is reported to accelerate the rate of the Baylis-Hillman reaction of aldehydes and a$-unsaturated esters and nitriles in the presence of DABC0.13 At room temperature, these reactions can be notoriously sluggish, sometimes requiring 14 days for complete reaction. Using microwaves, the reactions are complete within 40 minutes.Tetraallyltin is a chemoselective allylator of aldehydes; reaction of these components in aqueous HCl/THF mixtures gives an excellent yield of homoallylic alcohol (Scheme 9),14 This contrasts very favourably with the less selective behaviour of many 66 Contemporary Organic SynthesisBut 9 -But 0 TMSO R2 s-H + /)-OR' -1 0 "c. 9 (2-5 mol% ) Etg, 4 h TBAF, THF 1 1 OH 0 R 2 d O R l R2 ee (%) R' = Et R1 = Me P h w ' 93 97 C6H11 94 95 Ph 93 96 Scheme 6 via: H R' R2 Yield (%) de(%) Me Ph 84 60 Me P i 95 64 Me But 91 76 BU p i 81 78 Bu But 78 80 Bu Ph 76 85 P i Ph 90 >96 P i Pr' 64 >96 P i Bu' 88 >96 Scheme 7 carbonyl allylators. Dials may react to give lactols (Scheme 10). Titanocene monochloride facilitates a Prins-type reaction of cycloheptatriene with aldehydes (Scheme ll).I5 Yields are moderate and diastereoselectivities mediocre.The combination of trichlorosilane and a catalytic amount of Pd(PPh3)4 effects another high- l l a l l b R' R2 Base Ymld of l l a (%) Yield of l l b (%) H H H H H Me Me Me El El El Hex Ph Pr Bu Hex Hex CeH,B- DABCO BuLi DABCO BuLi BuLi BuLi BuLi BuLi BuLi 41 58 54 56 66 0 0 0 64 0 0 0 0 0 73 61 59 0 Scheme 8 tetraallyltin. HCI (aq.), THF; OH 98% yield Scheme 9 H LJH Scheme 10 tetraallyltin, HCI (aq.). THF high dilution _I___) 78% yield yielding Prins-type reaction of 1,3-dienes with aldehydes (Scheme 12). Under these conditions, however, the reactions are highly diastereoselective, in favour ofsyn isomer.I6 Allylic sulfones may be used as equivalents of allylic anions (Scheme 13) and used to prepare homoallylic alcohols.17 Ytterbium triflate catalytically promotes allylation of aldehydes by allyltributyltin, in contrast to most other promoters which must be present in stoichiometric amounts." Germanium iodide promotes allylation of aldehydes by allylic bromides" in the presence of diiodomethane.Zinc mediates allylation of aldehydes and ketones with cinnamyl chloride in an aqueous medium (Scheme 14).*' The enhanced thermal stability of fluorinated propenylzinc reagents compared to the Hau, Jawis and Sweeney: Alcohols, ethers and phenols 67Pd(PPh& (5 ITIOW~); A S O p P h 0 ZnEt,. RCHO I via: R 28-91 % yield ckmo RCHO 6 Scheme 13 \ Scheme 11 OH Cl$W, Pd(PPh3)j; e RCHO. DMF R1& + R ’ L p h R’ dnnamyl chloride k o - R2 Zn.NH&I.THF R2 ’* Ph I Scheme 14 major minor Diene Aldehyde Product Yield (YO) Stereoselectivity s RCHO WCUcl (cat.) DMF.pyridine. vBr - \*OH 70-95% yield CF3 0 PhCHO d p h 91 >91%syn OH roomtern. + 50 “c h PhCHO Y P h 94% syn h OHC-Ph +Ph 92% syn h OHC+ Ph +p,, / 92 92% syn H PhCHO g P h 92 - 0 R’ CI bC1 + $-R2 Li, DTBB (5 ml%) THF, 0 “c, 1 h; ~~~ ~ Me Me 72 1.3:l Et Et 60 1.6:l Scheme 12 corresponding lithium2’ and magnesium species2* allows high-yielding preparation of 2 (trifluoromethy1)allylic alcohols via a Barbier-type reaction of 2-bromo-3,3,3-trifluoropropene with aldehydes (Scheme 15).23 The use of 1,3-dichloropropene as a source of 1,3-dilithiopropene has been reported in full.24 Reaction of 1,3-dichloropropene with lithium metal in the presqnce of a catalytic amount of 4,4’-di-tert- butylbiphenyl (DTBB) and two equivalents of non- enolisable ketones and aldehydes gives substituted pent-3-ene-1,5-diols in moderate to good yield (Scheme 16).The reactions are believed to proceed Scheme 16 by sequential metal-halogen exchange/carbonyl addition processes. 2 : E ratios approach unity. of sulfonium ylid leads to an efficient vinylation reaction to give allylic alcohols (Scheme 17). The reaction involves nucleophilic addition to give a p-sulfonium alkoxide from which dimethyl sulfide is eliminatively removed by the excess lid.^' involving organostannanes have continued to be of Treatment of carbonyl compounds with an excess Asymmetric carbonyl alkylation reactions 68 Contemporary Organic SynthesisTi(OPi), Scheme 17 m S n B u 3 / R RCHo 1 3 ~ 1 4 R Yield (%) ee (%) Catalyst R Yield (YO) ee (configuration) (YO) Ph 88 95 13 C7H15 83 C5H11 75 97.4 ( R ) 98.4 ( R ) 92.6 (S) 88.8 (S) 82.0 ( S ) 80.2 ( S ) 95 92 14 14 89 P h A .77 (y 75 P h d # 98 96 14 89 96 13 73 96 13 Scheme 18 Scheme 19 interest. Chiral binaphthyl titanates catalyse asymmetric allylation of aldehydes by allyltributyl tin, as has been described by several groups during the period covered by this review. (S)-Binaphthol- derived dichlorotitanate 12 asymmetrically catalyses the allylation of aromatic and aliphatic aldehydes with good to excellent enantioselectivity (Scheme 18).26 The presence of molecular sieves is vital to the success of the reaction. In a similar study, Keck et al.report that reaction of titanium tetra- isopropoxide with either one or two equivalents of enantiomerically-pure BINOL gives catalysts 13 or 14 which exhibit good to excellent enantiocontrol in the allylation of a range of aryl, aliphatic and heteroaromatic aldehydes (Scheme 19).27 BINOL with either a full or one half equivalent of Ti(OPri)4 asymmetrically mediate the reaction of aryl and aliphatic aldehydes with allenyltributyl- stannane (Scheme 20).28 Allenyl alcohols 15 rather than homoprop-2-ynylic alcohol 16 dominate the reaction mixtures; extensive conjugation in the carbonyl component leads to only allenic product, perhaps due to the concomitant rigidity of such systems. Although the reactions require stoichiometric amounts of catalyst and are not uniformly high-yielding, the enantioexcesses obtained are of useful levels (3 82% ee, often (290% ee).The Lewis acids derived from the reaction of (R)- ?H OH RCHO (R)-BINOL, Ti(OPr')d * R b R 15 16 ~~~~ ~ ee R Ti(OPi), (mop/,) Yield (%) 15 (%) 15:16 50 100 50 100 50 100 50 100 50 100 48 58 50 52 25 27 76 80 64 82 >99 95 94 94 82 82 95 92 89 89 14:l 7 1 >95:5 ("traces of B') >955 ("traces of B') 1oo:o 100:o 23:l 11:l 4: 1 4: 1 Scheme 20 69 Hau, Jarvis and Sweeney: Alcohols, ethers and phenolsStoichiometric asymmetric allylation reactions have also been reported. The double asymmetric induction in the reaction of mannose-derived homochiral allylstannane 17 with homochiral aldehydes is pronounced; 17, it is suggested, has a preference for si-face attack, but this preference is inherently weak, as shown in its reaction with achiral aldehydes.A mechanistic rationale, based on a Felkin-Ahn transition state, is proposed, to explain the underlying motives for matched and mismatched bond formation (Scheme 21).29 induction in reaction of &amino and b-hydroxy- allyl~tannanes’~ with aldehydes has been extra- polated to allow an efficient 1,7-asymmetric induction. Thus, homochiral 6-hydroxyallylstannanes 18 react with aryl and aliphatic aldehydes in the presence of tin( IV) bromide to give predominantly syn-(Z)-hept-4-ene-l,7-diols in moderate to good yield (Scheme 22).” A review has appeared concerning the utility of such homochiral &oxygenated allylstannanes in the asymmetric allylation of aldehydes.’* The demonstrated utility of remote asymmetric I-, 17 L-Quebrachitol has been employed as a chiral auxiliary in the asymmetric [3 + 21-cycloaddition reaction of allylsilanes with a-ketoesters.Diastereocontrol and enantiocontrol in the reaction is impressive (Scheme 23).” Acylsilanes may be enantioselectively allylated using B-ally1 diisopinocampheylborane. Enantio- excesses are moderate to low (Scheme 24).’4 Soai has described the asymmetric alkenylation of prochiral enals using diastereoface-selective delivery of vinylzinc reagents (Scheme 25).’5 Using proline- derived chiral chaperones, the yields and enantio- excesses of the reaction were moderate. The chemo- and enantioselective alkylative addition reactions of ketoaldehydes with diethylzinc in the presence of ( - )-A( N-dibutyl norephedrine [ ( - )-DBNE] has been described in full by the same group (Scheme 26).’6 Enantioexcesses were moderate ( x 80%) while chemoselectivity was excellent.Grignard reagent in the presence of tetrapropyl titanate or tributyl vanadate is known to give a-alkylcyclopropanols.37 Corey has found that use of The reaction of esters with a double equivalent of 0 0 TBDMso-2 I 7 1 1.2 : 1 1 1.5 RO r3 0 - TBDMSO BF3aEi2 18:l (matched) 70% yield OH : OR BF@Ei, 16:l (mismatched) 80% yield 1.5 0 0.2 Scheme 21 70 Contemporary Organic SynthesisR 18 anti OH R Yield ("A) syn :anti Ph 4-CI-CeH4 4-MeCeH4 2-Naphthyl Pi Me Et But BU' 72 71 47 65 63 36 61 58 38 92:8 92:8 89:ll 93:7 89:ll 9 o : l O 91 :9 85:15 95:5 Scheme 22 R' = TBDMS SiR23 Yield ("A) de(%) ee(%) ~~ ~ ~ Me3Si 72 >98 95 PhMe,Si 78 >98 >98 Bu'Me2Si 83 >98 96 Bu'Ph2Si 85 >98 98 Scheme 23 catalytic amounts of chloro(triisopropy1oxy)- titanium(1v) in place of the full alkoxide and use of an excess of magnesium allows a diastereoselective synthesis of cis-1 ,Zdisubstituted cyclopropanols from esters (Scheme 27).38 The reaction is not R' SiR23 Yield (%) 88 (910) 2-thienyl SiepPh 81 17 4-CH346H4 SiMe2Ph 65 26 c-C5Hg SiMe2Ph 70 42 4-CF3-C6H4 SiMe2Ph 81 36 plenyl TMS 72 89 Scheme 24 R' R2 R3 Yield(%) eerh) Ph H Bu 59 77 Ph Me Bu 56 75 Ph Me (CH2),2CH3 39 73 Scheme 25 0 0 Et2Zn (-)-DBNE OH Ph-"- 0 ph+NB~2 OH (-)-DBNE Scheme 26 applicable to benzoates and a-branched esters.When TADDOL catalysis was applied, moderate enantioselectivity was obtained ( - 70% ee). Takeda et al.have found that a 3-exo-trig reaction of a Brook rearrangement derived a-silyloxy anion 19 allows preparation of 1,2-dihydroxycyclopropanes 20-22 in good yields (Scheme 28).'9 Anion 19 is generated by reaction of an acyl silane with a lithium enolate of a methyl ketone. cis-Isomers predominate, but in these isomers the silyl group is scrambled between both hydroxy groups. When silylvinyl ketones are employed in the reaction, yields are lower because of competing Michael addition, but no migration of silicon is observed and only trans-diastereoisomers are obtained (Scheme 29). The same authors also reported a similar Brook rearrangement at the heart of a novel Hau, Jawis and Sweeney: Alcohols, ethers and phenols 71l W ! cis R Hex Hex PM=%CH2 PhCH2CH2 H H Me Me Et Et Hex Et Me Hex Ph Me Ph 79 81 80 79 03 72 80 80 83 Scheme 27 ox OTMS P h - - - f # Y + Ph--f@ R OH 20, X = TMS, Y = H 21, X=H,Y=TMS 22 LiO P h T R 0 TMSO ____) Ph? R 0 19 Yield (%) R 20 21 22 Et 64 21 0 PP 59 21 0 p i 9 0 7 0 But 75 0 9 3 T B D M S LIO I kR Scheme 29 I R I 23 O A R 24 Yield (%) R 23 24 Et 3 5 5 3 P f 30 51 But 36 21 P i 4 0 5 0 via: 0- 25 26 27 28 Scheme 28 Yield (%) R 25 26 27 28 Pr’ 55 19 17 19 Et 70 5 70 83 od 71 8 66 73 PP 74 7 n a7 [3 + 21-cyclopentene annulation reaction between 3-heterosubstituted a$-unsaturated acyl silanes and ketone enolates (Scheme 30).40 The reaction was utilised in a synthesis of clavulone I1 (Scheme 31).by 4-em-trig cyclisation of 0-acyl benzylic anions (Schemes 32 and 33).4’ The recent popularity for oxazaborolidine- mediated asymmetric reactions has led to a concomitant demand for homochiral 2,Zdialkylated amino alcohols.Luche et al. have reported a simple racemisation-free method for preparation of such dialkylated aminols from L-valine (Scheme 34).42 Benzocyclobuten-1-01 derivatives may be prepared Scheme 30 1,l -Dichloro-2- hydroxynitroalkanes may be prepared efficiently via a Reformatsky-like version of the Nef reaction. Thus trichloronitromethane reacts with aryl and aliphatic aldehydes in the presence of tin(1r) chloride to give the coupled 72 Contemporaly Organic Synthesiscbvubne Il Scheme 31 Me0 Me0 V C O P h OMe LDA, THF. -78 "C TMSCI. -78 d I Me0 COPh OMe + 65% LDA, THF. -78 'c TMSCI. -78 'C 1 Ph Me0 OM8 Scheme 32 Ph Me0 OMe 1 w/o LDA, THF, -78 "c; 'q R COBu' NH&l(w.) OMe R = H, 76% R = OMe, 59% Scheme 33 1.1.2 Alcohol synthesis by reductive addition to carbonyl compounds Homochiral a-amino aldehydes may be pinacol- coupled using the well-documented low-valent metal reagents of Pedersen (Scheme 36).Thus, a slight excess of an aliphatic aldehyde reacts with such R' YieM ("A) Me 84 Bun 71 ClOH21 48 Bu' 87 Ph 78 mo45H11 10 Scheme 34 SnCl& Et&. 0 "C; CI3CN02 - RCHO; H30+ 5 2 - 9 s yield Scheme 35 OH NHC02R3 R1 R2 OH 30 R' R2 R4 R5 Yield(%) de PS Pr' H But 70 >20:1 PhCH,CH, PhW2 H But 67 >20:1 Bu' PhCH2 H But 67 >20:1 c-C6Hl1 ZNH(CH2)4 H Bn 75 >20:1 C,,HS BnOCH, H Bn 54 .20:1 Scheme 36 aldehydes in the presence of low-valent vanadium reagent 29 to give 1,2-syn-2,3-syn-2-amino- 1,2-diols of general formula 30, in good yield."4 Allylic alcohols may be clectrochemically-coupled with ketones to give 1,4-diols (Scheme 37).45 Full details of what is claimed to be the first efficient asymmetric hydrosilylation protocol for reduction of aryl ketones has been unveiled by S .L. Buchwald et al. (Scheme 38).46 Thus chiral catalyst 31 mediates hydrosilylation of aryl alkyl ketones by polymethylsiloxane according to the previously proposed mechanistic pathway (Scheme 39).47 Enantioselectivities arc generally high ( 3 90% ee). Polymethylsiloxanc (PHMS) also reduces carboxylic Huu, Jawis und Sweeney: Alcohols, ethers and phenols 736H via: &face attack Scheme 37 31 4.5 moPh BuLi (2 eq.); Me3Si0 2'- iMe3 (5 eq.); I:+ ArCOR; TBAF or HCI (aq.) H ° F R Ar Configuration Ar R of product Yield (%) ee (%) Ph Me S 73 97 2-Naphthyl Me S 84 95 2-CCC,H4 Me S 78 90 4-Me-C6H4 Me S a4 96 4-F&-C& Me S 66 65 Scheme 30 via: rather than: Scheme 39 esters to give silylated primary alcohols in the presence of titanates and zirconates (Scheme 40).48 Alcohols are liberated from the silyl ethers by alkaline hydrolysis.Carboxylic acids are also reduced to primary alcohols (6340% yield). a$-Epoxyketones may be reduced to the appropriate alcohol by trimethoxysilane in the presence of lithium methoxide catalyst (Scheme 41). R'C4Me R'-OSiR2, Equivalents Equivalents Yiild of silyl R d PHMS d M(OR2), ether ("A) Ph 0.1 1 86 Bn 0.1 1 76 0.1 1 65 0.1 1 82 Ph # Scheme 40 R1&R4 $ 0 (Me0)3SiH (1.2 eq.) solvent LOMe (4 mi%) 1 R' R2 R3 R4 Solvent Yeld(%) syn:anti H H H P h H H Me Ph Me H H Ph Me Me H Ph H H H B u H H Me Bu H H H P h H H Me Ph Me H H Ph Me Me H Ph H H H B u H H Me Bu Et20 Et2O Et20 Et20 Et20 E t20 HMPA HMPA HMPA HMPA HMPA HMPA 100 91 99 88 78 84 98 91 99 100 88 90 8:92 34% 9:91 0: 100 11:89 11:89 9o:lO 72:28 93:7 60:40 81:19 44:s Scheme 41 The diastereoselectivity of the process is solvent- dependent, allowing for choice of chelation- controlled or Felkin-Ahn-type transition states.At best, exclusive anti or very predominantly syn products may be obtained. Yields are generally A pronounced 177-asymmetric induction is seen when boronate-containing P-y-unsaturated ketones 74 Contemporary Organic Synthesis(prepared by 1,4-addition of boronomethylzinc reagents to enones) are reduced using borane complexes (Scheme 42).” Thus, ketoborinates are reduced with high enantioselectivity by achiral borane-dimethylsulfide.The authors propose a pseudo-axial attack of hydride on a half-chair chelated conformer to rationalise the results (Scheme 43). Evans and co-workers have described the results of their studies into asymmetric catalysis of the Meerwein-Ponndorf-Verley reduction of prochiral ketone^.^' The authors replaced the aluminium isopropoxide of the classical reaction by samarium( iv) species 32, readily prepared from benzylamine and commercially available @)-styrene oxide. This complex catalyses a highly enantioselective reduction of aryl alkyl ketones (Scheme 44). L LJ-J - ‘r R BH3*SMe2, 0 “C; NaOH.Hf12 ! major minor R ee (Oh) Yield (“1’) Me Pent Hex Ph CI(CH2)3 WCH2)lO n O L Me02C(C H2)4 85 42 >98 97 93 97 98 >96 83 87 85 95 97 81 a9 95 Scheme 42 highenergy I H- low energy k Substrate Yield of alcohol ee (“A) (“A) 96 74 95 31 77 78 63 82 95 97 96 96 92 94 68 73 96 97 Scheme 44 Oxazaborolidines derived from (S)-indoline- 2-carboxylic acid asymmetrically catalyse the reduction of prochiral ketones. Whilst in itself not entirely without precedent, the ability to prepare from a common precursor chiral controllers which provide either enantiomer of an alcohol is of interest (Scheme 45).’2 Noroyi et al. have reported the reduction of carbonyl compounds using a simple metal hydride H A HO - c h2 THF BH3 A + BH, R’ R’R~CO (R kconfiguration BOYo ee HO )_R2 THF BH3 B +BH3 R’R~CO R’ (S )-configuration 290% ee Scheme 43 Scheme 45 Hau, Jawis and Sweeney: Alcohols, ethers and phenols 75(Scheme 46).53 The authors found that the combination of commercial LiH and TMSCl in the presence of a catalytic amount of metallic zinc or a zinc(ir) salt would reduce aldehydes and ketones to the corresponding TMS ethers in good yield.Silica gel enhances remarkably the carbonyl- reducing activity of B u , S ~ H . ~ ~ Aryl and aliphatic ketones and aldehydes undergo reduction, but the reduction is chemoselective, with the carbonyl of greater electrophilicity reacting preferentially (Scheme 47). R' FP Catalyst Yiild of siiyl ether (%) Scheme 46 OMe 0 & Me H ?Me HO H 78% yield OMe + & 0 CH, Bu3SnH. SiO2 C H & , 24 h ?Me + 0 y-6 Me CH3 90% yield Scheme 47 Prop-2-ynylic cyclic carbonates may be reduced to either (2)-homoallylic alcohols or homoprop- 2-ynylic alcohols by catalytic hydrogenolysis using Pd( acac)2 (Scheme 48).55 The former are obtained by carrying the reaction out at the boiling point of toluene, whilst the latter result from reduction at ambient temperature.In a related reaction, alkynyl cyclic carbonates are reduced to either homoprop- 2-ynylic alcohols or a-allenyl alcohols by a ligand- tuneable catalytic hydrogenolysis using Pd(dba)* (Scheme 49).56 Simple monodentate phosphine ligands favour formation of alkynes, while biphosphines favour allenes. 0 II Pd(acac)&uoP NHCOgH4 (1 q.) R I O a R 2 R'O 8, room temp. A 2 286% yield Pd(aca+-Bu3P reflux NHCOfiH4 (4 q.) - R2 1 ?H R'O- 274% yield Scheme 48 0 Pd(dba)* BUJP 4 HCO&I Et3N = R Rk*=L HO Scheme 49 1.2 Oxidative methods for alcohol synthesis Full details have appeared concerning the utility of (R)- 1 -[ (S)-2-( diphenylp hosp hino)ferrocenyl]- ethyldicyclohexylphosphine 33, better and more comfortably christened (R)-(S)-josiphos (after the technician involved in its preparation).This catalyst allows highly enantioselective hydroboration of alkenes to give, after usual peroxidative work-up, enantiomerically enriched alcohols. Yields of the process are good and enantioselectivities are moderate to high (Scheme The catalyst also mediates asymmetric reduction of P-ketoesters, but the ee's of the P-hydroxyesters produced are not as high as Noroyi's Ru-BINAP system (84-97% versus ~ 9 9 % ee). Samarium( 111) iodide catalyses the hydroboration of alkenes by catechol borane (Scheme 51).58 The samarium species is present in one-tenth stoichiometry and was selected as the best catalyst from a range of lanthanide complexes. The reactions do not proceed to completion in several cases and high selectivity is not ubiquitous.of cyclohexenones may be selectively hydroxylated The usually less reactive conjugated double bond 76 Contemporary Organic Synthesisto either cis- or anti-1,3-diols by a two-step reduction-oxidation process (Scheme 52).59 Thus, reaction of pulegone with a higher-order phenyl- dimethylsilyl cuprate gives the chromatographically- separable 1,4-addition products which may be selectively reduced: dissolving metal reduction of the addition products followed by peroxidative 9 #Q (R)-(S )-josiphos 33 [Rh(NDP)@F4 (1 md%) ( R )-( S )-josiphB, -78 "C VH 65%yield i\ 91.5%- Ph ph* catechol borane, DME; * NaOH, 25 "c 65% yield 91.5% 88 (Rh(NDP)#F, (1 MI%) (R)-(S)-josipho~, -78 "C catechol borane, DME; NaOH, H@a 25 "C OH Scheme 50 ph+Ph O P h 0, Ph? 79(98) 5O:l (primary:secondary) 47(59) 5:l (primary:secondary) 81 (91) >99:1 (primary:tertiary) 2:l (syn :anti) W99) Scheme 51 A A t Li, NH3, THF-EtOH, -78 "C; TBAF, THF, 25 "c; 30% H@a KHC03, MeOH.25 "c I 1 1 I (PhMe,,Si)&uCNLi, P h M e 2 S i v + P h M e 2 S i u * oo THF, -23 "C, 85% yield A I I A 5 : l A Scheme 52 Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 77desilylative hydroxylation gives anti-diols exclusively, whereas use of L-SelectrideTM as reducing agent gives the syn-isomer.The Schenk reaction has been employed to good effect in a concise synthesis of homochiral a-methylene lactones. Thus, homochiral 3-tributyl- stannyl ally1 alcohols react with singlet oxygen in a highly diastereoselective fashion to give (after reductive work-up) mainly trans-diols (Scheme 53). The major product of the reaction was converted in a two-step process to a-methylene lactones, including dihydromanubanolide B 34.60 OH ''4 + H O E + "$ \ R Bu3Sn R 7% 5% Bu,Sn Bu3Sn 8148% NI(C0)2(PPh3)* THF I 0 Scheme 53 Interest in asymmetric dihdroxylation (AD) of alkenes has continued unabated, as expected. A review of the area has appeared:' along with a review of the general ligand-accelerated catalysis,62 the cornerstone of the AD reaction. What is surprising is an example of AD which apparently violates the predictive mnemonic of Sharpless.Hale and co-workers have reported that l,1-disubstituted alkenes in which one of the substituents is a silyloqmet hyl moiety undergo AD with opposite enantioinduction to that expected (Scheme 54).63 In most cases, enantioexcesses are low, perhaps indicating that these inverted preferences are to do with steric inhibition. YTBS HO" T <OH Scheme 54 Methanesulfonamide-accelerated AD was also used in the synthesis of a conditurol. Thus, the benzylidine acetal of ck-l,2-dihydroxycyclohexa- 3,s-diene underwent diastereo- and enantio- selective dihydroxylation, and deprotection of the resulting diol gave (+)-conduritol E (Scheme 55).64 The same group further reports that acetonide diol 35 may be subjected to a Mitsunobu reaction to give (after deprotection) ( + )-conditurol-F (Scheme 5Q6' 9" >8!% ee >loo% de 1 bn efxc;ge Ho..&; (t)-conduritol E Scheme 55 Scheme 56 78 Contemporary Organic SynthesisSeveral other interesting reports have emerged from the Scripps Institute: firstly, an improved method for the asymmetric dihydroxylation of tetrasubstituted alkenes.66 The use of the 'methane- sulfonamide addition effect' 67 leads to good yields of cis-diols: enantioselectivities are, however, variable (20-97% ee).Terminal alkenes undergo dihydroxylation with improved enantioexcess using cinchona alkaloids bonded to pyrimidines and phthalizines (36 and 37 respectively) (Scheme 57)." (DHQD),-PYR 36 Scheme 57 VDHQD ODHQD (DHQD)p-PH AL 37 WoMe DHQD An improvement to the reaction of cis-allylic and homoallylic alcohols has been reported.69 This paper reports the results of the study into the suitability of the various AD-mixes with such substrates: these data are summarised diagrammatically in Scheme 58.The enantioselectivity of the reaction is AD-mix, 0 "C OH ee ("h) (absolute configuration) Substrate (DHDQ),-PHAL (DHQ),-PHAL DHQD-IND 57 31 73 72 (2R, 3 s ) (2S,3R) (2R, 35) (25,3R) (2R, 35) (2S, 3R) 64 51 Scheme 58 moderate, but the authors point out that, in the homoallylic example, the near symmetry of the alkene makes any selectivity surprising. The authors suggestion of an hydrogen-bonding r61e for the OH group is reinforced by the poor ee shown in dihydroxylation of the corresponding methyl ethers (Scheme 59).(DHW)z-PHAL R' AD-mix OH R' R2 ee (%) Me0 CH20Bu 23 MeO Ph 13 H Ph 35 MeOCH, Et 0 Scheme 59 Homochiral 2,3-epoxyalcohols may be prepared from allylic halides in a two-step sequence involving asymmetric dihydroxylation followed by ring-closure (Scheme 60).70 Yields and enantioexcesses are moderate to excellent. OH 12-98% ee 50-89% yield (DHQD),-PHAL; R -Hal - NaOH R Scheme 60 Sharpless and Wong have joined forces to devise a chemoenzymatic synthesis of carbohydrate^.^' When the products of the AD reactions of a$-unsaturated aldehydes (or equivalents) are subjected to reaction with hydroxy acetone monophosphate in the presence of aldolase enzymes, ketotetrols are obtained in high enantioexcess (Scheme 61).reported: the reaction is chemoselective in the presence of sulfides, dithianes and di~ulfides.~~ Sharpless has reported at length on the mechanistic studies underway to elucidate the exact species involved in the AD rea~tion.~' Full details have appeared concerning the highly diastereo- and enantio-selective asymmetric dihydroxylation reaction of polyenes using phthalazine-modified AD An impressive example of the ease of use of the Sharpless AD reaction has been reported to allow a 'solid-to-solid' asymmetric synthesis of hydrobenzoin on a kilogram scale (Scheme 62).75 Bu'OH lowers the solubility of stilbene, thereby approximating the optimal 'slow addition' protocol required for high enantioexcess. Furthermore, hydrobenzoin is also poorly soluble in the solvent.Thus, the reaction is marked by the slow disappearance of solid substrate The AD of olefins containing sulfur has been Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 790 I -Q R' .. R'R2NH, LiBF, I c8H'7B CH,CN,80"C * OH R-0' R' R2 Yield(%) But H 95 Et Et 88 PS PS 92 Ph H 98 rn 86 W 0 R OH OH Pd(OH)% H,, MeOH 1 Pd(0H)a H2, MeOH I Scheme 63 occurs at the carbon atom of lesser substitution (Scheme 63). been demonstrated to be effective in the regioselective ring opening of epoxides (Scheme 64). These complexes (previously used in ROMP processes79) are highly soluble in organic solvents, have ligand-tuneable Lewis acidity and a high tolerance of spectator functionality. Metal ions examined were Cr(v), Cr(vi), Mo(vr) and W(vr) and this order reflects the order of electrophilicity." Organoimido complexes of transition metals have R&CHO R R = Me, H, >95% 178% 88 68 R = Ph, >95% w R q C H O 1 OH I Rha aldolase; acid phosphatase Rha aldolase; acid phosphatase ,+OH OH OH OH OH R &Nu= R E O H nucleophile, catalyst, * H30* + Scheme 61 A B Yield of Yield of Reaction R Nucleophile Nu Catalyst A(%) B(%) time(h) 0.25 mop/.ligand 0.2 ml% K20s0,(OH)4 NMO (60% in H20) BU'OH. room temp. * P h q p h Ph/\\/ Ph OH 1 kg 1.04 kg 99% ee Ph Ph Ph Ph Bun Bun Ph Ph Ph Ph TMSN3 TMstJ3 NSN3 TMSN3 NSN3 TMSN3 BU'NHTMS BU~HTMS Et2NHTMS Et2NHTMS N3 N3 N3 N3 N3 N3 BuhH BU'NH Et2NH Et2NH 1 2 3 4 1 4 1 2 1 2 31 0 0 0 26 0 27 7 15 8 64 95 45 95 39 80 33 68 25 23 3 12 48 120 72 120 120 240 120 240 Scheme 62 and the concomitant appearance of solid enantio- merically pure product.This is probably as close as research chemists will get to Cornforth's idea of a process chemist's ideal reaction (a one-armed man pouring reagents into a bath and collecting pure product from the drain pipe)! Catalysts: 1. Cr(NBu')C13(dme) 2. Cr(NBu'),CI, 3. Mo(NB~')~Ck(drne) 4. W(N Bu'),(NHBu'), Scheme 64 1.3 Alcohol synthesis Crotti's work on selectivity and efficacy of epoxide heterolysis continues unabated. Lanthanide( 111) trifluoromethanesulfonates have been unveiled as the latest catalyst for such reactions, in particular for aminolysis of monosubstituted epoxides and cycloalkene A similar reaction using cuprate reagents has been published details of the LiBF4-promoted aminolysis of ~ x e t a n e s .~ ~ Ring-opening nucleophilic attack Crotti has also The impressive work of the Jacobsen group concerning asymmetric processes involving epoxides continues. The most recent report of their studies concerns asymmetric ring cleavage of meso-epoxides by TMSN3 (Scheme 65).8' Furthermore, the process may also be used to allow a kinetic resolution of racemic mixtures of monosubstituted epoxides (Scheme 66). The reaction may be performed with the utmost 'atom economy': for instance, no solvent 80 Contemporary Organic Synthesisdiethylamine. The (R)-enantiomer reacts more slowly than the (S)-antipode, so that the ring- opened product has primarily the (S)-configuration, but ee's of the products (both epoxide and amino alcohol) are mediocre.is strongly catalysed by tetrabutylammonium fluoride. The isomer 39 formed via nucleophilic attack at the carbon atom of lesser substitution, is usually observed (Schemes 68 and 69)." Regioselective ring opening of epoxides by thiols 36 (2 mow.), Et20 R AR TMSN3 CSA, MeOH R R > Bu NEt2 Et2NH, catalyst BU BU" OH (R,R)-36 M = CCl ~~ ~~ ~~ 88 ee Catalyst Conversion (%) epoxide (%) amino alcohol (%) Epoxide Yield (%) ee ("h) Ti(OPS),@INOL 45 22 27 Et2ACVBINOL 48 48 24 EtACI@INOL 47 52 58 Et&BINOL 59 75 91 88 94 94 98 98 0 Fmoc 95 95 0 0 p c F 3 PhSH, TBAF (5 mol%) Rl&R2 + R ' Y R 2 R3 SPh SPh 39 40 B 95 95 Yield ("h) R' R2 R3 39:40 72 81 PhOCH2 H MeOCH, H H 'p' H Ph C6H13 H Ph H cis -Ph Ph trans-Ph Ph -(CH*)4- -(c H2)4- H H H 1oo:o 1oo:o 1oo:o 65" 82 isolated as the TMS ether H 94:6 Scheme 65 H H H H H Ph 99: 1 64:34 100.0 1000 1oo:o 64:23 38 (2 mow.), Et20 "4 TMSN,, 78% cower& ''do 98% ee conf g urat ion unspecified 0 38 (2 m~l%), Et20 P h A TMSN3, 80% convesn Scheme 68 0 ?H Scheme 66 - Pho+ PhSH, TBAF (5 moW.) 25-100 "C SR PhO is necessary and, when the product of the reaction is distilled from the neat mixture, the catalyst may be recycled four times, performing sequential asymmetrical ring-openings of different epoxides without any loss of enantioselectivity.BINOL-derived Lewis acids effect a kinetic resolution of racemic chiral epoxides via nucleo- philic ring cleavage by secondary amines (Scheme 67).82 Thus, mixtures of aluminium and titanium Lewis acids and (R)-( +)-binaphthol mediate the ring opening of simple monosubstituted epoxides by R Yield ("h) PhCH2 96 98 88 HO Scheme 69 81 Hau, Jawis and Sweeney: Alcohols, ethers and phenolsLow-valent titanium radicals promote reductive ring cleavage of epoxides to give alcohols arising from (overall) proteolysis at the most hindered carbon atom (Scheme 70).84 When the epoxide contains a remote alkenic functionality, intra- molecular cyclisations are observed.Epoxide Product Yield (%) L P h 41 (R = Ts) 94 (cis :trans = 1:l) Scheme 70 The direct conversion of epoxides to a-hydroxy- acids is accomplished by a copper-mediated hydrolytic oxidative ring opening (Scheme 71).85 The reaction is only synthetically useful when the substrates are perfluorinated. HO R =- )-C02H HN03. Cu metal R ~ ~~~ R Reaction conditions Yield (Yo) i.LDA or LHMDS ii. Et$CI c R' R'CH,CO,Bu' 1246% yield syn:anti = 955 to 56:44 Scheme 72 14% ee Scheme 73 NaOH f Ky ~ nucleophile 85% yield F3C Nucleophile Y Yield (%) ee ("A) NaN3 N3 65 96 NaCN CN 65 96 LiAIH4 H 70 96 C5H1 ,M!m C5Hll 75 96 PhH, AICIs Ph 72 96 Scheme 74 84 Tetracyanoethylene (TCNE) catalyses the F3C Me 12% HN03 (5 eq.), Cu (3%), 80 "C 15 C 6 H ~ 37% HN03 (5 eq.), Cu (3%), room temp. 2 60% HN03 (5 eq.), Cu (a0/,)), 80 "C alcoholysis of trisubstituted epoxides (Scheme 75).R8 The reaction is highly regioselective, with nucleo- philic attack occurring at the more substituted carbon atom, and yields of ring-opened products are high for attack by primary alcohols. Disubstituted F,C6 35% HN03 (5 eq.), Cu (3%), 80 "C 93 Scheme 71 Lithium enolates react with epoxides in the presence of Lewis acid to give b-hydroxy esters in moderate yield (Scheme 72 and 73).*' The reaction exhibits only moderate stereoselectivity (and, in the cases of the menthyl esters, virtually no diastereoselectivity), but these data represent the first stereoselective epoxide opening by ester enolates.(S)-Trifluoromethyloxirane may be prepared in 96% ee via (-)-DIP chloride mediated reduction of trifluoromethyl bromomethyl ketone. The ring opening reactions of trifluoromethyloxirane have been studied in detail by the same workers (Scheme 74)? R TCNE eq. Yield (%) Me 0.1 ally1 0.1 prop-2-ynyl 0.1 Pr' 0.2 Bn 0.2 97 95 91 61 71 Scheme 75 82 Contemporary Organic Synthesisand terminal epoxides do not undergo selective alcoholysis under the conditions.The mechanism of the process is unproven, but is postulated to involve SET. The reactions of 2,3-epoxytosylates have caused some controversy during the period covered by this review. The ring opening of 2,3-epoxytosylates by halide ions in acetonitrile in the presence of Amberlyst 15 resin is highly regio- and diastereo- selective (Scheme 76).x9 No epoxide was obtained despite what might be expected. These authors reported that it is not possible to reduce 2,3-epoxytosylates to alcohols as the former are easily over-reduced; but Chong and Johannsen have clearly shown that this is not the case by exposing such epoxytosylates to up to eight equivalents of DIBAL to give (after work-up) 2-hydroxytosylates in excellent yield (Scheme 77).90 The nature of the solvent employed in the reaction was important: only in dichloromethane and ether was the reaction feasible.Use of THF gave only starting materials (returned in greater than 95% yield) and hexane solvents induced over-reduction to 2-alkanols. I Lii, MeCN Arnberlyst 15 - ' yoTs 99% yield OH OTs ?Ts 98% yield Lit, MeCN 00 Arnberlyst15 * Scheme 76 DIBAL (3 eq.) CHzCIz,-40"C * @ OH R2 R' R2 Yield (%) C10H21 H H H H Me Me C6H13 H H Ph Cl OH21 C6H13 c-C6H11 96 96 94 96 98 96 03 91 Scheme 77 A variant of the Wharton rearrangement allows for a highly stereoselective alkylative elimination of tosylhydrazones derived from homochiral a,P-epoxy aldehydes (Scheme 78). Thus, hydrazones 41 react with Grignard reagents to give diazo anions 42 as intermediates. These species lose diatomic nitrogen Rl&\N,#Ts 0 R2hAgBr (3 eq.) 0 "C, Et20, 30 mn 41 Epoxyhydrazone R2 Yield of allylic alcohol ("A) 68 66 58 0 Bu 65 Et 67 BnO Ph 70 H *? \ NTs N' Bu Et BU Bu Ph H 65 62 71 62 60 Scheme 78 with concomitant epoxide ring cleavage to give (E)- allylic alcohols in acceptable yields." Imines 43 derived from a,p-epoxyaldehydes and N-amino-1-phenylaziridine undergo thermal fragmentation to give x-hydroxy methylene carbenes 44, which insert into a C-H bond five atoms distant to give cyclopent-s-enols in moderate to good yield (Scheme 79).92 The authors demonstrated that the 43 I 45 Scheme 79 OH 44 1 OH 68% yield OH Ph 44% yield Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 83C-H insertion process is not homolytic by examining the reaction of stannylepoxide 45.Had the insertion been homolytic, one would (the authors suggest) have expected to see a preferential C-Sn insertion: this reaction was not observed. 1.4 Alcohol synthesis via biotransformations An oxidoreductase from Geotrichum candidum effects highly diastereo- and enantio-selective reduction of ethyl 2-methyl ketobutyrate (Scheme solution) was incubated with substrate in the Thus, the isolated enzyme (as a 10% glycerol The previously known” enantioselective hydrolysis of cyclohexene oxide by Corynosporium cassiicola has been re-investigated in depth.96 The authors found that racemic diol46 and meso-diol47 could be converted into the same single enantiomer 48 of trans-cyclohexane-l,2-diol with very high enantiomeric purity.This, along with similar findings using other diols, suggests that C. cassiicola contains two or more dehydrogenase enzymes which operate a tandem oxidation-reduction transformation (Scheme 82). presence of glucose, using GDH to regenerate NADPH. anti-Ethyl-(2S,3S)-2-methyl-3-hydroxy- 5 days butanoate was isolated in 69% yield with >99% de OH 50% yield and 94% ee after 48 h. (i)-46 48, >99%ee 47 0 0 OH 0 69% yield * y o E t >99%de >94% 88 oxidoreductase, GDH Scheme 80 Two features of Geotrichum candidum-mediated reductions of carbonyl compounds have been exploited to allow for improvement to the enantioselectivity of such biotransformations (Scheme 81).94 Thus, immobilisation of the microorganism upon a water-absorbent polymeric support and addition of alcohols to the reaction mixture leads to high levels of enantioselection in reductions of arylmethyl ketones.The r6le of the alcoholic component is to improve recycling of NAD’ by inducing activity of the glycerol dehydrogenase present in the cell. immobilized Geofdrhum candidum Ho Ar k hexan-2-oVhexane * Ar Absolute Ar Additive Yield (%) ee (“A) configuration none 52 propan-2-01 29 cyclopentanol 58 hexan-2-d 73 hexan-2-d 38 hexan-2-d 81 hexan-2-d 99 hexan-2-d 81 hexan-2-d 41 hexan-2-d 59 hexan-2-01 60 hexan-2-d 40 28 >99 >99 >99 >99 89 >99 92 >99 >99 99 9a R S S S S S S S S S S S Scheme 81 dehydrogenase 2 reduction l a::::: dehydrogenase 1 oxidation of (R)-OH dehydrogenase 2 reduction 1 a:: Scheme 82 A one-pot sequence of three sequential asymmetric aldol reactions involving three equivalents of a chiral aldehyde component is carried out by the enzyme 2-deolryribose- 5-phosphate aldolase (DERA).The general reaction is shown in Scheme When three equivalents of acetaldehyde and one equivalent of a substituted acetaldehyde are employed in the reaction, substitute pyranosides may be obtained from the reaction (Scheme 84). The products of these reactions are useful synthons for analogues of HMG-CoA reductase inhibitors. Since DERA has been overexpressed in E. coli, large quantities of this enzyme are available, thereby making the transformation of considerable synthetic utility. The interest in bacterial hydroxylation reactions has continued unabated. The reaction of 1,4-disubstituted aromatics in the presence of strains 84 Contemporary Organic Synthesisx] CHsCHO;DERA_ OH OH - H I CHGHO; E R A 20% yield I I kH I VoH Scheme 03 ‘)-H + 3 eq.Scheme 84 H 20 OH <3 OMe 65 CI 70 Br - N3 23 OH R Yield (“A) off? Putida is tuneable, with different strains having different substrate preferences, thus allowing preparation of both enantiomers of benzenoid cis- 1,2-diols (Scheme 85). para-Dihalobenzenes and para-iodotoluene react in the presence of mutant UV4 to give cis-diols of opposite configuration to those usually obtained from the wild-type oxidation, although the enantioexcesses of these diols is inferior to that normally observed in the ‘natural’ oxidation. Hydrogenolysis of the C-I bond furnishes diols which may then be exposed to wild-type NCIMB8859: this organism selectively oxidises the ‘natural’ cis-diols, thereby leading to an enantiomeric enrichment of the ‘unnatural’ antipode.Other wild-type and mutant strains of P Putida were examined by the authors and found to cis-hydroxylate naphthoquinones, indenes and homologues with variable enantiocontrol (35 to >98% ee).98 An isolated P-ketoester reductase from Baker’s yeast allows introduction of multiple asymmetry, via an enantioselective reduction and a dynamic kinetic res01ution.~~ Thus, when racemic ketoesters 49, in which the ester component contains an a-asymmetric centre, are reacted with reductase L-enzyme-1”) in the presence of NADPH (regenerated using the G6P couple) one diastereoisomer of 49 is reduced to give enantio- merically pure (>99% ee) stereotriad 50.The W4 mutant I X = Me, Br, CI 6H 1548%- OH P. Pulida wild type NClMB 8850 0lH OH 30% yield 98% ee Scheme 85 unreacted diastereoisomers undergo epimerisation at the acidic C-H position under the reaction conditions, but the configuration of the stereocentre of the pendant ester moiety remains intact (Scheme 86). Double reduction of 2-benzylidenecyclohexanone has recently been shown to be highly selective 49 L-Enzyme-1 MOPS0 buffer pH 7.0,30 OC, 18 h I GGPIGGPDH couple 51 50 Yield of 51 (“A) Yield of 50 (“A) R (-) (”/I (ee) (%) de of 50 (%) C6Hll 64 (32) 34 (>99) 66 Ph 9 (68) 48 (>99) 74 4-CI-CGH4 69 (36) 31 (>99) 77 4-Me-C& 56 (58) 44 (>99) 75 4-NOz-C& 9 (35) 41 (>99) 80 2-CCCeH4 64 (39) 36 (>99) 70 Scheme 86 Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 850 LiAIH4 U M F , reflux U 76% yield Scheme 87 (Scheme 87).'" When the same enone is subjected to reductive biotransformation (on a 50 g scale), the reaction exhibits variable levels of stereocontrol (Scheme 88).Io2 Thus, under typical conditions, 1,2- and 1,4-reduced products are obtained in roughly equal amounts. When forcing conditions (twice the amount of yeast) are employed, double reduction is observed but the reaction is poorly diastereoselective.Ph Baker's yeast 85% yield I 1 : 1.5 : trace : trace - E L 1 Baker's yeast : 2 'forcing conditions' 80% yield Scheme 88 Both enantiomers of 3-hydroxypyrrolidin-2-one are accessible via lactate dehydrogenase (LDH) reduction of N-protected 4-amino-2-keto- carboxylates (Scheme 89).lo3 1.5 Miscellaneous methods for alcohol synthesis Capitalising upon the fact that oxazolidinones are good leaving groups, the N-benzoyloxazolidinone 52 derived from tert-leucinol acts as an asymmetric benzoyl transfer reagent upon reaction with secondary alcohols.IM Racemic aryl alkyl carbinols react, in large excess (10 equivalents), with 52 in the presence of methyl magnesium bromide to give (I?)- benzoates.Lack of an aryl group in the alcohol leads to poor enantioexcess. Halophenols are easily exhaustively hydrogenated to the corresponding dehalogenated cyclohexanols upon reaction with Raney nickel-aluminium alloy in saturated barium hydroxide solution. The reduction is independent of the number of halogen atoms Scheme 89 Ph "y 52 H ~ ~~ ~~~ ~ Halophenol Product X R &(OH), (ml) Ni-AI alloy (9) YieM ("A) ~~~~~~~ ~ 3Br H 60 4-Br H 60 2.4-Br H 60 2,4,6-Br3 H 55 3CI-2,4.6-Br3 H 130 2,3,4,6-Br4 H 130 2,4,6-CI, H 50 2,3,4.6-C14 H 50 2,3,4,5,6-C15 H 100 2,4,BCI3 3-Me 20 2,6-C12 4-Me 50 8 54 9 74 10 65 12 42 16.5 62 16.5 52 8.3 65 8.3 62 12.0 91 8.0 30 cis, 45 m s 20.0 45 cis, 49 trans Scheme 90 present, but chlorophenols are reduced more easily than bromophenols (Scheme 90).'05 Lautens and Delanghe have reported in detail their studies on the cyclopropanation of a-allenic alcohols.Io6 Following a thorough screening of a wide range of cyclopropanation protocols, the samarium metal-chloroiodomethane combination was shown to deliver the best diastereoselectivity (Scheme 91).86 Contemporaiy Organic SynthesisRe'@-?- OH Sm (low.) CICH21 (10 q.) THF, -78 "C -+ room temp. I &+&' + J - + c 6 H I l OH OH 9 1 82% yield Scheme 91 A highly stereoefficient asymmetric Simmons- Smith cyclopropanation of allylic alcohols using the boronate 53 derived from (+)-N,N,","- tetramethyl tartaric acid diamide has been reported.Thus, at room temperature, allylic alcohols are cyclopropanated in 91-94% ee by Zn(CH21)2 in the presence of stoichiometric amounts of 53 (Scheme 92). lo' 53 (l.leq.), Zn(CH,J), OH Rw CH,CI,,25 "C, 2 h Me,N(O)Ch CONMe, I Bu 53 R Yield (%) ee (%) Ph >98 93 Pr 80 93 (Z)-Et 90 93 (Z)-TBDMSOCH, 80 91 Scheme 92 Dianions derived from (2-hydroxy)ethylphenyl sulfone may be dialkylated efficiently to give cx-disubstituted hydroxy sulfones 54.These products may be cyclised via iodetherification to give substituted iodomethyl tetrahydrofuranyl sulfones 55 which may in turn be converted by double elimination to 2,4-disubstituted furans (Scheme 93).Io* Yields of the overall process are good. Alkylidenephosphoranes undergo an insertion reaction with 1,2-dioxetanes to give phosphorinanes in quantitative yield.'" These species may be converted to the monoethers of 1,2-diols 56 or to 2-oxyvinylalcohols (Scheme 94). An asymmetric Meisenheimer rearrangement allows the asymmetric preparation of allylic alcohols of high ee (Scheme 95).'" Thus, C-2 symmetric pyrrolidine 58 is converted into a range of allylic tertiary amines and oxidised to the N-oxide, which undergoes asymmetric [2,3]-rearrangement to give PhS02 R'Br, THF, PhSO2 LoLi -70 "C + room temp; R2&Br , THF, -40 "C Li OH 54 NaHC03,12 room temp., 1 h THFIH20 (21) 1 BU'OK, THF, o oc t'- A 7589% yield Scheme 93 quantitative NaOH, MeOWHfl; PhCHO 57 56 Scheme 94 hydroxylamines 59 in good yield and mediocre de (62-73%).These compounds were purified by HPLC and converted to allylic alcohols 60 of ~ 9 3 % ee. 2 Preparation of ethers and phenols A review has appeared delineating the use of a-haloethers in preparation of ethers."' Jacobsen and Larrow have observed a kinetic resolution in effect during the authors' previously well-documented Mn-salen catalysed asymmetric epoxidation process (Scheme 96).Il2 The authors observed that the ee of the product of asymmetric epoxidation of 1,2-dihydronaphthalene increased with reaction time, at the expense of yield.Surmising that there was a secondary kinetic resolution process in effect, they exposed racemic 1 -2-dihydronaphthalene oxide to the system utilised in asymmetric epoxidation, whereupon they observed a benzylic oxidation reaction; the enantiomer which reacted slower was that corresponding to the major product from the Hau, Jawis and Sweeney: Alcohols, ethers and phenols 870% OMe I 58 OH HPLC; mCPBA; [2,3]-rearrangement I 60 >93% 88 59 ~~ ~ R ee of 60 (%) Configuration Me 95.2 R Et 91.5 R P f 96.3 R P i 96.0 R But 93.1 S Scheme 95 93 : 7 Ph Ph -'.a- X catalyst62 fast 'I 86% ee 98% ee 53% yield Scheme 97 pseudo-axial hydrogen atom leads to a pseudo-axial hydroxy group. This was confirmed when epoxides having little energetic difference between pseudo- axial and pseudo-equatorial C-Hs were shown to react with poor diastereoselectivity. An umpolung may be exploited to allow the efficient preparation of 2-aryloxyphenols by means of a two-step analogue of the Ullman alkylated in high yield by phenols to give tht: corresponding 2'-formylbiphenylethers which undergo Baeyer-Villiger reaction to give the aforementioned aryloxyphenols (Scheme 98).Thus, 2-fluorobenzaldehyde is CHO I mCPBA, CH2C12 OCHO room temp., 1 h R But' \ But (R,R)-61, X=OMe (R ,R )-a, X = Bu' Scheme 98 Scheme 96 epoxidation of 1,2-dihydronaphthalene, while the enantiomer which is the minor product of epoxidation was rapidly oxidised to syn-epoxy alcohol. Thus the authors devised a one-pot, two- catalyst system to allow rapid epoxidation and subsequent rapid C-H oxidation to take place (Scheme 97).The mechanism does not involve an epoxide-directed C-H insertion reaction, as might naively be expected, but rather a stepwise radical process in which preferential abstraction of a R Yield (%) H 96 CI 89 Br 90 But 87 OMe 79 OPh 85 Radical cyclisation of the 3-hydroxybutyrate- derived oxygen-tethered a$-unsaturated ester 63 gives cis-2,5-disubstituted tetrahydrofuran-3-ones with high syn-selectivity (Scheme 99). Slow addition (syringe pump) is vital, and so the reaction may be less feasible on a large aromatisation of 2-alkylthiocyclohexanones in the presence of molecular bromine (Scheme a,a-Difluoroethers and acetals formally derived from carbonyl difluoride may be prepared by fluorinative desulfonylation of thioesters and 0-Alkylthiophenols may be prepared by 88 Contemporary Organic SynthesisYYo 0 SePh k O & k ___) 63 Reaction conditions syn :anti Yield (%) Ph3SnH.AIBN, A, 3 h 88:12 82 Ph3SnH, EtJ3, air, rt, 96 h 2955 63 Bu3SnH, AIBN, A, 2.5 h 8515 94 Ph3SnH. Et36, air, A, 4 h 94:6 97 Scheme 99 812 - R Yield (%) Scheme 100 R' R2 Yield (%) Me Bu 37 Me 4-biphenyl 74 Et 4-biphenyl 77 Ph El 43 Ph Bn 76 Ph Ph 76 Scheme 101 thiocarbonates respectively (Scheme l O l ) . ' l6 Tetrabutylammonium perfluoride is the reagent which allows these transformations to be realised. Rozen's method' l 7 allows preparation of %,a-difluoroethers from thioesters, but uses the more exotic BrF,. 3 References 1 D. A. Evans, M. J. Dart and J.L. Duffy, Tetrahedron 2 D. A. Evans, M. J. Dart and J. L. Duffy, Tetrahedron Lett., 1994, 35, 8537. Lett., 1994, 35, 8537. 3 T. J. Leitereg and D. J. Cram, J. Am Chem. SOC., 1968,90,4011. 4 C. Copkrat, E. Negishi, Z. Xi and T. Takahashi, Tetrahedron Lett., 1994,35, 695. 5 T. Luker and R. J. Whitby, Tetrahedron Lett., 1994, 35, 785. 6 M. Chiro, T. Matsumoto and K. Suzuki, Synlett, 1994, 359. 7 N. Auner, J. Grobe and R. Damrauer, J. Organomet. Chem., 1980, 188, 25; N. S. Namekin, N. V. Ushakov and M. V. Vdovin, Zh. Obshch. Khim., 1974,44, 1970; P. Jutzi and P. Langer, J. Organornet. Chem., 1977, 132, 45. 8 S. E. Denmark, B. D. Griedel, D. M. Coe and M. E. Schnuti, J. Am. Chem. SOC., 1994, 116, 7026. 9 E. M. Carriera, R. A. Singer and W. Lee, J. Am. Chem. SOC., 1994, 116, 8837.10 H. Nitta, D. Yu, M. Kudo and A. Mori, J. Am. Chem. SOC., 1992, 114, 7969. M. Hayashi, Y. Miyamoto, T. Inoue and N. Ogumi, J. 0%. Chem., 1993,58, 1515. 11 B. R. Lago, H. M. Crane and D. C. Liotta, J. 0%. Chem., 1993, 58,4191. 12 S. Tsuboi, H. Kuroda, S. Takatsuka, T. Fukawa, T. Sakai and M. Utaka, J. 0%. Chem., 1993,58,5952. 13 M. K. Kundu, S. B. Mukherjee, N. Balu, R. Padmakumar and S. V. Bhat, Synlett, 1994,444. 14 A. Yanagisawa, H. Inone, M. Morodome and H. Yamamoto, J. Am. Chem. SOC., 1993, 115, 10 356. 15 J. Synoniak, D. Felix and C. Moi'se, Tetrahedron Lett., 1994,35, 8617. 16 S. Kobayashi and K. Nishio, Synthesis, 1994,457. 17 J. M. Clayden and M. Julia, J. Chem. SOC., Chem. Commun., 1994, 2261. 18 H. C. Aspinall, A. F. Browning, N. Greeves and P.Ravenscroft, Tetrahedron Lett., 1994, 35, 4639. 19 Y. Hashimoto, H. Kagoshima and K. Saigo, Tetrahedron Lett., 1994, 35, 4805. 20 R. Sjoholm, R. Rairama and M. Ahonen, J. Chem. SOC., Chem. Commun., 1994, 1217. 21 J.-F. Normant,J. Organomet. Chem., 1990, 400, 19. 22 R. N. Haszeldine, J. Chem. SOC., 1954, 1273. 23 F. Hong, X. Tang and C. Hu, J. Chem. SOC., Chem. Commun., 1994,289. 24 A. Guijario and M. Yus, Tetrahedron, 1994, 51, 13 269. 25 J. J. Harnett, L. Alcarez, C. Miokowski, J. P. Martel, T. Le Gall, D.-S. Shin and J. R. Falck, Tetrahedron Lett., 1994, 35, 2009. 26 A. L. Costa, M. G. Piazza, E. Tagliavini, C. Trombini and A. Umani-Ronchi, J. Am. Chem. SOC., 1993,115, 7001. Chem. SOC., 1993, 115, 8467. Tetrahedron Lett., 1994,35, 8323. Chem. SOC., 1994, 116, 8536.Commun., 1994, 285. Commun., 1994, 283. 27 G. E. Keck, T. H. Tarbet and L. S. Cieraci, J. Am. 28 G. E. Keck, D. Krishnamurthy and X. Chen, 29 W. R. Roush and M. S. van Nieuwenhze, J. Am. 30 S. J. Stanway and E. J. Thomas, J. Chem. SOC., Chem 31 J. S. Carey and E. J. Thomas, J. Chem. SOC., Chem. 32 A. H. McNeill and E. J. Thomas, Synthesis, 1994, 322, 33 T. Akiyama, T. Yasusa, K. Ishikawa and S. Ozaki, 34 J. D. Buynak, B. Geng, S. Uang and J. B. Strickland, 35 K. Soai and K. Takahashi, J. Chem. SOC., Perkin Trans. 36 M. Watanabe and K. Soai, J. Chem. SOC., Perkin Tetrahedron Lett., 1994, 35, 8401. Tetrahedron Lett., 1994, 35, 985. I , 1994, 1257. Trans. I , 1994, 3125. Hau, Jawis and Sweeney: Alcohols, ethers and phenols 8937 0. G. Kulinkovich, V.L. Sorokin and A. V. Kelin, Zh. 0%. Khim., 1993, 29, 66. 38 K. Takeda, S. A. Rao and M. C. Noe, J. Am. Chem. SOC., 1994, 116, 9345. 39 K. Takeda, J. Nakatani, H. Nakamura, K. Sako, E. Yoshi and K. Yamaguchi, Synlett, 1993, 841. 40 K. Takeda, M. Fujisawa, T. Makino and E. Yoshii, J. Am. Chem. SOC., 1993, 115, 9351. 41 K. Kobayashi, M. Kawakita, T. Mannami and H. Konishi, Tetrahedron Lett., 1995, 36, 733. 42 P. Delair, C. Einhorn, J. Einhorn and J. L. Luche, J. Org. Chem., 1994, 59, 4680. 43 A. S. Demir, C. Tanyeli, A. S. Mahawneh and H. Aksoy, Synthesis, 1994, 155. 44 A. W. Konradi, S. J. Kemp and S. F. Pedersen, J. Am. Chem. SOC., 1994,116, 1317. 45 T. Shono, Y. Morishima, N. Moriyoshi and M. Ishifume, J. 0%. Chem., 1994, 59, 273. 46 M. B. Carter, B. Schifltt, A.GutiCrrez and S. L. Buchwald, J. Am. Chem. SOC., 1994,116, 11 667. 47 J. W. Lauher and R. Hoffman, J. Am. Chem. SOC., 1976,98, 1729. 48 S. W. Breedon and N. J. Lawrence, Synlett, 1994, 833. 49 M. Hojo, A. Fujii, C. Murakami, H. Aihara and A. Hosomi, Tetrahedron Lett., 1995, 36, 571. 50 G. A. Molander and K. L. Bobbitt, J. Am. Chem. SOC., 1993,115, 7517. 51 D. A. Evans, S. G. Nelson, M. R. GagnC and A. R. Muci, J. Am. Chem. SOC., 1993, 115, 9800. 52 Y. H. Kim, D. H. Park and I. S. Bynn, J. 0%. Chem., 1993, 58, 511. 53 T. Ohkuma, S. Hashiguchi and R. Noroyi, J. 0%. Chem., 1994,59,217. 54 B. Figadere, C. Chaboche, X. Franck, J.-F. Peyrat and A. CavC, J. 0%. Chem., 1994,59, 7138. 55 S. K. Kang, D. C. Park, D. G. Cho, J. U. Chung and K. Y. Jung, J. Chem. SOC., Perkin Trans.I , 1994, 237. 56 C. Dariel, S. Bartoch, C. Bruneau and P. H. Dixneuf, Synlett, 1994, 457. 57 A. Togni, C. Breutel, A. Schnyder, F. Spindler, H. Landert and A. Tijani, J. Am. Chem. SOC., 1994, 116, 4062. Chem., 1993,58,5307. Tetrahedron Lett., 1995, 36, 351. 58 D. A. Evans, A. R. Muci and R. Sturmer, J. 0%. 59 D. F. Taber, L. Yet and R. S. Bhamidipati, 60 W. Adam and P. Klug, Synlett, 1994, 567. 61 H. C. Kolb, M. S. van Nieuwenhze and K. B. Sharpless, Chem. Rev., 1994,94, 2483. 62 D. J. Berrisford, C. Bolm and K. B. Sharpless,Angew. Chem., Int. Ed. Engl., 1995, 34, 1059. 63 K. J. Hale, S. Mahaviazar and S. A. Peak, Tetrahedron Lett., 1994, 35,425. 64 S. Takano, T. Yoshimitsu and K. Ogasawara, J. 0%. Chem., 1994,59,54; 1995, 60, 1478. 65 T. Yoshimitou and K.Ogasawara, Synlett, 1995,257. 66 K. Morikawa, J. Park. P. G. Anderson, T. Hashiyana and K. B. Sharpless, J. Am. Chem. SOC., 1993, 115, 8463. 67 K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. S. Hartung, K.-S. Jeong, H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu and X.-L. Zhang, J. 0%. Chem., 1992,57,2768. 68 G. A. Crispino, K. S. Jeong, H. C. Kolb, Z. M. Wang, D. Xu and K. B. Sharpless, J. 0%. Chem., 1993,543, 3785. Tetrahedron Lett., 1994, 35, 843. Sharpless, Tetrahedron Lett., 1994, 35, 3469. 69 M. S. van Nieuwenhze and K. B. Sharpless, 70 K. P. M. Vanhessche, Z. M. Wang and K. B. 71 I. Henderson, K. B. Sharpless and C. H. Wong, J. Am. Chem. SOC., 1994,116,559. 72 P. J. Walsh, P. T. King, S. B. King and K. B. Sharpless, Tetrahedron Lett., 1994,35, 5 129.73 H. C. Kolb, P. G. Anderson, Y. L. Bennani, G. A. Crispino, K. S. Jeong, H. L. Kwong and K. B. Sharpless, J. Am. Chem. SOC., 1993, 115, 12 226; T. Gobel and K. B. Sharpless, Angew. Chem., Znt. Ed. Engl., 1993,43, 1329; D. V. McGrath, G. D. Brabson, K. B. Sharpless and L. Andrews, Inoq. Chem., 1993, 32,4164; H. C. Kolb, P. G. Anderson and K. B. Sharpless, J. Am. Chem. SOC., 1994, 116, 1278; P. 0. Norrby, H. C. Kolb and K. B. Sharpless, Organometallics, 1994, 13, 344. 74 H. Becker, M. A. Soler and K. B. Sharpless, Tetrahedron, 1995, 51, 1345. 75 Z.-M. Wang and K. B. Sharpless, J. 0%. Chem., 1994, 59, 8302. 76 M. Chini, P. Crotti, L. Favero, F. Macchia and M. Pineschi, Tetrahedron Lett., 1994,35,433. 77 Y. Yamamoto, N. Asao, M. Meguro, M. Tsukada, H.Nemoto, N. Sayadori, J. G. Wilson and H. Nakamura, J. Chem. SOC., Chem. Commun., 1993, 1201. 78 M. Chini, P. Crotti, L. Favero and F. Macchia, Tetrahedron Lett., 1994, 35, 761. 79 R. R. Schrock, Acc. Chem. Res., 1991,23, 1580. 80 W. H. Leung, E. K. F. Chow, M. C. Wu, P. W. K. Kum and L. L. Yeung, Tetrahedron Lett., 1995, 36,107. 81 L. E. Martinez, J. L. Leighton, D. H. Carsten and E. N. Jacobsen, J. Am. Chem. SOC., 1995, 117,5897. 82 M. Brunner, L. Mussmann and D. Vogt, Synlett, 1994, 69. 83 D. Albanese, D. Landini and M. Penso, Synthesis, 1994, 34. 84 T. V. Rajan Babu and W. A. Nugent, J. Am. Chem. SOC., 1994, 116, 987. 85 T. Katagiri, F. Obara, S. Toda and K. Furahashi, Synlett, 1994, 507. 86 S. K. Taylor, J. A. Fried, Y. N. Grassl, A. E. Marelewski, E. A. Pelton, T.-J. Poel, D. S. Rezanka and M. R. Whittaker, J. 0%. Chem., 1994,59, 7304. 87 P. V. Ramachandran, B. Gong and H. C. Brown, J. 0%. Chem., 1995, 60, 41. 88 Y. Masaki, T. Miura and M. 0. Chiai, Synlett, 1993, 847. 89 C. Bonini, L. Chiammiento and M. Funicello, Tetrahedron Lett., 1994,35, 797. 90 J. M. Chon and J. Johannsen, Tetrahedron Lett., 1994, 35, 7 3 7 . 91 S. Chandrasekhar, M. Takhi and J. S. Yadav, Tetrahedron Lett., 1995, 36, 307. 92 S. Kim and C. M. Cho, Tetrahedron Lett., 1994,35, 8405. 93 Y. Kawai, K. Tananobe, M. Tsujimoto and A. Ohno, Tetrahedron Lett., 1994, 35, 147. 94 K. Nakamura, Y. Inoue and A. Ohno, Tetrahedron Lett., 1995,36, 265. 96 A. J. Carnell, G. Iacazio, S. M. Roberts and A. J. Willetts, Tetrahedron Lett., 1994, 35, 331. 97 H. J. M. Gijsen and C.-H. Wong, J. Am. Chem. SOC., 1994,116, 8422. 98 C. C. R. Allen, D. R. Boyd, H. Dalton, N. D. Sharma, I. Brannigan, N. A. Kerly, G. N. Sheldrake and S. C. Taylor, J. Chem. SOC., Chem. Commun., 1995, 117. Tetrahedron Lett., 1995, 36, 591. 100 K. Nakamura, Y. Kawai, N. Nakajima and A. Ohno, J. 0%. Chem., 1991,56,4778; K. Nakamura, Y. Kawai, T. Miyai, S. Honda, N. Nakajima and A. Ohno, Bull. Chem. SOC. Jpn., 1991, 64, 1467. 99 Y. Kawai, K. Hida, K. Nakamura and A. Ohno, 90 Contemporary Organic Synthesis101 K. Koch and J. H. Smitrovich, Tetrahedron Lett., 1994, 35, 1137. 102 G. Fronza, G. Fogliato, C. Fuganti, S. Lanati, R. Rallo and S. Servi, Tetrahedron Lett., 1995, 36, 123. 103 J. M. Bentley, H. J. Wadsworth and C. L. Willis, J. Chem. SOC., Chem. Commun., 1995,231. 104 D. A. Evans, J. C. Anderson and M. K. Taylor, Tetrahedron Lett., 1993, 34, 5563. 105 T. Tsukinoki, T. Kakinami, Y. Iida, M. Ueno, T. Mashimo, H. Tsuzuki and M. Tashiro, J. Chem. SOC., Chem. Commun., 1995, 209. 106 M. Lautens and P. H. M. Delanghe, J. Am. Chem. SOC., 1994, 116, 8526. J. Org. Chem., 1993, 58, 5037 107 A. B. Charette and H. Juteau, J. Am. Chem. SOC., 1994, 116, 2651. 108 J. H. Jung, J. W. Lee and D. Y. Oh, Tetrahedron Lett., 1995, 36, 923. 109 W. Adam, H. M. Harrer and A. Treiber, J. Am. Chem. SOC., 1994, 116, 7581. 110 D. Enders and H. Kempen, Synlett, 1994, 969. 11 1 T. Benneche, Synthesis, 1995, 1. 112 J. F. Larrow and E. N. Jacobsen, J. Am. Chem. SOC., 113 G. W. Yeager and D. N. Schissel, Synthesis, 1995, 28. 114 P. A. Evans and J. D. Roseman, Tetrahedron Lett., 115 V. V. Samashin and K. V. Kudrayavtser, Tetrahedron 116 M. Kuorboshi and T. Hiyama, Synlett, 1994, 251. 117 S. Rozen and E. Mishani, J. Chem. Soc., Chem. 1994, 16, 12 129. 1995,36, 31. Lett., 1994, 35, 7413. Commun., 1993, 1761. Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 91

ISSN:1350-4894    

DOI:10.1039/CO9960300065

出版商:RSC    

年代:1996

数据来源: RSC