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 (nek 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, Universiti de Montrial Professor M. Julia, Universiti de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, 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 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, and environment, and new materials, will also be encompassed.Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field. Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be submitted to the Senior Editor (Reviews), Books and Reviews Department, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF.Members of the Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way. All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 lHN, England. 1995 subscription rate: EEA 2165, USA $303, Canada 2173 (plus GST), Rest of the World 2173. Air freight and mailing in the USA by Publications Expediting Inc., 200 Meacham Avenue, Elmont 1103; USA Postmaster, send address changes to Contemporary Organic Synthesis, Publications Expediting Inc. Second class postage is paid at Jamaica, New York 11431. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe.0 The Royal Society of Chemistry, 1995 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording, or otherwise, without the prior permission of the publishers. Typeset by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho LtdContemporary Organic Synthesis Editorial Board Professor G. Pattenden, FRS (Chairman), University of Nottingham Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nek 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, Universitk de Montrkal Professor M. Julia, Universitk 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, and environment, and new materials, will also be encompassed. Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field.Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be submitted to the Senior Editor (Reviews), Books and Reviews Department, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF. Members of the Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way. All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 lHN, England. 1995 subscription rate: EEA 2165, USA $303, Canada 2173 (plus GST), Rest of the World 2173. Air freight and mailing in the USA by Publications Expediting Inc., 200 Meacham Avenue, Elmont 1103; USA Postmaster, send address changes to Contemporary Organic Synthesis, Publications Expediting Inc. Second class postage is paid at Jamaica, New York 11431. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. 0 The Royal Society of Chemistry, 1995 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording, or otherwise, without the prior permission of the publishers. Typeset by Unicus Graphics Ltd Printed in Great Britain by Whitstable Litho Ltd

ISSN:1350-4894    

DOI:10.1039/CO99502FX005

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

EUCHEM Conference on Tycloadditions and Related Reactions: Theory and Practice” Vulcano Island, Italy, 21-24 June, 1995 Address for Correspondence: Prof. Mario Gattuso - Universith di Messina Dpt di Chimica Organica e Biologica - Salita Spemne 31, S. Agata 98166 MESSINA, Italy - FAX +39 90 392840EUCHEM Conference on Tycloadditions and Related Reactions: Theory and Practice” Vulcano Island, Italy, 21-24 June, 1995 Address for Correspondence: Prof. Mario Gattuso - Universith di Messina Dpt di Chimica Organica e Biologica - Salita Spemne 31, S. Agata 98166 MESSINA, Italy - FAX +39 90 392840

ISSN:1350-4894    

DOI:10.1039/CO99502BX007

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

ISSN 1350-4894 COGSE6 2 (2) 65-132 (1995) Contemporary Organic Synthesis A journal of cuwent developments in Organic Synthesis V O L U M E 2 N U M B E R 2 C O N T E N T S Catalytic applications of transition metals in organic synthesis By Christopher G. Frost and Jonathan M. J. Williams Reviewing the literature published between 1 September 1993 and 31 August 1994 65 I (87% e.e.) I OSiMe3 + PhN2B F4 O"C, 2h NHNHPh - RKC02Me NH RAb02Me 0 dMe Organic halides By Peter L. Spargo Reviewing the literature published between 1 July 1993 and 30 June 1994 Carboxylic acids and esters By T. Harrison and T. Laduwahetty Reviewing the literature published between 1 January 1993 and 31 July 1994 85 107 Hypervalent iodine in organic synthesis: a-functionalization of carbonyl compounds By Om Prakash, Neena Saini, Madan I? Tanwar, and M.Moriarty Reviewing the literature published up to February 1995 121Cumulative Contents of Volume 2 Number 1 1 Aromatic heterocycles as intermediates in natural product synthesis (up to the end of 1993) Michael Shipman 19 The hydrometallation, carbometallation, and metallometallation of heteroalkynes (up to August 1994) Sharon Casson and Philip Kocienski 35 Serotonin, sumatriptan, and the management of migraine Alexander Oxford 43 Stoichiometric organotransition metal complexes in organic synthesis (1 September 1993 to 31 August 1994) Julian Blagg Number 2 65 85 107 121 Catalytic applications of transition metals in organic synthesis ( 1 September 1993 to 31 August 1994) Christopher G. Frost and Jonathan M. J. Williams Organic halides ( 1 July 1993 to 30 June 1994) Peter L. Spargo Carboxylic acids and esters (1 January 1993 to 31 July 1994) T. Harrison and T. Laduwahetty Hypervalent iodine in organic synthesis: a-functionalization of carbonyl compounds (up to February 1995) Om Prakash, Neena Saini, Madan I? Tanwar, and M. Moriarty Articles that will appear in forthcoming issues include Ene-diynes D. Grierson Acylation and alkylation of aromatics and heteroaromatics H. Heaney Aldehydes and ketones I? Steel a-Cations of amino acids I? D. Bailey, A. N. Boa, and J. Clayson Saturated and unsaturated hydrocarbons R. I? C. Cousins Saturated nitrogen heterocycles T. Harrison Nitro and related nitrogen based functional groups G. M. Robertson Imines and related nitrogen based functional groups G. M. Robertson Synthesis and use of cyclic peroxides K McCullough Synthetic developments in host-guest chemistry Jeremy D. Kilburn

ISSN:1350-4894    

DOI:10.1039/CO99502FP009

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

128 G. Handke and N. Krause, Tetrahedron Lett., 1993,34, 129 C. Darcel, S. Bartsch, C. Bruneau and P.H. Dixeuf, 130 T. Moriya, N. Miyaura and A. Suzuki, Synlett, 1994, 131 H. Bienaym6, Tetrahedron Lett., 1994,35,7387. 132 Y.S. Lee, K.H. Nam, S.H. Jung and H. Park, 133 P. Rochet, J-M. Vatkle and J. Go&, Synthesis, 1994, 134 H-F. Chow, X-P. Cao and M. Leung, J. Chem. SOC., 135 F. Toda, K. Tanaka and H. Nawata, J. Chem. SOC., 136 B.J.L. Royles and D.M. Smith, J. Chem. SOC., Perkin 137 V. Ratovelomanana, Y. Rollin, C. GCbkhenne, 6037. Synlett, 1994, 457. 149. Synthesis, 1994, 792. 795. Chem. Commun., 1994,2121. Perkin Trans. 1, 1994, 2043. Trans. 1, 1994, 355. C. Gosmini and J. Perichon, Tetrahedron Lett., 1994, 35, 4777. 138 D. Grandjean, P. Pale and J. Chuche, Tetrahedron Lett., 1994,35, 3529.139 K. Kusuda, K. Kawamura, Y. Ueno and T. Toru, Tetrahedron Lett., 1993, 34, 6587. 140 K. Miwa, T. Aoyama and T. Shioiri, Synlett, 1994, 107. 141 G.G. Melikyan, R.C. Combs, J. Lamirand, M. Khan and K.M. Nicholas, Tetrahedron Lett., 1994, 35, 363. 142 K. Iida and M. Hirama, J. Am. Chem. SOC., 1994,116, 10310. 143 M. Yoshimatsu, H. Yamada, H. Shimizu and T. Kataoka, J. Chem. SOC., Chem. Commun., 1994, 2107. Lett., 1993, 34, 5403. Tetrahedron Lett., 1994,35, 7615. 5975. 59, 6877. SOC., Chem. Commun., 1994, 1845. 1829. 4738. 713. 144 M. Alami, F. Ferri and G. Linstrumelle, Tetrahedron 145 T. Mandai, Y. Tsujiguchi, S. Matsuoka and J. Tsuji, 146 S. Ikeda and Y. Sato, J. Am. Chem. SOC., 1994, 116, 147 S. Ikeda, D.-M. Cui and Y. Sato, J. 0 ~ .Chem., 1994, 148 C. Darcel, C. Bruneau and P.H. Dixeuf, J. Chem. 149 K.K. Wang and Z. Wang, Tetrahedron Lett., 1994,35, 150 Z. Wang and K.K. Wang, J. 0%. Chem., 1994,59, 151 M.E. Maier and D. Langenbacher, Synlett, 1994, 152 J. Isihara, N. Kanoh, A. Fukuzawa and A. Murai, 153 K.K. Wang, Z. Wang and Y.G. Gu, Tetrahedron Lett., 154 H. Hopf and M. Theurig,Angew. Chem., Znt. Ed. 155 M. Moniatte, M. Eckhardt, K. Brickmann, Chem. Lett., 1994, 1563. 1993,34,8391. Engl., 1994,33, 1099. R. Bruckner and J. Suffert, Tetrahedron Lett., 1994, 35, 1965. Tetrahedron Lett., 1994, 35, 5689. Tetrahedron Lett., 1994, 35, 5645. 50,5335. 156 M. Yamaguchi, K. Omata and M. Hirama, 157 C. Meyer, I. Marek, J-F. Normant and N. Platzer, 158 D. Chemin and G. Linstrumelle, Tetrahedron, 1994, 159 S.A.Hitchcock, S.H. Boyer, M.Y. Chu-Moyer, S.H. Olson and S. J. Danishefsky, Angew. Chem., Znt. Ed. Engl., 1994, 33, 858. 160 T. Brandstetter and M.E. Maier, Tetrahedron, 1994, 50, 1435. 161 H. Audrain, T. Skrydstrup, G. Ulibarri, C. Riche, A. Chiaroni and D.S. Grierson, Tetrahedron, 1994, 50, 1469. K.M. Pham, D.M. Vyas and M.D. Wittman, Tetrahedron, 1994, 50, 1519. 482. 35, 37. 35, 2655. Tetrahedron Lett., 1994,35, 7997. R.A. Fairhurst, J. Chem. SOC., Chem. Commun., 1994, 1543. Danishefsky, Angew. Chem., Znt. Ed. Engl., 1994,33, 2477. 169 M.D. Shair, T. Yoon and S.J. Danishefsky, J. 0%. Chem., 1994,59,3755. 170 M.F. Braiia, M. Moran, M.J.P. de Vega and I. Pita- Romero, Tetrahedron Lett., 1994,35, 8655. 171 K. Toshima, K. Yanagawa, K. Ohta, T. Kano and M.Nakata, Tetrahedron Lett., 1994, 35, 1573. 172 P. Magnus, Tetrahedron, 1994,50, 1397. 173 D. Elbaum, T.B. Nguyen, W.L. Jorgensen and S.L. 162 J.F. Kadow, D.J. Cook, T.W. Doyle, D.R. Langley, 163 T. Nishikawa, S. Shibuya and M. Isobe, Synlett, 1994, 164 J.M. Nuss and M.M. Murphy, Tetrahedron Lett., 1994, 165 R.S. Huber and G.B. Jones, Tetrahedron Lett., 1994, 166 T. Nishikawa, M. Yoshikai, K. Obi and M. Isobe, 167 P. Magnus, D. Parry, T. Iliadis, S.A. Eisenbeis and 168 M.D. Shair, T. Yoon, T-C. Chou and S.J. Schreiber, Tetrahedron, 1994,50, 1503. Cousins: Saturated and unsaturated hydrocarbons 461128 G. Handke and N. Krause, Tetrahedron Lett., 1993,34, 129 C. Darcel, S. Bartsch, C. Bruneau and P.H. Dixeuf, 130 T. Moriya, N. Miyaura and A. Suzuki, Synlett, 1994, 131 H.Bienaym6, Tetrahedron Lett., 1994,35,7387. 132 Y.S. Lee, K.H. Nam, S.H. Jung and H. Park, 133 P. Rochet, J-M. Vatkle and J. Go&, Synthesis, 1994, 134 H-F. Chow, X-P. Cao and M. Leung, J. Chem. SOC., 135 F. Toda, K. Tanaka and H. Nawata, J. Chem. SOC., 136 B.J.L. Royles and D.M. Smith, J. Chem. SOC., Perkin 137 V. Ratovelomanana, Y. Rollin, C. GCbkhenne, 6037. Synlett, 1994, 457. 149. Synthesis, 1994, 792. 795. Chem. Commun., 1994,2121. Perkin Trans. 1, 1994, 2043. Trans. 1, 1994, 355. C. Gosmini and J. Perichon, Tetrahedron Lett., 1994, 35, 4777. 138 D. Grandjean, P. Pale and J. Chuche, Tetrahedron Lett., 1994,35, 3529. 139 K. Kusuda, K. Kawamura, Y. Ueno and T. Toru, Tetrahedron Lett., 1993, 34, 6587. 140 K. Miwa, T. Aoyama and T. Shioiri, Synlett, 1994, 107.141 G.G. Melikyan, R.C. Combs, J. Lamirand, M. Khan and K.M. Nicholas, Tetrahedron Lett., 1994, 35, 363. 142 K. Iida and M. Hirama, J. Am. Chem. SOC., 1994,116, 10310. 143 M. Yoshimatsu, H. Yamada, H. Shimizu and T. Kataoka, J. Chem. SOC., Chem. Commun., 1994, 2107. Lett., 1993, 34, 5403. Tetrahedron Lett., 1994,35, 7615. 5975. 59, 6877. SOC., Chem. Commun., 1994, 1845. 1829. 4738. 713. 144 M. Alami, F. Ferri and G. Linstrumelle, Tetrahedron 145 T. Mandai, Y. Tsujiguchi, S. Matsuoka and J. Tsuji, 146 S. Ikeda and Y. Sato, J. Am. Chem. SOC., 1994, 116, 147 S. Ikeda, D.-M. Cui and Y. Sato, J. 0 ~ . Chem., 1994, 148 C. Darcel, C. Bruneau and P.H. Dixeuf, J. Chem. 149 K.K. Wang and Z. Wang, Tetrahedron Lett., 1994,35, 150 Z. Wang and K.K. Wang, J. 0%. Chem., 1994,59, 151 M.E.Maier and D. Langenbacher, Synlett, 1994, 152 J. Isihara, N. Kanoh, A. Fukuzawa and A. Murai, 153 K.K. Wang, Z. Wang and Y.G. Gu, Tetrahedron Lett., 154 H. Hopf and M. Theurig,Angew. Chem., Znt. Ed. 155 M. Moniatte, M. Eckhardt, K. Brickmann, Chem. Lett., 1994, 1563. 1993,34,8391. Engl., 1994,33, 1099. R. Bruckner and J. Suffert, Tetrahedron Lett., 1994, 35, 1965. Tetrahedron Lett., 1994, 35, 5689. Tetrahedron Lett., 1994, 35, 5645. 50,5335. 156 M. Yamaguchi, K. Omata and M. Hirama, 157 C. Meyer, I. Marek, J-F. Normant and N. Platzer, 158 D. Chemin and G. Linstrumelle, Tetrahedron, 1994, 159 S.A. Hitchcock, S.H. Boyer, M.Y. Chu-Moyer, S.H. Olson and S. J. Danishefsky, Angew. Chem., Znt. Ed. Engl., 1994, 33, 858. 160 T. Brandstetter and M.E.Maier, Tetrahedron, 1994, 50, 1435. 161 H. Audrain, T. Skrydstrup, G. Ulibarri, C. Riche, A. Chiaroni and D.S. Grierson, Tetrahedron, 1994, 50, 1469. K.M. Pham, D.M. Vyas and M.D. Wittman, Tetrahedron, 1994, 50, 1519. 482. 35, 37. 35, 2655. Tetrahedron Lett., 1994,35, 7997. R.A. Fairhurst, J. Chem. SOC., Chem. Commun., 1994, 1543. Danishefsky, Angew. Chem., Znt. Ed. Engl., 1994,33, 2477. 169 M.D. Shair, T. Yoon and S.J. Danishefsky, J. 0%. Chem., 1994,59,3755. 170 M.F. Braiia, M. Moran, M.J.P. de Vega and I. Pita- Romero, Tetrahedron Lett., 1994,35, 8655. 171 K. Toshima, K. Yanagawa, K. Ohta, T. Kano and M. Nakata, Tetrahedron Lett., 1994, 35, 1573. 172 P. Magnus, Tetrahedron, 1994,50, 1397. 173 D. Elbaum, T.B. Nguyen, W.L. Jorgensen and S.L. 162 J.F. Kadow, D.J. Cook, T.W. Doyle, D.R. Langley, 163 T. Nishikawa, S. Shibuya and M. Isobe, Synlett, 1994, 164 J.M. Nuss and M.M. Murphy, Tetrahedron Lett., 1994, 165 R.S. Huber and G.B. Jones, Tetrahedron Lett., 1994, 166 T. Nishikawa, M. Yoshikai, K. Obi and M. Isobe, 167 P. Magnus, D. Parry, T. Iliadis, S.A. Eisenbeis and 168 M.D. Shair, T. Yoon, T-C. Chou and S.J. Schreiber, Tetrahedron, 1994,50, 1503. Cousins: Saturated and unsaturated hydrocarbons 461

ISSN:1350-4894    

DOI:10.1039/CO99502BP011

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

Catalytic applications of transition metals in organic synthesis CHRISTOPHER G. FROST and JONATHAN M. J. WILLIAMS Department of Chemistry, Loughborough University of Technology, Loughborough, Leicestershire, LEI I 3TU, UK Reviewing the literature published between 1 September 1993 and 31 August 1994 1 2 2.1 2.2 2.3 2.4 2.5 3 3.1 3.2 3.3 3.4 4 4.1 4.2 4.3 4.4 5 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 6 7 8 9 10 11 12 Introduction Oxidation E poxidat ion Dihydroxylation Oxidation of alcohols Oxidation of hydrocarbons Other oxidations Hydrogenation and related processes Hydrogenation H ydrosilylation Hydroboration and diboration Hydroformylation Lewis acids Friedel-Crafts Ally lation Diels- Alder Carbonyl-ene reactions Coupling reactions Heck reactions Suzuki coupling Stille coupling Coupling of other organometallics Allylic substitution Carbonylation and related reactions C y clizations Cyclizations to form aryl rings Tandem and cascade reactions Reactions involving metal carbenoids Conjugate addition and substitution Catalysed nucleophilic additions Metathesis Miscellaneous Conclusion References 1 Introduction This review highlights the advances in transition metal catalysis made in the period 1 September 1993 to 3 1 August 1994.During this period, there have been many advances in the field of homogeneous transition metal catalysed reactions. One of the most prominent areas of research within the field has been the further development of asymmetric catalysis using enantiomerically pure ligands associated with transition metal catalysts. There are a growing number of catalytic reactions in which the enantiomeric excess of the product is > 90%.There has been such a huge volume of publications concerned with transition metal catalysts that it is not possible to provide a fully comprehensive account. We have endeavoured, however, to summarize current areas of interest and to provide commentary on the important advances. Only homogeneous applications have been considered for this review. 2 Oxidation Two important objectives with oxidation reactions are selectivity and efficiency. There are examples here of transition metal catalysed oxidation reactions which are chemoselective as well as stereoselective. The cheapest oxidant is air, and catalytic systems which employ air as the stoichiometric oxidant are especially appealing.2.1 Epoxidation Further developments within asymmetric epoxidation using enantiomerically pure manganese salen complexes have been reported. Jacobsen and co-workers have described the sterically and electronically optimized (sa1en)Mn complex 1, which was employed in the catalytic oxidation of the diene 2 to the monoepoxide 3' and also of l-phenylcyclohexene (4) to the corresponding epoxide 5.2 H Q H 0.2 eq. P h C N + - O - cat. 1 4"C, €120, NaOCl 2 45% yield 3 (64% e.e.) O'C, CH&12 4 5 (92% e.e.) Frost and Williams: Catalytic applications of transition metals in organic synthesis 65The related catalyst 6 has been prepared by Katsuki and co-workers, and has provided high levels of asymmetric induction for the epoxidation of conjugated cis-alkenes, such as the conversion of 7 into 8.3 PhIO cat.6 8 (94%e.e.) a 8% a ' c yield - 7 A remarkable enantioselective aerobic epoxidation of alkenes catalysed by the manganese complex 9 has been rep~rted.~ The (2)-alkene 10 is converted into the epoxide 11 with 80% e.e.in the presence of oxygen and pivaldehyde. However, the yield and diastereoselectivity of the reaction are less satisfactory. 9 BU'CHO 3 ~ 1 % 9 1 atm. air P P M e r.t., benzene 10 80% 8.8. 63:37 cis :trans 2.2 Dihydroxylation There still remains considerable debate over the precise mechanism of the enantioselective osmium-catalysed dihydroxylation of alkenes in the presence of cinchona-derived catalysts 12 and 13.5-7 However, the synthetic importance of this reaction is evident from the increasing range of substrates which have been successfully employed.The Sharpless group have provided many examples recently, including the conversion of the allyl halide 148 and the allyl sulfide 169 into the corresponding diols 15 and 17 with excellent levels of asymmetric induction. DHQ DHQD buffered AD-ma-B *cl O%, Bu'OH-H~O -- 14 MeSOzNHz OH 75% yield 15 (95%e.e.) OH E Ph!3&Ph buffered A M i - B P h S d Ph O'C, Bu'OH-HpO 16 75% yield 6H 17 (98%e.e.) Hale and co-workers have reported that the conversion of the silyl protected allyl alcohol 18 into the product 19 occurs with good enantioselectivity, but with an opposite sense of asymmetric induction to that predicted based solely on the steric demands of the substituents on the a1kene.I' Me OSiPhz13ut Me OSiPhzBut K O%, AD-ma-B Bu'0H-H20 HC!? (91 Yo e.e.) 70% yield 18 2.3 Oxidation of alcohols Backvall's group has provided two interesting examples of the transition metal catalysed oxidation of secondary alcohols to the corresponding ketones.Treatment of cyclohexanol(20) with manganese dioxide and potassium carbonate and catalytic amounts of both the ruthenium complex 2 1 and the quinone 22, afforded cyclohexanone (23)." -8 20 MlYo 22 0.5 MI% 24 2 MI% 25 0.6-1.5% O2 in N2 W% yield 20 23 But In a related system, it was possible to use air as the stoichiometric oxidant, in conjunction with an additional catalyst 25. The alternative ruthenium 66 Contemporary Organic Synthesiscatalyst 24 was employed, and cyclohexanol was converted into cyclohexanone in 89% yield with this unusual triple catalytic system.' 24 2.4 Oxidation of hydrocarbons Selective oxidation of alkanes is a daunting objective, and whilst there is still some way to go before chemo- and stereo-selective oxidation of alkanes can be reliably achieved with high efficiency, there are a few examples of highly selective reactions.For example, the functionalization of alkanes with sulfuryl chloride, catalysed by the cobalt complexes 26 and 27, has been described.13 These reagents are highly chemoselective, with catalyst 26 converting cyclohexane (28) into the chloride 29, whilst the use of catalyst 27 affords the c hlorosulfonate 30. so*cr I CI I 0- :7 0 : -0 29 72% yield 74% yield 30 20 2.5 Other oxidations Goti and Romani have described a catalytic oxidation of secondary amines into the corresponding imines,14 a reaction which has received much less attention than the related oxidation of alcohols to ketones.The secondary amine 3 1 was converted into the imine 32 by treatment with N-methylmorpholine N-oxide (NMO) and catalytic amounts of tetra-n-propylammonium perruthenate (TPAP). Phn'Nn Ph 32 0.05 eq. TPAP phAyAph 1.5eq.NMO * H r.t.. MeCN 88% yield 31 Murahashi and co-workers have reported the osmium trichloride catalysed oxidation of alkenes with peracetic acid to afford a-ketols. These workers indicate how this is quite different from the osmium tetroxide catalysed oxidation of alkenes to afford di01s.l~ Oct-1-ene (33) was converted into the a-ketol 34 by treatment with peracetic acid in the presence of catalytic amounts of OsC1,.3 Hydrogenation and related processes Transition metal catalysed hydrogenation reactions have been known for a long time, and even asymmetric variations of this reaction are over twenty years old. There is still room for progress, however, as the following examples illustrate. 3.1 Hydrogenation The effective cationic rhodium catalyst 37 for the hydrogenation of aldehydes and ketones 35 under mild conditions into the corresponding alcohols 36 has been reported by Burk and co-workers.16 0 cat. [(COD)Rh(DiPFc)]+OTf(37) OH II b I Di P Fc=l , 1 '&is( d iisapropylphosphino)ferrocene Lemaire and co-workers have demonstrated that the ligand 38 is effective in the rhodium-catalysed transfer hydrogenation of methyl benzoylformate to the product 39 giving over 99% e.e.and 100% conver~ion.'~ Other substrates, however, afforded lower levels of asymmetric induction. OH 39 (99%e.e.) Me Me r.t KOH The range of substrates which are efficiently hydrogenated in the presence of the titanocene catalyst 40 has been extended.I8 The enamine 4 1 is converted into the amine 42 with 92% e.e.," and the alkene 43 is hydrogenated to 44 with 99% e.e.20 (li) 2.5 q. PhSiH3 W 'active catalyst' 40 15 p.8.1. H2 r.t PhACH2 75%yield Ph+Me 42 (92%e.e.) 41 Frost and Williams: Catalytic applications of transition metals in organic synthesis 67L P h 5 ' % 4 0 - * r.t.. 48 h Ph Aph Ph 43 91% yield 44 (99%e.e.) Burk and co-workers have also reported the synthesis of a range of amino acid derivatives via asymmetric hydrogenation with DuPHOS rhodium catalysts.21 The ( E ) - and (Z)-enamides 45 and 46 were both converted into the same enantiomer of product 47 with very high enantioselectivity upon treatment with ligand 48 and a rhodium catalyst under two atmospheres of hydrogen.Faller and Tokunaga have provided a further example of chiral poisoning.22 Treatment of the racemic ruthenium complex 49 with (1 R,2 S)-ephedrine (50) deactivates one of the enantiomers of the catalyst. The unpoisoned enantiomer remains available to effect a kinetic resolution in the hydrogenation of racemic cyclohexenol5 1. At 77% conversion, recovered cyclohexenol5 1 was found to have > 95% e.e. and Jac~bsen,*~ with their respective co-workers have independently described enantiomerically pure bimetallic complexes, 55a and 55b.These complexes are anticipated to afford two-point binding for suitable substrates, and the Kagan group have shown that catalyst 55a is able to catalyse asymmetric hydrogenation reactions. It may be possible to use such bimetallic complexes to provide highly selective reactions, and it seems likely that this design strategy will afford interesting results in the future. r 7 + L 56a Kagan J r l+ L 55b Jacobsen J m i H A C -1 0.1 mol% [(COD$3h+lOff 45 47 (99.6% e.e.) NHAc 0.1 mOl%m -NHAc 2 atm. H2 -CO2Me c ~ H A C I 0.1 mot% [ ( w R h + p T f C02Me 0.1 mOl%48 46 47 (99.4% e.e.) 48 OH Takaya and co-workers have shown that the H,-BINAP ruthenium complex 52 is an effective asymmetric hydrogenation catalyst.23 For example, the alkene 53 was converted into the anti-inflammatory drug (S)-ibuprofen (54) with 97% e.e.In some cases this catalyst proved to be superior to the more normal BINAP derived catalysts. I I 3.2 Hydrosilylation Takeuchi and co-workers have reported a highly selective hydrosilylation of propynylic alcohols with complete control over regiochemistry and alkene geometry.26 Alkyne 56 was converted into the vinyl silane 57 with 92% yield. 2 4 Ho 56 HPsiEt3 0.5 m ~ l % Rh(C00)2BF4 1 mot% PPhi 1.5 eq. EtSiH 50°C. acetone, - 16h -u 02% yield 57 Kobayashi and Nishio have described a one-pot preparation of homoallylic alcohols from 1,3-dienes via a hydrosilylation-aldehyde-coupling sequence.27 Cyclopentadiene (2) is reacted with trichlorosilane and a palladium catalyst, and the intermediate allylsilane 58 is reacted with benzaldehyde to form the alcohol 59 with high yield and excellent syn selectivity.90 'C 2 PhCHO 0%. DMF 01% yield OH I A palladium-catalysed silylstannylation of alkenes has been reported.28 For example, treatment of the silylstannane 60 and norbornene (61) with a palladium catalyst affords the derivative 62 in 89% yield. 6, 130%, toluene, 16h 95% yield 62 68 Contemporary Organic Synthesis3.3 Hydroboration and diboration Brown and co-workers have reported that the rhodium complex 63 is able to effect hydroboration of styrenes 64 with good enantioselectivities, as determined after conversion into the corresponding alcohols 6 5 .29 65 (78-94% e.e.) 64 20 *c H& I HO- -9% yield 63 An unusual platinum( o )-catalysed diboration of alkynes has been described.30 The reaction of alkyne 66 with the diboron species 67 with 3 mol% of Pt(PPh,), affords the addition product 68 in 86% yield.68 3.4 Hydroformylation Doyle and co-workers have reported a highly regioselective hydroformylation of alkenes catalysed by [Rh( COD)( OAC)],.~' Thus styrene is hydroformylated to afford a 96 :4 ratio of the branched to linear aldehydes 69 and 70. Takaya and co-workers have shown that in the same process the phosphinephosphite ligand 7 1 provides good enantioselectivity in the reaction, but with a 90: 10 ratio of the branched to linear aldehydes.32 90: 70 10 4 Lewis acids Ruthenium complexes have continued to be used as Lewis acids. Ma and Venanzi have used the ruthenium catalyst 72 to effect the acetalization of o-salicaldehyde (73) with 1,2-ethanediol(74) to afford the 1,3-dioxolane 75.33 The same workers have also reported the hydrolysis of acetals, including 1,3-dioxolanes by the use of a ruthenium catalyst.34 Nitriles are converted into esters on reaction with an alcohol in the presence of the ruthenium catalyst 76.35 For example, the nitrile 77 and methanol are converted into the methyl ester 78 in 86% yield. The same catalyst in the presence of water converts nitriles into the corresponding primary a m i d e ~ .~ ~ I I azeotropic diaillatbn 7 3 0 90% yield 72 = R~(MeCN)(triphos)(OTf)~ 3 mot% RuH,(PP& 76 C11H&O*Me C11H23CN l.Mq.H@. MeOH * eealedtube 77 18O'C, 24h -yield 78 4.1 Friedel-Crafts The use of scandium triflate as a catalyst has been further developed.This catalyst has been applied to Friedel-Crafts acylation reactions. Thus, treatment of anisole (79) and acetic anhydride with 20 mol% scandium triflate afforded the acetylated product 80 in 89% yield.37 The use of 1 mol% catalyst under otherwise identical conditions afforded a 62% yield of product. The catalyst could be recovered from the aqueous layer by simple extraction. 20 50%. m ~ l % AC20 MeNOa Sc(OTr), 4h * $ -vleld 6 79 Me 80 4.2 Allylation Scandium triflate has also been reported to catalyse the allylation of carbonyl compounds with tetraall~ltin.~~ Thus, treatment of o-salicaldehyde 73 with tetraallyltin in water/tetrahydrofuran ( 1 :9) and 5 mol% scandium triflate affords the adduct 8 1. It would be expected that most other Lewis acids would not tolerate the presence of water or the presence of the phenol.73 81 The related catalyst, scandium perchlorate, has been employed in the C-glycosidation reaction between 82 and 83 to afford the product 84 with excellent a-~electivity.~~ Frost and Williams: Catalytic applications of transition metals in organic synthesis 69OBn I Keck and Geraci have reported a simple procedure for the enantioselective allylation of aldehydes with allyltributylstannane 87 using catalytic amounts of pre-mixed titanium tetraisopropoxide and ( R)-BINOL.40 Using this methodology, benzaldehyde ( 8 5 ) was converted into the product 86 with 96% e.e. b S n B u 3 / 87 H ,OH 0 phAM 10 mi% Ti(OPrJ), Ph'- . .. .. 20 ml% ( R )4 INOL 85 -20%. C H & , 50h 86 (96?he.e.) 98% yield 4.3 Diels-Alder Asymmetric catalysis with scandium reagents has been achieved in the Diels-Alder reaction.41 A catalyst 88,42 derived from scandium triflate, ( R )-( + )- l,l'-bi-2-naphtho17 and cis- 172,6-trimethylpiperidine, was employed in catalytic amounts in the enantioselective Diels-Alder reaction of the dienophile 89 and cyclopentadiene (2) to afford the cycloadduct 90.Evans and co-workers have employed catalysts based upon copper( 11) triflate and the diimine 9 1 to catalyse Diels-Alder reactions on similar substrates with 83-94% e.e.43 90 (92% e.e.) 89:ll edo:exo H WOiN< 0\ I H Ar FN N Y A r 91 Corey and co-workers have employed the titanium catalyst 92 in the enantioselective Diels-Alder reaction between 2-bromoacrolein (93) and cyclopentadiene (2) which affords the cycloadduct 94 in 93% e.e.44 =(cHo Q &CHO \ Br 10 mot% 92 - Br -78%.CHZCIZ 94 (93%e.e.) 67:l exomdo 94% yield 93 4.4 Carbonyl-ene reactions Terada and Mikami have used the p-0x0 complex 95 to catalyse the carbonyl-ene reaction between a-methylstyrene (96) and methyl glyoxylate to afford the product 97 with very high enantio~electivity.4~ The same group have also further developed the use of the complex 98 to a more extensive range of ~ubstrates.~~ 0 f l C O * M e HKC02Me 0.2 md% 95 Ph 96 a%, CHg12. 2h 88% yield 97 (98.7% e.e.) Ph Mikami and Matsukawa have described an aldol-type reaction between the ketene silyl acetal99 and the aldehyde 100 catalysed by titanium complex 98 to afford the product 10 1 with high enantio~electivity.~' Whilst the outcome of this reaction indicates an aldol reaction, these authors postulate that the reaction pathway may in fact involve a silatropic ene reaction.OTMS oms BnOJH EtS L O B n 101 (94%e.e.) 0% toluene 2h Ets 819/0 yield 100 Q ' o,-p 98 5 Coupling reactions There have been many hundreds of examples of metal-catalysed coupling reactions reported recently, which is a testament to the synthetic utility of these reactions. Palladium has a dominant position as the main metal of choice for conventional coupling reactions, such as the Stille reaction and carbonylation 70 Contemporary Organic Synthesisreactions. However, other transition metals have been examined, and as described here provide useful methods for what have been collected together as ‘coupling reactions’.5.1 Heck reactions Various methods for optimizing Heck reactions have been described. For example, it has been reported that Heck reactions are accelerated by high pressure condition^.^^ Jeffery has reported that Heck reactions can take place in water in the presence of added tetrabu t ylammonium salt sJY of their work on the enantioselective intermolecular Heck reactions0 The reaction of phenyl triflate (102) with 2,3-dihydrofuran (103) in the presence of catalytic amounts of palladium acetate and ( R )-BINAP affords the products 104 and 105 with configurations opposite to each other. Japanese workers have provided a detailed account 103 3 eq. PtZNEt 104 105 82V’e.e. 92 18 60%e.e. 57%yield 6% yield Achiwa and co-workers have achieved good enantioselectivity in a related reaction employing phenyl triflate ( 102) and norbornene 6 1 as coupling partners to afford the product of hydroarylation 106 in the presence of a palladium catalyst and the ligand 107.” Ozawa, Hayashi, and co-workers looked at a similar reaction using the vinyl triflate 108 as the coupling partner to afford the product of hydroalkenylation 109 in 93% enantiomeric excess? PhOTf 102 1.2 m ~ l % Pd(0AC)z EbN, 2.4 md% 107 65%.DMSO. 20h 61 106 (71.4% 0.e.) 73.6% yield NHS02M0 p+&PPk 107 Me H 111 piperidine. HCOd 113 70’C, DMF. 6.5h HBr I AcOH r.t., 22h 74% yield H 1 I W’ H 110 transformed into ( k )-epibatidine (1 10) upon treatment with HBr/acetic acid. The Heck reaction has provided some useful examples of cyclization reactions on complex substrates.sJ For example, Masters and co-workers obtained a 52% yield in the Heck cyclization of precursor 114 into the taxol analogue 1 15.5s Overman and co-workers have provided another example of an enantioselective intramolecular Heck reaction: treatment of compound 116 with an enantiomerically pure palladium catalyst, followed by acidic hydrolysis afforded the cyclization product 117 in high enantiomeric excess.56 This compound was converted into the naturally occurring alkaloid ( - )-physostigmine ( 1 18).0 114 0 115 116 10% Pdz(dba)&HCb (S )-BINAP.100 “c 84% yield OzCHNMe 1 108 L ___c Me 61 MezN 109 (93% 0.0.) I 117 (95% 0.0.) 63% yield Clayton and Regan have reported the synthesis of racemic epibatidine ( 1 lo), an alkaloid which has received much synthetic attention recently.The key step in their synthesis is a reductive palladium-catalysed Heck-type coupling.s3 The reaction between compounds 1 1 1 and 1 12 using a palladium catalyst with piperidine and formic acid afforded the coupled product 113, which was Me 118 5.2 Suzuki coupling Wallow and Novak have reported increased catalytic efficiency by using phosphine-free palladium sources in Suzuki coupling reaction^.^' Soderquist and Colberg have shown that the silylated vinylborane 119 could be converted into trans-vinylsilanes 120 via Suzuki coupling in good yields.58 Frost and Williams: Catalytic applications of transition metals in orgunic synthesis 71R RBr BBN 120 SiMe3 rdlux.THF, 1% 2.5% Pdddba)~ = p w co (56 p.s.1.) LEI 80% yield 70%. NMP 584996 yield Johnson and Braun have employed a Suzuki coupling reaction in the preparation of the prostaglandin PGE, methyl ester 12 1 .5y Treatment of a suitable vinyl iodide and borane with a palladium catalyst afforded the coupled product, which was converted into prostaglandin PGE methyl ester 12 1 in two further steps (73% yield).0 0 ~TBDMS 25%. D M ~ T H F M ~ ~TBDMS Jl BBN = 9-borabiidononane HO . ' W C s H 4 I 121 OH 5.3 Stille coupling The Stille coupling process has provided efficient synthetic routes to many natural products. Indeed there have been several recent examples which demonstrate the versatility of this powerful reaction. Overman and co-workers employed a Stille coupling between the vinyl stannane 122 and the aryl iodide 123 to afford the coupled product 124 which they use in the total synthesis of ( - )-strychnine.b0 Falck and co-workers converted the stannane 125 into the ketone 126 on treatment with benzoyl chloride and a palladium catalyst? Stereoselective reduction and debenzylation afforded the natural product goniofufurone ( 12 7).Similar acyclic examples were also reported to proceed with retention of configuration.6 0 MeN NMe L N ) b' 123 OTI PS OBU' 0 H 126 H 127 Danishefsky and co-workers have reported an extraordinary palladium-catalysed coupling between (2)-bis( trhethylstanny1)ethylene ( 128) and the bis( iodoalkyne) 129 to afford the cyclic enediyne 130 in an incredible 80% yield!63 10?6Pd(PPh& 60% DMF, l h OTBS 80% yleld 129 1 Om 130 Boden and Pattenden have reported a macrocyclization strategy based on the intramolecular Stille coupling of a vinylstannane with an ally1 ~hloride."~ Thus, substrate 13 1 undergoes macrocyclization on treatment with a palladium catalyst to afford the product 132 in 38% yield.131 132 Kilburn and co-workers have described an unusual Stale-type 4,4'-biaryl formation as a macrocyclization step.65 Treatment of substrate 133 with a palladium catalyst afforded the macrocycle 134, albeit in modest yield. 7 2 Contemporary Organic SynthesisBr 98% yield 139 140 An application of zinc reagents to the preparation of homophenylalanine derivatives has been provided by Jackson and co-workers.6Y The reaction of zinc reagent 142 with the aryl iodide 143 in the presence of a palladium catalyst affords the homophenylalanine derivative 144 in 65% yield.Casson and Kocienski have shown that a-alkoxyalkenylzinc reagents such as 145 are suitable for palladium-catalysed reactions with various coupling partners, including the vinyl triflate 146 to give the coupled product 147.70 133 lMmo L 2 w2(dba)3 4 ml% Ph&s r.t., MF 6796 yield 134 In a process somewhat related to the Stille coupling, Hartwig66 and B~chwald,~~ with their respective co-workers, have independently reported the coupling between arylbromides and aminostannanes. For example, the in situ conversion of the secondary amine 135 into the aminostannane 136 upon treatment with ( N,N-diethylamino)tributyltin, and subsequent reaction with the aryl bromide 137 in the presence of a palladium catalyst affords the tertiary amine product 138.r 1 rPh Et#tSnBu3 Me H-N, L J 135 136 1 molx WCl2 (P(o -Tol)3)2 137 105% toluene 2h l - E t O & e N, rPh Me 138 5.4 Coupling of other organometallics Untiedt and de Meijere have shown that the palladium-catalysed coupling of the unusual zinc reagent 139 proceeds efficiently to afford the phenyl derivative 140 in excellent yield, when treated with iodobenzene (141) and a palladium catalyst."* 145 147 Two groups have employed ortho-directing groups to prepare zinc reagents, and coupled these organometallics with aryl triflates. Koch and co-workers ortho-lithiated the aryl oxazoline 148, generated the zinc reagent via transmetallation, and coupled this to iodobenzene ( 14 1 ) using palladium catalysis, thereby obtaining the product 149 in 75% yield.7 N, 0 * -6 (iii) 141.a. Pd(PPh44 75% yield 148 149 A similar strategy was employed by Snieckus and co-workers to form the coupled product 150 from the carbamate 15 1 and the aryl triflate 152. Both groups found that this strategy was effective with other ortho-directing groups.72 OCONEti &Me 672 EtZNOCO On 151 OMe 150 85% yleld Frost and Williams: Catalytic applications of transition meta Is in organic synthesis 73An unusual coupling involving cyclopropyl Grignard reagents 153 with benzylic dithioacetals 154 has been reported.73 The rearrangement of an intermediate cyclopropylcarbinylnickel intermediate accounts for the observed product 155. bromide 165 with potassium triisopropylsilanethiolate (166) to afford the vinyl silane 167.77 Coupling reactions between aryl halides and 166 were also achieved.Me, An unusual palladium-catalysed decarbonylative coupling reaction has been investigated by Tsuji and co-worker~.~~ Benzoyl chloride (168), hexamethyldisilane (169), and butadiene (170) are coupled together by a palladium catalyst to afford the allylsilane 17 1 in which decarbonylation has occurred. Hiyama and co-workers have employed alkyltrifluorosilanes as coupling partners.74 For example, the palladium-catalysed reaction between hexyltrifluorosilane ( 156) and p-bromoacetophenone ( 157) is promoted by tetrabutylammonium fluoride to give the coupled product 158 in 63% yield. 0 PhACI 157 5 md% Pd(PPh& 100°C. THF. 37h 03% Yield C6H13-SiF3 156 C6H13 158 5 m ~ l % W(dba)o 168 169 Me3Si-SiMe3 c /\//\/SiMe3 80% toluene 4h ph 171 86% yield w 170 The regiochemistry of coupling reactions involving an allyltrifluorosilane 1 59 with p-bromoacetophenone (157) was found to be highly dependent upon the ligand employed.75 The use of triphenylphosphine as the ligand afforded the y-product 16 1, whereas the use of the bidentate ligand dppp [Ph2qCH2),PPh2 (162)] afforded predominantly the a-product 160.5.5 Allylic substitution The main interest in allylic substitution has been in enantioselective palladium-catalysed allylic substitution. The conversion of acetate 172 into the substitution product 173 upon treatment with dimethylmalonate and a palladium catalyst with a suitable ligand has been achieved with high enantioselectivity by a number of research groups. 1 57 Me bsiF3 5mof96PdCI& 159 5 m ~ l % L.BuANF 120°C. MF 6OMe AOMe 160 161 L = PPha 0 100 = Ph*P(CH&PPk (162) 99 1 Brown and co-workers have developed the QUINAP ligand 174,7y whilst Wills and co-workers have shown that a monodentate ligand 175 is also effective.80 Koga and co-workers employed the C2 symmetric bis( pyrrolidines) 1 76,81 whereas Tanner and co-workers have used C, symmetric bis( aziridines) 1 77.82 Williams and co-workers have examined the use of ligands 1 7 v 3 and 1 79.84 The diamine ligand 180g5 has also been applied to this process, whilst Togni and co-workers have demonstrated that the chelating diphosphine ligand 181 is a useful ligand for a number of catalytic processes, including palladium-catalysed allylic substitution.86 A French group has reported an efficient palladium-catalysed reaction between terminal alkynes and vinyl and aryl halides.76 Iodobenzene ( 14 1 ) was coupled to the alkyne 163 to afford the product 164 in 96% yield.The added base was critical to the success of the reaction. Piperidine as the added base afford this high yield, whereas the use of either triethylamine or diethylamine gave no product! OH I ) PhI 141 -- f 5 m0R6 W(PPhd4 3 PPh2 1 74 / \ Ph piperidine 96% yield 163 Et2NH 0% yield 164 Soderquist and co-workers have demonstrated that thiolates may be employed as coupling partners in the palladium-catalysed cross-coupling between the vinyl affords up to 98% 8.8. affords up to 91 5% 8.8. 74 Contemporary Organic Synthesispalladium catalysis in the presence of these ligands, afforded high levels of enantioselectivity in the product 190.affords rq to 91% 8.8. affords ~96% e .e . MeHN 'hxph NHMe 180 affords up to 88% 8.8. affords Up t0 959/0 8.8. affords Up t0 93% 8.8. Helmchen, Pfaltz, and co-workers have extended the use of the ligand 182 to palladium-catalysed allylic amination?' Thus, treatment of the same allylic acetate 172 with a variety of nitrogen nucleophiles, including the sodium salt of p-toluenesulfonamide, afforded the allylic substitution product 183 with excellent levels of asymmetric induction. Ph+rPh TsNHNa TsHN PhqPh 1 mol% [(allyl)PdCI]2 172 183 (97% e.e.) Trost and Bunt have shown that the ligand 184 is particularly effective in enantioselective reactions involving 3-( acyloxy )cycloalkenes. For example, the reaction of the allyl acetate 185 with potassium phthalimide in the presence of a palladium catalyst and an enantiomerically pure ligand afforded the substitution product 186 with very high enantioselectivity.88 These workers have also shown that, in some cases, the addition of some tetraalkylammonium salts can have a remarkably beneficial effect on product enantioselectivity." 0 CH2C12 84% yield 186 (98% e.e.) 185 184 Hayashi and co-workers have also employed the Treatment of the allyl ligands 187 and 188 in the palladium-catalysed reduction of allylic carbonate 189 with formic acid and a base, under 188 1 87 with 187; 95% yield, 76% e.e.with 188; 99% yield, 85% 8.8. The cyclization of allyl acetates 191 and 192 under palladium-catalysed allylic substitution conditions has been shown to afford either the benzazepinium salt 193 or the alternative five-membered ring compound 194.92 The preference for one regioisomer over the other was found to be due to thermodynamic control.OAc I 191 R = H 192 R=Ph 194 R = Ph 81 % yield Whilst allylic substitution reactions catalysed by metals other than palladium continue to receive less attention, Takahashi and co-workers have provided examples of a regioselective carbon-carbon bond-forming reaction between an allyl ether 195 and a Grignard reagent catalysed by zirconocene dichloride to afford the product 196.93 Kobayashi and Ikeda have shown that the allylic carbonate 197 reacts with 2-furylborate 198 in the presence of a nickel catalyst to give 199.94 Frost and Williams: Catalytic applications of transition metals in organic synthesis 755.6 Carbonylation and related reactions The aryloxy carbonylation of 4-bromobipheny1(200) with the phenoxide 20 1 has been reported as an efficient synthesis of the hindered esters 202.95 carbonylation protocol in the preparation of 2-arylbenzimidazoles."" For example, the palladium-catalysed reaction between iodobenzene (14 1) and o-phenylenediamine (203) affords 2-phenylbenzimidazole (204).The reaction proceeds via a monoamide, which cyclizes in situ. Perry and Wilson have used a palladium-catalysed Bu! P h o B r 200 R 202 PhI 141 co (95 p.s.1.) - c k P h ' N NH2 1.2 ea. 2.6-btidine . I 1.5 ml% PdCb(PPh& - 140 C,' M%NCOMe rl 204 203 75% yield An interesting variant on standard carbonylation procedures has been devised by Grushin and A l ~ e r .~ ~ The carbon monoxide is generated in situ from chloroform and hydroxide. In a typical reaction, iodobenzene (141) and chloroform are treated with a palladium catalyst and potassium hydroxide, which after acidic work-up affords benzoic acid (205) in 72% yield. cat. PdC&(PPh& PhCO2H 205 60% Z&KOH Ph1+CHC'3 22%. CHCb 24h * 141 then H1O+ 5.7 Cyclizations There are many possible cyclization reactions which rely upon the previously described coupling processes. A few examples are given here. Murai and co-workers have reported the cyclization of the enyne 206 with a ruthenium catalyst to afford the product 207 in which a skeletal rearrangement has taken place.98 206 207 The palladium-catalysed oxaspirocyclizations of substrates such as 208 has been reported by Swedish workers.y9 The reaction with a palladium catalyst affords the spiro-product 209 with high diastereoselectivity using acetate as the external nucleophile.Hong and Overman have used a palladium-catalysed cyclization reaction in the construction of the pentacyclic opiate 2 1 1 (which can be converted into morphine) from the precursor 2 10.'O0 Ho\ b 2eq. o+ - * 3 eq. L I f i 5 m ~ l % Pd(0AC)z HOAc:Me&O (1 a) 24h. 86%yie# A&'* 209 208 OH 21 0 21 1 Takacs and Chandramouli have reported a highly diastereoselective palladium-catalysed tetraene cyclization.lo1 The enantiomerically pure substrate 2 12 was cyclized to the product 2 13 as a single diastereomer. c 0.1 5 eq. Ph3P 65%, THF 21 2 65% yield 21 3 A highly stereoselective cyclization of the unsaturated aldehyde 2 14 into the cyclopentanone 2 15 using a cationic BINAP-derived rhodium complex with > 99% e.e.and high trans-selectivity has been reported.'O* The use of a neutral rhodium complex afforded a cis-selective reaction. 76 Contemporary Organic SynthesisOHC * $Me 214 215 cat. RhCl/ (R MINAP 97 3 cat. Rh+ClOd-/ (R)-BINAP 3 97 In a related study, Bosnich and co-workers have cyclized the substrate 2 16 into the cyclopentanone 2 17 with > 99% e.e. using a similar cationic rhodium complex.103 217 (99%e.e.) The trans-selective zirconocene-catalysed cyclization of the diene 2 18 into the cyclopentane 2 19 with the trans-isomer predominating has been reported by Knight and Waymouth.lo4 Hiemstra, Speckamp, and co-workers have examined a copper-catalysed cyclization of trichloroacetates which takes place via a chlorine-transfer process.105 Treatment of the trichloroacetate 220 with the copper catalyst 22 1 affords the eight-membered lactone 222 as a single diastereomer in 74% yield. then H+M& -w 21 9 21 8 220 reflux.CICHCHGI. 18h- 222 .CI 5.8 Cyclizations to form aryl rings Cyclizations in which aryl rings are formed are particularly impressive. In retrosynthetic planning, most research groups consider modification rather than construction of aryl groups, although with the increasing number of transition metal catalysed aryl-forming reactions this situation may start to change. Hidai and co-workers have carbonylated the dienyl acetate 223 in the presence of acetic anhydride and triethylamine, and isolated 2-acetoxybiphenyl (224) in 74% yield.lo6 The reaction proceeds via the carbonylated, cyclized intermediate 2 25, which tautomerizes and is acetylated under the reaction conditions.An aromatization reaction involving the incorporation of two equivalents of carbon monoxide has been reported by Murai and c o - w ~ r k e r s . ~ ~ ~ Thus, the diyne 226 is cyclized to the aromatic compound 227 upon treatment with a ruthenium catalyst in the presence of carbon monoxide and a silane. OAc CO (50 atm) A@ NEb 140°C. benzene.3h ~ i Z ( P P h d 2 - \ / \ / 74% yield OAc 224 223 via Ph 0 225 EtO2C COpEt II n I I 226 EtO& CO2Et HSIBU~M% ~ U d W 1 2 my3 -8 CO (50 atm) 140°C. MeCN. Mh 74% yield Me2Bu'SiO OSiBu'Me2 227 Barry and Kodadek have designed an aromatization of the bis-vinyltriflate 228.Treatment with tributylvinylstannane and a palladium catalyst affords the aromatic compound 229. The reaction proceeds via a Stille coupling to one vinyl triflate and a Heck coupling to the other vinyl triflate to give the intermediate 230 which tautomerizes to the product .l O8 - OTf OTf via 228 e S n B u 3 4 md% Pd(PPh& - 75°C. NMP 55% yield 230 8 229 -Me 5.9 Tandem and cascade reactions Tandem and cascade reactions provide an opportunity for transition metal catalysts to effect remarkable transformations. The standard coupling reactions can be linked together in a sequence to afford products in which many new bonds have been created. Some of the synthetic applications recently achieved are reviewed here.Palladium catalysis has been exploited by Balme and Bouyssi for the cyclization of the alkene 23 1, which affords the tricyclic product 232, which was subsequently conberted into capne1lene.lo9 Frost and Williams: Catalytic applications of transition metals in organic synthesis 77C02Me 6 ' KH I25 % I M F 5 m ~ l % Pd(0Ac)z 64% yield 232 Weinreb and co-workers have examined the three component coupling between the vinyl bromide 233, the alkene 234, and dimethylmalonate (235), which is deprotonated under the reaction conditions.' l o Initially, the bromide and alkene undergo a Heck coupling to form a palladium ally1 intermediate 236, which undergoes nucleophilic addition by the malonate to afford the products 237 and 238. In an intramolecular variation of this reaction, where the nucleophilic component is a tethered sulfonamide 239, the reaction proceeds to afford the bicyclic product 240.' +C4HQ 233 Pd(OAc), P( o -T0l)3 237 Bu~NCI I NaH / DMF @C4Hg loo%, 42h I 234 58% yield I II 5 mol% Pd(0AC)t Ye 10 mow P(o -Tol)i mHTs loo%, N a g 3 DMF, Bu,NCI 24h * 84% yield 239 240 A catalytic tandem oxy-palladation, vinylation reaction has been reported by Semmelhack and Epa.'l2 The hydroxy alkene 24 1 is treated with catalytic palladium acetate in the presence of copper chloride and air as re-oxidant.This affords the intermediate 243, which is trapped with the alkene 242 in Heck fashion to afford the reaction product 244. MeOC 0 2 89%yield qMB r.t., DMF, a 0 243 Grigg and co-workers have reported more examples of palladium-catalysed reactions leading to polycyclic products.113 For example, treatment of the indole 245 with a palladium catalyst afforded the spiro product 246 obtained in a remarkable 91% yield.li4 The starting material undergoes initial oxidative addition with the Pdo catalyst (formed in situ), followed by the stitching indicated to provide the expected product.S C H O A scHo 3 10 m ~ l % Pd(0Ac)z c 20 m ~ l % PPh3 KOAc 130%. PhOMe, 24h 91% yield 245 246 Overman and co-workers have designed an impressive palladium-catalysed bis-Heck cyclization which takes place with complete stereocontrol.' l 5 The vinyl iodide 247 cyclizes as indicated to afford the tricyclic product 248 as a single diastereomer in 82% yield. \ (i) 10 mot% Pd(0Ac)z (ii) TBAF 2O%PhP 1 23% THF 3 P T H F I 248 OH 6 Reactions involving metal carbenoids Rhodium and copper are the most commonly used metals for effecting reactions which proceed via metal carbenoids.Ironically, the metal carbenoids of copper and rhodium are too unstable to isolate, and so the exact structures of such species can only be assumed. Nevertheless, the behaviour of catalytic reactions involving metal carbenoids is now becoming fairly well rationalized. An interesting synthesis of epoxides from aldehydes has been provided by Aggarwal and co-workers.'16 Dirhodium tetraacetate catalyses the formation of sulfur ylides from diazo-compounds and sulfides. The so-formed sulfur ylide reacts with the aldehyde to form an epoxide and regenerates the sulfide, which can therefore be used catalytically. For example, benzaldehyde (249) was converted into stilbene oxide (250) in 74% yield.2 0 d % M G 1 m ~ l % R ~ ~ O A C ) ~ * & Ph 86 :12 trans :as N&HPh Ph 74% yield PhCHO 249 BubMe I CH2C12 24h 250 78 Contemporary Organic SynthesisSeveral diastereoselective rhodium-catalysed transformations controlled by chiral auxiliaries have been reported."7 Davies and co-workers used the pantolactone ester 25 1 in a diastereoselective cyclopropanation reaction, to afford the product 252.' l 8 0 0 Landais and Planchenault have examined diastereoselective rhodium-catalysed insertions into the Si-H bond. The rhodium-catalysed reaction of the diazoacetate 253 with a silane 254 affords the product 255 with moderate diastereoselectivity.' l y -,SiMe2Ph PhMe,SiH (254) 73% yield A C-H insertion reaction which proceeds with very high diastereocontrol and enantiocontrol has been reported by Doyle, Muller, and co-workers.''O The diazoacetate 256 cyclizes to the product 257 on treatment with the and 97% e.e. 256 Rhp4 = 258 rhodium catalyst 258 with 98% d.e.cat. Rh& reflux, CH2Cb 70% yield H 257 (97% e.e.) ( ) Q 4 O 2 4 ? ,Rh Rh 7 Conjugate addition and substitution Van Koten and co-workers have further developed the use of enantiomerically pure arenethiolatocopper( I ) complexes 26 1 as catalysts for enantioselective conjugate addition.122 In the presence of catalyst 26 1, methylmagnesium iodide can be added to the a,P-unsaturated ketone 262 to afford the product of 1,4-conjugate addition 263 with high enantioselectivity.261 M s c u Ph-0 c Ph?o Me 0%, MeMgI EtzO Me Me 262 97% yield 263 Zhou and Pfaltz have used the related copper catalyst 264 to provide asymmetric induction in the addition of isopropylmagnesium chloride to 2-cycloheptenone (265), which affords the product 266.123 (y 265 s - c u 264 * Pr'MgCI 55% yield -78 %, THF/HMPA 266 (87%e.e.) Backvall, van Koten, and co-workers have reported the extraordinary finding that treatment of geranyl acetate 267 with the achiral catalyst 268 and butylmagnesium iodide (addition over 120 min.) affords the product of y-substitution 270 when conducted in diethyl ether at O T , whilst the product of a-substitution, 269, was obtained when the reaction was conducted in THF at - 30°C (with Grignard addition over 5 min.).124 The enantioselective cyclopropanation of alkenes with diazoacetates catalysed by the ruthenium complex 259 has been reported.121 Styrene is converted into the cyclopropane 260 with high enantioselectivity and diastereoselectivity.268 270 259 Ph v C O 2 B u ' 94% d.e. MYo 8.8. N&HCO~BU~ Ph- cat. 259 20%, CH&&.8h 260 65% yield 267 269 269 : 270 0 "C Et20 2h addition 0 : 100 -30 "C M F 5 min. addition 100 : 0 S C U 8 Catalysed nucleophilic additions Miura and co-workers have reported the copper-catalysed reaction of aryl iodides with active methylene compounds.'*' For example, the reaction between iodobenzene ( 14 1) and ethylcyanoacetate (27 1) affords the substituted aromatic compound 272 in 89% yield. Frost and Williams: Catalvtic amlications of transition metals in nrmnir wnthmiv 7910 mot% PhI 141 CuBr * Ph4'" CN 120%.DMSO COPE1 89%yie# - 271 272 Rhodium catalysts have been employed to effect nucleophilic additions to imines.126 Thus, the reaction between the imine 273 and the methylmalonitrile 274 affords the product of nucleophilic addition 275 using a rhodium catalyst. A palladium(o) catalyst was also found to be effective. Y 273 27s 9 Metathesis Grubbs and co-workers have extended their ring-closing metathesis methodology to include a wider range of substrates. The reaction of enol ether 276 with the molybdenum catalyst 277 affords the ring-closed product 278 in 88% yield.127 The ruthenium catalyst 279 was also found to be able to catalyse ring-closing metathesis reactions, including the conversion of 280 into 281.12* Martin and co-workers have used similar methodology to afford fused nitrogen-heterocycles." Thus, treatment of the diene 282 with catalyst 277 affords the products 283 in 80-90% yields. Me I cPh * o O n P h 12mot%m 20%.pentane, 3.91 88% yleld 278 276 277 * oco2H 2mOpx279 20%. C&. lh 281 3c02H 280 87% yield 283 n = 1,2 x = 1 9 Hoveyda and co-workers have provided a further example of a metathesis/cyclization reaction, using the ruthenium catalyst 279.I3O The diene 284 is cyclized to the racemic pyran 285. By treatment of the so-formed reaction mixture with an enantiomerically pure zirconium catalyst and ethylmagnesium chloride, a kinetic resolution process takes place, allowing recovery of the pyran 285 as a single enantiomer. 1 mdsc279 %Me Then: 10 mi% zr conpiex EtMgCl Me 25to70'C.THF 285 (>Woe.e.) 10 Miscellaneous Frauenrath and Kaulard have examined an interesting asymmetric isomerization of the achiral substrate 286 into the enantiomers 287 and er~t-287.'~~ Using an enantiomerically pure ruthenium catalyst, the product is obtained with modest enantioselectivity. Trost and co-workers have continued to find synthetic applications for the unusual ruthenium-catalysed addition of alcohols and a~ety1enes.l~~ For example, the reaction of the alkyne 288 with ally1 alcohol 289 with a ruthenium catalyst affords the addition product 290, which was further elaborated to rosefuran (291).133 286 287 h O x 0 Ph H ent-287 291 A Japanese group has reported the remarkable ruthenium-catalysed dimerization of norbornadiene (292) to pentacyclotetradecadiene (293) in 85% yield.134 It has been assumed that this reaction proceeds by repeated activation of one or more C-C bonds.292 NMP 293 80 Contemporary Organic Synthesis11 Conclusion Transition metal catalysed reactions have continued to grow in importance. The areas of asymmetric catalysis, and the development of tandem and cascade sequences are examples which demonstrate the efficiency of transition metal catalysed reactions, both in terms of potential and of the tremendous achievements already attained. 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ISSN:1350-4894    

DOI:10.1039/CO9950200065

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

Organic halides PETER L. SPARGO Process R &D Department, Pfizer Central Research, Sandwich, Kent, CT13 9NJ, UK Reviewing the literature published between 1 st July 1993 and 30th June 1994 1 2 2.1 2.2 2.3 2.4 3 3.1 3.2 3.3 3.4 4 4.1 4.2 5 6 7 8 9 9.1 9.2 9.3 10 Introduction Alkyl halides By halogenation of alkanes By halogenation of alkenes By nucleophilic substitution By other methods Vinyl halides From alkynes From other vinyl derivatives By C=C bond formation By other methods Aryl halides By electrophilic substitution By nucleophilic substitution Alkynyl halides 1,l -Dihalo compounds I, 1 -Halohydrins and related compounds 1,2-Dihalo compounds 1,2-Halohydrins and related compounds By addition to alkenes By epoxide opening By other methods References 1 Introduction Organic halides continue to be a cornerstone of organic synthesis, with new and selective methods for their preparation constantly being sought.This review covers the literature published between 1 July 1993 and 30 June 1994 and is necessarily selective, with particular emphasis being given to procedures likely to be of wide use or interest to the practising synthetic organic chemist. The chemistry of perfluoroalkyl and hypervalent iodine compounds will not be discussed here. Apart from the previous review in this series,' no general reviews on organic halides have appeared this year. In contrast, the synthesis of organofluorine compounds has been the subject of a number of review^,^-^ covering such topics as nucleophilic fluoride transfer reagents2 and fluorinated organ~metallics.~ A special edition of Tetrahedr0n:Asymmetry was devoted to the enantiocontrolled synthesis of fluoro-organh6 Preparative procedures of potential general interest include a convenient and economic way of producing anhydrous hydrogen bromide by heating hydrogen triphenylphosphonium bromide (Ph,PHBr),' and a new method for making triphenylphosphine dichloride (Ph,PC12) by reaction of triphenylphosphine with triphosgene.* A solid hydrogen fluoride equivalent, PVPHF [ poly-4-vinylpyridinium poly( hydrogen fluoride)], has been developed and used to hydrofluorinate alkenes and alkynes, to convert secondary and tertiary alcohols into alkyl fluorides, and (when combined with an electrophilic bromine source) to effect 1,2-bromofluorination of alkenesY The preparation of a range of chiral brominating and chlorinating agents has also been described,'() although their synthetic utility has yet to be reported.2 Alkyl halides 2.1 By halogenation of alkanes The halogenation of unactivated alkanes has made limited progress since the previous review in this series.' Reports published this year concern the electrophilic fluorination of methane to methyl fluoride using N2F+ and NF,' salts," continuation of work in the Barton group using GoAgg" systems in the halogenation of cycloalkanes,'2 and a 1,2-fluorohydrin synthesis from alcohols using the 'Selectfluor' reagent F-TEDA-BF, ( 1, Scheme 1 ). A, R=M€?,At Scheme 1 Benzylic bromination of phenylalanine and tyrosine derivatives with N-bromosuccinimide has been used in the synthesis of diastereomers of /?-hydroxyphenylalanine and /?-hydroxytyrosine, but the halogenation step lacked stereo~electivity.'~ Regiocontrol has been observed in the uncatalysed benzylic bromination of polymethyl substituted thiophenes (Scheme 2),15 and in the bromination of a dihydropyridine derivative for the synthesis of the calcium antagonist nivaldipine (Scheme 3).16 Spargo: Organic halides 85Scheme 2 C02POM DMAP.HBr.Br2 M302* 1 or pyridine.HBr. BrIC Br 01 collidine. HBr. Br2 Meo2c2i H 56-65% The related diastereoselective bromination of enolates of oxazolidinone-derived amides continues to be a focus of the Hruby g r ~ u p , ~ ~ . ~ ~ but unlike the previous example, the stereocontrol is exerted by the #?-alkyl substituent (Scheme 6). This hypothesis is supported by the chemistry depicted in Scheme 7, where the oxazolidinone is a ~ h i r a l .~ ~ d N A (i) MeMgBr. CuBr-SMe, Ar uO ( i i ) W z 8 % Ar I Ph Z N A * Br tJ Ph > 99% d.e. Scheme 3 Scheme 6 The halogenation of enol derivatives, especially enolate anions, continues to be a powerful way of synthesizing a-halo-carbonyl compounds. The long-established conditions for the 2-halogenation of 1,3-dicarbonyl compounds using cupric chloride (CuCl,) or cupric bromide (CuBr,) have been further explored this year, with particular emphasis on their application to P-ketoesters' and cyclic #?-diketones.' These mild conditions enable excellent chemoselectivity to be achieved in cases where other unsaturated functionality such as an alkene or an alkyne is present.For fluorination of 173-dicarbonyl systems, the Selectfluor reagent F-TEDA-BF4( 1) has been found to give high yields." N-Fluorobenzenesulfonimide (PhSO,),NF is the preferred reagent for the diastereoselective fluorination of 2 (giving a modified taxol side-chain) (Scheme 4),** and of 3, where the stereocontrol is exerted by the homochiral oxazolidinone group (Scheme 5).21 PhCONH PhCONH 2 81 : 19 anti : syn Scheme 4 > 99% d.e. Scheme 5 86 Con temporary Organic Synthesis R O O R O O u N K (i) Bu2BOTf. Pr"Et2 Ar 0 (ii)NBS,-78'C Ar > 99% d.e. Scheme 7 Other a-halogenation procedures of note include the (diastereoselective) a,a'-diiodination of ketones with iodine and ceric ammonium nitrate (CAN) (Scheme 8),25 and an a-bromination of acetals (Scheme 9)26 which proceeds via a transient enol ether intermediate.The latter procedure is reported to be suitable for large scale work. Finally, a-halomethylketones have been prepared from vinyl halides as indicated in Scheme 0 Q I n 1 67:33 2 92: a 3 100: 0 4 0:lOO Scheme 8 OMe Br2, TMSCI, NaBr RAoMe MeCN/MeOH. 40 % Br 8748% Scheme 9X1 0 RA NCS MeCNfHP or NBS or NIS R&X2 5245% X' = CI, Br x2= CI, Br, I Scheme 10 2.2 By halogenation of alkenes Hydrogen-halogen addition to alkenes is a relatively infrequently used synthetic approach to alkyl halides, but this year has seen a new and general hydrofluorination procedure using the solid hydrogen fluoride reagent PVPHEY Hydrobromination is a key step in an improved preparation of 2-( 2-bromoethyl)-l,3-dioxan (Scheme 1 1),28 and two reports of asymmetric induction in the hydrochlorination of acrylate derivatives have appeared (Schemes 1 229 and 1330).Although the observed diastereoselectivities in the latter chemistry may not seem particularly high by today's standards, there are very few reported methods for the asymmetric addition of halide ions to crotonates. Scheme 11 R = (S)-1-(1-naphthy1)ethyl 78% d.e. Scheme 12 CI 0 0 BCIAOP CH&I, t ) -78 (2.5 'c eq.) M e & k , 3 (80% d.e.) )-{ Carbon-halogen addition to alkenes is also an area of continuing interest, much of the published work has centred around radical additions of polyhaloalkanes. Some representative examples of these are shown in Schemes 14,3' 15,32 16,33 17,34 18,35 and 19.36>37 Polyhalogenated precursors are not essential, however, and additions of monohaloalkanes across double bonds have been described in both intermolecular (Scheme 20)38 and intramolecular senses, the latter giving heterocycles according to the generalized transformation of Scheme 2 1 .39340 A related * CI 60% Scheme 14 Scheme 15 Scheme 16 Scheme 17 (single diastereomer) Scheme 18 R = H 22178 R = 1-amyls 100 : 1 Scheme 19 Scheme 20 Scheme 21 Spargo: Organic halides 87transformation can also be achieved ionically (Scheme 22)?1 A completely different ionic cyclization process or fluorides by treatment with boron t r i b r ~ m i d e ~ ~ or PVPHF (the previously mentioned solid hydrogen fluoride source9) respectively.Meanwhile, primary and which nevertheless results in net addition of carbon and chlorine across a double bond is depicted in Scheme 23.This approach has been used to prepare a wide range of oxygen-:* nitr~gen-;~,~~ and selenium-45 containing halogen substituted heterocycles. (81% &) Scheme 22 CI Scheme 23 2.3 By nucleophilic substitution The counter-thermodynamic Finkelstein conversion of primary alkyl chlorides into bromides of high ( > 99%) purity has been achieved by repeated treatment (the second after aqueous work-up) with 10 equivalents (each) of lithium bromide in refluxing pentan-2-0ne.~~ The most popular precursors to alkyl halides continue to be alcohols, of course. A correction to a previously reported chemo- and stereo-selective fluorination has been published: treatment of polyol4 with diethylaminosulfur trifluoride (DAST ) gives 5 exclusively and not the isomer 6 (Scheme 24).47 Meanwhile, the conversion of methanol or ethanol into the corresponding alkyl chloride by reaction with thionyl chloride has been the focus of some detailed mechanistic physical organic chemistry.48 secondary alcohols are transformed into the corresponding iodides in good yields by treatment with thionyl chloride and potassium iodide in DMF (Scheme 25).50 The use of DMF is significant, since one of the reaction intermediates is the formamidinium species 7 (as evidenced by the formation of the corresponding formate ester ROCHO under slightly different reaction conditions).DMF is also important in the conversion of alcohols into alkyl chlorides using phosphorus oxychloride ( P O C ~ ~ ) . ~ ~ 7 W% Scheme 25 Milder conditions for phosphorus-based activation of alcohols towards halide displacement continue to find regular application; examples reported this year include the combination of triphenylphosphine with CBr452 and with I , / i m i d a ~ o l e , ~ ~ ~ ~ ~ smooth inversion of configuration being not unexpectedly observed in the case of a secondary alcohol.54 In addition, triphenylphosphine iodochloride (Ph,PICl) has been used to convert silyl ethers of perfluoroalcohols into perfluoroalkyl iodides.55 Examples of secondary alcohol halogenation with inversion of configuration by prior conversion into the corresponding triflate56 or m e ~ y l a t e ~ ~ ? ~ ~ have been described. In the latter case, it was shown that displacement with fluoride ion can be used for the stereospecific introduction of fluorine a-to a carbonyl group57 and in benzylic positions of electron-deficient aromatic^.^^.^^ It was noted, however, that a-fluorophenylacetic acid could only be obtained in racemic form under these conditions because the basicity of the fluoride ion causes epimerization of the chiral centre.This deficiency might be mitigated by the use of an enzymic resolution of the a-haloester, a process whose mechanistic aspects have recently been discussed in some detail.5Y prepared by way of the novel approach depicted in Scheme 26.6O This transformation proceeds through the 1,l-dichloroepoxide 8, but its stereochemical aspects have yet to be disclosed. a-Fluoro-carbonyl compounds can also be 5 6 / Scheme 26 Scheme 24 More general, synthetically useful procedures include the conversions of secondary and tertiary (but not primary) alcohols to the corresponding bromides The cleavage of cyclic ethers (particularly tetrahydrofurans) to halides has been studied by a number of groups.Acylative cleavage of tetrahydrofuran was reported using Sm12,61 and it was 88 Contemporary Organic Synthesisalso shown that the related cleavage of 2-methyltetrahydrofuran could be controlled to give either regioisomer (Scheme 27).h2 Regioselective cleavage was also observed on treatment of 9 with trimethylsilyl chloride in the presence of sodium iodide (Scheme 28)P3 Silyl ethers themselves can be converted into fluorides (with inversion) using a piperidine analogue of DAST,64 and a conversion of chiral amhe ditosylates to secondary alkyl chlorides has been described (Scheme 29).65 RCOCI, NaI MeCN, r.t.(R t ELI', CC15 C3F7) 5645% 140COR Scheme 27 9 67-75% Scheme 28 NTs2 NH&I -80% R A DMForDMSO R 0434% inversion Scheme 31 fluorodecarboxylation of cyclopropane carboxylic acids has also been reported using elemental fluorine in a basic aqueous sodium fluoride solution.@ Radical conditions can also be used to convert organocobalt species into alkyl chlorides (Scheme 32),70 while by judicious choice of reagent, the zirconacyclopentene 10 can be chemoselectively converted into the homoallyl bromide 1 1 (Scheme 33).71 Scheme 32 10 Scheme 33 Sr 11 The reduction of 1,l -dihalocyclopropanes to monohalocyclopropanes (Scheme 34) has been reported under a number of conditions, including NaH or ButOK in DMS0,72 hydrazine followed by Raney or VC1,-Zn-qOEt)3.74 NaHlDMSO ~ ( l ) NHzNHa (U) R a n ~ NI.KOH ~4 4~vCl&+P(OEt)3 RI Scheme 29 R' Lastly, it has been found advantageous to use catechyl phosphorus tribromide instead of triphenylphosphorus dibromide or gaseous HBr for ~~ the preparation of 1,4-dibromobutane from tetrahydrofuranP6 X', X2 = Br, CI 2.4 By other methods A recent procedure for the direct conversion of trialkylboranes into alkyl halides uses elemental 30)P7 The reaction proceeds with retention of configuration and all three alkyl groups end up as alkyl halides. Scheme 34 Other more obscure but nevertheless interesting alkyl halide syntheses published this year include a Scheme 3575), and the halogenation of 4-substituted phenols (and anisoles) to give 4-halo-cyclohexadienones (Scheme 36) using pyridine poly( hydrogen fluoride) in combination with either iodobenzene diacetate (giving the fluoride)79 or SbF, in CH,Cl, [giving the chloride ( sic)].8o chlorine (or bromine) under (Scheme number of oxidative fragmentation reactions75-78 ( e.g.R = norbomyl 0 Scheme 30 Radical halodecarboxylation of acids via thiopyridylhydroxamate ('Barton') esters continues to be a method of choice for the preparation of bridgehead halides (Scheme 31),68 although direct 46% Scheme 35 Spargo: Organic halides 89Hal = F, CI Scheme 36 3. Vinyl halides 3.1 From alkynes The hydrohalogenation of alkynes has been studied in some detail by Kropp and Crawfordsl who have found that appropriately prepared silica gel or alumina can mediate the reaction with a good degree of stereocontrol.Even more conveniently, acid halides such as SOCl,, (COCI),, PBr,, (COBr),, AcBr, PI,, and AcI can be used as the source of hydrogen halide since, in the presence of silica or alumina, hydrogen halide is generated in situ. Thus, 1-propynylbenzene 12 can be converted into the syn addition product 13 or, on extended treatment, to the thermodynamically more stable (2)-isomer 14 (partly through addition-elimination via a geminal dihalide intermediate) (Scheme 37). (To put this method into context, 12 does not react at all with HC1 in CH,Cl,.) An added benefit of this heterogeneous chemistry is that HBr addition gives only the Markovnikov isomer, in contrast to the mixture of regioisomers more typically obtained under homogeneous conditions.X Ph+Me- P h + n L Me 12 13 X =CI, Br, I 14 Scheme 37 Another hydrohalogenation procedure of some generality is the regio- and stereo-specific hydrohalogenation of 2-alkynoic acids and their derivatives (Scheme 38).*, s29c Me' Scheme 38 More specialized hydrohalogenation procedures reported this year include a novel supported liquid-phase rhodium catalyst for the mercury-free production of vinyl chloride from acetylene,83 the regiospecific (but low yielding) tritiobromination of alkenes under zirconium catalysis (Scheme 39),84 and a novel stereoselective hydrohalogenation- deconjugation reaction (Scheme 40).85 widely applied to cyclizations, either radi~ally~~9~~ ( e.g. Scheme 4 1 86) or under palladium catalysis,s8-90 Carbon-halogen addition to alkynes has been Scheme 40 FP Scheme 41 an example of the latter being depicted in Scheme 42.'O Intermolecular carbon-halogen addition processes are also a powerful synthetic approach to vinyl halides, as the transformations shown in Schemes 43:' 44,Y2 45y3 46y4 and 4795 illustrate.M ~ N 7141% Scheme 42 Scheme 43 Scheme 44 Scheme 45 Scheme 39 Scheme 46 90 Contemporary Organic SynthesisCI. ,Bu 9 8 Scheme 47 Scheme 52 Heteroatom-halogen additions to alkenes and alkynes are exemplified by the cyclization reactions depicted in Schemes 4 V 6 and 49,"7 while a more unusual approach to vinyl iodides from propargylic alcohols uses Koser's reagent PhI(0H)OTs as catalyst and N-iodosuccinimide as iodine source (Scheme 50).'8 Scheme 48 Scheme 49 Scheme 50 3.2 From other vinyl derivatives The monochlorination of quinonesgg and coumarins'OO is readily achieved with copper( 11) chloride on alumina in chlorobenzene,YYJOO and with dichlorine monoxide in carbon tetrachloride,'"' the latter process being significant in that aromatic chlorination is not observed in naphthoquinone systems (Scheme 5 1).Bromination of related systems can be achieved by adaptation of the former process,100 or by a completely different method using bromoform (CHBr,) (Scheme 52). O2 For iodination, benzyltrimethylammonium dichloroiodate (BTMA-ICl,) has been found particularly effective (Scheme 53).lo3 ij 0 X = CHZCHZ, 0, S Scheme 53 An area of detailed study is the regio- and stereo-selective bromination of dehydroamino acids (Scheme 54), which can be carried out with controllable retention or inversion of alkene configuration.lo4 The kinetically favoured (E)-isomers are obtained using hindered amine bases (e.g. lithium 2,2,6,6-tetramethylpiperidide, sodium hexamethyldisilazide) for deprotonation of the a-bromoimine intermediate 15, whereas use of DABCO as base yields the thermodynamically favoured (Z)-isomer by isomerization. The picture is not quite as simple as this, however, as the nature of the brominating agent also influences the stereoselectivity. 049105 U I Scheme 54 Conversions of a number of alkenyl metal compounds into vinyl iodides according to Scheme 55 have appeared regularly in the literature, the most common precursors being vinyl stannanes,106-108 with isolated examples of vinyl zirconiurnloY or germanium' lo precursors. Vinyl silanes can also be used to prepare the corresponding vinyl bromides as the example in Scheme 56 illustrates.' M=Sn,Zr,Ge Scheme 51 Scheme 55 Spargo: Organic halides 910 0 Scheme 56 Interconversion of vinyl halides is possible under certain conditions (Scheme 57),l l2 and vinylic hypervalent iodine derivatives 16 have proved useful as synthetic precursors to (2)- 1,2-ethylene dihalides (Scheme 58).l l 3 Steroidal vinylic 1,2-dihalides have also been accessed from vinyl sulfides as Scheme 59 shows.' l 4 Reduction of 1,l-dihaloalkenes by bromine-zinc exchange followed by protonolysis also offers access to vinyl halides (Scheme 60).Il5 Scheme 57 16 Scheme 58 0 &p Br & 0 Scheme 59 double bond itself offers an alternative and less widely used approach to these systems, mostly by way of Wittig-type procedures, typified by the vinyl iodide synthesis depicted in Scheme 6 1 A number of syntheses of a-fluoro-a,/?-unsaturated esters have been described using Wittig' 17-1 l 9 and non-Wittig chemistry (Scheme 62),11' as well as the unusual stereoselective transformation shown in Scheme 63.120 Scheme 61 Scheme 62 0 21 E ,8020 Scheme 63 3.4 By other methods The patent literature reports the conversion of ketones into vinylic fluorides by treatment with DAST and sulfuric acid.121 Meanwhile, more established methodology for vinyl iodide synthesis (reaction of ketone hydrazones with iodine and base) has been applied in the preparation of a calyculin fragment.122 The direct transformation of ketones to vinylic bromides using pyrocatechyl phosphorus tribromide and methyl formate has been examined in some detail and proceeds via a geminal dibromide intermediate as shown in Scheme 64.123 Related vinyl halide preparations by base-catalysed elimination of HBr from 1,l-dibromoalkanes' 24 or 1,l-bromoflu~roalkanes~ 25 have also been described. In addition, the regioisomeric 1,2-dibromides are useful vinylic bromide precursors,l 26-1 2y with particularly interesting examples illustrated in Schemes 65 12* and 66.12' Hal = CI.Br Scheme 60 3.3 By C=C bond formation While many vinylic halide preparations start from a often %loo% preformed alkyne or alkene as described in Sections isdable wed 3.1 and 3.2 above, the synthesis of the carbon-carbon Scheme 64 92 Contemporary Organic Synthesis9‘ 4 Aryl halides 4.1 By electrophilic substitution 7396 Scheme 65 THF,-70“C /-- 73% e.e.> 99% Aromatic chlorination, bromination, and iodination of polyalkylbenzenes can be effected with PhI( 0H)OTs (‘Koser’s reagent’) in the presence of the requisite halide ion (Scheme 7 1 ).’ 34 Interestingly, benzene, toluene, and acetophenone do not react under these conditions, which also do not permit fluorination. Indeed, reports of electrophilic aromatic fluorination are few and far between, the most significant this year being the use of xenon difluoride to fluorinate pyrroles carrying an electron-withdrawing group and without NH protection (Scheme 72).135J36 Scheme 66 X A one-pot conversion of saturated lactams into a-halo-a,/?-unsaturated lactams is shown in Scheme 67,130 while reductive elimination of bromine can be used to synthesize strained bromocyclopropenes (Scheme 68).131 (9 UHMDS R R R=H.Me Scheme 67 Scheme 68 A synthetic equivalent of the 1-fluoroethylene anion is the silyl stannane 17, which undergoes a range of palladium-catalysed couplings followed by desilylation to yield vinyl fluorides (Scheme 69).132 17 awl Scheme 69 Finally, a novel one-step homologative process for the synthesis of a-chloro-a,/?-unsaturated ketones has been developed with in situ generated dichlorocarbene as the key reactive species (e.g.Scheme 70).133 Scheme 71 Scheme 72 In contrast to fluorination, bromination continues to be a very active area of research.A para-selective, high-yielding, economical, and environment ally safe bromination of anilines, anilides, phenols, and phenol ethers has been described using an ammonium molybdate catalyst with H202/KBr,13’ and there has been a Russian report of phenol monobromination using bis( dimethy1acetamido)hydrogen tribromide. 38 Attempts to control the regiochemistry of bromination of phenols and N,N-dialkylanilines using cyclodextrin~~ 39 or surf act ant^,'^^ respectively, have met with modest success. Direct bromination of benzaldehyde usually gives the rneta-substituted product, but temporary masking of the aldehyde as an 0-methyl oxime allows para-bromination to be achieved in high overall yield (Scheme 73).141 Regiocontrolled chlorination can also be achieved using this methodology.CHO I CHO I I Br 72% Scheme 70 Scheme 73 Spargo: Organic halides 93Theoretical chemists continue to challenge the mechanistic understanding of synthetic chemists, this time with calculations suggesting that the rapid bromination of 1,4-benzodithian proceeds by way of vicarious nucleophilic substitution rather than electrophilic substitution (Scheme 74).14, I I I Br- Br Br- Br Scheme 74 The trialkoxynaphthalene 18 can be converted into any one of three possible monobromination products by combinations of selective bromination, debromination, and bromine migration; 143 and enzymatic bromination of the pyrrole ring of compounds such as 19 using chloroperoxidase and H,O,/MBr has also been described.144 Turning to aromatic iodination, procedures have appeared using iodine in combination with mercury( 11) salts145 or silver(1) ~u1fate.l~~ While the electrophilic methods described above all involve replacement of hydrogen with halogen, silanes and stannanes also continue to be useful precursors to halides.In particular, iodination of furans is often best achieved via a ~ i l a n e , ' ~ ~ and thanks to advances in regioselective silylation, iodobenzenes with less-common substitution patterns are now more readily acces~ib1e.l~~ A straightforward and general method for the preparation of aryl fluorides from aryl silanes has been described using xenon difl~oride,'~~ while 2- and 3-fluoroindoles have been prepared by treatment of the corresponding 2- and 3-trimethylstannylindoles with either caesium fluoroxysulfate or with the Selectfluor reagent F-TEDA-BF4( 1 ) .I 5 O Aryl stannanes have also been used as precursors to radiolabelled aryl iodides using iodine- 12 5 .I5 More unusual preparations of aryl halides reported this year include the conversion of aryl lead triacetates into aryl fluorides using boron trifluoride etherate,15, and a palladium-catalysed conversion of arylsulfonylchlorides into aryl iodides.' 53 The other common approach to aryl halides using electrophilic halogens is via directed lithiation, which has proved particularly useful for the ortho-fluorination of aryl amides, carbamates, phenol ethers, sulfoxides, sulfones, sulfonamides, and oxazolines (Scheme 75).154J55 With N,N-diethylbenzamide as substrate, and using N-fluorobenzenesulfonimide, (PhSO,),NF, as the electrophilic fluorine source, unexpected transfer of OMe od Me0 a "-0-0 0 OAc csr 18 19 DMG = directed metallation group CONHBU' OCSNEt2 S02NHMe eNR32 (R3 = Me, Et) OMe oxazoline CONEtp S(O),,Bd (n = 1,2) Scheme 75 the PhSO, group was observed,154 whereas use of N-fluoroqumuclidinium fluoride gave the expected f l ~ 0 r i d e .l ~ ~ Other examples of metallation-halogenation have been described in pyrr01e'~~ and ~ y r i d i n e ' ~ ~ systems, and an interesting 'halogen dance' has been observed (Scheme 76).'58 Finally, an unusual cyclization of substituted benzotriazoles to halogenated dihydrobenzofuranyl systems has been described (Scheme 77).15Y A transient aryne intermediate is proposed. I (I) LDA, THF (U) MeI, -75 OC (W H P 93% Scheme 76 Scheme 77 4.2 By nucleophilic substitution Nucleophilic substitution with halide ion is a less common approach to aryl halides.The synthesis of fluorides by this approach has been the subject of a review which places particular emphasis on 94 Contemporary Organic Synthesismechanistic aspects.160 Perhaps the most significant development in the area is a high-yielding and facile preparation of aryl fluorides from aromatic diazonium tetrafluoroborates under photochemical conditions (Scheme 78).161 The transformation can also be achieved thermally, but yields are much more variable (and often poor). The substitution of heterocyclic chlorides with fluoride ion via quaternary ammonium intermediates has been applied to the synthesis of potential prodrugs of acyclovir and ganciclovir (Scheme 79).'62 KF + * ArF HF-pyrMine hv 80-94% ArN2'BFd DMF A 56-6096 Scheme 78 Scheme 79 R 43 HO Bu3SnH c AIBN, A W% HO Scheme 81 20 Scheme 82 using DAST has been described,166 as well as the preparation of 1 , 1 -halofluoroalkanes from geminal bis-triflates (Scheme 83).167 Geminal difluoroalkanes were prepared from ketones via oximes [using NOBF, and pyridine poly( hydrogen fluoride)],168 imines (using BrF,),*69 and dithioacetals [using SO,Cl, and pyridine poly( hydrogen fluoride)], 70 while related transformations were also reported for higher oxidation state carbonyl compounds such as esters (Scheme 84),171 amides,17, and t h i o ~ a r b o n a t e s .' ~ ~ , ~ ~ ~ In addition to these procedures, a method for the synthesis of 1,l -dibromoalkanes from ketones has already been mentioned in Section 3.4 (Scheme 64).123 OTf Bu"4N+ Ph3SnF2- OTf Bu"4N+ X- RAoTf CH&12, 0 oc * RAF CHsI, r.t. * JF 5 Alkynyi halides The only new literature in this area describes an improved procedure for aldehyde to alkyne Scheme 83 homologation via 1 , 1-dibromoalkenes (Scheme 80).163 7- 8648% Scheme 80 6 1,l-Dihalo compounds The preparations of some 1 , 1 -dihaloalkanes from 1 , 1 , 1-trihalomethyl units have already been mentioned in this review (e.g.Schemes 15-18, Section 2.2). While in those examples the radical resulting from the alkene addition step was trapped with a halogen radical, trapping with a hydrogen radical has also been reported (Scheme 81).164 Another variation on the same theme is the cyclization of the l,l,l-bromodifluoro alkyne 20 (Scheme 82).'65 The most widely used approach to the synthesis of 1 , 1-dihaloalkanes starts from carbonyl compounds or their derivatives.During the period under review, the conversion of aldehydes to geminal difluoroalkanes X = CI, Br, I (W% overall) Scheme 84 A detailed study of the photochemical benzylic di- and tri-bromination of methyl-, dimethyl-, and trimethyl-benzenes with N-bromosuccinimide has been made;175 it was found that l,l,l-tribromination was facile, except in the presence of an ortho substituent, in which case 1 , 1-dibromination was preferred. 1 , 1 -Dihalocyclopropane derivatives can be prepared either by phase-transfer catalysed addition of dichlorocarbene (from CHClJNaOH) to acrylates and crotonates (Scheme 85),176 or by the addition of ethyl diazoacetate to 1,l -difluoroethylene (Scheme 86).177 Other approaches to 1 , 1-dihaloalkanes include the double hydrofluorination of alkynes using the solid hydrogen fluoride source PVPHF (Scheme 87),9 and the oxidative acetal halogenations shown in Scheme 88.178,179 Spargo: Organic halides 95R3 CI, ,CI cat.Me4NBr "' 11-7836 EWG = CN, C 0 2 d Scheme 85 - quanf.Scheme 86 Scheme 87 Me (i) trichbroisocyanuric ac# >rCO2Me Y (U)MeOH/ac#orbacre X R2 634896 X = H +Y = CI X=Br+Y=Br Scheme 88 Syntheses of vinylic geminal dihalides appeared regularly in the year's literature. In addition to that already mentioned in Section 5 above, a general preparation of 1,l-diiodoalkenes by Wittig type procedures (Scheme 89),' 8o an unusual approach to geminal difluoroenol ethers (Scheme 9O),l8l a synthesis of 1,l -fluoroiodoalkenes by functional group manipulation of 1 -fluoro- 1 -sulfonylalkenes (Scheme 9 1 ), 82 and further examples of previously described Scheme 89 Scheme 90 rearrangement reactions to give 1,l-bromoiodoalkenes (Scheme 92)' 83 were reported. 1,l-Bromochloroalkenes are readily prepared from 1,l-dibromoalkenes as shown in Scheme 93.115 Other vinylic dihalides arose from elimination reactions (Scheme 94) in rather specialized will therefore not be discussed here.and V V Scheme 92 Scheme 93 LG = Leaving GLoup Scheme 94 7 1,l-Halohydrins and related compounds Non-glycosidic 1,l-fluorohydrins are not particularly common, but a novel method for the preparation of fluoromethyl phenol ethers has been reported (Scheme 95).' 88 Meanwhile, another unusual and not particularly chemoselective approach to 1,l-halohydrins is the chlorination of ethers with sulfuryl chloride (Scheme 96).18y Scheme 95 38 : 4 : 4 4 : 4 Scheme 91 Scheme 96 96 Contemporary Organic SynthesisOf wider synthetic interest are the glycosyl halides.There have been reports of glycosyl fluoride preparations from a range of different precursors, including glycosidic acetals ( HF/MeNO2),Igo azides (Scheme 97),19' and bromides, the latter proceeding with inversion of configuration at the anomeric centre as indicated in Scheme 98.Ig2 Inversion of configuration is also observed in the preparation of a-glycosyl bromides from acetals containing mandelonitrile as the anomeric activating group (Scheme 99).lg3 a-Glycosyl bromides are the preferred products of glycal bromination with tetraalkylammonium tribromides as Scheme 100 indicates.* y4 ACO O G N 3 OAc Scheme 97 E+E - (E - COZBu') 75% ACO \ ACO' & MeCN 61- Scheme 98 + ACO Br Scheme 99 OBn OBn Fluoromethylsulfides are readily prepared from methyl thioethers by treatment with either xenon d i f l ~ o r i d e ~ ~ ~ or diethylaminosulfur tritluoride (DAST)1y6J97(Scheme 101). RS-F XeF2 or RSMe DAST Scheme 101 8 1,2-Dihalo compounds The direct fluorination of alkenes with molecular fluorine19s is a difficult and rarely used synthetic procedure, the capricious nature of which was borne out by a recent attempt to repeat a literature fluorination of 4-cholesten-3-one. While earlier workers have reported a 70% yield of the cis-difluoride 22 from 21, the repeat reaction proceeded in only 17% yield (Scheme 102).19y This was nevertheless used as a fairly direct way of introducing a fluorine atom to a carbonyl group as indicated in the Scheme.Xenon difluoride can also be used to difluorinate alkenes, but phenyl substitution of the alkene is required.200 t 21 22 Scheme 102 A new transition metal catalysed alkene 1,2-dichlorination has been described which proceeds in the presence of a number of functional groups such as hydroxyl, carboxyl, and activated methylene (Scheme 103).201~202 Scheme 103 Bromination of alkenes has once again been the focus of theoretical calculations,203 and the influence of cyclodextrins on the bromination of chalcone has been investigated and shown to be very modest (Scheme 1 04).204 without p-cydodexlrin-100 : 0 (49ryU~m: threo) with &cydodextrin-W : 20 (erythro: threo) Scheme 100 Spargo: Organic halides Scheme 104 97Bromofluorination of alkenes can be effected with the new solid hydrogen fluoride source PVPHF, when combined with NBS or DBH.' 9 1,2-Halohydrins and related compounds 9.1 By addition to alkenes This year saw the publication of a detailed review on the intermolecular addition of halogen and either oxygen or nitrogen nucleophiles to alkenes (a transformation termed 'cohal~genation').~~~ The review discusses the regio-, chemo-, and stereo-selectivity of the process, and presents examples of cohalogenation with a wide variety of nucleophiles (water, hydrogen peroxide, carboxylic acid derivatives, alcohols, ethers, nitriles, amines, and pseudohalogens).New procedures in the primary literature include the application of the Selectfluor reagent F-TEDA-BF4( 1),06 (or C S S O , ~ ~ ~ ) to the preparation of vicinal fluoro ethers (Scheme 105), and the first practical method for selective heteroatom-directed chlorohydroxylation of alkenes (Scheme 1 06).207 In the latter paper, up to 76% diastereomeric excess was reported for allylic amines carrying a chiral ( R3 = a-methylbenzyl) substituent. Scheme 105 6941% - X =S, NR3 Scheme 106 The formation of bromohydrins from o-alkenyl glycosides 23 has been studied in some detail,208 and this paper contains an interesting account of the transfer of Br + from cyclic bromonium ions to alkenes.23(n=3,4) A one-pot procedure for regioselective bromine-alcohol addition to acrylates has described (Scheme 107).20' Although this been method accommodates a wide variety of alcohols, the generally modest yields and the stoichiometric use of mercury bis( trifluoroacetate) will probably limit its wider application. Scheme 107 Bromolactonization with an unexpected stereochemical outcome has been described (Scheme 108),210 as well as biocatalytic bromohydrin formation using haloperoxidase enzymes (Scheme 1 09).21 The products obtained in the latter case were racemic. Scheme 108 Scheme 109 Perhaps not surprisingly, the halogen most widely used in cohalogenation chemistry continues to be iodine. Iodolactonization is regularly applied in synthesis,212 and many of the iodolactonization protocols described in the previous review in this series' have been developed further.These include seven- to eleven-membered ring-forming procedures2 enhanced by geminal dimethyl substitution,214 and the enhancement of diastereoselectivity in intramolecular iodocarbonation by using IBr instead of I, (Scheme 1 There have been other publications concerning the stereochemistry of iodocarbonation,2 iodo~arbamation,~~~ and iodolactonization ( e.g. double diastereoselectivity, Scheme 1 1 1),,18 but space limitations preclude further discussion of these. An interesting use of iodolactonization chemistry for the mild hydrolysis of y,d-unsaturated amides is depicted 0 0 d.e.(IBr)A.e.(Iz) Scheme 110 >95% d.e. Scheme 11 1 98 Contemporary Organic Synthesisin Scheme 1 12.21y Of perhaps more general interest is a new and general iodolactonization procedure for P,y- and y,b-unsaturated carboxylic acids via the oxidation of iodide with sodium persulfate in aqueous solution.220 This method is fast, very high yielding, and exceptionally clean. Scheme 112 (Scheme 1 1 7),227 and electronic effects can strongly influence the stereoselectivity of cyclization of the allylic amines 24 (Scheme 1 1 8).228 Other unusual and interesting stereoselective examples are illustrated in Schemes 1 1922y and 120.230 Finally, cis-selective iodoetherification has been applied in the synthesis of N-aryl morpholinyl systems, although concomitant aromatic iodination also occurs unless the para position of the N-aryl group is blocked (Scheme 12 1 ).231 H H i Intermolecular iodoacylation can be mediated by Scheme 117 lead (Scheme 1 13),221 and by the use of N-iodo-p-nitrobenzamide as electrophilic iodine diastereospecificity source (Scheme 1 14).222 is observed Meanwhile, in the NyJH r, N W ' + N 8 ; y 1 C iodohydroxylation of 1 -acetoxycyclohexene by way of N-3 as-sssc intramolecular oxygen delivery (Scheme 1 1 5).223 Regioselective alkoxy- and, more unusually, nitrato-iodination of a,p-unsaturated carbonyl R=COMe 24:76 compounds has also been described, using iodine and cerk ammonium nitrate (Scheme 1 16).224 24 RzS02CF3 9317 Scheme 118 Scheme 11 3 I* 98% Scheme 11 9 Scheme 11 4 Scheme 115 0 xo 0 1 (X = R3 or N02) Scheme 116 OMe I Q Scheme 120 Scheme 121 Other heteroatoms which have been added across alkenes simultaneously with halide include nitrogen232-234 and selenium,235 but these will not be discussed further in this review.Intramolecular iodoetherification has been widely used in the synthesis of tetrahydrofuranyl systems.225-230 For example, high levels of stereocontrol can be realized in the formation of bicyclic systems by using strictly anhydrous conditions Spargo: Organic halides 999.2 By epoxide opening The regio- and chemo-selective synthesis of halides has been the subject of a detailed review by experts active in the area.236 The review covers a range of metal counter-ions and discusses the influence of proximate functional groups such as alcohols and carbonyl groups. bromide, or iodide ion has been shown to occur chemoselectively as shown in Scheme 122,237 while cyclohexene epoxides can be opened regioselectively using dilithium tetrachlorocuprate ( Li2CuC1,) or dilithium tetrabromonickelate (Li,NiBr,) ( e.g.Scheme 1 23).23x HF-atnine ~ .i&F + Ri.&,oH 1,2-halohydrins by the cleavage of epoxides with metal R2 R2 f# Scheme 125 &R ~(oph82 PhH R HO , HO The reaction of 2,3-epoxy-l-tosylates with chloride, Hb **O 538% Scheme 126 " w CN R2 0 2 R 3 HF-pyridine CH2cI2 c R 2 w C 0 2 R 3 F O H -9 MHal R L O T S R+oTs Amberlpt 15 6H Scheme 127 96egqc Hal = CI, Br, I Scheme 122 Scheme 123 A general and regioselective conversion of epoxides into 1,2-bromohydrins has been developed using tetrabutylammonium bromide and magnesium nitrate (Scheme 1 24).239 The very high regioselectivity of this particular process is underlined by the observation that styrene oxide (R = Ph), which under most conditions affords the secondary halide (not shown) by nucleophilic attack at the benzylic position, gives the primary halide preferentially (83 : 17 mixture).OH Scheme 128 Scheme 129 Cyclic sulfites are useful epoxide surrogates in the synthesis of halohydrins, as the example in Scheme 130 Meanwhile, a novel approach to enantiomerically enriched bromohydrins from homochiral N-tosylsulfoximino-oxiranes 25 has been described, which gives products of 70 to 91% e.e. (Scheme 13 1 ).245 Finally, ring opening of aziridine~~,~ and t h i i r a n e ~ ~ ~ ~ with halide ion have also been reported in the period under review. Scheme 124 8 The levels of stereo- and regio-control in the phqs& L i c I Z A P h q M conversion of optically active epoxides into vicinal Me OH fluorohydrins by treatment with HF-amine mixtures (Scheme 125) have been examined in some Depending on the nature of R1 and R2 and the precise conditions used, this reaction may proceed with reasonable (and sometimes excellent) regioselectivity, and also with clean inversion, or with partial racemization owing to carbonium ion formation.A number of other papers describe regioselective epoxide openings with fluoride, and examples of these are shown in Schemes 126,24127,242 128,243 and 129.64 Scheme 131 Scheme 130 Pho m J R 1: 0. MgBra B u ~ N B ~ ,s* R Et@.CH2cL, 6745% TsN ' 25 7041% 8.8. 100 Contemporary Organic Synthesis9.3 By other methods An unusual fluorohydrin synthesis has already been mentioned in Section 2.1 (Scheme 1 ), and while Sections 9.1 and 9.2 above cover the chemistry used most widely in the synthesis of 1,2-halohydrins and related compounds, there are nevertheless other methods available.These range from reactions of aldehydes with a-halo carbanion equivalent^,^^^-^^' as exemplified by Scheme 132,252 to the asymmetric cyclopropane synthesis depicted in Scheme 1 33.2537254 a-Halo- (and a,a-dihalo-) ketones have been accessed by way of the chemistry shown in Scheme 134,255 while a novel synthesis of fluoromethylketones from aldehydes has been demonstrated (Scheme 1 35).256 The high temperatures required for the latter approach render it perhaps less useful than it first appears. 0 OH 0 PhCHO + ?'sH11 Srn(HMDSh THF, -30 (0.1 Y: eq.) * P h v C s H 1 1 CI CI 909c Scheme 132 98% 8.8.67% Scheme 133 0 0 CH&a LiBr then MeLi (X' = H) or CH$'X2. 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ISSN:1350-4894    

DOI:10.1039/CO9950200085

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

Carboxylic acids and esters ~~ ~~~ T. HARRISON AND T. LADUWAHETTY Merck Sharp and Dohme, Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM202QR, UK Reviewing the literature published between 1 January 1993 and 31 July 1994 1 2 2.1 2.2 2.3 2.4 2.5 2.6 3 3.1 3.2 3.3 3.4 3.5 3.6 4 Introduction Carboxylic acids Asymmetric syntheses Homologation reactions Acids from esters and amides Heterocyclic carboxylic acids Carboxylic acid synthons Miscellaneous substituted carboxylic acids Carboxylic acid esters General synthesis Halo esters Miscellaneous methods of synthesis Hydroxy esters Keto esters Unsaturated esters References 1 Introduction This review only covers the literature pertaining to carboxylic acids, and to carboxylic esters and some of their simple derivatives.The chemistries associated with amides and amino acids, and also lactones and macrolides are covered in separate articles in Contemporary Organic Synthesis. 2 Carboxylic acids 2.1 Asymmetric syntheses Conjugate addition reactions of copper-catalysed Grignard reagents to the 4-phenyloxazolidinone 1 proceed with good to excellent diastereoselectivity to afford the adducts 2 which after hydrolysis provide the B,#l’-disubstituted carboxylic acids 3 (Scheme 1 ) in 90- 100% yield.’ The reactions involve initial complexation of the dicarbonyl system in 1 by the metal cation, with the incoming nucleophile approaching anti to the phenyl group. The bicyclic carbohydrate-derived oxazolidinone 4 is also a useful chiral auxiliary for the synthesis of homochiral B,P-disubstituted carboxylic acids.* Organoaluminium reagents undergo conjugate additions to 4 with excellent facial selectivity (Scheme 2).The authors rationalize their results in terms of the 1 R’ = Ph R2 = R3 = alkyl or aryl R3MgBr CuBr-Me2S 2 d.e.=5&1000/0 R2 3 Scheme 1 ph-NKo 0 0 4eq. RfiICI PivO p i v O Q 3 1 4eq. MeAlCI, h* ‘ h ~ N ~ o R O O or 4 R=alkyl d.r. (2R :2RS) 96:4 - > 99:l 5 Scheme 2 bis-organoaluminium intermediate 5 where the chloride bridge apparently enhances the electron density of the aluminium near the double bond, resulting in a [ 1 s,5s] sigmatropic shift of the alkyl group. desymmetrization of meso-dicarboxylic anhydrides has been observed when certain substrates are treated with an alcohol in the presence of ( - )-cinchonidhe and diethylzinc (Scheme 3).3 The enantioselectivity is attributed to one of the enantiotopic carbonyl groups complexing to a metallocycle formed between the alkaloid and the zinc reagent.In the absence of diethylzinc the alkaloid gives the product 6 in only 8% e.e. Moderate enantioselectivity in the Harrison and Laduwahetty: Carboxylic acids and esters 107?H + 1 7 6 (57%, 91% e.e.) 3 0 I 9 (90.9% d.s.) 10 (95.7% d.s.) Scheme 3 A diastereoselective method for preparing homochiral2,7-nonadiene-5-carboxylic acids, such as 9 and 10, involves an iterative Claisen rearrangement starting with the secondary alcohols 7 and 8 which in turn are available from ( - )-ethyl lactatea4 The [3,3] sigmatropic rearrangements proceed through the expected chair transition state to provide the carboxylic acids in > 90% d.s.Reduction of the a-keto ester 11 (Scheme 4) derived from the corresponding chiral cyclitol is a 11 lM+ L attack 12 1 H Ph R = Bu'Me2Si K-selectride, THF 96 : K-selectride, THF, 18-crown-6 4 : Scheme 4 H Ph 4 96 means of obtaining a-hydroxy acids with excellent enantiomeric p ~ r i t y . ~ The alcohol obtained is the product resulting from attack on the re face in the chelated transition state 12 where the ester exists in an s-cis configuration. There is a complete reversal of facial selectivity in the presence of 18-crown-6 in THF where the product resulting from attack on the si face predominates. This interesting result is quoted as one of the first examples in the literature where both antipodes of a compound are obtained from the same substrate under different conditions.Improvements in the enantioselective enzymatic hydrolyses of chiral esters in organic solvents are observed in the presence of a crucial amount of a base such as pyrrolidine.6 The presence of the base increases the solubility of the acids in water saturated organic solvents. The formation of an ion pair with the carboxylic acid which is produced leads to the formation of a second phase in the reaction which also facilitates the isolation of the product. The background chemical hydrolysis, which occurs under aqueous conditions, resulting in the lowering of the e.e.'s, is also prevented in organic solvents. Amides obtained by the coupling of racemic carboxylic acids, such as 2-tetrahydrofuran carboxylic acid, with amino acids can be separated by distillation.Hydrolysis of the individual diastereoisomers then leads to optically pure carboxylic acids.' 2.2 Homologation reactions Whilst the trialkyltin ester radical 13 adds only to electron-rich olefins, the radical derived from 14 participates in Michael-type reactions with electron-deficient double bonds to give the homologated acids 15 in moderate yield (Scheme 5).8 Since the dianion of acetic acid adds to acrylate esters to give only 1,2-addition products, this methodology is a useful alternative. 0 .AOS"Bu, 13 Bun3SnCI (0.5 eq.) NaBH, (4eq.), AIBN, EtOH + c 0 I3OH 14 Z = CO,Me, CONMe2, CN, CI Scheme 5 0 H O I C / Y ' R 15 (15-609h) The nickel-acycles 16 and 17, synthesized from (2,2-bipyridyl) (cycloocta-1,5-diene)-nickel(O) and succinic or glutaric anhydrides (Scheme 6), are useful homoenolate synthons.' They react with the relatively hindered primary iodide 18 in the presence of 108 Contemporary Organic Synthesis= - P I 18 16 n = l 17 n = 2 (i) MI2, DMF, toluene, 18) (ii) CH2N2 I 6942% Scheme 6 manganese iodide to give the homologated steroid in one step.The reaction is vastly improved by exposure to ultrasound. Carbonylations of primary allenyl alcohols to give a-vinyl acrylic acids can be achieved in the presence of [(Cy,P),Pd(H)(H,O)]BF,, an air-stable source of Pd0.lo A variety of disubstituted dienoic acids such as 19 are isolated in 6 1-74% yield with exclusively (E)-geometry (Scheme 7). Trisubstituted acids such as 20 are obtained in 43°/~-640/~ yield as mixtures of double bond isomers (Scheme 8).L 21 4" - 19 (61%) Scheme 7 25 can be achieved via the chloro-sulfoxide adduct 23 (Scheme 9).11J2 Initial enolization of 23a with KH, followed by ligand exchange with Bu'Li results in rearrangement to give 24, while direct ligand exchange on 23b with EtMgBr leads to 25. Rl&:.& * CI 23a R' = alkyl, R2 = H b R' =OR, R2 =alkyl (i) KH (ii) Bu'Li 1 Y KO-R' - C'HoMgBr R2 OH R' CI I 1 NaOH R1CH2C02H 24 (85%) R2-yH-C02H CI 25 (67%) Scheme 9 Ketones can be homologated smoothly to give a ,P-unsaturated carboxylic acids using the difluorovinyl-lithium reagent 26 (Scheme 10). the Corey methodology can be converted into a-fluoro-carboxylic acids in 76- 100% yields using CsF together wtih Bun4 NF.14 The use of alternative fluoride sources, including CsF and Bu",NF, independently give significant amounts of the chloro carboxylic acid.Trichloroalcohols obtained from aldehydes using E Li lC0 PcY3 /4=L Scheme 10 20 (64%) Scheme 8 p-Toluenesulfonic acid is necessary to protonate the starting alcohol, which is displaced by the Pdo species to form a n-allenyl Pd complex such as 2 1. Rearrangement of 2 1 to the corresponding n-ally1 species 22, followed by CO insertion, then leads to the conjugated diene 19. corresponding acids 24 or a-chloro carboxylic acids One-carbon homologations of esters to the 1 0 F O H 2.3 Acids from esters and amides An extensive review of methods for the chemical deprotection of the ester functional group has been undertaken by Masceretti et al.15 Primary amides or 0-methyl hydroxamates can be hydrolysed to the corresponding acids under mild conditions by treatment with catalytic TiC1, [or Ti(OR),] and one equivalent of HC1.16 Strongly acidic or basic conditions that are traditionally used for such transformations result in racernization of adjacent chiral centres.Neutral or acidic alumina, when subjected to microwave irradiation, can hydrolyse benzyl esters in the presence of a variety of other protecting groups, including benzyl ethers." Harrison and Laduwahetty: Carboxylic acids and esters 1092.4 Heterocyclic carboxylic acids Pyrazine formation (Scheme 1 1) is a problem encountered in the direct cyclization of pyrroles 27 or 28 to 6-azaindole-5-carboxylic acid 29, but can be circumvented by initial reduction of the intermediate imine (Scheme 12).18 The amine thus obtained can be cyclized successfully under Lewis acidic conditions to give 29 in excellent yield after deprotection.2.5 Carboxylic acid synthons A phenyl group can be successfully oxidized to a carboxylic acid (Scheme 14) under mild conditions without loss of stereochemical integrity. Whilst the Sharpless methodology employing RuC1,-NaIO, appears to be successful only when the oxygen protecting groups are electron withdrawing esters,20(a) Jones et al. have found that RuO, . xH,O provide an excellent yield of the carboxylic acid even in the absence of electron-withdrawing protecting groups.20(b) E t 0 9 0 2 E t QcHo + EtoIoEt Et3N 4A ~ W N Ph CO2H A H2N CO&t molecular sieves A Rlo+ N HBoc RuCI,.NaIO4 - RlO+NHb OR2 OR2 R' = TBDMS, R2 = MOM; 18% R',R2 = Ac; 59% 1 27 R = H 28 R=Ts TcbocN H i : &,Ph R"Oz.xH20_ T c k N e C 0 2 H H : ! TBDMS~) TBDMSO 87% Scheme 11 TS 28 (9 TcI~, A, cgr, (809;) (ii) NaOEt (soo/.) 2.6 Miscellaneous substituted carboxylic acids Amino acids can be oxidized to the corresponding nitro carboxylic acids with the powerful oxygen transfer reagent HOEMeCN, obtained by bubbling fluorine through aqueous acetonitrile.2 Despite the fact that this reagent can oxidize aromatic rings, 1 atop H 29 Scheme 12 The existing methods for the syntheses of 5-substituted pyrrole carboxylic acids are hampered by the need for starting materials which pose special handling problems. A new route to such compounds involves the ring-opening of the lactam 30, and deprotection of the Boc-protected amine, followed by oxidation of the resulting imine ion (Scheme 13).19 RMgBr ~ R h c o 2 c 2 H 5 0 G c 0 2 c 2 H 5 Boc R = aryl alkyl or BocNH 30 especially activated ones, the very short reaction time ( 5 min.) ensures selective oxidation of the amine. Serine is oxidized to the corresponding nitro derivative in 70% yield, establishing that even primary hydroxyl groups are stable.Remote chiral centres are also not racemized under these strong oxidizing conditions. a-Alkoxy cyclic ketones can be converted into the corresponding acetal lactones when treated with Ni( dmp), in the presence of oxygen and an aldehyde (Scheme 15).,, These acetal lactones can be ring-opened under acidic conditions to obtain carboxylic acid-acetals, such as 31 and 32.required several steps to synthesize, can be obtained by simply treating a-keto acids with Lochman's base (BunLi/ButOK) in the presence of an alkylating agent (Scheme 16).,, The reaction is limited to small alkyl groups, such as methyl and ethyl, and higher yields are obtained by using the dialkyl sulfate rather than the alkyl triflates or bromides. Increasing substitution on the acid leads to a dramatic reduction in yield. acids, such as 35, are available through a variety of a-Alkoxyacrylic acids 33, which have previously Although trans-substituted cyclopropane carboxylic Scheme 13 synthetic methods, cyclization of the cyan0 epoxide 34 1 10 Contemporary Organic SynthesisOMe 1 mol% Ni(dmp)2, O2 isovaleraklehyde (3eq.) 47 0 0 MeOHI HCI e o ! e 31 (67%) 0 0 8 - H O 2 C Y o M e OMe Oxidations of alcohols to carboxylic acids by Pd(OAc), in the presence of Pd-C and 0, in a Wacker-type process25 and the oxidation of aryl/heteroaryl aldehydes to carboxylic acids with hydrogen peroxide in formic acid at low temperatures,26(a) have also been reported.stoichiometric Jones reagent is an efficient, mild method for the oxidative cleavage of alkenes to carboxylic acids.26(b) The reaction can be performed on multigram scale and furthermore allows for the presence of basic amines. The combination of a catalytic amount of OsO, and 3 Carboxylic acid esters 32 (98%) 3.1 General synthesis Scheme 15 0 (i) Bu"Li, BdOK R' R2CKC02H THF-Hexane-HMPA H (ii) R,Y 33 Scheme 16 being one, the methods for the synthesis of cis-cyclopropane carboxylic acids such as 38 are more rare.Activation of a cyano epoxide by a sulfonyl group, as in 36, followed by intramolecular cyclization provides a novel means of obtaining the cis-substituted carboxylic acid via the corresponding lactone 37 (Scheme 1 7).24 34 35 ' I V NC 36 1 NaOEt P h o 2 S - 4 H - N C . 4 NC PhOpS AH AH J 95% 37 38 Scheme 17 The search for simple, mild procedures for the esterification of carboxylic acids continues. Thus, Weinreb et aZ.27 have reported that esters are generated in good yields under mild conditions from carboxylic acids and alcohols in the presence of Appel's salt ( 4,5-dichloro-l,2,3-dithiazolium chloride, 39). This route is mechanistically similar to the 2-halopyridinium salt methodology developed by Mukaiyama.28 Esters are also formed in excellent yields from near equimolar amounts of free carboxylic acids and alcohols at room temperature by the combined use of 4-( trifluoromethy1)benzoic anhydride and a catalytic amount of active Ti'" salt together with chlorotrimethylsilane.2Y The presence of chlorotrimethylsilane is critical to the success of this reaction.Triisopropylsilyl diazomethane 40 is thermally stable and produces the corresponding silylmethyl esters upon reaction with carboxylic acids3' Unlike the reaction with trimethylsilyldiazomethane, concomitant desilylation is not a problem. These silylmethyl esters are considerably more resistant to hydrolysis than the corresponding methyl esters. Triethylorthoacetate is reported to be superior to triethylorthoformate for the preparation of ethyl esters from carboxylic acids under neutral condition^.^ The rate enhancement is presumably due to the improved stability of the cationic intermediate.t-Butyl esters can be prepared without racemization from chiral acid bromides and t-butyl alcohol in the presence of basic alumina.32 Clearly basic alumina suppresses the formation of ketene intermediates which would lead to racemization. The beneficial use of microwave irradiation in the synthesis of esters has also been reported.33 The use of the thionyl chloride/DMF complex for the conversion of a hydroxyl group into the corresponding chloride is a well known procedure. If this reaction is carried out at or below 0°C in the presence of LiI, attack of halide onto the alkoxyformamidinium intermediate 4 1 is precluded and hydrolysis yields the corresponding formate ester 42 in high yield (Scheme 18).34 These conditions are much milder than those involving the widely used acetic formic anhydride.Harrison and Laduwahetty: Carboxylic acids and esters 111CI, ,CI 39 40 Cl$W-DMF/LII H O ROH - [h@h=CH-OR] ROCHO 41 42 Scheme 18 The direct oxidation of primary alcohols to methyl esters is a useful synthetic procedure; calcium hypochlorite in methanol achieves this transformation in high yield.35 Both aliphatic and benzylic alcohols undergo the reaction, and hypochlorous acid is believed to be the oxidizing species. Ketene acetal derivatives such as 43 have been shown to be useful derivatives for the acylation of alcohols (Scheme 19).These novel species can be prepared from carboxylic acids and ethoxyacetylene using a catalytic amount of RuCl,(p-cymene),, and they react smoothly with alcohols to provide the corresponding esters in excellent yield.36 R'C02H + =OEt R'C0,'OEt 43 1 R~OH R' C02R2 Scheme 19 3.2 Halo esters a-Halo esters are important synthons for the elaboration of glycidic esters via the Darzens reaction. Recent work has shown that caution should be demonstrated when considering an aldol-type reaction dealing with a-halo esters, since a ketone-enolate-carbenoid manifold exists for a-halo ester enolates. Sodium enolates of a-bromo esters decompose faster than they react with formaldehyde, whereas lithium enolates of a-chloro esters do not decompose at room temperature and they react smoothly with formaldehyde to furnish glycidic esters.37 a-Chloro esters are generally prepared through halogenation of carboxylic acids or their derivatives.A particularly mild halogenation of stabilized ester enolates ( e g . 44) can be achieved using cupric chloride.38 Enolates containing unsaturated functionality react with high chemoselectivity. An alternative route to 2-halo esters involves the oxidation of 2-chloro aldehyde dimethyl acetals using trichloroisocyanuric acid in DMF.3Y The method has recently been extended to the synthesis of a,a-dichloro esters by the oxidation-chlorination of cyclic acetals using this reagent.40 3-Halo substituted esters are more difficult to obtain since they can suffer spontaneous dehydrohalogenation if the conditions are too drastic.Compounds of this type can be prepared from the corresponding P-hydroxy or doxy esters 45 and a trimethyl silyl halide (Scheme 20). For the preparation of the chloride derivatives, activation of the silicon-chlorine bond by catalytic bismuth( 111) chloride facilitates the reaction.'" 44 45 Scheme 20 3.3 Miscellaneous methods of synthesis The vicinal dialkylation of an a#-unsaturated ester using radical intermediates has been reported by Keck et al.42 In this reaction the initially formed electron-rich dimethoxymethyl radical reacts more rapidly with the electron-deficient olefin 46, and the resulting electron-deficient a-carbonyl radical then reacts with the nucleophilic stannane. In general, diastereoselectivity is not high.Methods for the stereoselective formation of ( E ) - and (Z)-silyl ketene acetals continue to be developed, as these are important intermediates in the ester enolate Claisen rearrangement. In a reinvestigation of the earlier work of Ireland, Otera et al. have shown that ketene silyl acetals of propionate esters with high (E)-stereochemical purity (e.g. 48) can be obtained by increasing the size of the alkoxy group of the starting ester 47, whereas employment of an excess of ester relative to base leads to high (2)-selectivity 49 (Scheme 2 R3 H/OMe R 3 A p PhSC, (W.) OMe OMe 0.W PhH, h 46 (i) LDA. THF, DMPU (i9 R1$3iCI, HMPA * 0 or DMPU OR (0-48 40R 47 \ (0 LDA ( O a s e s . ) , THF- Jz: HMPA or DMPU (ir) R'3SiCI (4-49 Scheme 21 Silyl ketene acetals of a-hydroxy esters are also valuable synthetic intermediates since they allow the stereoselective positioning of hydroxyl groups adjacent to an ester carbonyl via Claisen rearrangement.Yamamoto et al. have recently described methods for the stereoselective formation of either ( E ) - or (2)-silyl 1 12 Contemporary Organic SynthesisI LTMP, Me3SiCIITHF ketene acetals starting from a-siloxy esters 50 (Scheme 22).44 Since it seems likely that it is geometric constraints in the transition states for , -100°C (internal trap) ~ C,JX / s ~ OSiMe3 deprotonation which govern the outcome of these proton abstraction by LTMP (deprotonation control). generate the (Z)-enolate selectivity via transition state 52 (complexation control). (2)-57 I selective enolations, it has been suggested that there QJOMe ( 0 5 7 may be a preferred pericyclic transition state 5 1 for Improved chelation in the presence of the weaker base 56 (ii) Bu'MefiiCI L / \ (i) LHMDWTHF-HMPA C,J--J;;rt I LHMDS and the less reactive TBDMSCl would thus -100°C / \ LTMP, -100°C TMSCl (internal quench) L I THF 0 50 (i) LiN(SiMed2, THF-HMPA (ii) Bu'Me2SiC1, -100°C OSiMe3 &OMe Buknefiid (0 t 51 L J 52 OSiMeBu' J Buk4e&iO&oMe (a Scheme 22 Yamamoto has extended this method to allow the selective formation of either ( E ) - or (2)-ketene silyl acetals 54 from /3-hydroxy ketones 53, avoiding problems of /3-elimination (Scheme 23).45 LTMP, Me3SiCvn-IF Me3Sii OMe -100°C (internal trap) uOSiMe3 / = b OR 0 (4-54 0) LDA(2eq.l Me3Si OSiMe3 * uOMe uOMe 53 (ii) Me3SiCI (3eq.) -78°C (R = H) (3-54 Scheme 23 Similar conditions allow the preparation of ( E ) - or (2)-silyl ketene acetals 57 starting from appropriately protected a-amino esters 56 (Scheme 24).45 Scheme 24 The direct preparation of a-amino esters by electrophilic amination of esters is an important synthetic process.Tanaka et al. have reported that arene diazonium tetrafluoroborates 58 react with ketene-silyl ketals yielding a-hydrazone esters 59 which are converted into a-amino esters by hydrogenation (Scheme 2 5).46 Interestingly, the less nucleophilic silyl enol ethers of ketones react with 58 in pyridine via a radical mechanism to give a-aryl ketones with concomitant loss of nitrogen. ,NHPh N' O"C, 2h RKC02Me ' Y O M e + PhN2BF4 - OSiM+ 58 59 JH2 NH RAk02Me Scheme 25 The oxaziridine 60 is a useful reagent for transfer of an N-Boc group to N- and C-nucleophiles.Thus 60 reacts with ester enolates at - 78°C affording N-Boc protected a-amino esters dire~tly.4~ Reagents analogous to 60 but containing alternative N-protecting groups can also be prepared. one-pot operation via insertion of diazoacetates into readily available dialkyl or diarylchlorosilanes, followed by reaction with an appropriate alcohol (Scheme 26).48 This chemistry exploits the dual reactivity of chlorosilanes 6 1 towards nucleophiles and carbenes. The esters 62 can be alkylated with a range of electrophiles under standard conditions. To date efforts to oxidize the a-silyl esters to a-hydroxy esters under Tamao conditions have proved unsuccessful. important class of therapeutically valuable non-steroidal anti-inflammatory agents.The biologically active (S)-enantiomers can be prepared by hydrogenation of aryl propenoic acids 64 using a chiral catalyst (Scheme 27). A new route to these hydrogenation precursors involves the Pd-catalysed coupling of the a-stannyl acrylate 63 to an aryl iodide a-(Alkoxysily1)acetic esters 62 can be prepared in a 2-Arylpropanoic acid derivatives represent an Harrison and Laduwahetty: Carboxylic acids and esters 113Reactivity of chlorosihnes towards towards N C O C V 7 N - - B o ; nucl-phil-2, 6 Carbenes 0 F\ 60 61 (R20)R',Si 0 Scheme 26 63 j(PhpP)dPd. CuI-DMF 64 65 66 Scheme 27 or triflate.4Y The use of 0.75 eq. CuI is critical for the success of this reaction. In a related approach, a range of 2-( heteroaryl) propanoic acid derivatives 66 have been prepared by the palladium-catalysed reaction of heteroaryl halides with ( E ) - 1-methoxy- 1-trimethylsiloxypropene 65.Thallium acetate has been found to be a useful additive in this reaction. Halo-pyridines, pyrimidines, quinolines, and isoquinolines have been used as the heteroaryl coupling partner; the reaction is sensitive to steric effect sS0 can be achieved directly by the chemoselective addition of ethyl( tributylstanny1)acetate 67 to acyl pyridinium salts (Scheme 28).51 The resulting dihydropyridines 68 are useful precursors to a variety Carboethoxymethylation of functionalized pyridines R' R' @ R2 + Bu3snCH2C02Et 6r 20 min. OAOMe 68 Scheme 28 1 14 Contemporary Organic Synthesis of heterocycles.Quinolinium and isoquinolinium salts can also be used as acceptors. The Michael additions of lactams and amides to a , /3-unsaturated esters are generally unfavourable processes; however, high yields of the addition products 69 can be obtained using an equimolar amount of Si( OEt), and catalytic CsF (Scheme 29).52 In this reaction the Si(OEt), plays a dual role whereby generation of EtO- is followed by trapping of the enolate adduct as the corresponding silyl ether, hence suppressing the normally problematic retro-Michael reaction. &. + e C 0 2 E t 7 SI(0Et). Q-co2Et 69 Scheme 29 The formation of esters by additions of nucleophiles to carbonates is a synthetic method which has received little attention. During work aimed at preparing C-2 analogues of taxol, Nicolaou et al.have observed that esters are formed by the regioselective ring-opening of cyclic carbonates 70 with nucleophiles (Scheme 30). The only side-product observed was the diol72, and in general the less substituted ester 7 1 is the major or exclusive product. A range of nucleophiles has been successfully employed in the reaction.s3 OH OH "fi NU- "fl + OH O K N u THF O K 0 0 70 0 71 72 Scheme 30 3.4 Hydroxy esters A widely used route for the preparation of optically pure a-hydroxy esters is stereoselective reduction of the corresponding a-keto esters bearing a chiral auxiliary. The borneol derivatives 73 and 74 provide extremely high levels of stereocontrol during reductions of the keto esters 75 with LiA1H(OCEt,)3.s4 The auxiliaries can be removed by mild saponification (LiOH, THF-H,O, r.t.) without racemization of the reduced products.the addition of organometallic reagents to the keto esters 76 bearing a binaphthalen-2-01 auxiliary has been reported. The sense and degree of diastereoselectivity is dependent on the Lewis acidity of the nucle~phile.~~ High diastereoselectivity can be obtained in the direct oxidation of enolates with dimethyldioxirane if the initially formed lithium enolates are transmetallated to the corresponding titanium species prior to oxidation.56 Furthermore, the aldol reaction of A detailed investigation of the diastereoselectivity ofNHS02Ar R NHS02Ar 73 74 75 OH R O 76 the enolate with acetone, the unavoidable medium for dimethyldioxirane, is completely suppressed. The titanium enolates react with much higher diastereoselectivity (up to 96% e.e.) than the corresponding sodium enolates or silyl enol ethers.esters can be prepared by stereoselective reduction of 2-methyl-3-keto esters 77 (Scheme 31). Thus reduction of 77 with NaBH, in the presence of catalytic MnC1, provides the erythru isomer 7 8 via a chelated six-membered ring transition state, while reduction of 77 with Bu",NBH, provides the corresponding threu isomer 7 9 via Felkin-Anh control.57 A further enzymatic method for the diastereo- and enantio-selective reduction of P-keto esters 77 has been reported.s8 Either erythro-78- or threo-79-/3-hydroxy-a-methyl OH 0 etythm78 Me OH 0 Scheme 31 An enantioselective version of the Reformatsky reaction utilizing the bromo-ester 80 and various prochiral methyl ketones in the presence of a chiral ligand provides P-hydroxy esters 8 1 in moderate yield (Scheme 32).s9 E.e.'s of up to 74% have so far been obtained using N,N-dialkyl norephedrine derivatives as chiral ligands.The e.e.'s are much lower when ( - )-sparteine is used as the chiral controller. The Reformatsky reaction has also been used to prepare biologically important a, a-difluorinated ester derivatives. In a modification of this reaction a,a-difluoro-/3-hydroxy esters 83 are formed in reproducible yield by activation of ethyl Rl-C-Me BrZnCH2C02But L' 80 81 Scheme 32 bromodifluoroacetate 82 using Zn (2 eq.), AgOAc (0.3 eq.), and Et,AlCl (l.l-2 eq.) to generate a nucleophilic species in the presence of an aldehyde or ketone (Scheme 33). When the carbonyl compound is a-substituted, the stereoselectivity is low.6o 0 R' BrCF2CO2Et R2+CFzC02Et 82 OH 83 Scheme 33 4-Alkoxybutanoates (86, n = 1) and 5-alkoxypentanoates (86, n = 2) can be prepared under mild conditions and in high yield by alcoholysis of the corresponding lactones 84 in the presence of an appropriate orthoester (Scheme 34).6' Mechanistic studies have shown that the ether linkage is formed by an SN2-like opening of an activated intermediate 85 formed from the lactone and the orthoester.The reaction is much slower for E-caprolactone derivatives and for lactones which are substituted at the a-position. 0 84 Scheme 34 ' OR O A O R 85 - RO &OR 86 3.5 Keto esters Phenylhydrazones of a-keto esters ( 8 7 ) are cleaved efficiently using hypervalent iodine compounds [ e.g.PhI (OCOCF,),]. The reaction proceeds under mild conditions and thus provides a method of protection for the carbonyl group of an a-keto ester.62 and they can be prepared in high yield and purity and on a large scale by reaction of acid chlorides with potassium ethyl malonate 88 using a magnesium chloride/triethylamine base system (Scheme 35). The method may be of real value in large scale production.h3 Alternatively, 3-acyloxazolidin-2-ones 89 undergo Reformatsky reactions with a-bromo esters in the presence of zinc and ultrasound to provide P-keto esters in moderate to good yield.64 P-Keto esters are important synthetic intermediates, Harrison and Laduwahetty: Carboxylic acids and esters 115N,NHPh 0 0 C02K 88 (i) EtOAdMgCIdEt3N c (ii) RCOCl 0 4 25°C (93-99-34) R JJOEt I .89 Scheme 35 A different approach to the synthesis of P-keto esters involves the hydrolysis of b-alkoxy- a$-unsaturated ketones 9 1, which are prepared by conjugate addition of sodium propargyl oxide to the acetylene 90 (Scheme 36).65 R20/ 90 R'O W O R 2 92 Scheme 36 Chemoselective cleavage of the enol ether moiety occurs under neutral conditions in the presence of a catalytic amount of Pd" complex, affording the acid-sensitive /3-keto esters 92 in good or (S)-chiral quaternary centre can be prepared by asymmetric alkylation of the chiral enamine derivatives 93 (Scheme 37). Either enantiomer can be prepared from the same chiral enamine 93 simply by variation of the solvent.67 A subsequent publication has revealed that chiral enamines such as 93 also undergo a highly stereoselective Michael addition to a,a-Dialkyl B-keto esters 94 having either an ( R ) - R' J J o R 3 A2 Bub \ L o 93 (i) LDA, toluene (ii) q 2 B u ' C02Bu' 95 f b02But Scheme 37 or Alternatively, the radical species 98 can be generated from an a-bromo- or a-iodo ester by reaction with BEt, in DMSO in the presence of air.70 Reaction with silyl enol ethers again provides y-keto esters 97 in moderate yield.Better yields are observed with a-iodo esters than with a-bromo esters (Scheme 38). Bun3SnbC02R + 96 TBACN K2C05 OSiBu'M& MN. ooc. 21. Scheme 38 The activation of Sn-heteroatom bonds by coordination of ligands such as phosphine oxides has already been rep~rted.'~ This has been used for the preparation of y-keto esters by the reaction of tin enolates 99 with a-halo esters 100 (Scheme 39).Unlike the previous two examples, this reaction does not occur via a radical mechanism, but rather by direct substitution at the halide moiety.72 R' the reactive &lic hael accept or di- t - bu t y 1 meth y lene malonate 95. The absolute configuration of the newly formed quaternary centre is again predictable, being Enantiomeric purities of > 90% have been y-keto esters have appeared in the literature. predominantly in the C-metallated form, can be ,u3sno+ R3 0 R3 dependent upon the solvent system used. R2 '1 + #+Br 'F- p f i R 1 Several related reports detailing the synthesis of 0 Bu3SnBr 0 a-Stannyl esters 96, which are known to exist oxidized using Ce'" reagents to the corresponding a-radicals 98.These species undergo efficient Bu3Sn& R' 100 0 99 coupling with electron-rich olefins ( e.g. enol ethers) providing y-keto esters 97 in good yield.69 Scheme 39 1 16 Contemporary Organic SynthesisEu3+ has been reported to be an efficient catalyst for the Michael addition of 1,3-dicarbonyl compounds to a, p-unsaturated esters generating d-keto ester^.'^ Two reports detailing the diastereoselectivity of Michael additions of ketone7, and ester75 enolates to a,/?-unsaturated esters have appeared. 3.6 Unsaturated esters An interesting approach to a, P-unsaturated esters 102 involves alkylation of the cyclopropyl anion 10 1 with an appropriate alkyl halide, followed by hydrolysis with TiCl, in CH,Cl, and elimination of the phenyl sulfonyl group (Scheme 40).76 In this reaction, pr SO2Ph BuUl-78"C THF/HMPA PhO, ,OPh I rPh0, ,OPh 1 101 111 m m Li*C02Ph (i) TCI,, CH& (ii) DBIJITI-IF 0 PhO A & 0 R 103 102 Scheme 40 the cyclopropyl anion is functioning as the /?-lithi0 acrylate synthon 103.To date it has not proved possible to react the anion 10 1 with carbonyl compounds. In an extension of their earlier work Brown et al. have described a highly enantioselective synthesis of conjugated acyclic a-chiral (E)-alkenones 105 from enantiomerically pure ( E ) - 1-alkenyl alkyl borinic esters 104 which are in turn prepared by asymmetric hydroboration (Scheme 4 1).77 Reaction of the esters 104 with a,a-dichloromethyl ether (DCME) in the presence of a hindered base followed by oxidation with H,O, in pH 8 phosphate buffer provides the desired chiral (E)-alkenones 105 with > 99% e.e.The chiral group (R) can be cyclic or acyclic. R' H H (i) CI2CHOMe, Et3COLI R ' A R' Ro''+R' (ii) H202, pH 8 _ _ H O H 104 105 Scheme 41 Pirrung et al. have described the fluoroacrylate cation equivalent 106. This highly functionalized aldehyde reacts with organometallic reagents and enolates to yield allylic alcohol products 107 which can be rearranged under acid conditions to medicinally important (2)-2-fluoroacrylate thioesters 108 (Scheme 42).7s MeS OH b;qcHo lP!L* (ii) HgCI, M e S v R F F 106 107 p2 0 111 F 108 Scheme 42 a ,/?-Unsaturated esters bearing a trifluoromethyl group at the /?-carbon can be prepared with either ( E ) - or (Z )-configuration by reaction of the fluorinated phosphorane 109 with a Grignard reagent (Scheme 43).The resulting B-oxido ylides 110 are converted into trifluoromethylated a,/?-unsaturated esters 1 1 1 with either (2)- or (E)-configuration depending on the acid used to protonate the intermediate.7Y 0- 109 110 1.' 0- 111 Scheme 43 /?, y-Unsaturated esters are often prepared by deconjugation of a,/?-unsaturated esters using base; alternatively, trialkyl silyl triflates and a tertiary base can be used.80 A usual limitation of this method is that mixtures of ( E ) - and (2)-/?, y-unsaturated esters are formed. Stereochemically defined (E)-/?, y-unsaturated esters can be formed by reaction of (E)-[2-( tributyltin)alkenyl] boranes 1 12 with the ylide 113 followed by oxidation. Overall yields are generally good (Scheme 44).The reaction proceeds via 112 (i) Me2&HC02Et (ii) H#&Ac 113 1 R' F? Scheme 44 Harrison and Ladu wahetty: Carboxylic acids and esters 117preferential migration of the alkenyl moiety from boron to carbon followed by protonolysis of the resulting alkenyltin intermediate with retention of configuration.8 The carbonylation of allylic compounds provides a very mild and efficient method for the preparation of P, y-unsaturated carbonyl compounds. Allylic phosphates 114 have been shown to be highly reactive substrates for transition metal catalysed transformations, and they react with CO (20 atm.) at 50°C in the presence of a rhodium catalyst and an alcohol to provide p, y-unsaturated esters 1 15 in good yield (Scheme 45).82 The reaction in the presence of an amine or H 2 0 provides the corresponding P, y-unsaturated amides and acids respectively.These carbonylations occur with high regioselectivity at the less substituted carbon of the ally1 unit. R’-OP(OEt), ? + CO + HNU Rh6(C0)16 Bu~NCI I R ’ V N ” 114 0 115 Scheme 45 The Pd* catalysed coupling of alkenylboronic acids has become a ubiquitous reaction in organic synthesis. A recent report has described the Pd-catalysed coupling of 1-( E)-alkenylboronic acids 116 with a-bromo- a ,P-unsaturated esters providing (E,E)-dienoates 1 17 in moderate to good yield (Scheme 46). 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ISSN:1350-4894    

DOI:10.1039/CO9950200107

出版商:RSC    

年代:1995

数据来源: RSC

摘要:

Hypervalent iodine in organic synthesis: a-functionalization of carbonyl compounds OM PRAKASH, NEENA SAINI, MADAN P. TANWAR, Department of Chemistry, Kurukshetra University, Kurukshetra-132 11 9 (Havana), India and ROBERT M. MORIARTY Department of Chemistry, University of Illinois at Chicago, P. 0. Box 4348, Chicago IL 60680, USA Reviewing the literature published up to February 1995 1 2 2.1 2.2 3 3.1 3.2 4 4.1 4.2 4.3 4.4 4.5 5 5.1 5.2 5.3 5.3.1 5.3.1.1 5.3.1.2 5.3.2 5.3.2.1 5.3.2.2 5.3.2.3 5.3.3 5.3.3.1 6 8 Introduction a-Functionalizations of carbonyl compounds using iodobenzene diacetate (1BD)-KOH/MeOH Formation of a-hydroxydimethylacetals: a useful route to a-hydroxyketones Oxidations of a$-unsaturated ketones Direct a-sulfonyloxylations of carbonyl compounds and the preparation of other a-functionalizations via a-tosyloxyketones a-Sulfonyloxylations of carbonyl compounds a-Functionalized ketones via a -t osyloxy ketones a-Functionalizations of carbonyl compounds from the oxidations of silyl enol ethers a-Hydroxylations a-Alkoxylations a-Acetoxylations, tosyloxylations, and mes y loxy lations a-Trifloxylations 1,4-Diketones by carbon-carbon bond formation Miscellaneous examples of a-functionalizations of carbonyl compounds a-Phosphoryloxylations a-Functionalizations of p-dicarbonyl compounds using iodosobenzene Synthesis of oxygen-containing heterocycles by intramolecular participation Using IBD-KOH/MeOH 2-Aroylcoumaran-3-ones Steroidal spiro-oxetan-3-ones Using HTIB, MeCN, or CH,C1, 2-Aroylcoumaran-3-ones Coumaran- 3-ones via their dimet hylace tals Oxolactones Using (PhIO),-F3B.0Et,,H,0 Coumaran-3-ones Conclusions References 1 Introduction Despite the fact that hypervalent iodine compounds have been known since 1886,' it is only comparatively recent that their versatility as reagents in organic synthesis has been recognized.,-13 From 1980 onwards a surge of interest in the use of organo 1"' reagents in organic synthesis has been observed, and these studies have been summarized in several reviews.One of the most interesting features of hypervalent iodine reagents is their use in the direct a-functionalization of ketones and of some other carbonyl compounds. Since a-functionalized ketones are extremely useful and versatile precursors in organic synthesis, their ready access via the iodine( 111)-mediated approach has simplified many synthetic (and mechanistic) problems in organic chemistry.The first report of the a-functionalization of ketones was published by Mizukami et all4 who introduced a method for a-acetoxylation of ketones and @diketones by the action of iodobenzene diacetate (IBD) and sulfuric acid (H,SO,). Later, Moriarty et aZ.15 and Koser et all6 developed methods for the a-hydroxylation and a-tosyloxylation of ketones using IBD-KOH/MeOH and [hydroxy( tosyloxy )iodo]benzene (HTIB), respectively. Following these studies, the two reagents IBD and HTIB have gained significant importance in bringing about a wide variety of a-functionalizations, and this review summarizes recent work in this important area of synthesis. The major accomplishments in the area of a-functionalization of carbonyl compounds can be classified according to the type of reagent system/substrate involved in the reactions.Therefore, for convenience, the subject matter in this article has been discussed in four parts: (i) the application of IBD-KOH/MeOH for a-hydroxylations of carbonyl compounds; (ii) a-sulfonyloxylations of carbonyl compounds using HTIB, [hydroxy( mesyloxy )iodo]benzene, etc. and their uses in preparing various a-functionalized carbonyl compounds; (iii) a-functionalizations of carbonyl compounds by oxidations of silyl enol ethers using iodosobenzene-boron trifluoride etherate; (iv) miscellaneous examples of a-functionalizations of carbonyl compounds, including the formation of Prakash, Saini, Tanwar, and Moriarty: Hypemalent iodine in organic synthesis 121oxygen-containing heterocycles by intramolecular participation.mechanistic pathway for the oxidation reactions by hypervalent iodine described in this review, is the electrophilic addition of the hypervalent iodine reagent PH-I (X)-Y onto the enol form of the ketone/silyl enol ether/enolate, leading to intermediates of type 1 (Scheme 1 ). The intermediate 1 can then lead to the formation of various products via different routes depending upon the reaction conditions. Several such possibilities are illustrated in the discussion of results at appropriate places in the text. It is worth mentioning that a significant step in the 1 Ph-I-XJ (Z = H, K, SiMe,) 1 Scheme 1 2 a-Functionalizations of carbonyl compounds using iodobenzene diacetate (1BD)-KOH/MeOH 2.1 Formation of a-hydroxydimethylacetals: a useful route to a-hydroxyketones Hypervalent iodine oxidations of enolizable ketones 2 using IBD-potassium hydroxide or sodium hydroxide provide an efficient route to a-hydroxydimethylacetals 3.The acid hydrolyses of these acetals then lead to a-hydroxyketones 4 (Scheme 2). 2 OH 3 OH 4 Scheme 2 Although the conversions 2 --* 3 + 4 are quite general, some exceptions, where treatment of a ketone with IBD-KOH/MeOH does not give the expected acetals, have also been noted. For example, it has recently been found that 2,4-dihydroxyacetophenones undergo interesting rearrangement reactions leaving acetyl or enolizable ketonic groups unaffected.’ Since the results of this reaction (2 --+ 3) covering the literature up to early 1986 have been reviewed earlier,6 only the mechanism (Scheme 3) and newer applications (Chart 1) are presented here.Some noteworthy features of the results presented in Chart 1 are as follows: (i) The oxidizing conditions work successfully on ‘nitrogen’ and ‘sulfur’ containing heterocyclic ketones18 (5 -+ 7, via 6) without affecting the hetero atoms. 0- -0Me I 0 I I R’-c-cH~-R~ - R’-C=CH--R~ I OAc IPh-i. K O W H p h - y p A c OMe A V II -0Me R’-C-(pR2 4 h I --OM0 0 OMe / \ R‘-~--CH-R~ 4 Ph -I- OMe 1:: OMe I Me0 OH R‘- Y-~H-R’ Scheme 3 (ii) Tropan-3-one 8 on oxidation using IBD-KOH/MeOH gives 9 which upon acid hydrolysis produces 2 a-hydroxytropan-3-one’” ( 10). The oxidation of tropine with LTA is known to give the same compound, among other products.27 Studies based on X-ray analysis19(b) finally proved that the reported compound 10 was in error.(iii) The synthesis of the new chiral AB-SynthOn 19 for preparing the optically active anthracyclinones 20 was attained through a stereospecific nucleophilic addition of trimethylsilylethynylmagnesium chloride to the chiral2-tetralone-1-acetal 1 K2* The latter acetal was prepared via 17 by way of hypervalent iodine oxidation of the ketone 16. (iv) Cis-3-Hydroxyflavanones 23, which are not widely known in the literature, are now available in a regio- and stereo-specific manner as shown in Chart 1 (f).23-25 This reaction is quite general, and is also applicable to chroma none^^^ and 2-f~rylchromanones.~~ 2.2 Oxidations of a$-unsaturated ketones A particularly fascinating feature of the hypervalent iodine reagent in the presence of -0Me ion is the oxidation of a,/?-unsaturated ketones, which do not contain an enolizable ketone group.For instance, chalcones 25 on treatment with IBD-KOH/MeOH give, interestingly, a -hydroxy-/?-meth~xydimethylacetals~~ 2 6 (Scheme 4). This methodology has a distinct advantage as it can be employed to effect C( 3)-hydroxylations of chromones, flavones, and a-naphthoflavones, which is an important reaction in flavonoid hemi is try.^^?^^^^' OMe OMe II IBD-KOWMeOH I I 0 Ar-C-CH=C: - Ar-Y-FH-yH Ar Me0 OH Ar 25 26 Scheme 4 The use of the reagent system IBD-KOH/MeOH becomes important in building oxygen-containing heterocyclic systems where intramolecular participation by a suitably placed hydroxyl group occurs (vide infra, section 5.3.1).122 Contemporary Organic Synthesis(a) a-Hydroxylations of thiazdyl and benzothiazdyl ketones" (b) Regib- and stereo-specific formation 0s 2a-tropan-3-one1@ (c) a-Hydroxylations of some steroidal ketones - 11 12 HO& H30+ 1 0 0 0 13 (e) Asymmetric synthesis of anthracyciinones using chiral aceta122 0 O M 14 15 (f) cis - and trans -3-Hydroxyflavanones, chromanones, and 2-iury1 anaiogues2*26 MOMO 16 MOM0 17 HO OH I PDClcat. Ac@ MOM0 19 lstePS 0 OH 0 OH 20 MOM0 18 Chart 1 0 21 I (i) 0 R' = H, OMe R2 = H, CI, Me R3 = Ph, Substituted phmyl, 2 - f u ~ l Reagent: (i) Iodobenzene diacetate(IBD)-KOHmAeOH Prakash, Saini, Tanwar, and Moriarty: Hypervalent iodine in organic synthesis 1233 Direct a-sulfonyloxylations of carbonyl compounds and the preparation of other a-functionalizations via a-tosyloxyketones 3.1 a-Sulfonyloxylations of carbonyl compounds There is considerable interest in various a-sulfonyloxy carbonyl compounds because of their potential in organic synthesis30 and in studies of their photochemical rea~tivity.~' Approaches toward their preparation not requiring the availability of a-hydroxyketones and involving enolic ketone derivatives have been s~mmarized.~~ The direct introduction of a tosyloxy or mesyloxy group to ketones and #I-dicarbonyl compounds has been affected by using HTIBl6 or HMIB,32133 respectively in MeCN or CH2Cl, (Scheme 5).The reagents HTIB and HMIB can also be used when generated in situ from IBD-P-TsOH~~ and iodosobenzene-methanesulfonic acid,35 respectively.for obtaining various a-[( + )( 10-camphorsulfonyl)]oxyketones by using [hydroxy(( + ) 1 0-camphorsulfonyl)oxy]iodo]benzene (HCIB), (Scheme 5). p-Diketones, p-keto esters, and diethyl malonate also react with HCIB to give corresponding a-( + ) 1 0-camphorsulfonyloxylated derivative^.^^ In the case of benzoylacetone, the crude product 29 was determined to be a 3: 1 mixture of diastereoisomers. However, an attempt to separate the diastereomers by chromatography resulted in isomerization thereby yielding a nearly 1 : 1 mixture36 of the two diastereomers. An interesting feature of this reagent is the steric bulk of the camphorsulfonate ligand which allows the regioselective formation of the less hindered product, e.g. 4-methyl-2-pentanone 30 apparently gives only the C-1 camphor~ulfonate~~ 3 1 (Scheme 6).A general mechanistic scheme is shown in Scheme 7. Thus, the I"' intermediate 32 loses water to give the a-phenyliodonioketone sulfonate 33. Nucleophilic addition of - OS02R3 at the a-carbon in 33 then Varvoghs et aZ.36 have employed a similar approach 0 affords the a-sulfonyloxylated product with the simultaneous expulsion of PhI (34). The validity of this mechanism is provided by the isolation of the proposed intermediate a-phenyliodoniosulfonates 33 from the reaction of p-diketones such as dimedone,16 ( a-thienoyl)trifluor~acetone,~~ and indane-l,3-di0ne~~ with HTIB in MeCN at room temperature. 29 HCIB, MeCN 30 ncHpa 3 Scheme 6 & H 2 9 0 0 OH R' 27 I PhI(W)OSO$i3 OH I Ho-:LPh R1 - OSO~R~ 32 I-HP PhI + R l q R 2 Rl%f 34 OSO~R~ IPh 0s02R3 28 Scheme 7 0 27 x 28 33 Condition X R' R2 R' R~ Ref.(in cyclic ketones) (i) = HTIB, MeCN OTs dkyll H, Ph, +CH2)4-, 16,34,39, 42148 =, 33.35 ac 3 corn, 2-thienyl. COMe, or CH2CI2 arvl, 2-ben~0- CO2C2HS thiazolyl 0 (ii) = HMIB, MeCN OMs aryl, H, Ph, +CH2)4-, 36 or CH2C12 cycbbutyl COPh, 2-thienyl, COMe, c02c2b HI Me +cH2)4- -p %!I (iii) = HCIB, MeCN OSOSH~ or CH,CI, 0 Scheme 5 124 Contemporary Organic Synthesis3.2 a-Functionalized ketones via a-tosyloxyketones Recent ~ o r k ~ ~ * ~ ~ - ~ ~ and previous s t ~ d i e s ~ ~ y ~ ~ have established that a-halogenoketones (HK) and a-tosyloxyketones (TK) mostly behave analogously. For example, the most common property of both HK and TK is to undergo nucleophilic substitution to give various a-substituted ketones.This is an important observation because the TK-mediated approach can offer a better and safer alternative to a large number of organic syntheses involving highly lachrymatory and toxic HK in their conventional approach. The further advantage of the 1"' based TK mediated approach is that it is generally not necessary to isolate TK, and the ketones are directly transformed into products. It is also noteworthy that the a-functionalized ketones thus obtained are precursors for a wide variety of heterocyclic compounds. The results of these investigations have provided a large variety of a-functionalized ketones and some of these are summarized in tabular form in Scheme 8. It should be noted that the formation of 37 [X = OH, condition (ix)] from 36 occurs via acid hydrolysis of the corresponding a-hydroxydimethylacetal38, and a reasonable pathway for the conversion of 36 into 38 is outlined in Scheme 9.48 35 36 37 Conditions X Ref.(i) = PPh, (ii) =(N) (iii) = Me2S (iv) = KSCN (v) = ArNH2 (vi) = NaN02, H20 (vii) = ArC02H-Et3N (viii) = ArOH-anh.K2C03/EtOH (ix) = (a) KOH-MeOH, 0-5 "C (b) H,O+ + PPbOTs- Q I +SMqOTs- SCN NHAr OH OCOAr OAr OH 46 46 46 43 42 47 34 34 48 Scheme 8 L J 36 OMe Me0 R 38 -F-(?l-OH I * [ -3!\fi] Scheme 9 4 a-Functionalizations of carbonyl compounds from the oxidations of silyl enol ethers 4.1 a-Hydroxylations The results presented earlier indicate the wide applicability of IBD-KOH/MeOH to bring about a-hydroxylations of ketones and some a,B-unsaturated ketones. Nevertheless, the a-hydroxylation route suffers from the following shortcomings: (i) hydrolysis of some acetals to ketones is problemati~.~~-~' (ii) certain compounds which contain groups sensitive to strong basic conditions are affected during oxidation, thereby giving poor results.(iii) the method is limited to a-hydroxyketones. To overcome the aforementioned limitations, Moriarty et aL50 have developed an alternative 1"' mediated route for the direct a-hydroxylation of ketones. Their original procedure involved the treatment of silyl enol ethers of acetophenones and acetylpyridines with iodosobenzene-boron-trifluoride- etherate-water in dichloromethane at - 40°C.so However, these conditions were not successful when applied to the a-hydroxylations of aliphatic ketones, propiophenones, and several heterocyclic ketones.Improved experimental conditions developed later on used iodosobenzene in water as a solvent at O-5"Cs' (Scheme 10). This was an extremely useful development because it not only solved the problem of a-hydroxylation of ketones but also formed the basis for superior alternatives to other existing methods for the a-functionalization of ketones. For example, one of the major advantages of this methodology is that a-hydroxylations of esters can also be effected using similar conditionss2 (Scheme 1 1 ). Perhaps the most significant aspect of the development, however, is the versatility of the approach in introducing several other functionalities at the a-positions of carbonyl compounds, and the following portions of this section are devoted to brief details of these results.30 OH 40 R2 = H, Me Scheme 10 R'R* = - ( c H ~ ) ~ - 41 R = alkyl, aryl Scheme I 1 0 42 Prakash, Saini, Tanwar, and Moriarty: Hypewalent iodine in organic synthesis 125The mechanistic pathway for the reactions involving silyl enol ethers is given in Scheme 12. Thus 39 first leads to the intermediate 43, the synthetic equivalent of a carbocation, and the reaction is completed by nucleophilic attack of water or some other nucleophile (Scheme 12). 39 (PhIO), BF3, EtZO (PhI-OBFzF-) Ph 43 A 0 0 R3 = H; a-hydroxy R3 = Me, Et, efc.; a-alkoxy Scheme 12 4.2 a-Alkoxylations Ketones, esters, and lactones are smoothly converted into their corresponding a-alkoxylated carbonyl compounds, 4453,54 and various examples showing the generality of this methodology are outlined in Scheme 13.OSiMe, (PhIO),-MeOH R’ &p FaB.OEt2 - R ’ q p OMe 39 44 R’ = ~ l , mt I But 0 S R~ = H, Me, Et, p i , OMe R’ ,R2 = -(CH2)4-, -(CH2)*-0-, +CH2)34- Scheme 13 An interesting point to note in the a-alkoxylations of ketones is that neither a-hydroxydimethylacetals (Section 2) nor rearranged products, 2-arylalkanoates (formed in the hypervalent iodine oxidation of alkyl aryl ketones in MeOH or trimethyl orth~formate)~~ are formed under these reaction conditions. 4.3 a-Acetoxylations, tosyloxylations, and mesyloxylations Silyl enol ethers of ketones have also been successfully converted into a-acetoxy- (45, X = OAc), tosyloxy- (45, X = OTs) and mesyloxy-ketones (45, X = OMS) by using IBD,54,56 HTIB,57 and HMIB,57 respectively (Scheme 14).Although the methods of Mizukami et aZ.14 and Koser et aZ.16 provide a direct approach for a-functionalizations of ketones, the major drawback of their approaches is that these reactions proceed with x 45 R = alkyl, aryl, 0; N N 0 o s OSiMe, (i)-(iii) 46 47 H X R’ %OR2 \ (i)-(iii) * R’ +OR2 OSiMe, 0 40 40 R’ = alkyl, aryl; R2 = Me, C2H5 .x 50 n = 1,2,3 51 ~~~ ~~ Condition X Ref. (i) IBD-F3B.0Et2 OAc 54156 (ii) HTIB, CH2C12, r.t. OTs 57 (iii) HMIB, CH2C12, r.t. OMS 57 Scheme 14 relatively low regioselectivity. However, sulfonyloxylations involving silyl enol ethers are regioselective. For example, 2-methyl-6-tosyloxycyclohexanone 53 can be prepared regioselectively from 1-trimethylsilyloxy-6-methylcyclohex- 1-ene 52 with HTIB in dichl~romethane~~ (Scheme 15).OSiMe3 b- HTIB CH2C12 Tso& 52 53 Scheme 15 Furthermore, another advantage of this approach is that it permits the preparation of a-sulfonyloxyketones 45 which contain acid sensitive or oxidizable ring systems, such as furan and ~ y r i d i n e ~ ~ ( a-sulfonyloxylated products are not accessible by the original Koser approach). This approach has also been found to be suitable for the a-functionalizations of esters 48 -+ 49 and lactones 50- 51, as shown in Scheme 14.54357 126 Contemporary Organic Synthesis4.4 a-Trifloxylations The treatment of silyl enol ethers with iodosobenzene in the presence of trimethylsilyl triflate in dichloromethane has been shown to afford good yields of a-( trifluoromethanesulfony1oxy)ketones (54, Scheme 16).s8 It seems likely that the active reagent in these reactions is [ trimet hy lsilyloxy( trifluoromethanesulfonyloxy )iodo] benzene.39 R' = aryl, mf? = H, Me OTf 54 5 Miscellaneous examples of a-functionalizations of carbonyl compounds 5.1 a-Phosphoryloxylations Koser et al.62 have reported that a-phosphoryloxylations of ketones can be achieved using [ hydroxy( bis( phenyloxy )phosphory )oxoiodo] benzene in acetonitrile (Scheme 19). The reaction proceeds through a pathway similar to a-sulfonyloxylation, where in this case the nucleophile is -O-P(OPh),O. * R 1 h R 2 PhI(OH)OPO(OPh), R' R', R2 = alkyl, aryl Scheme 19 Scheme 16 4.5 1,4-Diketones by carbon-carbon bond formation Hypervalent iodine oxidations of silyl enol ethers of ketones with iodosobenzene/boron trifluoride etherate in dichloromethane, in the absence of any external nucleophile result in carbon-carbon coupling reactions leading to the formation of the corresponding butane- 1,4-dione~.">~~ (55, Scheme 17).The 1,4-diones, of course, are important intermediates in the synthesis of pyrroles, furans, and thiophenes (Scheme 17). However, the synthesis of unsymmetrical 1,4-diones by this method has not been so successful under the same reaction conditions. The reaction pathway is analogous to Scheme 12. In this case one equivalent of silyl enol ether gives the a-ketocarbonium ion equivalent 43, which then couples with another equivalent of silyl enol ether (acting as nucleophile) to give the product (Scheme 18).0 55 R = alkyl, aryl, heterocyclyl Scheme 17 OSiMel 43 55 Scheme 18 Following earlier reports, joint efforts from Russian and American research groups61 have solved the problem of the synthesis of unsymmetrical carbon-carbon coupled products by the in situ generation of the highly reactive iodonium salt [Ph-I+-CH,-COPhIBF, and making use of (Ph-IO),-HBF, at - 78°C. OPO(OPh), 56 5.2 a-Functionalizations of B-dicarbonyl compounds using iodosobenzene Iodosobenzene, which is polymeric in nature, has been employed successfully to effect one-pot a-functionalizations of various P-dicarbonyl compounds. For example, treatment of the P-dicarbonyl compounds 57 with iodosobenzene and azidotrimethylsilane in chloroform under reflux gives a-azido-P-dicarbonyl compounds34 58, X = N,.Similarly, use of methanesulfonic acid and alcohol in place of azidotrimethylsilane has provided a-mesyloxy- and a-alkoxy-P-dicarbonyl compounds, re~pectively~~ (Scheme 20). When two equivalents of the P-dicarbonyl compounds 57 are treated with 1.2 equivalents of (Ph-IO),,-F,B.OEt, (1.3 equivalents) in chloroform, self-coupling at the a-position occurs34 leading to the dimers 59 (Scheme 2 1). R ' V f ? (PhIO), -F3B.OEt2 X-, CHC13 R' R2 57 x 58 R' = Me, Ph R2 = Me, OMe, OC2H5 X = N, OMe, OC2H5, OS02Me Scheme 20 R' = Me, Ph R2 = Me, OMe, OC2H5 Scheme 21 .. .. 0 0 59 Prakash, Saini, Tanwar, and Moriarty: Hypervalent iodine in organic synthesis 127In all these transformations, iodosobenzene and the nucleophile afford hypervalent iodine reagents (60 or 61) as outlined in Scheme 22.A mechanism for the formation of 58 is given in Scheme 23, and the mechanism of the self-coupling leading to 59 is analogous to that shown in the synthesis of 174-diketones 55. R-X 7 * Ph--f OY X 60 61 7 (PhIO), + Y-X - Ph--f Y = H, SiMe,; X = N3, OSO,Me, OMe Scheme 22 57 x-!T Ph 1-x- r l r L Ph - .. LO Scheme 23 5.3 Synthesis of oxygen-containing heterocycles by intramolecular participation An important application of the methodologies shown above lies in the formation of oxygen-containing heterocyclic compounds when intramolecular participation by a suitably placed oxygen-containing functional group occurs. These results are presented in the following subsections (5.3.1-5.3.3) according to the type of reagent used. 5.3.1 Using IBD-KOH/MeOH 5.3.I. 1 2-Aroylcoumaran-3-ones The synthesis of coumaran-3-ones involving the intramolecular participation of an o-hydroxyl group has been described in a previous review.6 In a continuation of these studies, it has been found that the oxidation of a-aroyl-o-hydroxyacetophenones (62, P-diketones) using IBD-KOH/MeOH provides a useful route for obtaining 2-aroylcoumaran-3-0nes~~ 63. A noticeable feature of this reaction is that the P-diketones 62 do not give ylides 64, a fact well established in the literature64 for other /3-dicarbonyl compounds (Scheme 24). qy 0 0 62 I IBD-KOWMeOH 0 Ph 63 64 Scheme 24 5.3.1.2 Steroidal spiro-oxetan-3-ones Taruta et aZ.65 have shown that 17p-acetyl- 17 a-hydroxysteroids 65 on oxidation with IBD-KOH/MeOH at 20°C give the novel steroidal spiro-oxetan-3-ones 67.This is an interesting example of intramolecular participation where the C- 17 a-hydroxyl group is an intramolecular nucleophile (66 -c 67), as compared to -0Me which acts as an intermolecular nucleophile (Scheme 25). 1 L 66 67 Scheme 25 5.3.2 Using HTIB, MeCN, or CH,CI, 5.3.2.1 2-Aroylcoumaran-3-ones The oxidations of o-aroyloxyacetophenones 68 with HTIB, followed by Baker-Venkataraman rearrangement of the resulting 1 2 8 Contemporary Organic Synthesiso-aroyloxy-a-tosyloxyacetophenones 69 with potassium hydroxide in dioxan or THF at reflux temperature leads to the formation of 2-aroylcoumaran-3-ones 70 (Scheme 26).66 R2 K E HTIB ::q OCOk CH24Ts R’ 0 0 68 60 \HTIB, KOH, dioxan or THF \ k R’ R’ 70 R1=H,0Me;R2=H R’ = CI; R2 = H, M e Scheme 26 5.3.2.2 Coumaran-3-ones via their dimethylacetals Treatment of 2-( a-tosy1oxy)acyl phenyl benzoate 72, obtained from o-benzoyloxyacetopropiophenones 7 1 using HTIB, with methanolic potassium hydroxide at 0-5°C leads to the formation of coumaran-3-one dimethylacetals 73 by way of intramolecular cyclization.These dimethylacetals 73 then undergo hydrolysis to the corresponding coumaran-3-ones 74 either by treatment with dilute HC1 or by keeping them at room temperature for a few days (Scheme 27).“7 It is interesting to note that normal a-tosyloxyketones on similar treatment with KOH/MeOH give a-hydroxydimethylacetals of type 38 (Scheme 9).48 OCOPh OCOPh R’ OTs 0 0 71 a-8 72 a-e OMe R’ R’ 0 74 a-8 73 a-8 71-74 R’ R2 R3 a H H H b M e H H C CI H H d CI Me H e H H M e Scheme 27 Two alternative pathways which can be proposed to explain the transformation 72 + 73 are outlined in Schemes 28 and 29.According to the first pathway (Scheme 28), the reaction starts with attack of methoxide onto the ketonic group, which simultaneously attacks the carbonyl group associated with the ester, leading to the intermediate 76. Loss of the benzoyloxy group from 76, followed by addition of methoxide and cyclization then leads to the product, viz. 76 -., 77 -+ 73. fO R’ R2 R’ n f ) C H R 3 f-7 A 3 - OMe Me0 77 1 -6Ts ,5 OTs 1 OTs 76 OMe R’ MeO 73 Scheme 28 Alternatively, the reaction may proceed via the a-hydroxydimethylacetal79, formed according to Scheme 29, [72 -+ 78 -+ 791 which leads to a second intermediate 80 by nucleophilic attack of alkoxide or alcohol onto the carbonyl function of the benzoyloxy group.Finally, the cyclic product 73 is obtained by intramolecular participation of phenoxide ion accompanied by displacement of the benzoyloxy group. 72 78 1 0 80 1 &OPh 73 Scheme 29 Prakash, Saini, Tanwar, and Moriarty: Hypervalent iodine in organic synthesis 1295.3.2.3 Oxolactones When the 5-oxocarboxylic acids 8 1 and 83, and the 4,6-dioxo-carboxylic acids 85 and 87 are treated separately with HTIB in dichloromethane, intramolecular participations by the carboxyl groups take place leading to the formation of the corresponding oxolactones 82 and 84, and dioxo-d-lactones 86 and 88, respectively6s (Scheme 30). 6 Conclusions It is evident from the foregoing discussion that the applications of organo I1I1 reagents have offered a large number of simple alternatives to existing methods to bring about a-functionalizations of carbonyl compounds.The hypervalent iodine approach mostly involves one-step direct procedures, with simple experimentation, and generally gives good yields of products. Another attractive feature of hypervalent-iodine mediated synthesis is their non-toxic nature as compared to methods involving Hg("), TI("'), and Pb(Iv) reagents. U 81 a2 0 0 \ CH2COZH 83 84 A C O 2 H .o- (p 65 0 87 00 Reagent : (i) HTIB, CH2CI2 Scheme 30 5.3.3 Using (PhIO),-F,B.OEt,, H 2 0 5.3.3.1 Coumaran-3-ones The oxidation of 1 -trimethylsilyloxy- 1- ( 2- trimet hy lsily loxy pheny 1 ) ethane 8 9 with (PhIO),F,B.OEt,, H,O results in the formation of coumaran-3-one 90 as the major product, by a route involving intramolecular participation of the o-hydroxyl group, in addition to minor amounts of the expected a-hydroxylated product 9 16y (Scheme 31).OSiMe3 o;"... ' OSiMe3 89 Scheme 31 0 91 7 References 1 C. Willgerodt, J. Prakt. Chem., 1886,33,154. 2 D.F. Banks, Chem. Rev., 1966,66,243. 3 A. Varvoglis, Chem. SOC. Rev., 1981,10,377. 4 G.F. Koser, 'The Chemistry of Functional Groups, Supplement D', ed. S. Patai and Z. Rappoport, Wiley, 1983, Chapter 25, p. 1265. 5 A. 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ISSN:1350-4894    

DOI:10.1039/CO9950200121

出版商:RSC    

年代:1995

数据来源: RSC