MARCH’S ADVANCED ORGANIC CHEMISTRY MARCH’S ADVANCED ORGANIC CHEMISTRY REACTIONS, MECHANISMS, AND STRUCTURE SEVENTH EDITION Michael B Smith Professor of Chemistry Copyright # 2013 by John Wiley & Sons, Inc All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 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Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002 Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic formats For more information about Wiley products, visit our web site at www.wiley.com Library of Congress Cataloging-in-Publication Data: Smith, Michael, 1946 Oct 17- March’s Advanced Organic Chemistry : Reactions, Mechanisms, and Structure – 7th Edition / Michael B Smith, Professor of Chemistry pages cm Includes index ISBN 978-0-470-46259-1 (cloth) Chemistry, Organic I Title II Title: Advanced organic chemistry QD251.2.M37 2013 547—dc23 2012027160 Printed in the United States of America 10 CONTENTS PREFACE xiii COMMON ABBREVIATIONS xxi BIOGRAPHICAL STATEMENT xxv PART I INTRODUCTION Localized Chemical Bonding 1.A 1.B 1.C 1.D 1.E 1.F 1.G 1.H 1.I 1.J 1.K 1.L Covalent Bonding Multiple Valence Hybridization Multiple Bonds Photoelectron Spectroscopy Electronic Structures of Molecules Electronegativity Dipole Moment Inductive and Field Effects Bond Distances Bond Angles Bond Energies Delocalized Chemical Bonding 2.A Molecular Orbitals 2.B Bond Energies and Distances in Compounds Containing Delocalized Bonds 2.C Molecules that have Delocalized Bonds 2.D Cross-Conjugation 2.E The Rules of Resonance 2.F The Resonance Effect 2.G Steric Inhibition of Resonance and the Influences of Strain 2.H pp–dp Bonding Ylids 2.I Aromaticity 2.I.i Six-Membered Rings 2.I.ii Five, Seven, and Eight-Membered Rings 2.I.iii Other Systems Containing Aromatic Sextets 2.J Alternant and Nonalternant Hydrocarbons 3 11 14 15 18 19 21 25 27 31 32 35 37 42 43 45 46 49 50 54 57 62 63 v vi CONTENTS 2.K Aromatic Systems with Electron Numbers other than Six 2.K.i Systems of Two Electrons 2.K.ii Systems of Four Electrons: Antiaromaticity 2.K.iii Systems of Eight Electrons 2.K.iv Systems of Ten Electrons 2.K.v Systems of more than Ten Electrons: 4n ỵ Electrons 2.K.vi Systems of more than 10 Electrons: 4n Electrons 2.L Other Aromatic Compounds 2.M Hyperconjugation 2.N Tautomerism 2.N.i Keto–Enol Tautomerism 2.N.ii Other Proton-Shift Tautomerism 65 66 67 71 72 74 79 82 85 89 89 92 Bonding Weaker Than Covalent 96 3.A Hydrogen Bonding 3.B p–p Interactions 3.C Addition Compounds 3.C.i Electron Donor–Acceptor Complexes 3.C.ii Crown Ether Complexes and Cryptates 3.C.iii Inclusion Compounds 3.C.iv Cyclodextrins 3.D Catenanes and Rotaxanes 3.E Cucurbit[n]Uril-Based Gyroscane Stereochemistry and Conformation 4.A Optical Activity and Chirality 4.A.i Dependence of Rotation on Conditions of Measurement 4.B What Kinds of Molecules Display Optical Activity? 4.C The Fischer Projection 4.D Absolute Configuration 4.D.i The CAHN–INGOLD–PRELOG System 4.D.ii Methods of Determining Configuration 4.E The Cause of Optical Activity 4.F Molecules with more than One Stereogenic Center 4.G Asymmetric Synthesis 4.H Methods of Resolution 4.I Optical Purity 4.J cis–trans Isomerism 4.J.i cis-trans Isomerism Resulting from Double Bonds 4.J.ii cis–trans Isomerism of Monocyclic Compounds 4.J.iii cis–trans Isomerism of Fused and Bridged Ring Systems 4.K Out–In Isomerism 4.L Enantiotopic and Diastereotopic Atoms, Groups, and Faces 4.M Stereospecific and Stereoselective Syntheses 4.N Conformational Analysis 4.N.i Conformation in Open-Chain Systems 96 103 104 104 108 113 116 118 121 122 122 124 125 136 137 138 141 145 146 149 154 160 162 162 165 167 168 170 173 173 175 CONTENTS 4.N.ii Conformation in Six-Membered Rings 4.N.iii Conformation in Six-Membered Rings Containing Heteroatoms 4.N.iv Conformation in Other Rings 4.O Molecular Mechanics 4.P STRAIN 4.P.i Strain in Small Rings 4.P.ii Strain in Other Rings 4.P.iii Unsaturated Rings 4.P.iv Strain Due to Unavoidable Crowding Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes 5.A Carbocations 5.A.i Nomenclature 5.A.ii Stability and Structure of Carbocations 5.A.iii The Generation and Fate of Carbocations 5.B Carbanions 5.B.i Stability and Structure 5.B.ii The Structure of Organometallic Compounds 5.B.iii The Generation and Fate of Carbanions 5.C Free Radicals 5.C.i Stability and Structure 5.C.ii The Generation and Fate of Free Radicals 5.C.iii Radical Ions 5.D Carbenes 5.D.i Stability and Structure 5.D.ii The Generation and Fate of Carbenes 5.E Nitrenes Mechanisms and Methods of Determining them 6.A 6.B 6.C 6.D 6.E 6.F 6.G 6.H 6.I 6.J Types of Mechanism Types of Reaction Thermodynamic Requirements for Reaction Kinetic Requirements for Reaction The Baldwin Rules for Ring Closure Kinetic and Thermodynamic Control The Hammond Postulate Microscopic Reversibility Marcus Theory Methods of Determining Mechanisms 6.J.i Identification of Products 6.J.ii Determination of the Presence of an Intermediate 6.J.iii The Study of Catalysis 6.J.iv Isotopic Labeling 6.J.v Stereochemical Evidence 6.J.vi Kinetic Evidence 6.J.vii Isotope Effects vii 180 186 188 190 192 193 199 201 204 208 208 208 209 218 221 221 228 233 234 234 245 248 249 249 253 257 261 261 262 264 266 270 271 272 273 273 275 275 275 277 277 278 278 285 viii CONTENTS Irradiation Processes in Organic Chemistry 7.A Photochemistry 7.A.i Excited States and the Ground State 7.A.ii Singlet and Triplet States: “Forbidden” Transitions 7.A.iii Types of Excitation 7.A.iv Nomenclature and Properties of Excited States 7.A.v Photolytic Cleavage 7.A.vi The Fate of the Excited Molecule: Physical Processes 7.A.vii The Fate of the Excited Molecule: Chemical Processes 7.A.viii The Determination of Photochemical Mechanisms 7.B Sonochemistry 7.C Microwave Chemistry Acids and Bases 8.A Brønsted Theory 8.A.i Brønsted Acids 8.A.ii Brønsted Bases 8.B The Mechanism of Proton-Transfer Reactions 8.C Measurements of Solvent Acidity 8.D Acid and Base Catalysis 8.E Lewis Acids and Bases 8.E.i Hard–Soft Acids–Bases 8.F The Effects of Structure on the Strengths of Acids and Bases 8.G The Effects of the Medium on Acid and Base Strength Effects of Structure and Medium on Reactivity 9.A 9.B 9.C 9.D Resonance and Field Effects Steric Effects Quantitative Treatments of the Effect of Structure on Reactivity Effect of Medium on Reactivity and Rate 9.D.i High Pressure 9.D.ii Water and Other Non-Organic Solvents 9.D.iii Ionic Solvents 9.D.iv Solventless Reactions PART II INTRODUCTION 10 Aliphatic Substitution, Nucleophilic and Organometallic 10.A Mechanisms 10.A.i The SN2 Mechanism 10.A.ii The SN1 Mechanism 10.A.iii Ion Pairs in the SN1 Mechanism 10.A.iv Mixed SN1 and SN2 Mechanisms 10.B SET Mechanisms 289 289 289 291 292 294 295 296 301 306 307 309 312 312 313 320 323 324 327 330 331 334 343 347 347 349 352 361 362 363 364 366 367 373 373 374 379 383 387 389 958 ADDITION TO CARBON–CARBON MULTIPLE BONDS The corresponding b-1-alkynyl-9-BBN compounds also give the reaction.1262 Since the product 97 is an a,b-unsaturated ketone, it can be made to react with another BR3, the same or different, to produce a wide variety of ketones (98) O H CH3 CH3 R3B–O2 H2O R 97 O R'3B–O2 H2O R' CH3 R 98 O Vinyl boranes add to conjugated ketones in the presence of a Rh catalyst (with high asymmetric induction in the presence of BINAP).1263 Alkynyl-boranes also add to conjugated ketones, in the presence of BF3.1264 Other boron reagents add to conjugated carbonyl compounds.1265 Tetraphenylborates add to conjugated alkynes in the presence of a Pd catalyst in a reaction known as hydrophenylation.1266 Alkynyl boronate esters (Reaction 12-28) give conjugate addition1267 in the presence of boron trifluoride etherate,1268 as arylboronic acids (Reaction 12-28) with a Rh,1269 Pd,1270 or a Bi catalyst.1271 Diethylzinc has also been used.1272 Aryl boronic acids add to the double bond of vinyl sulfones in the presence of a Rh catalyst.1273 Vinylboronic acids add directly to conjugated ketones.1274 An Ir catalyzed 1,6-addition of arylboronic acids is known.1275 Conjugated alkynes undergo conjugate addition with arylboronic acids in the presence of a Cu catalyst.1276 Organocatalysts have also been used for the conjugate addition of arylboronic acids to conjugated systems.1277 Potassium vinyltrifluoroborates (see Reactions 10-59, 13-10, and 13-13) give 1,4-addition with a Rh catalyst,1278 as Sinclair, J.A.; Molander, G.A.; Brown, H.C J Am Chem Soc 1977, 99, 954 See also, Molander, G.A.; Brown, H.C J Org Chem 1977, 42, 3106 1263 Takaya, Y.; Ogasawara, M.; Hayashi, T Tetrahedron Lett 1998, 39, 8479 1264 Fujishima, H.; Takada, E.; Hara, S.; Suzuki, A Chem Lett 1992, 695 1265 Kabalka, G.W.; Das, B.C.; Das, S Tetrahedron Lett 2002, 43, 2323 1266 Zeng, H.; Hua, R J Org Chem 2008, 73, 558 1267 Wu, T.R.; Chong, J.M J Am Chem Soc 2005, 127, 3244; Pellegrinet, S.C.; Goodman, J.M J Am Chem Soc 2006, 128, 3116 1268 Chong, J.M.; Shen, L.; Taylor, N.J J Am Chem Soc 2000, 122, 1822 1269 Paquin, J.-F.; Defieber, C.; Stephenson, C.R.J.; Carreira, E.M J Am Chem Soc 2005, 127, 10850; Shintani, R.; Duan, W.-L.; Hayashi, T J Am Chem Soc 2006, 128, 5628; Duan, W.-L.; Iwamura, H.; Shintani, R.; Hayashi, T J Am Chem Soc 2007, 129, 2130; Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R J Am Chem Soc 2008, 130 2172; Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T J Org Chem 2005, 70, 2503; Stemmler, R.T.; Bolm, C J Org Chem 2005, 70, 9925; Paquin, J.-F.; Stephenson, C.R.J.; Defieber, C.; Carreira, E.M Org Lett 2005, 7, 3821; Martina, S.L.X.; Minnaard, A.J.; Hessen, B.; Feringa, B.L Tetrahedron Lett 2005, 46, 7159 1270 Lu, X.; Lin, S J Org Chem 2005, 70, 9651 1271 Sakuma, S.; Miyaura, N J Org Chem 2001, 66, 8944 1272 Dong, L.; Xu, Y.-J.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z Synthesis 2004, 1057 1273 With a chiral ligand, see Mauleon, P.; Carretero, J.C Org Lett 2004, 6, 3195 1274 Wu, T.R.; Chong, J.M J Am Chem Soc 2007, 129, 4908 1275 Nishimura, T.; Yasuhara, Y.; Hayashi, T Angew Chem Int Ed 2006, 45, 5164 1276 Yamamoto, Y.; Kirai, N.; Harada, Y Chem Commun 2008, 2010 1277 Sugiura, M.; Tokudomi, M.; Nakajima, M Chem Commun 2010, 7799 1278 Duursma, A.; Boiteau, J.-G.; Lefort, L.; Boogers, J.A.F.; de Vries, A.H.M.; de Vires, J.G.; Minnaard, A.J.; Feringa, B.L J Org Chem 2004, 69, 8045 1262 REACTIONS 959 aryltrifluoroborates.1279 The Rh catalyzed addition of vinyl tetrafluoroborates has been reported.1280 In the presence of a Rh catalyst, LiBPh(OMe)3 gave conjugate addition of the phenyl group to a,b-unsaturated esters.1281 The fact that these reactions are catalyzed by free radical initiators and inhibited by galvinoxyl1282 (a free radical inhibitor) indicates that free-radical mechanisms are involved 15-28 Radical Addition to Activated Double Bonds Hydro-alkyl-addition O + R1-X R1 H Bu3SnH hν or a radical initiator R O R1 In a reaction similar to 15-25, alkyl groups can be added to alkenes activated by such groups as COR0 , CO2R0 , CN, and even Ph.1283 This is a radical addition reaction.1284 In the method illustrated above, the R group comes from an alkyl halide (R ¼ primary, secondary, or tertiary alkyl; X ¼ Br or I) and the hydrogen from the tin hydride (H atom transfer agents) The reaction of tert-butyl bromide, Bu3SnH and AIBN (Sec 14.A.i), for example, adds a tert-butyl group to a conjugated ester via 1,4addition.1285 An alkene is converted to an alkylborane with catecholborane (Reaction 12-28) and when treated with a conjugated ketone and O2, radical conjugate addition leads to the b-substituted ketone.1286 The Bu3SnH can also be generated in situ, from R3SnX and NaBH4 Like Reaction 15-27, these additions have free radical mechanisms The reaction has been used for free radical cyclizations of the type discussed in Reaction 15-30.1287 Such cyclizations normally give predominant formation of fivemembered rings, but large rings (11–20 members) have also been synthesized by this reaction.1288 Navarre, L.; Martinez, R.; Genet, J.-P.; Darses, S J Am Chem Soc 2008, 130, 6159; Navarre, L.; Pucheault, M.; Darses, S.; Gen^et, J.-P Tetrahedron Lett 2005, 46, 4247 1280 Lalic, G.; Corey, E.J Tetrahedron Lett 2008, 49, 4894; Gendrineau, T.; Genet, J.-P.; Darses, S Org Lett 2009, 11, 3486 1281 Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.; Hayashi, T Tetrahedron Asymmetry 1999, 10, 4047 1282 Kabalka, G.W.; Brown, H.C.; Suzuki, A.; Honma, S.; Arase, A.; Itoh, M J Am Chem Soc 1970, 92, 710 See also, Arase, A.; Masuda, Y.; Suzuki, A Bull Chem Soc Jpn 1976, 49, 2275 1283 Giese, B Radicals in Organic Synthesis: Formation of Carbon–Carbon Bonds, Pergamon, Elmsford, NY, 1986, pp 36–68; Giese, B Angew Chem Int Ed 1985, 24, 553; Larock, R.C Organomercury Compounds in Organic Synthesis, Springer, NY, 1985, pp 263–273 See Larock, R.C Comprehensive Organic Transformations, 2nd ed., Wiley–VCH, NY, 1999, pp 1809–1813 1284 Srikanth, G.S.C.; Castle, S.L Tetrahedron 2005, 61, 10377 1285 Hayen, A.; Koch, R.; Metzger, J.O Angew Chem Int Ed 2000, 39, 2758 1286 Ollivier, C.; Renaud, P Chem Eur J 1999, 5, 1468 1287 See Jasperse, C.P.; Curran, D.P.; Fevig, T.L Chem Rev 1991, 91, 1237; Curran, D.P Adv Free Radical Chem (Greenwich, Conn.) 1990, 1, 121; Giese, B Radicals in Organic Synthesis: Formation of Carbon–Carbon Bonds, Pergamon, Elmsford, NY, 1986, pp 151–169 See Larock, R.C Comprehensive Organic Transformations, 2nd ed., Wiley-VCH, NY, 1999, pp 413–418 1288 See Porter, N.A.; Chang, V.H J Am Chem Soc 1987, 109, 4976 1279 960 ADDITION TO CARBON–CARBON MULTIPLE BONDS A BEt3 (see Sec 14.A.i) initiated reaction of conjugated amides with an alkyl iodide, in the presence of Bu3SnH and O2, leads to conjugate addition of the alkyl group.1289 Enantioselective radical addition has been reported.1290 Conjugate addition is possible using photolysis The photoinduced 1,4-addition of indoles to enones proceeds when irradiated at 350 nm.1291 OS VII, 105 15-29 Radical Addition to Unactivated Double Bonds1292 Alkyl-hydro-addition R1 + R—X radical initiator H-transfer agent R1 R H Radical addition to alkenes is usually difficult, except when addition occurs to conjugated carbonyl compounds (Reaction 15-24) An important exception involves radicals bearing a heteroatom a to the carbon bearing the radical center Such radicals are much more stable and can add to alkenes, usually with anti-Markovnikov orientation, as in the radical induced addition of HBr to alkenes (Reaction 15-2).1293 Examples of this type of reaction include the use of alcohol-, ester-,1294 amino-, and aldehyde-stabilized radicals.483 The alkyl group of alkyl iodides adds to alkenes with BEt3/O2 as the initiator and in the presence of a tetraalkylammonium hypophosphite.1295 The radical generated from (EtO)2POCH2Br adds to alkenes to generate a new phosphonate ester.1296 a-Bromo esters add to alkenes in the presence of BEt3/air to give a g-bromo ester.1297 a-Bromo amides add the Br and the acyl carbon to an alkene using Yb(OTf)3 with BEt3/O2 as the radical initiator.1298 a-Iodo amides add to alkenes using a water-soluble azobis initiator (see Sec 14.A.i) to give the iodo ester, which cyclizes under the reaction À ÀO)ÀÀCÀÀSC(À À ÀS)OEt] conditions to give a lactone.1299 b-Keto dithiocarbonates [RC(À À À generate the radical in the presence of a peroxide and add to alkenes.1300 2-Fluoropyridyl derivatives of allylic alcohols react with xanthates in the presence of lauroyl peroxide to give alkenes.1301 Malonate derivatives add to alkenes in the presence of a mixture of Mn/Co catalyst, in oxygenated acetic acid.1302 Sibi, M.P.; Petrovic, G.; Zimmerman, J J Am Chem Soc 2005, 127, 2390; Sibi, M.P.; Patil, K Org Lett 2005, 7, 1453; He, L.; Srikanth, G.S.C.; Castle, S.L J Org Chem 2005, 70, 8140 Also see Sibi, M.P.; Zimmerman, J J Am Chem Soc 2006, 128, 13346 1290 Lee, S.; Lim, C.J.; Kim, S.; Subramaniam, R.; Zimmerman, J.; Sibi, M.P Org Lett 2006, 8, 4311 1291 Moran, J.; Suen, T.; Beauchemin, A.M J Org Chem 2006, 71, 676 1292 See Smith, M.B Organic Synthesis, 3rd ed., Wavefunction Inc./Elsevier, Irvine, CA/London, England, 2010, pp 1278–1282 1293 See Curran, D.P Synthesis 1988, 489 (see pp 497–498) 1294 Deng, L.X.; Kutateladze, A.G Tetrahedron Lett 1997, 38, 7829 1295 Jang, D.O.; Cho, D.H.; Chung, C.-M Synlett 2001, 1923 1296 Bałczewski, P.; Mikołajczyk, M Synthesis 1995, 392 1297 Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K.; Omoto, K.; Fujimoto, H J Org Chem 2001, 66, 7776 1298 Mero, C.L.; Porter, N.A J Am Chem Soc 1999, 121, 5155 1299 Yorimitsu, H.; Wakabayashi, K.; Shinokubo, H.; Oshima, K Bull Chem Soc Jpn 2001, 74, 1963 1300 Ouvry, G.; Zard, S.Z Chem Commun 2003, 778 1301 Charrier, N.; Quiclet-Sire, B.; Zard, S.Z J Am Chem Soc 2008, 130, 8898 1302 Hirase, K.; Iwahama, T.; Sakaguchi, S.; Ishii, Y J Org Chem 2002, 67, 970 1289 REACTIONS 961 Other radicals can add to alkenes, and the rate constant for the addition of methyl radicals to alkenes has been studied.1303 The rate of radical additions to alkenes in general has also been studied.1304 The kinetic and thermodynamic control of a radical addition regiochemistry has also been studied.1305 Alkynes are generally less reactive than alkenes in radical coupling reactions.1306 Nonradical nucleophiles usually react faster with alkynes than with alkenes, however.1307 15-30 Radical Cyclization1308 Alkyl-hydro-addition X radial initiator H-transfer agent R v-Haloalkenes generate radicals upon treatment with radical initiator reagents (e.g., AIBN) or under photolysis conditions,1309 and the radical carbon adds to the alkene to form cyclic compounds.1310 This intramolecular addition of a radical to an alkene is called radical cyclization In a typical example, haloalkene (101) reacts with the radical produced by AIBN to give radical 100 The radical can add to the more substituted carbon to give 102 via a 5-exo-trig reaction (Sec 6.E).1311 If the radical adds to the less substituted carbon, 103 is formed via a 6-endo-trig reaction.1312 In both cases, the product is another radical, which must be converted to an unreactive product This is generally accomplished by adding a hydrogen-transfer agent1313 [e.g., tributyltin hydride (Bu3SnH)], which reacts with 102 to form methylcyclopentane and Bu3Sn , or with 103 to give cyclohexane The Bu3Sn formed in both cases usually dimerizes to form Bu3SnSnBu3 Cyclization can compete with hydrogen transfer1314 from Bu3SnH to 100 to give 99, the reduction product Atom-transfer cyclization is possible with other atoms (e.g., halogen), catalyzed by InCl31315or CuBr.1316 Tin-free radical cyclizations are known using peroxyacids.1317 Zytowski, T.; Fischer, H J Am Chem Soc 1996 118, 437 Avila, D.V.; Ingold, K.U.; Lusztyk, J.; Dolbier, Jr., W.R.; Pan, H.-Q J Org Chem 1996, 61, 2027 1305 Leach, A.G.; Wang, R.; Wohlhieter, G.E.; Khan, S.I.; Jung, M.E.; Houk, K.N J Am Chem Soc 2003, 125, 4271 1306 Giese, B.; Lachhein, S Angew Chem Int Ed 1982, 21, 768 1307 Dickstein, J.I.; Miller, G.I in The Chemistry of Carbon Carbon Triple Bonds, Vol 2, Patai, S (Ed.), Wiley, NY 1978 1308 See Smith, M.B Organic Synthesis, 3rd ed., Wavefunction Inc./Elsevier, Irvine, CA/London, England, 2010, pp 1283–1295; Rheault, T.R.; Sibi, M.P Synthesis 2003, 803 1309 See Pandey, G.; Reddy, G.D.; Chakrabarti, D J Chem Soc., Perkin Trans 1996, 219 1310 Chang, S.-Y.; Jiang, W.-T.; Cherng, C.-D.; Tang, K.-H.; Huang, C.-H.; Tsai, Y.-M J Org Chem 1997, 62, 9089 See McCarroll, A.J.; Walton, J.C J Chem Soc., Perkin Trans 2001, 3215 1311 Chatgilialoglu, C.; Ferreri, C.; Guerra, M.; Timokhin, V.; Froudakis, G.; Gimisis, Z.T J Am Chem Soc 2002, 124, 10765 See Guan, X.; Phillips, D.L.; Yang, D J Org Chem 2006, 71, 1984 1312 See Ishibashi, H.; Sato, T.; Ikeda, M Synthesis 2002, 695 1313 See Ha, C.; Horner, J.H.; Newcomb, M.; Varick, T.R.; Arnold, B.R.; Lusztyk, J J Org Chem 1993, 58 1194 1314 See Furxhi, E.; Horner, J.H.; Newcomb, M J Org Chem 1999, 64, 4064; Tauh, P.; Fallis, A.G J Org Chem 1999, 64, 6960 1315 Cook, G.R.; Hayashi, R Org Lett 2006, 8, 1045 1316 Clark, A.J.; Wilson, P Tetrahedron Lett 2008, 49, 4848 1317 Smith, D.M.; Pulling, M.E.; Norton, J.R J Am Chem Soc 2007, 129, 770 1303 1304 962 ADDITION TO CARBON–CARBON MULTIPLE BONDS X n-Bu3SnH 101 AIBN 102 5-exo-trig H 6-endo-trig 99 100 103 In general, formation of the five-membered ring dominates the cyclization, but if ÀC unit is relatively slow, the reduction product is formed preferentially addition to the CÀ Radical rearrangements can also diminish the yield of the desired product.1318 Given a choice between a larger and a smaller ring, radical cyclization generally gives the smaller ring,1319 but not always.1320 Formation of other size rings is possible of course A 4-exo-trig radical cyclization has been studied,1321 selectivity in a 7-endo versus 6-exo cyclization,1322 and also an 8-endo-trig reaction.1323 In radical cyclization to form large rings, 1,5- and 1,9-hydrogen atom abstractions can pose a problem1324 Ring expansion during radical cyclization is possible when the terminal intermediate is a cyclobutylcarbinyl radical.1325 The mechanism of this reaction has been discussed.1326 Cyclization via 5-endo-dig transition states require reorientation of the radical orbital needed to reach the in-plane acetylene p orbital in the bond-forming step, with accompanying loss of conjugative stabilization, and an increase in the activation energy Therefore, many 5-endo cyclizations undergo H abstraction or equilibration with an isomeric radical.1327 In cases where hydrogen atom transfer gives primarily reduced products, one solution to promote cyclization generates the radical by photochemical cleavage of Bu3SnÀÀSnBu3 and the resulting carbon radical can cyclize (see Reaction 15-46).1328 A halogen atom transfer agent (e.g., iodoethane) is used rather than a hydrogen-transfer agent, so the final product is an alkyl iodide A mixture of a Grignard reagent and CoCl2 has been used to initiate aryl radical cyclizations.1329 Titanium(III)-mediated radical cyclizations are known,1330 and SmI2 Mueller, A.M.; Chen, P J Org Chem 1998, 63, 4581 Bogen, S; Malacria, M J Am Chem Soc 1996 118, 3992.; Beckwith, A.L.J.; Ingold, K.U in Vol of Rearrangements in Ground States and Excited States, de Mayo, P., Ed., Academic Press, NY 1980, pp 162–283 G omez, A.M.; Company, M.D.; Uriel, C.; Valverde, S.; Lopez, J.C Tetrahedron Lett 2002, 43, 4997 1320 Mayon, P.; Chapleur, Y Tetrahedron Lett 1994, 35, 3703; Marco-Contelles, J.; Sanchez, B J Org Chem 1993, 58, 4293 1321 Jung, M.E.; Marquez, R.; Houk, K.N Tetrahedron Lett 1999, 40, 2661 1322 Kamimura, A.; Taguchi, Y Tetrahedron Lett 2004, 45, 2335 1323 Wang, Li.C J Org Chem 2002, 67, 1271 1324 Kraus, G.A.; Wu, Y J Am Chem Soc 1992 114, 8705 1325 Zhang, W.; Dowd, P Tetrahedron Lett 1995, 36, 8539 1326 Bailey, W.F.; Carson, M.W Tetrahedron Lett 1999, 40, 5433 1327 Alabugin, I.V.; Manoharan, M J Am Chem Soc 2005, 127, 9534 1328 Afor a polymer-bound Sn catalyst see Hernan, A.G.; Kilburn, J.D Tetrahedron Lett 2004, 45, 831 1329 Clark, A.J.; Davies, D.I.; Jones, K.; Millbanks, C J Chem Soc., Chem Commun 1994, 41 1330 Barrero, A.F.; Oltra, J.E.; Cuerva, J.M.; Rosales, A J Org Chem 2002, 67, 2566 1318 1319 REACTIONS 963 mediated reactions are possible in the presence of a Ni catalyst.1331 Organoboranemediated radical cyclizations are known (see Sec 14.A.i).1332 The influence of the halogen atom on radical cyclization has been studied.1333 Both phenylthio1334 and phenylseleno groups1335 can be used as “leaving groups” for radical cyclization, where S or Se atom transfer leads to formation of the radical A seleno ester (R2NÀÀCH2C(ÀÀO)SeMe) has also been used with (Me3Si)3SiH (tristrimethylsilylane, TTMSS) and AIBN to generate R2NCH2 1336 O-Phosphonate esters have also served as the leaving group.1337 N-(2-bromophenylbenzyl)methylamino have been used as leaving groups for formation of a radical.1338 Radical cyclization reaction often proceeds with high diastereoselectivity1339 and high asymmetric induction when chiral precursors are used Internal alkynes are good substrates for radical cyclization,1340 but terminal alkynes tend to give mixtures of exo/ endo-dig products (Sec 6.E).1341 Radical cyclization has been used to transfer asymmetry from transient atropisomers to form lactams.1342 Radical cyclization is compatible with the presence of other functional groups, and heterocyclic rings may be formed via radical cyclization.1343 Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aq H3PO2 and NaHCO3 in ethanol.1344 Cyclization of vinyl radicals1345 and allenyl À ÀCH2 derivatives ÀC(R1)À radicals1346 are also well known Treatment of XCH2CON(R)À À (X ¼ Cl, Br, I) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization.1347 Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam,1348 and there are other examples of radical cyclization with molecules containing a lactam unit1349 or an amide unit.1350 b-Lactams can be produced by radical Molander, G.A.; St Jean, Jr., D.J J Org Chem 2002, 67, 3861 Becattini, B.; Ollivier, C.; Renaud, P Synlett 2003, 1485 1333 Tamura, O.; Matsukida, H.; Toyao, A.; Takeda, Y.; Ishibashi, H J Org Chem 2002, 67, 5537 1334 See Ikeda, M.; Shikaura, J.; Maekawa, N.; Daibuzono, K.; Teranishi, H.; Teraoka, Y.; Oda, N.; Ishibashi, H Heterocycles 1999, 50, 31 1335 See Ericsson, C.; Engman, L Org Lett 2001, 3, 3459 1336 Quirante, J.; Vila, X.; Escolano, C.; Bonjoch, J J Org Chem 2002, 67, 2323 1337 Crich, D.; Ranganathan, K.; Huang, X Org Lett 2001, 3, 1917 1338 Andrukiewicz, R.; Loska, R.; Prisyahnyuk, V.; Stalinski, K J Org Chem 2003, 68, 1552 1339 See Bouvier, J.-P.; Jung, G.; Liu, Z.; Guerin, B.; Guindon, Y Org Lett 2001, 3, 1391; Bailey, W.F.; Longstaff, S.C Org Lett 2001, 3, 2217; Stalinski, K.; Curran, D.P J Org Chem 2002, 67, 2982 1340 See Sha, C.-K.; Shen, C.-Y.; Jean, T.-S.; Chiu, R.-T.; Tseng, W.-H Tetrahedron Lett 1993, 34, 764; Miyabe, H.; Takemoto, Y Chemistry: European J 2007, 13, 7280 1341 Kano, S.; Yuasa, Y.; Asami, K.; Shibuya, S Chem Lett 1986, 735; Robertson, J.; Lam, H.W.; Abazi, S.; Roseblade, S.; Lush, R.K Tetrahedron 2000, 56, 8959 1342 Petit, M.; Lapierre, A.J.B.; Curran, D.P J Am Chem Soc 2005, 127, 14994 1343 Majumdar, K.C.; Basu, P.K.; Mukhopadhyay, P.P Tetrahedron 2005, 61, 10603, Tetrahedron 2007, 63, 793 1344 Yorimitsu, H.; Shinokubo, H.; Oshima, K Chem Lett 2000, 104 1345 Sha, C.-K.; Zhan, Z.-P.; Wang, F.-S Org Lett 2000, 2, 2011 1346 Wartenberg, F.-H.; Junga, H.; Blechert, S Tetrahedron Lett 1993, 34, 5251 See Shi, J.; Zhang, M.; Fu, Y.; Liu, L.; Guo, Q.-X Tetrahedron 2007, 63, 12681 1347 Gilbert, B.C.; Kalz, W.; Lindsay, C.I.; McGrail, P.T.; Parsons, A.F.; Whittaker, D.T.E J Chem Soc., Perkin Trans 2000, 1187 See El Bialy, S.A.A.; Ohtani, S.; Sato, T.; Ikeda, M Heterocycles 2001, 54, 1021; Liu, L.; Wang, X.; Li, C Org Lett 2003, 5, 361 1348 Keusenkothen, P.F.; Smith, M.B J Chem Soc., Perkin Trans 1994, 2485 1349 Padwa, A.; Rashatasakhon, P.; Ozdemir, A.D.; Willis, J J Org Chem 2005, 70, 519 1350 Beckwith, A.L.J.; Joseph, S.P.; Mayadunne, R.T.A J Org Chem 1993, 58, 4198 1331 1332 964 ADDITION TO CARBON–CARBON MULTIPLE BONDS cyclization, using Mn(OAc)3.1351 Radical cyclization occurs with enamines as well.1352 Radical cyclization occurs with oximes to form the corresponding heterocyclic ring.1353 Phenylseleno N-allylamines led to cyclic amines.1354 v-Iodo acrylate esters cyclize to form À lactones,1355 and allylic acetoxy compounds of the type CÀ À ÀCÀÀCÀÀO2CÀÀCH2I cyclize in a similar manner to give lactones.1356 Iodolactonization (see Reaction 15-41) occurs under standard radical cyclization conditions using allylic acetoxy compounds1357 and HGaCl2/BEt3 has been used to initiate the radical process.1358 a-Bromo mixed acetals give a-alkoxy THF derivatives1359 and a-iodoacetals cyclize to give similar products.1360 The reaction of an o-alkynyl aryl isonitrile with AIBN and 2.2 equiv of Bu3SnH gave an indole via 5-exo-dig cyclization.1361 Indole derivatives have also been prepared from o-iodoaniline derivatives, using AIBN and TTMSS.1362 Samarium(II) has been used to initial 5-exo-trig ketyl-alkene coupling, and the mechanism of the reaction has been examined.1363 Acyl radicals can be generated and they cyclize in the usual manner.1364 Molecular orbital calculations have shown that acyl, as well as silyl radicals, simultaneously use SOMO–LUMO (SOMO ¼ singly occupied molecular orbital and LUMO ¼ lowest unoccupied molecular orbital) and LUMO–HOMO interactions in reactions with alkenes.1365 A polyene-cyclization reaction generated four rings, initiating the sequence by treatment of a phenylseleno ester with Bu3SnH/AIBN to form the acyl radical, which added to the first alkene unit.1366 The newly formed carbon radical added to the next alkene, and so on Acyl radicals generated from Ts(R)NCOSePh derivatives cyclize to form lactams.1367 Radical cyclization of iodo aldehydes or ketones, at the carbon of the carbonyl, is effectively an acyl addition reaction (16-24 and 16-25) This cyclization is often reversible, and there are many fewer examples of addition to an alkene or alkyne In one example, a d-iodo aldehyde was treated with BEt3/O2 to initiate formation of the radical, and in the presence of Bu3SnH cyclization gave a cyclopentanol.1368 The reaction of an D’Annibale, A.; Nanni, D.; Trogolo, C.; Umani, F Org Lett 2000, 2, 401 See Lee, E.; Kim, S.K.; Kim, J.Y.; Lim, J Tetrahedron Lett 2000, 41, 5915 For a related reaction with tin hydride, see Curran, D.P.; Guthrie, D.B.; Geib, S.J J Am Chem Soc 2008, 130, 8437 For a discussion of mechanism, see Snider, B.B Tetrahedron 2009, 65, 10738 1352 Glover, S.A.; Warkentin, J J Org Chem 1993, 58, 2115 1353 Kitamura, M.; Narasaka, K Bull Chem Soc Jpn 2008, 81, 539 1354 Gupta, V.; Besev, M.; Engman, L Tetrahedron Lett 1998, 39, 2429 1355 Ryu, I.; Nagahara, K.; Yamazaki, H.; Tsunoi, S.; Sonoda, N Synlett 1994, 643 1356 Ollivier, C.; Renaud, P J Am Chem Soc 2000, 122, 6496 1357 Ollivier, C.; Bark, T.; Renaud, P Synthesis 2000, 1598 1358 Mikami, S.; Fujita, K.; Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K Org Lett 2001, 3, 1853 1359 Villar, F.; Equey, O.; Renaud, P Org Lett 2000, 2, 1061 1360 Fujioka, T.; Nakamura, T.; Yorimitsu, H.; Oshima, K Org Lett 2002, 4, 2257 1361 Rainer, J.D.; Kennedy, A.R.; Chase, E Tetrahedron Lett 1999, 40, 6325 1362 Kizil, M.; Patro, B.; Callaghan, O.; Murphy, J.A.; Hursthouse, M.B.; Hobbs, D J Org Chem 1999, 64, 7856 1363 Sadasivam, D.V.; Antharjanam, P.K.S.; Prasad, E.; Flowers II, R.A J Am Chem Soc 2008, 130, 7228 1364 See Jiaang, W.-T.; Lin, H.-C.; Tang, K.-H.; Chang, L.-B.; Tsai, Y.-M J Org Chem 1999, 64, 618 1365 Schiesser, C.H.; Matsubara, H.; Ritsner, I.; Wille, U Chem Commun 2006, 1067 1366 Pattenden, G.; Roberts, L.; Blake, A.J J Chem Soc., Perkin Trans 1998, 863; Also see, Pattenden, G.; Smithies, A.J.; Tapolczay, D.; Walter, D.S J Chem Soc., Perkin Trans 1996, 1367 Rigby, J.H.; Danca, D.M.; Horner, J.H Tetrahedron Lett 1998, 39, 8413 1368 Devin, P.; Fensterbank, L.; Malacria, M Tetrahedron Lett 1999, 40, 5511 1351 REACTIONS 965 aldehyde-alkene with AIBN, 0.5 PhSiH3 and 0.1 Bu3SnH generated a radical from the alkene, which cyclized at the aldehyde to give cyclopentanol derivatives.1369 An aldehyde– O-methyloxime generated a radical adjacent to nitrogen under standard conditions, which cyclized at the carbonyl to give a cyclic a-hydroxy N-methoxyamine.1370 Alternatively, an ÀNOMe unit under electrolytic condia-bromoacetal–O-methyl oxime cyclized at the CÀ tions in the presence of cobaloxime.1371 Alkynyl-imines are cyclized to the imino carbon to form alkylidene lactams under radical conditions in the presence of CO.1372 The attacking radical in radical cyclization reactions is not limited to a carbon, and a number of heterocycles can be prepared.1373 Amidyl radicals are known and give cyclization reactions.1374 Aminyl radical cyclizations have been reported.1375 N-Chloroamine-alkenes give an aminyl radical when treated with TiCl3ÁBF3, and cyclization gave a pyrrolidine derivative with a pendant chloromethyl group.1376 N-(S-substituted) amines give similar results using AIBN/Bu3SnH.1377 Oxime-alkenes cyclize to imines when treated with PhSSPh and TEMPO (Sec 5.C.i).1378 An oxygen radical can be generated under photochemical conditions, and they add to alkenes in a normal manner.1379 Note that radical substitution occurs, and reaction of Ph3SnH/AIBN and an O-amidyl compound having a phosphonate ester elsewhere in the molecule gave cyclization to a THF derivative.1380 15-31 Conjugate Addition with Heteroatom Nucleophiles X + Z2 X Z2 H Heteroatom nucleophiles add to conjugated systems to give Michael-type products Conjugated carbonyl compounds react via conjugate addition with amines to give b-amino derivatives (See Reaction 15-31)1381 Conjugate addition of nitrogencontaining compounds is often called the aza-Michael reaction.1382 Amines add to conjugated systems in the presence of In,1383 Pd,1384 Sm,1385 Bi,1386 Cu,1387 Hays, D.S.; Fu, G.C Tetrahedron 1999, 55, 8815 Naito, T.; Nakagawa, K.; Nakamura, T.; Kasei, A.; Ninomiya, I.; Kiguchi, T J Org Chem 1999, 64, 2003 1371 Inokuchi, T.; I.; Kawafuchi, H Synlett 2001, 421 1372 Tojino, M.; Otsuka, N.; Fukuyama, T.; Matsubara, H.; Ryu, I J Am Chem Soc 2006, 128, 7712 1373 See Majumdar, K.C.; Basu, P.K.; Mukhopadhyay, P.P Tetrahedron 2004, 60, 6239; Bowman, W.R.; Cloonan, M.O.; Krintel, S.L J Chem Soc., Perkin Trans 2001, 2885 1374 Clark, A.J.; Peacock, J.L Tetrahedron Lett 1998, 39, 6029 See Prabhakaran, E.N.; Nugent, B.M.; Williams, A.L.; Nailor, K.E.; Johnston, J.N Org Lett 2002, 4, 4197 1375 Martinez, II, E.; Newcomb, M J Org Chem 2006, 71, 557  1376 Hemmerling, M.; Sj€oholm, A,; Somfai, P Tetrahedron Asymmetry 1999, 10, 4091 1377 Guindon, Y.; Guerin, B.; Landry, S.R Org Lett 2001, 3, 2293 1378 Lin, X.; Stien, D.; Weinreb, S.M Org Lett 1999, 1, 637 1379 For a review, see Hartung, J Eur J Org Chem 2001, 619 1380 Crich, D.; Huang, X.; Newcomb, M Org Lett 1999, 1, 225 1381 See Cossu, S.; DeLucchi, O.; Durr, R Synth Commun 1996, 26, 4597 1382 Yamagiwa, N.; Qin, H.; Matsunaga, S.; Shibasaki, M J Am Chem Soc 2005, 127, 13419 See MunroLeighton, C.; Blue, E.D.; Gunnoe, T.B J Am Chem Soc 2006, 128, 1446 1383 Loh, T.-P.; Wei, L.-L Synlett 1998, 975 1384 Takasu, K.; Nishida, N.; Ihara, M Synlett 2004, 1844 1385 Yadav, J.S.; Reddy, A.R.; Rao, Y.G.; Narsaiah, A.V.; Reddy, B.V.S Synthesis 2007, 3447 1386 Srivastava, N.; Banik, B.K J Org Chem 2003, 68, 2109 1387 Xu, L.-W.; Wei, J.-W.; Xia, C.-G.; Zhou, S.-L.; Hu, X.-X Synlett 2003, 2425 1369 1370 966 ADDITION TO CARBON–CARBON MULTIPLE BONDS Ce,1388 La,1389 or Yb compounds1390 to give b-amino derivatives This reaction can be initiated photochemically1391 or with microwave irradiation.1392 Aniline derivatives add to conjugated aldehydes in the presence of a catalytic amount of DBU,1393 and indeed, DBU promotes the aza-Michael reaction.1394 Lithium amides add to conjugated esters to give the b-amino ester.1395 Amidocuprates add to conjugated systems to give b-nitrogen compounds, and a b-silyl group has an activating effect of the amidocuprate.1396 A solvent-free conjugate addition of amines occurs on alumina in the presence of a Ce catalyst.1397 Boric acid has been used as a catalyst of azaMichael reactions in water.1398 An intramolecular addition of an amine unit to a conjugated ketone in the presence of a Pd catalyst, or photochemically, led to cyclic amines.1399 Amines add to conjugated thiolactams.1400 There are asymmetric versions of the aza-Michael reaction,1401 and high enantioselectivity is possible using an organocatalyst.1402 Chiral catalysts lead to enantioselective reactions.1403 Chiral additives (e.g., chiral Cinchona alkaloids1404 or chiral naphthol derivatives)1405 have also been used Chiral imines add in a highly stereoselective manner.1406 Chiral catalysts have been used for the conjugated addition of carbamates.1407 Indoles add to nitro alkenes in the presence of an organocatalyst.1408 Other N-heterocycles add with good enantioselectivity in the presence of an organocatalyst.1409 Lactams have been shown to add to conjugated esters in the presence of Si(OEt)4 and CsF.1410 Phthalimide adds to alkylidene malononitriles via 1,4-addition with a Pd catalyst, and the resulting anion can be alkylated with an added allylic halide.1411 Alkylidene Bartoli, G.; Bosco, M.; Marcantoni, E.; Petrini, M.; Sambri, L.; Torregiani, E J Org Chem 2001, 66, 9052 Matsubara, S.; Yoshioka, M.; Utimoto, K Chem Lett 1994, 827 1390 Jenner, G Tetrahedron Lett 1995, 36, 233 1391 Das, S.; Kumar, J.S.D.; Shivaramayya, K.; George, M.V J Chem Soc Perkin Trans 1, 1995, 1797 1392 Moghaddam, F.M.; Mohammadi, M.; Hosseinnia, A Synth Commn 2000, 30, 643 1393 Mark o, I.E.; Chesney, A Synlett 1992, 275 1394 Yeom, C.-E.; Kim, M.J.; Kim, B.M Tetrahedron 2007, 63, 904 1395 Doi, H.; Sakai, T.; Iguchi, M.; Yamada, K.-i.; Tomioka, K J Am Chem Soc 2003, 125, 2886 1396 Bertz, S.H.; Ogle, C.A.; Rastogi, A J Am Chem Soc 2005, 127, 1372 1397 Bartoli, G.; Bartolacci, M.; Giuliani, A.; Marcantoni, E.; Massaccesi, M.; Torregiani, E J Org Chem 2005, 70, 169 1398 Chaudhuri, M.K.; Hussain, S.; Kantam, M.L.; Neelima, B Tetrahedron Lett 2005, 46, 8329 1399 Zhang, X.; Jung, Y.S.; Mariano, P.S.; Fox, M.A.; Martin, P.S.; Merkert, J Tetrahedron Lett 1993, 34, 5239 1400 Sosnicki, J.G.; Jagodzinski, T.S.; Liebscher, J J Heterocyclic Chem 1997, 34, 643 1401 Vicario, J.L.; Badıa, D.; Carrillo, L.; Etxebarria, J.; Reyes, E.; Ruiz, N Org Prep Proceed Int 2005, 37, 513; Krishna, P.R.; Sreeshailam, A.; Srinivas, R Tetrahedron 2009, 65, 9657 1402 Chen, Y.K.; Yoshida, M.; MacMillan, D.W.C J Am Chem Soc 2006, 128, 9328; Sibi, M.P.; Itoh, K J Am Chem Soc 2007, 129, 8064; Vesely, J.; Ibrahem, I.; Rios, R.; Zhao, G.-L.; Xu, Y.; Cordova, A Tetrahedron Lett 2007, 48, 2193; Lu, X.; Deng, L Angew Chem Int Ed 2008, 47, 7710; Fadini, L.; Togni, A Helv Chim Acta 2007, 90, 411 1403 Sugihara, H.; Daikai, K.; Jin, X.L.; Furuno, H.; Inanaga, J Tetrahedron Lett 2002, 43, 2735 1404 Jew, S.-s.; Jeong, B.S.; Yoo, M.-S.; Huh, H.; Park, H.-g Chem Commun 2001, 1244 1405 Yamagiwa, N.; Matsunaga, S.; Shibasaki, M J Am Chem Soc 2003, 125, 16178 1406 Ambroise, L.; Desma€ele, D.; Mahuteau, J.; d’Angelo, J Tetrahedron Lett 1994, 35, 9705 1407 Palomo, C.; Oiarbide, M.; Halder, R.; Kelso, M.; Gomez-Bengoa, E.; Garcıa, J.M J Am Chem Soc 2004, 126, 9188 1408 Ganesh, M.; Seidel, D J Am Chem Soc 2008, 130, 16464 1409 Diner, P.; Nielsen, M.; Marigo, M.; Jørgensen, K.A Angew Chem Int Ed 2007, 46, 1983 1410 Ahn, K.H.; Lee, S.J Tetrahedron Lett 1994, 35, 1875 1411 Aoyagi, K.; Nakamura, H.; Yamamoto, Y J Org Chem 2002, 67, 5977 1388 1389 REACTIONS 967 ÀC(NHAc)CONHR, react with secondary amines in water to give the amido-amides, CÀ b-amino amido amide.1412 Amines also add in a conjugate manner to alkynyl phosphonate esters, CÀ ÀCÀÀPO(OEt)2, using a CuI catalyst.1413 Hydroxylamines add to conjugated nitro compounds to give 2-nitro hydroxylamines.1414 N,O-Trimethylsilyl hydroxylamines add to conjugated esters, via nitrogen, using a Cu catalyst.1415 Trimethylsilyl azide with acetic acid reacts with conjugated ketones to give the b-azido ketone.1416 Sodium azide adds to conjugated ketones in aq acetic acid and 20% PBu3.1417 An interesting variation involves a double Michael addition of amido amines, amido alcohols or amido thiols to conjugated alkynes, forming pyrrolidine, oxazolidine, or thiazolidine derivatives.1418 The nitrogen of carbamates adds to conjugated ketones with a Pt,1419 Pd,1420 Cu,1421 or with a bis(triflamide) organocatalyst.1422 The amine moiety of a carbamate adds to conjugated ketones with a polymer-supported acid catalyst,1423 or with BF3 OEt2.1424 The reaction of ammonium formate with 1,4-diphenylbut-2-en-1,4-dione, in PEG-200 and a Pd catalyst under microwave irradiation, gave 2,5-diphenylpyrrole.1425 Phosphines react similarly to amines under certain conditions Conjugate addition of R2PH and a Ni catalyst give conjugate addition to a,b-unsaturated nitriles.1426 A Pd catalyzed addition of diarylphosphines proceeds with good enantioselectivity to give chiral phosphines.1427 Phosphites add to nitroalkenes in the presence of a chiral organocatalyst to give the corresponding nitro phosphite compound.1428 Alcohols add to conjugated ketones with a PMe3 catalyst to give the b-alkoxy ketone.1429 This reaction is called an oxy-Michael reaction.1430 Alcohol addition is catalyzed by N-heterocyclic carbenes1431 and other organocatalysts,1432 often with enantioselectivity.1433 The conjugate addition of peroxide anions (HOOÀ and ROOÀ) to a,b-unsaturated carbonyl compounds is discussed in Reaction 15-48 An intramolecular variation is known that produces dihydropyrones.1434 Á Naidu, B.N.; Sorenson, M.E.; Connolly, J.P.; Ueda, Y J Org Chem 2003, 68, 10098 Panarina, A.E.; Dogadina, A.V.; Zakharov, V.I.; Ionin, B.I Tetrahedron Lett 2001, 42, 4365 1414 O’Neil, I.A.; Cleator, E.; Southern, J.M.; Bickley, J.F.; Tapolczay, D.J Tetrahedron Lett 2001, 42, 8251 1415 Cardillo, G.; Gentilucci, L.; Gianotti, M.; Kim, H.; Perciaccante, R.; Tolomelli, A Tetrahedron Asymmetry 2001, 12, 2395 1416 Guerin, D.J.; Horstmann, T.E.; Miller, S.J Org Lett 1999, 1, 1107 1417 Xu, L.-W.; Xia, C.-G.; Li, J.-W.; Zhou, S.-L Synlett 2003, 2246 1418 Sriramurthy, V.; Barcan, G.A.; Kwon, O J Am Chem Soc 2007, 129, 12928 1419 Kakumoto, K.; Kobayashi, S.; Sugiura, M Org Lett 2002, 4, 1319 1420 Gaunt, M.J.; Spencer, J.B Org Lett 2001, 3, 25 1421 Wabnitz, T.C.; Spencer, J.B Tetrahedron Lett 2002, 43, 3891 1422 Wabnitz, T.C.; Spencer, J.B Org Lett 2003, 5, 2141 1423 Wabnitz, T.C.; Yu, J.-Q.; Spencer, J.B Synlett 2003, 1070 1424 Xu, L.-W.; Li, L.; Xia, C.-G.; Zhou, S.-L.; Li, J.-W.; Hu, X.-X Synlett 2003, 2337 1425 Rao, H.S.P.; Jothilingam, S Tetrahedron Lett 2004, 42, 6595 1426 Sadow, A.D.; Haller, I.; Fadini, L.; Togni, A J Am Chem Soc 2004, 126, 14704 1427 Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L J Am Chem Soc 2010, 132, 5562 1428 Terada, M.; Ikehara, T.; Ube, H J Am Chem Soc 2007, 129, 14112 1429 Stewart, I.C.; Bergman, R.G.; Toste, F.D J Am Chem Soc 2003, 125, 8696 1430 Also called hydroalkoxylation See Ramachary, D.B.; Mondal, R Tetrahedron Lett 2006, 47, 7689 1431 Phillips, E.M.; Riedrich, M.; Scheidt, K.A J Am Chem Soc 2010, 132, 13179 1432 Kano, T.; Tanaka, Y.; Maruoka, K Tetrahedron Lett 2006, 47, 3039 1433 Kano, T.; Tanaka, Y.; Maruoka, K Tetrahedron 2007, 63, 8658 1434 Baker-Glenn, C.; Hodnett, N.; Reiter, M.; Ropp, S.; Ancliff, R.; Gouverneur, V J Am Chem Soc 2005, 127, 1481 1412 1413 968 ADDITION TO CARBON–CARBON MULTIPLE BONDS Thiophenol and butyllithium (lithium phenylthiolate) adds to conjugated esters.1435 Similar addition is observed with selenium compounds (RSeLi).1436 Thiols react with conjugated amides via 1,4-addition with the addition of 10% Hf(OTf)4 or other lanthanide triflates1437 or to conjugated ketones in ionic solvents.1438 Alkyl thiols add to conjugated carbonyl compounds with high enantioselectivity using an organocatalyst.1439 Iron(III)catalyzed addition of thiols occurs under solvent-free conditions.1440 Thiols add without a catalyst in water1441 in PEG,1442 or in ionic liquids.1443 Thiol addition is also catalyzed by iodine under solvent-free conditions.1444 Ceric ammonium nitrate promotes the conjugate addition of thiols.1445 Thioaryl moieties can be added in the presence of Yb1446 or a catalytic amount of (DHQD)2PYR (a dihydroquinidine, see Reaction 15-48).1447 Thioalkyl units (e.g., BuSÀÀ) add to conjugated ketones using BuSÀÀSnBu and InÀ ÀI.1448 Addition of 1449 Dithiocarbamates conjugated lactones is possible to produce b-arylthiolated lactones are prepared by the reaction of an amine, CS2, and a conjugated carbonyl compound.1450 a,b-Unsaturated sulfones undergo conjugate addition of a cyano group using Et2AlCN.1451 15-32 Acylation of Activated Double Bonds and of Triple Bonds Hydro-acyl-addition O O R1 + X O R R1 O R Under some conditions, acid derivatives add directly to activated double bonds Acetic anhydride, Mg metal, and Me3SiCl react with conjugated esters to give a g-keto ester.1452 Similar reaction with vinyl phosphonate esters leads to a g-keto phosphonate ester.1453 Thioesters undergo conjugate addition to a,b-unsaturated ketones in the presence of ÀO)SiMe3, add in a SmI2.1454 Using DBU and a thioimidazolium salt, acyl silanes, Ar(CÀ 1435 Kamimura, A.; Kawahara, F.; Omata, Y.; Murakami, N.; Morita, R.; Otake, H.; Mitsudera, H.; Shirai, M.; Kakehi, A Tetrahedron Lett 2001, 42, 8497 1436 Zeni, G.; Stracke, M.P.; Nogueira, C.W.; Braga, A.L.; Menezes, P.H.; Stefani, H.A Org Lett 2004, 6, 1135 1437 Kobayashi, S.; Ogawa, C.; Kawamura, M.; Sugiura, M Synlett 2001, 983 1438 Yadav, J.S.; Reddy, B.V.S.; Baishya, G J Org Chem 2003, 68, 7098 1439 Marigo, M.; Schulte, T.; Franzen, J.; Jørgensen, K.A J Am Chem Soc 2005, 127, 15710; Kumar, A.; Akanksha Tetrahedron 2007, 63, 11086 1440 Chu, C.-M.; Huang, W.-J.; Lu, C.; Wu, P.; Liu, J.-T.; Yao, C.-F Tetrahedron Lett 2006, 47, 7375 1441 Khatik, G.L.; Kumar, R.; Chakraborti, A.K Org Lett 2006, 8, 2433 1442 Kamal, A.; Reddy, D.R.; Rajendar Tetrahedron Lett 2005, 46, 7951 1443 ; Kotrusz, P Org Biomol Chem 2006, 4, 1420 Me9ciarova, M.; Toma, S 1444 Chu, C.-M.; Gao, S.; Sastry, M.N.V.; Yao, C.-F Tetrahedron Lett 2005, 46, 4971; Gao, S.; Tzeng, T.; Sastry, M.N.V.; Chu, C.-M.; Liu, J.-T.; Lin, C.; Yao, C.-F Tetrahedron Lett 2006, 47, 1889 1445 Chu, C.-M.; Gao, S.; Sastry, M.N.V.; Kuo, C.-W.; Lu, C.; Liu, J.-T.; Yao, C.-F Tetrahedron 2007, 63, 1863 1446 Taniguchi, Y.; Maruo, M.; Takaki, K.; Fujiwara, Y Tetrahedron Lett 1994, 35, 7789 1447 McDaid, P.; Chen, Y.; Deng, L Angew Chem Int Ed 2002, 41, 338 1448 Ranu, B.C.; Mandal, T Synlett 2004, 1239 1449 Nishimura, K.; Tomioka, K J Org Chem 2002, 67, 431 1450 Azizi, N.; Aryanasab, F.; Torkiyan, L.; Ziyaei, A.; Saidi, M.R J Org Chem 2006, 71, 3634 1451 Ruano, J.L.G.; Garcıa, M.C.; Laso, N.M.; Castro, A.M.M.; Ramos, J.H.R Angew Chem Int Ed 2001, 40, 2507 1452 Ohno, T.; Sakai, M.; Ishino, Y.; Shibata, T.; Maekawa, H.; Nishiguchi, I Org Lett 2001, 3, 3439 1453 Kyoda, M.; Yokoyama, T.; Maekawa, H.; Ohno, T.; Nishiguchi, I Synlett 2001, 1535 1454 Blakskjær, P.; Høj, B.; Riber, D.; Skrydstrup, T J Am Chem Soc 2003, 125, 4030 REACTIONS 969 similar manner.1455 Under microwave irradiation, aldehydes add to conjugated ketones using DBU/Al2O3 and a thiazolium salt.1456 The conjugate addition of acyl zirconium complexes in the presence of BF3ÁOEt2 is catalyzed by palladium acetate.1457 O ether + R-Li + Ni(CO)4 O O R H 104 An acyl group can be introduced into the position of an a,b-unsaturated ketone by treatment with an organolithium compound and nickel carbonyl1458 to give a 1,4-diketone (104) The R group may be aryl or primary alkyl The reaction can also be applied to alkynes, which need not be activated, in which case molar equivalents add and the ÀCH ! RCOCHR0 CH2COR).1459 In a different product is also a 1,4-diketone (e.g., R0 CÀ procedure, a,b-unsaturated ketones and aldehydes are acylated by treatment at À110 C with R2(CN)CuLi2 and CO This method is successful for R ¼ primary, secondary, and tertiary alkyl.1460 For secondary and tertiary groups, R(CN)CuLi, which does not waste an R group, can be used instead.1461 O R + H –CN R H O CN O OH R + CN 105 HO R NC O –HCN 104 H The reaction of an aldehyde and cyanide ion (See Reaction 16-52) in a polar aprotic solvent (e.g., DMF or DMSO) leads to a cyanohydrin, which generates a diketone via loss of HCN.1462 This method has been applied to a,b-unsaturated ketones, esters, and nitriles to give the corresponding 1,4-diketones, g-keto esters, and g-keto nitriles, respectively (see also, Reaction 16-55) The initial product of this reaction is ion 105, which is a synthon for À the unavailable RÀCÀ ÀO anion (see Reaction 10-68) It is a masked R CÀ ÀO anion that upon reaction with the conjugated carbonyl gives 104 after loss of HCN from the cyanohydrin addition product Other masked carbanions that have been used in this À 1465 reaction are the RCÀ(CN)NR ion,1463 the EtSCRSOEt ion,1464 the CH2À ÀC OEt ion, 1466 1466 À À ÀC(OEt)Cu2Li, À ÀCMe(SiMe3), CH2À CH2À and the RC (OCHMeOEt)CN ion.1467 À À In the last case, best results are obtained when R is a vinylic group Anions of 1,3-dithianes Mattson, A.E.; Bharadwaj, A.R.; Scheidt, K.A J Am Chem Soc 2004, 126, 2314 Yadav, J.S.; Anuradha, K.; Reddy, B.V.S.; Eeshwaraiah, B Tetrahedron Lett 2003, 44, 8959 1457 Hanzawa, Y.; Tabuchi, N.; Narita, K.; Kakuuchi, A.; Yabe, M.; Taguchi, T Tetrahedron 2002, 58, 7559 1458 Corey, E.J.; Hegedus, L.S J Am Chem Soc 1969, 91, 4926 1459 Sawa, Y.; Hashimoto, I.; Ryang, M.; Tsutsumi, S J Org Chem 1968, 33, 2159 1460 Seyferth, D.; Hui, R.C J Am Chem Soc 1985, 107, 4551 See also, Lipshutz, B.H.; Elworthy, T.R Tetrahedron Lett 1990, 31, 477 1461 Seyferth, D.; Hui, R.C Tetrahedron Lett 1986, 27, 1473 1462 See Stetter, H.; Kuhlmann, H Org React 1991, 40, 407–496; Stetter, H.; Kuhlmann, H.; Haese, W Org Synth., 65, 26 1463 Enders, D.; Gerdes, P.; Kipphardt, H Angew Chem Int Ed 1990, 29, 179 1464 Herrmann, J.L.; Richman, J.E.; Schlessinger, R.H Tetrahedron Lett 1973, 3271, 3275 1465 Beockman Jr., R.K.; Bruza, K.J.; Baldwin, J.E.; Lever, Jr., O.W J Chem Soc., Chem Commun 1975, 519 1466 Boeckman Jr., R.K ; Bruza, K.J J Org Chem 1979, 44, 4781 1467 Stork, G.; Maldonado, L J Am Chem Soc 1974, 96, 5272 1455 1456 970 ADDITION TO CARBON–CARBON MULTIPLE BONDS (Reaction 10-71) not give 1,4-addition to these substrates (except in the presence of ÀO group instead (Reaction 16-38) HMPA, see Reaction 15-25), but add 1,2 to the CÀ Interestingly, acylation occurs at the a-position of an enone when and a,b-unsaturated ketone is treated with an acid chloride and Et2Zn in the presence of a Rh catalyst.1468 In another procedure, acyl radicals derived from phenyl selenoesters (ArCOSePh) (by treatment with Bu3SnH) add to a,b-unsaturated esters and nitriles to give g-keto esters and g-keto nitriles, respectively.1469 OS VI, 866; VIII, 620 15-33 Addition of Alcohols, Amines, Carboxylic Esters, Aldehydes, and so on Hydro-acyl-addition, and so on Formates, primary and secondary alcohols, amines, ethers, alkyl halides, compounds of the ÀZ0 , and a few other compounds add to double bonds in the presence of free type ZÀÀCH2À radical initiators.1470 This is formally the addition of RH to a double bond, but the “R” is not just any carbon, but one connected to an oxygen or a nitrogen, a halogen, or to two Z groups (defined as in Sec 15.A.ii) Formates and formamides1471 add similarly: O O + H W H W W = OR, NH2 Alcohols, ethers, amines, and alkyl halides add as follows (shown for alcohols): + R H R OH OH H H R The ZCH2Z0 compounds react at the carbon bearing the active hydrogen1472: + H H H Z Z' Z H Z' + Z Z' H H Similar additions have been successfully carried out with carboxylic acids, anhydrides,1473 acyl halides, carboxylic esters, nitriles, and other types of compounds.1474 Similar reactions have been carried out on acetylene.1475 In an interesting variation, thiocarbonates add to alkynes in the presence of a Pd catalyst to give a b-phenylthio a,b-unsaturated ester.1476 Aldehydes add to alkynes in the presence of a Rh catalyst to give 1468 Sato, K.; Yamazoe, S.; Yamamoto, R.; Ohata, S.; Tarui, A.; Omote, M.; Kumadaki, I.; Ando, A Org Lett 2008, 10, 2405 1469 Boger, D.L.; Mathvink, R.J J Org Chem 1989, 54, 1777 1470 See Giese, B Radicals in Organic Synthesis: Formation of Carbon–Carbon Bonds, Pergamon, Elmsford, NY, 1986, pp 69–77; Vogel, H Synthesis 1970, 99; Dang, H.-S.; Roberts, B.P Chem Commun 1996, 2201 1471 Elad, D Fortschr Chem Forsch 1967, 7, 528, see pp 530–543 1472 See Hajek, M.; Malek, J Coll Czech Chem Commun 1979, 44, 3695 1473 de Klein, W.J Recl Trav Chim Pays-Bas 1975, 94, 48 1474 Cadogan, J.I.G Pure Appl Chem 1967, 15, 153, pp 153–158 See also, Giese, B.; Zwick, W Chem Ber 1982, 115, 2526; Giese, B.; Erfort, U Chem Ber 1983, 116, 1240 1475 See DiPietro, J.; Roberts, W.J Angew Chem Int Ed 1966, 5, 415 1476 Hua, R.; Takeda, H.; Onozawa, S.-y.; Abe, Y.; Tanaka, M J Am Chem Soc 2001, 123, 2899 REACTIONS 971 conjugated ketones.1477 In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopentanone with a Rh complex catalyst.1478 An intramolecular acyl addition to an alkyne was reported using silyl ketones, acetic acid, and a Rh catalyst.1479 Formamides add to alkynes in the presence of a Pd catalyst to form conjugated amides.1480 OS IV, 430; V, 93; VI, 587, 615 15-34 Addition of Aldehydes Alkyl-carbonyl-addition O R R1 H cat O R R1 In the presence of metal catalysts (e.g., Rh1481 or Yb1482), aldehydes can add directly to alkenes to form ketones Additives play an important role in such reactions.1483 The reaction of v-alkenyl aldehydes with a Rh catalyst leads to cyclic ketones,1484 with high enantioselectivity if chiral ligands are employed A carbene organocatalyst was used for an enantioselective intramolecular reaction.1485 b,g-Unsaturated ketones are prepared by the Rh catalyzed addition of aldehydes to dienes.1486 The addition of aldehydes to activated double bonds, mediated by a catalytic amount of thiazolium salt in the presence of a weak base, is called the Stetter reaction,1487 An internal addition of an alkynyl aldehyde, catalyzed by a Rh complex, led to a cyclopentenone derivative.1488 These reactions are not successful when the alkene contains electron-withdrawing groups (e.g., halo or carbonyl groups) A free radical initiator is required,1489 usually peroxides or UV light The mechanism is illustrated for aldehydes, but is similar for the other compounds: Kokubo, K.; Matsumasa, K.; Miura, M.; Nomura, M J Org Chem 1997, 62, 4564 Fairlie, D.P.; Bosnich, B Organometallics 1988, 7, 936, 946 Also see, Barnhart, R.W.; Wang, X.; Noheda, P.; Bergens, S.H.; Whelan, J.; Bosnich, B J Am Chem Soc 1994, 116, 1821 1479 Yamane, M.; Amemiya, T.; Narasaka, K Chem Lett 2001, 1210 1480 Fujihara, T.; Katafuchi, Y.; Iwai, T.; Terao, J.; Tsuji, Y J Am Chem Soc 2010, 132, 2094 1481 Willis, M.C.; Randell-Sly, H.E.; Woodward, R.L.; McNally, S.J.; Currie, G.S J Org Chem 2006, 71, 5291; Imai, M.; Tanaka, M.; Nagumo, S.; Kawahara, N.; Suemune, H J Org Chem 2007, 72, 2543 For a discussion of the mechanism, see Roy, A.H.; Lenges, C.P.; Brookhart, M J Am Chem Soc 2007, 129, 2082 1482 Curini, M.; Epifano, F.; Maltese, F.; Rosati, O Synlett 2003, 552 1483 See Jo, E.-A.; Jun, C.-H Tetrahedron Lett 2009, 50, 3338 1484 Barnhart, R.W.; McMorran, D.A.; Bosnich, B Chem Commun 1997, 589 1485 de Alaniz, J.R.; Rovis, T J Am Chem Soc 2005, 127, 6284; Liu, Q.; Rovis, T J Am Chem Soc 2006, 128, 2552; Kundu, K.; McCullagh, J.V.; Morehead, Jr., A.T J Am Chem Soc 2005, 127, 16042; Enders, D.; Han, J.; Henseler, A Chem Commun 2008, 3989 1486 Omura, S.; Fukuyama, T.; Horiguchi, J.; Murakami, Y.; Ryu, I J Am Chem Soc 2008, 130, 14094 For a related reaction, see Shibahara, F.; Bower, J.F.; Krische, M.J J Am Chem Soc 2008, 130, 14120 1487 Stetter, H.; Kuhlmann, H Org React 1991, 40, 407; Kerr, M.S.; Rovis, T J Am Chem Soc 2004, 126, 8876; Pesch, J.; Harms, K.; Bach, T Eur J Org Chem 2004, 2025; Mennen, S.; Blank, J.; Tran-Dube, M.B.; Imbriglio, J.E.; Miller, S.J Chem Commun 2005, 195 See also, Mattson, A.E.; Bharadwaj, A.R.; Scheidt, K.A J Am Chem Soc 2004, 126, 2314 1488 Tanaka, K.; Fu, G.C J Am Chem Soc 2002, 124, 10296 1489 See Lee, E.; Tae, J.S.; Chong, Y.H.; Park, Y.C.; Yun, M.; Kim, S Tetrahedron Lett 1994, 35, 129 for an example 1477 1478 972 ADDITION TO CARBON–CARBON MULTIPLE BONDS O R O O initiator H O + R + H R R R O O H R R etc O + In the presence of BF3 and a Ag salt, aldehydes add to alkynes to give the corresponding conjugated ketone.1490 Polymers are often side products Photochemical addition of aldehyde to conjugated CÀ ÀC units can be efficient when a triplet sensitizer (Sec 7.A.vi, category 5, e.g., benzophenone) is used.1491 A variation that is more of an acyl addition (Reaction 16-25) involves the reaction of an allylic alcohol with benzaldehyde With a Ru catalyst and in an ionic liquid, the CÀ ÀC unit reacts with the aldehyde, with concomitant oxidation of the allylic alcohol unit, to give a 1492 In b-hydroxy ketone, PhCHO ỵ C CCH(OH)R ! PhCH(OH)CH(Me)COR another variation, formate esters add to alkenes using a Ru catalyst to give an alkyl ester via a formylation process.1493 15-35 Hydrocarboxylation Hydro-carboxy-addition + CO + H2O H+ pressure H COOH The acid-catalyzed hydrocarboxylation of alkenes (the Koch reaction) can be performed in a number of ways.1494 In one method, the alkene is treated with CO and water at 100–350 C and 500–1000-atm pressure with a mineral acid catalyst However, the reaction can also be performed under milder conditions If the alkene is first treated with CO and catalyst and then water added, the reaction can be accomplished at 0–50 C and 1–100 atm If formic acid is used as the source of both the CO and the water, the reaction can be carried out at room temperature and atmospheric pressure.1495 The formic acid procedure is called the Koch–Haaf reaction (the Koch–Haaf reaction can also be applied to alcohols, see Reaction 10-77) Nearly all alkenes can be hydrocarboxylated by one of these procedures However, conjugated dienes are polymerized under these conditions Hydrocarboxylation can also be accomplished under mild conditions (160 C and 50 atm) by the use of nickel carbonyl as catalyst Acid catalysts are used along with the nickel carbonyl, but basic catalysts can also be employed.1496 The Ni(CO)4 catalyzed oxidative carbonylation with Rhee, J.U.; Krische, M.J Org Lett 2005, 7, 2493 Kraus, G.A.; Liu, P Tetrahedron Lett 1994, 35, 7723 1492 Yang, X.-F.; Wang, M.; Varma, R.S.; Li, C.-J Org Lett 2003, 5, 657 1493 Na, Y.; Ko, S.; Hwang, L.K.; Chang, S Tetrahedron Lett 2003, 44, 4475 1494 See Lapidus, A.L.; Pirozhkov, S.D Russ Chem Rev 1989, 58, 117; Anderson, G.K.; Davies, J.A in Hartley, F.R.; Patai, S The Chemistry of the Metal-Carbon Bond, Vol 3, Wiley, NY, 1985, pp 335–359, 335– 348; in Falbe, J New Syntheses with Carbon Monoxide, Springer, NY, 1980, the articles by Mullen, A pp 243–308; and Bahrmann, H pp 372–413; Falbe, J Carbon Monoxide in Organic Synthesis, Springer: Berlin, 1970, pp 78–174 1495 Haaf, W Chem Ber 1966, 99, 1149; Christol, H.; Solladie, G Bull Soc Chim Fr 1966, 1307 1496 Sternberg, H.W.; Markby, R.; Wender, P J Am Chem Soc 1960, 82, 3638 1490 1491 ... 11 -11 11 -13 ! 11 -15 11 -14 ! 11 -17 11 -15 ! 11 -18 11 -16 - deleted 11 -17 - deleted 11 -18 11 -19 11 -20 11 - 21 11- 22 11 -23 11 -24 11 -25 11 -26 11 -27 11 -28 11 -29 11 -30 11 - 31 11- 32 11 -33 11 -34 11 -35 11 -36... 10 -10 1 10 -10 2 10 -10 3 10 -10 4 10 -10 5 10 -10 6 10 -10 7 10 -10 8 10 -10 9 10 -11 0 10 -11 1 10 -11 2 10 -11 3 10 -11 4 10 -11 5 10 -11 6 10 -11 7 10 -11 8 10 -11 9 10 -12 0 10 -12 1 10 -12 2 10 -12 3 10 -12 4 10 -12 5 10 -12 6 10 -12 7 10 -12 8... 16 -89 16 -90 16 -10 0 16 -10 1 16 -10 2 16 -10 3 16 -10 4 16 -10 5 11 -1 ! 11 -1 11- 2 ! 11 -2 11 -3 ! 11 -3 11 -4 ! 11 -4 11 -5 ! 11 -5 11 -6 ! 11 -6 11 -7 ! 11 -7 11 -8 ! 11 -8 11 -9 11 -10 ! 11 -9 11 -11 ! 11 -10 11 -12 ! 11 -11