Organic synthesis workbook III

T Kinzel , F Major, C Raith , T Redert, F Stecker, N Tólle, J Zinngrebe G?WllEY-VCH Organic Synthesis Workbook 111 Foreword by Matthias Beller Tom Kinzel, Felix Major, Thomas Redert, FIarían 5tecker, Julia Zinngrebe, Nina Talle, and Christian Raith Organic Synthesis Workbook 111 1807-2007 Knowledge for Generations Each generation has its unique needs and aspirations When Charles Wiley first opened his small printing shop in lower Manhattan in 1807, it was a generation of boundless potential searching for an identity And we were there, helping to defme a new American literary tradition Over half a century later, in the midst of the Second Industrial Revolution, it was a generation focused on building the future Once again, we were there, supplying the critical scientific, technical, and engineering knowledge that helped frame the world Throughout the 20th Century, and into the new millennium, nations began to reach out beyond their own borders and a new international community was born Wiley was there, expanding its operations around the world to enable a global exchange of ideas, opinions, and know-how For 200 years, Wiley has been an integral part of each generation s journey, enabling the flow of information and understanding necessary to meet their needs and fulfill their aspirations Today, bold new technologies are changing the way we live and learn Wiley will be there, providing you the must-have knowledge you need to imagine new worlds, new possibilities, and new opportunities Generations come and go, but you can always count on Wiley to provide you the knowledge you need, when and where you need it! a ~~ William J Pesce President and Chief Executive Officer Peter Booth Wiley Chairman of the Board Tom Kinzel, Felix Major, Thomas Redert, Florian Stecker, Julia Zinngrebe, Nina Talle, and Christian Raith Organic Synthesis Workbook 111 BICENTENNIAL J iz • o z~ ~z @WILEY z~ ~ • 2007 ~ > r WI LEY-VCH Verlag GmbH & Co KGaA The Authors Tom Kinzel, Felix Major, Thomas Redert, F/orian Stecker, Julia Zinngrebe, Nina Tlille, Christian Raith U niversity of Giittingen Institute for Organic and Biomolecular Chemistry Tammannstr 37077 Giittingen Germany All books published by Wiley-VCH are careful1y produced Nevertheless, authors, editors, and publisher not warrant the information contained in these books, including this book, to be free of errors Readers are advised to keep in mind that statements, data, illustrations, procedural detalls or other items may inadvertently be inaccurate Library of Congress Card No.: Applied for British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library Bibliographic information published by the Deutsche Nationalbibliothek Die Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available in the Internet at © 2007 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim All rights reserved (including those of translation into other languages) No part of this book may be reproduced in any form - by photoprinting, microfilm, or any other means - nor transmitted or translated into a machine language without written permission from the publishers Registered names, trademarks, etc used in this book, even when not specifically marked as such, are not to be considered unprotected by law Printing Strauss GmbH, Miirlenbach Bookbinding Litges & Dopf GmbH, Heppenheim Anne Christine Kegler, Grafik-Designerin, Karlsruhe Wiley Bicentennial Logo Richard Cover J Paófico Printed in the Federal Republic of Germany Printed on aód-free papero ISBN: 978-3-527-31665-6 The Authors Tom IGnzel, born in 1977 in Erfurt, Germany, started studying chemistry at the University of Giittingen, Germany, in October 1998 After staying in the Peoples Republic of China in 2001/2002 studying Chinese at the University ofNanjing and joining the working group ofProfessor Wolfgang Hennig at the Chinese Academy of Sciences in Shanghai, he returned to Giittingen and received his diploma in Chemistry in July 2004 He is now a doctoral researcher in the research group of Professor Lutz F Tietze and employs experimental and theoretical techniques for mechanistic studies and method development in the field of stereoselective homoallylic ether synthesis Dr Felix Major, born in 1977 in Wittmund, Germany, started studying chemistry at the University of Giittingen, Germany, in October 1998 After joining the group of Professor Jonathan Clayden at the University of Manchester for three months in 2002 he returned to Giittingen and accomplished his diploma in September 2003 under the guidance ofProfessor Lutz F Tietze In November 2006, he gained his doctorate in the same research group with a thesis on the synthesis and biological evaluation of prodrug analogues of the antibiotic CC-1065 for a selective treatment of cancer Christian Raith was born in 1980 in Giittingen, Germany, and started studying chemistry at the University of Giittingen, Germany, in October 2001 He joined the research group of Professor Lutz F Tietze in May 2005 and received his diploma in January 2006 He is now doing his doctoral research in the same group studying palladium-catalyzed enantioselective dominoreactions for the synthesis of chromanes Organic Synthesis Workbook 1JI Tom Kinzel Felix Major, Thomas Redert, Florian Stecker, Julia Zinngrebe, Nina Tolle Christian Raith Copyright © 2007 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim ISBN: 978-3-527-31665-6 Thomas Redert, bom in 1978 in Gieí?en, Germany, started studying chemistry at the University of Gottingen, Germany, in October 1999 After staying in the United Kingdom in 2002/2003 at the University ofNewcastle upon Tyne and joining the working group of Dr Julian G Knight, he retumed to Gottingen and received his diploma in chemistry in July 2004 He is currently a doctoral researcher at the University of Gottingen in the research group of Prof Lutz F Tietze His research deals with the application of Palladium-catalyzed dominocyclizations for the synthesis of natural product analogues FIorían Stecker, bom in 1980 in Eutin, Germany, received his diploma in organic chemistry from the University of Gottingen, Germany, in July 2004 He started studying chemistry in Gottingen in October 1999 and worked at the Université Pierre et Marie Curie, Paris VI, France, under the direction of Professor Max MaIacria in 2002/2003 Shortly thereafter, he joined the group of Professor Lutz F Tietze in Gottingen, where he is currently a doctoral researcher He is committed to the palladium catalyzed domino-Wacker-Heck reaction for the enantioselective synthesis of vitamin E and other closely related chromanes and chromenes Nina Tolle, bom in 1981 in Osnabrück, Germany, started studying chemistry at the University of Gottingen, Germany, in 2001 She joined the research group of Professor Tietze in 2005 and received her diploma in 2006 She stayed in the same group for her doctoral research which deals with Lewis-acid mediated dominoreactions for the synthesis of spiroamine structures with the objective of natural product synthesis Dr Julia Zinngrebe, bom in 1979 in Eschwege, Germany, started studying chemistry at the University of Gottingen, Germany, in October 1998 After joining the group of Professor Clayden at the University of Manchester for three months in 2002 she returned to Gottingen and accomplished her diploma in September 2003 under the guidance of Professor Tietze In January 2007, she gained her doctorate in the same research group with a thesis on Palladium-catalyzed domino-reactions for the enantioselective synthesis of Vitamin E Dedicated to our PhD supervisor Pro! Dr Dr h c L F Tietze on the occasion ofhis 65th birthday Foreword Organic synthesis is at the heart of chemistry Although today interdisciplinary areas between chemistry and biology or between chemistry and material sciences are ofien believed to provide the main driving forces for the advancement of chemistry, I am convinced that the development of efficient and environmentally benign synthetic methods is still one of the most important goals of current chemical research Significantly, a majority of all chemists doing research in industry or academia are faced in their daily lives with demands for the efficient synthesis of new molecules It is thus important to attract the interest of talented students for this area and to provide high quality education From the beginning, the Organic Synthesis Workbook has been devoted to a significant extent to the training and education of students and younger researchers in this direction The main concept is to present challenging synthetic problems to the reader, which are selected from state-of-the-art syntheses of natural products The present 3rd volume successfully follows this track The new Organic Synthesis Workbook - similar to its predecessors - has been carefully devised and realized by a group of creative young students from the Institute of Organic and Biomolecular Chemistry ofthe Georg-August-University ofGottingen, Germany.1t covers 14 wellselected synthetic problems including modern catalytic coupling reactions and metathesis chemistry, together with recent developments in stereoselective carbon-carbon and carbonoxygen bond formation More specifically, each problem is introduced to the reader in a general marmer Afier this introduction the key chemistry of the respective synthesis is explained Then, the various synthetic problems are presented in a clear and understandable manner The major difference to classical teaching books is the active interaction ofthe reader with the content One could ask, is the concept ofthis book still timely? In my opinion, definitely yes! Obviously, information pours out from all kinds of scientific journals, PowerPoint presentations, and especially the internet However, to acquire long-Iasting knowledge of organic synthesis, and to transfer this knowledge, it is essential not only to consume facts and data but to apply it to real synthetic problems Thus, in addition to students for Masters and PhD degrees, everyone interested in synthetic chemistry is encouraged to train actively with books such as this Finally, wish to congratulate the authors for their excellent achievement It remains for me to hope that readers will enjoy working with this volume and discover aspects that will stimulate their own future research Matthias Beller Rostock, 20.11.2006 14 (-)-Dactylolide 14.6 References 10 11 12 13 14 15 A Cutignano, Bruno, G Bifulco, A Casapullo, C Debitus, L Gomez-Paloma, R Riccio, Eur J Org Chem 2001,775-778 J Tanaka, T Higa, Tetrahedron Lett 1996,37, 5535-5538 A B Smith, I1I, G Safonov, R M Corbett, J Am Chem Soco 2001,123,12426-12427 T R Hoye, M Hu, J Am Chem Soco 2003, 125,9576-9577 Louis, N L Hungerford, E J Humphries, M D McLeod, Org Lett 2006, 8, 1117-1120 L Claisen, Chem Ber 1912,45,3157-3166 R E Ireland, R H Mueller, J Am Chem Soco 1972, 94, 58975898 R E Ireland, R H Mueller, A K Willard, J Am Chem Soco 1976,98,2868-2877 a) A G Dossetter, T F Jamison, E N Jacobsen, Angew Chem 1999, 111, 2549-2552; Angew Chem Int Ed 1999, 38, 23982400; b) Paterson, M Tudge, Tetrahedron 2003, 59, 68336849 J R Parikh, W V E Doering, J Am Chem Soco 1967, 89, 5505-5507 R H Grubbs, S Chang, Tetrahedron 1998, 54,4413-4450 a) M Scholl, S Ding, C W Lee, R H Grubbs, Org Lett 1999, 1, 953-956; b) A Ffustner, O R Thiel, L Ackermann, H.-J Schanz, S P Nolan, J Org Chem 2000, 65,2204-2207; e) G Hughes, M Kimura, S L Buchwald, J Am Chem Soco 2003, 125, 11253-11258 D B Dess, J C Martin, J Am Chem Soco 1991, 113, 72777287 T Imamoto, N Takiyama, K Nakamura, T Hatajima, Y Kamiya, J Am Chem Soco 1989, 111, 4392-4398 a) O Mitsunobu, M Yamada, Bull Chem Soco Jpn 1967,40, 2380-2382; b) O Mitsunobu, Synthesis 1981, 1-28 275 277 Abbreviations Ac AcOH AIBN alloc aq acetyl acetic acid azo bisiso butyronitrile allyloxycarbonyl aqueous 9-BBN BINAl Bu Bz 9-borabicyclo[3.3.1 ]nonane 2,2'-dihydroxy-l,I'-binaphtylaluminium hydride 2,2'-bis(diphenylphosphino)1,1'-binaphthyl tert-butyloxycarbonyl 2,2'-bis(oxazolyl)-1,1'binaphthyl based on recovered starting material butyl benzoyl CAN cat CBS Cbz CIP COD CSA Cy ceric ammonium nitrate catalytic Corey, Bakshi, Shibata carboxybenzyl Cahn, Ingold, Prelog cis,cis-cycloocta-1,5 -diene 10-camphorsulfonic acid cyclohexyl dba DBU dibenzylideneacetone 1,8-diazabicyclo[ A.O]undec7-ene dichloroethane dichloromethane dichloro dicyano quinone diethyl azodicarboxylate diastereomeric excess diethyl tartrate 3, 4-dihydro- 2H- pyran diisopropyl azodicarboxylate diisobutylaluminium hydride BINAP BOC BOXAX brsm DIOP DIPT DMAP DMB DMDO DME DMF DMP DMPU DMS DMSO DPPA dppf dppp dr DCE DCM DDQ DEAD de DET DHP DIAD DIBAL EDC ee Et EtOAc eq 2,2-dimethyl-l,3-dioxolan4,5 -bis(methy lene )bis( diphenylphosphine) diisopropyl tartrate 4-dimetyhlaminopyridine 3,4-dimethylbenzyl dimethyldioxirane dimethoxyethane N,N-dimethylformamide Dess-Martin periodinane N,N'-dimethylpropyleneurea dimethy lsulfide dimethy lsulfoxide diphenylphosphoryl azide 1, 1'-bis(diphenylphosphany1)ferrocen 1,3-bis(diphenylphosphino)propane diastereomeric ratio 1-ethy1-3-(3 -dimethylaminopropyl) carbodiimide hydrochloride enantiomeric excess ethyl ethyl acetate equivalents HWE highest occupied molecular orbital high performance liquid chromatography Horner, Wadsworth, Emmons i-Bu IBX IC IC 1m IPC iso-butyl 2-iodoxybenzoic acid inhibition concentration internal conversion imidazoyl isopinocamphenyl HOMO HPLC 278 Abbreviations i-Pr ISC iso-propyl intersystem crossing r.t RCM room temperature ring closing metathesis KHMDS potassium hexamethyldisilazide S S SET singulet total spin single electron transfer LA LDA LO LiHMDS LUMO Lewis acid lithium diisopropylamide leaving group lithium hexamethyldisilazide lowest unoccupied molecular orbital T TAS-F m-CPBA MDR Me Mes MOM MPO MS MW meta-chloroperbenzoic acid multidrug resistance methyl mesityl methoxymethyl methoxypyridine N-oxide molecular sieves microwave reactor n-Pr NaHMDS NaNHTP NBS NMO NMP NMR Nu n-propyl sodium hexamethyldisilazide N-hydroxy-2-thiopyridone sodium salt N-bromo succinimide N-methylmorpholine N-oxide N-methy1-2-pyrrolidone nuclear magnetic resonance nucleophile OTFA o-Tol trifluoroacetate ortho-tolyl PCC Ph Piv PMB PMP pyridinium-chlorochromate phenyl pivaloyl para-methoxybenzyl 1,2,2,6,6-pentamethylpiperidine pyridinium p-toluenesulfonate paclitaxel para-toluenesulfonic acid pyridine TS Ts TsOH triplet tris( dimethylamino )sulfonium difluorotrimethylsilicate tetra-n-butylammonium fluoride tert-butyldimethylsilyl tert-butyldiphenylsilyl tert-butylhydroperoxide tert-buty ldimethylsily1 tert-butyl trichloroacetimidate 2,4,6-trichlorobenzoyl chloride triethylbenzyl ammonium chloride tetramethylpiperidine N-oxyl triethylsilyl triflate, trifluoromethanesulfonyl trifluoroacetic acid trifluoroacetic acid anhydride tetrahydrofuran tetrahydropyran triisopropy lsily1 tetramethy lethy lenediamine trimethylsilyl tetrapropylammonium perruthenate transition state tosyl, 4-toluenesulfonic para-toluenesulfonic acid UV ultraviolet PPTS PT p-TsOH py TBAF TBDMS TBDPS TBHP TBS t-Bu TCA TCBC TEBAC TEMPO TES Tf TFA TFAA THF THP TIPS TMEDA TMS TPAP 279 Index Entries in bold indicate target compounds of total syntheses or topics that are exp1ained in detail in a key chemistry part presented in the individual chapters aceta1 82, 118, 127, 129, 133, 165, 166, 169,180,183,199,200,209,218, 222,224,254,266 mechanism 225 acetal exchange 127, 130 mechanism 127 acetonide 129 activation enthalpy 114 activation entropy 114, 133 acylation 16,207 addition 1,227,89,104,107,240 1,4107,163,166,244 AIBN 167,226 a1dol condensation 64, 88 a1do1 reaction 22-23,29,31,60,61,64, 88,122,128,224,239,245 asymmetric 21,29,30,31,38 chiral a1dehydes 128 N-acetyl oxazo1idinone 122 a1kyltripheny1phosphonium salt 35, 124 ally1 ch10ride 28 ally1si1ane 209 ally1ation 209 asymmetric 200 allylic alcohol 13,28, 144, 182, 183, 187, 194,212,213,264,270,274 allylic strain 122,219 A1pine Borane 140 anhydride, mixed 55, 114, 133 antitumor activity 21,41, 135 Appel reaction 124, 125 mechanism 125, 153 aromatic SE 82 ate complexe 9,53, 108, 109 azadiene 42,48 Bakshi, R K Barbas IlI, C F 141 59,61 Bart1ett, P A 210 Barton decarboxy1ative bromination 242 Barton ester 241 9-BBN BF 'Et2 166,222 biologica1 activity antibiotic 114,157 antifunga1 217 antitumor 21,41,135 antiulcerative 157 antiviral 157 cytotoxic 41, 157, 172, 193,253 mycotoxic 157 BIRT-377 59 bishydroxylation 120 Bn 83 Boc 10,13 Boeckman, R K 139, 145 Boger, D L 41,42 boron enolate 29,88 BrCCl3 242 bromination 242,245 2-bromopropene 27,264 Brown allylation 200 Brown,H C 140 Brown 's ch1oroborane 140 175,191 Brückner, R 29 BU2BOTf Bu}SnH 167,188,242 102,222 CAN 21, 113 cancer 219,224,225 carboxenium ion carboxy1ic acid activation acid ch10ride 241 EDC 265 CBS 139,141,144,153,154,155 Cbz 71,74 cellu1ar efflux system 113, 135 280 Index Chauvin, y 94 chelation control in Grignard reaction 264 chiral pool 21,59, 74 CIP-ru1es 257 cis-dio1 120 127 (COC1h Comins' reagent 7,9,163 condensation 50,57,82, 119, 189, 191,195 copper 1,4-addition 163, 166 Sonogashira cross coup1ing 168 Corey, E J 141,176,233,250 cross coup1ing Kumada 204 mechanism 9,205 Sonogashira 168 mechanism 168 Stille 9,47,53,189,191,228,230 mechanism 228 Suzuki 9,53,57 mechanism 217,218-219,222,231 croty1ation CSA 131 119, 163, 165,244 cuprate (+)-cyanthiwigin U 93 34,42,43,48,94, 101, cyc1oaddition 126,223,234,235,238,268 [2+2] 94,126,234,235,238,268 [3+2] 34,38,223,239 [4+2]42,43,48,57,60,101,109 cy1indramide 157 cystothiazo1e B 217 (-)-dactylo1ide 253 152 DBU DDQ 35,151,261,267 235,238,243,250 de Mayo reaction DEAD 115,271,272 decarbony1ation 148 57,242 decarboxy1ation decarboxy1ative bromination 242 deforrny1ative diazo transfer 239,247 Dess-Martin periodinane 16,26,36,66, 104,146,150,151,158, 187,211,249,270,274 DHP 118 diazine 42,43,48,57 DIBAL 23, 124, 182, 186, 187, 189, 248,249,269 50,57 Dieckmann condensation 42,43,48,57,60, Diels-Alder reaction 101, 109 Jacobsen hetero260,274 diene 101,148,154,183,201,269 dienophi1e 47,101 dihydropyran 118, 202 diimine 195,250 ~-diketone 104, 172 di1ithium tetrachlorocuprate(lI) 119 dio1 32, 103, 120, 130, 139, 144,269,273,274 1,2-diol 32 133 dioxirane 21,33,38, 1,3-dipo1ar cycIoaddition 223,239 dipo1arophi1e 33 dipo1e minimization 30 33,223 1,3-dipo1e 194,212 DIPT 33,36, 115, 132, DMAP 167, 185,241,265 102 DMB 134, 149 DMDO DMP see Dess-Martin periodinane DMPU 257,266 DMSO 29,53,66, 72, 85,127, 158, 159,165,222,262 domino- Wacker-Heck reaction 78-79 dppp 148 265 2,3, 11, 13, 14, 15,21, 29,34,78,89,99,124, 151,154,170,176,177, 185,191,205,224,226, 241,243,246,249,262 enamine cata1ytic cyc1e see organocatalysis EDC e1imination 281 Index enolate 29,88 boron 22 E 50,256,257,266 ester fonnation 22,87 geometry 256 7,204,239,245 kinetic lithium 16, 149, 185 122 U -configuration 128 Z zinc 121, 128 epothilone 113 113, 133, 135 analogue epoxidation 12,37,38,133,149,155, 187,191,194-195,212,213 epoxide 12,21, 133, 149, 193,213 ester hydrolysis 118 esterification 51,68,124,145,264,271 tosylate 118 triflate 7,9,10,185,204 Evans aldol reaction 21,29,31,38 Evans, D A 22, 122 Fenical, W Finney, N S fluorescence fonnylation C-glycosidation Grignard reaction Grubbs catalyst Grubbs, R H H2 H SiF6 Hamann, M T Hayash, Y Heck reaction Heck, R F hemi-acetal HF·NEt3 HF·pyridine 41 158 234 238,247 202 104, 119, 180,263, 265,270,274 95, 100, 104, 267,273,274 95 87 132 93 61 2-3, 10, 15, 18, 77,78,87,90,95 21,83,124,149,150,224 36 132 68, 131 Hoel Hofle, G 113 Horner-Wadsworth-Emmons reaction Ando variant 176,177,183,191 Still-Gennari variant 176, 177,208 Hoveyda, A H 95 HPLe, preparative 191,213,264 hydantoin 59,72,73 hydroboration 8, 200 1,2-hydrogen shift 26, 187 hydrogenation 85,90,95, 148, 171 hydrogenolysis 37 hydrostannylation 188, 191,226 mechanism 226 ro-hydroxy alkanoic acid 114 70, 124 26,29,35,36,158, 159,162,165,249 29 mechanism 234 le 14, 195 imidazole 10,12 iminium ion 1,4-induction 23 125,271 inversion of configuration 64 ionic liquid 128 Ireland model Ireland-Claisen rearrangement 254-257 lrie, T 139 234,235 Ise 54,55,72,74 isocyanate 184,189,193,210,212 isomerization 140 isopinocamphenyl 34,37 isoxazoline 34 isoxazoline route 140 Itsuno, s 12 IBX Jacobsen, E N Jeffery, T Johnson, W s Jmgensen, K A Julia olefmation Kang,H Katsuki, T 16~ 176, 177, 19~ 195 15 210 61 191 41 194 282 Index Katsumura, S Kelly, T A ketene KHMDS kinetic enolate 175 59 240 17,190,204,208 7,204,239,245 269 184,253,268,269,273 233,243,247 157 193 139 23,121,128,162,165,185, 187,224,249,256,266 Lewis acid 22,56,65,107,140, 141, 163, 166,200,202, 210,218,245,271 Lewis base 60 Ley, S V 61 Liaaen-Jensen, S 175 LiAIH4 18, 106, 118, 140, 146,182,203,267 LiBH4 23,26,31,33 LiHMDS 16,73,266 List, B 61 Lombardo reaction 84 2,6-lutidine 123,129,228,271 lactol lactone ladderane Laschat, S laulimalide (+)-laurenyne LDA MacMillan, D W C macrocycle 61 113,115,131,132, 133, 157,209,211 macrocyclization 210,273 macrolactone 113,115,131,133 macrolactonization 114-115,132,171 Massiot, G McLeod, M D 253,254 m-CPBA 12,37 222 Me3NO metathesis 94-95, 100, 101, 104, 109,201,268,274 methoxycarbonylation 185, 191 2-methyl-2-butene 68, 131 Mg 119 Michael addition 107,244 microtubulin system 113 mlcrowave minfiensine Mitsunobu reaction Mizoroki, T Mn02 MO(CO)6 MOM Mtb multicomponent reaction multidrug resistance Mulzer, J myriaporone 11,234 115,271 184 37 211 93 218 41,113,135 193 21 NaAIH4 182 NaCI0 68, 131 7,125,169,238,244,247 NaHMDS NaHTe 246,247 NaI04 31,120 NaNHTP 241 NaOCI 26,68,131,249 NBS 244 n-BuLi 35,98, 125, 150 Nicolaou, K C 159 ningalinD 41 nitrene-complex 37 nitrosium ion 26 NMO 32,249 N-oxoammonium salt 26 nuc1eophilic substitution 27,28,123,228 olefination organocatalysis organocerium reagent organostannane OS04 Overman, L E oxaphosphetane oxazolidinone auxiliary oxidants Dess-Martin IBX Jones m-CPBA 176-177 60-61 270 47,188,226, 228,229,230 32, 120 1,92, 139 126,181 22, 121 36, 104, 158, 186, 206,211,270,274 29,35,158-159,162,165 158 12,37 Index Mn02 NaC10 NaI04 OS04 ozone PCC Swem TEMPO oxidation a-c1eavage alcohol to carbonyl 184 68,131 32, 120 32, 120 223 107,224 66,86, 103, 127, 130,131,248,262 26 102 26,29,35, 36, 66, 86, 103, 127, 158-159, 184,248,262 aldehyde to carboxylic acid 67, 130 c1eavage of diol 31 IBJC 29,35,158-159,162,165 ofketones to Michael systems 158-159 olefine to carbonyls 120, 223 olefine to diol 31 olefine to epoxide 12,37, 133, 149, TMS-enol ether oxidative addition Oxone ozonolysis 155,187,194-195,212 158, 162 2,8, 11,47,53, 148,164,228 134, 195 223 pac1itaxel 113, 193 Palomo, C 93 Panek,J.S 217 Parikh-Doering oxidation 262, 264 Paterno-Büchi reaction 235 PCC 107,224 (+)-pentacyc1oanammoxic acid 233 pericyclic reaction see cyc1oaddition peridinin 175 Peterson olefination 176, 187 p-gp glycoprotein 41, 113 phenyl isocyanate 33,34 Phillips, A J 93, 109 phosphorescence 234 photochemical cyc1oaddition 234-235 photochemistry 234-235,238,243 Piv 103 pivaloyl PMB polyketide PPh3 PPTS n-PrN02 283 103 26,35,151,261,267 21,217 3,47,53, 115, 121, 124, 171, 185,188,226,230,271 26, 165, 169 33 protecting group acetal 82,118,127,165,166, 169,183,199,200,209, 218,222,225,266 acetyl 84, 177 alloc 12,14 83,85,261 Bn 12,13 Boc 7,9,10,18,69,71,272 carbamate Cbz 71 methyl ether 56 MOM 211 Piv 103 PMB 26,35,102,261,267 TBDPS 207 TBS 33,36,123,130,132,152, 185,188,244,263,267,270,273 TES 203,260 THP 118, 125 TIPS 10 TMS 68,153,166,205,245,254,266 PT 113 p-TsOH 88,118, 127, 129,20~211 pyrrole 41,42 43,48 pyrrole synthesis 42 43 radical attack 241 radical chain process 167,242 rearrangement 146,254-255,266 Claisen 187 Colvin mechanism 187 Curtius 55,57 Woljf 240,247 reductants Brown 's chloroborane 140 DIBAL 23, 124, 186, 187, 248,249,269 284 diimine H2 Index 195,250 86,87 18, 106, 118, 140, 146,267 23,26,31,33 17, 18, 140, 167, 182,203 LiAlH4 LiBH4 NaBH4 reduction a1kyne to olefine 171 amide to alcohol 31, 33 azide to amine 171 carbonyl to alcohol 17, 144, 166,203 carboxylic acid to alcohol 103 CBS 141, 144, 153, 155 ester to alcohol 18,26, 118, 124, 146,182,248 isoxazo1ine, N-O-cleavage 37 Michael system 65 N-N cleavage 74 olefine 85,87,90, 147, 171,246,247,249 Staudinger 171 triflate-enol ether 164 reduction ofketones 140 -41 reductive elimination 9, 10,47,53, 119, 148, 164, 169, 190, 205,229 reductive ring contraction 42 -43 Regitz diazo transfer 239 Reichenbach, H 113 retention of configuration 132 retro-Michael reaction 211 ring strain 114, 145, 147,233, cyclobutane 238,243,247,268 Roche ester 118 saponification ScheringAG Schrock, R R Schütt, F Scott, J W Sharpless epoxidation Sharpless, K B Shibasaki, M Shibata, T si-face attack 53,85,240,271 113 95 175 82 187,194-195,212 194 141 122,128,200 158,162,166,245 si1y1 eno1 ether silyl ketene acetal 255-257,266 silyl protecting group 207 TBDPS 33,36,123,130,131, TBS 132, 152, 185, 188,244, 263,267,270,273 TES 203,260 TIPS 10 68, 153, 166,205, TMS 245,254,266 234-235 singulet state 123 SN2 28 SNi-reaction 27,123,228 Swreaction SOC12 28,241 234 spin inversion Staudinger reduction 171 Stille reaction 47,189,228,230 strain allylic 122,219 114 Baeyer 114 Pitzer 114 transannular 262 sulfonium ylide 234 suprafacia1 Swern oxidation 66,86, 103, 127, 130,158,248 mechanism 86 151,176 194,213 38 113,135 21 16,36,132,207,230, 246,260,263,271 207 194 33,36,123,130,131, 132,152,185,188,244, 263,267,270,273 31,33,36,123,130,185,267 31,123,129,130,228,271 27,227,228,264 Takai olefination tartrate TAS-F taxanes Taylor, R E TBAF TBDPS TBHP TBS TBSCl TBSOTf t-BuLi 285 Index TCBC 114,132 TEBAC 153, 154 TEMPO 26 TES 203,260 tetrazine 42-43,48 TFA 10,11,12,43,48,184 TFAA 69 thiazole 230 241 thiohydroxamate Thompson, A S 139 Thomson, R H 139 THP 118,125,253,260,274 3,77,78,90,91,92,223 Tietze, L F TIPS 10 TLC, preparative 243 TMEDA 98 TMS 68,153,166,205,245,254,266 TMSCl 162,165,245,256,266 TMS-enol ether 166,245 a-tocopherol 77 tosylate 14, 118, 119, 165, 169 TPAP 249 transacetalization 200 transamination 6, 23 transesterification 123 transition state 23,28,30,31,37,61,67, 101, 114, 121, 129, 134, 140, 141, 144, 145, 146, 153,170,200,218,219, 223,256,257,264,266 boat-like 140 chair-like 122, 129, 147,200, 202,255,266 closed 22,28, 122, 140,218,256 open 122,170,218,219,257 transmetallation 9,47,53, 121, 164, 168, 205,228,264,270 triazoline trichloromethyl radical trimethylsilyl diazomethane triplet state Trost, B M TsCl 239 242 68 234-235,243 78 118 U -configuration ultrasound umpolung UV-light 122 234 227 234 Vilsmeier-Haack reagent vinylogous vitamin E 242 242 77 Weinreb amide 23, 180, 181, 182 Wilkinson hydrogenation 147 Wittig reaction 35, 124, 126, 150, 176, mechanism Schlosser variant Wolff rearrangement 181,249,250,262,269 126 X-ray christallography 177 240,247 12, 122, 139, 193,233 Yamaguchi- Yonemitsu macrolactonization Yee, N K ylide (-)-zampanolide Zemplén-reaction ZK-EPO 114-115, 132 59 84, 125, 126, 176, 177,181,183,208, 249,250,262,269 253 85 113,134 Related Titles Gewert, J.-A., Gorlitzer; J., Gotze, S., Looft, J., Menningen, P., Nobel, 1, Schirok, H., Wulff, C Wyatt, P Organic Synthesis Workbook Organic Synthesis Strategy and Control 2000 ISBN 978-3-527-30187-4 2007 ISBN 978-0-471-48940-5 Bittner; c., Busemann, A S., Griesbach, U., Haunert, F., Krahnert, \XL-R., Modi, A., Olschimke, J., Steck, P L Organic Synthesis Workbook 11 c., Sorensen, E J Classics in Total Synthesis Targets, Strategies, Methods c., Snyder; s A Classics in Total Synthesis 11 More Targets, Strategies, Methods 2003 ISBN 978-3-527-30684-8 Warren, S The Strategy of Organic Synthesis Workbook 2007 ISBN 978-0-471-92964-2 Fuhrhop, J.-H., Li, G Organic Synthesis Concepts and Methods 2003 ISBN 978-3-527-30273-4 1995 ISBN 978-3-527-29231-8 Nicolaou, K Name Reactions and Reagents in Organic Synthesis 2005 ISBN 978-0-471-73986-9 2001 ISBN 978-3-527-30415-8 Nicolaou, K Mundy B P Schmalz, H.-G., Wirth, (Eds.) Organic Synthesis Highlights V 2003 ISBN 978-3-527-30611-4 , B.1k'ooI