Essential reagents for organic synthesis by André B. Charette, Philip L. Fuchs, and Tomislav Rovis

41Ynq5yrGL._SX218_BO1204203200_QL40_.jpg Author André B. Charette, Philip L. Fuchs, and Tomislav Rovis
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Essential Reagents for Organic Synthesis Essential Reagents for Organic Synthesis Edited by Philip L. Fuchs Purdue University, West Lafayette, IN, USA André B. Charette Université de Montréal, Montréal, Québec, Canada Tomislav Rovis Colorado State University, Fort Collins, CO, USA Jeffrey W. Bode ETH Zürich, Switzerland This edition first published 2016 © 2016 John Wiley & Sons Ltd Registered office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. 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, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Names: Fuchs, Philip L., 1945- editor. | Charette, A. B. (André B.), 1961editor. | Rovis, Tomislav, 1968- editor. | Bode, J. W. (Jeffrey W.), editor. Title: Essential reagents for organic synthesis / edited by Philip L. Fuchs, Andre B. Charette, Tomislav Rovis, Jeffrey W. Bode. Description: Chichester, UK ; Hoboken, NJ : John Wiley & Sons, 2016. | Includes index. Identifiers: LCCN 2016021468| ISBN 9781119278306 (paperback) | ISBN 9781119279877 (epub) Subjects: LCSH: Chemical tests and reagents. | Organic compounds–Synthesis. Classification: LCC QD77 .E77 2016 | DDC 547/.2–dc23 LC record available at A catalogue record for this book is available from the British Library. ISBN 13: 978-1-119-27830-6 Set in 9½/11½ pt Times Roman by Thomson Press (India) Ltd., New Delhi. Printed and bound in Singapore by Markono Print Media Pte Ltd. e-EROS Editorial Board Editor-in-Chief Philip L. Fuchs Purdue University, West Lafayette, IN, USA Executive Editors André B. Charette Université de Montréal, Montréal, Québec, Canada Tomislav Rovis Colorado State University, Fort Collins, CO, USA Jeffrey W. Bode ETH Zürich, Switzerland Founding Editor Leo A. Paquette The Ohio State University, Columbus, OH, USA Contents Preface ix Short Note on InChIs and InChIKeys xi General Abbreviations xiii Bis(dibenzylideneacetone)palladium(0) 9-Borabicyclo[3.3.1]nonane Dimer Boron Trifluoride Etherate N-Bromosuccinimide n-Butyllithium N,N -Carbonyl Diimidazole Cerium(IV) Ammonium Nitrate m-Chloroperbenzoic Acid N-Chlorosuccinimide Chlorotrimethylsilane Chlorotris(triphenylphosphine)-rhodium(I) (Diacetoxyiodo)benzene Diazomethane 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone Diisobutylaluminum Hydride 4-Dimethylaminopyridine Dimethyldioxirane 1-Ethyl-3-(3 -dimethylaminopropyl) carbodiimide Hydrochloride N-Iodosuccinimide Iodotrimethylsilane 2-Iodoxybenzoic Acid Lithium Aluminum Hydride Lithium Diisopropylamide Lithium Naphthalenide Manganese Dioxide Osmium Tetroxide Oxalyl Chloride Oxalyl Chloride–Dimethylformamide Ozone 2 17 27 43 54 72 80 87 98 108 121 136 145 152 164 170 176 184 188 194 206 212 224 241 248 264 283 288 290 Pinacolborane Potassium Hexamethyldisilazide Potassium Monoperoxysulfate Potassium tert-Butoxide Ruthenium(II), Tris(2,2 -bipyridineκN1,κN1 )-, (OC-6-11)Samarium(II) Iodide Scandium Trifluoromethanesulfonate Sodium Azide Sodium Borohydride Sodium Cyanoborohydride Sodium Hexamethyldisilazide Sodium Hydride Sodium Periodate Tetrabutylammonium Fluoride Tetrakis(triphenylphosphine)-palladium(0) Tetra-n-propylammonium Perruthenate p-Toluenesulfonyl Chloride Triethylsilane Trifluoromethanesulfonic Acid Trifluoromethanesulfonic Anhydride Trimethylsilyl Trifluoromethanesulfonate Trimethylsilyldiazomethane Zinc–Acetic Acid 306 313 334 353 List of Contributors 557 Subject Index 565 370 378 388 398 406 419 428 438 447 458 467 476 480 489 498 507 524 543 554 Preface This handbook is a subset of the Encyclopedia of Reagents for Organic Synthesis (EROS), a knowledge base with detailed information on organic-chemical reagents and catalysts. As of mid-2016, the online collection offers reviews on 4959 different reagents and catalysts that are regularly updated. To keep up with the continual evolution in the field, about 200 new or updated reagent articles are added per year to the online database. In addition to the complete collection that is available only online (see, a number of highly focused single-volume handbooks in print and electronic format on editor-selected subjects have been published (Handbook for Reagents in Organic Synthesis, HROS). Recent titles in the HROS series include: • Reagents for Organocatalysis Edited by Tomislav Rovis (2016) • Reagents for Heteroarene Functionalization Edited by André B. Charette (2015) • Catalytic Oxidation Reagents Edited by Philip L. Fuchs (2013) • Reagents for Silicon-Mediated Organic Synthesis Edited by Philip L. Fuchs (2011) • Sulfur-Containing Reagents Edited by Leo A. Paquette (2010) • Reagents for Radical and Radical Ion Chemistry Edited by David Crich (2009) Data mining of EROS user downloads guided by editorial adjudication has yielded the present collection of 52 often-used reagents that will facilitate the daily laboratory endeavor of every organic chemist. The collection contains oxidants (15), reductants (10), metal and organic catalysts (11), Brønsted and Lewis acids (8), and bases (6), to cite a few general mechanistic categories. We hope that this handbook will prove to be an invaluable primary resource for both beginning graduate students and experienced Ph.D. researchers. Philip L. Fuchs Purdue University, West Lafayette, IN, USA André B. Charette Université de Montréal, Montréal, Québec, Canada Tomislav Rovis Colorado State University, Fort Collins, CO, USA Jeffrey W. Bode ETH Zürich, Switzerland Short Note on InChIs and InChIKeys The IUPAC International Chemical Identifier (InChITM ) and its compressed form, the InChIKey, are strings of letters representing organic chemical structures that allow for structure searching with a wide range of online search engines and databases such as Google and PubChem. While they are obviously an important development for online reference works, such as Encyclopedia of Reagents for Organic Synthesis (e-EROS), readers of this volume may be surprised to find printed InChI and InChIKey information for each of the reagents. We introduced InChI and InChIKey to e-EROS in autumn 2009, including the strings in all HTML and PDF files. While we wanted to make sure that all users of e-EROS, the second print edition of EROS, and all derivative handbooks would find the same information, we appreciate that the strings will be of little use to the readers of the print editions, unless they treat them simply as reminders that e-EROS now offers the convenience of InChIs and InChIKeys, allowing the online users to make best use of their browsers and perform searches in a wide range of media. If you would like to know more about InChIs and InChIKeys, please go to the e-EROS website: www. and click on the InChI and InChIKey link. General Abbreviations Ac acac AIBN Ar acetyl acetylacetonate 2,2 -azobisisobutyronitrile aryl BBN BCME BHT BINOL bipy BMS Bn Boc BOM bp Bs BSA Bu Bz borabicyclo[3.3.1]nonane dis(chloromethyl)ether butylated hydroxytoluene (2,6-di-t-butyl-pcresol) 2,2 -dihydroxy-1,1 -binaphthyl-lithium aluminum hydride 2,2 -bis(diphenylphosphino)-1,1 binaphthyl 1,1 -bi-2,2 -naphthol 2,2 -bipyridyl borane–dimethyl sulfide benzyl t-butoxycarbonyl benzyloxymethyl boiling point brosyl (4-bromobenzenesulfonyl) N,O-bis(trimethylsilyl)acetamide n-butyl benzoyl CAN Cbz CDI CHIRAPHOS Chx cod cot Cp CRA CSA CSI Cy cerium(IV) ammonium nitrate benzyloxycarbonyl N,N -carbonyldiimidazole 2,3-bis(diphenylphosphino)butane =Cy cyclooctadiene cyclooctatetraene cyclopentadienyl complex reducing agent 10-camphorsulfonic acid chlorosulfonyl isocyanate cyclohexyl d DABCO DAST dba DBAD DBN DBU DCC DCME DDO DDQ de density 1,4-diazabicyclo[2.2.2]octane N,N -diethylaminosulfur trifluoride dibenzylideneacetone di-t-butyl azodicarboxylate 1,5-diazabicyclo[4.3.0]non-5-ene 1,8-diazabicyclo[5.4.0]undec-7-ene N,N -dicyclohexylcarbodiimide dichloromethyl methyl ether dimethyldioxirane 2,3-dichloro-5,6-dicyano-1,4-benzoquinone diastereomeric excess BINAL-H BINAP DEAD DET DIBAL DIEA DIOP diethyl azodicarboxylate diethyl tartrate diisobutylaluminum hydride =DIPEA 2,3-O-isopropylidene-2,3-dihydroxy-1,4bis-(diphenylphosphino)butane DIPEA diisopropylethylamine diphos =dppe DIPT diisopropyl tartrate DMA dimethylacetamide DMAD dimethyl acetylenedicarboxylate DMAP 4-(dimethylamino)pyridine DME 1,2-dimethoxyethane DMF dimethylformamide dmg dimethylglyoximato DMPU N,N -dimethylpropyleneurea DMS dimethyl sulfide DMSO dimethyl sulfoxide DMTSF dimethyl(methylthio) sulfonium tetrafluoroborate dppb 1,4-bis(diphenylphosphino)butane dppe 1,2-bis(diphenylphosphino)ethane dppf 1,1 -bis(diphenylphosphino)ferrocene dppp 1,3-bis(diphenylphosphino)propane DTBP di-t-butyl peroxide EDA EDC EDCI ee EE Et ETSA EWG ethyl diazoacetate 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide =EDC enantiomeric excess 1-ethoxyethyl ethyl ethyl trimethylsilylacetate electron withdrawing group Fc Fmoc fp ferrocenyl 9-fluorenylmethoxycarbonyl flash point Hex HMDS HMPA HOBt HOBT HOSu n-hexyl hexamethyldisilazane hexamethylphosphoric triamide l-hydroxybenzotriazole =HOBt N-hydroxysuccinimide Im Ipc IR imidazole (imidazolyl) isopinocampheyl infrared xiv GENERAL ABBREVIATIONS KHDMS potassium hexamethyldisilazide LAH LD50 LDA LDMAN LHMDS LICA LiHMDS LiTMP LTMP LTA lut lithium aluminum hydride dose that is lethal to 50% of test subjects lithium diisopropylamide lithium 1-(dimethylamino)naphthalenide =LiHMDS lithium isopropylcyclohexylamide lithium hexamethyldisilazide lithium 2,2,6,6-tetramethylpiperidide =LiTMP lead tetraacetate lutidine m-CPBA MA MAD m-chloroperbenzoic acid maleic anhydride methylaluminum bis(2,6-di-t-butyl-4methylphenoxide) methylaluminum bis(2,4,6-tri-tbutylphenoxide) methyl methyl ethyl ketone (2-methoxyethoxy)methyl methyl isocyanate magnesium monoperoxyphthalate methoxymethyl oxodiperoxomolybdenum(pyridine)(hexamethylphosphoric triamide) melting point =PMB mesyl (methanesulfonyl) mass spectrometry; molecular sieves methyl t-butyl ether methylthiomethyl methyl vinyl ketone MAT Me MEK MEM MIC MMPP MOM MoOPH mp MPM Ms MS MTBE MTM MVK n NaHDMS Naph NBA nbd refractive index sodium hexamethyldisilazide naphthyl N-bromoacetamide norbornadiene (bicyclo[2.2.1]hepta2,5-diene) NBS N-bromosuccinimide NCS N-chlorosuccinimide NIS N-iodosuccinimide NMO N-methylmorpholine N-oxide NMP N-methyl-2-pyrrolidinone NMR nuclear magnetic resonance NORPHOS bis(diphenylphosphino)bicyclo[2.2.1]-hept5-ene Np =Naph PCC PDC Pent Ph phen Phth pyridinium chlorochromate pyridinium dichromate n-pentyl phenyl 1,10-phenanthroline phthaloyl Piv PMB PMDTA PPA PPE PPTS Pr PTC PTSA py pivaloyl p-methoxybenzyl N,N,N ,N ,N -pentamethyldiethylenetriamine polyphosphoric acid polyphosphate ester pyridinium p-toluenesulfonate n-propyl phase transfer catalyst/catalysis p-toluenesulfonic acid pyridine RAMP rt (R)-1-amino-2-(methoxymethyl)pyrrolidine room temperature salen SAMP SET Sia bis(salicylidene)ethylenediamine (S)-1-amino-2-(methoxymethyl)pyrrolidine single electron transfer siamyl (3-methyl-2-butyl) TASF tris(diethylamino)sulfonium difluorotrimethylsilicate TBAB tetrabutylammonium bromide TBAF tetrabutylammonium fluoride TBAD =DBAD TBAI tetrabutylammonium iodide TBAP tetrabutylammonium perruthenate TBDMS t-butyldimethylsilyl TBDPS t-butyldiphenylsilyl TBHP t-butyl hydroperoxide TBS =TBDMS TCNE tetracyanoethylene TCNQ 7,7,8,8-tetracyanoquinodimethane TEA triethylamine TEBA triethylbenzylammonium chloride TEBAC =TEBA TEMPO 2,2,6,6-tetramethylpiperidinoxyl TES triethylsilyl Tf triflyl (trifluoromethanesulfonyl) TFA trifluoroacetic acid TFAA trifluoroacetic anhydride THF tetrahydrofuran THP tetrahydropyran; tetrahydropyranyl Thx thexyl (2,3-dimethyl-2-butyl) TIPS triisopropylsilyl TMANO trimethylamine N-oxide TMEDA N,N,N ,N -tetramethylethylenediamine TMG 1,1,3,3-tetramethylguanidine TMS trimethylsilyl Tol p-tolyl TPAP tetrapropylammonium perruthenate TBHP t-butyl hydroperoxide TPP tetraphenylporphyrin Tr trityl (triphenylmethyl) Ts tosyl (p-toluenesulfonyl) TTN thallium(III) nitrate UHP urea–hydrogen peroxide complex Z =Cbz B Bis(dibenzylideneacetone)palladium(0) 9-Borabicyclo[3.3.1]nonane Dimer Boron Trifluoride Etherate N-Bromosuccinimide n-Butyllithium Essential Reagents for Organic Synthesis, Edited by Philip L. Fuchs, André B. Charette, Tomislav Rovis, and Jeffrey W. Bode. ©2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd. 2 17 27 43 54 2 BIS(DIBENZYLIDENEACETONE)PALLADIUM(0) Bis(dibenzylideneacetone)palladium(0) Tris(dibenzylideneacetone)dipalladium O (PhCH CHCOCH CHPh)2Pd Ph [32005-36-0] C34 H28 O2 Pd (MW 575.01) InChI = 1S/2C17H14O.Pd/c2*18-17(13-11-15-7-3-1-4-8-15)1412-16-9-5-2-6-10-16;/h2*1-14H;/b2*13-11+,14-12+; InChIKey = UKSZBOKPHAQOMP-SVLSSHOZSA-N (catalyst for allylation of stabilized anions,1 cross coupling of allyl, alkenyl, and aryl halides with organostannanes,2 cross coupling of vinyl halides with alkenyl zinc species,3 cyclization reactions,4 and carbonylation of alkenyl and aryl halides,5 air stable Pd0 complex used as a homogeneous Pd0 -precatalyst in the presence of additional external ligands) Alternative Name: palladium(0) bis(dibenzylideneacetone). Physical Data: mp 135 ◦ C (dec). Solubility: insoluble in H2 O, soluble in organic solvents (dichloromethane, chloroform, 1,2-dichloroethane, acetone, acetonitrile, benzene, and others) Form Supplied in: black solid; commercially available. Preparative Method: prepared by the addition of sodium acetate to a hot methanolic solution of dibenzylideneacetone (dba) and Na2 [Pd2 Cl6 ] (from Palladium(II) Chloride and NaCl), cooling, filtering, washing with MeOH, and air drying, gives Pd(dba)2 ; which is formulated more correctly as [Pd2 (dba)3 ]dba.6,12a Alternatively, palladium(II) chloride, sodium acetate, and dba can be added to a 40 ◦ C methanolic solution, cooled, filtered, and washed copiously with H2 O and acetone, in succession, and dried in vacuo.112a Handling, Storage, and Precautions: moderately air stable in the solid state; slowly decomposes in solution to metallic palladium and dibenzylideneacetone. Tris(dibenzylideneacetone)dipalladium(0)-Chloroform O Ph Ph Pd 2 [52522-40-4] C52 H43 Cl3 O3 Pd2 (MW 1035.14) InChI = 1/3C17H14O.CHCl3.2Pd/c3*18-17(13-11-15-7-3-1-48-15)14-12-16-9-5-2-6-10-16;2-1(3)4;;/h3*1-14H;1H;;/ b3*13-11+,14-12+;;; InChIKey = LNAMMBFJMYMQTO-FNEBRGMMBW Alternative Name: dipalladium-tris(dibenzylideneacetone)chloroform complex. Physical Data: mp 131–135 ◦ C,111 122–124 ◦ C (dec).6,112 Solubility: insoluble in H2 O; soluble in chloroform, dichloromethane, and benzene. Form Supplied in: purple solid; commercially available. Preparative Method: the reaction of Na2 [Pd2 Cl6 ] and dba give Bis(dibenzylideneacetone)palladium(0), [Pd(dba)2 dba], recrystallization from chloroform displaces the uncoordinated dba with chloroform to gives the title reagent as deep purple needles.112a Ph Pd2•CHCl3 3 [51364-51-3] C51 H42 O3 Pd2 (MW 915.72) InChI = 1/3C17H14O.2Pd/c3*18-17(13-11-15-7-3-1-4-8-15)1412-16-9-5-2-6-10-16;;h3*1-14H;;/b3*13-11+,14-12+;; InChIKey = CYPYTURSJDMMP-WVCUSYJEBM Alternative Name: dipalladium-tris(dibenzylideneacetone). Physical Data: mp 152–155 ◦ C.6a Form Supplied in: dark purple to black solid; commercially available. Preparative Method: prepared from dba and sodium tetrachloropalladate.6a Original Commentary John R. Stille Michigan State University, East Lansing, MI, USA Allylation of Stabilized Anions. Pd(dba)2 is an effective catalyst for the coupling of electrophiles and nucleophiles, and has found extensive use in organic synthesis (for a similar complex with distinctive reactivities, see also Tris(dibenzylideneacetone)dipalladium). Addition of a catalytic amount of Pd(dba)2 activates allylic species, such as allylic acetates or carbonate derivatives, toward nucleophilic attack.1 The intermediate organometallic complex, a π-allylpalladium species, is formed by backside displacement of the allylic leaving group, and stereochemical inversion of the original allylic position results. Subsequent nucleophilic attack on the external face of the allyl ligand displaces the palladium in this double inversion process to regenerate the original stereochemical orientation (eq 1).7 The allylpalladium intermediate can also be generated from a variety of other substrates, such as allyl sulfones,8 allenes,9 vinyl epoxides,10 or α-allenic phosphates.11 In general, the efficiency of Pd(dba)2 catalysis is optimized through the addition of either Triphenylphosphine or 1,2-Bis(diphenylphosphino)ethane (dppe). CO2Me OAc 1% Pd(dba)2, dppe NaCH(CO2Me)2 CO2Me (1) THF, rt, 48 h 83% >95% cis The anions of malonate esters,12 cyclopentadiene,12 βketo esters,13 ketones,13,14 aldehydes,14 α-nitroacetate esters,15 Meldrum’s acid,15 diethylaminophosphonate Schiff bases,16 βdiketones,17 β-sulfonyl ketones and esters,17 and polyketides18,19 represent the wide variety of carbon nucleophiles effective in this reaction. Generation of the stabilized anions normally is Essential Reactions for Organic Synthesis, First Edition. Edited by Philip L. Fuchs. © 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd. BIS(DIBENZYLIDENEACETONE)PALLADIUM(0) accomplished by addition of Sodium Hydride, Potassium Hydride, or basic Alumina15 However, when allyl substrates such as allylisoureas,14 allyl oxime carbonates,17 or allyl imidates20 are used, the allylation reaction proceeds without added base. Nitrogen nucleophiles, such as azide10 and nucleotide21 anions, are useful as well. The coupling reaction generally proceeds regioselectively with attack by the nucleophile at the least hindered terminus of the allyl moiety,22 accompanied by retention of alkene geometry (eq 2). Even electron-rich enol ethers can be used as the allylic moiety when an allylic trifluoroacetyl leaving group is present.23 When steric constraints of substrates are equivalent, attack will occur at the more electron rich site.19 Although this reaction is usually performed in THF, higher yields and greater selectivity are observed for some systems with the use of DME, DMF, or DMSO.14,16,20 Alternatively, Pd(dba)2 can promote efficient substitution of allylic substrates in a two-phase aqueous–organic medium through the use of P(C6 H4 -m-SO3 Na)3 as a phase transfer ligand.24 1% Pd(dba)2, dppe NaCHE2 OAc (E) isomer (Z) isomer + THF, rt, 48 h E = CO2Me 47% 62% (2) CHE2 CHE2 AcO NO2 CO2Me CO2Bn + Bu3Sn Cl E O NaH, Pd(dba) , PPh 2 3 AcO E E E = CO2Me THF, 65 °C, 10 h 75% H E O (3) Ph N Ph CO2Me 3. 10% HCl 4. K2CO3 60% 57% ee N H CO2Me 3% Pd(dba)2 PPh3 CO2Bn (6) THF, 5 °C 87% Similar methodology is used for the coupling of alkenyl halides and triflates with 1) alkenyl-, aryl-, or alkynylstannanes,35 2) alkenylzinc species,3,36 or 3) arylboron species.37 This methodology is applied in the synthesis of cephalosporin derivatives (eq 7),35 and can be used for the introduction of acyl3,36 and vinylogous acyl3 equivalents (eq 8). H E E >98% cis H RN Asymmetric Allylation Reactions. Employing chiral bidentate phosphine ligands in conjunction with Pd(dba)2 promotes allylation reactions with moderate to good enantioselectivities, which are dependent upon the solvent,27 counterion,28 and nature of the allylic leaving group.27 Chiral phosphine ligands have been used for the asymmetric allylation of α-hydroxy acids (5–30% ee),29 the preparation of optically active methylenecyclopropane derivatives (52% ee),22 and chiral 3alkylidenebicyclo[3.3.0]octane and 1-alkylidenecyclohexane systems (49–90% ee).27 Allylation of a glycine derivative provides a route to optically active α-amino acid esters (eq 4).28 The intramolecular reaction can produce up to 69% ee when vicinal stereocenters are generated during bond formation (eq 5).30 1. LDA, –78 °C, THF 2. CH2=CHCH2OAc 1.5% Pd(dba)2 (+)-DIOP (5) THF, –51 °C, 3 h 65% 69% ee Cross-coupling Reactions. Allylic halides,5,31 aryl diazonium salts,32 allylic acetates,33 and vinyl epoxides34 are excellent substrates for Pd(dba)2 catalyzed selective cross-coupling reactions with alkenyl-, aryl-, and allylstannanes. The reaction of an allylic halide or acetate proceeds through a π-allyl intermediate with inversion of sp3 stereochemistry, and transmetalation with the organostannane followed by reductive elimination results in coupling from the palladium face of the allyl ligand. Coupling produces overall inversion of allylic stereochemistry, a preference for reaction at the least substituted carbon of the allyl framework, and retention of allylic alkene geometry. In addition, the alkene geometry of alkenylstannane reagents is conserved (eq 6). Functional group compatibility is extensive, and includes the presence of CO2 Bn, OH, OR, CHO, OTHP, β-lactams, and CN functionality. 95 (E only):5 76 (Z only):23 Intramolecular reaction of a β-dicarbonyl functionality with a π-allyl species can selectively produce three-,25 five-,25 or sixmembered26 rings (eq 3). NO2 7% Pd(dba)2 (–)-CHIRAPHOS K2CO3 N H 3 NH2 CO2Me (4) H RN 2% Pd(dba)2, P S N O Ph2CHO2C OTf Bu3Sn O , ZnCl2 25 °C 65% O S 3 N O Ph2CHO2C (7) R = Ph OEt ZnCl Br 1. 5% Pd(dba)2 PPh3, THF Ph 2. HCl, H2O 68% + O (8) Ph Intramolecular Reaction with Alkenes. Palladium π-allyl complexes can undergo intramolecular insertion reactions with alkenes to produce five- and six-membered rings through a ‘metallo-ene-type’ cyclization.4 This reaction produces good stereoselectivity when resident chirality is vicinal to a newly formed stereogenic center (eq 9), and can be used to form tricyclic and tetracyclic ring systems through tandem insertion reactions.38 In the presence of Pd(dba)2 and triisopropyl phosphate, α,β-alkynic esters and α,β-unsaturated enones undergo intramolecular [3 + 2] cycloaddition reactions when tethered to 4 BIS(DIBENZYLIDENEACETONE)PALLADIUM(0) methylenecyclopropane to give a bicyclo[3.3.0]octane ring system (eq 10).39 BnO OAc 7% Pd(dba)2 PPh3 Ph F. Christopher Pigge University of Iowa, Iowa City, IA, USA BnO (9) AcOH, 80 °C 6h 72% trans:cis = 93:7 Ph 11% Pd(dba)2 P(O-i-Pr)3 H Ph (10) Ph toluene, 110 °C 42 h 47% O O H Carbonylation Reactions. In the presence of CO and Pd(dba)2 , unsaturated carbonyl derivatives can also be prepared through carbonylative coupling reactions. Variations of this reaction include the initial coupling of allyl halides with carbon monoxide, followed by a second coupling with either alkenyl- or arylstannanes (eq 11).5 This reaction proceeds with overall inversion of allylic sp3 stereochemistry, and retains the alkene geometry of both the allyl species and the stannyl group. Similarly, aryl and alkenyl halides will undergo carbonylative coupling to generate intermediate acylpalladium complexes. Intermolecular reaction of these acyl complexes with HSnBu3 produces aldehydes,35,40 while reaction with MeOH or amines generates the corresponding carboxylic acid methyl ester41 or amides, respectively.42 Bis(dibenzylideneacetone)palladium(0) or Pd(dba)2 continues to be a popular source of Pd(0), used extensively in transition metal-catalyzed reactions. The reagent is widely available from commercial sources and exhibits greater air stability than Pd(PPh3 )4 . The dba ligands are generally viewed as weakly coordinated and so are readily displaced by added ligands (usually mono- or bidentate phosphines) to generate active catalysts. Detailed mechanistic studies, however, have revealed that dba ligands are not as innocent as originally thought and exert a profound influence upon catalyst activity through formation of mixed ligand species of the type (dba)PdL2 (L = phosphine).46 The reagent is also a convenient source of phosphine-free Pd(0). Synthetic applications of Pd(dba)2 include catalysis of allylic alkylation reactions, various cross-coupling reactions, Heck-type reactions, and multi-component couplings. Allylation of Stabilized Anions. Electrophilic π-allyl Pd(0) complexes can be generated from Pd(dba)2 and functionalized allylic acetates, carbonates, halides, etc. These complexes are susceptible to reaction with a range of stabilized nucleophiles, such as malonate anions. Alkylation usually occurs at the less-substituted allylic terminus. Silyl-substituted π-allyl complexes undergo regioselective alkylation at the allyl terminus farthest removed from the silyl group (eq 14).47 OAc OMe EtO2C First Update Br + 3% Pd(dba)2 PPh3 OMe O EtO2C (11) 55 psi CO THF, 50 °C 75% Bu3Sn THPO 600 psi CO 5% Pd(dba)2 OH O OMe O O (12) O (13) DME, 150 °C 48 h 80% (14) EtO2C CO2Et SiMe3 67% 2 equiv MeOH NEt3, 36 h 73% 20 atm CO 4% Pd(dba)2 dppb NaCH(CO2Et)2 THF THPO Palladium acyl species can also undergo intramolecular acylpalladation with alkenes to form five- and six-membered ring γ-keto esters through exocyclic alkene insertion (eq 12).43 The carbonylative coupling of o-iodoaryl alkenyl ketones is also promoted by Pd(dba)2 to give bicyclic and polycyclic quinones through endocyclization followed by β-H elimination.44 Sequential carbonylation and intramolecular insertion of propargylic and allylic alcohols provides a route to γ-butyrolactones (eq 13).45 I SiMe3 5% Pd(dba)2 5% dppe Allylic alkylation catalyzed by Pd(dba)2 and (i PrO)3 P has been used for incorporation of nucleobases (pyrimidines and purines) into carbocyclic nucleoside analogs.48 In certain cases, unstabilized nucleophiles have been found to participate in allylic alkylation reactions. For example, an allenic double bond is sufficiently nucleophilic to react with the π-allyl complex generated upon heating Pd(dba)2 and 1 in toluene (eq 15).49 Formation of the trans-fused product (2) was interpreted to arise via the double inversion pathway commonly observed in conventional Pdcatalyzed allylic alkylation reactions. Interestingly, changing to a coordinating solvent (CH3 CN) resulted in allene insertion into the π-allyl complex to form the isomeric cis-fused product (3). Asymmetric Allylation Reactions. Enantioselective allylic alkylation is used extensively in asymmetric synthesis with chiral nonracemic phosphines often serving as the source of enantiodiscrimination.50 A monodentate phosphabicyclononane derivative in conjunction with Pd(dba)2 was found to be effective in promoting the asymmetric allylation of 2-substituted cyclopentenyl and cyclohexenyl carbonates with malonate and sulfonamide nucleophiles with ee’s ranging from 50 to 95% (eq 16).51

Author André B. Charette, Philip L. Fuchs, and Tomislav Rovis Isbn 9781119278306 File size 7MB Year 2016 Pages 640 Language English File format PDF Category Chemistry Book Description: FacebookTwitterGoogle+TumblrDiggMySpaceShare From Boron Trifluoride to Zinc, the 52 most widely used reagents in organic synthesis are described in this unique desktop reference for every organic chemist. The list of reagents contains classics such as N-Bromosuccinimide (NBS) and Trifluoromethanesulfonic Acid side by side with recently developed ones like Pinacolborane and Tetra-n-propylammonium Perruthenate (TPAP). For each reagent, a concise article provides a brief description of all important reactions for which the reagent is being used, including yields and reaction conditions, an overview of the physical properties of the reagent, its storage conditions, safe handling, laboratory synthesis and purification methods. Advantages and disadvantages of the reagent compared to alternative synthesis methods are also discussed. Reagents have been hand-picked from among the 5000 reagents contained in EROS, the Encyclopedia of Reagents for Organic Synthesis. Every organic chemist should be familiar with these key reagents that can make almost every reaction work.     Download (7MB) Oxidizing And Reducing Agents, Handbook Of Reagents For Organic Synthesis Synthesis of Carbon-Phosphorus Bonds (2nd Edition) Carbon Nanomaterials for Gas Adsorption Compendium of Organic Synthetic Methods (Volume 13) Organic Chemistry of Explosives Load more posts

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