Practical Synthetic Organic Chemistry / Практическая синтетическая органическая химия

856 Pages·2016·38.29 MB·English

by  Caron S.

PRACTICAL SYNTHETIC
ORGANIC CHEMISTRY
PRACTICAL SYNTHETIC
ORGANIC CHEMISTRY
Reactions, Principles, and Techniques
Edited by
STE´PHANE CARON
Copyright 2011byJohnWiley&Sons,Inc.Allrightsreserved
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PublishedsimultaneouslyinCanada
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LibraryofCongressCataloging-in-PublicationData:
Practicalsyntheticorganicchemistry:reactions,principles,andtechniques/editedbySt(cid:1)ephaneCaron.
p.cm.
Includesindex.
ISBN978-0-470-03733-1(pbk.)
1.Organiccompounds–Synthesis. I.Caron,St(cid:1)ephane.
QD262.P6882011
547’.2–dc22
2011008293
PrintedintheUnitedStatesofAmerica
oBooKISBN:978-1-118-09355-9
ePDFISBN: 978-1-118-09357-3
ePubISBN: 978-1-118-09356-6
10 9 8 7 6 5 4 3 2 1
CONTENTS
Foreword vii
Preface ix
Contributors xi
1 AliphaticNucleophilicSubstitution 1
JadeD.Nelson
2 AdditiontoCarbon–HeteroatomMultipleBonds 73
RajappaVaidyanathanandCarrieBrockwayWager
3 AdditiontoCarbon–CarbonMultipleBonds 167
JohnA.Ragan
4 NucleophilicAromaticSubstitution 237
Ste´phaneCaronandArunGhosh
5 ElectrophilicAromaticSubstitution 255
Ste´phaneCaron
6 SelectedMetal-MediatedCross-CouplingReactions 279
Ste´phaneCaron,ArunGhosh,SallyGutRuggeri,NathanD.Ide,JadeD.Nelson,
andJohnA.Ragan
7 Rearrangements 341
DavidH.B.Ripin
8 Eliminations 383
SallyGutRuggeri
v
vi CONTENTS
9 Reductions 419
SallyGutRuggeri,Ste´phaneCaron,PascalDube´,NathanD.Ide,
KristinE.Price,JohnA.Ragan,andShuYu
10 Oxidations 493
DavidH.BrownRipin
11 SelectedFreeRadicalReactions 557
NathanD.Ide
12 Synthesisof“Nucleophilic”OrganometallicReagents 575
DavidH.BrownRipin
13 SynthesisofCommonAromaticHeterocycles 609
Ste´phaneCaron
14 AccesstoChirality 649
RobertW.Dugger
15 SyntheticRouteDevelopmentofSelectedContemporary
PharmaceuticalDrugs 661
Ste´phaneCaron
16 GreenChemistry 683
JuanC.Colberg
17 NamingCarbocyclesandHeterocycles 703
HeatherN.FrostandDavidH.BrownRipin
18 pKa 771
DavidH.BrownRipin
19 GeneralSolventProperties 805
Ste´phaneCaron
20 PracticalChemistryConcepts:TipsforthePracticingChemistor
ThingsTheyDon’tTeachYouinSchool 819
SallyGutRuggeri
FunctionalGroupInterconversionIndex 837
Index 845
FOREWORD
Whileallpractitionersintheartrecognizethatsyntheticorganicchemistryservessociety,it
isnotalwaysappreciatedtheotherwayaround;namelythatsocietydoesnotassociatethe
phenomenal rewards that are derived from our ability to assemble complex functional
molecules. Indeed,theachievementsofthepharmaceutical industryareunderpinnedby
moleculardesignandsynthesisofvirtuallyallthehealingdrugsubstancesthatarecurrently
onthemarket,whichbenefitmankindandcurehumandiseases.
Thereis,inmyview,nothingnoblerthanthisworthwhiletask. However,synthesisofthe
complexfunctionalarchitecturesisnotatrivialorroutineprocess.Thisisalwaysmademore
difficult on scaling up of the chemistries to comply with current standards of safety,
robustness, costs, quality, and environmental impact. I, therefore, very much welcome
this new textbook, Practical Synthetic Organic Chemistry: Reactions, Principles, and
Techniques, which gives us an inspiring and pragmatic glimpse at the most commonly
usedandeffectivesynthesisproceduresonscale. Thisuniquetextbookhasbeenwrittenby
experts in the field and provides an insight and critique of the key effectivemethods for
molecularassembly.Itwillbeagreatstartingpointforanyonedevelopingtheircareerinthis
worthyindustry.
The organization and chapter titles reflect a refreshing approach to explaining a
complicated science covering all the major bond construction methods and functional
controlelementsnecessaryformodernsyntheticplanningandexecution.
Theauthorshaveincorporatedchaptersonimportanttopicssuchastheeffectivenessof
rearrangementprocesses,radicalreactions,accesstochirality,andgreenchemistry,which
are not captured as a group in more traditional texts. Furthermore, the educational
component of this book highlighting nomenclature, pKa knowledge, solvent properties,
andtipsofthetradefromthepracticingchemistagainaddsvalueinprovidingafeastof
information that otherwise is dispersed over many sources or is simply locked up in the
personaldatabaseofknowledgeofthoseexperiencedintheart.
vii
viii FOREWORD
Thecreativespiritofthisareaofscienceinbringingnewfunctional molecules inour
worldforthefirsttimeforthebettermentofusallisenduringandwillcontinuetoseednew
discoveriesformanyyearstocome.
STEVEN V. LEY
Cambridge,UK
2011
PREFACE
Despitetherelativematurityofthefieldoforganicchemistry,moleculescontinuetopresent
syntheticchemistswithsignificantchallenges,especiallyastheexpectationsforsynthetic,
material,andenergyefficiencycontinuetointensify.Inresponsetothesechallenges,organic
chemists have continued to develop innovative new synthetic methods. Many of these
recently developed synthetic methods allow for achievement of ever more impressive
chemo-, enantio-, diastereo-, and regioselectivity. Additionally, new synthetic methods
are providing chemists with novel reactions and enabling synthetic strategies that would
havepreviouslybeenimpracticalorimpossible.
Whilewearefascinatedbythemultitudeofpowerfulsyntheticmethodsthathavebeen
developed in recent years, these methods were not the direct inspiration for this book.
Instead, the impetus for this book was actually an article request for a special issue of
Chemical Reviews on process chemistry (Vol. 106, No. 7, July 2006). A group of Pfizer
processchemists,attheGroton(CT)site,electedtowriteareviewofoxidationsperformed
onlargescale.Thisreviewwasdividedamongseveralauthorsandservedasthebasisfor
Chapter 10 in this book.1 My personal contribution to the review articlewas the section
coveringC–Ooxidations,andIwassurprisedbywhatIlearneduponfurtherinvestigationof
thisseeminglymundanetopic.Whileanumberofeffectivemethodsexistfortheconversion
ofprimaryalcoholstoaldehydes,onlytwogeneralmethodshavebeenusedconsistentlyand
successfully on manufacturing scale: Moffatt-type and TEMPO-mediated oxidations.
Upon completion of this review, I asked myself if this would be true for other chemical
transformations.Beyondsimplecuriosity,thisquestionisrelevantbecausesearchengines
like SciFinder(cid:1) and Reaxys(cid:3) can rapidly search through the chemical literature and
identifylargenumbersofpotentiallyrelevantreactions/references.Forexample,asimple
searchforthenitrationofanareneresultsinthousandsofexamplesofthistransformation.
Howdoesonesortthroughthisincrediblewealthofinformation?
1Caron,S.;Dugger,R.W.;Ruggeri,S.G.;Ragan,J.A.;Ripin,D.H.B.Chem.Rev.2006,106,2943.
ix
x PREFACE
In this age of information overload, we thought that a simple collection of proven
methodologiesmightbeofvaluetopracticingsyntheticchemists.Whilemanytextbooks
offeracompendiumofthemanysyntheticmethodsthatareavailable,wesetouttocreatea
guidethatwouldhelpselectthefirstfewconditionstoattemptforagiventransformation.
This might be of particular value when the substrate of interest is difficult to access in
sufficientquantitiesforalargescreenofreactionconditions.Theauthorsagreedthatthe
objectivewouldnotnecessarilybetofindtheoriginalreportortheverybestprocedurefora
givenreaction, butrather to identify reaction conditions that work reliably well over the
broadestpossiblerangeofsubstrates.Itwasaprerequisiteforthereferencescitedinthis
textbook that experimental data was provided, preferably on a multi-gram scale, and
preferablyusingreactionconditionsthatwouldbeamenabletoscale-up.Intherarecases
wheresuchexperimentaldatawasnotidentified,theauthorsusedtheirdiscretiontoselect
reactionconditionsthatwewouldexpecttoscaleupreasonablywell.Notsurprisingly,many
oftheexamplescitedinthistextbookcomefromOrganicSynthesesorfromjournalslike
Organic Process Research and Development and The Journal of Organic Chemistry.
Wealsoagreedthatpatentliteraturewouldbeavoided,ifpossible,since itisnotalways
easily accessed and/or interpreted. Finally, we made an effort to focus on references
publishedafter1980.
Inadditiontothecompilationofreliablemethodsforaccomplishingvariouschemical
transformations,wehavetriedtoprovidethereaderwithsomeinformationthatmaynotbe
commonknowledgeoutsideofprocesschemistrygroups.Thesecondportionofthisbook
focuses on this type of information. How can chiral building blocks be accessed most
efficiently? What are the most reliable methods for preparing and naming common
heterocycles? Why are some solvents favored over others? How does the synthesis of a
drugevolvethroughoutdevelopment?Whatdoesitmeantohaveagreensynthesis?Wehope
thatreaderswillfindsomeusefulandpracticalinformationinthissectionofthebook.
Thecompletionofthisendeavorwouldhaveneverbeenpossiblewithoutthecommitment
ofseveralofmycolleaguesatPfizerwhoagreedtothepreparationandcollectivereviewof
thechapters.Wearealsoextremelygratefultoourmanagementforsupportingtheproject.
I would specifically like to thank Jodi Gaynor, Lisa Lentini, and Kim White for their
administrativesupport.IwouldalsoliketothankKrisN.Jonesforherassistanceinediting
thebook.ThecommitmentandsupportofourcollaboratorsatWiley-Intersciencearevery
muchappreciated.Weespeciallyappreciatedtheirpatienceasourdeadlinecameandpassed.
Building each chapter of this manuscript served as an excellent chemistry refresher
coursefortheauthors,andwelearnedalotofnewchemistryintheprocess.Wesincerely
hopeyouenjoythesameexperienceasyoureadthisbook.