Stereochemistry and Organic Reactions: Conformation, Configuration, Stereoelectronic Effects and Asymmetric Synthesis

638 Pages·2021·18.77 MB·english

by  Dipak Kumar Mandal

Stereochemistry and Organic Reactions
Conformation, Configuration, Stereoelectronic Effects and
Asymmetric Synthesis
Stereochemistry and
Organic Reactions
Conformation, Configuration, Stereoelectronic
Effects and Asymmetric Synthesis
Dipak K. Mandal
Formerly ofPresidency College/University
Kolkata,India
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Preface
Organicstereochemistryisavastandimportantsubject.Itisanintrinsicpartof
allorganicchemistry.Planningandexecutingstereoselectivesynthesistopre-
pare single enantiomers as well as single diastereomers is an exhilarating
sciencethathasregisteredenormousprogressovertheyears,andstillisinfast
development. Understanding of the factors that determine the high levels of
three-dimensionalcontrolinorganicsynthesisisanessentialandfundamental
topic for all students of organic chemistry. It is not surprising therefore that
stereochemistry is covered in every undergraduate, advanced undergraduate
andgraduatecourseinorganicchemistry.Itismyinvolvementinteachingthis
subjecttoundergraduateandgraduatestudentsformorethan30yearsthathas
inspired me to write this book. The purpose of this endeavour is entirely
pedagogic,keepinginviewthatourstudentsdesperatelycraveunderstanding,
not factual knowledge alone. Understanding requires a ‘feel’ for the set of
principles that influence the stereochemistry of organic molecules and their
reactions,whichisintheheartofthisbook;thehistoricaldevelopmenthasbeen
generally given short shrift.
Thebookisprimarilystructuredinthreeparts(PartI–III),andeachpartis
factoredintoseveralchapters.AnappendixisincludedinPartIV.PartIdeals
with the stereochemistry—conformation and configuration—of acyclic
molecules (Chapters 1 and 2) and cyclic molecules (Chapter 3). The stereo-
chemistryoforganicreactionsfollowsthereafter.PartIIprovidesanintroduc-
tion to perturbation molecular orbital theory for the origin of stereoelectronic
effects (Chapter 4) and an introduction to the principles of stereoselectivity
and hierarchical levels or generations of asymmetric synthesis (Chapter 5) as
a background aid to follow the reaction stereochemistry covered in Part III.
Ihopethisuniquestylewouldhelpenhancethepedagogyofthistext.Theste-
reochemistryofreactionswithparticularemphasisondiastereoselectivityand
asymmetricsynthesisarepresentedinsevenchaptersalongthelinesofmech-
anisticclasses.Twoelaboratechapters(Chapters6and7)aredevotedtoionic
reactions,themostabundantclass,twoforpericyclicreactions(Chapters8and
9), andone each for transitionmetal-catalysedreactions(Chapter 10),radical
reactions(Chapter11) andphotochemical reactions (Chapter 12).
The book is distinct from other contemporary textbooks in that it brings a
holistic approach by providing, within the limits of space and time, separate
chapters on the stereochemistry of reactions of all mechanistic types ranging
xvii
xviii Preface
fromionic,pericyclic,transitionmetal-catalysedtoradicalandphotochemical.
Thiswouldundoubtedlyhelprevealtheunifyingprinciplesforstereochemical
understandingandprediction.Anotherimportantdifferencebetweenthisbook
andothersistheemphasisontheworkingofstereochemistry,specificallyhow
todelineatethestereochemistryofproducts.Learningstereochemistryishard
work. I have found that students are often not quite comfortable to work
stereochemistry for themselves. They need some more help. To address their
concerns,Ihavealwaysbeenlookingforinnovativeapproachestostereochem-
icalissues.Myeffortshaveproducedsomesimpleandgeneralstereochemical
rules/guidelines, some of which have been published in three papers in the
Journal of Chemical Education. These published (also some unpublished)
rules/mnemonics have been used extensively in the relevant chapters as an
aid to draw quickly and correctly the product stereochemistry in organic
reactions.
Asanelementoflearningandpedagogy,Ihaveprovidedover150problems
withinthechapters,reinforcingthemainthemesinthetext.Ihopethatstudents
couldtesttheirlearningimmediatelywhilereadingthroughthechapters.These
problemsetsshouldbeconsideredanintegralpartofthecourse.Thedetailed
answers to the problems with references, wherever necessary, are given in
Appendixin Part IV. Ihave provided atotal ofabout 1,400 references topri-
mary and review literature, with each chapter containing a reference list at
itsend.Thesereferenceswillenablethereaderstogofurtherintothesubject.
Theapproachpresentedinthisbookisdistinctandclasstested.Ihavetried
tofindaleveltosuiteveryoneinhis/herownwayfromtheundergraduatetothe
research level. I hope this book will be of value and interest to the students,
teachers and researchers of organic, biological and medicinal chemistry, and
alsotoawidercircleofreadersincludingbiologists,pharmacologists,polymer
chemistsandchemistsworkinginindustrywhomightwishtohaveanoverview
ofthis highly fascinating field of chemistry.
Iwouldliketothanktheanonymousreviewersforhelpfulsuggestions.Iam
grateful to the editorial members Emily M. McCloskey and Allison Hill,
production manager Paul P. Chandramohan, and their colleagues at Elsevier
for excellent support and cooperation. Finally, I thank my wife Tapasi and
my daughter Sudipta for their continuous support and my son Tirtha for his
active help in artwork and referencing. I could not finish without thanking
mylittlegranddaughterAdritawhohasprovidedmethenecessaryfillipduring
the preparation ofthis book.
DipakK. Mandal
Kolkata,India
Abbreviations
Ac acetyl (MeCO)
(cid:1)
acac acetylacetonato (MeCOCHCOMe )
AIBN azobisisobutyronitrile [Me C(CN)N]N(CN)CMe ]
2 2
Alpine-Borane B-isopinocamphenyl-9-borabicyclo[3.3.1]nonane
AQN anthraquinone
9-BBN 9-borabicyclo[3.3.1]nonane
BINAL-H binaphthyllithiumaluminium hydride
BINAP 2,20-bis(diphenylphosphino)-1,10-binaphthalene
BINOL 1,10-bi-2-naphthol
Bn benzyl (PhCH )
2
Boc tertiary-butoxycarbonyl (Me COC]O)
3
box bis-oxazoline
bpy 2,20-bipyridine
Bs brosylor p-bromobenzenesulphonyl (4-BrC H SO )
6 4 2
Bu butyl [Me(CH ) ]
2 3
i-Bu isobutyl(Me CHCH )
2 2
s-Bu secondary-butyl [MeCH C(Me)H]
2
t-Bu tertiary-butyl(Me C)
3
Bz benzoyl(PhCO)
CAN cerium(IV) ammoniumnitrate [Ce(NH ) (NO ) ]
4 2 3 6
Cbz benzyloxycarbonyl (PhCH OC]O)
2
CD circular dichroism
CE Cottoneffect
CIR chiral inducingreagent
cod 1,5-cyclooctadiene
mCPBA meta-chloroperbenzoic acid (3-ClC H CO H)
6 4 3
CSP chiral stationary phase
Cy cyclohexyl (C H )
6 11
DAIB 3-exo-(dimethylamino)isoborneol
dba trans,trans-dibenzylideneacetone [(PhCH]CH) CO]
2
de diastereomeric excess
DET diethyl tartrate
DHQ dihydroquinine
DHQD dihydroquinidine
DIBAL-H diisobutylaluminium hydride (i-Bu AlH)
2
DIP-Cl diisopinocamphenylboronchloride(Ipc BCl)
2
xix
xx Abbreviations
DIPT diisopropyl tartrate
DMAD dimethylacetylenedicarboxylate (MeO CC^CCO Me)
2 2
DME 1,2-dimethoxyethane (MeOCH CH OMe)
2 2
DMF N,N-dimethylformamide (Me NCH¼O)
2
DMSO dimethylsulphoxide (Me S]O)
2
dr diastereomer ratio
DTBP 2,6-di-t-butylpyridine
2
e electron
ee enantiomeric excess
ESR electronspin resonance
Et ethyl(MeCH )
2
FMO frontier molecular orbital
fod 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedionate
1G/2G/3G/4G first/second/third/fourthgeneration
gb gauche-butane
GC gas chromatography
HOMO highest occupied molecular orbital
HMPA hexamethylphosphoramide [(Me N) P]O]
2 3
HPLC high performance liquid chromatography
IND N-carboxy-indoline
IR infrared
ISC intersystem crossing
Ipc BH diisopinocamphenylborane
2
Ipc BOTf diisopinocamphenylborontriflate
2
KHMDS potassium hexamethyldisilazide [(Me Si) NK]
3 2
LCAO linear combinationof atomic orbitals
Lcp left circularly polarized
LDA lithiumdiisopropylamide (i-Pr NLi)
2
L-DOPA (S)-30,40-dihydroxyphenylalanine
LiHMDS lithiumhexamethyldisilazide[(Me Si) NLi]
3 2
LiTMP lithiumtetramethylpiperidide
L-Selectride lithiumtri(sec-butyl)borohydride [Li(s-Bu) BH]
3
LUMO lowest unoccupied molecular orbital
2,6-Lutidine 2,6-dimethylpyridine
Me methyl (CH )
3
Meerwein’s trimethyloxonium tetrafluoroborate (Me O+BF (cid:1))
3 4
salt
Ms mesylormethanesulphonyl (MeSO )
2
NAD+ nicotinamide adeninedinucleotide
NADH nicotinamideadeninedinucleotidehydride(reducedformof
NAD+)
NaHMDS sodiumhexamethyldisilazide [(Me Si) NNa]
3 2
NBS N-bromosuccinimide
NGP neighbouring-group participation
Abbreviations xxi
NMO N-methylmorpholine-N-oxide
NMR nuclear magnetic resonance
op optical purity
ORD optical rotatorydispersion
Oxone potassium peroxymonosulphate (2KHSO (cid:3)KHSO (cid:3)K SO )
5 4 2 4
Ph phenyl (C H )
6 5
PHAL phthalazine
PHOX phosphinooxazoline
PMP 1,2,2,6,6-pentamethylpiperidine
PPTS pyridinium p-toluenesulphonate
Pr propyl [Me(CH ) ]
2 2
i-Pr isopropyl (Me CH)
2
2-Py 2-pyridinyl
QP quinine hypophosphite
QDP quinidine hypophosphite
RAMP (R)-1-amino-2-(methoxymethyl)pyrrolidine
Red-Al sodiumbis(2-methoxyethoxy)aluminiumhydride
[NaAlH (OCH CH OMe) ]
2 2 2 2
Rcp right circularly polarized
r.t. room temperature
SAEP (S)-1-amino-2-(1-ethyl-1-methoxypropyl)pyrrolidine
SAMP (S)-1-amino-2-(methoxymethyl)pyrrolidine
SET single electron transfer
SOMO singlyoccupied molecular orbital
TADDOLs α,α,α0,α0-tetraaryl-1,3-dioxolane-4,5-dimethanols
TAPA α-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)
propionic acid
TEMPO 2,2,6,6-tetramethylpiperidine-1-oxyl
TBDMS tertiary-butyldimethylsilyl (t-BuMe Si)
2
TBDPS tertiary-butyldiphenylsilyl (t-BuPh Si)
2
Tf triflyl or trifluoromethanesulphonyl (CF SO )
3 2
TFA trifluoroaceticacid (CF CO H)
3 2
TFAE 2,2,2-trifluoro-1-(9-anthryl)-ethanol
2 (cid:1)
TfO triflate(CF SO )
3 3
THF tetrahydrofuran
TIPS triisopropylsilyl (i-Pr Si)
3
TLC thin layer chromatography
TMEDA N,N,N0,N0-tetramethylethylenediamine[Me N(CH ) NMe ]
2 2 2 2
TMS trimethylsilyl (Me Si)
3
TOT tri-o-thymotide
Ts tosylorp-toluenesulphonyl(4-MeC H SO )
6 4 2
TS transition structure
UV ultraviolet
Part I
Stereochemistry of organic
molecules
Amoleculeisamicroscopicgroupingofatomslinkedtogetherbybonds,andits
structureisaconceptatthemolecularlevel,whereasaphysicalpropertyrefers
toanassemblyofmoleculesorcompoundatthemacroscopiclevel.PartIcom-
prisesthreechapters(Chapters1–3)whichdealwiththeconceptsofsymmetry,
chirality, conformation, configuration and topicity in organic molecules, and
methods based on physical properties to achieve resolution of racemates and
to determineconformation, configuration andenantiomeric composition.