Stereochemistry of Organic Compounds

ERNEST L ELIEL, SAMUEL ! "ILEN, LE"IS N! MAN#ER

$! INTRO#UCTION
1.1. Scope 1
1.2. History 2
1.3. Polarimetry and Optical Rotation 6
%! STRUCTURE
2.1. Meaning, Factorization, Internal oordinates. Isomers 11 !Mari"a#
2.2. onstit$tion 1% !&iene#
2.3. on'ig$ration 1( !)ace#
2.*. on'ormation 2+ !Samir#
2.%. )etermination o' Str$ct$re 2* !,nna#
2.6. , Priori alc$lation o' Str$ct$re 32 !,nna#
2.-. Molec$lar Models *+ !,nna#
&! STEREOISOMERS
3.1. .at$re o' Stereoisomers */ !0at"a#
a. 1eneral */
2. 3arriers 2et4een Stereoisomers. Resid$al Stereoisomers %*
3.2. 5nantiomers %( !Sarmite#
3.3. )iastereomers 62
a. 1eneral ases 62
2. )egenerate ases 6%
'! S(MMETR(
*.1. Introd$ction -1
*.2. Symmetry 5lements -1 !,igars#
*.3. Symmetry Operators. Symmetry Point 1ro$ps -* -1 !,igars#
a. Point 1ro$ps ontaining 6iral Molec$les -6
2. Point 1ro$ps ontaining Only ,c6iral Molec$les -/
*.*. )esymmetrization ((
*.%. ,7eraged Symmetry /1
*.6. Symmetry and Molec$lar Properties /2
a. Rotation o' Polarized &ig6t /3
2. )ipole Moment /*
c. Symmetry .$m2er /6
)! CON*I+URATION $,$
%.1. )e'initions8 Relati7e and ,2sol$te on'ig$ration 1+1
%.2. ,2sol$te on'ig$ration and .otation 1+3
%.3. )etermination o' ,2sol$te on'ig$ration 113
a. 3i"7oet Met6od 113
2. 96eoretical ,pproac6es 11%
c. Modi'ication o' rystal Morp6ology in t6e Presence o' ,dditi7es 116
%.*. Relati7e on'ig$ration and .otation 11-
%.%. )etermination o' Relati7e on'ig$ration o' Sat$rated ,lip6atic ompo$nds 12*
a. :;Ray Str$ct$re ,nalysis 12*
2. 6emical Intercon7ersion .ot ,''ecting 3onds to t6e Stereogenic ,tom 126
c. Met6ods 3ased on Symmetry onsiderations 12(
d. orrelation 7ia ompo$nds 4it6 6iral enters o' 94o 9ypes 13+
e. 96e Met6od o' <$asi;racemates 132
'. 6emical orrelations ,''ecting 3onds to a 6iral ,tom in a =0no4n= >ay. 13*
g. orrelation 2y Stereoselecti7e Synt6esis o' =0no4n= Stereoc6emical o$rse 13/
6. 6iroptical, Spectroscopic, and Ot6er P6ysical Met6ods 1**
%.6. oncl$sion8 .et4or? ,rg$ments 1*-
-! .RO.ERTIES O* STEREOISOMERS! STEREOISOMER #ISCRIMINATION $)&
6.1. Introd$ction 1%3
6.2. Stereoisomer )iscrimination 1%3
6.3. 96e .at$re o' Racemates 1%/
6.*. Properties o' Racemates and o' 96eir 5nantiomer omponents 162
a. Introd$ction 162
2. Optical ,cti7ity 163
c. rystal S6ape 16*
d. )ensity and Racemate 9ype 16%
e. Melting Point 16-
'. Sol$2ility 1-3
g. @apor Press$re 1-/
6. In'rared Spectra 1(3
i. 5lectronic Spectra 1(*
" . .$clear Magnetic Resonance Spectra 1(%
?. :;Ray Spectra 1(6
1. Ot6er P6ysical Properties 1(-
m. &iA$id State and Inter'acial Properties 1(/
n. 6romatograp6y 1/*
o. Mass Spectrometry 1/-
p. Interaction 4it6 Ot6er 6iral S$2stances 1/-
A. 3iological Properties 2+1
r. Origins o' 5nantiomeric Homogeneity in .at$re 2+/
6.%. )etermination o' 5nantiomar and )iastereomer omposition 21*
a. Introd$ction 21*
2. 6iroptical Met6ods 21-
c. .MR Met6ods 3ased on )iastereotopicity 221
d. 6romatograp6ie and Related Separation Met6ods 3ased on )iastereomeric Interactions 2*+
e. 0inetic Met6ods 26%
'. alorimetric Met6ods 26(
g. Isotope )il$tion 26/
6. Miscellaneo$s Met6ods 2-2
/! SE.ARATION O* STEREOISOMERS! RESOLUTION! RACEMI0ATION %1/
-.1. Introd$ction 2/-
-.2. Separation o' 5nantiomers 2y rystallization 2/(
a. rystal Pic?ing. 9riage 2/(
2. onglomerates 2//
c. Pre'erential rystallization 3+*
d. Pre'erential rystallization in t6e Presence o' ,dditi7es 311
e. ,symmetrie 9rans'ormation o' Racemates. 9otal Spontaneo$s Resol$tion 31%
-.3. 6emical Separation o' 5nantiomers 7ia )iastereomers 322
a. Formation and Separation o' )iastereomers. Resol7ing ,gents 322
2. Resol$tion Principles and Practice 3**
c. Separation 7ia ompleBes and Incl$sion ompo$nds 3%1
d. 6romatograp6ie Resol$tion 3%/
e. ,symmetrie 9rans'ormations o' )iastereomers 36*
'. 1eneral Met6ods 'or t6e Separation o' )iastereomers 3-*
-.*. 5nantiomeric 5nric6ment. Resol$tion Strategy 3(1
-.%. &arge Scale Resol$tion 3((
a. )iastereomer;Mediated Resol$tion 3(/
2. Resol$tion 2y Pre'erential rystallization 3/2
c. 0inetic Resol$tion 3/*
-.6. 0inetic Resol$tion 3/%
a. 96eory. Stoie6iometric and ,2iotic atalytic 0inetic Resol$tion 3/%
2. 5nzymatic Resol$tion *+/
-.-. Miscellaneo$s Separation Met6ods *16
a. Partition in Heterogeneo$s Sol7ent MiBt$res *16
2. 9ransport across Mem2ranes *21
-.(. Racemization *2*
a. Racemization Processes *26
2. Racemization o' ,mino ,cids *36
2! ETEROTO.IC LI+AN#S AN# *ACES 3.ROSTEREOISOMERISM, .ROCIRALIT(4 '-)
(.1. Introd$ction. 9erminology *6%
(.2. Signi'icance. History *6-
(.3. Homotopic and Heterotopic &igands and Faces *-+
a. Homotopic &igands and Faces *-+
2. 5nantiotopic &igands and Faces *-3
c. )iastereotopic &igands and Faces *--
d. oncepts and .omenclat$re *(2
(.*. Heterotopicity and .$clear Magnetic Resonance *((
a. 1eneral Principles. ,nisoc6rony *((
2. .MR in ,ssignment o' on'ig$ration and o' )escriptors o' Prostereoisomerism */2
c. Origin o' ,nisoc6rony *//
d. on'ormationally Mo2ile Systems %+2
e. Spin o$pling .oneA$i7alence !,nisogamy# %+-
(.%. Heterotopic &igands and Faces in 5nzyme;atalyzed Reactions %+(
a. Heterotopicity and Stereoelecti7e Synt6esis %+(
2. Heterotopicity and 5nzyme;atalyzed Reactions %+/
(.6. Pro2;6iral enters8 6iral Met6yl, P6osp6ate, and S$l'ate 1ro$ps %1(
a. 6iral Met6yl 1ro$ps %1(
2. 6iral P6osp6ate 1ro$ps %26
c. 6iral S$lp6ate 1ro$ps %2/
d. Pro3;6iral enters8 96e 6iral 96iop6osp6ate 1ro$p %3+
1! STEREOCEMISTR( O* AL5ENES )&1
/.1. Str$ct$re o' ,l?enes. .at$re o' cis;trans Isomerism %3/
a. 1eneral %3/
2. .omenclat$re %*1
c. $m$lenes %*3
d. ,l?enes 4it6 &o4 Rotational 3arriersC .onplanar ,l?enes %**
e. 96e D. and .D. )o$2le 3onds %%+
/.2. )etermination o' on'ig$ration o' cis;trans Isomers %%%
a. 6emical Met6ods %%%
2. P6ysical Met6ods %62
/.3. Intercon7ersion o' cis;trans Isomers8 Position o' 5A$ili2ri$m and Met6ods o' Isomerization %-*
a. Position o' cis;trans 5A$ili2ria %-*
2. Met6ods o' 5A$ili2ration %-(
c. )irected cis;trans Intercon7ersion %(*
$,! CON*ORMATION O* AC(CLIC MOLECULES )1/
1+.1. on'ormation o' 5t6ane, 3$tane, and Ot6er Simple Sat$rated ,cyclic Molec$les %/-
a. ,l?anes %/-
2. Sat$rated ,cyclic Molec$les 4it6 Polar S$2stit$ents or 6ains. 96e ,nomeric 5''ect 6+6
1+.2. on'ormation o' Ensat$rated ,cyclic and Miscellaneo$s ompo$nds 61%
a. Ensat$rated ,cyclic ompo$nds 61%
2. ,l?yl2enzenes 62*
c. Miscellaneo$s ompo$nds 62-
1+.3. )iastereomer 5A$ili2ria in ,cyclic Systems 62/
1+.*. P6ysical and Spectral Properties o' )iastereomers and on'ormers 63*
a. 1eneral 63*
2. )ipole Moments 63%
c. 3oiling Point, Re'racti7e IndeB, and )ensity 63(
d. In'rared Spectra 63/
e. .MR Spectroscopy 6*1
1+.%. on'ormation and Reacti7ity8 96e >instein;Holness 5A$ation and t6e $rtin;Hammett Principle 6*-
$$! CON*I+URATION AN# CON*ORMATION O* C(CLIC MOLECULES --)
11.1. Stereoisomerism and on'ig$rational .omenclat$re o' Ring ompo$nds 66%
11.2. )etermination o' on'ig$ration o' S$2stit$ted Ring ompo$nds 66/
a. Introd$ction 66/
2. Symmetry;3ased Met6ods 66/
c. Met6ods 3ased on P6ysical and 6emical Properties 6-1
d. orrelation Met6ods 6-%
11.3. Sta2ility o' yclic Molec$les 6-%
a. Strain 6-%
2. 5ase o' yclization as a F$nction o' Ring Size 6-(
c. 5ase o' Ring los$re as a F$nction o' t6e Ring ,toms and S$2stit$ents. 96e 96orpe;Ingold 5''ect
6(2
d. 3ald4inFs R$les 6(*
11.*. on'ormational ,spects o' t6e 6emistry o' SiB;Mem2ered Ring ompo$nds 6(6
a. yclo6eBane 6(6
2. Monos$2stit$ted yclo6eBanes 6/+
c. )is$2stit$ted and Polys$2stit$ted yclo6eBanes -++
d. on'ormation and P6ysical Properties in yclo6eBane )eri7ati7es -+/
e. on'ormation and Reacti7ity in yclo6eBanes -2+
'. sp2 Hy2ridized yclo6eByl Systems -26
g. SiB;Mem2ered Sat$rated Heterocycles -*+
11.%. 6emistry o' Ring ompo$nds Ot6er 96an SiB;Mem2ered Ones -%*
a. 96ree;Mem2ered Rings -%*
2. Fo$r;Mem2ered Rings -%%
c. Fi7e;Mem2ered Rings -%(
d. Rings &arger 96an SiB;Mem2ered -62
e. 96e oncept o' I Strain -6/
11.6. Stereoc6emistry o' F$sed, 3ridged, and aged Ring Systems --1
a. F$sed Rings --1
2. 3ridged Rings -(-
c. Paddlanes and Propellanes -/*
d. atenanes, RotaBanes, 0nots, and MG2i$s Strips (++
e. $2ane, 9etra6edrane, )odeca6edrane, ,damantane, and 3$c?minster'$llerene (+6
$%! STEREOSELECTI6E S(NTESIS 2&)
12.1. Introd$ction (3%
a. 9erminology (3-
2. Stereoselecti7e Synt6esis (3(
c. ategories o' Stereoselecti7e Synt6esis (3/
d. on7ergent Synt6eses (*3
12.2. )iastereoselecti7e Synt6esis o' ,c6iral ompo$nds (*%
a. yclanes (*%
2. )iastereoselecti7e Synt6eses o' ,l?enes (*6
12.3. )iastereoselecti7e Synt6esis (%(
a. Introd$ction (%(
2. Strategies 'or Stereocontrol in )iastereoselecti7e Synt6esis (%/
c. )iastereoselecti7e Synt6eses 3ased on 6iral S$2strates o' .at$ral Origin (-2
d. .$cleop6ilic ,dditions (-%
e. 5lectrop6ilic Reactions o' ,l?enes (/*
'. 96e ,ldol Reaction /13
g. Pericyclic Reactions /2+
6. atalytic Hydrogenations /32
i. Free Radical Reactions /3%
12.*. 5nantioselecti7e Synt6eses /3/
a. Introd$ction /3/
2. 5nantioselecti7e Synt6eses 4it6 6iral .onracemic Reagents /*1
c. 5nantioselecti7e Reactions 4it6 6iral .onracemic atalysts /*-
d. .onlinear 5''ects in atalysis /%/
e. 5nzyme 3ased Processes /6+
'. 5nantioselecti7e Synt6esis In7ol7ing )iscrimination 2et4een 5nantiotopic 1ro$ps /62
g. 5nantiocon7ergent Synt6eses /63
12.%. )o$2le Stereodi''erentiation /6%
a. Introd$ction /6%
2. Interactions 2et4een Principal 6iral Reactants /6-
c. Reagent ontrol /6/
d. 0inetic ,mpli'ication /-+
12.6. oncl$sion /-1
$&! CIRO.TICAL .RO.ERTIES 11$
13.1. Introd$ction //1
13.2. Optical ,cti7ity. ,nisotropie Re'raction //2
a. Origin. 96eory //2
2. Optical Rotatory )ispersion ///
13.3. irc$lar )ic6roism. ,nisotropie ,2sorption 1++3
13.*. ,pplications o' Optical Rotary )ispersion and irc$lar )ic6roism 1++-
a. )etermination o' on'ig$ration and on'ormation. 96eory 1++-
2. lassi'ication o' 6romop6ores 1+13
c. Sector and Helicity R$les 1+1/
d. 5Bciton 6irality 1+*3
e. Ot6er ,pplications. Ind$ced OR) and ) 1+%+
'. Fl$orescence )etected irc$lar )ic6roism 1+%/
g. irc$lar )ic6roism o' 6iral Polymers 1+6+
13.%. ,pplications o' Optical ,cti7ity 1+-1
a. Polarimetry 1+-1
2. 5mpirical R$les and orrelations. alc$lation o' Optical Rotation 1+(+
13.6. @i2rational Optical ,cti7ity 1+/3
13.-. irc$lar Polarization o' 5mission. ,nisotropie 5mission 11++
$'! CIRALIT( IN MOLECULES #E6OI# O* CIRAL CENTERS $$$1
1*.1. Introd$ction. .omenclat$re 111/
1*.2. ,llenes 1122
a. Historical. .at$ral Occ$rrence 1122
2. Synt6esis o' Optically ,cti7e ,llenes 112*
c. )etermination o' on'ig$ration and 5nantiomeric P$rity o' ,llenes 112%
d. yclic ,llenes, $m$lenes, 0etene Imines 1132
1*.3. ,l?ylidenecycloal?anes 1133
1*.*. Spiranes 113(
1*.%. 3ip6enyls. ,tropisomerism 11*2 H
a. Introd$ction 11*2
2. 3ip6enyls and Ot6er ,tropisomers o' t6e sp2;sp2 Single;3ond 9ype 11*3
c. ,tropisomerism a2o$t sp2;sp3 Single 3onds 11%+
d. ,tropisomerism a2o$t sp3;sp3 3onds 11%3
1*.6. Molec$lar Propellers and 1ears 11%6
a. Molec$lar Propellers 11%6
2. 1ears 116+
1*.-. Helicenes 1163
1*.(. Molec$les 4it6 Planar 6irality 1166
a. Introd$ction 1166
2. yclop6anes 1166
c. ,nn$lenes 11-+
d. trans;ycloal?enes 11-2
e. Metallocenes and Related ompo$nds 11-%
1*./. yclostereoisomerism 11-6