Chap.

2 Stereochemistry
Structural representations that convey 3-D information

CH3 Cl H CH2CH3

CH3

Cl

H CH2CH3

Cl H

CH3 CH2CH3

Cl

CH3

CH2CH3

Fischer projection.
CH3 CH3 H Cl H3C H H H Cl

Ball & Stick

CH3 H CH3 H

H H H3C

H Cl

O Ph Ph N H

Sawhorse representation.
AcO O O HO H H H AcO OCPh O O OH

Newman projection

Taxol

 Isomerism
Isomers Different compounds that have the same molecular formula.

Conformational IsomerStereoisomers that are superimposable by rotation around a single bond. Enantiomer Isomers that are non-superimposable mirror images to each other.chiral DiastereomerIsomers that are non-superimposable, not mirror images. Cis-trans isomer ( geometric isomer ) configurational isomers differ around a double bond or cyclic structure.

 Symmetric, Asymmetric, Dissymmetric and Nondissymmetric molecules.

Symmetry operation reflection in a plane inversion through a centeri rotation about a proper axisCn , for 360 /n rotation about an improper axisSn ( = rotation about an axis, followed by reflection though a plane perpendicular to the axis )

H3C H

CH 3 H

CH 3 H

C2, v, v

CH 3

C2, h

H F1 D1 H

Cl2 D2 F2 i F2 D2

H2

Cl1 D1 F1

Cl1

Cl2 C2 D2 Cl2 H2 F2 F1 H1 Cl1 D1

H1

C2hi S2

Y Ci

X Cs X

X C2

X X

X C2v X C2h X X

X X D2h X

X X X D2d

ChiralityMolecules that are not superimposable with their mirror image chiral. (enantiomeric ) dissymmetric molecules molecules without Sn axis (including n=1). Dissymmetric molecules are chiral, chiral molecules are dissymmetric. Dissymmetrical with a chiral center (asymmetric): asymmetric moleculesmolecules without any symmetry element, except C1.
CH2CH3 Br O F Cl CH3 Ph S H3CH2CH2C H3C P

CO2H
2 3

N Nu CH3 R3

HO2C

slow inversion, chiral

achiral due to fast inversion

H Br

CO2H

Dissymmetrical molecules belonging to Cn or Dn group

O O H H O O O O O O

C2

O O O H O

C6
H H H

C3

D2

D2

D3

chirality along an axis

axis of chirality
H C H3 C C C H H3 C CH3 H C C C H CH2CH3

axis of chirality

has C2, chiral, dissymmetric

Cl H3C CH3 H2N Cl
CO2H O2N

C1
H

NH2

axis of chirality

chiral

axis of chirality
NO2 HO2C

chiral due to restricted rotation (atropisomer)

chirality about a plane

(CH2)2

* * *
CO2H

Non-dissymmetric moleculeshaving Ci, Cs, Cnv, Cnh, Dnh, H3C H Dnd, Td, Oh or Sn symmetry.
H H H3C N H CH3 CH3

( S1, S2i )

H3C N CH3

CH3

achiral

with S4 symmetry, achiral

CH3

 Designation of Molecular Configuration (CahnIngold-Prelog convention)

Chirality about a point 1. Determine the priority of four groups. 2. With least priority group pointing away, determine the direction of 123 priority, clockwise R, counterclockwise S Criteria for priority 1. higher atomic number higher priority Br > Cl > C > H 2.if the two have same atomic number, count substituent next to it. 3. double bond counted twice, triple bond counted three times for both ends 4. tricoordinatea group of atomic number of 0 assigned for the long pair
-CH2Cl < -CHCl2
O C O
C N

-CH2CHFCH3 > -CH2CH2CH2Cl

O C O C CH3 O C O
C CH

COOH > COCH3 > CHO

C OH

C H

>

CH

NH

>

>

CH

CH 2 >

CH 2

CH 3

H3C CH H3C

HO HC

OCH3 CH CH2CH3
Cl

(S)

C
CH3

Cl

H2C C

CH2 HC HC OH

CH3

H2C HC HC OH

H CH2

C
H

(S)

H2C

CH2

3
CH3 H

CH3 H

2
ClH2C

(R)
1
CHCl2 BrH2C

(S)
1 2
CHCl2

CH3 HO
4' 8'

H3C CH3

CH3 CH3

CH3

(2R, 4R, 8R)

H CH3
CH2OH H

H CH3

CH3 17 13

20 C H

OH

1 2
H3CH2CH2C H3C P

OH

(S)
3

13R, 17S, 20R

Chirality about an axis Start from the near end to determine the priority, then to the far end.
HO2C C H C C H CO2H
B

CO2H C

H H

CO2H

NO2 C O2N HO2C CO2H NO2

A

O2N CO2H

CO2H

Fischer Projection, popular in sugar chemistry, relate the config. at an assym. center to that of (+)glyceraldehyde, the standard
HO C HOH2C CHO H

D-(+)-glyceraldehyle
CHO H OH H CH2OH

CHO OH CH2OH

Rules C 1.most highly oxidized HOH2C CHO L-(-)-glyceraldehyle carbon on top. 2.vertical bonds CHO point backward 3.horizontal HO H bonds point forward CH OH

OH

Compare the configuration around an asymm. center, and assign DL

CHO H H * OH OH HO * OH CHO

D-erythrose

D
highest no.
H2N CH2OH CH2OH

L
CHO H R

D-threose

L-alanine

There is no direct correlation between R S and D L, configuration

H HO HO H

CH 2 OH O H H OH OH

H HO H HO H

CH 2 OH O H H OH H

OH

CH H OH H H OH

-D-Glucopyranose
2 OH

-D-Glucopyranose

O H

H OH

OH

epi
CHO HO HO H HO H epimeric HO OH OH CH2OH HO H CHO H H H OH CHO

D-(+)-Mannose epimers meso

CHO Cl HO H Cl CH2OH

D-(+) Talose

CH3

CH3

erythroCHO H H OH OH CH2OH

threoCHO HO H H OH CH2OH
H3CS

Similar to threose
OH CH2OH NH2

CH2OH H2N H H OH

SCH3

D-Erythrose

D-Threose

Threo-(1R,2R)-2-amino-

Other Stereochemical Nomenclature

Cl Br CO 2H CH 3

close a reference
t-4-bromo-c-4-chloro-1-methyl-rcyclohexanecarboxylic acid

Alkene cis,trans based on the shape of the molecules E, Z based on priority rule used for R,S.
A

H 3C H

CO 2 H Cl

Cl Br

CH 3 I

cisE-

Z-

OH N H 3 CH 2 C H 3 CH 2 C N OH

sym-based on size Zoutside

H 3C H H CH 3

anti-propiophenone oxime E-

For bicyclo systemsexo-, endo-,

H 3C CH 3 H H

i n si

de

exo, endo-2,4-dimethyl
H Cl

exo, exo-2,4-dimethyl
exo exo
HN AcO H OH

inside

endo-2-chloronorbornane
H HO HO H

6-exo-(acetyloxy)-8azabicyclo-[3.2.1]octan2-exo-ol

3--Cholestanol

3- -Cholestanol

Stereoselective ReactionA reaction in which one stereoisomer (or pair of enantiomer) is formed or destroyed at greater rate or to a greater extent than other possible stereoisomer.
O LAN H OH HO H

90%
HCO2H O OCH
CH3 H Ph CHO CH3MgI H Ph CH3 OH H CH3

10%

CH3 OH H Ph H CH3

erythro 67%

threo 33%

Stereospecific ReactionA reaction in which stereoisomerically different reactants yield stereoisomerically different products.
H3C Br Ph H H3C Ph H H H Ph OTs NaSPh H H3C TsO H NaSPh C H3C CH3 CH3 H H3C C CH3 CH3 C CH3 CH3 H H3C H C CH3 CH3 PhS H Br KOCH2CH3 Ph KOCH2CH3 H3C Ph Ph H

H3C Ph H

H Ph

SPh

homotopic vs. heterotopic

H H HO H OH D HO D OH

H OH
OH

homotopic

HO
HO

prochiral center pro-R

HO OH HR HS

HO H H

OH

H HO D

D OH H

pro- S

heterotopic

re face vs. si face

re
H3C O H

enantiotopic (if other chiral center present) diastereotopic

HS HR CO2NH3+
H

OH H3C

re
clockwise

si

H
OH H3C H

si
Vinylmagnesium bromide

Counter clockwise

Optical Activity
Enantiomers can exhibit optical activityrotation of plane polarized light. The two enantiomers rotate light to opposite direction, but to the same magnitude. rotation clockwise (d) counterclockwise ( l) for pure +)-glyceraldehyde, specific rot. +14 for a mixture of enantiomeric glyceraldehyde giving +12.6, 12.6 the excess is = 90% 95%+-and 5% --cpd.
14

Configuration and Optical Activity

R,S, D,L,- erythro- threo- are artificial molecular notation, based on arbitrary rules. , are molecular property, obtained by exptl observation. Configuration and optical activity are not directly related.
CO2H

Fischer assigned

H HO

OH H CO2H

(+)-Tartaric acid

confirmed by X-ray

To relate absolute config. and configuration Prediction of optical activity

B A D C

if polarizability is A >B >C >D Dextrorotatory, +,

Ph Br H CH3

correlating
C O 2H H 2N H C H 2O C O C H 2N H 2 H 2N C O 2H H C H 2O H

chlorination rxn H 2N

C O 2H H C H 2C l

(S)-()-Azaserine

(S)-()-Serine
by X-ray by exptl

(R)-( )-2-Amino-3chloropropanoic acid

by assigning

the bonds connected to chiral center are not broken the abs. configuration remains.
CO 2 H Cl H CH 3

OHinversion

CO 2 H H OH CH 3

(S)-()-2-Chloropropanoic acid

(R)-()-Lactic acid