Chapter 5

Stereochemistry

Chirality and isomers

Stereoselectivity of reactions
Isomers Ch 5 #2

configurational
isomers

geometric isomers (optical isomers)

Chirality = handedness Ch 5 #3

 chiral object or molecule has

 non-superimposable mirror image
 asymmetric center

 achiral object or molecule has plane of symmetry

Br

C
H
H3CH2C
H
 Ch 5 #4

 chiral? achiral? Find

 asymmetric center [= C with 4 different groups]  chiral
 plane of symmetry  achiral ~ always true

not always
true

Me
Me
Me

O O Me Et Me Et

Cl Cl Cl Br
Asymmetric center Ch 5 #5

 atom bonded to 4 different groups

= asymmetric carbon = chiral(ity) center = chiral carbon

 stereocenter and asymmetric center

Enantiomer(s) Ch 5 #6

enantiomer(s)

 Fischer projection
 Horizontal bonds project above the paper;
vertical bonds projects behind the paper.
 Usually, C-C vertical, subs horizontal
CH3 CH3

Br H H Br

CH2CH3 CH2CH3
R,S designation of enantiomers Ch 5 #7

1. Find the asymmetric center.

2. Assign priority of the groups (1, 2 , 3, 4).
 Using Cahn-Ingold-Prelog rules
3. View from asymmetric center to group 4.
4. Determine the direction from group 1 to 2.
 Clockwise ~ (R)
 Counterclockwise ~ (S) 1 2
4 4

R ~ rectus [‘right’]
3 2 3 1
S ~ sinister [‘left’]
‘R for right-turn’ (S)
(R)
 Ch 5 #8

 Practice!

1
2 OH
OMe H Ph
H
3 Et C 4
Cl
Me 1
4

OH

C
Cl Et
Me
 Ch 5 #9

 R,S in Fischer projection

Cl Cl
Et Pr Pr Et

H H

Me Me

H OH HO H

Et Et
Properties of enantiomers Ch 5 #10

 For an enantiomeric pair:

 properties that are not chiral are the same
 properties observed in achiral environment
 mp, bp, ∆Hcombustion,
 solubility to achiral solvent, reactivity to achiral comp’d
 properties that are chiral are different hand
 properties observed in chiral environment mitten
glove
 solubility to chiral solvent
 reactivity with an enantiomer of a chiral comp’d
 odor, drug [medicine]
 optical rotation
Optical activity Ch 5 #11

 Chiral compounds are optically active, and rotate plane-

polarized light.

 clockwise rotation ~ dextrorotatory ~ (+) or (d)

 counterclockwise rotation ~ levorotatory ~ (–) or (l)
 no rotation ~ not optically active [achiral] or racemic
 racemate [racemic mixture] ~ 50/50 mixture of (+) and (–)
 (±) or (d,l) D/L ~ for carbohydrates

 relation between R/S and +/–? NO relation!

 Observed rotation indicates only chirality and existence or
excess of one enantiomer.
 Ch 5 #12

 specific rotation

 T ~ temperature (°C)
 λ ~ wavelength (usually, D ~ sodium D-line, 589 nm)
 α ~ observed raotation (degree)
 l ~ length of sample tube (dm = 10 cm)
 c ~ concentration (g/mL)
 specific rotation for
one enantiomer
 not for racemate
 enantiomeric excess [ee]
 ee = observed [α] / [α] of pure enantiomer (%)
 If [α] = 2.875 observed, ee = 50%. (50+25)% R + 25% S.
More than 1 asymmetric center Ch 5 #13

 # of stereoisomers
 for molecules with n asymmetric centers [C*]
 maximum number of stereoisomers = 2n
 with 2 C*’s
* *
 4 stereoisomers
RR SS
OH

enantiomers
RS SR diastereomers
 2 enantiomers + 2 diastereomers
 for 1 isomer, 1 enantiomer + 2 diastereomers
 with n C*’s
 for 1 isomer, 1 enantiomer and 2n – 2 diastereomers
 Ch 5 #14

 Diastereomers are stereoisomers that are not enantiomers.

 enantiomers ~ same achiral properties (mp, bp, ---)
different chiral properties (+/– optical rotation)
 diastereomers ~ different chiral and achiral properties
 Cis-trans isomers are diastereomers.
 Ch 5 #15

 erythro ~ similar group on the same side

 threo ~ on opposite sides in Fischer projection (eclipsed!)
 Ch 5 #16

Br CH3 Br CH3

H3C CH3 H3C CH3 H3C CH3 H3C CH3

Meso compound Ch 5 #17

2 C*’s, only 3 stereoisomers

(1 meso and its 2 diastereomers)

Br CH3
H
C C
H
H3C Br

CH3
Br H
Br H
CH3

 meso compound [meso-stereoisomer]

 superimposable mirror image ~ achiral
 The 2 C*’s are bonded to the same 4 groups.
 Ch 5 #18

 Me2-cp

H3C
=
CH3 H3C CH3 H3C CH3 H3C CH3

 Br2-cx

Still, achiral and meso

R,S for diastereomers Ch 5 #19

(2S,3R) =
Absolute and relative configurations Ch 5 #20

 absolute config ~ R or S
 relative config ~ changed or not [the same or different]
 the same relative config  not breaking bond to C*

absolute config also the same

absolute config changed

 relative config may change  breaking bond to C*

Separation of enantiomers Ch 5 #21

 difficult, tedious, and costly

(1) converting to diastereomers
-
(R)-RCOO (R)-R’NH + 3
+ mixture of
(R)-R’NH2 -
(S)-RCOO (R)-R’NH3+
diastereomers (R)-RCOOH
+
(R)-RCOOH (S)-RCOOH
+ separation by
-
(R)-RCOO (R)-R’NH3+
(S)-RCOOH chromatography
or recrystallization +
racemate -
(S)-RCOO (R)-R’NH3+
HCl

(2) selectively reacting one enantiomer with

chiral reagent and/or chiral catalyst
(3) chromatography with chiral stationary phase
Other chiral compounds Ch 5 #22

 other tetrahedral comp’ds

 pyramidal comp’ds
 not separable

 separable
 Ch 5 #23

 substituted allenes
 Ch 5 #24

 substituted biphenyls

 rings perpendicular ~ no plane of symmetry

 helical molecules

[α] = 3640
 right-handed and left-handed
Stereochemistry of reactions Ch 5 #25

 regioselectivity

 eg, Markovnikov addition

 if completely regioselective ~ regiospecific
 stereoselectivity

 moderately, highly, completely

 stereospecificity

 All stereospecific reactions are stereoselective. Not vice versa.

Addition rxn creating 1 C* Ch 5 #26

 reactant with no C*

 gives racemate

enantiomers

 = not stereoselective
 not stereospecific ~ both cis- and trans- gives racemate
 Ch 5 #27

 reactant with C*

 gives racemate?
 R  RS + RR

 stereoselective
 diastereomers ~ RS > RR or RS < RR
 stereospecific
 S  SR + SS
Addition creating 2 C*’s Ch 5 #28

 through C+ intermediate

 gives 4 stereoisomers

 RR, RS, SS, SR

 not stereoselective and not specific
 Ch 5 #29

 catalytic addition
 ‘syn’ addition

 cis-isomer  erythro enantiomers

 symmetric cis  meso compound

 Ch 5 #30

 trans-isomer  threo enantiomers

 cycloalkenes  cis or meso

 Ch 5 #31

 peroxyacid addition
 syn addition  ‘concerted’
 cis to cis or meso
 trans to trans
 Ch 5 #32

 Hydroboration-oxidation
 syn addition  ‘concerted’
 stereoselective
 stereospecific
 Ch 5 #33

 halogenation, halohydrin formation

 ‘anti’ addition
 through cyclic intermediate
 cis  threo
 trans  erythro or meso
Ch 5 #34
Summary of addition reactions Ch 5 #35

 through C+ interm
 hydrohalogenation, hydration
 regioselective to specific
 not stereoselective or specific
 through 3-membered cyclic interm
 halogenation, halohydrin, oxymercuration-reduction
 regiospecific
 stereoselective and specific (anti addition)
 concerted addition
 epoxydation, hydroboration-reduction
 regiospecific
 stereoselective and specific (syn addition)
 catalytic hydrogenation
 stereoselective and specific (syn addition)
Chiral catalyst Ch 5 #36

 enzyme ~ protein catalyst for bio-reaction

 (completely) stereoselective

S only, no R

 stereospecific

 other chiral catalyst

Chiral reagents Ch 5 #37

 enzyme

‘lock-and-key’

 receptor
 smells
 drugs