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
