Stereo Notes

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

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Chapter 5

Chirality and isomers

geometric isomers (optical isomers)

 chiral object or molecule has

 achiral object or molecule has plane of symmetry

 chiral? achiral? Find

 atom bonded to 4 different groups

 stereocenter and asymmetric center

1. Find the asymmetric center.

 R,S in Fischer projection

 For an enantiomeric pair:

 Chiral compounds are optically active, and rotate plane-

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

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

 Diastereomers are stereoisomers that are not enantiomers.

 erythro ~ similar group on the same side

H3C CH3 H3C CH3 H3C CH3 H3C CH3

2 C*’s, only 3 stereoisomers

 meso compound [meso-stereoisomer]

Still, achiral and meso

absolute config also the same

absolute config changed

 relative config may change  breaking bond to C*

 difficult, tedious, and costly

(2) selectively reacting one enantiomer with

 other tetrahedral comp’ds

 rings perpendicular ~ no plane of symmetry

 eg, Markovnikov addition

 moderately, highly, completely

 All stereospecific reactions are stereoselective. Not vice versa.

 RR, RS, SS, SR

 cis-isomer  erythro enantiomers

 symmetric cis  meso compound

 trans-isomer  threo enantiomers

 cycloalkenes  cis or meso

 halogenation, halohydrin formation

 enzyme ~ protein catalyst for bio-reaction

 other chiral catalyst

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