PROCHIRALITY
Prochirality
Prochirality
Pro prochiral Prochiral Chiral
Prochiral centre
Nicotinamide adenine dinucleotide (NADH)
Homomorphic groups/ligands/atoms
■ Homomorphic ligands are indistinguishable when considered in isolation
■ Examples
– Two hydrogen atoms or two bromine atoms
– Groups must have same constitution and configuration
– two methyl or phenyl groups
– Two secondary butyl groups of same chirality (R/S)
Topicity
■ Describes geometrical or stereochemical relationships between
homomorphic atoms/groups/ligands in a molecule
Homotopic ligands
Stereoheterotopic ligands
Enantiotopic ligands Diastereotopic ligands
How to determine topicity of ligands?
Two methods
Symmetry criterion Addition/substitution criterion
Homotopic ligands
Homomorphic ligands in identical environment:
Addition/substitution criterion
Same molecule
Homotopic ligands
Symmetry criterion
Homorphic ligands are homotopic if they can interchange their positions by rotation
about a simple axis
CH2Cl2, CHCl3,
Homotopic ligands
Symmetry criterion
Homotopic ligands
Addition/substitution criterion
Homotopic ligands
Addition/substitution criterion
Homotopic faces
Two faces of a double bond are homotopic if addition to either face generates
identical molecule
Homotopic faces
Ethylene has homotopic faces
Stereoheterotopic ligands/faces ligands
The spatial relation of homomorphic ligands with the rest of molecule is different,
they are termed as stereoheterotopic
Enantiotopic ligands/faces
Symmetry criterion
Enantiotopic ligands /faces are interchangeable by σ plane, centre of symmetry or
alternating axis of symmetry, but cannot be interchanged by simple axis of rotation
Enantiotopic ligands/faces
Symmetry criterion
Enantiotopic Homotopic Enantiotopic
Enantiotopic ligands
Substitution-addition criteria
??
Enantiotopic ligands
Pro-R and Pro-S
Pro-R
Pro-S
Enantiotopic faces
Diastereotopic ligands/faces
Diastereotopic ligands/faces
Diastereotopic ligands/faces
Stereochemistry of chemical reactions
Stereochemistry of Addition Reactions
Stereochemistry of bromine addition
Stereochemistry of bromine addition
Anti-addition
Stereochemistry of bromine addition
Syn-addition
Stereochemistry of hydrogenation reaction
Syn-addition
Conformational Isomerism
Conformational isomerism
Open chain alkane conformations: Staggered, eclipsed, and gauche conformers.
Conformational isomerism
Chair and boat conformers in cyclic molecules.
Conformational isomerism
Atropisomerism: A molecule can become chiral due to restricted rotation about a
bond.
Dihedral angle
The angle created by two intersecting planes.
Stability of conformers
Angle strain
The increase in potential energy of a molecule due to bond angles deviating from
the ideal values
Torsional strain
Torsional strain or eclipsing strain is the increase in potential energy of a molecule
due to repulsion between electrons in bonds that do not share an atom
Steric strain
Repulsive interactions between non-bonded atoms in close proximity
Conformations of ethane
Conformations of butane
Conformations of butane
Stability of confomers
Gauche conformation is more favored over anti conformation
Cyclopropane
Cyclobutane and cyclopentane
Cyclohexane
Chair conformation
Boat conformation
Drawing Cyclohexane in chair conformation
Cyclohexane:
• Chair conformation (all bonds staggered)
• Rapid interconversion at 25 °C (Ea = 10 kcal/mol, 20 kcal/mol available at 25 °C).
• Hax and Heq are indistinguishable by 1H NMR at 25 °C.
• At temperatures < –70 °C, Heq and Hax become distinct in 1H NMR.
Cyclohexane:
Newman projection of chair conformation
Cyclohexane:
Cyclohexane:
Cyclohexane:
Mono-substituted cyclohexanes:
Mono-substituted cyclohexanes:
Stability of substituted cyclohexanes: A value
A Value (–ΔG°) = Free energy difference between equatorial and axial substituent on a
cyclohexane ring.
Stability of substituted cyclohexanes: A value
Stability of substituted cyclohexanes: A value
❑ The chair conformation of cyclohexane is the most stable conformation and
derivatives of cyclohexane almost always exist in the chair conformation
❑ Mono substitute cyclohexane preferred to stay at equatorial position
Stability of substituted cyclohexanes
[Link]
Stability of substituted cyclohexanes
[Link]
Stability of substituted cyclohexanes
40% 60%
cis -trans Isomers in 1,2-disubstituted cyclic alkanes
H H CH3 H
CH3 CH3 H CH3
cis-1,2-dimethylcyclohexane trans-1,2-dimethylcyclohexane
cis -trans Isomers in 1,2-disubstituted cyclic alkanes
H CH3 H H
H H
H H
H H H
CH3 H H
CH3
H
H
H
H
H
H
CH3
√
H CH3 H H
H CH3
trans-1,2-dimethylcyclohexane a, a e, e
H H H
H CH3 H
H H
H H H CH3
H H H H
CH3 H
H H
H H
CH3 CH3 H
a, e
H
√
H
e, a
CH3
√
cis-1,2-dimethylcyclohexane
cis -trans Isomers in 1,3-disubstituted cyclic alkanes
H CH3 H H
CH3 H H
H CH3
H H H CH3
H H H
H H
H H H
H
√ √
CH3
H H H
CH3 H
trans-1,3-dimethylcyclohexane a, e e, a
H H H
CH3
CH3 H H
CH3 H
H H H CH3
CH3 H H
H H
H H H
H CH3
H H
a, a
H H
e, e
H
√
cis-1,2-dimethylcyclohexane
cis -trans Isomers in 1,4-disubstituted cyclic alkanes
H CH3 H H
H CH3 H H
H H
H H H CH3
H H3C
CH3 H
H
H
H
H
H
H
√
CH3 H H H
trans-1,4-dimethylcyclohexane
a, a e, e
H H H
CH3 H
H3 C CH3 H
H H
H H H CH3
H3C H
H H
H H H H
H H
cis-1,4-dimethylcyclohexane
H
a, e
H
√
CH3
e, a
H
√
cis-1-tert-Butyl-3-Methylcyclohexane
CH3
H3C
H C CH3 H H
H H CH3
CH3 H
H H H C
CH3
H H
H H CH3
H H
H CH3
H H H
e, e
H
√
a, a
Q. Consider the molecule below. What is the maximum number of
methyl groups that can be in the equatorial position at the same
time?
A. 0
B. 1
C. 2
D. 3
E. 4
trans-1-chloro-2-methylcyclohexane
Up–down relationship is unaffected by the chair interconversion
Cis-1-chloro-2-methylcyclohexane
Up–down relationship is unaffected by the chair interconversion
Ester hydrolysis
COOMe
COOMe
Vs
Ktrans
= 20
Kcis
Ester hydrolysis
OR OR OH
H O H O- OH H O
H H H
OH-
H H H
H
OH H
H
O O- O
OH-
OR OR OH
Elimination reactions
Elimination reactions
Elimination reactions
OH NaNO2/HCl
NH2
OH
Ph
H+
OH
Ph
N