Organic Chemistry Prochirality

Lecture Outline

PROCHIRALITY
Prochiral molecules are those that can be converted from a achiral molecule to a chiral
molecule in a single step.

Prochirality may be the result of an sp2 carbon being converted to a chiral sp3 carbon via a
reaction (see Nu acyl addition below) or by substitution of a “prochiral” substituent (usually
hydrogen) with another substituent that results in a chiral center.

PRO-R and PRO-S SUBSTITUENTS

OH

Ha Hb

substitute Ha with CH3 substitute Hb with CH3

OH OH

H3C Hb Ha CH3

R-configuration S-configuration
Ha is referred to as "pro-R" Hb is referred to as "pro-S"

PROCHIRALITY IN NUCLEOPHILIC ACYL ADDITIONS

Prochiral carbonyl carbons are carbons that when reacted with a nucleophile result in the
formation of a new chiral center.
Nu: Nu
Nu

R' R' R'

O OH
O
R R R

O OH
R'
O
R R' R'
Nu Nu
Nu: R R
Organic Chemistry Prochirality
Lecture Outline

The carbonyl group has a trigonal planar geometry (sp2). The two sides of the carbonyl
group (front and back) are referred to as "faces". When the priorities of three substituents of
the carbonyl group are oriented in a clockwise fashion (highest --> lowest), front face is
called the Re face and the back face is referred to as the Si face.

Front Back
O
"Si face"
O

R R'

R R'
"Re face"

orientation of substituents is
counterclockwise
"Si face"
1
O 1
O
flip over to put in
the proper orientation
3
2
2 3

"Re face" once it is in the proper orientation, assign

Re and Si faces

Nucleophiles may attack carbonyl groups from the Re face or the Si face. The
stereochemistry of the product depends on the priorities of the substituents and the priority of
the nucleophile.
Organic Chemistry Prochirality
Lecture Outline

1
OH
O MgBr
1.
2

3 H3C
H3C
2. H+
Stereochemistry of the new chiral center is S

Nu reacts on the Re face

1
OH
O
2

3 1. NaBH4 H3C
H
H3C
2. H+
H Stereochemistry of the new chiral center is R
Nu reacts on the Re face