Crams Rule

C X
*
diastereomeric
faces
X = C, O, N
stereogenic
center
How does this center control
The direction of attack at
The trigonal carbon?
R
M
S
L
O
L
R N u
O H
M
S
L
N u R
O H
M
S
Nu:
Less steric effects
Major product
Nu:
Minor product
O
M S
R
L
R
M
S
L
O
L
M
S
R
O
L
S
M
R
O
This is the important
interaction that must be
minimized. Thus, in this
approach the carbonyl
substituent plays the major
role.
Favored Conformer
for Attack
The interpretation of Felkin and Anh
Brgi-Dunitz
trajectory
109
Obtuse attack trajectory
minimizes unfavorable
interactions between these
orbitals
C O
R
M
L
S
s
p *
N u
Houk computational view:
The obtuse angle of attack supports the nonpassive role of the
R-group in ketones. Not only will there be steric interactions
between the S or M groups and the R-group, but also interactions
with the incoming nucleophile due to the attack trajectory. In this
model one would predict an increase of stereodifferentiation as the
size of R increases. This has been found experimentally
O
O
R R
Preferred conformation.
Less interaction between
the small group and the
R-group. Note that this
model "feels" the influence
of increasing size of R.
In this coformer, an
increased interaction
is seen between the
medium group and R.
Also, there is more
interaction with the
nucleophile.
A useful orbital approach by Cieplak
,
suggests that the nucleophile
will attack the carbonyl anti to the best donor ligand.
A.S. Cieplak, B.D. Yait and C.R. Johnson, J. Am. Chem. Soc., (1989), 111, 8447
A.S. Cieplak, J. Am. Chem. Soc., (1981), 103, 4548.

D o n o r
O
s
*
of nucleophile
Carbon
donor
s -bond
Nu:
E
Cases for Modification of the Models
Compare the "normal" situation with the influence of
a sterically bulky Lewis acid
L
S
M
O
H
O
H
S
M
L
Lewis acid
Nu:
As the bulk of the
Lewis acid increases
Lewis acid
:Nu
This gives the
Cram product
This gives the
"anti-Cram" product
Dipolar Model
often described as the Cornforth model

R'
R
H
Cl
R"M
R'
R
H
Cl
OH
R" O
Preferred direction
of attack.
favored conformer
S
X
L
O
R
X
L
S
O
R
Chelation Control
See: M.T. Reetz, Acc. Chem. Res., (1993), 26, 462.

R
L
S
H e t
O
M
Preferred
direction
of attack
Het = heteroatom
M = metal
L
S
H e t
O
R
M
O
Ti
O
Cl
Cl
Cl
Cl
H
Me
R
Ph
O
S
O
S
Me
Me
Me
Me
Me
Me
Ph
Ph
O
O
Mg
Me
I
MeMgI H
3
O
+
Predict a product from the following
reaction
A potentially useful extension of Cram's rule is the asymmetric
induction provided by a remote ester (Prelog's rule):
R
O
L
O
O
S
M
R'MgX
Why would you think this might not provide as
important directing influences?

Explain the following trends observed by Midland and coworkers
M.M. Midland and Y.C. Kwon, J. Am. Chem. Soc. (1983), 105, 3725.

H
M e
O
M e
H
M e
M e
O H
H
H
M e
M e
H
O H
H
H
H
N a B H
4
S i a
2
B H
G
G
5
:
1
1
:
10
Ratio