1. * Cram’s Rule How does this center control The direction of attack atX
diastereomeric
faces
X = C, O, N
stereogenic
center
How does this center control
The direction of attack at
The trigonal carbon?

2. S O M L R R
Less steric effects L
Nu:
Nu: S M O L L N u R R N u S M S M O H O H
Minor product
Major product

3. The interpretation of Felkin and AnhS O M
This is the important
interaction that must be
minimized. Thus, in this
approach the carbonyl
substituent plays the major
role. L R R R S M L L M S O O
Favored Conformer
for Attack

4. Houk computational view:
Obtuse attack trajectory
minimizes unfavorable
interactions between these
orbitals N u
109°
Bürgi-Dunitz
trajectory p * R C O S M s L

5. 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

6. E 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. E
Carbon
donor s
-bond D o n r s *
of nucleophile
Nu: O

7. Cases for Modification of the Models
Compare the "normal" situation with the influence of
a sterically bulky Lewis acid
Lewis acid
Lewis acid O O M
As the bulk of the M L S
Lewis acid increases L S H H
:Nu
Nu:
This gives the
Cram product
This gives the
"anti-Cram" product

8. Dipolar Model
often described as the Cornforth model

9. R S Preferred direction of attack S L R H e t O L M H e t O
Chelation Control
See: M.T. Reetz, Acc. Chem. Res., (1993), 26, 462. R S
Preferred
direction
of attack S L R H e t O L M H e t O
Het = heteroatom
M = metal M

10. Predict a product from the following
reaction

11. A potentially useful extension of Cram's rule is the asymmetric
induction provided by a remote ester (Prelog's rule): O
R'MgX O L R O M S
Why would you think this might not provide as
important directing influences?

12. M e M e M e O H H O M e M e M e H O H H G H H H H H G Ratio N a B H 5
Explain the following trends observed by Midland and coworkers
M.M. Midland and Y.C. Kwon, J. Am. Chem. Soc. (1983), 105, 3725. M e M e M e O H H O M e M e M e H O H H G H H H H H G
Ratio N a B H 4 5 : 1 S i a 2 B H 1 : 10