Crams RuleCX*X = C, O, NHow does this center controlThe direction of attack atThe trigonal carbon?

RMSLOLRMSLRMSNu:Less steric effectsMajor productNu:Minor productOMSRL

RMSLOLMSROLSMROThe interpretation of Felkin and Anh

109CORMLSsHouk 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 interactionswith the incoming nucleophile due to the attack trajectory. In this model one would predict an increase of stereodifferentiation as thesize of R increases. This has been found experimentally

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.

ONu:E

Cases for Modification of the ModelsCompare the "normal" situation with the influence of a sterically bulky Lewis acid LSMOHOHSMLLewis acidNu:As the bulk of theLewis acid increasesLewis acid:Nu

Dipolar Modeloften described as the Cornforth model

Chelation ControlSee: M.T. Reetz, Acc. Chem. Res., (1993), 26, 462.

RLSOMLSORM

Predict a product from the followingreaction

A potentially useful extension of Cram's rule is the asymmetricinduction provided by a remote ester (Prelog's rule):ROLOOSMR'MgXWhy would you think this might not provide as important directing influences?

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

HOHHHHHHHGG5:11:10Ratio