Enolization and alkylation of b-amino esters: Solution structures, rate studies, and proposed mechanism

ORGN 305

Anne J. McNeil1, David B. Collum1, Sithamalli Chandramouli2, Benoit Vanasse2, and Timothy A. Ayers2. (1) Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853, (2) Process Development, Aventis, Rt 202/206N, Bridgewater, NJ 08807
The increasing prevalence with which a-substituted b-amino acids are incorporated into non-natural polymers and active pharmaceutical ingredients underscores the need for convenient, stereoselective syntheses. The lithium hexamethyldisilazide (LiHMDS)-mediated enolization of unprotected b-amino esters was investigated. Subsequent enolate alkylation with benzyl bromide proceeds with high diastereoselectivity. Detailed rate studies combined with low temperature 6Li and 15N NMR spectroscopic studies reveal a monomer-based alkylation pathway. The mechanistic effects of solvent, b-amino ester substituents, optical purity, and solubility will be discussed.

 

New Reactions and Methodology
8:00 AM-12:00 PM, Tuesday, September 9, 2003 Sheraton New York -- Royal Ballroom B, Oral

Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003