Application of virtual ligand screening methods for asymmetric, rhodium catalyzed hydrogenations of enamides

ORGN 366

Patrick J Donoghue, pdonoghu@nd.edu1, Olaf Wiest, owiest@nd.edu1, Per-Ola Norrby2, and Paul Helquist1. (1) Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, (2) Department of Chemistry, Göteborg University, Kemigården 4, SE-412 96, Göteborg, Sweden
Unnatural α-amino acids are often prepared through asymmetric Rh catalyzed hydrogenations of N-acetyl enamides. Current ligand screening processes are based on trial and error and are often expensive and time consuming. Virtual screening methods would greatly reduce the cost of the screening, in both time and money. Here we present the development of a method to virtually screen chiral bis-phosphine ligands for the Rh catalyzed hydrogenation reaction. The developed FFs are specific for the rhodium catalyzed reaction and can be rapidly applied to large virtual libraries of ligands and substrates. The FFs have been screened against experimental results from the literature using common ligands, such as DuPHOS and BINAP derived ligands. Comparison of the screening data to these data not only shows the efficacy of the method, but may also offer insights into the key enantio-determining steps in the mechanism.

 

Asymmetric Reactions and Syntheses
1:00 PM-5:00 PM, Tuesday, March 27, 2007 McCormick Place East -- Room E351, Level 3, Oral

Division of Organic Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007