Abstract

Enantio- and Diastereoselective Additions to Nitroalkenes via N-Sulfinyl Urea Organocatalysis

by

Kyle Lawrence Kimmel

Doctor of Philosophy in Chemistry

University of California, Berkeley

Professor Robert G. Bergman, Chair

Chapter 1. An introduction to my work with sulfinyl ureas as a new class of hydrogen-bonding catalysts is presented. The conception of this type of catalysis is discussed, and highlights in the sulfinyl urea-catalyzed additions of thioacetic acid and Meldrum's acid are presented.

Chapter 2. The sulfinyl urea-catalyzed enantioselective addition of thioacetic acid to a broad range of &beta- and cyclic &alpha,&beta-disubstituted nitroalkenes is described. This method is shown to be useful for accessing pharmaceutically relevant 1,2-aminothiol products.

Chapter 3. The enantio- and diastereoselective addition of cyclohexyl Meldrum's acid to &beta- and &alpha,&beta-disubstituted nitroalkenes is presented. This method is demonstrated to be a viable route to &gamma-amino acid derivatives with multiple stereocenters.

Chapter 4. The conjugate addition-enantioselective protonation of Meldrum's acid with terminal nitroalkenes is described. This process utilizes a sulfinyl urea catalyst that is chiral solely at the sulfinyl group. Rapid conversion of the addition products to pharmaceutically relevant &alpha,&gamma-disubstituted &gamma-lactams is demonstrated.