MEDI 149 |
| Jonathan A. Ellman, Department of Chemistry, Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720-1460 |
| We will describe two distinct methods to efficiently prepare compounds incorporating nitrogen, which represent the large majority of drugs and drug candidates. The first method is based upon enantiomerically pure tert-butanesulfinamide, which is prepared using catalytic enantioselective methods in two steps from the extremely inexpensive starting material tert-butyl disulfide. Direct condensation of tert-butanesulfinamide with aldehydes and ketones provides sulfinyl imines in uniformly high yields. A variety of transformations, such as additions of nucleophiles, may then be performed upon the sulfinyl imines in high yields and with high diastereoselectivities to provide the desired amine products after cleavage of the sulfinyl group. Additional applications of tert-butanesulfinyl imines to parallel synthesis and asymmetric catalysis will also be described. In the second method, C-H activation directed by nitrogen coordination is followed by olefin insertion to access a range of heterocycles, including complex multicyclic structures. Reaction scope, applications, and mechanistic insight will be reported. |
|
ACS Award in Industrial Chemistry Symposium
8:45 AM-12:00 PM, Monday, March 24, 2003 Convention Center -- La Nourvelle Ballroom C, Oral
Division of Medicinal Chemistry |