Syntheses and reactions of a new series of twisted lactams

ORGN 527

Lei Yao, thundery@ku.edu, Aaron D. Wrobleski, adw@ku.edu, Jennifer E. Golden, and Jeffrey Aubé, jaube@ku.edu. Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Room 4070, Malott Hall, Lawrence, KS 66045
Twisted amides, in which the amide bond deviates significantly from the planar conformation, are of interest from both a structural and reactivity perspective. Such amides are viewed as unstable and typically undergo reactions that are more commonly associated with ketones than amides. These features have been ascribed to the loss of the conjugation between the amide nitrogen and the C=O π bond. We reported a new series of stable twisted amides that have been synthesized using the intramolecular Schmidt reaction. The features that influence the relative amounts of twisted versus standard lactams will be discussed. It has also been shown that these twisted amides undergo facile regioselective C-N bond cleavage reactions under several kinds of conditions (H2/Pd(OH)2, DDQ, and MeI). Theses results, along with a discussion of the hydrolytic stability of the lactams toward hydrolysis, will be discussed.