Construction of fully substituted stereocenters: Alkylation followed by reductive lithiation and cyclization of unsaturated α-aminonitriles

ORGN 26

Robert Joseph Bahde, rbahde@uci.edu and Scott D. Rychnovsky, srychnov@uci.edu. Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II, Irvine, CA 92697
Cyclizations were achieved through intramolecular carbolithiations of tertiary α-amino organolithiums onto append alkenes. The highly reactive organolithiums were generated by reductive decyanation of α-aminonitriles with lithium di-tert-butylbiphenylide (LiDBB). Nitrile alkylation was utilized to assemble both cyclic and acyclic α-aminonitrile substrates. Tertiary α-amino organolithium reagents generated from N-benzyl-2-cyanopiperidines successfully underwent spiroannulation to generate [5,4] spirocycles with high diastereoselectivity. Transition state models are proposed to rationalize the observed stereoselectivity. This investigation provides a route for synthesizing complex spirocyclic alkaloids. Intramolecular cyclization of acyclic tertiary α-amino organolithiums was also examined.

 

New Reactions and Methodology
8:00 AM-12:00 PM, Sunday, April 6, 2008 Morial Convention Center -- Rm. R04, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008