Computational study of the enantioselective deprotonation of a cyclopropanecarboxamide with an alkyllithium in the presence of sparteine.
The enantioselective deprotonation of N,N-diisopropy-1-methylcyclopropanecarboxamide (2) with i-PrLi-(-)-sparteine has been studied at theoretical levels up through B3LYP/6-311+G*. Thirty-six conformationally flexible intermediate complexes involving i-PrLi-(-)-sparteine and 2 were located via geometry optimizations The lowest energy complex would lead to abstraction of the pro-S hydrogen from 2, and several higher energy complexes would lead to loss of the pro-R hydrogen. The lowest energy complex was found to have the lowest activation energy leading to loss of the pro-S hydrogen of 2 as observed experimentally. The results demonstrate that the conformations of the N,N-diisopropyl groups in the amide moiety of 2 have a large effect on the enantioselectivity of the lithiation.
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States. kenneth.wiberg@yale.edu
Kenneth B
KB
Wiberg
William F
WF
Bailey