I. The synthesis of homoallylic amines via a 1,2-metalate rearrangement; II. The synthesis of bridged azabicyclic structures via ring-closing olefin metathesis
textA convergent, stereoselective route to homoallylic sulfonamides has been
described. Homoallylic sulfonamides with di- and trisubstituted double bonds were
prepared in good yields and with excellent control of alkene geometry via a cuprateinduced
1,2-metalate rearrangement of α-lithiated N-trisyl 2-pyrroline. Removal of
the N-trisyl group was achieved by sonication of the sulfonamides in the presence of
Li(0) wire and catalytic di-tert-butylbiphenyl. The utility of this method was
illustrated by its application toward the synthesis of a squalene synthetase inhibitor.
In other efforts, a versatile approach to bridged azabicyclic structures was
developed. This process involved the ring-closing metathesis (RCM) of cis-2,6-
dialkenyl N-acyl piperidines, which were prepared in six steps from glutarimide or in
three steps from 4-methoxypyridine. The N-acyl protecting group of these
piperidines played a crucial role in this sequence by stabilization of the C2,C6 bisaxial
conformers necessary for their RCM. In this manner, a diverse array of bridged
azabicyclic structures were obtained in excellent yields. Application of this RCM
strategy toward the synthesis of (±)-cocaine and compounds structurally related to
vellosimine has been reported.Chemistr