I. The synthesis of homoallylic amines via a 1,2-metalate rearrangement; II. The synthesis of bridged azabicyclic structures via ring-closing olefin metathesis
Neipp, Christopher Ernest
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A 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.