Formation and reductive ring opening reactions of indolyl bicyclic-isoxazolidines-II:7 access to novel natural product analogs

Abstract

Attempted reductive cleavage of indolyl-bicyclic-isoxazolidines (4a,b; R=benzyl, phenyl) with ammonium formate, methanol-THF solvents, at ambient temperature, in the presence of Pd/C lead to facile synthesis of indolyl-α-hydroxy-γ-lactams (5a–b), derived from reductive cleavage of the NO bond of bicyclic-isoxazolidines, followed by intramolecular recyclization. On the other hand, reaction of 4c (R=ethyl) under identical conditions follows a different course affording 6, an analogue of naturally occurring marine alkaloid, aplysinopsin. A mechanistic rationale of observed reactivity behavior, supported by DFT calculations, is provided.