Synthesis of Bridged Tetrahydrobenzo[b]azepines and Derivatives through an Aza-Piancatelli Cyclization/Michael Addition Sequence

Abstract

Herein, we report the preparation of bridged tetrahydrobenzo[b]azepines, which was accomplished through an aza-Piancatelli cyclization/Michael addition sequence in a one-pot fashion from readily available precursors. It is noteworthy that a general method to access these scaffolds was hitherto unprecedented. Additionally, the multifaceted aspects of this process have been exemplified through its application to the synthesis of 2-azabicyclo[3.2.1]octanes and bridged tetrahydrobenzo[b]oxepines, along with post-derivatizations.

Keywords: Lewis acid; electrocyclization; hexafluoroisopropanol; medium-size N-heterocycles; tetrahydrobenzo[b]azepines.