Bridged Bicyclic gamma-Sultams by Intramolecular Flow Photochemical [2+2] Cycloaddition

Abstract

An elegant synthetic approach to the construction of a novel saturated heterocycle – 2-thia-3-azabicyclo[2.1.1]hexane 2,2-dioxide – was designed. The key step included intramolecular flow photochemical [2 + 2] cycloaddition of appropriately substituted dienes, in turn obtained from readily available starting materials on a multigram scale. Further synthetic transformations of the resulting bicyclic compounds enabled the preparation of numerous functionalized derivatives useful for early drug discovery programs as promising isosteres of pyrrolidine, pyrrolidone, and gamma-sultams, and also demonstrated tolerance of the title bicyclic system towards typical organic chemistry reaction conditions.