Flavin‐Mediated Visible‐Light [2+2] Photocycloaddition of Nitrogen‐ and Sulfur‐Containing Dienes

Abstract

The [2+2] photocycloaddition mediated by 1‐butyl‐3‐methyl‐7,8‐dimethoxyalloxazine ( 1 ) has been found to be an effective tool for cyclising ω‐phenyl‐ and ω,ω′‐diphenyl‐4‐aza‐1,6‐heptadienes, in which the nitrogen atom is protected by acylation or quaternisation, towards the synthesis of a variety of phenyl‐ and diphenyl‐3‐azabicyclo[3.2.0]heptanes and their corresponding quaternary salts. Thia derivatives, with the sulfur atom in the form of a sulfone group, underwent an analogous cyclisation. Advantageously, visible light (400 nm) was used for the cycloadditions in the presence of 1 , in contrast to the previously described procedures affording azabicyclo[3.2.0]heptanes by using UV irradiation. Practical applications are demonstrated through the synthesis of bicyclic quaternary ammonium salts, 6‐phenyl‐azabicyclo[3.2.0]heptanes known to exhibit biological activity or chiral spiro ammonium salts. Flavin 1 was also found to promote the efficient E → Z isomerisation of electron‐rich cinnamyl derivatives to produce mixtures enriched with the Z isomer (with Z/E ratios of up to 77:23).