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

The [2+2] photocycloaddition mediated by 1-butyl-3-methyl-7,8-dimethoxyalloxazine (1) has been found to be an effective tool for cyclising omega-phenyl- and omega,omega'-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]heptanesknown 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).