Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst

Abstract

Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers. Go with the flow: A flow photochemical platform with a novel cone reactor has been used to facilitate significant improvement in the [2+2] photocycloaddition of cinnamate derivatives. A bis(thiourea) has been identified that significantly increases the conversion and diastereoselectivity with a number of substrates.