Stereoselective [2+2] photocycloaddition: a viable strategy for the synthesis of enantiopure cyclobutane derivatives

The synthesis of cyclobutanes has always attracted the attention of chemists, due to their presence in natural products and importance as biologically active compounds. In the last decade, the development of photochemistry opened new routes for the 4-member carbon ring assembly. Among others, recently, Raiser and co-worker showed that starting from a cinnamic ester is possible to obtain the corresponding cyclized products in high yields. Based on this seminal work, we have decided to develop a stereoselective strategy to synthesize enantiomerically enriched cyclobutane rings. To achieve this result, we introduced in the scaffold of the cinnamic derivatives a chiral auxiliary, a powerful tool widely used in asymmetric synthesis. The reaction, promoted by an iridium catalyst, under blue LEDs irradiation, of a wide range of cinnamic esters, with differently substituted aromatic rings was investigated, affording the products in 65-95% yield and, after chiral auxiliary removal, 70-98% e.e.. Moreover, the reaction was also performed under continuous flow conditions.