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 their importance as biologically active compounds. Recently, Raiser and co-workers 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 developed a stereoselective strategy to synthesise enantiomerically enriched cyclobutane rings. To achieve this result, we introduced a chiral auxiliary in the scaffold of the cinnamic derivatives, a powerful tool widely used in asymmetric synthesis. The reaction, promoted by an iridium catalyst, under blue LEDs irradiation, was applied to a wide range of cinnamic esters, with differently substituted aromatic rings and afforded the products in 65-95% yield and 70-98% e.e. Moreover, the reaction was also studied and efficiently performed under continuous flow conditions, using homemade photocatalytic flow reactor.