Intramolecular [2+2] Cycloaddition of N-Allylcinnamamines and N-Allylcinnamamides by Visible-Light Photocatalysis

The visible light-promoted intramolecular [2+2] cycloaddition of N-allylcinnamamines and N-allylcinnamamides in the presence of catalytic amounts of [Ir{dF(CF3)ppy}(2)(dtbpy)]PF6 is reported. Low energy visible light and a high triplet energy iridium-photosensitizer were efficient at promoting the cycloaddition reaction of N-allylcinnamamides and N-allylcinnamamines to the corresponding aryl-3-azabicyclo[3.2.0]heptanones and aryl-3-azabicyclo[3.2.0]heptanes, respectively, with high diastereoselectivity and under mild conditions. Azabicyclic fused rings have been employed as surrogates for piperidine motifs in drug discovery. Functional groups useful for deployment and/or elaboration in drug discovery campaigns were all shown to be tolerated, including halides, CF3, cyanide, ester, acetamide, acetate, CH3O, pyridyl, furan, carbamate, tosyl, benzyl, and benzoate.