Radical Cation Diels--Alder Cycloaddition Reactions By Visible Light Photocatalysis

Electronically mismatched Diels-Alder reactions have always been a challenge to perform under mild conditions, since conventional Diels-Alder cycloadditions typically involve an electron deficient dienophile and an electron rich diene. Given the synthetic utility of electronically mismatched Diels-Alder cycloadducts, which are ubiquitously found in numerous biologically useful natural products, the research herein describes an efficient way to synthesize these cycloadducts via visible light photocatalysis. Using ruthenium polypyridyl complexes as photocatalysts, mechanistically distinct pathways for the intra- as well as intermolecular cycloaddition reactions have been developed. Our understanding of the reaction systems enabled the design of a cleavable redox auxilliary that allows efficient access to simple unfunctionalized cyclohexene adducts. The synthetic utility of the method has been illustrated in the first reported biomimetic synthesis of the natural product heitziamide A. As such, this novel methodology enables easy access towards synthetically useful cycloadducts which would otherwise be difficult or impossible.