Chemoselective Reduction of Barbiturates by Photochemically Excited Flavin Catalysts

Abstract

Photocatalytic reductive cyclizations are powerful methods for obtaining structurally complex molecules. Achieving non-inherent reactivity in substrates with more than one potential site of reduction is a difficult challenge. We disclose the use of flavin catalysis for the chemoselective, reductive cyclization of barbiturates with additional reactive functional groups. Our method provides orthogonal selectivity in comparison to the well-established reductant samarium(II) iodide, which preferentially reduces substrate ketone groups. Flavin catalysis first leads to barbiturate reduction and allows a complete change of chemoselectivity in barbiturates with appended ketones. Additionally, flavin photocatalysis enables the reductive cyclization of substrates with appended oxime ethers in >99% yield, which is not possible with SmI2.