Distal Amidoketone Synthesis Enabled by Dimethyl Benziodoxoles via Dual Copper/Photoredox Catalysis

Herein, we report distal amidoketone and nitrogen-functionalized ketone syntheses from alcohols and N-H nucleophiles enabled by hypervalent iodine dimethyl benziodoxoles, BIm. Dimethyl benziodoxoles BIm dually activate alcohols and various N-H nucleophiles by forming key BIm-O and BIm-N complexes in which the BIm-N complex is characterized by X-ray crystallography and computationally investigated. Readily available N-H nucleophile imides, sulfonamides, carbamates, triazoles, indazoles, and sulfoximines engage in photoredox/copper catalysis to synthesize distal amidoketones and nitrogen-functionalized ketones with excellent regioselectivity and chemoselectivity. This reaction scales up to grams, applies to late-stage complex molecule modification, and streamlines synthetic routes.

Automated summary

In this study, the synthesis of distal amidoketones and nitrogen-functionalized ketones from alcohols and N-H nucleophiles using hypervalent iodine dimethyl benziodoxoles, BIm, is reported. BIm dually activates alcohols and various N-H nucleophiles by forming key BIm-O and BIm-N complexes, which were characterized by X-ray crystallography and computational investigation. Readily available N-H nucleophiles, including imides, sulfonamides, carbamates, triazoles, indazoles, and sulfoximines, engage in photoredox/copper catalysis to synthesize distal amidoketones and nitrogen-functionalized ketones with excellent regioselectivity and chemoselectivity. This reaction can be scaled up to grams, applied to late-stage complex molecule modification, and streamline synthetic routes.