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.

本研究报道了以醇与N-H亲核试剂为原料，在高价碘试剂二甲基苯碘氧杂环（dimethyl benziodoxoles, BIm）介导下合成远端酰胺酮与氮官能化酮的方法。二甲基苯碘氧杂环BIm可通过形成关键的BIm-O与BIm-N配合物，对醇及多种N-H亲核试剂实现双重活化；其中BIm-N配合物已通过X射线晶体学表征，并经计算化学研究验证。以易得的N-H亲核试剂（包括酰亚胺、磺酰胺、氨基甲酸酯、三唑、吲唑与亚砜亚胺）为底物，借助光氧化还原/铜催化体系，可获得具有优异区域选择性与化学选择性的远端酰胺酮及氮官能化酮产物。该反应可放大至克级规模，适用于复杂分子的后期修饰，且能够简化合成路线。