Strange IndiaStrange India


Cytochrome P450 enzymes are known to catalyze bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and desaturation5,6. Developing analogous catalytic systems for remote C−H functionalization remains a significant challenge14,15,16. Here we report the development of Cu(I)-catalyzed bimodal dehydrogenation/lactonization reactions of synthetically common N-methoxyamides via radical abstractions of the γ-aliphatic C−H bonds. The feasibility of switching from dehydrogenation to lactonization has also been demonstrated by altering reaction conditions. The use of a readily available amide as both radical precursor and internal oxidant allowed for the development of a redox-neutral C−H functionalization reactions with methanol as the sole side product. These C−H functionalization reactions using Cu(I) catalyst of loading as low as 0.5 mol% have been applied to the diversification of a wide range of aliphatic acids including drug molecules and natural products. The exceptional compatibility of this catalytic system with a wide range of oxidatively sensitive functionality demonstrates the unique advantage of using simple amide substrate as the mild internal oxidant.



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