Rh(iii)-catalyzed redox-neutral C-H alkenylation of benzamides with gem-difluorohomoallylic silyl ethers via β-H elimination

Fluorinated molecules are widely used in pharmaceutical and agrochemical industries. Herein we report the synthesis of 2-(3,3-difluoro-4-(silyloxy)but-1-en-1-yl)benzamides from the unprecedented rhodium(iii)-catalyzed alkenylation of various benzamides with difluorohomoallylic silyl ethers. The practicability of this protocol is demonstrated by its broad substrate compatibility, good functional group tolerance, ready scalability and high regioselectivity. The oxygen in difluorohomoallylic silyl ethers makes beta-H elimination feasible, which suppresses both the beta-F elimination and dialkenylation of benzamides. This redox-neutral reaction proceeds efficiently via N-O bond cleavage without external oxidants and thus provides new opportunities for the synthesis of elaborate difluorinated compounds from readily available fluorinated synthons.

Automated summary

We report the synthesis of 2-(3,3-difluoro-4-(silyloxy)but-1-en-1-yl)benzamides through the unprecedented rhodium(iii)-catalyzed alkenylation of various benzamides with difluorohomoallylic silyl ethers. This protocol demonstrates broad substrate compatibility, good functional group tolerance, easy scalability and high regioselectivity. The presence of oxygen in difluorohomoallylic silyl ethers enables β-H elimination, suppressing both β-F elimination and dialkenylation of benzamides. This redox-neutral reaction proceeds efficiently via N-O bond cleavage without external oxidants and provides new opportunities for the synthesis of elaborate difluorinated compounds.