Selective C(sp3)-C(sp3) Cleavage/Alkynylation of Cycloalkylamides Enables Aminoalkyne Synthesis with Hypervalent Iodine Reagents

Here, we report the selective C(sp(3))-C(sp(3)) cleavage/alkynylation of cycloalkylamides for the aminoalkyne synthesis under mild photoredox catalysis conditions. gamma- and delta-Aminoalkynes with versatile alkyne and amine substituents are efficiently constructed from cyclopropylamides and cyclobutylamides via amidyl radicals enabled by hypervalent iodine(III) reagents. The catalytic amount of cyclic iodine(III) BI'-OAc facilitated the single-electron oxidation and ring-opening alkynylation of cycloalkylamides, which were investigated by a series of mechanistic probing experiments. Various alpha-amino substitutions from the oxygen, sulfur, or carbon nucleophile trapping can be performed in gram scale, and the aminoalkyne products easily derivatize to indolizidines, presenting in versatile bioactive fused azacycles.

Automated summary

A selective C(sp(3))-C(sp(3)) cleavage/alkynylation of cycloalkylamides for aminoalkyne synthesis was reported under mild photoredox catalysis. γ- and δ-Aminoalkynes with diverse alkyne and amine substituents were efficiently constructed via amidyl radicals enabled by hypervalent iodine(III) reagents. Catalytic cyclic iodine(III) BI'-OAc facilitated the single-electron oxidation and ring-opening alkynylation of cycloalkylamides.