Access to 3,3‐Difluoroazetidines via Domino Amination of γ,γ‐Difluoro‐δ‐Iodo‐α,β‐Unsaturated Esters

Herein, we report the domino amination of γ,γ‐difluoro‐δ‐iodo‐α,β‐unsaturated esters with primary amines, providing synthetically and biologically important 2‐substituted‐3,3‐difluoroazetidines in good to excellent yields. Although there are two possibilities, like an aza ‐Michael reaction or an S N 2 reaction for the first amination reaction, aza ‐Michael reaction proceeds exclusively due to the low S N 2 reactivity of the C─I bond adjacent to the gem ‐difluoromethylene unit. The subsequent S N 2‐type amination by the already incorporated amine proceeds without difficulty because of its intramolecular nature, enabling cyclization under mild conditions at 30 °C.