Switchable Regioselective 6- or 5- Radical Cyclization via Photoredox Catalysis.

Controlling the regioselectivity of radical cyclizations to favor the 6- mode over its kinetically preferred 5- counterpart is difficult without introducing substrate prefunctionalization. To address this challenge, we have developed a simple method for reagent controlled regioselective radical cyclization of halogenated heterocycles onto pendant olefins. Radical generation occurs under mild photoredox conditions with control of the regioselectivity governed by the rate of hydrogen atom transfer (HAT). Utilizing a polarity-matched thiol-based HAT agent promotes the highly selective formation of the 5- cyclization product. Conversely, limiting the solubility of the HAT reagent Hantzsch ester (HEH) leads to selective formation of the thermodynamically favored 6- product. This occurs through an initial 5- cyclization, with the resulting alkyl radical intermediate undergoing neophyl rearrangement to form the 6- product. Development of this switchable catalysis strategy allows for two modes of divergent reactivity to form either the 6- or 5- product, generating fused heteroaromatic/saturated ring systems.