Work

Switchable Regioselective 6- endo or 5- exo Radical Cyclization via Photoredox Catalysis

Year: 2022

Type: article

Abstract: Controlling the regioselectivity of radical cyclizations to favor the 6- endo mode over its kinetically preferred 5- exo 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 N- 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- exo cyclization product. Conversely, limiting the solubility of the HAT reagent Hantzsch ester (HEH) leads to selective formation of the thermodynamically favored 6- endo product. This occurs through an initial 5- exo cyclization, with the resulting alkyl radical intermediate undergoing neophyl rearrangement to form the 6- endo product. Development of this switchable catalysis strategy allows for two modes of divergent reactivity to form either the 6- endo or 5- exo product, generating fused N- heteroaromatic/saturated ring systems.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.2c00192

Authors: Mark C. Maust, Cecilia M. Hendy, Nathan T. Jui, Simon B. Blakey

Institution: Emory University

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G3094633945, Novel Radical Reactions for C-C Bond Formation