Divergent Reactivity of 1,2,3-Benzotriazin-4(3H)‑ones: Photocatalytic Synthesis of 3‑Substituted Isoindolinones Achieved through a Nitrogen-Mediated Hydrogen Atom Shift

A regioselective visible-light-mediated denitrogenative alkene insertion of 1,2,3-benzotriazin-4­(3H)-ones was developed to access 3-substituted isoindolinones, an important structural motif present in many biologically active molecules and natural products. Notably, divergent reactivity was achieve...

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Published in:Journal of organic chemistry 2024-02, Vol.89 (3), p.1836-1845
Main Authors: Bokosi, Fostino R. B., Shiels, Oisin J., Richardson, Christopher, Trevitt, Adam J., Keaveney, Sinead T.
Format: Article
Language:English
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Summary:A regioselective visible-light-mediated denitrogenative alkene insertion of 1,2,3-benzotriazin-4­(3H)-ones was developed to access 3-substituted isoindolinones, an important structural motif present in many biologically active molecules and natural products. Notably, divergent reactivity was achieved by switching from reported nickel catalysis (where C3-substituted 3,4-dihydroisoquinolin-1­(2H)-ones form) to photocatalysis, where photocatalytic denitrogenation and a subsequent nitrogen-mediated hydrogen atom shift lead to exclusive 3-substituted isoindolinone formation. The developed photocatalytic reaction is compatible with activated terminal alkenes and cyclic α,β-unsaturated esters and ketones, with wide functional group tolerance for N-substitution of the 1,2,3-benzotriazin-4­(3H)-ones. The utility of this procedure is highlighted by a gram-scale synthesis and postsynthetic amidation. To understand the origin of this unique product selectivity, experimental and computational mechanistic studies were performed.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.3c02545