3,3-Disubstituted oxetanes have garnered considerable interest as isosteres of carbonyl groups and as new design elements for medicinal chemists. Despite their popularity, methods to access 3,3-disubstituted oxetanes are scarce, particularly for 3,3-dicarbon substitutions. Photoredox catalysis has emerged as a powerful method to forge challenging chemical connections, especially for carbon-carbon bond formation. Recently, access to oxetane and azetidine carboxylic acids was enabled through a short Friedel–Crafts/Furan oxidative cleavage sequence from the corresponding alcohols. Carboxylic acids are amongst the most popular precursors that under visible light and photocatalysts, can generate carbon-centered radicals upon decarboxylation under mild conditions. However, benzylic radicals—especially tertiary examples—remain underinvestigated due to their high steric demand around the reactive center and stabilized nature of the radical, which lead to low rate constants in intermolecular reactions.<br/><br/>This poster will describe the generation of unusual tertiary benzylic strained oxetane and azetidine radicals from 3-aryl-3-carboxylic acid oxetane and azetidine precursors under photoredox catalysis. The oxetane/azetidine radicals are reacted with activated alkenes to generate medicinally-relevant 3-aryl-3-alkyl substituted derivatives. The process is reproducible, easy to set up and insensitive to common deviations of the conditions. The reaction was showcased through the synthesis of 33 examples of oxetanes and azetidines including challenging sensitive polar functionalities and heterocycles. Notably, compared to other benzylic radicals (e.g. cyclobutane), oxetanes and azetidines showed a unique preference for the productive reaction pathway.

Visible light photoredox-catalyzed decarboxylative alkylation of 3-aryl-oxetanes and azetidines via benzylic tertiary radicals

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ACS Fall 2022

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