Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage–Independent Activation of Strong C–O Bonds

Abstract

Alcohols and carboxylic acids are ubiquitous functional groups found in organic molecules that could serve as radical precursors, but C–O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen centered nucleophile. We first show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H-atom trapping to afford the deoxygenated product. Using the same method, we demonstrate access to synthetically versatile acyl radicals which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge new C–O, C–N and C–C bonds in a single step.

Radical reactions promoted by trivalent tertiary phosphines

“…25). 49 They adopted this polar/SET crossover reaction platform in the direct deoxygenation of both alcohols and carboxylic acids (Fig. 25a, 171).…”

Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage–Independent Activation of Strong C–O Bonds

“…Thus, the combination of these three elementary steps has not been exploited to effect catalytic C−O activation. 26,27…”

Photoredox Ni-Catalyzed Selective Coupling of Organic Halides and Oxalates to Esters via Alkoxycarbonyl Radical Intermediates

“…Cross coupling of fluoro-, chloro-, or iodo-substituted aryl bromides produced the corresponding products 25-29 in moderate to good yields with retention of F, Cl, and I on the aryl ring, providing additional reaction cite for further synthetic elaborations of the ester products. 109 In addition, we found that this photoredox Ni-catalyzed radical coupling reaction tolerates a variety of heteroaryl groups, including pyridine (30-32), quinoline (33 and 34), isoquinoline (35), benzothiophene (36), indole (37), 7-azaindole (38), and indazole (39). Selective coupling of the corresponding heteroaryl bromides Page 8 of 25 CCS Chemistry and hemioxalates leaded to the desired esters 30-39 in moderate to good yields.…”