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

Abstract

Despite the prevalence of alcohols and carboxylic acids as functional groups in organic molecules and the potential to serve as radical precursors, 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 show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H atom trapping to afford the deoxygenated products. 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 C−O, C−N, and C−C bonds in a single step.

Deoxygenative Arylation of Carboxylic Acids by Aryl Migration

“…In 2018, our group [5] and Doyle et al [6] have independently developed photoredox phosphoranyl radical chemistry for redox-potential independent deoxygenation of carboxylic acids. This affords ap romising route for the construction of aryl-alkyl ketones and aldehydes directly from carboxylic acids.…”

Upgrading ketone synthesis direct from carboxylic acids and organohalides

“…Subsequently, we studied the substrate scope of aromatic bromides (Fig. 5) and found that many commercially available aromatic bromides can be used to deliver the desired ketones (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) in good yields. The excellent functional group tolerance of -COOR (28,33,44,45), -CN (29, 34), terminal unsaturated chemical bonds (43,44), and heteroarenes (38)(39)(40)(41)(42)(43)46) support the practicality of the reaction.…”

“…This could simplify and upgrade ketone synthesis from carboxylic acids and organic halides 13 . Very recently, our group and Doyle et al reported an elegant photoredoxpromoted mild deoxygenation of carboxylic acids generating acyl radicals [31][32][33][34][35] . Since photoredox and nickel-catalyzed C-O bond formation between carboxylic acids and aromatic bromides has been reported 36 to achieve the desired crosselectrophile coupling, acyl radical oxidative addition by a metallaphotoredox pathway [37][38][39][40][41] is essential to suppress the C-O bond formation (Fig.…”

Alkylation of Allyl/Alkenyl Sulfones by Deoxygenation of Alkoxyl Radicals

“…[14] Doyle disclosedanovel deoxygenative hydrogenation of benzylic alcohols by phosphine radical cation (Scheme 1, III). [15] Encouraged by these reports and other studies, [13,17] we envisioned that phosphine would complete such ap rocess due to strong PÀOb ond strength (148 kcal mol À1 for P(O)(OEt) 3 ). [18] Herein, we wish to report a novel deoxygenative alkylation of allyl/alkenyl sulfones from readily accessible N-alkoxyphthalimidesu nder visible light (Scheme 1, IV).…”