Bibenzyl is the key motif found in dihydrostilbenoid natural products, such as combretastatin. Conventional approaches to the synthesis of bibenzyls carry limited utility, due to the requirement of very strong reductants. One promising alternative to the existing methods is coupling of photocatalytically generated free benzyl radicals. Our catalytic protocol employs the Hantzsch ester (HEH) as a two-electron donor, potassium phosphate (K3PO4) as a redox-innocent Brønsted base, and [Ir(ppy)2(dtbbpy)]PF6 (ppy = 2-phenylpyridinate, dtbbpy = 4,4'-di(tert-butyl)-2,2'-bipyridine) as a photocatalyst. Blue LEDs photoirradiation of the reaction mixture furnished the desired bibenzyl products in high yields. The photoredox catalysis exhibits broad functional group tolerance. Synthetic utility of our protocol was further demonstrated by the preparation of a natural dihydrostilbenoid, brittonin A. Mechanistic study has been performed by employing photoinduced EPR, photophysical, and electrochemical techniques, as well as quantum chemical calculations. Our investigations establish the catalytic sequences which involve reductive quenching of the photoexcited catalyst by one-electron transfer from HEH, followed by subsequent electron transfer from the one-electron-reduced catalyst to benzyl bromide. The reduced benzyl bromide undergoes cleavage of the C-Br bond to generate the benzyl radical intermediate. Of interest is the presence of an additional electron-transfer pathway from the one-electron oxidized HEH to benzyl bromide after deprotonation by K3PO4. The occurrence of sequential two-electron reduction is evidenced by a Job plot analysis. Our mechanistic investigations collectively suggest that the catalysis cycle involves one-photon-induced two-electron mediation. We believe that the catalysis with improved photon economy will be valuable for a range of radical-mediated organic transformations.

Mechanism of the photoredox catalytic radical coupling of benzyl bromides

253rd National Meeting (2017)

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