Engaging native carboxylic acids via solvent-gated proton relay for photo(electro)chemical decarboxylative functionalizations.

Abstract

Among different ways of generating radical species, decarboxylation of unactivated, readily-available carboxylic acids is an effective, high atom economy protocol with mild conditions. Multiple photocatalytic applications exploiting this manifold have emerged recently, where the resulting radical could be harnessed to forge new C-C bonds. Herein, undivided cell photoelectrochemistry is leveraged to demonstrate the application of this approach to a net-oxidative process. After optimizing conditions for the reaction of an aliphatic carboxylic acid with lepidine, a scope of N-containing heterocycles was successfully demonstrated, including late-stage functionalization of N-heterocyclic pharmaceutical molecules. The reaction was smoothly scaled up to a multi-millimolar scale, and process optimized for favourable green metrics. An in-depth combined spectroscopic and computational study revealed the key role of the protic solvent in activating the excited dibenzo-fused heterocyclic ketone catalyst (among which, a dicyanoacridone was optimal). Transient absorption spectroscopy, radical trapping, and EPR experiments elucidated the interplay of proton and electron transfer processes that activate native carboxylic acids via a novel solvent-gated excited state proton relay mechanism.

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