Experimental and Theoretical Assessment of the Limited Viability of Alkyl Formates as Radical Precursors in Photocatalytic HAT/Decarboxylation Reactions

Abstract

Hydrogen atom transfer (HAT) is widely employed in photocatalytic radical generation, with reactivity commonly rationalized through bond dissociation energies and activation barriers. In this context, alcohol-derived formates represent attractive traceless activating groups for radical-mediated alcohol diversification via a HAT/decarboxylation sequence. Herein, combined experimental and theoretical studies were performed to evaluate the viability of alkyl formates as radical precursors under photocatalytic HAT/decarboxylation conditions. Experimentally, productive formyl-directed HAT/decarboxylation pathways could not be achieved under the investigated conditions; while competing hydrogen abstraction and substrate decomposition pathways dominated the observed reactivity. Computational analyses revealed that both thermodynamic and kinetic parameters predict the formyl C–H bond to be accessible to HAT, while decarboxylation of the model resulting methoxycarbonyl radical was found to be thermodynamically favorable and kinetically accessible. These results demonstrate that conventional descriptors such as bond dissociation energy (BDEs) and bond dissociation free energies (BDFEs) are insufficient to rationalize the observed reactivity and highlight the importance of substrate-catalyst interplay in photocatalytic HAT processes involving formate derivatives.