Making the Cut: Towards Photocatalytic Diol Cleavage via Proton Coupled Electron Transfer

Abstract

Through the successful realization of O–H homolysis via the proton coupled electron transfer (PCET) mechanism reported by the Knowles group, it has been demonstrated that PCET is a powerful tool for accessing alkoxy radicals that traditionally required harsh conditions, and for further enabling new reaction pathways directed by hydroxyl groups. An interesting synthetic application of the alkoxy radicals thus generated is the redox-neutral cleavage of 1,2-diols into carbonyl-containing and hydroxyl- containing products. Traditional methods for this transformation have used periodic acid or lead acetate, which are less desirable because of their reagent choices and the fact that the net-oxidative reaction results in chemically similar carbonyl groups in the products. With the mild, catalytic O–H PCET approach, we can access products that have differentiated functional groups at the cleavage locations. Herein, I investigate the methods previously developed within the Knowles lab to discover new possibilities in photocatalytic 1,2-diol cleavage. These protocols rely on an iridium-based photocatalyst and a phosphate base to abstract a hydrogen atom from one of the alcohol O–H groups, promoting beta- scission, and employ a thiol co-catalyst to reduce of the resultant alkyl radical, achieving a net redox-neutral reaction. Using cis- and trans-1,2-cyclooctanediols as the model substrates for reaction optimizations, I tested thiols, solvents, and additives to find an optimal condition that formed the basis for the exploration of the substrate scope. I was able to further improve the efficiency of the protocols for the photocatalytic PCET-enabled cleavage of these 1,2-diol compounds.