Interplay between Substrate and Proton Donor Coordination in Reductions of Carbonyls by SmI2–Water Through Proton-Coupled Electron-Transfer

The reduction of a carbonyl by SmI2–water is the first step in a range of reactions of synthetic importance. Although the reduction is often proposed to proceed through an initial stepwise electron-transfer–proton-transfer (ET-PT), recent work has shown that carbonyls and related functional groups are likely reduced though proton-coupled electron-transfer (PCET). In the present work, the reduction of an activated ester, aldehyde, a linear and cyclic ketone, and related sterically demanding carbonyls by SmI2–H2O was examined through a series of mechanistic experiments. Kinetic studies demonstrate that all substrates exhibit significant increases in the rate of reduction by SmI2 as [H2O] is increased. Under identical conditions, ketones and an aldehyde containing a methyl adjacent to the carbonyl are reduced slower than an unsubstituted variant by an order of magnitude, demonstrating the importance of substrate coordination. In the case of unactivated substrates, rates of reduction show excellent correlation with the calculated bond dissociation free energy of the O–H bond of the intermediate ketyl and the calculated free energy of intermediate ketyl radical anions derived from unhindered substrates: findings consistent with concerted PCET. Activated esters derived from methylbenzoate are likely reduced through stepwise or asynchronous PCET. Overall, this work demonstrates that the combination of the coordination of substrate and water to Sm­(II) provides a configuration uniquely suited to a coupled electron- and proton-transfer process.