Symbiotic Reagent Activation: Oppenauer Oxidation of Magnesium Alkoxides by Silylglyoxylates Triggers Second-Stage

The aldol reaction is the preeminent method for the introduction of the β-hydroxy carbonyl function, and its development has been marked by significant advances in utility to synthetic practitioners.1 The most recent chapter in this evolution is the introduction of catalysts and reagents that enable direct and selective formation of the nucleophilic enol component in the presence of the carbonyl electrophile.2 Although electrophile synthesis is not typically factored into the overall efficiency of a given aldol addition, it is instructive to consider that when the reaction is applied in complex fragment couplings, the aldolization step is often preceded by an obligatory oxidation event that provides the requisite aldehyde or ketone coupling partner. 3 A compelling argument may be advanced, therefore, that the most efficient direct aldol reaction would be one in which both the enolate nucleophile and carbonyl electrophile are simultaneously generated in situ. This communication provides the conceptual framework for such a process in the form of a symbiotic redox reaction between an alcohol and a silylglyoxylate that mutually activates both reaction components for aldolization in the second stage (eq 1). Silylglyoxylates4 1 and 5 were recently described as useful conjunctive agents for coupling alkynylzinc halides and aldehydes.5 The genesis of the current study was the observation of hydroxy-silane 6 and ynone 7 as minor byproducts in a reaction between zinc alkoxide 4 and silyl glyoxylate 5 (eq 2) that was designed to probe the mechanism of the aforementioned three-component coupling. We hypothesized that these byproducts resulted from an Oppenauer oxidation/Meerwein–Ponndorf–Verley (MPV) reduction6–8 between 4 and 5. In contrast to other nucleophiles that react with 5, the hydride transfer did not trigger [1,2]-Brook rearrangement.