Catalytic Asymmetric α-Alkylation of Aldehydes with Benzhydryl Cations

Significance

Jacobsen and co-workers report the highly efficient catalytic asymmetric α-alkylation of α-branched aldehydes with benzhydryl bromides using bifunctional thiourea catalyst 3. The proposed mechanism involves the formation of an enamine intermediate from aldehyde 1 and the catalyst. Furthermore, the thiourea moiety promotes the dissociation of the alkylating agent 2 by hydrogen-bonding interactions with the bromide anion, thus bringing the two reactants in close proximity. This S_N1-type scenario is supported by several mechanistic studies, such as competition and kinetic isotope experiments.