Asymmetric α-Alkylation With Activated and Unactivated Electrophiles by a Highly Productive and Recyclable Lewis...

Asymmetric alkylation is widely used for the construction of α-stereogenic carbonyl compounds, yet existing catalytic protocols typically suffer from several issues: (1) a limitation to π-activated electrophiles, (2) the need for unsatisfying catalyst loadings, (3) a lack of catalyst recyclability, and (4) sophisticated catalyst structures requiring multi-step syntheses. Herein, an efficiently accessible, air-stable bifunctional Cu(II)/imidazolium catalyst (prepared over four steps without chromatographies in 74% yield) is reported that enables highly enantioselective α-alkylations of 1,3-dicarbonyls with unmet productivity (TON up to 1740). The catalyst exhibits broad electrophile compatibility, efficiently engaging π-activated and non-π-activated alkylation agents. Remarkably, stereoretentive allylation with (E)- and (Z)-configured allylbromides was achieved. The catalyst can be recycled over multiple cycles (10+) without loss of efficiency by a simple protocol. EPR proves formation of a Cu(II)-enolate as resting state, for which detailed DFT calculations show that it is structurally anchored by hydrogen-bonding to the imidazolium C(2)H. This feature is essential for stereodifferentiation of both enolate faces. A continuous mechanistic shift from S_N1-like to S_N2-type pathways is likely, depending on the electronic properties of the electrophile. This new alkylation concept allows for high practicality, combined with broad applicability and might serve as design prototype for future alkylation catalysts.