Lewis Base Activation of Grignard Reagents with N-Heterocyclic Carbenes. Cu-Free Catalytic Enantioselective Additions to γ-Chloro-α,β-Unsaturated Esters

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Abstract
Direct activation of alkylmagnesium halides with a chiral bidentate N-hetrocyclic carbene (NHC), formed in situ from the imidazolinium chloride precursor, is reported. The Cu-free catalytic asymmetric allylic alkylation (AAA) of α-alkyl-γ-chloro-α,β-unsaturated esters with alkyl-based Grignard reagents is promoted in the presence of 5−10 mol % of the chiral imidazolinium salt to afford synthetically versatile β,γ-unsaturated esters. Products bear all-carbon quaternary sterogenic centers generated in 3.5−13.3:1 regioselectivity, 63−98% ee, and in up to 80% isolated yield of the SN2‘ product. The in-situ-generated chiral NHC promotes enantioselectivity while altering the reactivity of the Grignard reagents: there is only ∼30% conversion and <2% allylic alkylation in the absence of chiral carbene.