title: Lewis base activation of grignard reagents with N-heterocyclic carbenes. Cu-free catalytic enantioselective additions to gamma-chloro-alpha,beta-unsaturated esters.
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 alpha-alkyl-gamma-chloro-alpha,beta-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 beta,gamma-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 approximately 30% conversion and <2% allylic alkylation in the absence of chiral carbene.
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Lee
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hoveyda
mesh_terms: D000498:Allyl Compounds / Q000138:chemical synthesis*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006838:Hydrocarbons / Q000737:chemistry; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000498:Allyl Compounds; D004952:Esters; D006571:Heterocyclic Compounds; D006838:Hydrocarbons; D006843:Hydrocarbons, Chlorinated; C030011:carbene; D003300:Copper; D008697:Methane