A practical method for enantioselective synthesis of all-carbon quaternary stereogenic centers through NHC-Cu-catalyzed conjugate additions of alkyl- and arylzinc reagents to beta-substituted cyclic enones.
We present the first examples of Cu-catalyzed enantioselective conjugate additions of alkyl- and arylzinc reagents to unactivated cyclic beta-substituted enones. Transformations are promoted in the presence of 2.5-15 mol % of a readily available chiral NHC-based Cu complex, affording the desired products bearing all-carbon quaternary stereogenic centers in 67-->98% yield and in up to 97% ee. Catalytic enantioselective reactions can be carried out on a benchtop, with undistilled solvent and commercially available (not further purified) Cu salts. Mechanistic models, accounting for the observed levels and trends in enantioselectivity are provided.
Lee
Kang-sang
KS
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Brown
M Kevin
MK
Hird
Alexander W
AW
Hoveyda
Amir H
AH
D000473:Alkanes / Q000737:chemistry*; D000478:Alkylation; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D000473:Alkanes; D007659:Ketones; D009942:Organometallic Compounds; D002244:Carbon; D003300:Copper; D015032:Zinc