Enantioselective synthesis of boron-substituted quaternary carbons by NHC-Cu-catalyzed boronate conjugate additions to unsaturated carboxylic esters, ketones, or thioesters.
A Cu-catalyzed method for enantioselective boronate conjugate additions to trisubstituted alkenes of acyclic alpha,beta-unsaturated carboxylic esters, ketones, and thioesters is disclosed. All transformations are promoted by 5 mol % of a chiral monodentate NHC-Cu complex, derived from a readily available C(1)-symmetric imidazolinium salt, and in the presence of commercially available bis(pinacolato)diboron. Reactions are efficient (typically, 60% to >98% yield after purification) and deliver the desired beta-boryl carbonyls in up to >98:2 enantiomer ratio (er). Processes involving unsaturated thioesters proceed with higher enantioselectivity (vs carboxylic esters or ketones), and the resulting products can be functionalized by Ag-mediated or Pd-catalyzed reactions that furnish the derived carboxylic ester or various ketones. Routine oxidation affords beta-hydroxy ketones or carboxylic esters, ketone aldol products that cannot be otherwise prepared efficiently by an alternative catalytic enantioselective protocol.
O'Brien
Jeannette M
JM
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Lee
Kang-sang
KS
Hoveyda
Amir H
AH
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001896:Boron Compounds; D004952:Esters; D006571:Heterocyclic Compounds; D007659:Ketones; D013438:Sulfhydryl Compounds; C030011:carbene; D003300:Copper; D008697:Methane