title: Metal-free catalytic enantioselective C-B bond formation: (pinacolato)boron conjugate additions to α,β-unsaturated ketones, esters, Weinreb amides, and aldehydes promoted by chiral N-heterocyclic carbenes.
abstract: The first broadly applicable metal-free enantioselective method for boron conjugate addition (BCA) to α,β-unsaturated carbonyls is presented. The C-B bond forming reactions are promoted in the presence of 2.5-7.5 mol % of a readily accessible C(1)-symmetric chiral imidazolinium salt, which is converted, in situ, to the catalytically active diastereo- and enantiomerically pure N-heterocyclic carbene (NHC) by the common organic base 1,8-diazabicyclo[5.4.0]undec-7-ene (dbu). In addition to the commercially available bis(pinacolato)diboron [B(2)(pin)(2)], and in contrast to reactions with the less sterically demanding achiral NHCs, the presence of MeOH is required for high efficiency. Acyclic and cyclic α,β-unsaturated ketones, as well as acyclic esters, Weinreb amides, and aldehydes, can serve as suitable substrates; the desired β-boryl carbonyls are isolated in up to 94% yield and >98:2 enantiomer ratio (er). Transformations are often carried out at ambient temperature. In certain cases, such as when the relatively less reactive unsaturated amides are used, elevated temperatures are required (50-66 °C); nonetheless, reactions remain highly enantioselective. The utility of the NHC-catalyzed method is demonstrated through comparison with the alternative Cu-catalyzed protocols; in cases involving a polyfunctional substrate, unique profiles in chemoselectivity are exhibited by the metal-free approach (e.g., conjugate addition vs reaction with an alkyne, allene, or aldehyde).
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Suttipol
authors.initials: S
authors.lastname: Radomkit
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: O'Brien
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hoveyda
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D001895:Boron / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D004952:Esters; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000447:Aldehydes; D000577:Amides; D004952:Esters; D006571:Heterocyclic Compounds; D007659:Ketones; C030011:carbene; D003300:Copper; D001895:Boron; D008697:Methane