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

The first broadly applicable metal-free enantioselective method for boron conjugate addition (BCA) to alpha,beta-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 alpha,beta-unsaturated ketones, as well as acyclic esters, Weinreb amides, and aldehydes, can serve as suitable substrates; the desired beta-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 degrees 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).