title: Optimization of Reaction and Substrate Activation in the Stereoselective Cross-Coupling of Chiral 3,3-Diboronyl Amides.
abstract: A method has been developed for the chemo- and stereoselective Suzuki-Miyaura cross-coupling of optically enriched gem-diboronyl compounds with various aryl bromides. Experimental evidence suggests that the Lewis acidity of the second boron group in these substrates plays a significant role in facilitating these otherwise challenging cross-coupling processes. β-Diboronyl esters may be successfully cross-coupled in excellent yield and enantiomeric excess with prior conversion of the pinacol boronate to the corresponding trifluoroborate salt. In contrast, a substrate bearing a Weinreb amide can undergo direct coupling of the Bpin moiety, likely due to the stronger coordination of the more basic amide carbonyl group. The resulting optically enriched secondary boronate may be used in a second enantioselective cross-coupling to afford pharmaceutically relevant diarylmethane products. The use of a Weinreb amide substrate allows for facile postcoupling modification, as demonstrated by a transformation to the corresponding ketone.
authors.affiliation: Department of Chemistry, Centennial Centre for Interdisciplinary Science, University of Alberta, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Jack Chang Hung
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Centennial Centre for Interdisciplinary Science, University of Alberta, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Ho-Yan
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Centennial Centre for Interdisciplinary Science, University of Alberta, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Hall
mesh_terms: D000577:Amides / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000577:Amides; D001897:Boronic Acids; D001965:Bromides; D007659:Ketones; D058116:Lewis Acids