Asymmetric catalytic reactions of boronate nucleophiles

Boronate nucleophiles are valuable reagents in the synthesis of natural products and pharmaceuticals. Asymmetric reactions utilizing these reagents usually employ chiral auxiliaries to create enantioenriched products. Herein, we present our findings on asymmetric catalytic versions of these reactions.;Asymmetric catalytic allylborations of ketones and acyl imines were developed. These reactions utilized 3,3'-substituted BINOLs to form homoallylic alcohols and amines in good yields and high enantioselectivities. The synthesis of the HIV drug, maraviroc, was accomplished utilizing this allylboration methodology. Spectroscopic and kinetic studies showed the reactions were 1st-order in catalyst and the rate-limiting step was catalyst regeneration for the ketone reaction. Mechanistic evidence indicated a single-ligand exchange of catalyst and boronate occurred to form the active allyl transfer species.;An investigation of the diastereoselective Petasis reaction revealed a triple diastereoselective process when chiral diols are employed. The uncatalyzed reaction utilized enantiopure lactols and primary amino acid derivatives with nucleophilic boronates to form anti beta-amino alcohols in high diastereoselectivity. The use of catalytic 3,3'-Br2-BINOL gave the syn diastereomer in up to 7:1 d.r. A number of products were synthesized and the effect of each component on the diastereoselectivity was determined.;A chemoselective nucleophilic addition of boronic acids to the less reactive ketone of arylglyoxals was discovered. The reaction was run in a biphasic mixture of toluene and water with catalytic amounts of a quaternary ammonium salt. An asymmetric variant used a chiral thiourea catalyst to form the product in moderate enantioselectivity.;The asymmetric catalytic reaction of nucleophilic boronates with oxocarbeniums was developed. The optimized reaction conditions use a tartaramide catalyst and lanthanide triflate co-catalyst to promote the reaction between 2 H-chromene acetals and alkenyl- and arylboronates in high yield and enantioselectivity. Mechanism studies showed the diol catalyst and Lewis acid catalyst were found to react rapidly with the boronate to form the reactive dioxaborolane-Lewis acid complex. An analogous reaction with quinoline acetals was also developed.