Influences of Electronic Effects and Anions on the Enantioselectivity in the Oxazaborolidine-Catalyzed Asymmetric Borane Reduction of Ketones

Abstract

The influence of electronic effects on the enantioselectivity of the oxazaborolidine-catalyzed asymmetric borane reduction of ketones has been observed and investigated with use of para-substituted acetophenones and propiophenones with a variety of functional groups and B-unsubstituted and B-methoxyoxazaborolidines derived from (S)-2-(diphenylhydroxymethyl)pyrrolidine with borane and trimethyl borate as catalysts in toluene and THF. The results indicate that Hammett linear free energy electronic effects on the enantioselectivity in the asymmetric reduction were observed and rationalized. Tuning electronic effects of the catalyst can improve the enantioselectivity in the reduction. Another interesting finding to be noted is that anions heavily affect the enantioselectivity, especially for the B-methoxy catalyst, because of their coordination with the boron atom in the catalysts.

Enantioselectivity, swelling and stability of 4-hydroxyprolinol containing acrylic polymer beads in the asymmetric reduction of ketones

“…Since the selectivity in asymmetric reductions often depends on the electronic properties of the substrate ketone, 12,38,39 and the catalyst loading, the initial investigations were performed with 1-(4-bromophenyl)ethanone 1a as substrate, using 30 mol % catalyst in THF with borane dimethylsulfide complex as the hydride source (Scheme 2). In contrast to homogenous oxazaborolidine catalysts such as I, polymer based catalysis is most conveniently performed using an amino alcohol as the pre-catalyst.…”

Improving enantioselectivity via rationally tuning electronic effect of catalysts in the organocatalytic asymmetric aldol reaction

“…23 However, the reported catalysts possess some differences in stereo-structural features. 22,23 After investigating rational electronic tuning of catalysts to improve enantioselectivity in the asymmetric borane reduction of ketones, 21,24,28 we wished to study the correlation between the enantiomeric ratio of product and the Hammett constant of the catalyst substituent in the asymmetric aldol reaction system, to understand the electronic tuning by using the designed catalysts with very similar structural feature to completely exclude steric difference. …”

Synthesis of a new C2‐symmetric chiral catalyst and its application in the catalytic asymmetric borane reduction of prochiral ketones

“…It was found that the enantiomeric purity of the secondary alcohol product was greatly affected by the reaction temperature. [28][29][30] At low temperature (358C) the reaction gave product with poor ee's of 27.3% and 10.0% in THF and toluene, respectively. When the reaction was carried out at refluxing temperature, 70.3% (in THF) and 40.5% (in toluene) ee values were achieved (Table 1, entries 3 and 8).…”