Asymmetric reactions of trifluoroborate salts catalyzed by chiral biphenols
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Abstract
Trifluoroborate salts of the formula [RnBF4-n]-, are practical and reactive alternatives to traditional organoboron reagents, due to their stability towards both nucleophiles as well as environmental factors. Their ease of use and economical nature make them compelling reagents in both reaction development as well as the pharmaceutical industry. Herein, the synthetic utility of these reagents is demonstrated.
An asymmetric allylation of ketones via a practical trifluoroborate reagent mix was developed. Inspired by AD-mix used in the Sharpless asymmetric dihydroxylation, BTF-mix, a mixture of bench-stable allyl trifluoroborate salt and chiral biphenol (BINOL) catalyst, is used to easily facilitate the synthesis of chiral homoallylic alcohols in high yields (up to 99%) and enantioselectivities (up to 99:1 e.r.), with an expanded substrate scope including cyclic ketones. Crotyl trifluoroborate salts, are utilized in respective BINOL-trifluoroborate mixes to enable addition to ketones. Additionally, the reaction mechanism is elucidated using heteronuclear NMR and direct-inject mass spectrometry, identifying an active trivalent difluoroborane species.
In a further application of biphenols as chiral catalyst the asymmetric synthesis of tetrahydroquinolines is described. Historically, emphasis has been placed on the synthesis of 2-substituted tetrahydroquinolines (THQs), but the more challenging enantioselective synthesis of 2,4-disubstituted THQs has received less attention. A microwave-facilitated method for the rapid and efficient enantioselective multicomponent reaction of trifluoroborates, aldehydes and protected amines for the synthesis of 2,4-disubstituted THQs is described. The series of novel THQ products was developed in an environmentally friendly and efficient manner, obtaining products in up to 98% yield and 98:2 e.r.