Kinetic Resolution of BINOLs and Biphenols by Atroposelective, Cu-H-Catalyzed Si-O Coupling with Hydrosilanes

Abstract

A nonenzymatic kinetic resolution of monoprotected BINOL and biphenol derivatives by atroposelective Si-O coupling with hydrosilanes is described. The reaction relies on a previously unprecedented Cu-H-catalyzed silylation of phenols. The catalyst system consisting of CuCl, (R,R)-Ph-BPE, and NaOtBu enables the enantioselective coupling of the phenolic hydroxy group with a hydrosilane with moderate to good selectivity factors.

Scheme 1. Previous Approaches of Kinetic Resolution of BINOL and Biphenol Derivatives and Planned Silylation

Scheme 2. Substrate Scope I: Variation of Substituents in the 2′-Position of 2-Hydroxy-1,1′-binaphthalenes

See caption of Table 1 for details. n.d. = not determined. No 4 Å MS was added to the catalyst mixture. The products were not isolated, and HPLC analysis was conducted of the crude reaction mixture.

Scheme 3. Substrate Scope II: Variations of the Biaryl Backbone

See caption of Table 1 for details. No 4 Å MS was added to the catalyst mixture. A selectivity factor of s = 14 was obtained when the reaction was performed on a 1.0 mmol scale. The products were not isolated, and HPLC analysis was conducted of the crude reaction mixture. Purification was routinely done by flash-column chromatography, except for compounds 1x, 1y, 1a′, and 1b′, which were purified by preparative thin-layer chromatography.