Enantioselective Copper-Catalyzed B-H Bond Insertion Reaction of α-Diazoketones

Chiral organoboron compounds are widely used in organic synthesis, materials science; medicine, and other fields, and the development of methodologies for the synthesis of these compounds is a highly active and rewarding area of research. Enantioselective transition-metal-catalyzed carbenoid insertion into heteroatom-hydrogen (X-H) bonds is an efficient strategy for the formation of carbon-hdteroatom (C-X) bonds and related chiral centers. The enantioselective boron-hydrogen (B-H) bond insertion reaction provides an ideal approach to chiral organoboron compounds. In our previous study, we developed a copper-catalyzed asymmetric B-H bond insertion reaction of alpha-diazoesters with phosphine-borane adducts with high yields and high enantioselectivities. Herein, we report the first enantioselective B-H bond insertion reaction of alpha-diazoketones,another readily available carbene precursors. Firstly, various borane adducts were evaluated, and di-methylphosphine-borane gave the best result. Then, the reaction conditions were carefully optimized, and Cu(MeCN)(4)PF6/(R-a,S,S)-Ph-SpiroBOX proved to be the most efficient catalyst. Under optimal reaction conditions, the substrate scope of the reaction was investigated. A variety of a-diazoketones underwent the B-H bond insertion reaction affording the desired alpha-borylketones in good yields with moderate to good enantioselectivities (up to 83% ee). This reaction represents one of the few enantioselective X-H insertion reactions using alpha-diazoketones as carbene precursors. A typical procedure for the enantioselective copper-catalyzed B-H bond insertion of a-diazoketones is as follows: The powered Cu(MeCN)(4)PF6 (5.6 mg, 0.015 mmol, 5 mol%) and (R-a,S,S)-Ph-SpiroBOX (4a, 9.2 mg, 0.018 mmol, 6 mol%) were introduced into an oven-dried Schlenk tube in an argon-filled glovebox. After CH2Cl2 (3 mL) was injected into the Schlenk tube, the solution was stirred at 25 degrees C under the argon atmosphere for 2 h. Then dimethylphosphine-borane (2e, 22.8 mg, 0.3 mmol) and 1-diazo-1-phenylpropan-2-one (1a, 48.1 mg, 0.3 mmol) were introduced into the reaction tube subsequently. The resulting mixture was stirred at 25 degrees C until the diazo compound disappeared. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (petroleum ether/acetone, V : V=6 :1) to give (+)-1-(dimethylphosphineboryl)-1-phenylpropan-2-one (3ae, 52.4 mg, 0.252 mmol, 84% yield) as a colorless oil.