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

Abstract

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 effi- cient strategy for the formation of carbon-heteroatom (C—X) bonds and related chiral centers. The enantioselective bo- ron-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 α-diazoesters with phosphine-borane adducts with high yields and high enantioselectivities. Herein, we report the first enantioselective B—H bond insertion reac- tion of α-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)4PF6/(Ra,S,S)-Ph-SpiroBOX proved to be the most efficient catalyst. Under optimal reaction conditions, the sub- strate scope of the reaction was investigated. A variety of α-diazoketones underwent the B—H bond insertion reaction af- fording the desired α-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 α-diazoketones as carbene precursors. A typical procedure for the enantioselective copper-catalyzed B—H bond insertion of α-diazoketones is as follows: The powered Cu(MeCN)4PF6 (5.6 mg, 0.015 mmol, 5 mol%) and (Ra,S,S)-Ph-SpiroBOX (4a, 9.2 mg, 0.018 mmol, 6 mol%) were intro- duced 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 ℃ 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 ℃ 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-(dimethylphosphine- boryl)-1-phenylpropan-2-one (3ae, 52.4 mg, 0.252 mmol, 84% yield) as a colorless oil. Keywords asymmetric catalysis; carbene insertion; α-diazoketone; borane adduct; chiral spiro ligand