Enantioselective O-H Bond Insertion of α-Diazoketones with Alcohols Cooperatively Catalyzed by Achiral Dirhodium Complexes and Chiral Spiro Phosphoric Acids

Transition-metal-catalyzed asymmetric insertion of carbene into O-H bonds is a straightforward method for the synthesis of chiral alcohols and their derivatives. In recent years, a variety of chiral catalysts have been developed to achieve high enantioselective insertions of metal carbenes derived from alpha-diazoesters into O-H bonds of alcohols, phenols, carboxylic acids. and even water. However, there are few successful examples of the asymmetric O-H bond insertion using alpha-diazoketones as carbene precursors. In this paper, we report the first asymmetric O-H insertion of alpha-diazoketones with alcohols co-catalyzed by achiral dirhodium complexes and chiral spiro phosphoric acids. The reaction has high yields and high enantioselectivity (up to 95% ee). The present O-H bond insertion reaction provides an efficient method for the synthesis of very useful chiral alpha-alkoxy ketones, which are easily transformed to corresponding 1,2-diol derivatives with excellent diastereoselectivity. The density functional theory (DFT) calculation was performed to study the mechanism of the reaction. It is found that the chiral spiro phosphoric acid can promote the proton transfer process of enol intermediates generated from rhodium carbene and alcohol like chiral proton-transfer shuttle and realize enantioselectivity control accordingly. Water are likely to participate in this proton transfer step and has a remarkable effect on the enantiocontrol of the reaction. A typical procedure for the enantioselective O-H bond insertion of alpha-diazoketones is as follows. Powered Rh-2(TPA)(4) (2.9 mg, 0.002 mmol, 1 mol%) and chiral spiro phosphoric acid (R)-1k (3.3 mg, 0.004 mmol, 2 mol%) were introduced into an oven-dried Schlenk tube in an argon-filled glovebox. After CHCl3 (2 mL) was injected into the Schlenk tube, the solution was stirred at 25 degrees C under the argon atmosphere. A solution of benzyl alcohol (21.6 mg, 0.2 mmol) and 1-diazo-l-phenylpropan-2-one (2a, 33.8 mg, 0.21 mmol) in 1 mL of CHCl3 were then introduced into the Schlenk tube containing catalysts. The resulting mixture was stirred at 25 r until the diazo compound 2a disappeared. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate, V : V=15 : 1) to give (-)-1-(benzyloxy)-1-phenylpropan-2-one (4a, 43.2 mg, 0.18 mmol, 90% yield) as a colorless oil.