Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (11): 883-889.DOI: 10.6023/A18060234 Previous Articles     Next Articles

Special Issue: 有机小分子-金属协同催化 纪念南开大学化学学科创建100周年



李茂霖a, 陈梦青a, 徐彬a, 朱守非a, 周其林a,b   

  1. a. 南开大学化学学院元素有机化学研究所 天津 300071;
    b. 天津化学化工协同创新中心 天津 300072
  • 投稿日期:2018-06-15 发布日期:2018-08-14
  • 通讯作者: 朱守非, 周其林;
  • 基金资助:


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

Li Maolina, Chen Mengqinga, Xu Bina, Zhu Shoufeia, Zhou Qilina,b   

  1. a. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071;
    b. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072
  • Received:2018-06-15 Published:2018-08-14
  • Contact: 10.6023/A18060234;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21625204, 21532003, 21421062), the "111" Project of the Ministry of Education of China (No. B06005), the National Program for Special Support of Eminent Professionals and the Fundamental Research Funds for the Central Universities.

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 α-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 α-diazoketones as carbene precursors. In this paper, we report the first asymmetric O-H insertion of α-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 α-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 α-diazoketones is as follows. Powered Rh2(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℃ under the argon atmosphere. A solution of benzyl alcohol (21.6 mg, 0.2 mmol) and 1-diazo-1-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℃ 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-phenyl-propan-2-one (4a, 43.2 mg, 0.18 mmol, 90% yield) as a colorless oil.

Key words: metal carbene, asymmetric insertion reaction, chiral spiro phosphoric acid, α-diazoketone, chiral α-alkoxy ketone