化学学报 ›› 2015, Vol. 73 ›› Issue (4): 326-329.DOI: 10.6023/A15020125 上一篇    下一篇

研究通讯

铜催化α-重氮酮对硼氢键的不对称插入反应 2017 Awarded

程清卿, 许唤, 朱守非, 周其林   

  1. 南开大学元素有机化学研究所 天津化学化工协同创新中心 天津 300071
  • 收稿日期:2015-02-11 出版日期:2015-04-14 发布日期:2015-03-04
  • 通讯作者: 朱守非 E-mail:sfzhu@nankai.edu.cn
  • 基金资助:

    项目受国家自然科学基金、国家重点基础研究发展计划(973 计划,No. 2012CB821600)和教育部"111"引智计划(No. B06005)资助.

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

Cheng Qingqing, Xu Huan, Zhu Shoufei, Zhou Qilin   

  1. State Key Laboratory and Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071
  • Received:2015-02-11 Online:2015-04-14 Published:2015-03-04
  • Supported by:

    Project supported by the National Natural Science Foundation of China, the National Basic Research Program of China (973 Program, No. 2012CB821600) and the "111" Project of the Ministry of Education of China (No. B06005).

手性有机硼化合物在有机合成、医药、材料等诸多领域中有广泛的应用, 发展该类化合物的高效合成方法一直广受关注. 此前, 我们发展了过渡金属催化卡宾对硼氢键(B—H)的插入反应, 并实现了α-重氮酯对B—H键的不对称插入反应. 本文以手性螺环双噁唑啉配体和铜的络合物作为催化剂, 首次实现了α-重氮酮对膦-硼烷加合物的B—H键不对称插入反应, 获得了较高的收率和高达83% ee的对映选择性. 该研究成果是为数不多的以α-重氮酮作为卡宾前体的不对称杂原子氢键插入反应, 为手性α-硼取代酮化合物这类新的有机硼化合物的合成提供了有效方法.

关键词: 不对称催化, 卡宾插入反应, α-重氮酮, 硼烷加合物, 手性螺环配体

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-heteroatom (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 α-diazoesters with phosphine-borane adducts with high yields and high enantioselectivities. Herein, we report the first enantioselective B—H bond insertion reaction of α-diazoketones, another readily available carbene precursors. Firstly, various borane adducts were evaluated, and dimethylphosphine-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 substrate scope of the reaction was investigated. A variety of α-diazoketones underwent the B—H bond insertion reaction affording 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 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 ℃ 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.

Key words: asymmetric catalysis, carbene insertion, α-diazoketone, borane adduct, chiral spiro ligand