Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (13): 1451-1456.DOI: 10.6023/A12040145 Previous Articles     Next Articles



刘运林a, 周剑a,b   

  1. a 华东师范大学化学系 绿色化学与化工过程绿色化上海市重点实验室 上海 200062;
    b 南开大学元素有机重点实验室 天津 300071
  • 投稿日期:2012-04-23 发布日期:2012-05-24
  • 通讯作者: 周剑
  • 基金资助:

    项目受国家自然科学基金(Nos. 20902025, 21172075)和973 项目(No. 2011CB808600)资助.

Highly Enantioselective Organocatalytic Asymmetric Mukaiyama-aldol Reaction of Difluoroenoxysilanes with β,γ-Unsaturated α-Ketoesters

Liu Yunlina, Zhou Jiana,b   

  1. a Department of Chemistry, East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Shanghai 200062;
    b State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071
  • Received:2012-04-23 Published:2012-05-24
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 20902025, 21172075) and the 973 program (No. 2011CB808600).

We report the first example of catalytic asymmetric reaction of difluoroenoxysilanes 1 and β,γ-unsaturated α-ketoesters 2. In the presence of tertiary amine or tertiary amine-H-bonding donor bifunctional catalysts, it was found that the reaction selectively took place at the ketone moiety of ketoesters 2, and no conjugate reaction happened. Hydronquinine derived urea catalyst 11 was identified as a powerful catalyst for this Mukaiyama-aldol reaction to furnish α-difluoroalkyl substituted tertiary alcohols in good to high yield (44%—81%), with moderate to excellent enantioselectivity (72%—96%). The optimum reaction condition was determined to run the reaction at -40 ℃ using THF as the solvent, in the presence of 10 mol% of chiral catalyst 11. The reaction possibly proceeded via the dual activation of both reaction partners: the tertiary amine moiety of catalyst 11 working as a Lewis base to activate difluoroenoxysilanes 1, while the urea part of the catalyst as a Br?nsted acid to activate carbonyl group of ketoesters 2. Different aryl substituted difluoroenoxysilanes 1 and γ-aryl substituted β,γ-unsaturated α-ketoesters 2 all worked well under the established reaction condition, with 15 examples provided. The thus obtained chiral α-difluoroalkyl substituted tertiary alcohols were not only valuable in the medicinal research, but also versatile building blocks for the synthesis of a variety of difluoroalkyl-substituted chiral compounds. For example, the selective reduction of the ketone or ester group of product 3g has been realized by using NaBH4 or Et3SiH as the reducing agents, giving the triol 14 or diol 15 in moderate yield without the loss of ee.

Key words: organocatalytic, β,γ-unsaturated α-ketoester, difluoroenoxysilanes, Mukaiyama-aldol reaction, α-difluoroalkyl substituted tertiary alcohols