钴催化1,3-二烯与醛的区域选择性不对称氢烷基化反应研究

  过渡金属催化1,3-二烯氢烷基化反应是一种构建烯烃邻位C(sp³)-C(sp³)有效且具有步骤经济性的策略，然而精确控制反应的区域选择性和对映选择性仍然是该策略需要克服的重大挑战。基于此，本文开展了钴催化1,3-二烯与醛的区域选择性不对称氢烷基化反应研究。

  在羧酸作为质子源、锰粉作为还原剂的条件下，发展了钴催化2-烷基-1,3-二烯与醛的不对称1,2-氢烷基化反应，以良好的区域选择性（高达12:1）和优异的对映选择性（高达96% ee）得到2,2-双取代-高烯丙醇；在硅烷作为氢源的条件下，发展了钴催化2-烷基-1,3-二烯与醛的不对称3,4-氢烷基化反应，以优秀的区域选择性（大于20:1）和对映选择性（高达99% ee）得到2-取代-高烯丙醇。该策略实现了从相同的原料出发，通过催化策略的选择实现不同骨架手性高烯丙醇的合成。

  进一步发展了钴催化1-芳基-1,3-二烯与醛的不对称1,4-氢烷基化反应。使用BOX配体，以优秀的区域选择性（大于20:1）、非对映选择性（大于20:1）和对映选择性（高达95% ee）合成传统方法难以构建的Z式高烯丙醇化合物。

  综上，本文发展了几种钴催化1,3-二烯与醛的区域选择性不对称氢烷基化反应，构建了一系列结构多样的手性高烯丙醇化合物。

     1,3-Dienes are ubiquitous and cost-effective and have attracted great attention due to their profound chemical reactivity. Among which, transition-metal-catalyzed hydroalkylations of 1,3-dienes are one of the most promising and efficient strategy for creating vicinal C(sp³)-C(sp³) bonds. However, the regio- and enantioselectivity control associated with these reactions remains a formidable challenge. In this thesis, we focused on the cobalt-catalyzed regio- and enantioselective hydroalkylations of 1,3-dienes with aldehydes.

    With carboxylic acid as the proton source and manganese powder as the reductant, Co-catalyzed asymmetric 1,2-hydroalkylation of 2-alkyl-1,3-dienes with aldehydes has been developed, affording 2,2-disubstituted homoallyl alcohols with good regioselectivities (up to 12:1) and excellent enantioselectivities (up to 96% ee). Moreover, Co-catalyzed asymmetric 3,4-hydroalkylation of 2-alkyl-1,3-dienes with aldehydes has been achieved using silanes as hydrogen sources, delivering 2-substituted homoallyl alcohols regioselectivity (>20:1) and enantioselectivity (up to 99% ee). This strategy provides access to enantioenriched homoallylic alcohols with different architectures from identical starting materials.

    Next, cobalt-catalyzed enantioselective 1,4-hydroalkylations of 1-aryl-1,3-dienes with aldehydes has been established. Using BOX as ligand, a variety of 1-aryl-1,3-dienes and aldehydes could be transformed into enantioenriched Z-homoallylic alcohols with excellent regioselectivities (>20:1), diastereoselectivities (>20:1) and enantioselectivities (up to 95% ee).

    In summary, cobalt-catalyzed regioselective and enantioselective hydroalkylations of 1,3-dienes with aldehydes under mild reaction conditions have been developed, providing access to enantioenriched homoallylic alcohols with diverse architectures.

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