Practical Synthesis of Chiral Building Blocks by Highly Efficient Catalytic Asymmetric Acylation

近年来，外消旋醇和内消旋二醇的非酶不对称酰化反应受到了广泛的关注。我们已经证明了外消旋仲醇和内消旋-1，2-二醇在催化量的衍生自（S）-脯氨酸的手性1，2-二胺存在下通过与非手性苯甲酰卤反应的不对称酰化。近年来，以非手性酰化剂催化的醇的不对称酰化反应为基础的研究成果不断涌现。然而，这两种方法都没有发展到在有机合成中广泛使用的水平。我们建立了由（S）-脯氨酸衍生的手性1，2-二胺可以作为内消旋-1，2-二醇的催化不对称化的高效催化剂。在0。5mol%的手性二胺与化学计量的三乙胺结合，得到具有优异的对映选择性的相应的单苯甲酸酯。由此获得的4-苯甲酰氧基-2-环戊烯-1-醇通过重铬酸吡啶盐（PDC）的处理容易地转化为（R）-4-苯甲酰氧基-2-环戊烯-1-酮，其是各种野牡丹素的手性结构单元。内消旋-1，3-二醇的催化不对称酰化反应也已在仅0.5mol%的手性1，2-二胺与1.5当量三乙胺组合的存在下成功地进行。在仅0.3mol%的衍生自（S）-脯氨酸的手性1，2-二胺存在下，用取代苯甲酰氯也进行了外消旋伯醇的催化动力学拆分。这种高效的醇的不对称酰化反应提供了各种有用的手性结构单元。

Recently, much attention has been focused on the non-enzymatic asymmetric acylation of racemic alcohols and meso-diols. We have already demonstrated asymmetric acylation of racemic secondary alcohols and meso-l,2-diols by the reaction with achiral benzoyl halide in the presence of a catalytic amount of chiral 1 , 2-diamine derived from (S)-proline. Some papers, which are based on the catalytic asymmetric acylation of alcohols with achiral acylating agents , have emerged successively in recent years. However, neither methodology has been developed to such a level as to find widespread use in organic synthesis.We established that a chiral 1,2-diamine derived from (S)-proline could function as a highly efficient catalyst for the catalytic asymmetrization of meso- l , 2-diols. Catalytic asymmetric acylation of cw-2-cyclopentene- l ,4-diol has been successfully performed by the reaction with benzoyl chloride in the presence of 0. 5 mol% of chiral diamine combined with a stoichiometric amount of triethylamine to give the corresponding monobenzoate with excellent enantioselectivity. Thus obtained 4-benzoyloxy-2-cyclopenten-l-ol was readily converted to (R)-4-benzoyloxy-2-cyclopenten-1-one, a chiral building block for various prostaglandins, by the treatment of pyridinium dichromate (PDC). Catalytic asymmetric acylation of meso-1, 3-diols has been also successfully performed in the presence of only 0.5 mol% of chiral 1,2-diamine, combined with 1.5 equivalents of triethylamine. Catalytic kinetic resolution of racemic primary alcohols has been also performed with substituted benzoyl chloride in the presence of only 0.3 mol% of chiral 1,2-diamine derived from (S)-proline. This highly efficient asymmetric acylation of alcohols afforded various useful chiral building blocks.