Enantioselective decarboxylative chlorination of β-ketocarboxylic acids.
Enantioselective decarboxylative chlorination of β-ketocarboxylic acids.
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DOI：
10.1038/ncomms15600
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发表时间：
2017-06-05
影响因子：
16.6
通讯作者：
Iwasa S
中科院分区：
文献类型：
--
作者：
Shibatomi K;Kitahara K;Sasaki N;Kawasaki Y;Fujisawa I;Iwasa S
立体选择性卤化反应是一种非常有用的有机转化方法，可用于多步合成，因为所得的手性有机卤化物可作为各种医药相关衍生物的前体。尽管脂肪族羧酸的脱羧卤化是制备各种有机卤化物的有用和基本的合成方法，但该反应的对映选择性版本尚未报道。本文报道了在温和的有机催化条件下，β-酮基羧酸的高对映选择性脱羧氯化合成α-氯代酮。该方法也适用于α-氯代叔酮的不对称合成。还证明了在叔碳中心通过SN 2反应将所得α-氯酮转化为α-氨基酮和α-硫代取代酮。这些结果构成了一种有效的方法，用于合成手性有机卤化物，并有望提高对映体富集的手性化合物与杂原子取代的手性立体中心的可用性。由于产物的合成用途，立体选择性卤化是合成手性化合物的有力方法。在这里，作者报告了一种对映选择性脱羧氯化，可以获得一系列α-氯酮。
Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via SN2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres. Due to the synthetic utility of the products, stereoselective halogenation is a powerful method for the synthesis of chiral compounds. Here the authors report an enantioselective decarboxylative chlorination, giving access to a range of α-chloroketones.