Stereoselective Synthesis of β-Alkylated α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated Methylene C(sp3)-H Bonds with Primary Alkyl Halides
Stereoselective Synthesis of β-Alkylated α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated Methylene C(sp3)-H Bonds with Primary Alkyl Halides
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DOI：
10.1021/ja406484v
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发表时间：
2013-08-14
影响因子：
15
通讯作者：
Chen, Gong
中科院分区：
文献类型：
--
作者：
Zhang, Shu-Yu;Li, Qiong;Chen, Gong
我们报道了一系列基于钯催化的脂肪族喹啉基甲酰胺的亚甲基C(sp(3))-H键与α-卤代乙酸酯和碘甲烷的烷基化反应及其在各种β-烷基化α-氨基酸的立体选择性合成中的应用。这些反应代表了第一种普遍适用的方法，用于催化未受约束和未活化的亚甲基C-H键的烷基化反应，具有很高的合成相关性。当与简单的同位素富集剂一起使用时，它们还提供了一种方便而有效的手段，将同位素选择性地结合到氨基酸化合物的碳骨架中。
We report a new set of reactions based on the Pd-catalyzed alkylation of methylene C(sp(3))-H bonds of aliphatic quinolyl carboxamides with alpha-haloacetate and methyl iodide and applications in the stereoselective synthesis of various beta-alkylated alpha-amino acids. These reactions represent the first generally applicable method for the catalytic alkylation of unconstrained and unactivated methylene C-H bonds with high synthetic relevance. When applied with simple isotope-enriched reagents, they also provide a convenient and powerful means to site-selectively incorporate isotopes into the carbon scaffolds of amino acid compounds.