Highly enantioselective carbene insertion into N-H bonds of aliphatic amines
Highly enantioselective carbene insertion into N-H bonds of aliphatic amines
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DOI：
10.1126/science.aaw9939
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发表时间：
2019-11-22
期刊：
影响因子：
56.9
通讯作者：
Zhou, Qi-Lin
中科院分区：
文献类型：
--
作者：
Li, Mao-Lin;Yu, Jin-Han;Zhou, Qi-Lin
脂肪胺具有很强的配位作用，因此很容易抑制过渡金属催化剂的活性，这对氮氢（N-H）插入反应提出了显着的挑战。在这里，我们报道了使用两种串联催化剂：非手性铜络合物和手性氨基硫脲，将卡宾高度对映选择性地插入脂肪胺的 N-H 键。同蝎形配体的配位保护了激活卡宾前体的铜中心。然后手性氨基硫脲催化剂促进对映选择性质子转移以产生插入产物的立体中心。该反应偶联多种重氮酯和胺，生成手性 α-烷基 α-氨基酸衍生物。
Aliphatic amines strongly coordinate, and therefore easily inhibit, the activity of transition-metal catalysts, posing a marked challenge to nitrogen-hydrogen (N-H) insertion reactions. Here, we report highly enantioselective carbene insertion into N-H bonds of aliphatic amines using two catalysts in tandem: an achiral copper complex and chiral amino-thiourea. Coordination by a homoscorpionate ligand protects the copper center that activates the carbene precursor. The chiral amino-thiourea catalyst then promotes enantioselective proton transfer to generate the stereocenter of the insertion product. This reaction couples a wide variety of diazo esters and amines to produce chiral alpha-alkyl alpha-amino acid derivatives.