Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates
Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates
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N-杂环卡宾作为非共价手性模板的不对称催化
DOI：
10.1038/ncomms4437
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发表时间：
2014-03-01
影响因子：
16.6
通讯作者：
Huang, Yong
中科院分区：
文献类型：
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作者：
Chen, Jiean;Huang, Yong
N-杂环卡宾是一类通过作为杂环的一部分的相邻杂原子稳定的持久卡宾。它们在涉及二磷酸硫胺素的多种酶促生物合成反应中发挥核心作用。受这种生物催化机制的启发，N-杂环卡宾已经成为有机反应中最通用的有机催化剂之一。然而，通过非共价相互作用机制的碳-碳键的不对称合成以前尚未建立手性卡宾。在这里，我们报告了一个N-杂环卡宾催化的，高度对映选择性的过程，使用弱氢键中继不对称偏置。我们发现，催化量的六氟异丙醇是关键的质子穿梭，促进氢转移，以提供高反应速率和高对映选择性。我们证明，这种类型的成功的不对称反应可以通过合理的设计，平衡的pKa值的基板，卡宾前体和产品来完成。氮杂环卡宾是重要的有机反应催化剂。在这里，作者表明，它们可以通过非共价相互作用机制用于碳-碳键的不对称合成，并将其应用于高度对映选择性的迈克尔加成反应。
N-heterocyclic carbenes are a class of persistent carbenes stabilized by adjacent heteroatoms that are part of a heterocycle. They play a central role in multiple enzymatic biosynthetic reactions that involve thiamine diphosphate. Inspired by this biocatalysis machinery, N-heterocyclic carbenes have emerged as one of the most versatile classes of organocatalysts for organic reactions. However, the asymmetric synthesis of carbon–carbon bonds through a non-covalent interaction mechanism has not been previously established for chiral carbenes. Here, we report an N-heterocylic carbene-catalysed, highly enantioselective process that uses weak hydrogen bonds to relay asymmetric bias. We find that catalytic amounts of hexafluoroisopropanol are the critical proton shuttle that facilitates hydrogen transfer to provide high-reaction rates and high enantioselectivity. We demonstrate that a successful asymmetric reaction of this type can be accomplished through a rational design that balances the pKa values of the substrate, the carbene precursor and the product. N-heterocyclic carbenes are important catalysts for organic reactions. Here, the authors show that they can be used for asymmetric synthesis of carbon–carbon bonds through a non-covalent interaction mechanism, and apply this to a highly enantioselective Michael addition reaction.