Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong, China.
Department of Chemistry, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202202160. doi: 10.1002/anie.202202160. Epub 2022 Apr 11.
Despite the widespread existence of chiral 1,4-diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long-standing challenge. Here, we report a Cu-catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4-diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4-diamine structures. The desired products could be easily transformed into chiral 1,4-diamines and chiral NH -Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring-opening and cascade hydroamination sequence.
尽管手性 1,4-二胺在生物活性分子中广泛存在，并在不对称催化中得到了应用，但从易得的底物出发对这类结构进行催化和不对称合成仍然是一个长期存在的挑战。在这里，我们报道了一种 Cu 催化的不对称级联氢胺化方案，能够以高收率和优异的对映选择性（高达 95%的产率和高达>99%的对映体过量）构建广泛的手性 1,4-二胺衍生物。使用两种含有不同官能化氨基的羟胺酯，使我们能够增加最终 1,4-二胺结构的复杂性。所需的产物可以很容易地转化为手性 1,4-二胺和手性 NH-特非那定。机理研究表明，该反应通过氢胺化开环和级联氢胺化序列进行。
