College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
College of Plant Protection, Shaanxi Research Center of Biopesticide Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Nat Commun. 2022 Jun 10;13(1):3344. doi: 10.1038/s41467-022-31045-5.
Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct asymmetric reductive amination catalyzed by the iridium precursor and sterically tunable chiral phosphoramidite ligands. The density functional theory studies of the reaction mechanism imply the alkyl amine substrates serve as a ligand of iridium strengthened by a (N)H-O(P) hydrogen-bonding attraction, and the hydride addition occurs via an outer-sphere transition state, in which the Cl-H H-bonding plays an important role. Through this concise procedure, cinacalcet, tecalcet, fendiline and many other related chiral amines have been synthesized in one single step with high yields and excellent enantioselectivity.
直接不对称还原胺化是构建手性胺最有效的方法之一，其中适用的胺偶联试剂的范围仍然是一个重大挑战。在这项研究中，我们描述了伯烷基胺在铱前体和空间可调手性磷酰胺配体催化的直接不对称还原胺化中有效地作为 N 源。反应机理的密度泛函理论研究表明，烷基胺底物作为铱的配体，通过（N）H-O（P）氢键吸引得到加强，氢化物加成通过外球过渡态发生，其中 Cl-H H 键合起着重要作用。通过这种简洁的方法，西那卡塞、替卡格雷、芬地林和许多其他相关的手性胺都可以在一步反应中以高产率和优异的对映选择性合成。
