Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering , Shaanxi Normal University , Xi'an , 710062 , China.
Department of Chemistry , University of Liverpool , Liverpool , L69 7ZD , U.K.
J Am Chem Soc. 2019 Aug 28;141(34):13506-13515. doi: 10.1021/jacs.9b05221. Epub 2019 Aug 19.
Hydroamination allows for the direct access to synthetically important amines. Controlling the selectivity of the reaction with efficient, widely applicable, and economic catalysts remains challenging, however. This paper reports an iron-catalyzed formal anti-Markovnikov hydroamination and hydroamidation of allylic alcohols, which yields γ-amino and γ-amido alcohols, respectively. Homoallylic alcohol is also feasible. The catalytic system, consisting of a pincer Fe-PNP complex (1-4 mol %), a weak base, and a nonpolar solvent, features exclusive anti-Markovnikov selectivity, broad substrate scope (>70 examples), and good functional group tolerance. The reaction could be performed at gram scale and applied to the synthesis of drug molecules and heterocyclic compounds. When chiral substrates are used, the stereochemistry and enantiomeric excess are retained. Further application of the chemistry is seen in the functionalization of amino acids, natural products, and existing drugs. Mechanistic studies suggest that the reaction proceeds via two cooperating catalytic cycles, with the iron complex catalyzing a dehydrogenation/hydrogenation process while the amine substrate acts as an organocatalyst for the Michael addition step.
氢胺化反应可直接合成具有重要合成意义的胺类化合物。然而，利用高效、适用范围广且经济的催化剂来控制反应的选择性仍然具有挑战性。本文报道了一种铁催化的烯丙醇的形式反马氏加成的氢胺化和氢酰胺化反应，分别生成 γ-氨基和 γ-酰胺基醇。高烯丙醇也是可行的。该催化体系由钳式 Fe-PNP 配合物（1-4 mol%）、弱碱和非质子溶剂组成，具有独特的反马氏加成选择性、广泛的底物范围（>70 个实例）和良好的官能团容忍性。该反应可在克级规模下进行，并可应用于药物分子和杂环化合物的合成。当使用手性底物时，立体化学和对映过量都得到保留。该化学方法的进一步应用还包括氨基酸、天然产物和现有药物的功能化。机理研究表明，反应通过两个协同的催化循环进行，其中铁配合物催化脱氢/加氢过程，而胺底物作为迈克尔加成步骤的有机催化剂。
