Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan University, Kunming 650091, People's Republic of China.
Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
J Am Chem Soc. 2021 Feb 3;143(4):1959-1967. doi: 10.1021/jacs.0c11630. Epub 2021 Jan 22.
Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enecarbamates (-Cbz-protected enamines) and alkyl halides with high regio- and enantioselectivity. The method works for both nonactivated and activated alkyl halides and is able to produce enantiomerically enriched amines with two minimally differentiated α-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the postproduct functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bioactive compounds.
手性烷基胺作为生物活性分子和合成中间体无处不在。从易得的前体催化和对映选择性合成烷基胺具有挑战性。在这里，我们开发了一种镍催化的氢烷基化方法，从烯基氨基甲酸酯（-Cbz 保护的烯胺）和烷基卤化物中高区域和对映选择性地组装广泛的手性烷基胺。该方法适用于非活化和活化的烷基卤化物，并能够用两种最小差异的α-烷基取代基产生对映体富集的胺。温和的条件导致高官能团耐受性，这在许多天然产物和药物分子的后产物官能化以及手性构建块和生物活性化合物关键中间体的合成中得到了证明。
