Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL, 61801, USA.
Nat Commun. 2018 Mar 22;9(1):1185. doi: 10.1038/s41467-018-03535-y.
Amines bearing γ-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral γ-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents, which allows for a rapid and modular synthesis of many chiral γ-branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity.
含γ-手性中心的胺是许多生物活性化合物中非常重要的结构基序。然而，这些分子的报道的对映选择性合成是间接的，通常需要多个步骤。在此，我们报告了一种通过高度对映选择性异构化烯丙胺，然后进行烯胺交换和随后的选择性还原，一锅法合成手性γ-支链胺的通用不对称途径。该方案适用于建立各种叔立体中心，包括含有二烷基、二芳基、环状、三氟甲基、二氟甲基和硅基取代基的立体中心，这允许快速和模块化合成许多手性γ-支链胺。为了证明合成的实用性，使用该方法以高对映选择性合成了 Terikalant 和 Tolterodine。
