Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9038, USA.
Angew Chem Int Ed Engl. 2017 May 8;56(20):5536-5540. doi: 10.1002/anie.201701796. Epub 2017 Apr 13.
Heteroatom-containing organic molecules are of particular interest to medicinal chemists and materials scientists. A strategy to reach these architectures via direct difunctionalization of abundant 1,3-dienes is especially attractive. Herein, we describe the development of a regio- and diastereoselective 1,4-aminothiolation of 1,3-dienes with a sulfur diimide reagent, a copper catalyst, and alkyl Grignard reagents. This unique protocol provides remote nitrogen and sulfur functionalities with high levels of stereocontrol. The reaction proceeds via a tandem hetero-Diels-Alder cycloaddition of N,N'-bis(benzenesulfonyl)sulfur diimide with 1,3-diene followed by copper-catalyzed Grignard substitution. Mechanistic studies support a copper catalyzed formation of an unprecedented [10-S-4] sulfurane that reductively eliminates to afford a 3,6-dihydrothiazine, which is selectively converted to 1,4-aminothiols.
含杂原子的有机分子特别引起药物化学家和材料科学家的兴趣。通过直接官能化丰富的 1,3-二烯来达到这些结构的策略特别有吸引力。在此，我们描述了一种通过硫二亚胺试剂、铜催化剂和烷基格氏试剂对 1,3-二烯进行区域和立体选择性 1,4-氨硫代反应的方法。该独特的方案提供了具有高水平立体控制的远程氮和硫官能团。该反应通过 N,N'-双（苯磺酰基）硫二亚胺与 1,3-二烯的串联杂 Diels-Alder 环加成反应进行，然后进行铜催化的格氏取代反应。机理研究支持铜催化形成前所未有的 [10-S-4] 硫杂环丙烷，其还原消除得到 3,6-二氢噻嗪，该噻嗪可选择性转化为 1,4-氨硫醇。
