Asymmetric Net Cycloaddition for Access to Diverse Substituted 1,5-Benzothiazepines
Asymmetric Net Cycloaddition for Access to Diverse Substituted 1,5-Benzothiazepines
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DOI：
10.1021/acs.joc.7b02451
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发表时间：
2017-12-01
影响因子：
3.6
通讯作者：
Matsubara, Seijiro
中科院分区：
文献类型：
--
作者：
Fukata, Yukihiro;Yao, Koichi;Matsubara, Seijiro
本研究开发了异硫脲催化的各种α,β-不饱和羧酸衍生物与2-氨基苯硫酚的对映选择性形式[4+3]环加成反应。机理研究表明，该反应通过可逆的磺胺-迈克尔加成到α,β-不饱和酰基铵中间体上进行，然后对映选择性地形成七元环，从而能够轻松且发散地合成光学活性的2-和3-取代的1,5-苯并硫氮杂卓。该过程被证明是高度通用的，提供具有优异的区域选择性和高对映选择性的相应产物。此外，该方法能够以高区域选择性、对映选择性和非对映选择性合成手性 2,3-二取代 1,5-苯并硫氮杂卓。因此，该协议可用于构建有用的候选药物库。
In this study, the isothiourea-catalyzed enantioselective formal [4+3] cycloaddition of various alpha,beta-unsaturated carboxylic acid derivatives with 2-aminothiophenols was developed. Mechanistic studies suggested that the reaction proceeds via a reversible sulfa-Michael addition to alpha,beta-unsaturated acylammonium intermediates, followed by the enantioselective formation of a seven-membered ring, enabling the facile and divergent synthesis of optically active 2- and 3-substituted 1,5-benzothiazepines. This process was demonstrated to be highly versatile, affording the corresponding products in excellent regioselectivities and high enantioselectivities. Furthermore, this method enabled the synthesis of chiral 2,3-disubstituted 1,5-benzothiazepines in high regio-, enantio-, and diastereoselectivities. Hence, this protocol can be applied for the construction of a library of useful pharmaceutical candidates.