Asymmetric Net Cycloaddition for Access to Diverse Substituted 1,5-Benzothiazepines

作者：Fukata Yukihiro; Yao Koichi; Miyaji Ryota; Asano Keisuke^*; Matsubara Seijiro^*

来源：Journal of Organic Chemistry, 2017, 82(23): 12655-12668.

DOI：10.1021/acs.joc.7b02451

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.

• 出版日期2017-12-1