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

Author:
Fukata, Yukihiro, Yao, Koichi, Miyaji, Ryota, Asano, Keisuke, Matsubara, Seijiro
Source:
Journal of organic chemistry 2017 v.82 no.23 pp. 12655-12668
ISSN:
1520-6904
Subject:
chemical structure, cycloaddition reactions, enantioselectivity, organic chemistry, organic compounds
Abstract:
In this study, the isothiourea-catalyzed enantioselective formal [4+3] cycloaddition of various α,β-unsaturated carboxylic acid derivatives with 2-aminothiophenols was developed. Mechanistic studies suggested that the reaction proceeds via a reversible sulfa-Michael addition to α,β-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.
Agid:
5864586