Asymmetric Catalytic (2+1) Cycloaddition of Thioketones to Synthesize Tetrasubstituted Thiiranes

• Published in: Angewandte Chemie International Edition 2022-05, Vol.61 (19), p.e202201151-n/a
• Main Authors: Lin, Xiaobin, Pu, Maoping, Sang, Xinpeng, Li, Shiyang, Liu, Xiaohua, Wu, Yun‐Dong, Feng, Xiaoming
• Format: Article
• Language: English
• Subjects: Alkenes; Carbenes; Cobalt; Cobalt(II)/N,N′-Dioxide; Cycloaddition; Density functional theory; Enantiomers; Route selection; Stereoselectivity; Thiiranes; Thioketones; α-Diazo Compounds
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202201151

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α‐diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N′‐dioxide/cobalt(ΙΙ) complexes (2–5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins. Density functional theory calculations reveal that the reaction initiates from a doublet state cobalt(ΙΙ) carbenoid, which is followed by a quartet cobalt(ΙΙ)‐bound thiocarbonyl ylide pathway. This work provides a route for the selective construction of tetrasubstituted thiiranes and olefins that are otherwise difficult to access. The first example of catalytic enantioselective (2+1) cycloaddition of α‐diazo pyrazoleamides with thioketones is presented, catalyzed by chiral N,N′‐dioxide/CoΙΙ complexes. This method provides a rapid and facile access to a series of optically active tetrasubstituted thiiranes with good outcomes (up to 99 % yield, 97 % ee). The origin of stereoselectivity was well elucidated by DFT calculations.