Solvent-controlled stereodivergent synthesis of E- and Z-enamines via metal-free formal C(sp2)-H amination of α-substituted styrenes

• Published in: Green synthesis and catalysis 2024-11, Vol.5 (4), p.324-328
• Main Authors: Wang, Dangui, Yao, Jinbei, Zhang, Wentao, Zhang, Shuyue, Yu, Huaibin, Peng, Laihu, Yao, Weijun, Dai, Zhifeng, Wu, Guojiao, Zhong, Fangrui
• Format: Article
• Language: English
• Subjects: C(sp2)-H amination; Enamines; Hypervalent iodine; Metal-free; Stereodivergent synthesis
• ISSN: 2666-5549; 2666-5549
• DOI: 10.1016/j.gresc.2023.11.003

C(sp2)-H amination represents an attractive approach for the synthesis of enamines, which is intrinsically associated with the challenge of controlling of stereochemistry and primarily relying on transition-metal catalysis. Herein, a metal-free C(sp2)-H amination of α-substituted styrenes has been achieved, leading to stereodivergent formation of both E- and Z-enamines in 50 ​%–97 ​% yield under mild conditions by using PhI(OAc)2 as a green oxidant and ortho-phenylenediamines as nitrogen source. Interestingly, the Z/E selectivity can be controlled readily by switching the reaction medium. E-isomers were formed preferentially in THF, whereas n-hexane favored the formation of Z-isomers. Preliminary mechanistic studies suggested that in situ formed ortho-benzoquinone diimides are the key intermediates, and there is a correlation between solvent polarity and stereoselectivity. This study enriches the chemical repertoire of ortho-benzoquinone diimides particularly with respect to sustainable amination. A stereodivergent amination reaction of α-substituted styrenes under metal-free conditions was developed, allowing access to both E- and Z-enamines with excellent stereoselectivity from readily available starting materials by changing solvent. [Display omitted]