Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions

• Published in: Nature communications 2024-06, Vol.15 (1), p.5479-14, Article 5479
• Main Authors: Chen, Shanglin, Wang, Ya-Nan, Xie, Jinhui, Li, Wangyang, Ye, Mingxing, Ma, Xingxing, Yang, Kai, Li, Shijun, Lan, Yu, Song, Qiuling
• Format: Article
• Language: English
• Subjects: 119/118; 140/131; 140/58; 639/638/403/933; 639/638/549/933; 639/638/77/884; Alkenes; Alkynes; Aromatic compounds; Biological activity; Catalysis; Catalysts; Chemical engineering; Chemical reactions; Chemistry; Dienes; Humanities and Social Sciences; Hypotheses; Iodides; multidisciplinary; Natural products; Nickel; Perfluoroalkyl & polyfluoroalkyl substances; Reaction mechanisms; Reagents; Regioselectivity; Science; Science (multidisciplinary); Stereoselectivity; Success
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49870-1

1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is undeveloped and proves to be a significant challenge. Herein, we report a Nickel-catalyzed four-component reaction to access polysubstituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides, wherein the reaction forms three new C-C bonds in a single vessel and serve as a modular strategy to access polysubstituted 1,3-dienes with excellent chemoselectivity, good regioselectivity and exclusive stereoselectivity. Control experiments reveal the plausible reaction mechanism and DFT calculations explain the cause for the formation of this unusual four-component reaction. Furthermore, we successfully incorporate two biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases the diversity of molecular scaffolds and brings more potential values to medicinal chemistry, the synthetic utility of our protocol is further demonstrated by the late-stage transformations. Multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is challenging. Herein, the authors report a Nickel-catalyzed four-component reaction to access densely substituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides.