Electron-rich benzofulvenes as effective dipolarophiles in copper()-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

• Published in: Chemical science (Cambridge) Vol. 14; no. 2; pp. 546 - 5469
• Main Authors: Chang, Xin, Liu, Xue-Tao, Li, Fangfang, Yang, Yuhong, Chung, Lung Wa, Wang, Chun-Jiang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 24.05.2023; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Asymmetry; Chemistry; Chemistry, Multidisciplinary; Copper; Cycloaddition; Physical Sciences; Regioselectivity; Science & Technology; Stereoselectivity; Thermal stability; CATALYSIS; POTENT; FACILE SYNTHESIS; EFFICIENT APPROACH; MECHANISTIC INSIGHTS; STRATEGY; CONSTRUCTION; DERIVATIVES; EXO; MICHAEL ADDITION
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc00435j

A series of benzofulvenes without any electron-withdrawing substituents were employed as 2π-type dipolarophiles for the first time to participate in Cu( i )-catalyzed asymmetric 1,3-dipolar cycloaddition (1,3-DC) reactions of azomethine ylides. An intrinsic non-benzenoid aromatic characteristic from benzofulvenes serves as a key driving force for activation of the electron-rich benzofulvenes. Utilizing the current methodology, a wide range of multi-substituted chiral spiro-pyrrolidine derivatives containing two contiguous all-carbon quaternary centers were formed in good yield with exclusive chemo-/regioselectivity and high to excellent stereoselectivity. Computational mechanistic studies elucidate the origin of the stereochemical outcome and the chemoselectivity, in which the thermostability of these cycloaddition products is the major factor. Electron-rich benzofulvenes serve as 2π-components in Cu-catalyzed asymmetric 1,3-DC reactions of azomethine ylides, affording chiral spiro-pyrrolidines in high yields with exclusive chemo-/regioselectivity and moderate to excellent stereoselectivity.