Water enables diastereodivergency in bispidine-based chiral amine-catalyzed asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones. Issue 15 (25th March 2022)

• Record Type: Journal Article
• Authors: Li, Gonglin; Zhang, Yan; Zeng, Hongkun; Feng, Xiaoming; Su, Zhishan; Lin, Lili
• Is Part Of: Chemical science. Volume 13:Issue 15(2022)
• Page Start: 4313
• Page End: 4320
• Publication Date: 2022-03-25
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc00446a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A diastereodivergent asymmetric Mannich reaction of cyclic N -sulfonyl ketimines with ketones is realized by employing bispidine-based chiral amine as catalyst and additional water switching the diastereoselectivity. Abstract : Tuning diastereoselectivity is a great challenge in asymmetric catalysis for the inherent stereochemical bias of the substrates. Here, we report a diastereodivergent asymmetric Mannich reaction of cyclic N -sulfonyl ketimines with ketones catalyzed by a bispidine-based chiral amine catalyst, in which additional water switches the diastereoselectivity efficiently. Both chiral anti - and syn -benzosultams with potential anti -HIV-1 activity are obtained in excellent yields and good to excellent ee values. Control experiments and density functional theory (DFT) calculations were applied to study the diastereodivergent mechanism, which reveal that the diastereodivergent catalysis should be state-determined, and the water reverses the energies of states to realize the diastereodivergency. The findings are quite new and might inspire more diastereodivergent asymmetric synthesis.