Water enables diastereodivergency in bispidine-based chiral amine-catalyzed asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones

Chem Sci. 2022 Mar 22;13(15):4313-4320. doi: 10.1039/d2sc00446a. eCollection 2022 Apr 13.

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.

PMID:35509468 | PMC:PMC9006921 | DOI:10.1039/d2sc00446a

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