Abstract: The increasing role of polysubstituted pyrrolidines in pharmaceutical design necessitates the development of efficient and stereoselective methods for their synthesis. Double reductive amination of 1,4-dicarbonyl compounds is a common route to build the pyrrolidine ring, yet its catalytic version is challenging due to the competing reduction of C═O groups, formation of pyrroles through the Paal–Knorr reaction, and the difficulty of involving ammonia in the process. Here, we propose a solution to these fundamental issues through a two-step sequence involving smooth conversion of 1,4-diketones to dioximes followed by their reductive cyclization to NH-pyrrolidines on a heterogeneous nickel catalyst. The cyclization process is diastereoselective, high-yielding, scalable, and enables one-pot reductive amination and α-deuteration of the resulting NH-pyrrolidines. The method was applied to develop a practical synthesis of useful pyrrolidines from platform chemicals. Studies of the mechanism enabled the characterization of almost all organic intermediates in the reductive cyclization of 1,4-dioximes.

Cite: Pospelov E.V. , Sukhorukov A.Y.
Accessing NH -Pyrrolidines from 1,4-Dicarbonyl Compounds via Catalytic Dioxime Cyclization
Journal of Organic Chemistry. 2026. V.91. N20. P.7002-7012. DOI: 10.1021/acs.joc.6c00493 WOS Scopus OpenAlex

Dates:

Submitted:	Feb 26, 2026
Published online:	May 22, 2026

Identifiers:

≡ Web of science:	WOS:001760130700001
≡ Scopus:	2-s2.0-105039847648
≡ OpenAlex:	W7160520936

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