Base‐Controlled Stereodivergent Synthesis of Pyrrolidines Containing An Enaminone Moiety via Regioselective Formal (3 + 2) Cycloaddition Reactions†

An effective stereodivergent synthesis that provides access to both Z ‐ and E ‐stereoisomers is highly attractive in the fields of organic synthesis and medicinal chemistry. Herein, we demonstrate that base‐controlled stereodivergence allows for the synthesis of a series of cis −2,4‐disubstituted pyrrolidines featuring an exocyclic double bond via a formal (3 + 2) cycloaddition/isomerization strategy, starting from aminoalkyl α,β‐unsaturated esters and acyclic conjugated imines in an environmentally benign manner. This approach not only allows for the facile switching between Z ‐ and E ‐stereoisomers by varying the type of organic or inorganic base but also facilitates the production of pyrrolidines bearing two tertiary chiral centers with high yields (up to 97%) and excellent chemo‐, regio‐, and diastereoselectivities (in all cases, > 25:1 dr). Additionally, the synthetic utility of this method is further demonstrated via scale‐up reactions and synthetic transformations of the products. Furthermore, molecular docking studies have indicated that the de novo ‐synthesized pyrrolidines exhibit potential antibacterial activity.