Asymmetric [3+2] Annulations of Propargylic Carbonates and Vinylogous Nucleophiles via a Nickel-Catalyzed Alkenylation Pathway

Abstract

The alkenylation reaction of propargylic derivatives catalyzed by transition metals represents a powerful synthetic strategy, usually applied in a double-attack mode to access polyfunctional cyclic products. Whereas a few asymmetric alkenylation reactions involving palladium catalysis have been uncovered, we report here that a nonprecious Ni(0)-based chiral complex exhibits superior efficacy in assemblies of a diversity of propargylic carbonates and vinylogous donors. The reactions proceed through consecutive vinylogous activations of nucleophiles, finally giving [3+2] annulation frameworks by a double attack on nickel-activated species of propargylic carbonates. Both N-trifluoroethyl imines from activated ketones and all-carbon-based vinylogous donors can be utilized, and products embedding a 4-methylene-3,4-dihydro-2H-pyrrole core or a 3-methylenecyclopentene framework, respectively, are efficiently constructed with high regio-, diastereo-, and enantioselectivities. The substrate scope is broad, and further synthetic elaborations of the products permit access to more-versatile structures with emerging applications. Density functional theory calculations and control experiments were carried out to elucidate the reaction mechanism.

Key words

propargylic carbonates - vinylogous donors - nickel catalysis - alkenylation - [3+2] annulation - enantioselectivity

Publication History

Received: 28 December 2024

Accepted after revision: 14 February 2025

Accepted Manuscript online:
14 February 2025

Article published online:
28 March 2025

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