Diverse Remote Difunctionalization of Enyne-type Propargylic Carbonates: Regio-, Chemo-, and Stereoselective Access to Highly Functionalized Multisubstituted 1,3-Dienes
Year: 2026
Type: preprint
Abstract: Herein, we report the first catalytic heterodifunctionalization and homodifunctionalization of readily available 1-substituted enyne-type propargylic derivatives, proceeding via a multicomponent remote C2,C5-addition/substitution pathway. This palladium-catalyzed protocol enables the modular and straightforward assembly of tri-, tetra-, and penta-substituted 1,3-dienes with diverse functional groups from two heteroatom nucleophiles or one heteroatom nucleophile and one carbon nucleophile. The reaction exhibits high chemo-, regio-, and stereoselectivity, accommodates a broad spectrum of O-, N-, S-, and C-nucleophiles, and delivers highly substituted (Z, E)-1,3-dienes with precise stereocontrol. Notably, switching from O- to S-nucleophiles triggers a nucleophile-directed stereodivergence. The synthetic utility is further demonstrated through diverse downstream transformations, efficient synthesis of bioactive molecules, and late-stage functionalization of natural products. Mechanistic studies reveal the involvement of heteroatom-containing pentacoordinate π-allyl palladium and π-alkynyl palladium intermediates in this heterodifunctionalization process.
Source: ChemRxiv
Institutions: Shenzhen University, Yunnan University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7221576618