Enantioselective Synthesis of 2,3-Disubstituted Azetidines via Copper-Catalyzed Boryl Allylation of Azetines
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Disclosed here is a highly enantioselective difunctionalization of azetines for convenient access to chiral 2,3-disubstituted azetidines, a family of important scaffolds previously lacking general access. With Cu/bisphosphine as a catalyst, two versatile functionalities (boryl and allyl) were installed on azetine with concomitant construction of two new stereogenic centers. This represents a rare demonstration of Cu-catalyzed asymmetric boryl alkylation of electron-rich olefins and C═C bonds in strained heterocycles. The use of allyl phosphates proved critical not only to overcome the low reactivity of the borylated alkylcuprate intermediate toward alkylation but also to avoid competing side reactions. Remarkably, in almost all cases, single isomers were obtained with complete regio-, enantio-, and diastereoselectivies on the azetidine motif as well as excellent control on the double bond configuration. The mild conditions exhibited outstanding functional group compatibility and chemoselectivity. The versatile boryl and allyl functionalities allowed for easy transformations of the products to other useful chiral azetidines previously lacking straightforward access. Control experiments and kinetic studies indicated that the reaction proceeds by a fast boryl cupration of azetine followed by rate-determining allylation via an intrinsically controlled S N 2′ pathway.
DOI: 10.1021/jacs.5c07821
Authors: Minghui Zhu, Jianwei Sun
Institution: Hong Kong University of Science and Technology
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1162233175, Organocatalytic Asymmetric Construction of All-Carbon Quaternary Stereocenters in Congested Systems, G1678791140, Design of Chiral Catalysts and Organocatlytic Processes for Asymmetric Synthesis, Development of New Strategies for the Asymmetric Synthesis of α-Chiral Carbonyl Compounds, Chiral Phosphoric Acid-Catalyzed Asymmetric Electrochemical Transformations, Regioselective and Stereoselective Addition of Ynones and Siloxy Alkynes, G4227328392, G534716927, G637631384
OpenAlex ID: W4411583582