Issue 14, 2025

Asymmetric copper-catalyzed hydrophosphinylation of ethynylazaarenes to access P-chiral 2-azaaryl-ethylphosphine oxides

Abstract

We report a cost-effective approach for the enantioselective hydrophosphinylation of ethynylazaarenes utilizing a chiral copper catalytic platform. This strategy efficiently converts racemic secondary phosphine oxides (SPOs) into P-chiral tertiary phosphine oxides (TPOs) bearing functionalized olefin substituents with azaarene moieties, achieving high yields and exceptional enantioselectivities. These adducts serve as crucial intermediates in the development of valuable chiral 1,5-hybrid P,N-ligands. The facile introduction of diverse additional carbon-centered chirality through the transformation of the olefin moiety effectively enhances the enantioselectivity of asymmetric metal catalysis compared to ligands exhibiting solely P-chirality. Mechanistic investigations reveal that the interaction between the chiral Cu(I) complex and azaarenes promotes the kinetic resolution of SPOs. The robustness of this method is further demonstrated by its ability to incorporate deuterium atoms into the olefins, highlighting its potential relevance in pharmaceutical applications.

Graphical abstract: Asymmetric copper-catalyzed hydrophosphinylation of ethynylazaarenes to access P-chiral 2-azaaryl-ethylphosphine oxides

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Article information

Article type
Edge Article
Submitted
15 Jan 2025
Accepted
28 Feb 2025
First published
03 Mar 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2025,16, 5957-5966

Asymmetric copper-catalyzed hydrophosphinylation of ethynylazaarenes to access P-chiral 2-azaaryl-ethylphosphine oxides

J. Zhang, J. Guo, R. Xu, D. Zheng, K. Lian, Z. Zhang, S. Cao and Z. Jiang, Chem. Sci., 2025, 16, 5957 DOI: 10.1039/D5SC00358J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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