Issue 1, 2020

Enantioselective synthesis of P-chiral tertiary phosphine oxides with an ethynyl group via Cu(i)-catalyzed azide–alkyne cycloaddition

Abstract

We report the highly enantioselective synthesis of P-chiral tertiary phosphine oxides featuring an ethynyl group via Cu(I)-catalyzed azide–alkyne cycloaddition. Newly developed chiral pyridinebisoxazolines (PYBOX) bearing a bulky C4 shielding group play an important role in achieving excellent enantioselectivity while suppressing side bis-triazoles formation in desymmetrizing prochiral diethynylphosphine oxides. Notably, by tuning the size of the C4 shielding group, it is possible to achieve excellent remote enantiofacial control in desymmetrizing phosphole oxide-diynes with the prochiral P-center farther from the ethynyl group by four covalent bonds. Time-dependent enantioselectivity is observed for these desymmetric CuAAC reactions, suggesting a synergic combination of a desymmetrization and a kinetic resolution, and our ligands prove to be better than unmodified PYBOX in both steps. This finding contributes to a highly enantioselective kinetic resolution of racemic ethynylphosphine oxides. The resulting chiral ethynylphosphine oxides are versatile P-chiral synthons, which can undergo a number of diversifying reactions to enrich structural diversity.

Graphical abstract: Enantioselective synthesis of P-chiral tertiary phosphine oxides with an ethynyl group via Cu(i)-catalyzed azide–alkyne cycloaddition

Supplementary files

Article information

Article type
Edge Article
Submitted
01 Okt 2019
Accepted
05 Nov 2019
First published
06 Nov 2019
This article is Open Access

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

Chem. Sci., 2020,11, 97-106

Enantioselective synthesis of P-chiral tertiary phosphine oxides with an ethynyl group via Cu(I)-catalyzed azide–alkyne cycloaddition

R. Zhu, L. Chen, X. Hu, F. Zhou and J. Zhou, Chem. Sci., 2020, 11, 97 DOI: 10.1039/C9SC04938J

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