Issue 27, 2022

Ligand-dependent, palladium-catalyzed stereodivergent synthesis of chiral tetrahydroquinolines


The most fundamental tasks in asymmetric synthesis are the development of fully stereodivergent strategies to access the full complement of stereoisomers of products bearing multiple stereocenters. Although great progress has been made in the past few decades, developing general and practical strategies that allow selective generation of any diastereomer of a reaction product bearing multiple stereocentres through switching distinct chiral catalysts is a significant challenge. Here, attaining precise switching of the product stereochemistry, we develop a novel P-chirogenic ligand, i.e.YuePhos, which can be easily derived from inexpensive and commercially available starting materials in four chemical operations. Through switching of three chiral ligands, an unprecedented ligand-dependent diastereodivergent Pd-catalyzed asymmetric intermolecular [4 + 2] cycloaddition reaction of vinyl benzoxazinanone with α-arylidene succinimides was developed. This novel method provides an efficient route for the stereodivergent synthesis of six stereoisomers of pyrrolidines bearing up to three adjacent stereocenters (one quaternary center). Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to 98% ee. In addition, the synthetic utilities of optically active hexahydrocarbazoles are also shown.

Graphical abstract: Ligand-dependent, palladium-catalyzed stereodivergent synthesis of chiral tetrahydroquinolines

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Article information

Article type
Edge Article
18 May 2022
18 Jun 2022
First published
20 Jun 2022
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., 2022,13, 8131-8136

Ligand-dependent, palladium-catalyzed stereodivergent synthesis of chiral tetrahydroquinolines

Y. Wang, E. Li and Z. Duan, Chem. Sci., 2022, 13, 8131 DOI: 10.1039/D2SC02771B

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