Work

Enantioselective Synthesis of Spirocyclic Isoxazolones Using a Conia-Ene Type Reaction

Year: 2025

Type: article

Abstract: Stereoselective synthesis of spirocyclic compounds containing heterocyclic motifs represents a formidable challenge in enantioselective synthesis. Here, we present a cascade reaction between α,β-unsaturated aldehydes and isoxazolones under synergistic catalysis of a chiral secondary amine and a palladium(0) catalyst. This strategy allows access to chiral spiroisoxazolone derivatives with a large substrate scope tolerance and high levels of diastereoselectivity (dr up to 20:1) and enantioselectivity (up to 99% ee). Furthermore, the utility of this methodology is showcased by the transformation of chiral spiroisoxazolones into structurally attractive and enantiomerically enriched cyclopentene carboxylic acids with two stereogenic centers.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.4c02921

Authors: Martin Kamlar, Salil Putatunda, Ivana Císařová, Jan Veselý

Institution: Charles University

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Grantová Agentura České Republiky, European Regional Development Fund