Synthesis of γ-Alkylidene Lactones via Molecular Stitching of Carboxylic Acids and Olefins

11 April 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

In this study, we describe a direct palladium-catalyzed tandem β-C(sp3)–H olefination/lactonization strategy for the one-step synthesis of γ-alkylidene lactones. The reaction is enabled by an N-acyl sulfonamide ligand and utilizes readily available and inexpensive carboxylic acids and styrenes as coupling partners, enabling an efficient construction of structurally diverse γ-alkylidene lactones through the consecutive functionalization of three C–H bonds. Notable highlights include excellent functional group tolerance and derivatizations of the resulting γ-alkylidene lactones to obtain various synthetically useful motifs.

Keywords

γ-Alkylidene Lactones
Carboxylic Acids
Styrenes
Palladium Catalysis
C–H Activation
Ligand Design

Supplementary materials

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Supporting Information
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Description of experiments and analytical data.
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