摘要：Otto Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zuKiel, 24118 Kiel, Germany

转自：康龙化成

The Direct Pd-Catalyzed γ-Lactonizationof Aliphatic Carboxylic Acids

Tianxiao Xu,‡ Sourjya Mal,‡ and Manuel van Gemmeren*

‡T.X. and S.M. contributed equally.

Otto Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zuKiel, 24118 Kiel, Germany

—ACS Catal. 2025, 15, 2735−2741

Recommended by Feng Wang_SC

KEYWORDS: C–H activation, Pd catalysis (反应类型), C(sp3)–O (成键类型), carboxylic acids (原料),γ-lactones (产物), β-alanine-derived ligand, sodiumpercarbonate (其他)

ABSTRACT: A direct palladium-catalyzedγ-lactonization of free carboxylic acids via C−O reductive elimination as a keystep is described. Notable aspects of this protocol include the use ofconvenient and easily available sodium percarbonate as an oxidant and the developmentof a highly efffcient β-alanine-derived ligand. The reported method enables the functionalization ofa wide range of aliphatic acids including previously inaccessibleβ-nonquaternary acids. The regioselectivity and consequently substrate scope ofthis protocol proved complementary to established routes for the directlactonization of aliphatic carboxylic acids. Through this report, a valuablecompound library of γ-lactones with potential applications in various ffelds hasbecome available.

Background and this Work

Synthetic Application

Proposed Mechanism

Summary and comments

In summary, Prof. Gemmeren etal. have developed a Pd(II)-catalyzeddirect γ-C(sp3)−Hlactonization of aliphatic carboxylic acids basedon C−O reductive elimination. The use of sodium percarbonate as an oxidant and the developmentof a new β-alanine-derived ligand were key to establish this protocol, whichconverts a wide range of carboxylic acids, for the first time includingchallenging β-non-quaternary acids, into the corresponding lactones in a singlestep. Notably, this lactonization protocol iscomplementary to state-of-the-art methods for the direct lactonization of freecarboxylic acids and gives access to a wide library of lactones that werepreviously only accessible through multistep synthetic routes. Besides thesynthetic utility of the protocol described herein, the discovery of a catalystcapable of functionalizing βnon-quaternary acids is expected to encouragefurther research and substantially broaden the chemical space accessiblethrough the γ-C(sp3)−H activation of aliphaticcarboxylic acids.

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