One-Pot Carbon-Chain Extension for Nervonic/Carboxylic Acid Synthesis with the Assistance of Microwaves and Lithium Chloride

Abstract

AbstractA mild, green, and convenient synthesis of nervonic acid was developed through a one-pot carbon-chain extension with the assistance of microwaves and lithium chloride (55% total yield); this is preferable to a previous six-step method (10% total yield). Compared with the previous lengthy refluxing process (>80 hours) with corrosive reagents, which furnished a mixture of cis- and trans-isomers, this efficient microwave protocol was more than a hundred times faster and was free of configurational isomerization. Notably, LiCl played a dual role in a Krapcho decarboxylation and subsequent ester hydrolysis under neutral conditions that replace the corrosive saponification in the previously reported one-pot method. Finally, this mild and efficient protocol was successfully applied to various carboxylic acids, including natural products, verifying its wide utility, easy operations, and attractive properties in organic synthesis.