Three-component coupling approach toward the synthesis of a resorcylic acid lactone framework

A resorcylic acid lactone (RAL) framework was constructed based on a three-component coupling approach. The key step was the intermolecular alkylation of a protected cyanohydrin with an aromatic scaffold, and the subsequent carbonylative esterification of the aryl iodide with an alcohol. This sequence allowed the rapid assembly of three components without extra protection/deprotection steps. This synthetic strategy enables the ketone at the 2′ position to be masked as a protected cyanohydrin during the ester formation, thus avoiding an undesired isocoumarin formation. This method should be widely applicable to the synthesis of various types of RAL frameworks.

The efficient synthesis of a resorcylic acid lactone framework has been achieved via the alkylation of a protected cyanohydrin with an aromatic scaffold and carbonylation with an alcohol, followed by an RCM reaction. The key step is the alkylation/carbonylation sequence, which enables the rapid assembly of three components without extra protection/deprotection steps.Figure optionsDownload as PowerPoint slide