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

• Published in: Tetrahedron 2011-09, Vol.67 (35), p.6654-6658
• Main Authors: Sugiyama, Sakae, Fuse, Shinichiro, Takahashi, Takashi
• Format: Article
• Language: English
• Subjects: Assembly; Carbonylation; Chemistry; Cyanohydrin; Esters; Exact sciences and technology; Formations; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Iodides; Joining; Lactones; Multi-component coupling; Organic chemistry; Preparations and properties; Resorcylic acid lactone; Strategy; Synthesis (chemistry)
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.05.023

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. [Display omitted] 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.