Intramolecular Cyclization of (ω-Carboxyalkyl)sulfonium Salts. A Novel Synthesis of Macrocyclic Lactones

Article abstract of DOI:10.1021/jo00283a010

A useful method for the synthesis of macrocyclic lactones using (ω-carboxyalkyl)sulfonium salts was developed.Base-catalyzed intramolecular cyclization of (ω-carboxyalkyl)diphenylsulfonium salts 2 gave simple macrocyclic lactones in high yields at high dilution conditions. (ω-Carboxyalkyl)alkylphenylsulfonium salts 8 afforded simple macrocyclic lactone 6a and alkyl carboxylates 9.The reactions of (ω-carboxyalkyl)dialkylsulfonium salts 10 gave only esters without lactonization product 6a.The cyclization of S-(ω-carboxyalkyl)thiolanium salts 3 and S-(ω-carboxyalkyl)-2-methylthiolanium salts 4 took place readily under similar conditions to afford sulfur-containing macrocyclic lactones 13 and 15, respectively, in good yields.To investigate the reaction mechanism, sulfonium salt 25, having an optically active carbon atom, was prepared.The intramolecular cyclization of 25 took place with an inversion of configuration at chiral carbon atom to give ricinelaidic acid lactone (26; optical purity 66percent).