A Simple and Efficient Strategy for the Total Synthesis of 13-Methyl-(5Z,8Z)-Tridecadienolide

A simple and efficient approach was developed for the synthesis of 13-methyl-(5Z,8Z)-tridecadienolide (1) using commercially available starting materials, such as 5-hexynol (2) and methyl 5-hexynoate (7). The key intermediate, Tos-protected methyl diynoate (8), was stable in the crude oil and was obtained by coupling 7 with TBS- and Tos-protected oct-2-yne-1,7-diol (6), the latter being derived from 5-hexynol (2) through a series of reactions including Dess–Martin oxidation, Grignard reaction, TBS-protection, hydroxymethylation, and Tos-protection. Deprotection of the TBS group and the subsequent ester hydrolysis of intermediate 8 led to the diynoate precursor 9. This precursor was then converted into macrolide 1 through lactonization using the Yonemitsu method, achieving an overall yield of 30.7%.