A one-pot, sequential phosphate tether-mediated method for the synthesis of simplified 2-desmethyl sanctolide A analogs is reported. Western side-chain diversification was achieved using a pot-efficient, sequential cross metathesis (CM)/ring-closing metathesis (RCM)/H2/dephosphorylation procedure. Further diversification was achieved by Me3Al-mediated amide formation, Yamaguchi esterification, and RCM macrocyclization to access five C11/C12 Z-configured, 2-des-methyl sanctolide A analogs with improved stability.