Total synthesis of trifluoromethylated analogs of macrosphelide A

Trifluoromethylated analogs of macrosphelide A 1 and 2 were designed and synthesized. The key segment 6 was efficiently constructed via a series of high stereoselective transformations from trifluoromethylated diol 8. Methoxymethylation of compound 9 with 1.0 equiv of sodium hydride gave optically pure compound 23a in 73% yield. From 23a a novel route was developed to prepare key segment 7. The condensation and macrolactonization were smoothly proceeded under our modified Keck's protocol.