Synthetic studies on the upper tetrahydropyran subunit $C_{15}-C_{25}$ of lasonolide A

Abstract

For the synthesis of macrocyclic lasonolide A 1, stereoselective synthesis of $C_{15}-C_{25}$ subunit 53 has been accomplished. Synthesis of 53 started from 1,1,1-tris(hydroxymethyl)ethane 64. Asymmetric allylboronation was employed to generate homoallyl alcohol 68. After Swern oxidation of alcohol 65, diastereoselective allylation of 66 with Roush’s allylboronate afforded alcohol 68 in 78% ee. The key intermediate 89 for 118 was prepared from alcohol 68 by treatment with benzaldehyde in the presence of trifluoroacetic acid in toluene, which is considered as thermodynamic product derived probably by hydrogen-bonding. Tetrahydropyran alcohol 116 was oxidized to aldehyde 117 with Dess-Martin periodinane. Modified Julia olefination of aldehyde 117 with sulfone 98 using potassium bis(trimethylsilyl)amide in ethylene glycol dimethyl ether afforded trans-alkene 118.