合成路线1

The chiral tetrahydropyran intermediate (XI) has been obtained as follows. The reaction of (-)-pseudoephedrine propionamide (I) with the allyl bromide (II) by the Myers' method gives pentenamide (III), which is reduced with LiNH2BH3 in THF to yield 2(S)-methyl-4-penten-1-ol (IV). Swern oxidation of (IV) affords the corresponding aldehyde (V), which is submitted to an asymmetric aldol condensation with the silyl enol ether (VI) catalyzed by Cu(OTf)2, (S)-Tol-BINAP and (Bu4N)Ph3SiF2 in THF to provide the adduct (VII). The methanolysis of (VII) with Me-OH in refluxing toluene gives the beta-keto ester (VIII), which is treated with Et2BOMe, NaBH4 and HF to yield the chiral hydroxy lactone (IX). The reduction of (IX) with DIBAL in THF affords the lactol (X), which is finally methylated with Ts-OH in refluxing methanol to provide the target tetrahydropyran intermediate (XI).