合成路线1

The condensation of isobutyraldehyde (I) with triethyl phosphonoacetate (II) by means of NaH in THF gives 4-methyl-2-pentenoic acid ethyl ester (III), which is reduced with DIBAL in THF to yield the allyl alcohol (IV). The Sharpless asymmetric epoxidation of (IV) by means of Ti(O-iPr)4, (+)-diethyl tartrate ((+)-DET) and tBu-OOH in toluene affords the epoxy alcohol (V), which is treated with trichloroacetonitrile and DBU to provide the acetimidate (VI). The cyclization of (VI) by means of triethyl aluminum chloride in dichloromethane gives the oxazoline (VII), which is silylated with Tbdms-OTf and TEA in dichloromethane to afford the silyl ether (VIII). The cleavage of the oxazoline ring of (VIII) by means of HCl in THF yields the chiral amino alcohol (IX), which is protected with Tbdms-OTf as before to afford the silylated amine (X). The monoalkylation of (X) with 1,3-dibromo-2-methylpropene (XI) and Cs-OH in DMF provides the secondary amine (XII). The cyclization of (XII) by means of KHMDS in toluene/ethyl ether gives the non isolated intermediate (XIII) that rearranges to the pyrroline (XIV). The reaction of (XIV) with TPAP and NMO in acetonitrile yields the cyclic imine (XV), which is oxidized with NaClO2 to the 1-chloropyrrolin-2-one (XVI). The dechlorination of (XVI) by means of NaBH4 affords the pyrrolinone (XVII), which is selectively monodesilylated with TBAF in THF to provide the primary alcohol (XVIII). The cyclization of (XVIII) with benzaldehyde dimethylacetal and Ts-OH in refluxing toluene gives the bicyclic pyrrolo oxazole (XIX), which is finally deprotected by means of TBAF in THF to yield the target bicyclic intermediate (XX) (see scheme no. 23327701c intermediate (XXXII)).