INTRAMOLECULAR AND INTERMOLECULAR HETERO-DIELS-ALDER REACTIONS .34. ENANTIOSELECTIVE TOTAL SYNTHESIS OF THE MYCOTOXIN (-)-TALAROMYCIN-B BY A HETERO-DIELS-ALDER REACTION

(-)-Talaromycin B was formed in an overall yield of 5% in nine steps via a hetero Diels-Alder reaction of the exocyclic vinyl ether 3 and methyl O-benzoyldiformylacetate (4) as the key transformation. The enantiomerically pure vinyl ether 3 was prepared in 28% yield and ee > 98% by alkylation of the N-butyryloxazolidinone 5 with 1-bromo-4-(trimethylsilyl)-2butyne (6), followed by a reduction-hydrogenation-protodesilylation sequence to give 9, which was transformed into 3 by iodoetherification with iodine and elimination with DBU. Methyl O-benzoyldiformylacetate (4) was synthesized by formylation of methyl 3,3-dimethoxypropionate, followed by benzoylation. The cycloaddition of 3 and 4 gave predominantly the desired adduct 11 together with the other three possible diastereomers. (-)-Talaromycin B (2) was obtained from 11 by reduction with DIBAL-H and stereoselective hydrogenation with platinum as catalyst. For purification purposes, 2 was transformed into a cyclic silyl ether by reaction with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane.