合成路线1

The dehydro precursors (XXIa) and (XXIb) are prepared by the following sequences. Allylic bromination of β-cyclocitral (XXXVII) with N-bromosuccinimide in cold CH2Cl2 in the presence of CaO and NaHCO3 followed by elimination of HBr in boiling collidine gives α-safranal (XXXVIII). Subsequent cyclization of aldehyde (XXXVIII) with the lithium carbanion derived from ethyl 3,3-dimethylacrylate (XXXIX) in cold THF provides lactone (XLa). The analogous lactone containing an unconjugated cyclohexadiene ring (XLb) is obtained by MichaelWittig tandem reaction of ethyl 2-isopropylideneacetoacetate (XLI) with the phosphorous ylide derived from allyltriphenylphosphonium chloride (XLII) to produce the cyclic ester (XLIII). Subsequent LiAlH4 reduction of ester (XLIII) followed by Swern oxidation gives aldehyde (XLIV). After isomerization of aldehyde (XLIV) upon treatment with catalytic DBU in CH2Cl2 at room temperature, the isomeric cyclohexadienal (XLV) is condensed with ethyl 3,3-dimethylacrylate (XXXIX) as above to furnish lactone (XLb). Reduction of either lactone (XLa) or (XLb) with DIBALH followed by acid-catalyzed ring opening of the resulting lactols leads to the respective tetraenic aldehydes (XLVIa) and (XLVIb), which undergo Horner-Emmons olefination with diethyl 3-(ethoxycarbonyl)-2-methylprop-2-enylphosphonate (XIII) to furnish the corresponding esters (XXIa) and (XXIb) (9). Scheme 4.