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The aldehyde intermediates (V) and (XII) are produced starting from β-ionone (XXVI) by several different methods. The lithium enolate of ketone (XXVI) is acylated with diethyl chlorophosphate to produce an enol phosphate intermediate, which undergoes regioselective β-elimination in the presence of LDA to furnish acetylene (XXVII). Deprotonation of (XXVII) with butyl lithium followed by treatment with phenyl cyanate gives nitrile (XXVIII), which undergoes conjugate addition of dimethyl cuprate in cold THF to afford the cis-trienenitrile (XXIX). Subsequent reduction of nitrile (XXIX) using DIBALH in hexane at –78 °C provides the target aldehyde (V) as the major isomer (4). Alternatively, Reformatsky reaction of β-ionone (XXVI) with the organo zinc reagent derived from ethyl bromoacetate followed by acidic dehydration produces a mixture of cis- and trans-ionylideneacetates (XXX), which, after saponification to the corresponding carboxylic acids, are separated by fractional crystallization from acetonitrile. The desired cis-isomer (XXXI) is then esterified by treatment with iodomethane and potassium carbonate under nonisomerizing conditions to furnish the cis-methyl ester (XXXIIa) (14). Reduction of ester (XXXIIa) with LiAlH4 in cold THF followed by re-oxidation of the resulting alcohol with MnO2 in CH2Cl2 affords aldehyde (V) (3, 14). The analogous tritium-labeled intermediate is similarly obtained utilizing [3H]-LiAlH4 in the reduction step (3). The tricarbonyliron complex of β-ionone (XXXIII) can be conveniently prepared by treatment of (XXVI) with dodecacarbonyltriiron(0) in boiling benzene. Condensation of (XXXIII) with the lithium enolate of ethyl acetate in cold THF gives the hydroxy ester adduct (XXXIV), which is dehydrated by means of SOCl2 in pyridine to produce the (9Z)-conjugated ester (XXXV) as the major isomer. Reduction of ester (XXXV) with DIBALH in Et2O at –45 °C yields the trienol derivative (XXXVI), which is converted to aldehyde (XII) without decomplexation by mild oxidation of the corresponding bromomagnesium alkoxide with azodicarbonyldipiperidine under Mukaiyama’s conditions. Alternatively, decomplexation of (XXXV) with CuCl2 provides the ethyl ester (XXXIIb), which is reduced to aldehyde (V) following known procedures (5). Scheme 3.

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