Synthesis of Protected C15- and C2o-Dialdehydes

Procedures have been worked out [19] for the synthesis of the free and partially protected dials 36-39 and 40-43 and some of their C25- and Cso-isoprenologues, starting from the corresponding Cio-dials 8 and 6 and the Cs-phosphonium salt [13,19]. 

Condensation of the Grignard complex of 58 with triethyl orthoformate (59) gave a 75% yield of distilled hydroxyacetal 60. Partial hydrogenation of 60 to 61, followed by acidic hydrolysis, provided hydroxyaldehyde 62, which was isolated in the (all- -configuration. A Wittig reaction of 62 with the ylide of (a-ethoxycarbonylethyl)-tris(dimethylamino)-phosphonium bromide (63) furnished the hydroxyester 64. Treatment of 64 with ca. 0.5 mol equivalents of PBr3 in ether/hexane at -5°C in the presence of a small amount of pyridine gave an 84% yield of crystalline ester bromide 65, which could be transformed to the phosphonium bromide 55 (yield 93%) by reaction with triphenylphosphine in ethyl acetate. 

Li this procedure, 0.5 mol% of palladium dichloride bis(acetonitrile) is added to neat acetoxy-acetal 82. The mixture is stirred for one hour at 50°C and then cooled to room temperature. Separation of the catalyst is achieved by short-path distillation under reduced pressure. The allylic acetate 83 is obtained as a 91 9 fE j-mixture in 95% yield. 

A BASF patent [30] describes the transformation of 81 into 4-chloro-2-methylbut-2-enal (88), which is an ideal precursor for the preparation of (3-methyl-4-oxobut-2-enyl)-triphenyl-phosphonium chloride (89). The phosphonium salt 89 is usually acetalized before being used in Wittig condensations [19,31]. Acetylation of 88 with potassium acetate in anhydrous ethanol furnished the acetoxyaldehyde 73 in high yield [32]. 

Isoprene (90) has also been considered as a starting material for the building block 73. Selective oxidation of isoprene (90) with 82% peroxyacetic acid gave an 80% yield of 3,4-epoxy-3-methylbut-l-ene (91), which was transformed into the chloroaldehyde 88 by treatment with cupric chloride in the presence of lithium chloride [32]. A short synthesis of 73 from isoprene (90) has been worked out [33]. 3-Methyl-4-nitrobut-2-en-l-yl acetate (92), obtained in excellent yield by nitroacetyloxylation of isoprene (90), was reduced with iron in acetic acid to give a mixture of oxime 93 and acetoxyaldehyde 73. Steam distillation at pH 2.5 in the presence of formaldehyde furnished distilled 73 in a 40% overall yield based on 90. 

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