Hydroxyaldehydes Wittig reaction

Since 67 is a latent hydroxyaldehyde it can react directly with stabilized ylide 30 in a Wittig reaction to provide the (2 , 4Z)-diene ester 31. 

Recently, improved procedures have been developed [17] for the synthesis of the phosphonium bromide 30. Addition of the hydroxyaldehyde 29 to NBS/dimethylsulphide in CH2CI2 at -20°C provided (all- )-8-bromo-2,7-dimethylocta-2,4,6-trienal (31) in 86% yield. Reaction of 31 with triphenylphosphine in ethyl acetate furnished the phosphonium bromide 30 in 88% yield. In most applications carried out so far, the phosphonium salts 30 and 32 (prepared from 33 and 31) have been transformed to the corresponding dimethylacetals 27 and 28, prior to their use in Wittig condensations. However, protection of the aldehyde function of 30 is not always necessary [17]. Direct Wittig reaction between 30 and 34 afforded the Ci6-ketoaldehyde 35 in 43% yield. 

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. 

I- ol, and elaborated by conjugate addition of nitrile, ketal formation, conversion with diisobutylaluminium hydride to the hydroxyaldehyde (129) and then the sequence Wittig reaction, alcohol oxidation with chromium trioxide—sulphuric acid in dimelhylformamide, ketone reduction and ketal hydrolysis to give (1)-... 

---