Aldehydes from tetrahydropyranyl alcohols

A second problem with Sarett oxidation is the difficulty in isolating the products from a pyridine solution. An advantage of the technique, as mentioned above, is that alkenes, ketals, sulfides, and tetrahydropyranyl ethers are oxidized much slower than alcohols and rarely give competitive side reactions. Oxidation of secondary alcohols proceeds in good yield, but oxidation of primary aliphatic alcohols often gives low yields of the aldehyde. 2 Benzylic and allylic alcohols give good yields, however. 

A second new synthesis of squalene utilizes the observation that selenium dioxide oxidation of gem-dimethyl olefins or cis- and truns-allylic alcohols yields stereospecifically traus-aj3-unsaturated aldehydes. The olefin (4) or a mixture of cis- and truus-diols (5) were transformed by use of selenium dioxide, followed by reduction, into the truns-allylic diol (6). The corresponding bromide (7) was used to alkylate two moles of the ylide from trans-geranyltributylphosphonium bromide leading eventually to all-traus-squalene in 46% yield [from the diol (6)]. Protection of one of the p-alcohol groups of (6) as the tetrahydropyranyl ether opens the possibilities of unsymmetrical coupling and the introduction of specifically labelled fragments. 

Compound 32 was prepared in four steps from 4-hydroxy-2-butanone (36). Protection of the alcohol ftmction of 36, as a tetrahydropyranyl (THP) ether 37, was acconqjlished with dihydropyran (DHP) and NH4CI catalyst in refluxing THF (24). Wittig reaction of 37 with the ylide from butyl(triphenyl)phosphonium bromide (n-BuLi, THF) resulted in alkylidenation to form 38, but the yield was less than 5%, even with dropwise addition of the ylide to the aldehyde at -78 . Removal of the THP group, followed by oxidation of the alcohol directly to the acid under neutral conditions (PDC in DMF, 33) afforded 32. Mild oxidation conditions are required to prevent migration of the double bond from the 3-position to the 2-position. 

The propargylic alcohol (83) has been cleverly isomerized to the ajff-unsaturated aldehyde (84) by equilibrating its tetrahydropyranyl ether with the corresponding allenyl derivative in the presence of strong base. After selective hydrolysis of the allenyl acetal (vinyl ether) (85), (84) is easily separable from unchanged (86) by distillation. ... 

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