Citral oxidative rearrangement

Methods for oxidative transformations continue to receive attention. Nickel peroxide on graphite oxidizes geraniol to citral in 89% yield. Three groups report " the oxidative rearrangement of tertiary vinyl carbinols. Linalool is con-... 

The interesting sequence depicted in Scheme 13 for a sequential oxidative rearrangement and hydrox-ylation of citral shows some potential for this reaction in nonaromatic alkenes. This transformation affords an elegant, single-step approach to the 6,8-dioxabicyclo[3.2.1]octane skeleton, although the stereoselectivity for the two induced centers is poor. ... 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

Two key intermediates in the production of vitamin A are citral and the so-called C5 aldehyde. In the modem routes to these intermediates, developed by BASF and Hoffmann-La Roche, catalytic technologies are used (see Fig. 2.29 and 2.30). Thus, in the synthesis of citral, the key intermediate is 2-methyl-l-butene-4-ol, formed by acid-catalyzed condensation of isobutene with formaldehyde. Air oxidation of this alcohol over a silver catalyst at 500°C (the same catalyst as is used for the oxidation of methanol to formaldehyde) affords the corresponding aldehyde. Isomerization of 2-methyl-l-butene-4-ol over a palladium-on-charcoal catalyst affords 2-methyl-2-butene-4-ol. The latter is then reacted with the aldehyde from the oxidation step to form an enol ether. Thermal Claisen rearrangement of the enol ether gives citral (see Fig. 2.29). 

BASF carries out a synthesis of citral which requires, apart from isobutene and formaldehyde, only air for the oxidation. The only by-product is water. With the domino Claisen-Cope rearrangement one can obtain a value-added product in only a single step. 

---