Spiroketal pheromone

Different alcohols and protected alcohols (as hemiacetals, silyl, methoxymethyl or phenyl ethers) were lithiated at the d-position to give the corresponding organolithium compounds. In the case of alcohols, a previous deprotonation of the hydroxyl functionality is required. The chiral intermediate 197 was prepared from the phenylsulfanyl derivative 196 first by deprotonation followed by carbon-sulfur bond cleavage with LiDTBB at low temperature. The reaction of the dianionic system 197 with y- and d-lactones in the presence of cerium(III) salts gave, after hydrolysis, spiroketal pheromones 198 (Scheme 2.27) [163]. 

Now that you know about the anomeric effect, you should add it to your mental array of ways of explaining unexpected results. Here is an example. Many fruit flies have pheromones based around a spiroketal structure, which we could represent without stereochemistry as shown below. You can imagine the spiroketal (that is, an acetal of a ketone made of two rings joined at a single atom) being made from a dihydroxyketone—and, indeed, this is very often how they are made synthetically. But this is a bad representation because these compounds do have stereochemistry, and the stereochemistry is very interesting. 

The fact that the substituents on the side chains can control the conformation of the spiroketal centre means that it is not necessary to worry about that centre in a synthesis, provided you are trying to make the spiroketal that has the double anomeric stabilization (both oxygens axial) and that has any substituents equatorial on the rings. A recent (1997) synthesis of a single enantiomer of some fruit-fly pheromones from an aspartic acid-derived bromodiol is shown overleaf. It involves three different-sized oxygen heterocycles. 

There are many other scolytid species that utilize these and similar compounds to effect intraspecific communication. Francke et al. (18) have discovered several spiroketals as active components of scolytid pheromones. Additionally, several parasites and predators utilize the pheromones produced by their scolytid prey as kairomones. For example, the predatory beetle, Temnochlla chlorodla, responds specifically to exo-brevicomin produced by female D. brevlcomls (19). This same phenomenon has been demonstrated recently in Lepidoptera the egg parasite Trlchogramma sp. uses the Hellothls zea (Boddie) sex pheromone to locate the H. zea eggs (20). 

Two important spiroketals, such as l,7-dioxaspiro[5.6]undecane (29a), the major component of the olive fruit fly (Dacus oleae) sex pheromone (Baker et ah, 1980 Fanelli et ah, 1983), and ( )-2-methyl-l,7-dioxaspiro[5.6]dodecane (29b), a component of pheromone of Andrena haemorrhoa (Bergstroem et al., 1981 Katsurada and Mori, 1984), have been prepared in a cascade process from polyfunctionalized nitroalkanes (26) (Ballini and Petrini, 1992). 

Finally, oxidative cyclization (HgO, I2, hiA of tqjpropriately substituted alcoholic ethers formed the basis of Kay s stereoselective syntheses of both 4-hydroxy-l,7-dioxaspiro[S.S]undecane, an olive fly pheromone component, and ( )-talaromycin B (equations 4 and 5). More recently, Danishefsky et at have further extended the scope of this spiroketal-forming reactitm in their elegant total synthesis of avermectin Ai (equation 6). ... 

A neat approach (Scheme 37) to the spiroketal 213, a component of the pheromone of the olive fruit fly, involves a base-catalysed oxy-Michael addition between ketosugar 210 and 211 to give stereoselectively the adduct 212, convertible as indicated to the target. ... 

In complexation gas chromatography, semipreparative separations of spiroketals (among them pheromones) have been reported. The preparative invertomer separation of l-chloro-2,2-dimethylaziri-dine permitted the determination of chiroptical data, absolute configuration and inversion barrier. Very large separation factors a were observed for saturated hydrocarbons (cis- and tra s-pinane, camphene) on a mixture of a-cyclodextrin in form-amide impreg/nated on celite. The preparative enantiomer separation of a-ionone on (18) and of all-trans-perhydrotriphenylene on (25) has been described. The large separation factors observed for the inhalational anesthetics enflurane, isoflurane, and desflurane on (18) allowed their enantiomer separation for subsequent biomedical trials and acquisition of chiroptical data. The continuous preparative enantiomer separation of enflurane and... 

Spiroketals.- The discovery that this class of compounds includes insect pheromones has stimulated extensive synthetic effort. A variety of 1,6-dioxaspiro[4.4]nonanesand 1, 6-dioxaspiro[4.5]dec-anes have been prepared by reaction of lithium salts of protected alkynols with equimolar amounts of lactones followed by hydrogena tion and acid-catalysed deprotection and cyclisation (Scheme 16). 

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