Methyl chrysanthemate

METHYL CHRYSANTHEMATE DIMETHYL PYRETHRATE mixture contribute to the total monocarboxylic and dicarboxylic acids found. 

The first reported use of the DPM rearrangement in natural product synthesis can be found in the synthesis of methyl chrysanthemate, 71, reported by Pattenden and Whybrow (Scheme 18)35. This is produced directly by photolysis of 1,4-diene 70. While it should be noted that this reaction gave 71 in only 12% yield, it did furnish the desired product in a single step, with the correct relative stereochemistry. Bullivant and Pattenden also used a DPM rearrangement to form an advanced intermediate in the synthesis of the dideoxy derivative of the sesquiterpene taylorione, 7436. Irradiation of 72 afforded 73 in 45% isolated yield this was then simply converted to 74 using standard transformations. 

As mentioned earlier the DPM rearrangement has been used in the synthesis of methyl chrysanthemate 60 [44,45]. However, the 1-ADPM reaction should be considered as a better alternative since the DPM reaction of 59 afforded compound 60 in 12-15% only, after 30 h of irradiation (Sch. 22). 

To a stirred, cold ( 78°C) solution of LDA (30.0 mmol), prepared from i-PrjNH (3.03 g, 4.20 mL, 30.0 mmol) and BuLi (30.0 mmol) and kept under a N2 atmosphere, in dry THE (45 mL) was added methyl chrysanthemate (1.83 g, 10.0 mmol). The solution, which quickly turned yellow, was stirred at — 78 °C for 24 h and (MeS)2 (4.70 g, 50.0 mmol) was subsequently added. The resulting mixture was slowly allowed to reach rt and after 24 h, sat. aq NH,jCl (15 mL) was added. The phases were separated, the aqueous phase was extracted with f-BuOMe (2 x 20 mL), and the combined organic solutions were dried (MgS04). Filtration and evaporation of the solvent gave a crude product (3.86 g), from which, when distilled twice using a Kugelrohr apparatus, was obtained 1.40 g (61%) of pure product bp lOO C/0.5 Torr d.r. icisjtrans) 70 30. 

Poulter et al. have shown that the absolute configuration of natural santolinyl alcohol (62) is S, the same as that of natural methyl chrysanthemate (R, because of the change in priorities), by ring-opening dihydrochrysanthemyl alcohol (69)... 

Draw a mechanism to account for the formation of methyl chrysanthemate by the transformation shown below. 

Chrysauthemie esters. Belgian chemists noted that chrysanthemic acid could be formed from two isopropylidene units and, indeed, they obtained /rnns-methyl chrysanthemate (2) in 60% yield by reaction of methyl trans A-oxobutenoate (1) with isopropylidenetriphenylphosphorane (—78->20°). Cyclopentylidenetriphenylphosphorane reacts with (1) in the same way, but other dialkylmethylenetriplienylphosphoranes react to form dienoic esters. 

Three- and Four-membered Rings. Methyl chrysanthemate (75) has been obtained as a 1 2 mixture of cis- and trans-isomers by the di-ir-methane cyclization of the diene ester (74) (Scheme 24). Cyclopropanes may also be prepared by the photocyclization of allylmagnesium bromide. ... 

Figure 2. Infrared spectrum of methyl-trans-chrysanthemate Prepared from DL-trans-chrysanthemum acid and collected as pure ester from gas chromatograph...

The columns labeled PI reflect the total of pyrethrin I and cinerin I just as in the AO AC procedure. The gas chromatographic results are in terms of the total amount of the mixture but were analyzed as the methyl ester of chrysanthemic acid. The present state of the determination of PII (pyrethrin II plus cinerin II) is not complete because of the erratic extractability of the dicarboxylic acids from the hydrolysis mixture. The gas chromatographic pattern is distinct and straightforward. As the extraction procedure for PII is improved, the gas chromatographic method will be more applicable. The present recovery of PII is in the range of 80 to 90%. The average of the values shown in Table II for PI is 98.0%. 

For the synthesis of permethric acid esters 16 from l,l-dichloro-4-methyl-l,3-pentadiene and of chrysanthemic acid esters from 2,5-dimethyl-2,4-hexadienes, it seems that the yields are less sensitive to the choice of the catalyst 72 77). It is evident, however, that Rh2(OOCCF3)4 is again less efficient than other rhodium acetates. The influence of the alkyl group of the diazoacetate on the yields is only marginal for the chrysanthemic acid esters, but the yield of permethric acid esters 16 varies in a catalyst-dependent non-predictable way when methyl, ethyl, n-butyl or f-butyl diazoacetate are used77). 

A striking example for the preferred formation of the thermodynamically less stable cyclopropane is furnished by the homoallylie halides 37, which are cyclopro-panated with high c/s-selectivity in the presence of copper chelate 3891 The cyclopropane can easily be converted into cw-permethric acid. In contrast, the direct synthesis of permethric esters by cyclopropanation of l,l-dichloro-4-methyl-l,3-pentadiene using the same catalyst produces the frans-permethric ester (trans-39) preferentially in a similar fashion, mainly trans-chrysanthemic ester (trans-40) was obtained when starting with 2,5-dimethyl-2,4-hexadiene 92). 

The change in selectivity is not credited to the catalyst alone In general, the bulkier the alkyl residue of the diazoacetate is, the more of the m-permethric acid ester results 77). Alternatively, cyclopropanation of 2,5-dimethyl-2,4-hexadiene instead of l,l-dichloro-4-methyl-l,3-pentadiene leads to a preference for the thermodynamically favored trans-chrysanthemic add ester for most eatalyst/alkyl diazoacetate combinations77 . The reasons for these discrepandes are not yet clear, the interplay between steric, electronic and lipophilic factors is considered to determine the stereochemical outcome of an individual reaction77 . This seems to be true also for the cyclopropanation of isoprene with different combinations of alkyl diazoacetates and rhodium catalysts77 . 

In conclusion, all of the eight stereoisomers of norchrysanthemic acid methyl esters were synthesized in stereoselective manner starting from (1/ )-inmv-chrysanthemic acid or (+)-3-carene. All stereoisomers of metofluthrin were synthesized in our laboratory. Their structure-activity relationship will be published elsewhere. 

Oxidation reactions occur on several sites of the acid and alcohol moieties, depending on the chemical structures. For example, the trans methyl of the isobutenyl group in chrysanthemates is preferentially oxidized over the cis methyl group in rats, and the 4 -position of the phenoxy ring is oxidized to a larger extent as compared with other positions [8] (Fig. 1). 

Much effort this year has been expended on chrysanthemic acid syntheses. Aratani et al. have extended earlier work on asymmetric synthesis (Vol. 6, p. 21) by decomposing various alkyl diazoacetates in 2,5-dimethylhexa-2,4-diene in the presence of chiral copper complexes to yield up to 92% of rrans-chrysanthemic acid in 88% dextrorotatory enantiomeric excess. Mitra has used ozonolysis of (+)-a-pinene to obtain, stereospecifically, the bromo-ketone (104) which undergoes Favorskii rearrangement to yield the anticipated ester (105) from which (+)-trans-chrysanthemic acid is readily obtained a second paper reports another route from (+)-car-3-ene initially to methyl (—)-c/s-chrysanthemate or to (—)-dihydro-chrysanthemolactone (106), both of which are convertible into (+)-rra s-chrysan-... 

Tetramethrin, (l,3,4,5,6,7-hexahydro-l,3-dioxo-2RZ-isoindole-2-yl)-methyl ( )- i,/ra -chrysanthemate (mp 65—80°C), a mixture of four isomers, is soluble in water to 20 //g/L. The rat oral LD5Q is >5000 mg/kg. Tetramethrin produces rapid knockdown and is used in veterinary hygiene. 

S)-3-Methyl-2-phenylbutylamine, a new versatile synthetic resolving agent we have proposed, is effective for the resolution of chrysanthemic acid, ibuprofen, ketoprofen, naproxen and others.19... 

A more dramatic example is the synthesis of cA-chrysanthemic acid 11, the basis of most modern insecticides, from dimedone 8, whose synthesis we discussed in chapter 21. Methylation between the two carbonyl groups gives 9, with the complete skeleton of 11—a little reorganisation of the atoms is needed. Treatment with bromine and base gives the inevitably cis-fused bicyclic dione 10 and a further three simple steps produce chrysanthemic acid.3... 

The mechanism of carbamate-resistance, formerly considered to be enhanced hydrolysis (e.g. carbaryl to 1-naphthol), was found to derive almost exclusively from hydroxylation at various points on the molecule, not only the aromatic leaving group but also the N-methyl on the carbamate (Fig. 3), as well as some desmethylation for good measure (14). Pyrethrin-resistance, at first considered to be due to hydrolysis of the alcohol-acid linkage, was also found to be due to an oxidation, occurring at the transmethyl group of the isobutenyl side-chain of the chrysanthemic acid (15). 

Addition of (159, R = Et) to methyl 3,P-dimethylacrylate followed by Raney nickel desulphurisation also provides a convenient route to m-chrysanthemic acids 127>. 

Bu3SnLi adds to ,/3-unsaturated esters, and the resulting Li-enolate reacts with 3-methyl-2-butenal to afford 7-hydroxyalkyl tins which are treated with BF3-OEt2 to produce vinyl cyclopropane carboxylic esters (chrysanthemic acid) (Equation (111)).280... 

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