Chrysanthemic esters

Pyrethroids with Modified Chrysanthemate Esters. Newer pyrethroids incorporate optimized chrysanthemic acid components to retard detoxication by microsomal oxidases and these are esterified with a variety of optimized alcohol moieties therefore increasing persistence. 

Example Ester (59) was needed for a photochemical synthesis of chrysanthemate ester (60), a component of the pyrethrin insecticides. The a,B disconnection (59a) gives synthon (61) and aldehyde (62). This 8,y-unsaturated compound could be made by dehydration of (63) as the double bond can appear in only the required position. On page T 149 we discussed the synthesis of (62) by the aldol dimerisation of (64), An alternative strategy is to work at the ester oxidation level (65) which means synthon (66) is needed to combine with (64). 

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). 

Katsuda Y (1971) Novel chrysanthemate esters. In Proc Second International Congress on Pesticide Chemistry, pp 443 -53... 

Katsuda Y, Chikamoto T, Ogami H, Hirobe H, Kunishige T (1969) Novel insecticidal chrysanthemic esters. Agric Biol Chem 33 1361-1363... 

AUethrin [584-79-2] (d 1.005—1.015, vp 16 mPa at 30°C) is the aUyl homologue of pyrethrin I, ie, R = allyl, —CH2CH=CH2. The synthetic product contains 75—95% of eight enantiomers, 70% (d=)-trans and 30% (d=)-cis acids esterified with (A)-cyclopentenolone alcohol. The relative insecticidal activities of the enantiomers are shown in Table 2. The rat LD5Qs of aUethrin are 920 (oral) and 11,000 (dermal) mg/kg. BioaUethrin [584-79-2] is the (+)-/rwater solubility 4.6 mg/L). AUethrin is as effective as the natural pyrethrins against flies and mosquitoes but has a narrow spectmm of activity against other insect pests. 

Pyrethroids are commercially important insecticides that usually contain a cyclopropyl unit that is m-substituted and a cyanohydrin derivative. They are usually sold as a mixture of isomers. However, asymmetric routes have been developed, especially because these compounds are related to chrysanthemic esters (Chapter 12).251 The pyrethroids can be resolved through salt formation or by enzymatic hydrolysis.252... 

Carbene Chemistry and Asymmetric Synthesis Chrysanthemic Esters... 

Pyrethroids occupy a central position among insecticides because of their high selectivity and low toxicity [34]. Chrysanthemic esters (33), the carboxylic acid components of this important class of compounds, can be synthesized by asymmetric cyclopropanation of olefins (cf Section 3.1.7) by diazoacetates in the presence of a chiral Schiff base-Cu complex (Scheme 9 and Structures 34 and 35) [35-37]. 

Sulfur ylides can also be used in the synthesis of chrysanthemate esters (72) from hept-2-enoates (73) (Scheme 27). The natural insecticide pyrethrum is a complex chrysanthemate ester, and the formation of trans-chrysanthemic acid is consequently important for the synthesis of many synthetic pyrethroid insecticides. 

The syntheses of phenothrin analogues of lower insecticidal activity and of other chrysanthemate esters have been reported. Further pyrethroid papers concern the relationship between insecticidal toxicity and cyclopropane substituents in pyret-hroids, the photochemistry of the most potent known pyrethroid,and the metabolism of permethrin in rats (c/. Vol. 6, p. 13). " ... 

Conversion of cis-chrysanthemate esters to trans-esters is most easily carried out (for the methyl esters) by pyrolysis of the cis-ester at 240—260 C, when the trans-ester is obtained in good yield. ... 

Chromic anhydride-pyridine, 70 Chromium hexacarbonyl, 71 Chromones, 423 Chromous chloride, 73 Chrysanthemic acid, 49, 50, 207-208 Chrysanthemic esters, 183-184 Cinnamic esters, 362 CitroneUol, 5, 308, 309 Claisen rearrangement, 2, 372 Clemmensen reduction, 426 Cocaine, 384 Codeine, 236, 347, 348 Conjugate addition, 86, 102, 119-120, 133, 226-227, 253, 353, 400 Cope rearrangement, 66, 397 Copper, 73-74 Copper(I) acetate, 80 Copper(II) acetate, 39, 117, 126, 186 Copper(I) bromide-Lithium trimethoxy-aluminum hydride, 80 Copper(I) bromide, 79-80 Copper(I) chloride, 50, 80-81 Copper(II) chloride, 126, 79 Copper(l) cyanoacetate, 74 Copper halide nitrosyls, 73 CopperO) iodide, 81-82 Copper(I) methyltrialkylborates, 4,75 CopperGD perchlorate. 79 COpper(I) phenylacetylide, 237 Copper(II) sulfate, 117 CopperO) trifluoiomethanesulfonate, 75-76... 

A one-pot synthesis, which had been developed by Alain Krief and is almost unrivalled for elegance, converts a malealdehydic ester with two equivalents of isopropylidenetriphenylphosphorane to chrysanthemic ester. [82, 83] The first equivalent gives in a Wittig reaction the 5-methylsorbate ester, while the second equivalent performs a nudeophUic addition to this intermediate at the jS-position, and a cydoelimination leads then with the loss of triphenylphos-phine to the product. 

Alkoxycarbonylcarbenes, which are frequently used for cyclopropanation, have been reviewed by Marchand and Brockway.In conjunction with a copper complex of an asymmetric ligand, ethyl diazoacetate will condense with 2,5-dimethyl-hexa-2,4-diene to give optically active chrysanthemic ester.With a cobalt complex of (+ )-camphorquinone dioxime, enantioselectivities as high as 70 % could be obtained in the addition of diazoacetate to 1,1-disubstituted olefins. As would be expected, choice of both metal and chelate is critical in such asymmetric syntheses. ... 

Reaction scheme No. 3 applied on a higher unsaturated system 4 affords at first isopyrazoles 5 which allow an access to cis-chrysanthemic esters after reduction of the intermediate cyclopropene-system using a nickel boride-catalyst or diimine. (Reaction scheme 4) [19]. 

During the search for syntheses of ds-chrysanthemic esters as precursors for cis-caronaldehyde, decomposition of bicychc pyrazoUns 7 were of interest [22] ... 

Introduction of carbon No. 3 via carbene addition yielding chrysanthemic ester was accomplished by trapping the decomposition product 77 of methylmercapto-isopyrazole 12 with senecio ester to give 13 [23], followed by subsequent removal of the thio function with nickel (Reaction scheme 7). 

The diazo reaction with olefins as shown previously is still the fastest method to get hold of mixtures of diastereomers, often, however, with moderate yields due to the lack of reactivity of the olefins. Several nor-chrysanthemic esters [479], alkoxycyclopro-pane carboxylic esters [480,481], which are interesting because of their photostabihty and insecticidal activity [482], and 2,2,3,3-tetramethylcarboxyhc ester [483] were prepared by this route. Asymmetric synthesis using optically active iron carbonyl-olefin complexes afforded 1-R-configurated esters, i.e. precursors for caronaldehyde [484]. The addition of diazopropane across the double bond of olefinic esters via pyrazolines [485, 486] also provides a rapid access to sometimes more complex cyclopropane carboxylic esters with questionable purity, from which the pure compounds can be separated. 

Natural Cyclopropanes.—Synthetic pyrethroids have been the subject of a review.Krief and his co-workers continue their activity in this field. Their one-pot synthesis of chrysanthemic ester is outlined in Scheme 2. A noteworthy feature is their observation that cyclopropanation must occur at the betaine stage (18), since (19) does not react with the ylide to form (20). An alternative route to chrysanthemic acid (23) features the formation of the cyclopropane (22) by addition of cyanide ion to (21). ... 

A new synthesis of (l/J)-frfl/i5-chrysanthemic ester has appeared along with routes to its known chiral precursors. A remarkable illustration of the use of electrocyclizations in the synthesis of endiandric acids is reported which has important biosynthetic consequences. Other notable synthetic achievements this year include ( )-pisiferic acid, (+)-zizanoic acid, ( )-lysergic acid, and chorismic acid. ... 

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