Chrysanthemic acids, isomers

Syntheses of (l )-frans-isomers were reported by Crombie [24] and Elliott [25] starting from (1 /t Wran.v-chrysanthemic acid by means of the Wittig reaction. Their method were convenient to obtain (Z)-isomer (Scheme 10, step a) but not appropriate for the synthesis of ( )-isomer because of the (Z)-selective nature of the Wittig reaction in the case of nonstabilized ylides. It was very difficult to separate the pure ( )-isomer out of the (E)- and (Z)-mixture. This problem was overcome by use of the Takai s method (Scheme 10, step b) [26]. The ( )-selectivity of the double bond was fairly high (E Z = 89 11) (Scheme 10). 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

Synthetic pyrethroids are a group of ester compounds having excellent insecticidal activities. After the discovery of allethrin (1), a variety of useful synthetic pyrethroids have been produced mainly by structural modification of an alcohol having an asymmetric center. The insecticidal activities greatly depend upon the stereoisomers. Therefore, much effort has been expended to develop technologies for obtaining optically active isomers. However, contrary to the case of chrysanthemic acid, chemical methods of optical resolution were not very effective for these alcohols. 

Chrysanthemic acid esters, prepared according to Equation 28, belong to the family of pyrethroids, an important class of insecticides. Both the trans- and the cM-isomers possess insecticidal activity. The other two of the four possible... 

Reported here is the synthesis and insecticidal activity of some related pyrethroids represented by general formula 2 prepared by condensing methyl phenyl substituted pyrazole methanols with the more readily available dichloro chrysanthemic acid chloride (DV-acid Chloride). All of the pyrethroid samples were also prepared and tested as approximately a 4 3 trans/cis mixture of isomers. 

When phosphane-free nickel complexes, such as bis(cycloocta-l,5-diene)nickel(0) or te-tracarbonylnickel, are employed in the codimerization reaction of acrylic esters, the codimer arising from [2-1-1] addition to the electron-deficient double bond is the main product. The exo-isomer is the only product in these cyclopropanation reactions. This is opposite to the carbene and carbenoid addition reactions to alkenes catalyzed by copper complexes (see previous section) where the thermodynamically less favored e Jo-isomers are formed. This finding indicates that the reaction proceeds via organonickel intermediates rather than carbenoids or carbenes. The introduction of alkyl substituents in the /I-position of the electron-deficient alkenes favors isomerization and/or homo-cyclodimerization of the cyclopropenes. Thus, with methyl crotonate and 3,3-diphenylcyclopropene only 16% of the corresponding ethenylcyc-lopropane was obtained. Methyl 3,3-dimethylacrylate does not react at all with 3,3-dimethyl-cyclopropene, so that the methylester of tra 5-chrysanthemic acid cannot be prepared in this way. This reactivity pattern can be rationalized in terms of a different tendency of the alkenes to coordinate to nickel(O). This tendency decreases in the order un-, mono- < di-< tri- < tet-... 

Ueda, K., and Matsui, M., Studies on chrysanthemic acid. Part 20. Synthesis of four geometrical isomers of ( )-pyrethric acid, Agr. Biol. Chem.. 34. 1119. 1970. 

Certain kinds of cyclopropanecarboxylic acids are important in the production of pyrethroid, an insecticide with low mammalian toxicity [1]. For example, chrysanthemic acid is an acid component of allethrin (Fig. 1). Various kinds of alcohols have been developed to produce pyrethroids for special application [2]. Chrysanthemic acid has two chiral centers and there are four optical isomers. There is a close correlation between the chirality of a molecule and its biological activity [3]. In the case of chrysanthemic acid, the most effective isomer is shown to be the d-trans isomer, which is followed by the d-cis isomer whereas... 

In the chrysanthemic acid synthesis (Scheme 2), the ee of the product increased with the bulkiness of the R group [11]. The highest ee achieved was 70%, when R was methyl (the amino acid was alanine) and R was 2-octyloxy-5-tert-butylphe-nyl. The catalyst with the R-configuration (from D-amino acid) favored the formation of d-trans and d-cis isomers to that of l-trans and l-cis isomers, respectively. 

The problem of the utilisation of the wrong chrysanthemic acid [i.e. the (IS, 2S) isomer] has also been dealt with by Ueda and Matsui They used the pyrolysis product pyrocine (66) from chrysanthemic acid, and succeeded in racemising it by a fairly lengthy sequence of reactions. 

By modifying this process. Harper etal. (1951) obtained a mixture of the esters of the Z and E modifications, from which the active -isomer could be recovered by crystallisation. According to the findings of Matsumoto et al. (1963), using the t-butyl ester of diazoacetic acid in the presence of copper dust, ( )-chrysanthemic acid is formed stereoselectively. 

Pyrethric acid (18) and from this, by optical resolution, the pure (-l-)-isomer, forming the acid component of pyrethrin II (10), cinerin II (12) and jasmolin II (14), was prepared by Matsui and Yamada (1963) by the oxidation of ( )-chrysanthemic acid. 

Car-4-ene derivatives (79) are readily available from car-3-ene, and their ozonolysis leads to (+ )-cis-homocaronic acid dimethyl ester (80), easily convertible into (-l-)-trans-chrysanthemic acid. Purification of mixtures of cis- and trans-chrysanthemic acid by lactonization of the cis-acid with a Lewis acid is reported, as is an improved method for resolving the (+ )-trans-acid using L-lysine. A reinvestigation of the synthesis of pyrethric acid isomers has been carried out. Two studies of the metabolism of the insecticidal esters of... 

In a large number of carbene and carbenoid addition reactions to alkenes the thermodynamically less favored jjyn-isomers are formed The finding that in the above cyclopropanation reaction the an/i-isomer is the only product strongly indicates that the intermediates are organonickel species rather than carbenes or carbenoids. Introduction of alkyl groups in the 3-position of the electron-deficient alkene hampers the codimerization and favors isomerization and/or cyclodimerization of the cyclo-propenes. Thus, with methyl crotylate and 3,3-diphenylcyclopropene only 16 % of the corresponding vinylcyclopropane derivative has been obtained. 2,2-Dimethyl acrylate does not react at all with 3,3-dimethylcyclopropene to afford rranj-chrysanthemic acid methyl ester. This is in accordance with chemical expectations since in most cases the tendency of alkenes to coordinate to Ni(0) decreases in the order un-, mono-< di- tri- < tetrasubstituted olefines. 

The synthesis of chrysanthemic acid 1 as mixture of stereoisomers, as racemate of pure stereoisomers or as single optically active isomer was important before the advent of synthetic photostable pyrethroids. Because of the approved and favourable properties of pyrethrin I as a non-toxic and fast-acting contact insecticide, not only pyrethrum, but also other esters of chrysanthemic acids with similar properties are of commercial interest. Therefore cheap methods for the synthesis of this add or even total synthesis of the natural compound deserve the attention of chemists involved in synthesis. Many interesting reactions, involving rearrangements, eliminations and additions were apphed in the synthesis of this archetypical pyrethroid cydopropane carboxyhc acid. 

The decomposition, catalysed by copper at elevated temperatures, can be improved by palladium acetate [10] or rhodium acetate at room temperature [11]. Sterically hindered diazoacetic esters give a higher content of trans-isomer in the reaction product [12], as does the employment of diazoacetonitrile [13]. Intramolecular decomposition leads to precursors of cis-chrysanthemic acid [14]. Substituted furfu-ryldiazoacetats yield the final insecticides directly [15]. 

The isomer 31 of chrysanthemic acid is cychzed to the chrysanthemo-lactone 32, which after transesterification and saponification [46] affords the desired cis-chrysanthemic acid. 

For the conversion of one single isomer of chrysanthemic acid into its mirror image (1-S-trans 1-R-trans) two centers of asymmetry have to be inverted, which in this case is possible only under complete stereoisomerization and reversible rupture of the C —C -bond of the 3-membered ring of 7. This may be obtained radically by rough thermal treatment of the ester at 320 °C [102], or of the acid at 180 °C by... 

In terms of structure, chemical and biological properties nor-chlorochrysanthemic add 55, the add in which one methylgroup of chrysanthemic acid is exchanged for a chlorine atom, takes an intermediate position between chrysanthemic acid and permethric add. This acid, particularly the 1-R-cis isomer, could become of interest in the future, if a much cheaper synthesis can be found than for permethric add. For one promising route, starting from caren, see Sect. 1.3.6.5. 

Single isomers of permethric acid, the dihalovinylanalogues of chrysanthemic acid esters, which are sometimes easier to obtain, can also be ozonized to give optionally the optically active caronaldehyde [127, 245] or the epoxides. The epoxides of permethric acid can not be prepared by means of the most reactive peracids [246], the usual epoxidizing agents. 

Depending on the applied bases sodiumhydroxide or triethylamine, dehydro-bromination of this acid yields two different isomers [510] (Reaction scheme 184 page 95) interesting for testing s sake. Chrysanthemic acid can be hydrogenated catalytically without ring opening [511]. 

The same synthetic approach (i.e., varying the acid, alcohol, or both) resulted in the development of the coirnnercially successful active pyrethroid insecticides covered in this review this same approach also produced a host of relatively inactive isomers. The most potent constituent of resmethrin is the IR, 3R isomer (bioresmethrin), and is formed during the esterification of (-r) cis-, trans-chrysanthemic acid with 5-benzyl-3-furyImethyl alcohol to produce bioresmethrin and three other stereoisomers. Of greater interest to most chemists/biologists is the... 

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