Permethric ester

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). 

While Reaction 95 yields a precursor of permethric acid, Reaction 96, starting with the alkoxyacrylester 153, ends up with permethric ester [239]. 

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). 

The search for catalysts which are able to reverse the ratio of cyclopropane diastereomers in favor of the thermodynamically less stable isomer has met with only moderate success to date. Rh(II) pivalate and some ring-substituted Rh(II) benzoates induce cw-selectivity in the production of permethric acid esters 77,98 99 contrary to rhodium(II) acetate, which gives a 1 1 mixture 74,77,98), and some copper catalysts 98) (Scheme 10). 

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 . 

Cyfluthrin is excreted mainly as urinary metabolites but a portion of it is also excreted unchanged in feces. Toxicokinetic studies with " C-cyfluthrin in rats have shown that the initial step of biotransformation includes ester hydrolysis resulting in 3-phenoxy-4-fluorobenzyl alcohol intermediate and permethric... 

The process from the FMC company involves as the pivotal step an intramolecular stereoselective [2 + 1 [-cycloaddition. In a Prins reaction [94] of chloral and isobutene, followed by an isomerisation, a racemic, trichloromethyl-substituted aUyl alcohol is obtained. Reaction with the isocyanate from (R)-naphthylethyl-amine enables separation ofthe diastereomers by crystallisation. The carbamate is cleaved by trichlorosilane/triethylamine, thus permitting the recycling of the chiral auxiliary. The optically pure (R)-aUyl alcohol is reacted with diketene, to produce the / -keto-ester. After diazo transfer and basic cleavage, the diazoacetate is obtained catalysed by a copper salt, this is converted in a [2 + 1 ]-cyclo-addition into a bicyclic lactone. The Boord reaction (discovered by Cecil E. Boord in 1930) [95] finally gives (IR)-cis-permethric acid. [96]... 

A breakthrough in the use of pyrethroids as agricultural insecticides came with the discovery that esters of permethric acid are both highly potent and exhibit remarkable photostability. 

Mesityl oxide is the starting chemical for a synthesis (Reaction scheme 63) of permethric acid by subjecting it to the addition of the sulfur yhd 105 [168], forming the precursor acetyl-geminal-dimethylcyclopropanecarboxyhc ester 106 [169]. Effective synthesis of the sulfur yhd 105, chlorination of the side chain in 106 and removal of the oxygen constitute technical problems. Since sulfides do not react readily with... 

Therefore there are several strategies to obtain permethric acid by the synthesis of such butyrolactones. The Lehmann-Traube synthesis of the epoxide 129 and malonic ester (Reaction scheme 82) [214, 215] yields an product 128, isomeric to 102 in the preceding Reaction schemes 64, 79, 80, 81. 

A more classical sequence [220], involving no rearrangement, utiUzing diketene and isoprenol via the unsaturated acetic ester 134 produces the y-lactone 135 (Reaction scheme 85) for permethric acid. 

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. 

As already mentioned, the selective reduction of the add stage down to the aldehyde can be accomplished by reduction of an acylphosphonic ester 189. Based on this fact a synthesis of permethric acid is proposed, which comprises several typical synthetic advantages of Homer-Hoflfmann phosphonic acid reagents of ready accessibility (Reaction scheme 118). In fact, the trans-caronaldehyde adduct of diethylphosphite... 

The direct synthesis of cis-permethric acid has attracted a lot of attention from several research groups. Starting from the technical 3,3-dimethylpentenoic ester 111 (Reaction scheme 122, preceding page), radical addition of thiophenol followed by a-chlorination of the sulfide 191 gives a protected aldehyde ester 792, which on decomposition and subsequent, alkoxy-treatment cyclizes to the dihydropyrone 193. Light-induced... 

Resolution of racemic permethric acid also yields the unwanted IS-isomers. Transformation of one enantiomer into its mirror image demands the fission of the C —C -bond of the cyclopropane-ring. The complete isomerization to the equilibrated racemic cis/trans-mixture occurs under influence of fight and sensitizer in the case of ester and salts [346] or in an ionic manner [347] for the acid, involving the intermittent formation of the anhydride 205 and the acyl cation 206 (Reaction scheme 131). 

The Sagami-synthesis, starting with a meta-phenoxyphenyl ester of 3,3-dimethyl-pentenoic ester (Reaction scheme 263) gives permethrin 372, without having to go through the step of free permethric acid [181]. 

For the formation of permethrin, the Ulmann-reaction of permethric acid 3-bromobenzyl ester and phenolate is also a proposed alternative [916]. 

---