Pyrethroid precursors

T. Furukawa etal, US Patent 6,414,181 (July 2, 2002) Assignee Sumitomo Chemical Company, Limited Utility Pyrethroid Precursor... 

This catalyst has been used for the preparation of a pyrethroid precursor with some control of the optical purity. 

However, the best results with copper catalysts are those reported by Aratani using complex V [21]. This catalyst has been used for the preparation of pyrethroid precursors XXII with some control of the optical purity (8). 

Several attempts were also made to increase the substrate scope of (S)-selective HNLs. The active sites of HfcHNL from R brasiliensis and MeHNL from M. esculenta are accessible via a narrow hydrophobic tunnel harboring a tryptophan residue (W128), which hampers the passage of large substrates. Replacement of W128 by smaller residues led to improved conversions of sterically hindered substrates [154] like the industrially interesting 3-phenoxybenzaldehyde, whose (S)-cyanohydrin is a pyrethroid precursor (Scheme 25.7). 

In a recent study, chiral separations for pyrethroic acids, which are the chiral building blocks of synthetic pyrethroids and the primary metabolites of the acid part of these potent ester insecticides, have been developed [62], For example, a polar-organic mobile phase allowed the complete baseline resolution of all four stereoisomers of chrysanthemic acid (2,2-dimethyl-3-(2-methylprop-l-enyl)-cyclopropanecarboxylic acid) on a 0-9-(tcrt-butylcarbamoyl)quinine-based CSP(acjj = 1.20, oLtrans = 1-35, critical Rs = 3.03) (Figure 1,32a). This chiral acid is the precursor of pyrethroids like allethrin, phenothrin, resmethrin, and tetramethrin but not excreted as metabolite. The primary acid metabolite of these pyrethroids is chrysanthemum dicarboxylic acid (3-[(l )-2-carboxyprop-l-enyl]-2,2-dimethylcyclopropanecarboxylic acid) the stereoisomers of which could also be resolved with a reversed-phase eluent (acetonitrile— 30-mM ammonium acetate buffer 90 10, v/v pHa = 6.0) and employing an O-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSP ads = 1-09, atrans = 1-50,... 

When the carbinol substituents (R) were the bulky 5-ler -butyl-2-(n-octyloxy)phenyl group, optimum enantioselectivities were achieved with the catalytic use of the corresponding Cu(II) complex (2) in both enantiomeric forms. Specific applications of the Aratani catalysts have included the synthesis of chrysanthemic acid esters (Eq. 5.6) and a precursor to permethrinic acid, both potent units of pyrethroid insecticides, and for the commercial preparation of ethyl (S)-2,2-dimethylcyclopropanecarboxylate (Eq. 5.2), which is used for constructing cilastatin. Several other uses of these catalysts and their derivatives for cyclopropanation reactions have been reported albeit, in most cases, with only moderate enantioselectivities [26-29],... 

The oxidation of 3-carene to 3-caren-5-one (Figure 3.46) is a key step in the synthesis of the pyrethroid ester insecticide Deltamethrin [162,163]. This reaction is performed with air as the oxidant, catalyzed by 2 mol% of a Cr-pyridine complex (the catalyst precursors are CrCl3 and pyridine). Table 3.1 shows the turnover frequencies obtained using various Cr/pyridine ratios. 

Rhodium compounds and complexes are also commercially important catalysts. The hydroformylation of propene to butanal (a precursor of hfr(2-ethyUiexyl) phthalate, the PVC plasticizer) is catalyzed by hydridocarbonylrhodium(I) complexes. Iodo(carbonyl)rhodium(I) species catalyze the production of acetic acid from methanol. In the flne chemical industry, rhodium complexes with chiral ligands catalyze the production of L-DOPA, used in the treatment of Parkinson s disease. Rhodium(II) carboxylates are increasingly important as catalysts in the synthesis of cyclopropyl compounds from diazo compounds. Many of the products are used as synthetic, pyrethroid insecticides. Hexacyanorhodate(III) salts are used to dope silver halides in photographic emulsions to reduce grain size and improve gradation. 

Synthesis and Insecticidal Activity of Pyrethroids from Substituted Pyrazole Methanol Precursors... 

In this way, esters of chrysanthemic acid (2) [15,16,18] and permethrinic acid [17,18], which are important precursors for the synthesis of pyrethroid insecticides, can be prepared in >90% ee. Although enantioselective cyclopropanation cannot compete with conventional industrial syntheses of optically active pyrethroids, a technical process for the cyclopropanation of 2-methylpropene was successfully implemented at Sumitomo [18]. The product, ethyl (-l-)-2,2-dimeth-ylcyclopropanecarboxylate, serves as a starting material for the production of cilastatin, a dehydropeptidase inhibitor used as a drug to suppress the degradation of the P-lactam antibiotic iminipenem. 

The lactones shown in the Table include several representatives of recognized or potential value as starting materials in natural product synthesis. Lactone 1 is a precursor of grandisollactone 3 of some pyrethroids, lactone 6 of some prostaglandins, and lactone 7 of multistriatin, methynolide and monensin. ... 

For example, cycloaddition of carbethoxycarbene (from ethyl diazoacetate as precursor) on XXXIV (R=methyl, Cl, Br) in the presence of various rhodium carboxylates yields cyclopropanecarboxylic acid esters (pyrethroids) that are useful for their insecticidal activity [56] (slightly volatile, biodegradable, non toxic for mammalians). 

Irradiation of 5-benzoylbicyclo[2.2.2]octenone oximes (41) in the presence of triethylamine affords the corresponding bicyclo[3.2.1]octane derivatives via an electron transfer pathway. The synthesis of 2-vinylcyclo-propanecarbaldehydes, precursors of cyclopropane components present in pyrethroids, has been achieved by using the oxa-di-71-methane... 

Certain relations to the Faworski rearrangement may be involved in the alkaline ring contraction of chlorocyclobutanol acetate 251 (Reaction scheme 176) to a cyclopropane carbaldehyde 252 [500], a precursor for still somewhat active pyrethroids. 

Cyclopropane Pyrethroid Acids as Precursors for Other Pyrethroid Acids... 

The formation of the proper acid or alcohol component for a pyrethroid-ester insecticide may occur as a binary or ternary reaction as the very last step in the course of the usually lengthy process. On the one side this is of particular interest for circumvention of patent protection for any existing precursor. On the other hand it... 

Martin P, Eginhard S, BeUus D. Copper(I)-catalyzed radical additions of polyhalogenated compounds to olefins. Part 1. Synthesis of polyhalogenated hutyryl chlorides, precursors of pyrethroid haloketenes. Helv. Chim. Acta 1980 63 (7) 1947-1957. 

The development of the pyrethroids from the pyrethrins serves as an example of the most successful development of a commercially important synthetic insecticide from a natural precursor. The commercial pyrethroids are among the most active insecticides known and they control a wider range of insect and acarid pests at lower application rates than most other insecticides. Their high toxicity to insects and low mammalian toxicity make these compounds a role model for all present and future insecticides. 

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