Cyclopropane pyrethroids

Synthesis of Other Important Cyclopropane Pyrethroid Acids... 

Synthesis of Other Important Cyclopropane Pyrethroid Acids 1.7.5 Ring Contraction to Cyclopropane Carboxylic Acid... 

Natural Cyclopropanes.—Pyrethroids are available by cyclization of the epoxyamide (9) and dehydration with the sulphurane reagent (10) (Scheme 1). 

Figure 8b shows pyrethroid esters composed of an acid moiety without a cyclopropane ring and a phenoxybenzyl alcohol group. While a cyclopropane ring had long been considered an indispensable acid component constituting a pyrethroid skeleton, Ohno et al. [41] in 1974 developed fenvalerate (32), a-isopropylphenyl acetate derivative, with no cyclopropane ring in its acid moiety. This compound exhibits... 

There are two sites where stereospecificity must be maintained in order to achieve optimal insecticidal action. As seen in the acid moieties of the natural pyrethrin esters, all pyrethroids that possess a cyclopropane ring must have the If ... 

The synthesis of compounds 39, 41, and 43 by the ODPM rearrangement opens a novel photochemical route to chrysanthemic acid and other cyclopropane carboxylic acids present in pyrethrins and pyrethroids [52]. In fact, aldehyde 43 can be transformed to tran -chrysanthemic acid by simple oxidation. This new synthetic route to ecologically benign insecticides competes with the one previously described by us using the 1-ADPM rearrangement of p,y-unsaturated oxime acetates [30,53]. 

Mention was made of the natural product pyrethrins and the structure of pyrethrin I was given in this chapter, Section 3.1. Because of the unique structures of these cyclopropane-containing natural products and their high insecticidal properties, syntheses of analogs have been studied. The isobutenyldimethylcyclopropanecarboxylic acid moiety, called chrysan-themic acid, has been modified by using different ester groups. As a result a number of synthetic pyrethroids are available for certain specific uses. 

Both compounds included here are experimental and in each case the pyridine is a benzene replacement and is not essential for the activity. The urea (103) (79SAP7802440) is a member of a highly active series that kill insects by disrupting the formation of new insect cuticle, through inhibition of chitin synthesis. The cyclopropane ester (104) (78GEP2810881) is a heterocyclic analogue of the pyrethroid insecticides, an extremely successful new class which are active on a wide range of insects. 

Intramolecular cyclopropanation using diazoesters is a powerful synthetic tool. Diazoesters are readily prepared from the corresponding alcohol via House s methods56-57. Numerous examples using the application of this transformation in synthesis have been reported. These include the potent synthetic pyrethroid NRDC 182 (22)58, (1 R)-( )-cis-chrysanthemic acid (23)59, the highly strained bicyclic system 2460, antheridic acid 2561,62 and cycloheptadiene 26 (equations 33-37). 

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 fact that nature has chosen to use a cyclopropane skeleton to design a defense mechanism for certain pyrethrum flowers against insect attack has been known since 1924, when Staudinger and Ruzicka isolated and characterised (-t-)-Jrans-chrysanthemic acid 1 from the petals of these plants [1]. The active insecticidal ingredients in these plants are in fact esters of 1, which can be easily modified and which have been commercially exploited to give birth to one of the most successful classes of biomimetic insecticides, the pyrethroids. In 1997, the market value of this class of insecticides amounted to a staggering 1.5 billion US [2],... 

Chemical Name A-a-cyano-3-phenoxybenzyl (lR,3R)-3-(2,2-dibromovinyl)-2,2-dimethyl cyclopropan-1-carboxylate CAS Registry No 52918-63-5 Uses insecticide (pyrethroid)... 

Insecticides of the pyrethroid class, such as trans-chrysanthemic acid (190), have significant commercial value (see Chapter 31).241 An asymmetric synthesis of 190 has been achieved through the use of a chiral copper carbenoid reaction (Scheme 12.77).242 243 With ethyl diazoacetate, equal amounts of the cis- and trans-cyclopropanes were formed. However, when the size of the alkyl... 

Other cyclopropanecarboxylic acids, present in pyrethroids and of known insecticidal activity, are easily synthesized by the 1-ADPM reaction. Thus, triplet-sensitized irradiation of oxime acetates 74, 76, and 78 affords cyclopropanes 75, 77, and 79, respectively, in good yields. These photoproducts can be transformed to the corresponding carboxylic acids by using conventional routes (Sch. 33) [23]. 

Metal-catalyzed cyclopropanation of an alkene by a diazo compound, reaction 7.33, is another reaction where new C-C bonds are formed. This reaction finds use in the industrial manufacture of synthetic pyrethroids. The precatalysts for carbene addition reactions are coordination complexes of copper or rhodium. It should be noted that reaction 7.33 gives a mixture of isomers (syn plus anti) of the cyclopropane derivative. However, with some chiral catalysts, only one optical isomer with good enantioselectivity is obtained (see Section 9.5). 

A patent has been lodged dealing with the sensitized trans cis photoisomerization of the cyclopropane nitrile (185). The photostationary state contains ca. 65% of the cis-isomer. Many products are reported to be formed when the pyrethroid Allethrin (186) is irradiated as a thin film on a glass slide. From... 

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