Cyclopropane carboxylic acids, oxidation

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]. 

Panadiplon. The development of panadiplon as an anxiolytic drug was interrupted due to elevated transaminases (Ulrich et al. 2001). The drug is converted into cyclopropane carboxylic acid, which sequesters coenzyme A and carnitine and inhibits p-oxidation (Ulrich et al. 2001). 

Minisci, F. Recupero, F. Fontana, F. Bjorsvik, H. Liguori, L. Highly selective and efficient conversion of alkyl aryl and alkyl cyclopropyl ketones to aromatic and cyclopropane carboxylic acids by aerobic catalytic oxidation a free-radical redox chain mechanism. Synlett 2002, 610-612. 

Hydrolysis of the pyrethroids may occur prior to hydroxylation. For dichloro groups (i.e., cyfluthrin, cypermethrin and permethrin) on the isobutenyl group, hydrolysis of the trans-isomers is the major route, and is followed by hydroxylation of one of the gem-dimethyls, the aromatic rings, and hydrolysis of the hydroxylated esters. The cis-isomers are not as readily hydrolyzed as the tran -isomers and are metabolized mainly by hydroxylation. Metabolism of the dibromo derivative of cypermethrin, deltamethrin, is similar to other pyrethroids (i.e., cyfluthrin, cypermethrin, and permethrin) that possess the dichloro group. Type 11 pyrethroid compounds containing cyano groups (i.e., cyfluthrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, and fluvalinate) yield cyanohydrins (benzeneacetonitrile, a-hydroxy-3-phenoxy-) upon hydrolysis, which decompose to an aldehyde, SCN ion, and 2-iminothia-zolidine-4-carboxylic acid (TTCA). Chrysanthemic acid or derivatives were not used in the synthesis of fenvalerate and fluvalinate. The acids (i.e., benzeneacetic acid, 4-chloro-a-(l-methylethyl) and DL-valine, Af-[2-chloro-4-(trifluoromethyl) phenyl]-) were liberated from their esters and further oxidized/conjugated prior to elimination. Fenpropathrin is the oifly pyrethroid that contains 2,2,3,3-tetramethyl cyclopropane-carboxylic acid. The gem-dimethyl is hydroxylated prior to or after hydrolysis of the ester and is oxidized further to a carboxylic acid prior to elimination. 

Oxidation of trimethylsiloxycyclopropanes with AgBF4 results in the formation of 1,6-diketones [125], Lead(IV) tetraacetate, which is able to oxidize a cyclopropane ring [126], induces the fragmentation of both the a and b bonds of 229 in acetic acid to give the olefinic carboxylic acids 230 [127], (Scheme 91)... 

In contrast to the restricted occurrence of the secondary metabolites mentioned previously, all plants contain 1-amino-cyclopropane-l-carboxylic acid. This amino acid is the precursor of ethylene. In the course of the bios)mthesis of this gaseous phytohormone, 1-aminocyclopropane-l-carboxylic acid is oxidized and decomposed to yield ethylene, HCN, CO2 and water (John, 1997). 

Bridgehead carbons of adamantane [86], pinane [87], and fused norbornanes [85a, 88] undergo selective hydroxylation under similar reaction conditions. Alkyl-substituted cyclopropane is oxidized selectively at the a-position to cyclopropane ring (Eq. 3.54) [89]. The methyl group of toluene can be converted into the corresponding carboxylic acids (Eq. 3.55) [91]. 

A ring enlargement involving rupture of a cyclopropane ring on anodic oxidation is exemplified in the transformation of bicyclo[4.1.0]heptane-7-carboxylic acid in methanol to 3-methoxycycloheptene [23]. 

The replacement of the fluorine atoms by chlorine atoms led to the formation of 2,2-dimethoxy-2,3-dihydrofurans 18 as the result of a ring enlargement. As in the difluorocyclopropyl series, the cyclopropane carbon with the geminal halogen substituents reached the oxidation state of a carboxylic acid by a sequence of elimination, addition and substitution reactions of unknown order. 

Although the examples are less compared than for alkenes, cyclopropanes and allenes are also oxidized by Tl(lll) salts via oxythallation (Schemes 9.18 [22], 9.19 [23], and 9.20 [24]). Alkynes react with TTN to give a variety of oxidation products such as diketones and carboxylic acids via oxythallation, the products depending on the substitution pattern on the alkynes (Schemes 9.21-9.23 [25]). 

Cleavage of l-trimethyhilyloxybicyclo[n.l.O]alkanes. These cyclopropane derivatives (I) are cleaved by LTA in glacial acetic acid to acyclic oi-unsaturated carboxylic acids (equation I). An intermediate cyclopropanol (o) is formed initially and then two bonds of the cyclopropane ring are cleaved by oxidation. ... 

The remaining new approaches to muscone all rely upon methods of ring expansion. Ferric chloride treatment of l,4-bis(trimethylsilyloxy)-bicyclo[12,l 0]pentadecane (155), obtained by cyclopropanation of the cyclotetradecene (154) with diethylzinc and methylene iodide, resulted in a one-carbon ring expansion to a muscone precursor, the dione (156). Anodic oxidation of the potassium salt of the /8-hydroxy-carboxylic acid (158), formed by Reformat-sky reaction of the enone (157), led, also by a one-carbon ring enlargement, to a mixture of the I3y- and a/8-unsaturated ketones (159) which was converted into... 

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