Aryl-cyclopropane Carboxylic Acids

This class of acids 259 constituted a novel feature and a deviation from the natural model compound chrysanthemic acid. Originating from structure-activity considerations on the similarity of pyrethroid and DDT by Holan [512], they improved the understanding of molecular shape and insecticidal activity. The commercial result of this ideas is cycloprothrin. 

The preparation looks comparably simple (Reaction scheme 185), starting from basic chemicals. The reactions starting from 4-ethoxyacetophenones are of interest. 

The resolved acid [515] could be racemized only by a peculiar thionyl chloride of a certain purity [516]. Addition of sodiumdifluorochloro acetate to the phenyl-acrylate 260 produces the even more interesting difluoro-analogues [516]. Component of the pyrethroid cycloprothrin is the dichloro ester shown above. 

A still more pronounced but inactive hybrid 261 of permethrin and the Holan-esters was prepared by a chemically interesting sequence, comprising a Claisen rearrangement, followed by bromotrichloromethane addition of an initial phenylacetic acid dimethylallyl ester 262 according to reaction scheme 186 [518]. 

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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. 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

A lactone can be refunctionalized to an amino acid as well as a carboxylic acid. Reaction of 7.34 with potassium phthalimide opened the lactone ring to give a phthalimido-acid. Removal of the phthalimide group gave 2-methylamino-l-phenyl-cyclopropane-1-carboxylic acid, 7.35Amino acid 7.35 was tested as a potential antidepressant, and several aryl analogs were prepared the 4-chlorophenyl, the 4-methylphenyl, and the 4-methoxyphenyl derivatives. 

Other applications of NHC-based rhodium catalysts include the cyclization of acetylene carboxylic acids, cyclopropanation of olefins with diazo compounds, or aryl-aryl cross-coupling combined with dynamic kinetic resolution with the help of a lipase or Beckmann rearrangement. Thus, the chemistry of NHC-Rh catalysts is rich and varied, and we expect new catalysts and patterns of reactivity in the years to come. These will provide new tools for synthetic organic chemistry. 

Phenylacetic acids have been prepared from 2,2-dichlorostyrenes by sequential hydroboration and oxidation (Cr03-H2S04) of the intermediate trialkyl borane, and benzoyl benzoic acids (8), not readily available by other routes, have been obtained" in good yield by treatment of phthalic anhydride with aryl-lithiums at — lOO C. Syntheses of some bicyclo [1,1,0] butane-l-carboxylic acids (9) and a range of cyclopropane-1-carboxylic acids [(10) and (II)] have been described. 1-Hydroxy-cyclopropanecarboxylic acids (13) have been prepared from the hydroxy-cyclobutanone derivatives (12), following bromination and hydrolysis. 

An alternate approach, pioneered by Kunz and MacMillan, proceeds by reaction of sulfur ylides with a,(3-unsaturated iminium ions, formed by reaction of a,p-enals with enantiomerically pure amines. In this approach the sulfur ylide (9.87) reacts with a range of (3-aryl- and P-alkyl-substituted enals, including (9.88), in the presence of the dihydroindole (9.89) to give the cyclopropane with ees ranging from 89 to 96%. More recently, it has been shown that replacement of the carboxylate functional group in (9.89) with an isosteric tetrazolic acid gives an improved catalyst that effects cyclopropanation with 99% ees in all cases studied. 

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