Cyclopentanecarboxylic acid derivatives

Muenzer, D. F, Meinhold, P, Peters, M. W., Feichtenhofer, S., Griengl, H., Arnold, F H., Gheder, A., and De Raadt, A. 2005. Stereoselective hydroxylation of an achiral cyclopentanecarboxylic acid derivative using engineered P450s BM-3. Chem. Comm., 20, 2597-2599. 

Because some of the compounds with general structure 316 have noteworthy pharmacological activities, a number of alternative methods have been developed for the synthesis of the 2-substituted and 2,3-disubstituted derivatives 316. 2-Substituted derivatives of 316 cis, n = 1, 2, 3, 4 trans, n = 2, 3, 4) were prepared (77GEP2643384 80AUP507798) from 312-315 with ethyl benzimidates. The attempted ring closure of trans-2-amino-l-cyclopentanecarboxylic acid to rra/w-fused derivatives failed. In this reac-... 

Derivatives of triazole have been obtained by Fusco et al,280 from phenyl azide and 1-morpholinocyclohexene. Their decomposition leads to cyclopentanecarboxylic acid by elimination of nitrogen and ring contraction.281 The dienamine obtained from piperidine and... 

Oxidation of cyclohexanone. Oxidation of cyclohexanone with TTN in acetic acid at room temperature proceeds rapidly to give adipoin (5) in 84% yield. If the oxidation is performed at first at room temperature, the thallium(I) nitrate removed hy filtration, and then the filtrate heated to about 40° for a few minutes, the product is cyclopentanecarboxylic acid (4), obtained in 84% yield. McKillop et al. propose that both products are derived from a common precursor, an epoxy enol (3). 

E. Lee and co-workers demonstrated that the chlorohydrin derived from (+)-carvone undergoes a stereoselective Favorskii rearrangement to afford a highly substituted cyclopentane carboxylic acid derivative. This intermediate was then converted to (+)-dihydronepetalactone. When the THP-protected chlorohydrin was treated with sodium methoxide in methanol at room temperature, the rearrangement took place with excellent stereoselectivity (10 1) and high yield. Interestingly, the major product was the thermodynamically less stable cyclopentanecarboxylate. 

The synthetic potential of these reactions can be illustrated by their use for the construction of poly-functionalized cyclopentanecarboxylic acids and derivatives (Scheme 25). The Michael-induced... 

Table 4.8 Cinchona alkaloids and their derivatives promoted the enantioselective fluorination of 2-oxo-cyclopentanecarboxylic acid tert-butyl ester.

ATRC of alkyl 2,2-dichloro-6-heptenoates catalyzed by 3.7-12 mol% Fe[P(OEt)3]3Cl2 provided l-chloro-2-(chloromethyl)cyclopentanecarboxylates in 63-85% yield as a 1.8-5.3 1 trans/cis-diastereomeric mixture (cf. Part 1, Fig. 38 133 >134—137) [112, 113]. Small amounts of 6-endo cyclization products were also detected, but only traces of lactones, if at all. The corresponding free carboxylic acids, such as 52, gave in contrast 66-91% of lactones 53 together with small amounts of 6-endo cyclization product 54 (Fig. 12). Simpler 2-bromo- or 2-chloro-6-heptenoates furnished 48-93% of cyclized products under similar conditions [114]. The cisltrans-selectivity was not high for most acyclic substrates, but lactonization was facile for most cz. v-derivatives under the reaction conditions. 

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