Cyclopropanecarboxylates, substituted

Reaction of 2,3-dichloroquinoxaline 367 with sodium azide in ethanol has been used to synthesize bistetrazolo-[l,5- 5, l -c]quinoxaline 368 in 65% yield (Scheme 28) <1997JOC4082>. Similarly, reaction of 2,3-dichloroquinoxaline 367 with thiosemicarbazide 366 has been used to generate l,6-diamino-bis-l,2,4-triazolo[4,3- 3,4-f]quinoxaline 365 in 67% yield <2002AP389>. Condensation of cyclopropanecarboxylic acid hydrazide 369 meanwhile gives rise to the cyclopropyl-substituted tetracycle 370 in 93% yield in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base (Scheme 28) <2005JOC2878>. 

However, the real breakthrough came with the drastically facilitated preparation of 1-cyclopropylcyclopropanol (15) from methyl cyclopropanecarboxylate (19) applying the transformation of an alkoxycarbonyl group into a cyclopropanol fragment with ethylmagnesium bromide in the presence of Ti(zPrO)4 as developed by Kulinkovich et al. [13]. The optimized conversion of the alcohol 15 to the bromide 16 and its dehydrobromination makes the alkene 1 available in synthetically useful quantities of 40 -55 g within one week (Scheme 3) [ 14]. This sequence is also applicable to prepare substituted, especially spirocyclopropane-annelated, bicyclopropylidenes [ 14a]. 

The first nonintroductory section of the text starts with the observation made early in this century that cyclopropanes have significant olefinic character. That is, corresponding ethylene and cyclopropane derivatives have significant similarities. There are literature comparisons of the thermochemistry of direct counterparts such as the parent species (1 and 2, X = H), propene and methylcyclopropane with X = Me, and of methyl acrylate and methyl cyclopropanecarboxylate 8 with X = COOMe. But the chemistry of substituted eth-ylenes is far richer than just that of vinyl compounds. One can retrieve enthalpy of formation data for cumulenes ( cumulenated olefins) such as allene (3) and both cis- and trans-2,3,4-hexatriene (4a and 4b), and for conjugated olefins such as 1,3-butadiene (5) and both (Z)- and (E)-1,3,5-hexatriene (6a and 6b). For the cyclopropane chemist it is natural to... 

We acknowledge that methylcyclopropane is no less a substituted cyclopropane as is methyl cyclopropanecarboxylate. However, for the former species we use the hydrocarbon equation 3 with nc = 4, and for the latter species we use the substituted compound equation 4 with b = 10.5 (for esters) and flc = 5 (remember the carbonyl carbon in calculating the number of nonquaternary carbons). 

As mentioned in the last paragraph, the methodology employing Lewis acids for activation of siloxycyclopropanes has certain restrictions with regard to the substitution pattern. Therefore an alternative path to prepare hydroxyalkylated adducts would be most valuable. It can actually be achieved via enolates of methyl 2-siloxy-cyclopropanecarboxylates, which add cleanly to many carbonyl compounds (Eq. 83)96). 

J. S. Chickos, D. G. Hesse, J. F. Liebman and S. Y. Panshin, J. Org. Chem., 53, 3435 (1988). In the absence of a literature value suggested for a desired enthalpy of vaporization for a substituted hydrocarbon, this CHLP protocol will be used implicitly to estimate the desired quantity. We acknowledge that methylcyclopropane is no less a substituted cyclopropane as is methyl cyclopropanecarboxylate. However, for the former species we use the hydrocarbon equation 3 with Pic = 4, and for the latter species we use the substituted compound equation 4 with Z = 10.5 (for esters) and fic= 5 (remember the carbonyl carbon in calculating the number of nonquaternary carbons). 

Cyclopropanes via abnormal Hofmann elimination. This procedure provides ethyl 1-benzylcyclopropanecarboxylate in significantly improved yield and is generally applicable to the synthesis of I-substituted cyclopropanecarboxylic esters. 

Cyclohexene oxide and its 3-hydroxy derivatives have been opened regio- and stereospecifically with phosphodiesters. The mechanism of the reaction of oxiranes with sodium dialkyl phosphite and diphenylphosphines has been studied. Cyclopropanecarboxylic acid derivatives have been obtained from substituted oxiranes with triethylphosphonoacetate anion.The mechanism of formation of isomeric alkoxyalkylacetates from oxiranes with alkyl halides and mercuric acetate has been discussed. ... 

Cyclopropanecarboxylic acids and their derivatives generally achieve bisected conformations VI so that the n systems of the carboxy group and the A-component of the 3e orbital of 112 can interact conjugatively " This type of interaction is depicted for the HOMO of a cyclopropanecarboxylic acid in XXIII. In the liquid phase mostly mixtures of cis and trans (VIII, VI) conformers of cyclopropanecarboxylic acids are found. In the parent compound, cyclopropanecarboxylic acid, the cis form seems to be preferred For substituted cyclopropanecarboxylic acids, however, different conformer populations may... 

Thorough investigations on the deprotonation and diastereoselective alkylation of 2-siloxy and other substituted methyl cyclopropanecarboxylates, 243 and 244, respectively, have recently been published by Reissig . 

Fichter previously reported that electrolysis of cyclopropanecarboxylic acid yields no products with retained ring ". This was found to be the case in the oxidation of alkyl-substituted cyclopropanecarboxylic acids. Thus the anodic oxidation of 2,2,3,3-tetramethylcyclopropane-1-carboxylate (47) yielded no Kolbe dimer but six other main... 

Substituted cyclopropanecarboxylic acids undergo a ring-opening reaction under conditions for anodic methoxylation and give stereoisomeric products [281,282]. 

In a similar manner, the 2-cyano-6-oxazolopiperidine synthon is useful for the chiral synthesis of in-dolizidine (monomerine piperidine [(+)- and (-)-coniine and dihydropinidine] and quinolizidine alkaloids.2-Hydroxymethyl-1-amino-1-cyclopropanecarboxylic acid (-)-(2I )-hydroxy-(3S)-nonylamine and a-substituted phenylethylamines are obtained in optically active form from (-)-N-cyanomethyl-4-phenyloxazolidine. 

For the preparation of long chain alkanes from fatty acids it is useful to extract the electrolyte contin-ously with a high-boiling nonpolar solvent, e.g. 2-methylheptane. Cyclopropanecarboxylic acids in some cases have been dimerized, e.g. or (15) in other cases the radical is further oxidized to a carbocation which then undergoes ring opening and solvoiysis to allylic compounds. Specifically substituted 1,2-diphenyiethanes have been prepared from phenylacetic acids (Table 2, entries 22 and 23). A variety of 2,3-disubstituted succinic acids and their derivatives have become accessible from malonic... 

Table 3. Formation of Substituted 2-(Alk-l-enyl)cyclopropanecarboxylates by [2 + 1] Cycloaddition of 3,3-Disubstituted Cyclopropenes and Alkenes with Electron-Withdrawing Substituents in the Presence of Bis( -cycloocta-l,5-diene)nickel(0)...

The Wolff rearrangement of six- and five-membered a-diazocycloalkanones has been extensively applied to the synthesis of highly strained frameworks. The rearrangement of an (x-diazo-cyclobutanone was reported from 2-diazo-3,4-bis(diphenylmethylene)cyclobutanone (1). The diazo ketone (1) was prepared by treatment of the 3,4-bis(diphenylmethyl-ene)cyclobutane-l,2-dione tosylhydrazone with alumina in 95% overall yield from the corresponding cyclobutanedione. Irradiation in the presence of water, alcohols and aniline afforded 1-carboxy-, 1-alkoxycarbonyl- and 1-phenylcarbamoyl-substituted 2,3-bis(diphenyl-methylene)cyclopropanes 2, respectively, in 13-87% yields. Thermal decomposition in aqueous dioxane afforded the cyclopropanecarboxylic acid 2 (X = OH) in 52% yield. ... 

Substitution of a halomercury group attached to a cyclopropane has also been carried out via a cyclopropyl anion. When cii-2-(diisopropylaminocarbonyl)-2-methylcyclopropyltnercury chloride (2) was treated sequentially with an excess of methyllithium or methylmagnesium bromide and then with carbon dioxide, acidic aqueous workup gave, in very good yield, cis-2-(diisopropylaminocarbonyl)-2-methylcyclopropanecarboxylic acid (3a, 74% from 2), which was esterified with diazomethane to give methyl cw-2-(diisopropylaminocarbonyl)-2-methyl-cyclopropanecarboxylate (3b, 90% from 2 when 3a was not isolated). ... 

When treated with a tetraalkylammonium fluoride, various 1-substituted trimethylsilylcyclo-propanes are converted to tetraalkylammonium salts of the corresponding cyclopropyl anions. Such anions are trapped by performing the reaction in the presence of an aldehyde, a ketone or carbon dioxide. The reaction is carried out successfully with electron-donating and electron-withdrawing substituents a to the silyl moiety. The best yield was obtained when methyl 1-trimethylsilylcyclopropanecarboxylate was treated with tetrabutylammonium fluoride in tetra-hydrofuran and acetaldehyde, methyl l-(l-hydroxyethyl)cyclopropanecarboxylate (la) was obtained in 90% yield.Under similar conditions (Z)-2,6-dimethyl-l-[(l-trimethylsilylcy-clopropyl)methylene]cyclohex-2-ene was transformed to (Z)-l- [l-(l-hydroxy-l-methyl-ethyl)cyclopropyl]methylene -2,6-dimethylcyclohex-2-ene (2) in 90% yield in the presence of acetone.Similarly, when carbon dioxide was used as electrophile in the presence of cesium fluoride, typically 1-trimethylsilylcyclopropane-l-carbonitrile was converted quantitatively to 1-cyanocyclopropanecarboxylic acid (3a). ... 

Diazotization of 1-aminocyclopropanecarboxylic acid in the presence of a carbon nucleophile gives a-substituted cyclopropanecarboxylic acids in moderate yields. When this amino acid was allowed to react with sodium nitrite in trifluoroacetic acid or with nitrosyl tetrafluoroborate in acetonitrile in the presence of potassium cyanide, 1-cyanocyclo-propanecarboxylic acid (1) was obtained in 64% yield. Similarly, l-(3-trimethylsilylprop-yl)cyclopropanecarboxyIic acid (2) was isolated in 30% yield when diazotization was carried out in the presence of allyl trimethylsilane. ... 

Double substitution by successive elimination and addition also takes place when 1-chloro-cyclopropanecarboxylates and 1-chlorocyclopropyl cyclopropyl sulfone are treated with potassium ieri-butoxide in tetrahydrofuran. The best result was obtained with the sulfone, which was converted to 2-feri-butoxycyclopropyl cyclopropyl sulfone (3) in 82% yield. ... 

Dicarbonyl compounds can be cleaved oxidatively using peracids this protocol has been used to prepare cyclopropanecarboxylic acids from a dicyclopropylethanedione, e.g. 2 from 1 and several 2-cyclopropyl-2-oxoacetic acids. " An appropriately substituted 1,3-diketone has also been converted to a cyclopropanecarboxylic acid by basic hydrolysis. When a hydroxy group is attached p to the carbonyl group of an alkyl cyclopropyl ketone, periodate oxidation afforded a similar acid in quantitative yield. ... 

---