1-Hydroxycyclopropanecarboxylic acids

Hydroxycyclopropanecarboxylic acid phosphate HCP 34 is an analogue of phosphoenolpyruvate (PEP) 35 which is metabolized by various enzymes. HCP 34 is a potent competitive inhibitor of enzymes utilizing PEP 35, such as PEP carboxylase, enolase, pyruvate kinase, and probably other enzymes. It is a substantially better inhibitor than phospholactate 36 or phosphoglycolate 37, presumably because of the similarity of its geometric and electronic structures with phosphoenol pyruvate,Eq. 12 [28]. 

The high synthetic potential of 1-hydroxycyclopropanecarboxylic acid 42 with its two functionalities on the same carbon of the three-membered ring has only recently been recognized 92). 

As a matter of fact, 42 is readily accessible, starting with the acyloin condensation of succinic esters in the presence of trimethylsilylchloride to provide 1,2-disiloxycyclo-butene 161 in high yields 93). Bromination of 161 in pentane at low temperature, led to the 1,2-cyclobutanedione 162, which underwent acid or base induced ring contraction to 1-hydroxycyclopropanecarboxylic acid 4294). More conveniently, 42 was prepared in a one-pot reaction by first adding bromine in CH2C12 at —10 °C and then ice-water to 161 the hydroxyacid 42 was obtained by continuous extraction in 94 % yield, Eq. (52) 95-96). 

Caution Moisture must be avoided to prevent the ring contraction of the dione into 1-hydroxycyclopropanecarboxylic acid.2... 

The parent compound cyclobutane-1,2-dione itself was proposed as an intermediate in the acid- or base-catalyzed ring contraction of l,2-dichlorocyclobutyl-l,2-diylcarbonate (5), adduct of dichlorovinylene carbonate with ethene under photolysis, which on dissolution in cold dilute potassium hydroxide and subsequent acidification or on dissolution in hydrochloric acid, gave the 1-hydroxycyclopropanecarboxylic acid (6) as a single product. (For other examples of such a reaction, see ref 70.)... 

One-pot bromination of 1,2-bis(trimethylsiloxy)cyclobutenes and subsequent hydrolysis without isolating the intermediate cyclobutane-1,2-diones provided a convenient and ready route to 1-hydroxycyclopropanecarboxylic acids 8 (R = H). 

Thus, 1-hydroxycyclopropanecarboxylic acid provided an efficient and convenient precursor to 1 -donor-substituted 1 -vinylcyclopropane derivatives, whose high synthetic potential has been recently explored. It allows the easy preparation of hydroxy-protected (silyl- or acetal derivatives) 1 -hydroxycyclopropanecarbaldehyde. so- ... 

Slightly less than the equimolar amount of bromine in methylene chloride added dropwise at -10° to l,2-bis(trimethylsiloxy)-1-cyclobutane in the same solvent, poured on ice, and stirred 15 hrs. 1-hydroxycyclopropanecarboxylic acid. Y 90%. F. e., also hydrolysis with aq. NaOH, NagCOg, or NaHCOg, s. H.-G. Heine and D. Wendisch, A. 1976, 463. 

The ring contraction of 1,2-cyclobutanediones is promoted either by acids or by bases in protic media". The reaction products are a-hydroxycyclopropanecarboxylic acids or the corresponding esters. Rearrangements of some 2-alkylidenecyclobutanols to cyclopropyl carbonyl compounds are also known. 1,2-Epoxycyclobutanes afford cyclopropanecarbal-dehydes or cyclopropyl ketones under the catalytic action of protic acids, lithium iodide or lithium thiocyanate (equation 107) . Under the latter conditions, the reaction... 

The bicyclic a-hydroxy acid 10a was obtained from the ring contraction of the 7,8-bis(trimethyl-siloxy)bicyclo[4.2.0]oct-3,7-diene (product of an acyloin cyclization) either by selective bro-mination at — 40 °C and subsequent hydrolysis or by simple autoxidation under an air stream. On further bromination at 20 °C and subsequent solvolysis in aqueous sodium hydroxide the hydroxycyclopropanecarboxylic acid 10a was transformed into 4-bromo-6-oxatri-cyclo[3.2.1.0 ]octane-7-carboxylic acid (11) by intramolecular cyclization, resulting from the addition of the c <7o-hydroxy group to the cyclohexene double bond. Formation of the product resulting from the addition of the carboxy group was not observed. ... 

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