Asymmetric Synthesis of Protected 2-Substituted Cyclopropane Amino Acids (original) (raw)
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A Concise Stereoselective Synthesis of 2‐Substituted 1‐Aminocyclopropanecarboxylic Acids
European Journal of Organic Chemistry, 2009
A simple and stereoselective method for the preparation of (Z)‐2‐substituted 1‐aminocyclopropanecarboxylic acids is described. The common key step for these reaction sequences involves the stereoselective Ti‐mediated coupling of benzyloxy nitrile and homoallylic alcohol. The resulting 2‐hydroxyethyl‐substituted cyclopropylamine can be transformed shortly into various cyclopropane amino acid analogues on the gram scale, in good overall yields. Several syntheses of 2,3‐methanoamino acids, that is, ACCs derived from proteinogenic α‐amino acids or analogues, such as glutamic acid, arginine, homoarginine, and lysine derivatives are presented to exemplify the usefulness of the method. Additionally, starting from cyanoesters, spirocyclopropane γ‐amino acid analogues are available in this way. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Diastereoselective Synthesis of Cyclopropane Amino Acids Using Diazo Compounds Generated in Situ
The Journal of Organic Chemistry, 2003
A simple and high-yielding method for the preparation of cyclopropane amino acids is described. The novel method involves the one-pot cyclopropanation of readily available dehydroamino acids using aryl and unsaturated diazo compounds generated in situ from the corresponding tosylhydrazone salts. It was found that thermal 1,3-dipolar cycloaddition followed by nitrogen extrusion gave the cyclopropane amino acid derivatives with good E selectivity, while reactions in the presence of meso-tetraphenylporphyrin iron chloride gave predominantly the corresponding Z isomers. The synthetic utility of this process was demonstrated in the synthesis of (()- Z)-2,3-methanophenylalanine [(()-(Z)-1], the anti-Parkinson (()-(E)-2,3-methano-m-tyrosine [(()-(E)-2], and the natural product (()-coronamic acid [(()-3].
Stereoselective synthesis of cyclobutyl α-aminocyclopropyl carboxylic acid derivatives
Tetrahedron: Asymmetry, 2000
The highly stereoselective cyclopropanation of chiral cyclobutyl dehydro amino acids, synthesized from (−)-α-pinene or (−)-verbenone, has been achieved by means of a 1,3-dipolar cycloaddition with diazomethane. The proximity of the double bond to the neighbouring stereogenic center of the cyclobutyl moiety is crucial to obtain cyclopropanes as single diastereomers whose configuration has been determined by X-ray structural analysis. DFT theoretical
An asymmetric route to enantiomerically pure 1,2,3-trisubstituted cyclopropanes
The Journal of Organic Chemistry, 1992
Cycloaddition of various sulfur ylides to the chiral unsaturated lactame la, l b led to cyclopropanated products containing a monosubstituted appendage. The stereochemical outcome is such that all the products are mainly (or exclusively) the kinetically controlled endo-syn-8, -9, or endo-anti-10. The latter occurs by virtue of an epimerieation to the thermodynamically favored product. Removal of the chiral auriliary following Wittig reaction on the intermediate carbinol amines (11,16) gave chiral, nonracemic 1,2,3-trisubetituted cyclopropanes containing various functionalities (13, 16).
Australian Journal of Chemistry, 2013
A concise synthesis of both E-isomers of 2S-amino-3-(2′-aminomethyl-cyclopropyl)propionic acid, new methano-l-lysines, is described. The synthetic route includes nine steps from l-methionine, with a key step involving the cyclopropanation of an intermediate E-allylic alcohol. The resultant hydroxymethylcyclopropanes were readily separated and converted into the title α-amino acids. The stereochemistry around the cyclopropane rings was deduced by conducting the cyclopropanation in the presence of N,N,N′,N′-tetramethyl-d-tartaric acid diamide butylboronate, a chiral controller which is known to favour the production of S-hydroxymethyl cyclopropanes from allylic alcohols.
Helvetica Chimica Acta, 1998
The cyclopropenation of diethoxypropyne (1) with methyl diazoacetate in the presence of [ Rh 2 {(2S)-mepy} 4 ] (mepy methyl 5-oxopyrrolidine-2-carboxylate) proceeds with b 95% ee. The resulting cyclopropenecarboxylate 2 underwent stereoselective hydrogenation to the cis-cyclopropane 3. Hydrolysis of the acetal function of 3 liberated the formyl cyclopropenecarboxylate 4, which was transformed by Wittig reaction with the phosphonate 5 to afford dehydroamino acid 6 as a mixture of (Z)-and (E)-isomers in various proportions. The (Z)-isomer 6a was hydrolyzed, and the structure and the absolute configuration of the (Z)-dicarboxylic acid 7a were established by X-ray crystallography. The cis-divinylcyclopropane 11 (ee b 95%), in turn, was synthesized from 4 via Wittig reaction to afford 8, which was transformed to the aldehyde 10 and subjected to a second Wittig reaction. Thermolysis of 11 afforded ()-dictyopterene C' (12) in quantitative yield.