Ethyl Isocyanoacetate Research Articles

Catalytic enantioselective addition of isocyanoacetate to 3-methyl-4-nitro-5-styrylisoxazoles under phase transfer catalysis conditions

The reaction between 3-methyl-4-nitro-5-styrylisoxazoles and ethyl isocyanoacetate proceeded under phase transfer catalysis to give enantioenriched monoadducts in high enantiomeric excess (up to 99% ee). The resulting adducts were subsequently cyclised to give 2,3-dihydropyrroles and substituted pyrrolidines in identical high ees and as a single diastereoisomer.

ChemInform Abstract: Divergent Synthesis of 2,3‐Dihydro‐1H‐pyrroles, 3‐Alkyl‐1H‐pyrroles and 3‐Alkenyl‐1H‐pyrroles from 2,4‐Pentadienenitriles and Isocyanides.

An efficient and divergent one-pot synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from readily accessible 2,4-pentadienenitriles with isocyanide based on reaction condition selection has been described. The reaction of 2,4-pentadienenitriles with ethyl isocyanoacetate undergoes a formal [2 + 3] annulation either to generate 2,3-dihydro-1H-pyrroles in the presence of DBU (0.3 equiv.) in EtOH at room temperature or to give 3-alkyl-1H-pyrroles in the presence of DBU (2.0 equiv.) in EtOH under reflux. Moreover, the 2,3-dihydro-1H-pyrroles could be converted to 3-alkenyl-1H-pyrroles with DDQ as an oxidant.

Modified Synthesis of 2-Ethoxycarbonyl-3,4-Diethyl-Pyrrole and the Corresponding Octaethylporphyrin

In the synthesis of 2-ethoxycarbonyl-3, 4-diethyl-pyrrole (1) by the Barton-Zard reaction of 4-acetoxy-3-nitrohexane (1b) with ethyl isocyanoacetate, the organic base 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) and the solvent tetrahydrofuran (THF) were replaced with K2CO3 and ethanol, respectively. Moreover, the preparation of the intermediate 1b from 1a by acetylation reaction was carried out by employing acetyl chloride in boiling toluene solution instead of acetic anhydride and the catalyst concentrated sulfuric acid. After treatment of 1 with excess LiAlH4 at low temperature, the crude product 1c (α-hydroxymethyl-3, 4-diethyl-pyrrole) was immediately reacted via a tetramerization in the presence of the catalyst BF3.OEt2 in crude CHCl3,followed by oxidation of 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) to provide the corresponding octaethylporphyrin 2. The results indicate that using BF3.OEt2 as catalyst instead of p-toluenesulphonic acid (p-TsOH)in the synthesis of 2 from 1c can obviously increase the yield of product 2 up to 80% from 69%.

Divergent synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from 2,4-pentadienenitriles and isocyanides.

An efficient and divergent one-pot synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from readily accessible 2,4-pentadienenitriles with isocyanide based on reaction condition selection has been described. The reaction of 2,4-pentadienenitriles with ethyl isocyanoacetate undergoes a formal [2 + 3] annulation either to generate 2,3-dihydro-1H-pyrroles in the presence of DBU (0.3 equiv.) in EtOH at room temperature or to give 3-alkyl-1H-pyrroles in the presence of DBU (2.0 equiv.) in EtOH under reflux. Moreover, the 2,3-dihydro-1H-pyrroles could be converted to 3-alkenyl-1H-pyrroles with DDQ as an oxidant.

ChemInform Abstract: Microwave‐Assisted Synthesis of Ethyl 1,3‐Disubstituted‐1,6‐dihydropyrrolo[2,3‐c]pyrazole‐5‐carboxylates.

AbstractOptimum reaction conditions are examined for the synthesis of the title compounds (III) from substituted pyrazoles of type (I) and ethyl isocyanoacetate (II).

Ugi Multicomponent Reaction Product: The Inhibitive Effect on DNA Oxidation Depends upon the Isocyanide Moiety

The hydroxyl-substituted benzoic acid (as phenyl group A in the product), aniline (as phenyl group B in the product), benzaldehyde (as phenyl group C in the product), and four isocyanides are employed to synthesize bis-amide via an Ugi four-component reaction. The effects of the obtained 20 bis-amides on quenching radicals and inhibiting DNA oxidation are estimated. It is found that the antioxidant effectiveness of bis-amide generated by hydroxyl groups is markedly influenced by the structural feature derived from isocyanide. The phenolic hydroxyl group attaching to phenyl group A plays a major role in scavenging radicals, and the radical-scavenging property is reinforced by the structural moiety introduced from ferrocenylmethyl isocyanide. The same conclusion is also obtained when bis-amides are used to inhibit DNA oxidation. It is still found that the ferrocenylmethyl moiety enhances the antioxidant effect of hydroxyl group at phenyl group A in protecting DNA against the oxidation. Moreover, when the bis-amide is prepared by the same isocyanide, e.g. ethyl isocyanoacetate, it is found that the hydroxyl group at phenyl group C plays the major role in inhibiting DNA oxidation, followed by the hydroxyl groups attaching to phenyl groups B and A.

Microwave‐Assisted Synthesis of Ethyl 1,3‐Disubstituted‐1,6‐dihydropyrrolo[2,3‐c]pyrazole‐5‐carboxylates

A novel series of ethyl 1,3‐disubstituted‐1,6‐dihydropyrrolo[2,3‐c]pyrazole‐5‐carboxylates can be rapidly and efficiently synthesized in excellent yields by condensing a variety of 1,3‐substituted‐4‐formyl‐5‐chloropyrazole with ethyl isocyanoacetate in the presence of 1‐methyl‐3‐butylimidazolium hydroxide under microwave irradiation. The simple experimental procedure, DMSO‐free condition, short period of conversion, and excellent yields are the advantages of the present method. The structures of the novel compounds are confirmed by IR, 1H NMR, 13C NMR, MALDI‐TOF MS, and elemental analysis.

ChemInform Abstract: An Easy Access to 4,5‐Disubstituted Thiazoles via Base‐Induced Click Reaction of Active Methylene Isocyanides with Methyl Dithiocarboxylates.

AbstractThe method allows a simple and rapid approach to the title compounds (23 examples).

An Easy Access to 4,5-Disubstituted Thiazoles via Base-Induced Click Reaction of Active Methylene Isocyanides with Methyl Dithiocarboxylates

An efficient synthesis of 4,5-disubstituted thiazoles via base-induced cyclization of active methylene isocyanides such as tosylmethyl isocyanide, ethyl isocyanoacetate, and arylmethyl isocyanides with methyl arene- and hetarenecarbodithioates is reported. This synthesis could be a new click chemistry reaction, since it is simple, rapid, and often avoids purification steps. In addition, this method allow us a clear and general synthesis of novel 4,5-diarylthiazoles.

Reactions of β-alkoxyvinyl polyfluoroalkyl ketones with ethyl isocyanoacetate and its use for the synthesis of new polyfluoroalkyl pyrroles and pyrrolidines

The hitherto unreported reactions of β-alkoxyvinyl polyfluoroalkyl ketones with ethyl isocyanoacetate and equimolar amounts of potassium-tert-butoxide proceeded mainly in the β-position of the α,β-unsaturated ketones in cases of α-nonsubstituted 1a–e and α-methyl substituted ketones 1g–j. Other α- or β-substituted ketones 1f,k–o gave mainly products 4 of initial attack at the carbonyl carbon. Depending on the solvent, the major products of β-attack do exist in different tautomeric forms. Generally the openchain enol tautomers 5 predominate in the polar DMSO-d(6), while the cyclic γ-hemiaminals 8 are the major tautomers in the less polar CDCl(3). Acid treatment of the latter compounds 8 led to the hitherto unknown ethyl 5-polyfluoroalkyl-pyrrole-2-carboxylates 11 by elimination of formic acid. Catalytic hydrogenation of pyrrole 11a was used for the synthesis of earlier unknown 5-trifluoromethyl proline 16.

Double nucleophilic attack on isocyanide carbon: a synthetic strategy for 7-aza-tetrahydroindoles

A novel and efficient route for the synthesis of 7-aza-tetrahydroindoles from N-aryl/alkyl-alkenoylacetamides and ethyl isocyanoacetate is described. A mechanism, involving a stepwise [3+2] cycloaddition-intramolecular aza-Michael addition cascade, is proposed that explains the origin of the double nucleophilic attack on the isocyanide carbon atom.

Microwave-assisted synthesis of indole-2-carboxylic acid esters in ionic liquid

An improved procedure for the synthesis of indole-2-carboxylic acid esters in excellent yields has been achieved by the condensation of 2-halo aryl aldehydes or ketones and ethyl isocyanoacetate using ionic liquid under controlled microwave irradiation (100 W) at 50 °C. This method offers a number of advantages in terms of methodology, high-product yield, short period of conversion, mild reaction conditions and easy workup.

ChemInform Abstract: Simple and Efficient Copper(I)‐Catalyzed Access to Three Versatile Aminocoumarin‐Based Scaffolds Using Isocyanoacetate.

AbstractThe reaction of salicyl aldehydes and 2‐hydroxyacetophenones with ethyl isocyanoacetate (II) leads to 3‐formamidocoumarin derivatives which can be treated with HCl to afford the free aminocoumarins.

Direct Synthesis of 6‐Azabicyclo[3.2.1]oct‐6‐en‐2‐ones and Pyrrolizidines from Divinyl Ketones and Observation of Remarkable Substituent Effects

AbstractSubstituents create access to molecular diversity. Under basic conditions, 6‐azabicyclo[3.2.1]oct‐6‐en‐2‐ones 3 and pyrrolizidines 4 are efficiently synthesized, respectively, in a single step from ethyl isocyanoacetate 2 and divinyl ketones 1 bearing an aryl or alkyl group at the 2‐position. For comparison, only the corresponding pyrrolizidines 4′ can be obtained from divinyl ketones 1′ bearing a methoxycarbonyl group at the 2‐position.

Double Isocyanide Cyclization: A Synthetic Strategy for Two-Carbon-Tethered Pyrrole/Oxazole Pairs

A new strategy for the construction of the compounds with two different heterocycles, linked by a C(2)-tether via a domino process involving [5 + 1] annulation, ring-opening, and subsequent double isocyanide cyclization, from the reaction of ethyl isocyanoacetate with divinyl ketones (DVKs) has been developed. The chemoselective fragmentation of the cyclohexanone intermediate is the key for the formation of not only the C(2)-tether but also the two different heterocycles.

ChemInform Abstract: Tandem Michael Addition/Intramolecular Isocyanide [3 + 2] Cycloaddition: Highly Diastereoselective One Pot Synthesis of Fused Oxazolines.

A base-catalyzed tandem Michael addition/intramolecular isocyanide [3 + 2] cycloaddition of ethyl isocyanoacetate and Michael acceptors with tethered carbonyl groups is described. This reaction leads to the formation of fused oxazolines in a highly diastereoselective manner under very mild conditions.

ChemInform Abstract: Stereoselective Synthesis of β-Hydroxyamino Acids by Aldol Reaction of α-Isocyanocarboxylate with Arene-Chromium- Tricarbonyl Complexes.

Abstract High diastereoselectivity is obtained during the addition of ethyl isocyanoacetate 1 to chiral complexes 2 and 3 . The 2-oxazoline-4-carboxylic esters are intermediates for the synthesis of β-substituted serines in a stereoconservative process.

Practical Methods for the Synthesis of Symmetrically α,α-Disubstituted α-Amino Acids

This report provides an overview of the practical methods for preparing symmetrically α,α-disubstituted α-amino acids and their derivatives. Despite the growing application of this particular type of sterically constrained α-amino acid in the de novo design of peptides and peptidomimetics, synthetically important achievements in the field have not been summarized so far. Classical methods, such as the Bucherer-Bergs and Strecker reactions of sym-dialkyl and cyclic ketones, as well as recent methods involving dialkylation of nucleophilic glycine equivalents and Ugi reactions, are presented. 1 Introduction 2 Bucherer-Bergs and Strecker Reactions of sym-Dialkyl and Cyclic Ketones 3 Dialkylation of Schiff Bases Derived from Glycine Esters 4 Dialkylation of Ethyl Isocyanoacetate 5 Dialkylation of Ethyl Nitroacetate 6 Ugi Reaction 7 Conclusions

ChemInform Abstract: Ethyl Isocyanoacetate as a Useful Glycine Equivalent

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Porphyrin on a Half-Shell! Synthesis and Characterization of Corannulenoporphyrins

An efficient synthetic method for preparing corannulenoporphyrins is described. Nitrocorannulene was reacted with ethyl isocyanoacetate in the presence of a phosphazene base to generate the pivotal corannulenopyrrole intermediate. Following cleavage of the ethyl ester moiety with KOH in ethylene glycol at 180-190 degrees C, the heptacyclic system was reacted with acetoxymethylpyrroles under mildly acidic conditions to afford tripyrranes. The proton NMR spectra for these tripyrrolic intermediates suggest that they can take on helical geometries, but the conformations are dependent on the nature of the terminal ester groupings and may be altered by solvent interactions. Treatment of a di-tert-butyl ester tripyrrane with TFA cleaved the protective groups, and subsequent condensation with diformylpyrroles in TFA-CH(2)Cl(2), followed by oxidation with DDQ or ferric chloride, gave excellent yields of corannulenoporphyrins. Nickel(II), copper(II), and zinc complexes of this system were also prepared, and the nickel derivative was also further characterized by X-ray crystallography. The same synthetic strategy was also used to prepare a porphyrin with fused acenaphthylene and corannulene subunits. The fused bowl-shaped corannulene provides these porphyrins with a unique structural component that increases solubility by reducing pi-pi stacking interactions.