Ethyl Isocyanoacetate Research Articles

Porphyrins with exocyclic rings. Part 24. Synthesis and spectroscopic properties of pyrenoporphyrins, potential building blocks for porphyrin molecular wires

Porphyrins with fused pyrene units have been prepared by ‘2+2’ and ‘3+1’ methodologies. Nitration of 1,2,3,6,7,8-tetrahydropyrene, followed by oxidation with DDQ, gave 4-nitropyrene and this condensed with ethyl isocyanoacetate in the presence of DBU or a phosphazene base to generate a pyrenopyrrole ethyl ester. Ester saponification and decarboxylation with KOH in ethylene glycol at 190 °C gave the parent pyreno[4,5- c]pyrrole and this was further condensed with 2 equiv of acetoxymethylpyrroles to afford the corresponding tripyrranes protected at the terminal positions with tert-butyl esters. In a one pot procedure, the ester protective groups were cleaved with TFA and following dilution with dichloromethane, ‘3+1’ condensation with a pyrrole dialdehyde, and dehydrogenation with DDQ, the targeted pyrenoporphyrins were generated in good overall yields. A dialdehyde was also prepared from the pyrenopyrrole intermediate and this reacted to give an opp-dipyrenoporphyrin. The pyrenopyrrole ethyl ester reacted with dimethoxymethane in the presence of an acid catalyst to give a dipyrenopyrrolylmethane, and this was used to prepare an adj-dipyrenoporphyrin using the MacDonald ‘2+2’ approach. The pyrenopyrrole dialdehyde was also used to prepare a porphyrin with fused pyrene and phenanthroline moieties. Although the UV–vis spectra of these new porphyrin systems are unexceptional, pyrenoporphyrins show many of the features necessary for the construction of porphyrin molecular wires.

Ethyl Isocyanoacetate as a Useful Glycine Equivalent

In this account, we describe a useful synthetic approach to construct diverse constrained α,α-dialkylated amino acid derivatives using ethyl isocyanoacetate as a glycine equivalent. Various unusual amino acid derivatives, such as cyclophane-, benzocyclo­butene-, and diene-containing systems, are reported here.

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: Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Stereoselective Synthesis of Pyrrolizidines

Reported here is a DBU-mediated domino reaction of 1,4-dien-3-ones with ethyl isocyanoacetate allowing the formation of three C-C bonds and a C-N bond affording pyrrolizidine derivatives. Under the optimal conditions, the 1,4-dien-3-one 1 tolerates various aromatic, hetero­cyclic and alkyl groups R¹ to give single diastereo­isomers in moderate to good yields. The reaction was then extended to the 1,4-dien-3-ones 2 and 3 to lead to products bearing three and four adjacent stereocenters, respectively. A plausible mechanism involves a double Michael addition followed by an intramolecular cyclization and a final 1,3-acyl migration. The absolute configuration was determined by X-ray diffraction analyses on selected derivatives.

One-step synthesis of N-acetylcysteine and glutathione derivatives using the Ugi reaction

Fully protected natural and unnatural N-acetylcysteine, dipeptide Cys–Gly, glutathione, and homoglutathione derivatives were synthesized by the Ugi four-component reaction using various benzylthio aldehydes and ketones as carbonyl building blocks. The scope and limitations of the method were investigated. Formation of imidazoline by-products in the Ugi reaction was discussed. 2,2,2-Trifluoroethanol was shown to be a superior reaction media than methanol in some reactions. Also, the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl derivative (OBO-ester) of isocyanoacetic acid was shown to be superior to use than ethyl isocyanoacetate as a peptide synthesis precursor in cases when higher reactivity of an isocyanide is required.

Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines

Up to four adjacent stereocenters can be formed stereoselectively in the construction of a pyrrolizidine unit through a novel organocatalytic reaction that involves treatment of various dienones with ethyl isocyanoacetate (see scheme; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene). Mechanisms for this atom-economic, one-pot synthesis have been proposed.

Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines

AbstractBis zu vier benachbarte Stereozentren können stereoselektiv beim Aufbau eines Pyrrolizidinsystems eingeführt werden, indem man Dienone in einer neuartigen DBU‐katalysierten organokatalytischen Reaktion mit Ethylisocyanacetat umsetzt (siehe Schema; DBU=1,8‐Diazabicyclo[5.4.0]undec‐7‐en). Ein Mechanismus für dieses atomökonomische Eintopfverfahren wird vorgeschlagen.magnified image

Multi‐Step Synthesis and Biological Evaluation of Analogues of Insulin Secretagogue (2S,3R,4S)‐4‐Hydroxyisoleucine

AbstractA series of stereochemically defined analogues of (2S,3R,4S)‐4‐hydroxyisoleucine and related α‐hydroxy acids have been prepared by multi‐step routes from D‐glucose, whereas ketolization between TBDMS‐protected hydroxypropanone and ethyl isocyanoacetate led to racemic analogues. Bioassays showed that of eight newly synthesized compounds, two of them presented an interesting statistical trend to increase glucose‐induced insulin secretion when tested in isolated rat pancreatic islets in the presence of 8.3 mM glucose and at a concentration of 200 μM, which has previously been shown to be effective for (2S,3R,4S)‐4‐hydroxyisoleucine.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Palladium-, Platin- und Dieisenkomplexe mit Isocyanacetat: Ringschluß, säureinduzierte Ringöffnung, Diprotonierung

Palladium, Platinum, and Diiron Complexes with Isocyanoacetate: Ring Closure, Acid-Induced Ring Opening, Diprotonation Substitution by isocyanoacetate (CNCH2CO2−) of one chloro ligand in trans-[MCl2(PPh3)2] (M = Pd, Pt) results in the Δ2-oxazolin-5-on-2-ato complexes 4a, b, i.e. immediate cyclization occurs in contact with these metal(II) species. In contrast, the open-chain form of the functional isocyanide is retained in [K(18-crown-6][Fe2Cp2(CNCH2CO2)(CO)3] (16) in which it occupies a terminal position. Protonation (alkylation) of the platinum complex 4b proceeds with ring cleavage and formation of isocyano acetic acid 11 (ethyl isocyanoacetate 12) stabilized by metal ion coordination. Protonation of 16 requires two equivalents of acid to yield the aminocarbyne-bridged complex [{μ-C=N(H)CH2CO2H}Fe2Cp2(CO)3](BF4) (17) as the only isolable product. Here isocyanoacetate displays a third kind of reactivity pattern in addition to that at PdII/PtII and that at Cr0/W0 where the primary species [M(CO)5CNCH2CO2]− and [M(CO)5CNCH2CO2H] proved to be the most stable. All of the proposed structures are substantiated by analytical and the usual spectroscopic (IR, NMR{1H, 13C, 31P}, FAB-MS) data, that of 4b also by an X-ray structure determination which reveals a practically perpendicular arrangement of the coordination and the ring plane, and a long C2-O bond as the predetermined breaking point of the heterocycle.

Microwave assisted synthesis of novel annealed porphyrins

New pyrrole derivatives (isoindoles) have been readily prepared by the reaction of an α,β-unsaturated sulfone with ethyl isocyanoacetate in the presence of tert-BuOK in good yields. The isoindoles are converted into new porphyrins which undergo retro Diels–Alder reactions under microwave irradiation at 250 °C for 4 min to give novel annealed porphyrins in quantitative yields.

Preparation of Novel Cuprous Oxide−Fullerene[60] Core−Shell Nanowires and Nanoparticles via a Copper(I)-Assisted Fullerene-Polymerization Reaction

A copper(I) (Cu(I))-assisted fullerene (C60)-polymerization method has been developed for the seamless coating on nanosized objects of cuprous oxide (Cu2O), forming novel Cu2O−C60 core−shell nanostructures. It is based on a reaction of C60 and ethyl isocyanoacetate to form polymerized fulleropyrolines, catalyzed by and thus coated on the Cu2O nanomaterials. Cu2O nanoribbons and nanocubes were used in this work to demonstrate the nanocoating method. The Cu2O−C60 core−shell nanostructures were characterized comprehensively, revealing a uniform, covalently polymerized C60 shell that closely sheaths the Cu2O nanostructures. Details of the Cu(I)-assisted C60-polymerization process are proposed, which combines the solution chemistry and surface chemistry of C60. The Cu2O cores in the composite nanocubes could be removed, yielding monodispersed C60 nanoboxes. Preliminary measurements demonstrated enhanced photocurrent of the Cu2O−C60 nanoribbons arrayed on Cu foil compared to that of the Cu2O nanoribbons.

Dipolar Cycloaddition of Ethyl Isocyanoacetate to 3‐Chloro‐2‐(methylthio)/2‐(methylsulfonyl)quinoxalines: Highly Regio‐ and Chemoselective Synthesis of Substituted Imidazo[1,5‐a]quinoxaline‐3‐carboxylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Preparation of Biphenylene‐ and Benzocyclooctene‐Fused Heterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Dipolar Cycloaddition of Ethyl Isocyanoacetate to 3-Chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines: Highly Regio- and Chemoselective Synthesis of Substituted Imidazo[1,5-a]quinoxaline-3-carboxylates

An efficient route for regio- and chemoselective synthesis of substituted 3-(carboethoxy)imidazo[1,5-a]quinoxalines and novel diimidazo[1,5-a:5',1'-c]quinoxalines via base-induced cycloaddition of ethyl isocyanoacetate to unsymmetrically substituted 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines has been reported.

Preparation of Biphenylene- and Benzocyclooctene-Fused Heterocycles

Nitration of biphenylene with bismuth subnitrate and thionyl chloride give a mixture of 2-nitrobiphenylene, 2-chloro-6-nitrobiphenylene, and 5-chloro-10-nitrobenzocyclooctene. Reactions of 2-nitrobiphenylene and 5-chloro-10-nitrobenzocyclooctene with ethyl isocyanoacetate in the presence of t-BuOK gave the corresponding pyrimidine N-oxide and pyrrole, respectively.

Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl isocyanoacetate and the Suzuki–Miyaura cross-coupling reaction

Two synthetic routes to bis-armed-alpha-amino acid derivatives are described. The first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate under phase-transfer catalysis (PTC) conditions. The second route uses a palladium-mediated Suzuki-Miyaura cross-coupling reaction between a DL-4-boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.

Synthesis of the four stereoisomers of cyclobutane analogues of phenylalanine in enantiomerically pure form

All stereoisomers of 1-amino-2-phenylcyclobutanecarboxylic acid—c 4Phe—have been synthesized and the series c n Phe has thus been completed. The use of two different strategies based on a cyclization reaction, starting from ethyl isocyanoacetate and dialkyl malonate, respectively, gave both cis-c 4Phe and trans-c 4Phe in racemic form. HPLC resolution of one of the intermediates using a cellulose-derived chiral stationary phase allowed the isolation of the corresponding enantiomerically pure N-protected amino acids, prepared for incorporation into peptides. The relative stereochemistry of enantiopure compounds has been unambiguously assigned.

Alkaliisocyanacetate. Synthese und Struktur von [K(18-Krone-6)](O2CCH2NC)

Alkali-isocyanoacetates. Synthesis and Structure of [K(18-crown-6)](O2CCH2NC) The alkali isocyanoacetates M+[O2CCH2NC]− (M = Li,Na,K,Cs) (1a-d) are synthesized by reaction of ethyl isocyanoacetate with the respective alkali hydroxides in ethanol and characterized by IR, NMR (1H, 13C), and mass spectrometry (FAB). In alcoholic solution as well as in the gas phase ion pairs and higher aggregated species are observed. In contrast, [K(18-crown-6)][O2CCH2NC] (2) which is obtained from 1c and 18-crown-6, turns out to be a 1:1 electrolyte in solution (acetone); in the solid, the isocyanoacetate anion binds to K+ via the two carboxylate oxygen atoms resulting in an O8-coordinated metal atom.

Stereoselective Synthesis of 3‐Substituted Ethyl (Z)‐4,4,4‐Trifluoro‐2‐formylamino‐2‐butenoates.

AbstractFor Abstract see ChemInform Abstract in Full Text.