Showing papers on "Grignard reaction published in 2003"
TL;DR: Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes and new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.
Abstract: Organomagnesium reagents occupy a central position in synthetic organic and organometallic chemistry. Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. Functional groups such as esters, nitriles, iodides, imines, or even nitro groups can be present in a wide range of aromatic and heterocyclic organomagnesium reagents. Also various highly functionalized alkenyl magnesium species can be prepared. These recent developments as well as new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.
660 citations
TL;DR: A novel and mild synthesis of polyfunctional benzimidazoles and indoles is described, which results in functionalized heterocycles for nitroarenes and nitrenes.
Abstract: Phenylmagnesium chloride has been used for the conversion of selected nitroarenes into nitrenes. Their insertion into a neighboring sp2 CH bond yielded functionalized heterocycles. A novel and mild synthesis of polyfunctional benzimidazoles and indoles is described.
50 citations
TL;DR: By utilizing these properties, the absolute asymmetric synthesis of specifically the Delta or the Lambda enantiomer was achieved for both Grignard reagents.
Abstract: Two new six-coordinate Grignard reagents, cis-[(p-CH3C6H4)MgBr(dme)2] (1) and cis-[MgCH3(thf)(dme)2]I (2), have been synthesized and their crystal structures have been determined. Both reagents are cis-octahedral and therefore chiral. They crystallize as conglomerates and racemize rapidly in solution. By utilizing these properties, the absolute asymmetric synthesis of specifically the Δ or the Λ enantiomer was achieved for both Grignard reagents. Enantiopure 1 and 2 were then reacted with butyraldehyde or benzaldehyde to give the corresponding alcohol in up to 22 % enantiomeric excess. At −60 °C, the Grignard reagents crystallize as racemic phases instead of conglomerates. Consequently, the crystal structures of rac-cis-[(p-CH3C6H4)MgBr(dme)2]⋅DME (3) and rac-cis-[MgCH3(thf)(dme)2]I (4) could be determined.
48 citations
TL;DR: In this paper, an iodide-mediated ring expansion of N-ferrocenoyl-aziridine-2-carboxylic esters is described, with full stereocontrol, namely net retention of configuration.
Abstract: A synthesis of ferrocenyl-oxazolines is described using an iodide-mediated ring expansion of N-ferrocenoyl-aziridine-2-carboxylic esters. The ring enlargements take place with full stereocontrol, namely net retention of configuration. Modification of the ester function by a Grignard reaction leads to three new types of ferrocenyl-oxazoline carbinol ligands, which were used as chiral ligands in the asymmetric addition of diethylzinc to benzaldehyde (e.e.s ranging from 46 to 62%). The planar chiral ferrocenyl-oxazoline carbinol ligand gave a very good result (e.e. 90%) in the palladium-catalyzed allylic substitution of 1,3-diphenyl prop-2-enylacetate with dimethyl malonate.
40 citations
TL;DR: In this paper, a Suzuki cross-coupling reaction was used with two possible strategies: chromenization before the coupling with oligothiophenes or chromenisation after the coupling, the main intermediate being the diphenyl propargylic alcohol, the functionalized naphthol derivatives, and the thiophenic boronates.
39 citations
TL;DR: In this article, a stereoselective synthesis of 1,4-dideoxy-1,4imino-d-allitol 1 and formal synthesis of (2S,3R,4S)-3,4dihydroxyproline was achieved via the addition of vinylmagnesium bromide to the benzylimine derived from (R)-2,3-O-isopropylidene glyceraldehyde followed by N-allylation, ring-closing metathesis (RCM), and dihydroxylation.
38 citations
TL;DR: In this paper, the 10β-bromide derivatives of DHA with activated aromatic compounds, including naphthalenes, were shown to possess a chair pyranose ring with equatorial aryl group.
33 citations
TL;DR: The oxidative magnesiation of nitrogen-containing pi-deficient halogenoheteroaromatics using active magnesium was accomplished and enabled fused halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine or 2- chloroquinoxaline to magnesiate at a mild temperature.
Abstract: The oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium was accomplished. Both magnesiation followed by addition of a carbonyl compound (Grignard reaction) and magnesiation in the presence of a carbonyl compound (Barbier reaction) were carried out to afford the corresponding product. Especially, the latter method enabled fused halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine or 2-chloroquinoxaline to magnesiate at a mild temperature (−20 to 30 °C).
30 citations
TL;DR: In this article, the yields of addition and reduction products for the reactions of butylmagnesium chloride with diisopropyl ketone, methyl 2-methylpropanoate, and isophosphorus 2-mixture in toluene were determined at different THF, diethyl ether, and tert-butyl methyl ether contents in the Grignard reagent.
Abstract: Ratios of the yields of addition and reduction products for the reactions of butylmagnesium chloride with diisopropyl ketone, methyl 2-methylpropanoate, and isopropyl 2-methylpropanoate in toluene were determined at different THF, diethyl ether, and tert-butyl methyl ether contents in the Grignard reagent. Replacement of the alkoxy group in the ester leads to strikingly different results for very small additions of donors. The results are discussed in terms of the solvation of the species in the reaction mixture.
24 citations
TL;DR: Kinetics of the reactions of butylmag magnesium chloride and phenylmagnesium bromide with tetraethoxysilane and methyltrichlorosilane was investigated in diethyl ether and diethyle ether-toluene mixtures and established that the reaction with alkoxysILanes consists of replacement of a donor molecule at the magnesium center by the silane followed by subsequent rearrangement of the complex to products through a four-center transition state.
Abstract: Kinetics of the reactions of butylmagnesium chloride and phenylmagnesium bromide with tetraethoxysilane and methyltrichlorosilane was investigated in diethyl ether and diethyl ether-toluene mixtures Replacement of ether by toluene significantly accelerates the reaction with alkoxysilanes, while no effect was found for the reaction with chlorosilanes We established that the reaction with alkoxysilanes consists of replacement of a donor molecule at the magnesium center by the silane followed by subsequent rearrangement of the complex to products through a four-center transition state Chlorosilanes react differently without solvent molecule replacement but also via a four-center transition state Large negative activation entropies are consistent with formation of cyclic transition states Small activation enthalpy values together with remarkable exothermicity point to early transition states of the reactions
18 citations
TL;DR: In this article, a convenient synthesis of 4(5)-acyl-1H-imidazoles without N-protecting group is described, which can be synthesized from commercially available 4 (5)-IMIDazolecarboxaldehyde in one-pot.
Abstract: A convenient synthesis of 4(5)-acyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde without N-protecting group is described. 4(5)-Cyanoimidazole could be synthesized from commercially available 4(5)-imidazolecarboxaldehyde in one-pot. Treatment of 4(5)-cyanoimidazole with various alkylmagnesium bromides followed by addition of aqueous sulfuric acid afforded 4(5)-acyl-1H-imidazoles in good yield.
TL;DR: In this article, a simple one-pot method for the synthesis of phosphonites and H-phosphinates from triethyl phosphite and appropriate Grignard reagents is described.
TL;DR: In this article, the authors present the results of initial kinetic studies in which they have established that alkoxysilanes and chlorosilanes react with Grignard reagents in entirely different ways.
TL;DR: A practical synthesis of the tsetse fly attractant 3-n-propylphenol involves the Grignard reaction of 3-hydroxybenzaldehyde and ethylmagnesium bromide affording a benzylic alcohol-type phenol derivative that upon catalytic hydrogenation gives the title product in 75% overall yield as mentioned in this paper.
TL;DR: A series of optically active N-protected α-aminoketones were synthesized via the Grignard reaction of the Weinreb amides of the N-tert butoxycarbonyl amino acids as discussed by the authors.
Abstract: A series of optically active N-protected α-aminoketones were synthesized via the Grignard reaction of the Weinreb amides of the N-tert-butoxycarbonyl amino acids. Reduction of the α-aminoketones by sodium borohydride resulted in the corresponding 1,2-amino alcohols. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:603–606, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10195
TL;DR: In this paper, a concise route to the Trost A-ring precursor enyne for synthesizing 2a-substituted 1α,25-dihydroxyvitamin D3 was described, in which the 2asubstituents could be introduced via addition reaction of Grignard reagent towards the sugar epoxide, easily obtained from D-glucose.
Abstract: A concise route to the Trost A-ring precursor enyne for synthesizing 2a-substituted 1α,25-dihydroxyvitamin D3 (1) is described, in which the 2a-substituents could be introduced via addition reaction of Grignard reagent towards the sugar epoxide, easily obtained from D-glucose. In the reaction, the solvent effect was remarkable and the use of toluene gave higher chemical yield and chemical reactivity as compared with ethereal solvents.
TL;DR: Pyrimidinyl nitronyl nitroxides where the bis-N-oxy fragment is included in a six-membered ring were prepared from diacetonamine by a sequence of reactions including a Grignard reaction, a Ritter reaction and oxidation of the intermediate pyrimidine; the properties of the 2-phenyl-substituted representative are fully described as discussed by the authors.
TL;DR: In this paper, active magnesium was used to achieve the oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium.
Abstract: The oxidative magnesiation of nitrogen-containing π-deficient halogenoheteroaromatics using active magnesium was accomplished. Both magnesiation followed by addition of a carbonyl compound (Grignard reaction) and magnesiation in the presence of a carbonyl compound (Barbier reaction) were carried out to afford the corresponding product. Especially, the latter method enabled fused halogenodiazines such as 4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine or 2-chloroquinoxaline to magnesiate at a mild temperature (−20 to 30 °C).
TL;DR: All resulting compounds showed no or rather less antimicrobial activity against grampositive, gram‐negative bacteria and fungi compared to tetracycline or clotrimazol but high cytotoxic activity against HL 60 cell line determined in the MTT assay.
Abstract: 2, 5-Dialkylfuran and tetrahydrofuran compounds as structural elements of Annonaceae acetogenins like Asitrocinwere synthesized starting from furfural by Grignard reactions, lithiation of the furan ring and addition of aliphatic aldehydes. Hydrogenation of the furan rings over Pd-catalyst gave the corresponding tetrahydrofurans. All resulting compounds showed no or rather less antimicrobial activity against grampositive, gram-negative bacteria and fungi compared to tetracycline or clotrimazol but high cytotoxic activity against HL 60 cell line determined in the MTT assay.
Patent•
17 Jun 2003
TL;DR: In this paper, an improved process for the preparation of escitalopram of the formula-I which consists of a sequential double Grignard reaction on 5-bromophthalide, isolation of di-magnesium salt, neutralization of di magnesium salt, resolution of dihydroxy compound of formula-IV and cyclization of resolved compound of the formulae-IV, cyanation of compound using DMF and copper(I)cyanide.
Abstract: The present invention relates to an improved process for the preparation of escitalopram of the formula-I which consists of a sequential double Grignard reaction on 5-bromophthalide, isolation of di-magnesium salt, neutralization of di-magnesium salt, resolution of dihydroxy compound of the formula-IV and cyclization of resolved compound of the formula-IV, cyanation of compound of the formula-IV using DMF and copper(I)cyanide. The present process utilizes the insoluble property of di-magnesium salt of formula-XII in a mixture of THF and a non-polar organic solvent and separates it from impurities by simple filtration thereby making the isolation and purification process simple.
TL;DR: In this article, Dehalogenative Polycondensation using Magnesium and Aggregating Property of the Polymer in Solutions is used for the preparation of polyphenylenes with higher molecular weights.
Abstract: Preparation of Polyphenylenes with Higher Molecular Weights via Dehalogenative Polycondensation Using Magnesium and Aggregating Property of the Polymer in Solutions
TL;DR: All four diasteromeric 16,17-diols in the 3-methoxy-13alpha-estra-1,3,5(10)-triene series have been synthesized and some compounds, in spite of a 17beta-hydroxy group, had a conformation with a ring C chair form caused by intermolecular interaction in the solid state.
Patent•
10 Apr 2003
TL;DR: A polyarylethersulfone of formula (I) carrying a basic group is obtained by halogenating an unsubstituted polyary lether sulfone (II), followed by reacting with a metal and then with an anchoring compound of formula.
Abstract: A bisphenol A polyarylethersulfone carrying a basic group is obtained by halogenating an unsubstituted polyarylethersulfone, followed by reacting with a metal and then with an anchoring compound containing a basic group. A polyarylethersulfone of formula (I) carrying a basic group is obtained by halogenating an unsubstituted polyarylethersulfone of formula (II), followed by reacting with a metal and then with an anchoring compound of formula (X-A-B) m. X : a removable group; A : an anchoring group; B : a basic group; and m : 1, 2 or 3. [Image] [Image].
Patent•
07 Nov 2003
TL;DR: In this article, a method of preparation of derivatives of piperidinyl butylphenylacetic acids was proposed, in which the substances are prepared by Grignard reaction of alkylhalohydrins and suitably substituted aromatic aldehydes.
Abstract: The invention relates to a new method of preparation of derivatives of piperidinyl butylphenylacetic acids. The compounds are histaminically active. The substances are prepared by Grignard reaction of alkylhalohydrins and suitably substituted aromatic aldehydes. The resulting diols are subjected to subsequent substitution reaction.
Patent•
20 May 2003
TL;DR: In this paper, a method for producing the vinylbenzoic acid, comprising reacting carbon dioxide with a Grignard reagent prepared from a halostyrene, is characterized by using a mixture solvent of an aromatic hydrocarbon with tetrahydrofuran as a reaction solvent.
Abstract: PROBLEM TO BE SOLVED: To provide a method for producing vinylbenzoic acid, by which the vinylbenzoic acid can efficiently and economically be obtained in a high yield, while a conventional known method for producing the vinylbenzoic acid, comprising subjecting p-chlorostyrene to a Grignard reaction in tetrahydrofuran and then carbonylating the product with carbon dioxide, can not avoid the by-production of polymers in the Grignard reaction process, needs repeated purification processes for removing the polymers from the product contaminated with the polymers, and therefore is not an industrial production method SOLUTION: This method for producing the vinylbenzoic acid, comprising reacting carbon dioxide with a Grignard reagent prepared from a halostyrene, is characterized by using a mixture solvent of an aromatic hydrocarbon with tetrahydrofuran as a reaction solvent COPYRIGHT: (C)2005,JPO&NCIPI
Patent•
29 Jan 2003
TL;DR: In this paper, a new Grignard reaction using an alkyl halide was proposed to synthesize a compound of general formula R-X [R]-MX' (M is Mg or Zn; and R' is a group bound via Mg and C and selected from a primary or secondary alkyyl optionally having C=C and/or C≡C, unsaturated aliphatic group, aromatic group, alicyclic group and heterocyclic ring group; and X' is an atom selected from Br, I and Cl
Abstract: PROBLEM TO BE SOLVED: To provide a new Grignard reaction using an alkyl halide. SOLUTION: The new method comprises reaction of a compound of general formula R-X [R is a primary or secondary alkyl optionally having carbonyl, nitrile or hydroxy substituent and/or C=C and/or C≡C; and X is a halogen atom, OSO2 PhCH3 , OSO2 CF3 or OSO2 CH3 ] with a Grignard reagent of formula: R'-MX' (M is Mg or Zn; and R' is a group bound via Mg and C and selected from a primary or secondary alkyl optionally having C=C and/or C≡C, unsaturated aliphatic group, aromatic group, alicyclic group and heterocyclic ring group; and X' is a group selected from Br, I and Cl) in a polar organic solvent containing a Ni and/or a Ni complex catalyst and a hydrocarbon containing at least one C=C to synthesize the R-R' compound with the R and R' bound with a C-C bond.
Patent•
19 Sep 2003
TL;DR: In this article, an unsaturated and methyl-substituted macrocyclic ketone or lactone is manufactured by subjecting the corresponding ketolactone or diketone to a Grignard reaction using a methyl magnesium halide and a subsequent acid dehydration reaction.
Abstract: PROBLEM TO BE SOLVED: To develope an alternative method for manufacturing an unsaturated and methyl-substituted macrocyclic ketone or lactone which is interest in view of aromatic odor from a corresponding ketolactone or diketone. SOLUTION: The new unsaturated and methyl-substituted macrocyclic keton or lactone is manufactured by subjecting the corresponding ketolactone or diketone to a Grignard reaction using a methyl magnesium halide and a subsequent acid dehydration reaction. Since the manufacturing method does not use a Wittig reaction or a reaction with a large excess of methyl lithium, a manufacturing cost is reduced and also the operation on an industrial scale is facilitated. COPYRIGHT: (C)2004,JPO
Patent•
28 Aug 2003
TL;DR: In this paper, a process for the preparation of a 5-substituted l-(4-fluorophenyl)-1,3-dihydro-isobenzofuran of Formula (2), an intermediate for the manufacture of citalopram, is described.
Abstract: The present invention provides a process for the preparation of a 5-substituted-l-(4-fluorophenyl)-1,3-dihydro-isobenzofuran of Formula (2), an intermediate for the manufacture of citalopram, which process comprises: (a) carrying out a Grignard reaction on a corresponding 5-substituted phthalide of Formula (3) in a co-solvent system, comprising adding (i) prepared 4-fluorophenyl magnesium halide in an ether solvent to (ii) the 5-substituted phthalide in a suitable organic co-solvent to the ether solvent, to form a corresponding 4-substituted-2-hydroxymethyl-4'-fluorobenzophenone of Formula (4); (b) carrying out a ketone reduction of the 4-substituted-2-hydroxymethyl-4'-fluorobenzophenone of Formula (4) following the Grignard reaction, to form a corresponding 4-substituted-2-hydroxymethylphenyl- 1-(4-fluorophenyl) methanol of Formula (5); and (c) carrying out a cyclisation reaction on the 4-substituted-2 hydroxymethylphenyl- 1-(4-fluorophenyl) methanol of Formula (5) following the reduction reaction, to form said intermediate of Formula (2); wherein R represents Br or CN.
Journal Article•
TL;DR: In this paper, the authors present details of the recently introduced general method of homologation of monosaccharides, which is based on chain-elongation of a protected monosACcharide from the terminal carbon atom.
Abstract: The survey presents details ofthe recently introduced general method ofhomologation of monosaccharides. This method is based on chain-elongation of a protected monosaccharide from the terminal carbon atom. The terminal CH 2 OH group is oxidized to the aldehyde grouping and next reacted with an alkoxymethylmagnesium chloride (C 1 Grignard) to form directly stereoisomeric homologues. The yields of the homologation products are high. Experiments aiming at improvement of the stereoselectivity of the reactions are described. The application of another C 1 Grignard reagent, (phenyldimethylsilyl)methylmagnesium chloride, is presented. The advantages and disadvantages of the method are discussed. All syntheses connected with the important bacterial heptose, L-glycero-D-manno-heptose and its oligosaccharides are described.