Methylmagnesium Halides Research Articles

Investigation of the Structure of the Complex Oligomeric Mixture Formed During Grignard Tetramethylation of N-benzylphthalimide

TMIO or 1,1,3,3-tetramethylisoindolin-2-yloxyl (5, Scheme 1) is one of the most versatile isoindoline nitroxides due to its applications [1, 2] and a variety of important advantages such as thermal stability, low reactivity towards olefins [3], symmetrical nature [4], UV detectability [5] and relative inertness to free radical attack [4][4]. The most common and effective pathway for synthesizing 5 remains the Grignard-based approach in which N-benzylphthalimide 1 is treated with methylmagnesium halide in refluxing toluene, followed by subsequent debenzylation and oxidation of the resulting secondary amine

C-Methylation of Organic Substrates: A Comprehensive Overview. Part II—Methyl Metals as Methylating Agents

C-Methylation of organic substrates was achieved with a number of methyl metals, including trimethylaluminum (Me3Al), trimethylgallium (Me3Ga), trimethylindium (Me3In), dimethylzinc (Me2Zn), methyl zinc halide (MeZnX), methylboranes (MeBRR’), methylboronic acid (MeB(OH)2), methylboronates (MeB(OR)2), methylcopper (MeCu), methyllithium cuprate (Me2CuLi), methylmagnesium halides (MeMgX), tetramethyltin (Me4Sn), methyl lithium, and lead tetraacetate. Most of the related reactions required the presence of transition metal complexes as catalysts and phosphine ligands. Overall, the yields of the methylated products actually depended on the types of used catalyst and ligand. In some instances, additives were needed as specific promoters, such as p-benzoquinone in the methylation through coupling with methyl boron agents. Best of all, methylation of substrates with some of these methylating agents occurred with some features. For example, asymmetric reactions of carbonyl compounds could be accomplished using dimethyzinc along with a specific ligand, leading to moderate to excellent yields of the major enantiomer with high enantiomeric excess. Ortho-methylation regioselectively occurred on aromatic substrates when they bear moieties such as heteroarenes (pyridine), amide, azomethine, oxazoline, N-nitrosoamine, oxime, coined ‘ortho-directing groups’.

An efficient synthesis of 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one

An efficient preparative method for the synthesis of 3-methoxy-19-norpregna-1,3,5(10), 16-tetraen-20-one was suggested. This compound is a key intermediate product in the preparation of 3,20-dihydroxy-19-norpregnatrienes, antagonists of estrogen receptor and cytotoxic agents. The reaction of 16-dehydro-17-carbonitrile (obtained in two steps from estrone methyl ether) with methyl magnesium halides gave the target product in high yield. While studying this reaction, we isolated and characterized an unusual steroid dimer, a fused 16,17-pyridinosteroid substituted in the hetero ring of the second steroid molecule. A mechanism of its formation was suggested.

Chemical Bonding and the Equilibrium Composition of Grignard Reagents in Ethereal Solutions

A thorough analysis of the electronic structure and thermodynamic aspects of Grignard reagents and its associated equilibrium composition in ethereal solutions is performed. Considering methylmagnesium halides containing fluorine, chlorine, and bromine, we studied the neutral, charged, and radical species associated with their chemical equilibrium in solution. The ethereal solvents considered, tetrahydrofuran (THF) and ethyl ether (Et(2)O), were modeled using the polarizable continuum model (PCM) and also by explicit coordination to the Mg atoms in a cluster. The chemical bonding of the species that constitute the Grignard reagent is analyzed in detail with generalized valence bond (GVB) wave functions. Equilibrium constants were calculated with the DFT/M06 functional and GVB wave functions, yielding similar results. According to our calculations and existing kinetic and electrochemical evidence, the species R(•), R(-), (•)MgX, and RMgX(2)(-) must be present in low concentration in the equilibrium. We conclude that depending on the halogen, a different route must be followed to produce the relevant equilibrium species in each case. Chloride and bromide must preferably follow a "radical-based" pathway, and fluoride must follow a "carbanionic-based" pathway. These different mechanisms are contrasted against the available experimental results and are proven to be consistent with the existing thermodynamic data on the Grignard reagent equilibria.

Selectivity in the Grignard Reaction with Silanes

Selectivity problems in preparation of silanes by Grignard reaction were discussed. A quantitative approach in terms of LFE analysis was proposed. It appeared that the inductive effect controls the rate of replacement more considerably than steric requirements in the transition state. Rates of subsequent substitution reactions at silicon decrease stepwise. Only with methylmagnesium halides are the subsequent steps faster.

Advanced Procedure for the Preparation of cis‐1,2‐Dialkylcyclopropanols – Modified Ate Complex Mechanism for Titanium‐Mediated Cyclopropanation of Carboxylic Esters with Grignard Reagents

AbstractA procedure for the preparation of cis‐1,2‐dialkylcyclopropanols by titanium(IV) alkoxide‐mediated cyclopropanation of carboxylic esters with Grignard reagents, involving the addition of 1.5 equiv. of a higher homologue of ethylmagnesium halide to a mixture of 1 equiv. of carboxylic ester, 1 equiv. of titanium(IV) isopropoxide, and 1.5 equiv. of methylmagnesium halide in ether or tetrahydrofuran at room temperature, has been elaborated. This procedure minimizes the formation of secondary alcohol side products with chromatographic retention factors close to those of the cis‐1,2‐disubstituted cyclopropanols. Inhibitory action of carboxylic esters toward the reduction of titanium(IV) isopropoxide with Grignard reagents was observed. This observation, along with some other data, allowed us to suggest a modified ate complex mechanism for the cyclopropanation, proceeding via the corresponding octahedral titanium intermediates. In the context of this mechanism, a suitable explanation for the necessity to use an additional equivalent of Grignard reagent in a stoichiometric version of the reaction was found and experimentally verified. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Efficient access to 3-alkyl-trifluoromethylbenzenes using Kumada’s coupling reaction

3-Alkyl-trifluoromethylbenzenes are obtained in good yields by Kumada’s coupling reaction between methyl or ethyl magnesium halide and 3-bromo-trifluoromethylbenzene derivatives in the presence of Ni-Xantphos catalyst.

Selective iron-catalyzed cross-coupling reactions of grignard reagents with enol triflates, acid chlorides, and dichloroarenes.

Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)(3) are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n) generated in situ. Control experiments using the ate-complex [Me(4)Fe]Li(2) corroborate this interpretation.

Copper-Catalyzed Desymmetrization ofN-Sulfonylaziridines with Methylmagnesium Halides

Cyclohexene N-p-toluenesulfonylimine (1) undergoes enantioselective ring opening to 2b upon treatment with methylmagnesium halides or MeLi in the presence of chiral Cu-catalysts. No activation of the aziridine by Lewis acid is required. Enantioselectivities of up to 91% have been observed under optimized conditions with the chiral imine ligand derived from phenylalanine. The same system reacts with cyclohexene oxide to afford trans-2-methylcyclohexanol with 50% yield and 10% ee.

A density functional treatment of methylmagnesium halides

Density functional calculations were performed on the unsolvated methylmagnesium fluoride, chloride, and bromide. The calculations show that each of these species exists as halide bridging dimer. The fluoride Grignard has the largest dimerization energy of the three, which is consistent with experimental studies of solvated systems. Other structural isomers of the methylmagnesium chloride and bromide dimers were shown to be thermally accessible at 300 K, and may exist as reactive intermediates.

Diastereoselectivity in Addition of Methylmagnesium Halide to Benzoylformate of Chiral 1,1'-Binaphthalene-2,2'-diol.

The Grignard reactions of mono-benzoylformate ester of 1, 1'-binaphthalene-2, 2'-diol were examined to investigate the complex-induced proximity effect of the phenolic hydroxyl a+ C-2' under different reaction conditions. This hydroxyl group exerted a significant neighboring group participation in the reaction. The nucleophilic addition reaction proceeded with higher diastereoselectivity than that of a series of sterically similarly sized binaphtyl esters recently reported. The halogen ligand in methyl Grignard reagents plays a crucial role in controlling the degree and sense of diastereoselectivity. A plausible mechanism is also proposed.

Communication: Stereoselective Addition of Phenylsulfonylmethides and Methylmagnesium Halides to Pentodialdo-1,4-Furanoses

Additions of organometallics to chiral α-alkoxy and α,β-dialkoxy carbonyl compounds have recently attracted a great deal of attention since this methodology has a great potential for the synthesis of a variety of polyoxy natural products such as macrolide antibiotics and polyether ionophores. Interpretation of the stereochemical outcome of the addition of organometallics to α,β-dialkoxy carbonyls, however, is rather complex and inconclusive1 compared to that of α-alkoxy carbonyls.2.

Stereoselective additions to α,β-epoxy-aldehydes; the formation of “non-chelation controlled” products

The addition of methyl lithium, methyl magnesium halides, and allylstannanes to the α,β-epoxy-aldehydes (4) and (5) takes place with moderate to high stereoselectivity to give products which correspond to “non-chelation controlled” addition to the aldehyde group.

Synthesis of 14C‐radiolabelled trimethyllead chloride

AbstractTwo synthetic routes to 14C‐labelled trimethyllead chloride ((CH3)3PbCl) from 14C‐methyl iodide (CH3I) were investigated. Alkylation of (CH3)3PbCl with labelled methylmagnesium halide, on a microscale, was less efficient for the synthesis of tetramethyllead ((CH3)4Pb) than was an electrochemical reduction of labelled CH3I at a sacrificial lead cathode. In the Grignard approach, unlabelled decyl bromide served as an initiator for the reaction of 14C‐CH3l with excess Mg and as a carrier during the subsequent alkylation of (CH3)3PbCl. In the electrochemical approach a two‐compartment cell, using dimethylformamide as solvent and sodium perchlorate as supporting electrolyte, offered several advantages over a single compartment reactor. The labelled (CH3)4Pb from both reactions was isolated by extraction, converted to (CH3)3PbCl by controlled oxidation with HCl and purified by thin layer chromatography.

Alkylated steroids. Part 5. Formation of 17β-acetylenic steroids from hindered 20-oxo-compounds via Grignard derived enolates

Treatment of methyl 3β-acetoxy-16α,17α-dimethyl-5α-androst-9(11)-ene-l7-carboxylic acid (1), or 3β-hydroxy-16α,17α-dimethyl-5α-pregn-9(11)-en-20-one (4), with methylmagnesium halide in refluxing anisole gives the 20-yne (3). Similarly 3β-acetoxy-16α,17α-dimethylpregn-5-en-20-one (5) gives the 20-yne (6). The mechanism of the reaction is discussed in terms of the steric hindrance due to the 16- and 17-methyl groups. Acetylenes (3) and (6) are converted into compounds of potential pharmacological interest.

2-Methylisoborneol, improved synthesis and a quantitative gas chromatographic method for trace concentrations producing odor in water

Naturally occurring 2-methylisoborneol, responsible for objectionable odor in some domestic water supplies, has been shown to exist in the enantiomeric form related to d-camphor. The synthesis by the action of methyllithium or methylmagnesium halides on d-camphor has been improved by the demonstration that the large amount of d-camphor in the crude product can be eliminated readily as the oxime. A method has been developed for the quantitation of 2-methylisoborneol in water down to the threshold-odor concentration of 0.1 μ/1. Camphor is added to the water as internal standard and the solution is extracted with 2% (v/v) of methylene chloride. The extract is concentrated to very small volume and analysed by gas chromatography using a flame ionization detector.

ChemInform Abstract: THE REACTION OF ACYLFERROCENES WITH METHYLMAGNESIUM HALIDES, THE INTERVENTION OF CARBONIUM‐ION‐LIKE INTERMEDIATES

Chemischer InformationsdienstVolume 6, Issue 43 Organoelement Compounds ChemInform Abstract: THE REACTION OF ACYLFERROCENES WITH METHYLMAGNESIUM HALIDES, THE INTERVENTION OF CARBONIUM-ION-LIKE INTERMEDIATES R. E. BOZAK, R. E. BOZAKSearch for more papers by this authorR. G. RILEY, R. G. RILEYSearch for more papers by this authorW. P. FAWNS, W. P. FAWNSSearch for more papers by this authorH. JAVAHERIPOUR, H. JAVAHERIPOURSearch for more papers by this author R. E. BOZAK, R. E. BOZAKSearch for more papers by this authorR. G. RILEY, R. G. RILEYSearch for more papers by this authorW. P. FAWNS, W. P. FAWNSSearch for more papers by this authorH. JAVAHERIPOUR, H. JAVAHERIPOURSearch for more papers by this author First published: October 28, 1975 https://doi.org/10.1002/chin.197543399Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume6, Issue43October 28, 1975 RelatedInformation

THE REACTION OF ACYLFERROCENES WITH METHYLMAGNESIUM HALIDES. THE INTERVENTION OF CARBONIUM-ION-LIKE INTERMEDIATES

Abstract The reactions of several acylferrocenes with methylmagnesium halides are examined. Some carbinol stabilities with adsorbents are reported.

Dibenzothiophenes and related compounds. V. Reactions of 5-substituted dibenzothiophenium salts with organometallic reagents.

In order to compare the mechanisms of reactions of sulfonium salts with organolithiums and Grignard reagents, the reactions between 5-substituted dibenzothiophenium salts and methyllithium, methylmagnesium halides, and phenylmagnesium halides have been investigated to get a large difference as shown in Tables I and II, respectively. The reactions of 5-substituted dibenzothiophenium salts with methyllithium gave ring-opening products (I) as main products in Table I, whereas the reactions of those with methylmagnesium iodide gave no I or only little. Instead, these reactions gave ringopening products (III) as main products in Table II. The mechanisms of the formation of the products of the runs in Table I and II have been explained as shown in Chart 2 and Chart 4, respectively.

An abnormal Grignard product. The reaction of benzoylferrocene with methylmagnesium halides

An abnormal Grignard product. The reaction of benzoylferrocene with methylmagnesium halides