Arylmagnesium Halides Research Articles

A new general preparation of polyfunctional diarylamines by the addition of functionalized arylmagnesium compounds to nitroarenes.

The addition of functionalized arylmagnesium halides to nitroarenes in THF (-20 degrees C, 2 h) provides, after reductive workup (FeCl(2), NaBH(4)), various polyfunctional diarylamines in 63-86% yield. Heterocyclic arylated amines can be prepared by this one-pot procedure. A mechanistic rationale of this reaction is given.

Syntheses of substituted pyridines, quinolines and diazines via palladium-catalyzed cross-coupling of aryl Grignard reagents

The palladium-catalyzed cross-coupling reactions between arylmagnesium halides (phenylmagnesium chloride, mesitylmagnesium bromide, 4-(methoxycarbonyl)phenylmagnesium chloride and 4-cyanophenylmagnesium chloride) and halopyridines allowed the synthesis of substituted pyridines. Owing to the remarkably mild conditions used (often below 0°C), the reaction could be extended to the use of functionalized halopyridines, haloquinolines and halodiazines.

Copper-mediated cross-coupling of functionalized arylmagnesium reagents with functionalized alkyl and benzylic halides.

[reaction: see text]. Functionalized arylmagnesium halides, prepared via an iodine-magnesium exchange, undergo a smooth cross-coupling reaction with functionalized primary alkyl iodides and benzylic bromides in the presence of CuCN.2LiCl, either in stoichiometric (with trimethyl phosphite as an additive) or catalytic quantities.

Reaction of Grignard Compounds with 4-Chloro-2-methyl-3-butyn-2-ol in Diethyl Ether Equivalents.

Reactions of RMgX·THF complexes with 4-chloro-2-methyl-3-butyn-2-ol in aromatic hydrocarbons were studied. The complexes formed by arylmagnesium halides require the presence of anisole for the reaction to occur. 4-Chloro-2-methyl-3-butyn-2-ol can be synthesized by reaction of 2-methyl-3-butyn-2-ol with sodium hypochloride in the two-phase system water-benzene.

An improved synthesis of functionalized biphenyl-based phosphine ligands.

Functionalized dicyclohexyl- and di-tert-butylphosphinobiphenyl ligands are prepared by the reaction of arylmagnesium halides with benzyne, followed by the addition of a chlorodialkylphosphine. This one-pot procedure is considerably less expensive and time-consuming than the method used previously to prepare such ligands. The cost of introducing the dicyclohexylphosphine group can be decreased by preparing chlorodicyclohexylphosphine from PCl3 and cyclohexylmagnesium chloride, and using the reagent without further purification. The new method is significant, as a variety of ligands can be produced in useful amounts by a procedure that is simple, with starting materials that are relatively inexpensive, and, in most cases, without chromatographic purification.

Nickel-Catalysed 1,4-Addition of Aryl Groups to Enones Using Aryldialkylaluminum Compounds

The transmetallation of arylmagnesium halides or aryllithium with Me2AlCl results in the formation of aryldimethylaluminum compounds. These arylaluminum compounds are useful reagents for conjugate additions to enones in the presence of Ni(acac)2 as a catalyst. 3-Aryl ketones are obtained in good yields in these catalytic reactions. Starting from the 3-oxo-Δ1,4-steroids this method gives access to 1α-arylsteroids.

The first example of Ge-Ge and Sn-Sn bond cleavage by arylmagnesium halides

The first example of Ge-Ge and Sn-Sn bond cleavage by arylmagnesium halides

Reactions of in situ formed acyl tributylphosphonium ions with Grignard reagents as an effective route to ketones from acid chlorides

The reactions of acyl tributylphosphonium ions in situ generated from acid chlorides and Bu 3P in THF at −22°C with primary alkyl and arylmagnesium halides have proved to be a convenient and simple procedure to prepare ketones from acid chloride in one-pot.

Preparation of enantiomerically pure phosphine oxides by nucleophilic displacement chemistry using oxazaphospholidines

The synthesis of enantiomerically pure triaryl- and diarylvinyl-phosphine oxides from PCl3 by three sequential nucleophilic displacements at phosphorus is demonstrated. A single diastereoisomer of the P-chlorooxazaphospholidine 4 is treated with an arylmagnesium halide to effect displacement of chloride. The major stereoisomer is formed with retention of configuration. After oxidation to the phosphine oxide with tert-butyl hydroperoxide, a second Grignard reaction leads to regiospecific and stereospecific P–O ring cleavage so that a second aryl group is introduced with retention of configuration. For the final step, the P–N bond is subjected to acid-catalysed methanolysis, previously shown to occur with inversion of configuration, followed by P–OMe displacement with a third arylmagnesium halide. The overall yield of triarylphosphine oxide is up to 29% for the cited five steps. Simple methoxyaryl or 2-naphthyl residues are employed to demonstrate the methodology, which permits the multigram-scale preparation of this class of compound in 94% e.e. The stereochemical course of the nucleophilic displacements with arylmagnesium halides is consistent with a model in which the organomagnesium reagent is complexed to the oxo-group and attacks phosphorus cis-to it in a direction defined by both electronic and steric factors.

Ortho-Substituted unsymmetrical biaryls from aryl tert-butyl sulfones

Nickel-catalysed coupling of arylmagnesium halides with aryl tert-butyl sulfones, and in particular with those bearing ortrto-substituents introduced by ortholithiation, gives ortho-substituted unsymmetrical biaryls.

ChemInform Abstract: Transient and Stable Intermediates in Cross‐Coupling Reactions

The mechanism of catalytic cross coupling mediated by palladium complexes has been examined. This has involved the successful in situ generation of a biphosphine palladium(0) species, and then observation of the sequential formation of an η 2 -olefin complex and an η 1 -alkenyl bromide complex on addition of an alkene. The latter is a stable isolable species, which reacts rapidly with added arylmagnesium halides; only the η2-olefin complex is observed after this step at —80 °C. The contribution of these intermediates to the catalytic cycle of cross coupling was tested, employing a 13C-labelled alkenyl iodide, and determ ining the label distribution in both palladium complex and product. On this basis it was dem onstrated that the η 1 -alkenyl iodide is a true interm ediate in cross coupling, and the reaction cycle occurs w ithout the intervention of a second molecule of substrate. Platinum complexes are more stable than their isostructural palladium analogues. All the interm ediates in a slow but sustainable catalytic cycle have been characterised in solution. Oxidative addition of the alkenyl bromide is profoundly accelerated by one-electron oxidizing agents.

Arylation of alkenyl bromides catalysed by platinum complexes

Biphosphine platinum complexes catalyse the cross-coupling of arylmagnesium halides and arylethenyl bromides under mild conditions.

Transient and stable interm ediates in cross-coupling reactions

The mechanism of catalytic cross coupling mediated by palladium complexes has been examined. This has involved the successful in situ generation of a biphosphine palladium(0) species, and then observation of the sequential formation of an η 2 -olefin complex and an η 1 -alkenyl bromide complex on addition of an alkene. The latter is a stable isolable species, which reacts rapidly with added arylmagnesium halides; only the η2-olefin complex is observed after this step at —80 °C. The contribution of these intermediates to the catalytic cycle of cross coupling was tested, employing a 13C-labelled alkenyl iodide, and determ ining the label distribution in both palladium complex and product. On this basis it was dem onstrated that the η 1 -alkenyl iodide is a true interm ediate in cross coupling, and the reaction cycle occurs w ithout the intervention of a second molecule of substrate. Platinum complexes are more stable than their isostructural palladium analogues. All the interm ediates in a slow but sustainable catalytic cycle have been characterised in solution. Oxidative addition of the alkenyl bromide is profoundly accelerated by one-electron oxidizing agents.

ChemInform Abstract: Reaction of Fluorinated Magnesium‐Organic Compounds with Diethyl Dicarboxylates.

AbstractThe reactions between the fluorinated aryl magnesium halides (Ia)‐(Id) and (II), (IV) or (VI) afford the hydroxyacid esters (III), (V) and (VII) or the oxoacid esters (IX), (X) and (XI).

The stereoselective synthesis of substituted 1‐hydroxyazetidines

AbstractThe four‐membered cyclic nitrones (2,3‐dihydroazete l‐oxides) 1a‐d and 2a‐c react with a variety of nucleophiles by stereoselective addition to the nitrone moiety. Reaction of the nitrones 1 and 2 with alkyl‐, allyl‐, benzyl‐, and arylmagnesium halides yields the l‐hydroxyazetidines 3, 4, 5, and 6, with the nucleophile adding from the less hindered side of the molecule. The keto nitrone 1b reacts with potassium cyanide to give the l‐hydroxyazetidine 4f. Reduction of nitrone 1b to give the l‐hydroxyazetidines 7 and 8 is achieved by reaction with lithium aluminum hydride at 0°C and at room temperature, respectively. In contrast, nitrone 1d reacts with lithium aluminum hydride only at 45°C to give the l‐hydroxyazetidine 11. The differences in the reactivity of the nitrones 1 and 2 towards nucleophilic reagents are explained in terms of steric hindrance in the addition step. Oxidation of the l‐hydroxyazetidine 3b with lead(IV) oxide affords the 2,3‐dihydroazete l‐oxide 15. Reduction of nitrone 15 with sodium borohydride affords the 1‐hydroxyazetidine 16, the epimer of compound 3b. Reaction of l‐hydroxyazetidine 3d with PbO2 yields the dimeric structure 17. Nitrone 1a reacts with the sodium salt of nitromethane to yield the l‐hydroxyazetidine 12. Keto nitrone 1b reacts with 4‐nitrobenzaldehyde in the presence of a catalytic amount of potassium hydroxide to give the 4‐benzylidene‐2,3‐dihydroazete l‐oxide 13. Upon prolonged reaction, nitrone 13 isomerizes to oxime 14, probably by an electrocyclic ring opening of an intermediate l‐hydroxy‐1,2‐dihydroazete.

A New Convenient Synthesis of α-Arylpropionic Acid Esters and α-Arylpropionitriles

Abstract Various types of α-arylpropionic acid esters were effectively obtained by the coupling reaction of aryl Grignard reagents and α-bromopropionic acid esters in the presence of nickel catalysts. α-Arylpropionitriles, precursors of α-arylpropionic acids, were also synthesized by the reaction of α-methanesulfonyloxypropionitrile and arylcopper reagents prepared from equimolar amount of arylmagnesium halides and copper(I) bromide.

Preparation of solvated and/or unsolvated simple and mixed diarylmagnesiums

Arylation of arylmagnesium halides or magnesium halide etherates by aryllithium provides a convenient method of preparing Ar 2Mg(Et 2O) 2 or Ar 2Mg(THF) 2. The ether complexes can be completely desolvated but the THF complexes cannot. Mixed diarylmagnesium tetrahydrofuranates, Ar 1Ar 2Mg(THF) 2, although coordinationally saturated, have 1H and 13C NMR spectra which suggest that they are fluxional.

Organometallics from some fluorohalocompounds

Readily available fluorohaloethanes of the general formula CF 3CXYZ (X,Y = F,Cl,Br; Z = Cl,Br) were found to be versatile synthetic intermediates for introducing a fluoro- or fluorohaloethyl group into organic molecules via organometallic compounds of magnesium and zinc. The low temperature metal-halogen exchange reaction of the ethanes with alkyl- or aryl-magnesium halides affords Grignard reagents CF 3CXYMgHal which react with aldehydes and ketones to give alcohols. The Grignard compounds failed to react with acid derivatives and their carboxylation by carbon dioxide gave only poor yields of the acids. The carboxylic acids CF 3CXYCO 2H were easily prepared by the reaction of the ethanes CF 3CXYZ with zinc and carbon dioxide under atmospheric pressure. The yields of carboxylation were substantially enhanced by the application of ultrasound. The chlorine- and bromine-containing acids were smoothly reduced to fluoropropionic acids CF 3CFHCO 2H and CF 3CH 2CO 2H.

Grignard Reaction of 2-Substituted-3-Cyanoquinolines

Abstract Grignard reactions of 2-morpholino and 2-methylthio-3-cyanoquinoline, 2-chloro-3-cyanoquinoline, 2-chloro-3-cyano-6-methoxyquinoline and 2-chloro-3-cyano-7-methylquinoline with alkyl or aryl magnesium halides have been studied. It was found that 2-morpholino and 2-methylthio- 3-cyanoquinolines gave 1,4-addition products followed by rapid aromatisation. 2-Chloro-3- cyanoquinoline with alkyl magnesium halides furnished 1,4-addition products but with aryl magnesium halides 1,4- and 1,2-addition products were obtained. The cyano group of 4-aryl-2-chloro- 3-cyano-1,4-dihydroquinolines was found to participate in the Grignard reaction to yield 1,2- addition products. 2-Chloro-3-cyano-6-m ethoxyquinoline with alkyl and phenyl magnesium halides yielded exclusively 1,4-addition products. Similarly with p-m ethoxyphenyl magnesium bromide, 1,4-addition products were isolated which participated in the Grignard reaction to yield the expected adducts. Unlike the other chloroquinoline derivatives, 2-chloro-3-cyano-7-methylquinoline with alkyl magnesium halide formed 1 ,2-addition products but with aryl magnesium halides, 1,4-addition products were isolated. The 4-alkyl-2-chloro-3-cyano-l,4-dihydroquinolines were unstable as compared to their 4-aryl analogs. A couple of the Grignard reaction products were found to be unstable on activated surface.

Fluorohalogeno compounds. I. The grignard reaction of some fluorohalogenoethanes

An extension of the scope of the Grignard reaction of fluorinated compounds is reported. Fluorohalogenoethanes of the general formula CF 3CXYZ ( X = F,Cl,Br ; Y,Z = Cl,Br ) were found to undergo smoothly the metal-halogen exchange reaction with alkyl- or aryl-magnesium halides at low temperature to yield organometallic compounds CF 3CXYMgHal. The Grignard compounds were reacted with a series of aldehydes and ketones to give the corresponding alcohols in good to moderate preparative yields.