Arylmagnesium Halides Research Articles

Cobalt-catalyzed cross-coupling of nitrogen-containing heterocyclic phosphonium salts with arylmagnesium reagents

Cobalt-catalyzed cross-couplings of nitrogen-containing heterocyclic phosphonium salts with arylmagnesium halides proceeded efficiently with the aid of cobalt(II) catalyst and copper(I) salt in tetrahydrofuran at ambient temperature, producing the desired 4-arylated pyridine, quinoline, and quinoxaline in modest to good yields.

Rhenium‐Catalyzed Arylation–Acyl Cyclization between Enol Lactones and Organomagnesium Halides: Facile Synthesis of Indenones

A set of rhenium-catalyzed aryl-acylcyclization between (hetero)arylmagnesium halides and enol lactones through a cascade Csp 2 -Csp 2 /Csp 2 -Csp 2 bond formation has been developed under mild reaction conditions. Indeed, a wide range of functional groups on both organomagnesium halides and enol lactones are well tolerated by the simple rhenium catalysis, thus furnishing polyfunctionalized indenones in one-pot fashion and with complete control of the regioselectivity. Moreover, this approach also provides a straightforward synthesis to neo-lignan and ( iso )pauciflorol F . Mechanistic studies demonstrated that the reaction involves a sequential of syn -carborhenation and intramolecular nucleophilic addition process.

Rhenium‐Catalyzed Arylation–Acyl Cyclization between Enol Lactones and Organomagnesium Halides: Facile Synthesis of Indenones

AbstractA set of rhenium‐catalyzed arylation–acyl cyclizations between (hetero)arylmagnesium halides and enol lactones through a cascade C(sp2)−C(sp2)/C(sp2)−C(sp2) bond formation under mild reaction conditions has been developed. Indeed, a wide range of functional groups on both organomagnesium halides and enol lactones is well tolerated by the simple rhenium catalysis, thus furnishing polyfunctionalized indenones in one‐pot fashion and with complete control of the regioselectivity. Moreover, this approach also provides a straightforward synthetic route to neolignan and (iso)pauciflorol F. Mechanistic studies demonstrated that the reaction involves a sequence of syn‐carborhenation and intramolecular nucleophilic addition.

Синтез и воздействие третичных аминоспиртов пиперазинового ряда и их дигидрохлоридов на опухолевую ДНК в условиях <i>in vitro</i>

Взаимодействием 1-(4-бутоксифенил)-3-(4-замещенных пиперазин-1-ил)-2-фенилпропан-1-онов с алкил(арил)магнийгалогенидами синтезированы третичные аминоспирты пиперазинового ряда. Некоторые из конечных соединений переведены в дигидрохлориды. Изучено влияние синтезированных соединений на процессы метилирования опухолевой ДНК С-180 мышей в условиях in vitro: к гомогенату опухоли добавляли 3  10–6 М раствор исследуемых соединений и инкубировали в термостате при 37 °C в течение 24 ч. Сравнительно высокую активность (ингибирование метилирования на 51,6 %) показало соединение 1-(4-бутоксифенил)-3-[4-(4-фторфенил)пиперазин-1-ил]-1,2-дифенилпропан-1-ол, которое в положении 1 содержит фенильный радикал. Введение в орто-положение фенильного радикала метоксигруппы привело к снижению активности до 37,5 %.

Synthesis and Antitumor Activity of Piperazine-Based Tertiary Amino Alcohols and Their Dihydrochlorides

Aminomethylation of 1-(4-alkoxyphenyl)-2-phenyl(chlorophenyl)ethanones with paraformaldehyde and substituted piperazines in ethanol furnished 1-(4-alkoxyphenyl)-3-(4-R-piperazin-1-yl)-2-phenyl (chlorophenyl)propan-1-ones. Reaction of the latter with alkyl (aryl) magnesium halides resulted in the formation of tertiary amino alcohols of piperazine series, which were further converted to dihydrochlorides. The effect of synthesized compounds on the processes of tumor DNA methylation in vitro was studied.

Chromium(II)-Catalyzed Diastereoselective and Chemoselective Csp2-Csp3 Cross-Couplings Using Organomagnesium Reagents.

A simple protocol for performing chromium-catalyzed highly diastereoselective alkylations of arylmagnesium halides with cyclohexyl iodides at ambient temperature has been developed. Furthermore, this ligand-free CrCl2 enables efficient electrophilic alkenylations of primary, secondary, and tetiary alkylmagnesium halides with readily available alkenyl acetates. Moreover, this chemoselective C-C coupling reaction with stereodefined alkenyl acetates proceeds in a stereoretentive fashion. A wide range of functional groups on alkyl iodides and alkenyl acetates are well tolerated, thus furnishing functionalized Csp2-Csp3 coupling products in good yields and high diastereoselectivity. Detailed mechanistic studies suggest that the in situ generated low-valent chromium(I) species might be the active catalyst for these Csp2-Csp3 cross-couplings.

Synthesis of BR2 complexes of α-pyrrolyl dipyrrins

A series of BR2 complexes of α-pyrrolyl dipyrrin were synthesized from BF2 complex of α-pyrrolyl dipyrrin (3-pyrrolyl BODIPY) by treating it with various alkyl- and aryl magnesium halides under mild Grignard reaction conditions. The BR2 complexes were functionalized at α-position of the appended pyrrole ring with formyl, chloro and bromo functional groups and these functionalized BR2 complexes were used further to prepare various novel derivatives of BR2 complexes. The BR2 complexes were characterized by HR mass, NMR, absorption, fluorescence, and electrochemical techniques. Two of the BR2 complexes were structurally characterized by X-ray crystallography. Our studies revealed that the substitution of fluorine atoms at the boron center of 3-pyrrolyl BODIPYs with different alkyl/aryl groups significantly alters their structural, spectral and electrochemical properties. The DFT studies also support the alteration of the electronic properties of the BR2 complexes.

A telescoped Knochel-Hauser/Kumada-Corriu coupling strategy to functionalized aromatic heterocycles

The direct application of Knochel-Hauser derivative arylmagnesium halides in Kumada-Corriu couplings is described. By utilizing the in situ-generated Grignard reagents, the transmetalation with stoichiometric zinc salts to known Negishi coupling conditions is avoided, thereby streamlining the transformation. Several aromatic hetereocycles participate in the deprotonation and couple with a variety of phenyl iodides and bromides in isolated yields up to 81%. The parent system is demonstrated on 6 g scale with 79% yield, and monitored via ReactIR to show the stability of the Grignard and progression of the deprotonation/CC coupling reaction.

Heterogeneous catalytic 1,4-addition of arylmagnesium compounds to chalcones

Copper(II) on a 4 Å molecular sieve support catalyses the chemoselective addition of alkyl- and arylmagnesium halides to chalcones. Only the 1,4-addition products were obtained in high yields.

Preparation of Polyfunctional Naphthyridines by Cobalt-Catalyzed Cross-Couplings of Halogenated Naphthyridines with Magnesium and Zinc Organometallics.

CoCl2 (5%) catalyzes cross-couplings of various halogenated naphthyridines with alkyl- and arylmagnesium halides. Also, arylzinc halides undergo smooth cross-couplings with various naphthyridines in the presence of CoCl2·2LiCl (5%) and sodium formate (50%), leading to polyfunctional arylated naphthyridines. Two of these arylated naphthyridines are highly fluorescent, with quantum efficiencies reaching 95% and long excited-state lifetimes of up to 12 ns.

Synthesis of Bicyclo[1.1.1]pentane Bioisosteres of Internal Alkynes and para-Disubstituted Benzenes from [1.1.1]Propellane.

We report a general preparation of arylated bicyclo[1.1.1]pentanes through the opening of [1.1.1]propellane with various arylmagnesium halides. After transmetalation with ZnCl2 and Negishi cross-coupling with aryl and heteroaryl halides, bis-arylated bicyclo[1.1.1]pentanes are obtained. These bis-arylated bicyclo[1.1.1]pentanes may be considered as bioisosteres of internal alkynes. Bioisosteres of tazarotene and the metabotropic glutamate receptor 5 (mGluR5) antagonist 2-methyl-6-(phenylethynyl)pyridine were prepared and their physicochemical properties were evaluated.

Synthese von Bicyclo[1.1.1]pentan‐Bioisosteren von internen Alkinen und para‐disubstituierten Benzolen unter Verwendung von [1.1.1]Propellan

AbstractWir berichten über ein allgemeines Syntheseverfahren für arylierte Bicyclo[1.1.1]pentane durch die Öffnung von [1.1.1]Propellan mit verschiedenen Arylmagnesiumhalogeniden. Nach Transmetallierung mit ZnCl2 und einer Negishi‐ Kreuzkupplung mit Heteroaryl‐ oder Arylhalogeniden, werden diarylierte Bicyclo[1.1.1]pentane erhalten, die als Bioisostere von internen Alkinen betrachtet werden können. Bioisostere von Tazaroten und 2‐Methyl‐6‐(phenylethinyl)pyridin, einem Antagonisten des metabotropen Glutamat‐Rezeptors 5 (mGluR5), wurden hergestellt und deren physikochemischen Eigenschaften ausgewertet.

ChemInform Abstract: Iron‐Catalyzed Cross‐Coupling of Alkenyl Acetates.

AbstractThe mild and ligand‐free title reaction of cyclic and acyclic mono‐, di‐ and, trisubstituted alkenes with alkyl and arylmagnesium halides has a very broad substrate scope and tolerates a diverse range of functional groups.

Copper‐Catalysed Allylic Substitution Using 2,8,14,20‐Tetrapentylresorcinarenyl‐Substituted Imidazolium Salts

AbstractUnsymmetrical imidazolium salts, each having one nitrogen atom (N1) substituted by a cavity‐shaped TPR group (TPR = 2,8,14,20‐tetrapentylresorcinaren‐5‐yl), were tested in situ as proligands for the copper‐catalysed allylic arylation of cinnamyl bromide with arylmagnesium halides. The catalytic systems produced mixtures of linear (l) and branched (b) arylated compounds in variable proportions, with the b/l ratio being the highest (78:22) for the most crowded imidazolium salt used, namely that in which the second nitrogen atom (N2) was substituted by a mesityl group. An N‐heterocyclic carbene complex obtained from one of the imidazolium salts was characterised by an X‐ray diffraction study.

ChemInform Abstract: Practical Iron‐ and Cobalt‐Catalyzed Cross‐Coupling Reactions Between N‐Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents.

AbstractThe title reaction is applied to pyridyl, pyrimidinyl, and 1,3,5‐triazoyl halides and a variety of arylmagnesium halides.

ChemInform Abstract: A Practical Procedure for Iron‐Catalyzed Cross‐Coupling Reactions of Sterically Hindered Aryl‐Grignard Reagents with Primary Alkyl Halides.

AbstractThe use of an iron phosphine complex as catalyst renders possible the cross‐coupling of sterically hindered arylmagnesium halides with primary alkyl halides and tosylates.

A Practical Procedure for Iron‐Catalyzed Cross‐Coupling Reactions of Sterically Hindered Aryl‐Grignard Reagents with Primary Alkyl Halides

AbstractAlthough iron‐catalyzed cross‐coupling reactions of arylmagnesium halides with alkyl halides are well established and proceed effectively under a variety of experimental conditions, they often find limitations when working with sterically hindered aryl‐Grignard reagents. Outlined in this paper is a practical solution that allows this gap in coverage to be filled. Specifically, it is shown that bis(diethylphosphino)ethane (depe) crafts an effective coordination environment about Fe(+2). This commercially available ligand is slim enough not to interfere with the loading of the iron center even by ortho,ortho‐disubstituted arylmagnesium halides, yet capable of preventing premature reductive coupling of the resulting organoiron species, which seem to be hardly basic either. The reaction is compatible with various polar functional groups as well as with substrates containing β‐heteroatom substituents. Moreover, the procedure even allows encumbered neopentylic electrophiles to be arylated with donors as bulky as mesitylmagnesium bromide, whereas secondary alkyl halides tend to eliminate.magnified image

Subtle Steric Effects in Nickel‐Catalysed Kumada–Tamao–Corriu Cross‐Coupling Using Resorcinarenyl‐Imidazolium Salts

AbstractThree resorcinarene‐cavitands bearing a 3‐R‐1‐imidazolylium substituent (R = alkyl) grafted to the wider rim of the cavitand (1–3) were assessed in the Kumada–Tamao–Corriu cross‐coupling of aryl halides with arylmagnesium halides. Their combination with [Ni(cod)2] (cod = 1,5‐cyclooctadiene; 1:1 stoichiometry) resulted in highly efficient catalysts, the activities of which varied in the following order: R = n‐propyl (1) < isopropyl (2) ≈ benzyl (3). A remarkable turnover frequency of 60400 mol(ArX) mol(Ni)–1 h–1 was obtained in the coupling of 2‐bromo‐6‐methoxynaphthalene with PhMgBr (100 °C in dioxane, with precursor 2). The high activities of the cavitand derivatives were attributed to steric effects that facilitate the reductive‐elimination/product decoordination step. Comparative experiments carried out with a structurally modified resorcinarene, as well as cavity‐free imidazolium salts bearing 2‐methoxyaryl substituents, suggest that the efficiency of the catalysts mainly relies on steric interactions between the metal and the flexible substituents attached to two methine carbon atoms. These steric interactions are probably reinforced each time the metal binds one of the two oxygen atoms located next to the catalytic centre.

Highly chemoselective cobalt-catalyzed biaryl coupling reactions

A practical cobalt-catalyzed hetero-biaryl coupling reaction between aryl chlorides and arylmagnesium halides with unprecedented selectivity has been developed. The protocol utilizes 1 mol% of cheap Co(acac)3 as pre-catalyst and effects clean reactions of deactivated chlorostyrenes with only 1.1 equiv. of the Grignard reagent under mild conditions (30 °C, 5–30 min). Highly chemoselective reactions were realized even in the presence of activated bromoarenes. The olefin substituent facilitates the activation of the C–Cl bond by coordination to the catalyst. Kinetic studies indicate the operation of an arylcobaltate(I) catalyst species. Catalyst formation during the induction period was studied in the presence of cobalt(III), (I), and (−I) pre-catalysts.

Iron(III) Catalyzed Coupling of Aryl Halides: Synthesis of Terphenyl and Biphenyl Derivatives

Iron(III) mediated coupling of arylmagnesium halides with other aryl halides produced both homo- and cross-coupled products. The reaction of phenylmagnesium bromide with 1,4-dibromobenzene as well as with 4-chlorobromobenzene in presence of FeCl3 catalyst produced both cross-coupled p-terphenyl and homo-coupled biphenyl. Under the same condition only homo-coupled 4,4¢-dipropoxybiphenyl was obtained from 4-propoxyphenylmagnesium bromide. The coupling of 4-bromophenylmagnesium bromide with bromobenzene produced both homo- and cross-coupled biaryls.© 2013 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v5i1.12207 J. Sci. Res. 5 (1), 127-134 (2013)