Alkylmagnesium Bromides Research Articles

A Novel Route towards Bicyclo[1.1.1]pentane Sulfoxides from a Bench-Stable Starting Material

AbstractBicyclopentanes (BCPs) are non-classical bioisosteres that have gained a lot of interest in drug discovery as non-conjugated rigid hydrocarbons. There has been substantial progress in the synthesis of carbon- and nitrogen-substituted derivatives using [1.1.1]propellane as a precursor, while sulfur-substituted BCPs are rather underdeveloped. This work investigates a new method for the synthesis of BCP-sulfoxides. Herein, a previously reported bench-stable sodium BCP-sulfinate precursor is converted, using a range of aryl and alkyl magnesium bromides, into unsymmetrical BCP-sulfoxides via a convenient one-pot procedure. Furthermore, the conversion of the obtained sulfoxides into sulfoximines is explored.

Alkaline‐earth metal dimesitylphosphinites and their ether adducts – A structural study in solution and in the crystalline state

AbstractAlkaline‐earth metalation of dimesitylphosphane oxide Mes2P(O)H (1) in ethereal solvents with dialkylmagnesium and alkylmagnesium bromide as well as the homoleptic bis(trimethylsilyl)amides of calcium, strontium, and barium yields [(L)MgR(μ‐OPMes2)]2 (L/R=thf/Et (2‐Et), Et2O/Br (2‐Br)), [(thf)3Ca(hmds)(OPMes2)] (3‐hmds), [(thf)3Mg(OPMes2)2] (2‐thf) and [(thf)4Ae(OPMes2)2] (Ae=Ca (3‐thf), Sr (4‐thf), and Ba (5‐thf)), depending on the applied stoichiometry. Exchange of thf ligands in 3‐thf by oligodentate ethers allows isolation of [(thf)2(dme)Ca(OPMes2)2] (3‐dme), [(thf)2(diglyme)Ca(OPMes2)2] (3‐diglyme) and [(thf)(triglyme)Ca(OPMes2)2] (3‐triglyme). Contrary to this finding, oligodentate amines are unable to substitute ligated thf ligands in 3‐thf. In ethereal solutions, the heteroleptic complexes 2‐Et, 2‐Br and 3‐hmds show Schlenk‐type equilibria, interconverting these compounds into their homoleptic counterparts.

Magnesium tetraorganyl derivatives of group 13 metals as intermediate products in the synthesis of group 13 metal alkyls and aryls

Reactions of organomagnesium halides with group 13 metal halides lead to the formation of R3M type compounds (R = alkyl, aryl; M = Al, Ga, In) and are considered as the simplest methods of R3M compound syntheses. These seemingly simple reactions reveal a much more complex chemistry involving mixed magnesium‐group 13 metal compounds. To elucidate the reaction course of reactions of organomagnesium halides with group 13 metal halides, we have studied reactions of R3M with organomagnesium halides. The interaction of Et3M with R1MgX led to the formation of following products being mixtures of crystalline ionic complexes with the general composition of [Et4‐nR1nM]−[XMg (thf)5]+·(thf): [Et2.2Al(CH=CH2)1.8]−[BrMg (thf)5]+·(thf) (1), [Et3Ga(CH=CH2)]−[BrMg (thf)5]+·(thf) (2), [Et4Al]−[BrMg (thf)5]+·(thf) (3), [Et4Ga]−[BrMg (thf)5]+·(thf) (4), [Et2.9Al(C6H5)1.1]−[BrMg (thf)5]+·(thf) (5), [Et2.9Ga(C6H5)1.1]−[BrMg (thf)5]+·(thf) (6), [Et3.4GaMe0.6]−[IMg (thf)5]+·(thf) (7) and [Et4In]−[BrMg (thf)5]+·(thf) (8). A comparison of the production course of group 13 metal trialkyls R3M with a thermal decomposition of 1–8 products showed that reactions of MX3 with RMgX (X = Br, I; R = alkyl, aryl) yield initially intermediate ionic compounds, which must then be thermally decomposed to obtain pure R3M compounds. If group 13 metal bromides and iodides, and alkyl (aryl)magnesium bromides and iodides in thf are used, only intermediate products with the [R4M]−[XMg (thf)5]+·(thf) structure are formed.

Chromium-catalyzed para-selective formation of quaternary carbon centers by alkylation of benzamide derivatives

Selective creation of quaternary carbon centers has been a long-standing challenge in synthetic chemistry. We report here the chromium-catalyzed, para-selective formation of arylated quaternary carbon centers by alkylative reactions of benzamide derivatives with tertiary alkylmagnesium bromides at room temperature. The reaction, which was enabled by a low-cost chromium(III) salt combined with trimethylsilyl bromide, introduces a sterically bulky tertiary alkyl scaffold on the para-position of benzamide derivatives in a highly selective fashion without either isomerization of the tertiary alkyl group or formation of ortho-alkylated byproducts. Forming low-valent Cr species in situ by reaction of CrCl3 with t-BuMgBr accompanied by evolution of hydrogen can be considered, which serves as reactive species to promote the reaction. The para-alkylation likely occurs via a radical-type nucleophilic substitution of imino-coordination benzimidate intermediate.

Fluorographene Modified by Grignard Reagents: A Broad Range of Functional Nanomaterials.

Fluorographene is the youngest stoichiometric derivative of graphene; hence, its reactivity is only poorly explored. Compared to graphene, the significantly higher reactivity of C-F bonds makes this material a suitable platform for a large number of chemical modifications. Fluorographene is also the only member of the halographene family that can be prepared in the stoichiometric composition (C1 F1 ). Herein, the chemical modification of fluorographene with Grignard reagents, which are well known in organic synthesis for the formation of new C-C bonds, is presented. The reaction with alkyl magnesium bromides led to successful modification of fluorographene with ethyl, vinyl, ethynyl and propargyl groups. Chemical characterisation showed the presence of covalently bonded functional groups in a high concentration exceeding one functional group per C6 motif. The reactivity of Grignard reagents with fluorographene decreased from ethyl to ethynyl. The terminal carbon-carbon triple bonds were used for click reactions with organic azides leading to the formation of triazole rings. These findings open up a broad spectrum of opportunities for simple and robust modification of graphene by chemical reactions proceeding at room temperature under mild conditions. These results have major application potential in sensing, biomedical and energy-related applications.

Trinuclear magnesium complexes stabilized by aminoalkoxide ligands

New magnesium complexes, [Et2Mg3(dmamp)4] (1) and [(CH2=CH)2Mg3(dmamp)4] (2), were prepared by the reaction of alkylmagnesium bromide with sodium 1-dimethylamino-2-methyl-2-propoxide [Na(dmamp)] in THF. Complexes 1 and 2 were characterized by 1H and 13C NMR spectroscopies, FTIR spectroscopy, elemental analysis, and single-crystal X-ray diffraction (XRD) analysis. The XRD analysis showed that these complexes are trinuclear where the alkoxy O is the μ2-O bridge between the Mg ions. Among the three metal centers, the two terminal Mg ions are five coordinate and have a square–pyramidal geometry, whereas the central Mg is four coordinate with a distorted tetrahedral geometry. The combination of ethyl and vinyl groups with sterically bulky aminoalkoxide ligands plays an important role in stabilizing the molecule.

Polymeric Gel Electrolyte Based on a Rotaxane-Networked Polymer with Alkyl Magnesium Bromide and Ionic Liquid for Rechargeable Mg Batteries

Rechargeable magnesium (Mg) battery that uses metal Mg as the negative electrode is a potential candidate of the next-generation power sources for electric vehicles (EV) and other large scale applications. We previously reported that Mg is reversibly deposited and dissolved on a metal substrate in mixed solutions containing ionic liquid and alkyl magnesium bromide [1]. However, as the electrolyte system contains high vapor pressure THF, the resulting battery will have still practical problems in safety and reliability. Recently, we have synthesized a novel network polymer with a rotaxane structure, a complex consisting of secondary ammonium salt and 24-membered crown ether component [2]. In this study, a novel gel electrolyte based on a rotaxane-networked polymer has been prepared, in which ethyl magnesium bromide dissolved in triethylene glycol dimethyl ether (C2H5MgBr/Triglyme) and N,N-diethyl-N-methyl- N-(2-methoxyethyl)ammonium bis(trifluoromethylsulfonyl) imide (DEMETFSI) were included. The ionic conductance behavior and electrochemical behavior of the resulting gel electrolytes were investigated.A “rotaxane network” was synthesized in the same manner as our previous report [2] (Fig.1). The gel electrolytes were prepared by an impregnation method: the polymer film was immersed in the mixed solution of C2H5MgBr/Triglyme and DEMETFSI for 24 h. The resulting network polymer maintained the stable shape without decomposing after a month’s impregnation in 1M C2H5MgBr/Triglyme. The “rotaxane network” polymeric gel electrolyte impregnated in C2H5MgBr/ Triglyme + DEMETFSI exhibited an ionic conductivity of 2.8×10-4 S cm-1 at 20°C (swelling degree = ca. 60%). Highly reversible behavior was observed for cathodic deposition and anodic dissolution of Mg in this polymeric gel electrolyte system.AcknowledgmentThis research was financially supported by the Japan Science and Technology Agency (JST), Advanced Low Carbon Technology Research and Development Program (ALCA).

Parallel and Combinatorial Liquid-Phase Synthesis of Alkylbiphenyls Using Pentaerythritol Support

Unfunctionalized alkylbiphenyls were fabricated by a parallel and combinatorial synthesis using pentaerythritol as a tetrapodal soluble support for a sulfonate-based traceless multifunctional linker system. Nickel N-heterocyclic carbene-catalyzed reactions of pentaerythritol tetrakis(biphenylsulfonate)s with primary alkylmagnesium bromides generated the alkylbiphenyl derivatives by desulfitative cleavage/cross-coupling of the C-S bond without any "memory" of the attachment on the support. Though the reactions were completed with sufficient yields in 12 h at room temperature, even with only 1.5 equiv of nucleophiles, they still retained the benefits of facile isolation observed in polymer-supported reactions.

A New Method for the Synthesis of Phenanthridine Compounds

5-Methoxyphenanthridin-6(5H)-ones reacted with aryl Grignard reagents to afford phenanthridine compounds. The method has the advantages of mild reaction conditions with good yields and provides a new synthetic procedure for the phenanthridine derivatives. However, the products were phenanthridin-6(5H)-ones when alkyl magnesium bromide reacted with 5-methoxyphenanthridin-6(5H)-ones.

Enantioselective cyclopropanation of carboxylic esters with alkyl magnesium bromides in the presence of titanium(IV) (4R,5R)-TADDOLates

The reaction of isopropyl 4-chlorobutyrate with 3 equiv of n-BuMgBr in the presence of 1 equiv of titanium(IV) (4R,5R)-TADDOLate in diethyl ether led to the formation of (1S,2S)-(3-chloropropyl)-2-ethylcyclopropanol in 55–70% yield and 55–65% ee. The reaction was performed in the presence of 20 mol % of the catalyst without significant loss in yield and enantioselectivity when solutions of the carboxylic ester and the Grignard reagent were added simultaneously at an equal rate to a refluxing solution of the titanium catalyst in ether. The cyclopropanation of isopropyl propionate under the same conditions gave (1S,2S)-1-ethyl-2-propylcyclopropanol in 50% yield and 65% ee. Its absolute configuration was determined by chemical correlation through acid-catalyzed isomerization to enantiomerically enriched (R)-(−)-4-methyl-3-heptanone, known as a minor component of the trail pheromone of ant Aphaenogaster albisetosus and enantiomer of the alarm pheromone of leaf-cutting ants Atta texana.

ChemInform Abstract: Enyne Chlorides: Substrates for Copper‐Catalyzed Asymmetric Allylic Alkylation.

AbstractProchiral (E)‐configurated 1,3‐enyne chlorides are alkylated by different alkyl magnesium bromides to give 1,4‐enynes with excellent regioselectivities and good to excellent enantioselectivities.

ChemInform Abstract: Catalytic Asymmetric Conjugate Addition/Oxidative Dearomatization Towards Multifunctional Spirocyclic Compounds.

AbstractThe convenient one‐pot procedure includes conjugate addition of alkylmagnesium bromides to α,β‐unsaturated esters and subsequent oxidative cyclization.

An efficient synthesis of 6 H,7 H-chromeno[4,3- b]chromenes and 6,7-dihydrothio chromeno[3,2- c]chromenes as 9-substituted xanthene like analogs

An efficient synthetic route with good overall yields to access 7-aryl/heteroaryl/alkyl substituted 6 H,7 H-chromeno[4,3- b]chromene, and 6,7-dihydrothiochromeno[3,2- c]chromene scaffolds has been developed. The route to these xanthene-like analogs involves a three-step reaction sequence: (1) Michael addition of readily available phenol and thiophenol to 4-chloro-2,2-dimethyl-2 H-chromene-3-carbaldehyde, (2) Grignard reaction of different aryl, heteroaryl and alkyl magnesium bromides on the resulting carbaldehydes followed by (3) FeCl 3 catalyzed spontaneous intramolecular Friedel–Craft’s reaction on the diarylmethyl carbinols.

Catalytic Asymmetric Conjugate Addition/Oxidative Dearomatization Towards Multifunctional Spirocyclic Compounds

The convenient one-pot procedure includes conjugate addition of alkylmagnesium bromides to α,β-unsaturated esters and subsequent oxidative cyclization.

Synthesis of phosphinodiselenoic acid esters and their application as RAFT agents in styrene polymerization

Phosphinodiselenoic acid esters are synthesized from the reaction of chlorodiphenylphosphine and aryl- or alkyl-magnesium bromide in the presence of selenium powder. They are employed as RAFT agents in thermally initiated, styrene polymerization. The phosphinodiselenoic acid esters 6a and 6b showed some degree of control over the radical polymerization of styrene.

Synthesis of 1,1,3,3-Tetraalkylisoindolines Using a Microwave-Assisted Grignard Reaction

1,1,3,3-Tetraalkylisoindolines are important intermediates in the preparation of stable nitroxides, such as 1,1,3,3-tetramethylisoindolin-2-oxyl, 1, and 1,1,3,3-tetraethylisoindolin-2-oxyl, 2. The limiting step in their preparation is the Grignard reaction between N-benzylphthalimide and the appropriate alkyl magnesium bromide, which typically proceeds in yields of ~28–40%. A microwave-assisted variation of this reaction has been optimized to give improved yields and reduced reaction times (45–60% and 2 h, respectively).

Catalytic Enantioselective Conjugate Addition with Grignard Reagents

In this Account, recent advances in catalytic asymmetric conjugate addition of Grignard reagents are discussed. Synthetic methodology to perform highly enantioselective Cu-catalyzed conjugate addition of Grignard reagents to cyclic enones with ee's up to 96% was reported in 2004 from our laboratories. Excellent levels of stereocontrol were achieved with Cu(I) halides, alkylmagnesium bromides, and commercially available chiral ferrocenyl diphosphines. Studies carried out during the last 2 years demonstrated that these Cu-catalysts are very effective for the enantioselective conjugate addition of Grignard reagents to acyclic enones, alpha,beta-unsaturated esters, and thioesters. On the basis of this methodology, a diastereo- and enantioselective iterative route to deoxypropionate units was developed and applied to the synthesis of natural products. Finally, we summarize our recently conducted mechanistic investigations and the application of this catalytic system to the enantioselective SN2' substitution reactions of allylic bromides with Grignard reagents.

Synthesis of Purpurin Imide Derivatives by Modification of Peripheral Functional Groups of Methyl Pheophorbide-a

A series of novel purpurin-18 imide derivatives exhibiting long wavelength absorption and amphiphilicity were obtained from methyl pheophorbide-a (MPa) by modification of the peripheral functional groups. The vinyl group at 3-position was oxidized with OsO4 and NaIO4 to form the formyl group and the Grignard reaction of this aldehyde with the alkyl magnesium bromide was carried out to give the corresponding 3-(1-hydroxylalkyl) pheophorbide-a. The E-ring of these chlorines was converted into anhydride ring to give purpurin derivatives by air oxidation. The trans-32-alkyl purpurin derivatives were obtained by dehydration of hydroxyl group at 31-position. The N-hydroxyl purpurin imide was generated by treatment of the anhydride ring with hydroxylamine hydrochloride. The 31-alkylacyl-N-hydroxyl purpurin imides were obtained by oxidation of hydroxyl group at 31-position. The acylation of N-hydroxyl group was completed to afford N-acyloxy purpurin imides. The photocytoxicity of several compounds in vitro were tested.

Cu-Catalyzed Carbometallation of Propargylic Alcohols by Grignard Reagents

Herein, an optimized protocol for the highly regioselective carbometallation of terminal secondary propargylic alcohols by alkylmagnesium bromides is described. The reaction is catalyzed by copper salts and is completely anti-stereoselective. The conservation of the chiral information is observed, if an enantiopure substrate is used. The resulting vinylmagnesium species can be used further in Kumada coupling reaction or trapped by iodine to form (Z)-alkenyl iodides. For the latter, some further synthetic transformations are desribed.

Nickel‐Catalyzed Cross‐Coupling of Neopentyl Arenesulfonates with Methyl and Primary Alkylmagnesium Bromides.

AbstractFor Abstract see ChemInform Abstract in Full Text.