Magnesium Reagents Research Articles

Defluorination of HFCs by a magnesium reagent.

Reaction of a series of HFCs with a main group reagent containing a Mg-Mg bond results in defluorination to form the corresponding magnesium fluoride complex. In the case of 1,1,1,2-tetrafluoroethane (HFC-134a) generation of the fluoride occurs alongside selective formation of 1,1-difluoroethene. DFT calculations have been carried out to better understand the selectivity and compare the barriers for sp3 C-F bond activation with sp3 C-H bond activation in this system.

Room Temperature Defluorination of Poly(tetrafluoroethylene) by a Magnesium Reagent

Perfluoroalkyl substances (PFAS) are pervasive in the environment. The largest single use material within the PFAS compound class is poly(tetrafluoroethylene) (PTFE), a robust and chemically resistant polymer. Despite their widespread use and serious concerns about their role as pollutants, methods for repurposing PFAS are rare. Here we show that a nucleophilic magnesium reagent reacts with PTFE at room temperature, generating a molecular magnesium fluoride which is easily separated from the surface-modified polymer. The fluoride in turn can be used to transfer the fluorine atoms to a small array of compounds. This proof-of-concept study demonstrates that the atomic fluorine content of PTFE can be harvested and reused in chemical synthesis.

Thorium- and Uranium-Mediated C-H Activation of a Silyl-Substituted Cyclobutadienyl Ligand.

Cyclobutadienyl complexes of the f-elements are a relatively new yet poorly understood class of sandwich and half-sandwich organometallic compounds. We now describe cyclobutadienyl transfer reactions of the magnesium reagent [(η4-Cb'''')Mg(THF)3] (1), where Cb'''' is tetrakis(trimethylsilyl)cyclobutadienyl, toward thorium(IV) and uranium(IV) tetrachlorides. The 1:1 stoichiometric reactions between 1 and AnCl4 proceed with intact transfer of Cb'''' to give the half-sandwich complexes [(η4-Cb'''')AnCl(μ-Cl)3Mg(THF)3] (An = Th, 2; An = U, 3). Using a 2:1 reaction stoichiometry produces [Mg2Cl3(THF)6][(η4-Cb'''')An(η3-C4H(SiMe3)3-κ-(CH2SiMe2)(Cl)] (An = Th, [Mg2Cl3(THF)6][4]; An = U [Mg2Cl3(THF)6][5]), in which one Cb'''' ligand has undergone cyclometalation of a trimethylsilyl group, resulting in the formation of an An-C σ-bond, protonation of the four-membered ring, and an η3-allylic interaction with the actinide. Complex solution-phase dynamics are observed with multinuclear nuclear magnetic resonance spectroscopy for both sandwich complexes. A computational analysis of the reaction mechanism leading to the formation of 4 and 5 indicates that the cyclobutadienyl ligands undergo C-H activation across the actinide center.

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dichloroheteroarenes under Ligand-Controlled and Ligand-Free Systems.

Halides adjacent to nitrogen are conventionally more reactive in Pd-catalyzed cross-couplings of dihalogenated N-heteroarenes. However, a very sterically hindered N-heterocyclic carbene ligand is shown to promote room-temperature cross-coupling at C4 of 2,4-dichloropyridines with high selectivity (∼10:1). This work represents the first highly selective method with a broad scope for C4-coupling of these substrates where selectivity is clearly under ligand control. Under the optimized conditions, diverse substituted 2,4-dichloropyridines and related compounds undergo cross-coupling to form C4-C(sp2) and C4-C(sp3) bonds using organoboron, -zinc, and -magnesium reagents. The synthetic utility of this method is highlighted in multistep syntheses that combine C4-selective cross-coupling with subsequent nucleophilic aromatic substitution reactions. The majority of the products herein (71%) have not been previously reported, emphasizing the ability of this methodology to open up underexplored chemical space. Remarkably, we find that ligand-free "Jeffery" conditions enhance the C4 selectivity of Suzuki coupling by an order of magnitude (>99:1). These ligand-free conditions enable the first C5-selective cross-couplings of 2,5-dichloropyridine and 2,5-dichloropyrimidine.

A Cyaphide Transfer Reagent

The cyanide ion plays a key role in a number of industrially relevant chemical processes, such as the extraction of gold and silver from low grade ores. Metal cyanide compounds were arguably some of the earliest coordination complexes studied and can be traced back to the serendipitous discovery of Prussian blue by Diesbach in 1706. By contrast, heavier cyanide analogues, such as the cyaphide ion, C≡P–, are virtually unexplored despite the enormous potential of such ions as ligands in coordination compounds and extended solids. This is ultimately due to the lack of a suitable synthesis of cyaphide salts. Herein we report the synthesis and isolation of several magnesium–cyaphido complexes by reduction of iPr3SiOCP with a magnesium(I) reagent. By analogy with Grignard reagents, these compounds can be used for the incorporation of the cyaphide ion into the coordination sphere of metals using a simple salt-metathesis protocol.

Diastereoselectivity of the Addition of Propargylic Magnesium Reagents to Fluorinated Aromatic Sulfinyl Imines.

The addition of propargylmagnesium bromide to fluorinated aromatic sulfinyl imines gave homopropargyl amines with total regio- and diastereoselection. Complete reversal of diastereoselectivity can be achieved in some cases using coordinating (THF) or noncoordinating (DCM) solvents. Substituted propargylic magnesium reagents have been also tested toward fluorinated aryl sulfinyl imines affording chiral homoallenyl amines with good yields and selectivity control. DFT calculations helped to rationalize the origin of the experimental regio- and diastereoselectivities observed in each case.

Localization of Carbon-Carbon Double Bond and Cyclopropane Sites in Cardiolipins via Gas-Phase Charge Inversion Reactions.

Cardiolipins (CLs) are comprised of two phosphatic acid moieties bound to a central glycerol backbone and are substituted with four acyl chains. Consequently, a vast number of distinct CL structures are possible in different biological contexts, representing a significant analytical challenge. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) has become a widely used approach for the detection, characterization, and quantitation of complex lipids, including CLs. Central to this approach is fragmentation of the [CLs - H]- or [CL - 2H]2- anions by collision-induced dissociation (CID). Product ions in the resulting tandem mass spectra confirm the CL subclass assignment and reveal the numbers of carbons and degrees of unsaturation in each of the acyl chains. Conventional CID, however, affords limited structural elucidation of the fatty acyl chains, failing to discriminate isomers arising from different site(s) of unsaturation or cyclopropanation and potentially obscuring their metabolic origins. Here, we report the application of charge inversion ion/ion chemistry in the gas phase to enhance the structural elucidation of CLs. Briefly, CID of [CL - H]2- anions generated via negative ion ESI allowed for the assignment of individual fatty acyl substituents and phosphatidic acid moieties. Next, gas-phase derivatization of the resulting CL product ions, including fatty acyl carboxylate anions, was effected with gas-phase ion/ion charge inversion reactions with tris-phenanthroline magnesium reagent dications. Subsequent isolation and activation of the charge-inverted fatty acyl complex cations permitted the localization of both carbon-carbon double bond and cyclopropane motifs within each of the four acyl chains of CLs. This approach was applied to the de novo elucidation of unknown CLs in a biological extract revealing distinct isomeric populations and regiochemical relationships between double bonds and carbocyles.

Regioselective Bromine/Magnesium Exchange for the Selective Functionalization of Polyhalogenated Arenes and Heterocycles.

Using the bimetallic combination sBu2Mg⋅2 LiOR (R=2‐ethylhexyl) in toluene enables efficient and regioselective Br/Mg exchanges with various dibromo‐arenes and ‐heteroarenes under mild reaction conditions and provides bromo‐substituted magnesium reagents. Assessing the role of Lewis donor additives in these reactions revealed that N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine (PMDTA) finely tunes the regioselectivity of the Br/Mg exchange on dibromo‐pyridines and quinolines. Combining spectroscopic with X‐ray crystallographic studies, light has been shed on the mixed Li/Mg constitution of the organometallic intermediates accomplishing these transformations. These systems reacted effectively with a broad range of electrophiles, including allyl bromides, ketones, aldehydes, and Weinreb amides in good yields.

A new approach to removing and recovering phosphorus from livestock wastewater using dolomite

Recovering phosphorus from livestock wastewater could partly mitigate the global phosphorus resource crisis. Crystallization is a promising method for removing phosphorus from wastewater, but the costs of calcium- and magnesium-containing reagents are increasing. Cheap, available, efficient materials are required to replace conventional calcium and magnesium reagents. Here, we describe a new approach to removing and recovering phosphorus from livestock wastewater of a large pig farm, containing a high phosphorus concentration. The effects of the pH, stirring speed, stirring time, and extract dose (containing calcium and magnesium) on phosphorus removal from livestock wastewater were investigated. The product was characterized by X-ray diffractometry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Under optimized conditions (pH 9.0, stirring speed 200 r/m, stirring time 600 s, Ca 207.62 mg/L, Mg 122.86 mg/L), 92% of the phosphorus was removed from livestock wastewater. The product was mainly the hydroxyapatite (Ca5(PO4)3OH) precursor amorphous calcium phosphate but also contained 1.65% (by mass) magnesium ammonium phosphate (MgNH4PO4·6H2O) crystals. The cost of dolomite to treat 1 m3 of high-phosphorus wastewater was 0.20 yuan (45.9%, 25.9%, and 75.9% lower than for pure MgCl2, MgSO4, and CaCl2, respectively) in 2019. Using dolomite to provide calcium and magnesium effectively decreases the crystallization process cost and should encourage the use of crystallization to remove phosphorus from wastewater.

Regiodivergent and Stereospecific Aziridine Opening by Copper-Catalyzed Addition of Silicon Grignard Reagents.

A stereospecific ring opening of various 2-aryl-substituted aziridines with silicon Grignard reagents under copper catalysis is reported. The regiochemical outcome is governed by the steric demand of the silicon nucleophile. The LiCl introduced with the magnesium reagent R3 SiMgX⋅2 LiCl is shown to enhance the SN 2-type displacement of the carbon-nitrogen bond by coordination to the aziridine nitrogen atom.

Organosodium reagents step up

Organolithium and magnesium reagents are staples in chemical stockrooms. Useful in an array of reactions, they may experience their heaviest demand from cross-coupling reactions. In two such reacti...

Improving the Halogen–Magnesium Exchange by using New Turbo‐Grignard Reagents

This Minireview describes the scope of the halogen-magnesium exchange. It shows that the use of the turbo-Grignard reagent (iPrMgCl⋅LiCl) greatly enhances the rate of the Br- and I-Mg exchange. Furthermore, this magnesium reagent allows the performance of a fast sulfoxide-magnesium exchange. Also, the use of sBuMgOR⋅LiOR (R=2-ethylhexyl) enables a Br-Mg exchange in toluene leading to various Grignard reagents in toluene. Additionally, the new exchange reagent sBu2 Mg⋅2 LiOR (R=2-ethylhexyl) further increases the rate of the halogen-magnesium exchange allowing one to perform a chlorine-magnesium exchange for aromatic chlorides bearing an ortho-methoxy substituent in toluene.

Bench-Stable Stock Solutions of Silicon Grignard Reagents: Application to Iron- and Cobalt-Catalyzed Radical C(sp3 )-Si Cross-Coupling Reactions.

A robust method for the preparation of silicon-based magnesium reagents is reported. The MgBr2 used in the lithium-to-magnesium transmetalation step is generated in situ from 1,2-dibromoethane and elemental magnesium in hot THF. No precipitation of MgBr2 occurs in the heat, and transmetalation at elevated temperature leads to homogeneous stock solutions of the silicon Grignard reagents that are stable and storable in the fridge. This method avoids the preparation of silicon pronucleophiles such as Si-Si and Si-B reagents. The new Grignard reagents were applied to unprecedented iron- and cobalt-catalyzed cross-coupling reactions of unactivated alkyl bromides. The functional-group tolerance of these magnesium reagents is excellent.

Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one by Addition-Cyclization Process.

An approach to access 1-substituted isoquinolones has been developed through the addition-cyclization of imines with Grignard reagents in the presence of 2,2'-dipyridyl. A number of substituted aromatic magnesium reagents were amenable to this process, and the desired products were obtained with excellent yields and outstanding diastereoselectivities ( dr > 99:1). The utility of this convenient approach is demonstrated by the formal synthesis of ( S)-cryptostyline II. Moreover, N-methylmorpholine (NMM) was found to be an effective additive for the formation of 3-substituted isoindolin-1-ones using one-pot addition-cyclization-deprotection of imine with Grignard reagents.

Generation of Aryl and Heteroaryl Magnesium Reagents in Toluene by Br/Mg or Cl/Mg Exchange.

The alkylmagnesium alkoxide sBuMgOR⋅LiOR (R=2-ethylhexyl), which was prepared as a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides (ArMgOR⋅LiOR) in toluene. These Grignard reagents react with a broad range of electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides, epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu2 Mg⋅2 LiOR (R=2-ethylhexyl) undergoes Cl/Mg exchange with various electron-rich aryl chlorides in toluene, producing diorganomagnesium species of type Ar2 Mg⋅2 LiOR, which react well with aldehydes and allyl bromides.

Magnesium Reagents Featuring a 1,1′‐Bis(o‐carborane) Ligand Platform

The synthesis of two bis(carboranyl) (bc) magnesium reagents is described. Treatment of 1,1′‐bis(o‐carborane) (H2‐bc) or 8,8′,9,9′,10,10′,12,12′‐octamethyl‐1,1′‐bis(o‐carborane) (H2‐Mebc) with Mg(nBu)2 in 1,2‐dimethoxyethane (DME) affords (bc)Mg(DME)2 (1a,b) as crystalline solids. The magnesium compounds, which have been characterized by NMR spectroscopy and single‐crystal X‐ray crystallography in the case of 1a, serve as competent Grignard‐type reagents to generate bc‐containing species of tin from Me2SnCl2 (2a,b). The type of substitution of the bis(o‐carboranyl) ligand framework is found to strongly affect the electronic character of the tin center, as judged by 119Sn NMR spectroscopy. The disclosed compounds, which are stable solids under an atmosphere of dry nitrogen gas at room temperature, provide a new class of bc‐transfer reagents.

Poly(N-alkyl-3,6-carbazole)s via Kumada Catalyst Transfer Polymerization: Impact of Metal–Halogen Exchange

The preparation of poly(3,6-carbazole) via Kumada catalyst transfer polymerization (KCTP) is investigated and analyzed in detail by mass spectrometry to explore the scope of the applied protocols. Namely, common magnesium reagents were screened for the initial Grignard metathesis (GRIM) step and subsequently polymerized using [Ni(dppp)Cl2] (dppp is 1,3-bis(diphenylphosphanyl)propane). The metal–halogen exchange was monitored by GC, while the polymers were characterized by size exclusion chromatography (SEC) and 1H NMR spectroscopy. More importantly, the polymer end groups were investigated by means of mass spectrometry and isotope analysis, which revealed significant deviation from the chain-growth character of related poly(3-hexylthiophene). It was found that standard Grignard reagents led to incomplete GRIM even under extended reaction times and elevated temperatures, while the presence of LiCl greatly accelerated the metal–halogen exchange and also the KCTP. According to end-group analysis of the obtained polymers, side reactions occur that are attributed and explained in terms of catalyst dissociation and/or disproportionation. Namely, the replacement of the bromo-substituents by either alkyl groups via transmetalation or hydrogen via β-hydride elimination was observed. Finally, quantitative metal–halogen exchange was achieved using a magnesiate reagent, which also afforded the corresponding polymer in good isolated yield (66%). The end-group scrambling, dispersity, and observed molar masses support the proposed role of catalyst dissociation and/or disproportionation, even in the absence of excess of residual Grignard reagent.

ChemInform Abstract: Synthesis of N‐Boc‐Propargylic and Allylic Amines by Reaction of Organomagnesium Reagents with N‐Boc‐Aminals and Their Oxidation to N‐Boc‐Ketimines.

AbstractVarious N‐Boc protected propargylic and allylic aminals react with aryl, hetaryl, alkyl, alkenyl, and alkynyl magnesium reagents while efficiently forming the corresponding secondary amines.

Effects of the η(5)-C5H4(i)Pr Ligand on the Properties Exhibited by Its Tungsten Nitrosyl Complexes.

Reaction of Na[η(5)-C5H4(i)Pr] with W(CO)6 in refluxing THF for 4 days generates a solution of Na[(η(5)-C5H4(i)Pr)W(CO)3] that when treated with N-methyl-N-nitroso-p-toluenesulfonamide at ambient temperatures affords (η(5)-C5H4(i)Pr)W(NO)(CO)2 (1) that is isolable in good yield as an analytically pure orange oil. Treatment of 1 with an equimolar amount of I2 in Et2O at ambient temperatures affords (η(5)-C5H4(i)Pr)W(NO)I2 (2) as a dark brown solid in excellent yield. Sequential treatment at low temperatures of 2 with 0.5 equiv of Mg(CH2CMe3)2 and Mg(CH2CH═CMe2)2 in Et2O produces the alkyl allyl complex, (η(5)-C5H4(i)Pr)W(NO)(CH2CMe3)(η(3)-CH2CHCMe2) (3), as a thermally sensitive yellow liquid. Complex 3 may also be synthesized, albeit in low yield, in one vessel at low temperatures by reacting 1 first with 1 equiv of PCl5 and then with the binary magnesium reagents specified above. Interestingly, similar treatment of 1 in Et2O with PCl5 and only 0.5 equiv of Mg(CH2CH═CMe2)2 results in the formation of the unusual complex (η(5)-C5H4(i)Pr)W(NO)(PCl2CMe2CH═CH2)Cl2 (4), which probably is formed via a metathesis reaction of the binary magnesium reagent with (η(5)-C5H4(i)Pr)W(NO)(PCl3)Cl2. The C-D activation of C6D6 by complex 3 has been investigated and compared to that exhibited by its η(5)-C5Me5, η(5)-C5Me4H, and η(5)-C5Me4(n)Pr analogues. Kinetic analyses of the various activations have established that the presence of the η(5)-C5H4(i)Pr ligand significantly increases the rate of the reaction, an outcome that can be attributed to a combination of steric and electronic factors. In addition, mechanistic studies have established that in solution 3 loses neopentane under ambient conditions to generate exclusively the 16e η(2)-diene intermediate complex (η(5)-C5H4(i)Pr)W(NO)(η(2)-CH2═CMeCH═CH2), which then effects the subsequent C-D activations. This behavior contrasts with that exhibited by the η(5)-C5Me5 analogue of 3 which forms both η(2)-diene and η(2)-allene intermediates upon thermolysis. Sixteen-electron (η(5)-C5H4(i)Pr)W(NO)(η(2)-CH2═CMeCH═CH2) has been isolated as its 18e PMe3 adduct. All new organometallic complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of two of them have been established by single-crystal X-ray crystallographic analyses.