Magnesium Amide Research Articles

Regioselective Metalation and Functionalization of the Pyrazolo[1,5- a]pyridine Scaffold Using Mg- and Zn-TMP Bases.

A regioselective functionalization of the pyrazolo[1,5- a]pyridine scaffold using Mg- and Zn-TMP bases (TMP = 2,2,6,6-tetramethylpiperidyl) in the presence or absence of BF3·OEt2 is described. Also, various functionalized pyrazolo[1,5- a]pyridines bearing an ester function (and an NHBoc or ethyl group) are magnesiated and functionalized, leading to polysubstituted heterocycles. Additionally, a sulfoxide directed ortho-metalation, followed by the transition-metal-free amination of a pyrazolo[1,5- a]pyridine sulfoxide, using a magnesium amide, is reported.

Alkaline Earth-Centered CO Homologation, Reduction, and Amine Carbonylation.

Reactions of β-diketiminato magnesium and calcium hydrides with 1 atm of CO result in a reductive coupling process to produce the corresponding derivatives of the cis-ethenediolate dianion. Computational (DFT) analysis of this process mediated by Ca, Sr, and Ba highlights a common mechanism and a facility for the reaction that is enhanced by increasing alkaline earth atomic weight. Reaction of CO with PhSiH3 in the presence of the magnesium or calcium hydrides results in catalytic reduction to methylsilane and methylene silyl ether products, respectively. These reactions are proposed to ensue via the interception of initially formed group 2 formyl intermediates, an inference which is confirmed by a DFT analysis of the magnesium-centered reaction. The computational results identify the rate-determining process, requiring traversal of a 33.9 kcal mol-1 barrier, as a Mg-H/C-O σ-bond metathesis reaction, associated with the ultimate cleavage of the C-O bond. The carbonylation reactivity is extended to a variety of magnesium and calcium amides. With primary amido complexes, which for calcium include a derivative of the parent [NH2]- anion, CO insertion is facile and ensues with subsequent nitrogen-to-carbon migration of hydrogen to yield a variety of dinuclear and, in one case, trinuclear formamidate species. The generation of initial carbenic carbamoyl intermediates is strongly implicated through the isolation of the CO insertion product of a magnesium N-methylanilide derivative. These observations are reinforced by a DFT analysis of the calcium-centered reaction with aniline, which confirms the exothermicity of the formamidate formation (ΔH = -67.7 kcal mol-1). Stoichiometric reduction of the resultant magnesium and calcium formamidates with pinacolborane results in the synthesis of the corresponding N-borylated methylamines. This takes place via a sequence of reactions initiated through the generation of amidatohydridoborate intermediates and a cascade of reactivity that is analogous to that previously reported for the deoxygenative hydroboration of organic isocyanates catalyzed by the same magnesium hydride precatalyst. Although a sequence of amine formylation and deoxygenation may be readily envisaged for the catalytic utilization of CO as a C1 source in the production of methylamines, our observations demonstrate that competitive amine-borane dehydrocoupling is too facile under the conditions of 1 atm of CO employed.

Transition-Metal-Free Amination of Pyridine-2-sulfonyl Chloride and Related N-Heterocycles Using Magnesium Amides.

A new transition-metal-free amination of pyridine-2-sulfonyl chloride and related N-heterocycles using magnesium amides of type R2NMgCl·LiCl is reported. Additionally, the directed ortho-magnesiation of pyridine-2-sulfonamides using TMPMgCl·LiCl was investigated. Reaction of the magnesium intermediates with various electrophiles and subsequent amination using magnesium amides led to a range of 2,3-functionalized pyridines. Also, cyclization reactions providing an aza-indole and an aza-carbazole were carried out.

Magnesium amide catalyzed selective hydroboration of esters.

Magnesium amide complexes such as Mg{N(SiMe3)2}2 (1) xylLMgN(SiMe3)2·THF (2) [xylL = ArNC(NiPr2)NAr; (Ar = 2,6-Me2-C6H3)] and dippLMgN(SiMe3)2·THF (3) [dippL = ArNC(NiPr2)NAr; (Ar = 2,6-iPr2-C6H3)] are reported as highly efficient pre-catalysts for the hydroboration of a wide range of esters using pinacolborane (HBpin) under mild reaction conditions. Moreover, we have shown compound 1 catalyzed chemoselective reduction of esters in the presence of other reducible functional groups such as alkene, alkyne and nitro.

A Step-Efficient Pathway to Chlorine-Functionalized Thiophene Oligomers by Palladium-Catalyzed Deprotonative Coupling of Chlorothiophenes

Deprotonative metalation of 2-chloro-3-substituted thiophene at the 5-position of the thiophene ring is performed by using a bulky magnesium amide 2,2,6,6-tetramethylpiperidin-1-yl magnesium chloride lithium chloride salt (TMPMgCl·LiCl). The obtained metallic species reacts with bromothiophene to afford the regioregular head-to-tail-type chlorobithiophene, which is subjected to further end functionalization by the coupling reaction with the C–Cl bond. Deprotonative C–H coupling polycondensation of substituted chlorobithiophene derivatives gives polythiophene as a formal alternating copolymer.

Solvent dependence of the solid-state structures of salicylaldiminate magnesium amide complexes.

There are challenges in using magnesium coordination complexes as reagents owing to their tendency to adopt varying aggregation states in solution and thus impacting the reactivity of the complexes. Many magnesium complexes are prone to ligand redistribution via Schlenk equilibrium due to the ionic character within the metal-ligand interactions. The role of the supporting ligand is often crucial for providing stability to the heteroleptic complex. Strategies to minimize ligand redistribution in alkaline earth metal complexes could include using a supporting ligand with tunable sterics and electronics to influence the degree of association to the metal atom. Magnesium bis(hexamethyldisilazide) was reacted with salicylaldimines [1L = N-(2,6-diisopropylphenyl)salicylaldimine and 2L = 3,5-di-tert-butyl-N-(2,6-diisopropylphenyl)salicylaldimine] in either nondonor (toluene) or donor solvents [tetrahydrofuran (THF) or pyridine]. The structures of the magnesium complexes were studied in the solid state via X-ray diffraction. In the nondonor solvent, i.e. toluene, the heteroleptic complex bis{μ-2-[(2,6-diisopropylphenyl)iminomethyl]phenolato}-κ3N,O:O;κ3O:N,O-bis[(hexamethyldisilazido-κN)magnesium(II)], [Mg2(C19H22NO)2(C6H18NSi2)2] or [1LMgN(SiMe3)2]2, (1), was favored, while in the donor solvent, i.e. pyridine (pyr), the formation of the homoleptic complex {2,4-di-tert-butyl-6-[(2,6-diisopropylphenyl)iminomethyl]phenolato-κ2N,O}bis(pyridine-κN)magnesium(II) toluene monosolvate, [Mg(C27H38NO)2(C5H5N)2]·C5H5N or [{2L2Mg2(pyr)2}·pyr], (2), predominated. Heteroleptic complex (1) was crystallized from toluene, while homoleptic complexes (2) and the previously reported [1L2Mg·THF] [Quinque et al. (2011). Eur. J. Inorg. Chem. pp. 3321-3326] were crystallized from pyridine and THF, respectively. These studies support solvent-dependent ligand redistribution in solution. In-situ 1H NMR experiments were carried out to further probe the solution behavior of these systems.

A Soft Grip: Magnesium Complexes with a Phosphine-Modified Phosphonium Diylidic Lewis Base.

Simple strategies to obtain magnesium complexes with the soft chelating diylidic ligand [Ph2 PCHPPh2 (fluorenylidene)]- (dppmflu- ) were developed to evaluate the influence of the hard acid (cation) and soft base (anion) mismatch on the stability and reactivity of the formed derivatives. Deprotonation of the precursor Ph2 PCH2 PPh2 (flu) (dppmfluH) by an alkylmagnesium derivative or magnesium amide provided access to [{Mg(dppmflu)(μ-nBu)}2 ], [Mg(dppmflu){N(SiMe3 )2 }], and [{Mg(dppmflu)(μ-Me)}2 ], which were used as starting materials for further investigations. The reaction of [{Mg(dppmflu)(μ-nBu)}2 ] with PhSiH3 in the presence of THF allowed isolation of the magnesium hydride complex [{Mg(dppmflu)(μ-H)(thf)}2 ] without a stabilizing nitrogen donor ligand. Prolonged heating enforced ligand redistribution and [{Mg(dppmflu)(μ-H)(thf)}2 ] was converted to [Mg(dppmflu)2 ] and MgH2 . The homoleptic derivative [Mg(dppmflu)2 ], in which the magnesium center is in a very soft ligand environment, can open a THF molecule by frustrated Lewis pair reactivity to give [{Mg(dppmflu)(μ-OC4 H8 dppmflu)}2 ].

Expedient Access to Normal‐ and Abnormal‐ N‐Heterocyclic Carbene (NHC) Magnesium Compounds from Imidazolium Salts

Treatment of imidazolium salts (IPrH)Cl (1) and (IPrH)I (2) with MeMgI leads to the formation of normal N‐heterocyclic carbene (nNHC) compounds (IPr)MgCl(I) (3) and (IPr)MgI2 (4) [IPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene], respectively. By employing a similar strategy, the first magnesium compound (aIPrPh)MgI2(OEt2) (6) featuring an abnormal‐NHC [aIPrPh = 1,3‐bis(2,6‐diisopropylphenyl)‐2‐phenyl‐imidazol‐4‐ylidene] is prepared by the treatment of a C2‐arylated imidazolium salt (IPrPh)I (5) with MeMgI. While the deprotonation of 1 and 2 can be accomplished at room temperature, an elevated temperature is required to deprotonate 5 with MeMgI. This is most likely due to the higher pKa value of the C4‐H than that of the C2‐H hydrogen atom. Salt metathesis reaction of 6 with KN(SiMe3)2 cleanly leads to the formation of a magnesium amide derivative (aIPrPh)Mg{N(SiMe3)2}2 (7). Compounds 3, 4, 6, and 7 were characterized by elemental analyses and NMR spectroscopic studies. The molecular structures of 3, 4, and 6 were determined by single‐crystal X‐ray diffraction analyses.

Theoretical study on the hydrogen storage mechanism of the Li–Mg–N–H system

The gas-phase reaction mechanism of magnesium amide (Mg(NH2)2) and lithium hydride (LiH) to produce H2 is theoretically investigated using ab initio electronic structure and total energy calculations based on the density functional theory. The reaction with the addition of KH which has been reported to lower the activation energy is also considered. We identify intermediate complexes and transition states in the reaction pathways. Detailed processes are analyzed to show how each reactant (Mg(NH2)2 or LiH) contributes a H atom to produce a H2 molecule and KH induces a modified reaction mechanism with a lower reaction energy.

Synthesis of Poly(3-substituted thiophene)s of Remarkably High Solubility in Hydrocarbon via Nickel-Catalyzed Deprotonative Cross-Coupling Polycondensation

Polythiophenes bearing a siloxane moiety in a substituent at the 3-position are prepared by deprotonative polycondensation of 2-bromo-3-substituted-thiophene with a bulky magnesium amide chloromagnesium 2,2,6,6-tetramethylpiperidine-1-yl lithium chloride salt (TMPMgCl·LiCl) catalyzed by a nickel complex. Deprotonation takes place at 60 °C for 1 h to form the corresponding thiophene magnesium species, which is subjected to the polymerization by addition of 0.1–5 mol % NiCl2(PPh3)IPr (IPr: 1,3-bis(2,6-diisopropylphenyl)imidazole-2-yl). Polymerization proceeds in a highly regioregular manner, and the molecular weight of the thus-obtained polymer is controllable by the ratio of monomer feed/catalyst loading to indicate Mn of up to 280 000 with narrow molecular weight distribution. Chlorothiophenes are also found to induce polymerization in a deprotonative manner with TMPMgCl·LiCl or nBuLi (the Murahashi coupling polymerization). The obtained polymers bearing a siloxane moiety in the substituent is revealed to...

Kinetic Modification on Hydrogen Desorption of Lithium Hydride and Magnesium Amide System.

Various synthesis and rehydrogenation processes of lithium hydride (LiH) and magnesium amide (Mg(NH2)2) system with 8:3 molar ratio are investigated to understand the kinetic factors and effectively utilize the essential hydrogen desorption properties. For the hydrogen desorption with a solid-solid reaction, it is expected that the kinetic properties become worse by the sintering and phase separation. In fact, it is experimentally found that the low crystalline size and the close contact of LiH and Mg(NH2)2 lead to the fast hydrogen desorption. To preserve the potential hydrogen desorption properties, thermochemical and mechanochemical rehydrogenation processes are investigated. Although the only thermochemical process results in slowing the reaction rate due to the crystallization, the ball-milling can recover the original hydrogen desorption properties. Furthermore, the mechanochemical process at 150 °C is useful as the rehydrogenation technique to preserve the suitable crystalline size and mixing state of the reactants. As a result, it is demonstrated that the 8LiH and 3Mg(NH2)2 system is recognized as the potential hydrogen storage material to desorb more than 5.5 mass% of H2 at 150 °C.

Chromium(II)-Catalyzed Amination of N-Heterocyclic Chlorides with Magnesium Amides

We report a ligand-free chromium(II)-catalyzed amination reaction of various N-heterocyclic chlorides. CrCl2 regioselectively catalyzes the reaction of chloropyridines and dichloropyridines, dichloroquinolines, dichloroisoquinolines and dichloroquinoxalines with a range of aliphatic, allylic, benzylic and saturated (hetero)cyclic magnesium amides in the presence of lithium chloride as additive. The reactions were performed at 50 °C in THF and led to the desired aminated products in 56–96% yield.

ChemInform Abstract: Development of Chiral Heteroleptic Magnesium Amides; Asymmetric Deprotonations Mediated by Six‐Membered Metallocyclic Amidomagnesium Naphtholates.

AbstractA series of chiral six‐membered metallocyclic amidomagnesium naphthalates is prepared and used in the asymmetric deprotonation of prochiral ketones.

Synthesis of hydrides by interaction of intermetallic compounds with ammonia

Interaction of intermetallic compounds with ammonia was studied as a processing route to synthesize hydrides and hydridonitrides of intermetallic compounds having various stoichiometries and types of crystal structures, including A2B, AB, AB2, AB5 and A2B17 (A=Mg, Ti, Zr, Sc, Nd, Sm; B=transition metals, including Fe, Co, Ni, Ti and nontransition elements, Al and B). In presence of NH4Cl used as an activator of the reaction between ammonia and intermetallic alloys, their interaction proceeds at rather mild P–T conditions, at temperatures 100–200°C and at pressures of 0.6–0.8MPa. The mechanism of interaction of the alloys with ammonia appears to be temperature-dependent and, following a rise of the interaction temperature, it leads to the formation of interstitial hydrides; interstitial hydridonitrides; disproportionation products (binary hydride; new intermetallic hydrides and binary nitrides) or new metal–nitrogen–hydrogen compounds like magnesium amide Mg(NH2)2. The interaction results in the synthesis of the nanopowders where hydrogen and nitrogen atoms become incorporated into the crystal lattices of the intermetallic alloys. The nitrogenated materials have the smallest particle size, down to 40nm, and a specific surface area close to 20m2/g.

Catalytic C–N bond formation in guanylation reaction by N-heterocyclic carbene supported magnesium(II) and zinc(II) amide complexes

The catalytic activity of N-heterocyclic carbene (NHC) supported magnesium(II) and a zinc(II) amide complex towards the addition of N–H bond of amine to carbodiimide was studied. Treatment of a free carbene i.e., 1,3-di-tert-butylimidazol-2-ylidene (ItBu) with magnesium and zinc bis(amide) i.e., M[N(SiMe3)2]2, M = Mg or Zn in toluene led to the formation of ItBu:M[N(SiMe3)2]2, M = Mg(1) and Zn(2) compounds, respectively. Both 1 and 2 were characterized by multinuclear (1H, 13C and 29Si) NMR spectroscopy and single X-ray crystal structure analysis. Solid state structures revealed that both complexes are monomeric in nature and their magnesium and zinc atoms are three coordinated and distorted trigonal planar in geometries. Furthermore, compounds 1 and 2 were tested as catalysts for the guanylation reaction of addition of amine to carbodiimide and turned to be excellent catalysts.

Development of chiral heteroleptic magnesium amides; asymmetric deprotonations mediated by six-membered metallocyclic amidomagnesium naphtholates

A series of enantioenriched six-membered metallocyclic amidomagnesium naphtholates were prepared and used to probe the structure–reactivity/selectivity relationships of heteroleptic magnesium base complexes within asymmetric deprotonation reactions. An effective complex was identified and applied within enantioselective enolisation processes, delivering good levels of enantioselectivity and also revealing key structural requirements for achieving such selectivity.

Facile Preparation of Poly(3-substituted thiophene) Block Copolymers by Nickel-catalyzed Deprotonative Polycondensation without External Generation of Thiophene Organometallic Species

Abstract Thiophene-based block copolymers are synthesized by addition of bromothiophene and the Knochel–Hauser base (TMPMgCl·LiCl). Nickel-catalyzed deprotonative C–H coupling polycondensation of 3-substituted-thiophenes proceeds to give head-to-tail-type poly(3-substituted thiophen-2,5-diyl) bearing nickel at the polymer end. Block copolymers of thiophene derivatives are obtained by successive addition of 2-bromo-3-alkylthiophene and magnesium amide to a living polythiophene end. The use of nickel catalyst bearing an o-tolyl group gives the tolyl-group-terminated thiophene diblock copolymers in high efficiency. Triblock copolymer is also synthesized by the iterative addition of bromothiophene and TMPMgCl·LiCl.

ChemInform Abstract: Iron‐Catalyzed Aromatic Amination for Nonsymmetrical Triarylamine Synthesis.

AbstractThe key to the success of this novel protocol is the use of in situ generated magnesium amides in the presence of a lithium halide, which dramatically increases the product yield.

Directed Magnesiation of Polyhaloaromatics using the Tetramethylpiperidylmagnesium Reagents TMP2Mg⋅2 LiCl and TMPMgCl⋅LiCl

AbstractA convenient and efficient functionalization of polyhaloaromatics via regioselective magnesiation has been developed. Starting from simple, inexpensive but structurally challenging arenes, metallation by magnesium amide bases was achieved under mild conditions. The desired Grignard reagents were stable towards aryne formation, were obtained in good yields within short reaction times and could be reacted with a variety of typical electrophiles, providing attractive, functionalized building blocks in good to excellent yields. As an application we have prepared the antimicrobial natural product 2,6‐dichloro‐3‐phenethylphenol isolated from the New Zealand liverwort Riccardia marginata. This synthesis involves a mixed bimetallic compound prepared via metallation of a phenylboronic acid pinacol ester derivative and subsequent selective cross‐coupling.

Magnesium Catalysis of Imine Hydroboration

The β-diketiminato magnesium alkyl complex [LMgnBu] (L=CH{CMe(NDipp)}(2), Dipp=diisopropylphenyl) is shown to be a highly effective precatalyst for the hydroboration of alkyl and aryl substituted aldimines and ketimines with pinacol borane (HBpin). Catalysis is proposed to occur through a sequence of Mg-N/B-H metathesis and rate-determining Mg-H/N=C insertion steps, a proposal strongly supported by stoichiometric studies and kinetic analysis. The reactions are observed to proceed through the intermediacy of well-defined magnesium amides, two examples of which have been isolated and structurally characterized. Mechanistic investigations suggest that the catalytic rate-determining process occurs at an isolated magnesium center and requires the presence of two molecules of the imine substrate for effective turnover. This latter observation is rationalized as a requirement for the secondary substrate molecule to displace HBpin from the coordination sphere of the catalytic magnesium center.