Alkali Metal Amides Research Articles

Directed Aromatic Deuteration and Tritiation of Pharmaceuticals by Heavy Alkali Metal Amide Catalysts

Directed Aromatic Deuteration and Tritiation of Pharmaceuticals by Heavy Alkali Metal Amide Catalysts

Isolable rubidium and caesium derivatives of common organic carbonyl compounds.

Light alkali metal (Li, Na, K) amides have a long history of synthetic utility, but heavier (Rb, Cs) congeners have barely been studied. This study reveals remarkable structurally complex outcomes of reacting AM(HMDS) (AM = Rb, Cs; HMDS = hexamethyldisilazide) with benzaldehyde and acetophenone. Though complicated, reactions give a diversity of eye-catching isolated products, an enolate with a hexagonal prismatic network, two dienolates with distinct extended ladder motifs, and two β-imino-alkoxides comprising zig-zag chains of metal-oxygen bonds in infinite cages.

Synthesis and Reactivity of Alkali Metal Hydrido-Magnesiate Complexes which Exhibit Group 1 Metal Counter-Cation Specific Stability.

Reactions of the series of alkali metal amides M(HMDS) (M = Li-Cs; HMDS = [N(SiMe3)2]-) with the neutral magnesium(II) hydride compound [Mg(BDIDipp)(μ-H)]2 (BDIDipp = [CH{C(Me)NDipp}2], Dipp = 2,6-iPr2-C6H3) have been carried out. When M = Li or Na, the reactions yielded Mg(BDIDipp)(HMDS) and MH as the primary products. In the sodium amide reaction, [Na2(HMDS)][{Mg(BDIDipp)}2(H)3] was obtained as a low-yield by-product. When M = K-Cs, the reactions gave the group 1 metal hydrido-magnesiates, M2[Mg(BDIDipp)(HMDS)(H)]2·(benzene)n (n = 0 or 1), the thermal stability of which increases with the increasing molecular weight of the alkali metal involved. Reactions of Cs2[Mg(BDIDipp)(HMDS)(H)]2·(benzene) with 18-crown-6 and CO gave the first monomeric alkali metal hydrido-magnesiate [Cs(18-crown-6)][Mg(BDIDipp)(HMDS)(H)] and the ethenediolate complex Cs2[{Mg(BDIDipp)(HMDS)}2(μ-C2H2O2)], respectively. The new synthetic route to alkali metal hydrido-magnesiates described herein may facilitate further reactivity studies of this rare compound class.

Uncovering the Untapped Potential of the Use of Sodium Amides for Regioselective Arene Functionalisation.

Alkali-metal amides have become key reagents in synthetic chemistry, with special focus in deprotonation reactions. Despite the higher reactivity found in the heavier sodium and potassium amides, their insolubility and low stability has favoured the use of the more soluble lithium analogues, converting them into the most used non-nucleophilic bases. Studying the coordination effects of Lewis donor molecules such as tridentate amine PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) in combination with the sodium amide NaTMP (TMP = 2,2',6,6'-tetramethylpiperidide), we have been able to unlock the use of these reagents for the functionalisation of arenes, i.e. the deuterium incorporation by hydrogen isotope exchange and the deprotonative borylation of unactivated arenes. These findings show how sodium amides are not just a simple more sustainable replacement of their lithium counterparts, but also that they can display significantly enhanced reactivities allowing for the development of new transformations.

Comparative Study on Charge–Discharge Behavior of Graphite Positive Electrode in FSA- and FTA-Based Ionic Liquid Electrolytes with Different Alkali Metal Cations

Dual-carbon batteries (DCBs), in which both the positive and negative electrodes are composed of carbon-based materials, are promising next-generation batteries owing to their limited usage of scarce metals and high operating voltages. In typical DCBs, metal cations and anions in the electrolytes are consumed simultaneously at the negative and positive electrodes, respectively, which can rapidly deplete the charge carrier ions in the electrolytes. In this study, to solve this challenge, we focused on ionic liquids (ILs) as DCB electrolytes because they are solely composed of ions and are therefore intrinsically highly concentrated electrolytes. Charge–discharge behavior of the graphite positive electrodes was investigated in several IL electrolytes containing alkali metal cations (Li+, Na+, and K+) and amide anions (FSA− and FTA−; FSA = bis(fluorosulfonyl)amide, FTA = (fluorosulfonyl)(trifluoromethylsulfonyl)amide). It was found that FTA-based ILs conferred superior cycling stability and higher capacities to graphite electrodes compared to FSA-based ILs, which was explained by the suppression of the corrosion of the aluminum current collector at high voltages. The highest reversible capacity of approximately 100 mAh g−1 was obtained for the K-ion system using FTA-based ILs at 20 mA g−1, which involved the formation of FTA–graphite intercalation compounds, as confirmed by ex situ X-ray diffraction.

Structural characterization of the 1-metallo-2-t-butyl-1,2-dihydropyridyl rubidium and caesium complexes

With recent reports of alkali metal amides used in homogeneous catalytic chemistry where the reactivity down group one is dependent on the metal identity, esoteric rubidium and caesium amides are finding new admirers amongst chemists who usually study lithium, sodium, and potassium utility amides. Here, as a forerunner to their exploitation in catalysis, we report the X-ray crystallographic and NMR solution structures of the 1-metallo-2-t-butyl-1,2-dihydropyridyl (DHP) complexes of rubidium and caesium, thereby completing the homologous alkali metal series. Crystallized as monosolvated {[Rb(tBuDHP)·THF]2}∞ and hemisolvated {[Cs(tBuDHP)]2·THF}∞, both form spectacular supramolecular structures. While each shares a plethora of metallo-π-contacts with the DHP anion, their subunits differ. The former dimerizes in a ‘slipped’ fashion via interactions between the symmetrically-equivalent Rb centres and the π-system of the adjacent DHP ring, but the latter has distinct Cs centres within its dinuclear subunit, with one Cs engaging in σ-bonding to two tBuDHP anions, whereas the other Cs binds in a more side-on fashion to the π-system of the ring.

Na7RbTl4 – A New Ternary Zintl Phase Containing [Tl4]8− Tetrahedra

AbstractNa7RbTl4 has been prepared by solid state reaction from the elements. Single crystal X‐ray structure analysis suggested the presence of pseudo‐merohedral twinning. The final model could be derived in space group Pbam (a=16.3584(4) Å, b=16.3581(4) Å, c=11.3345(3) Å, V=3033.04(14) Å3, R1/wR2 0.0282/0.0402) and proved the presence of isolated [Tl4]8− anions, which are only known from two other solid state thallide phases so far. The structure of Na7RbTl4 is compared to the long‐known Na2Tl and the similarities and differences in the three‐dimensional arrangement within the crystal structures are reported on. DOS calculations revealed a pseudo‐band gap at EF. Dissolution experiments in the style of the chemistry of group 14 and group 15 Zintl anions in liquid ammonia yielded degradation of the thallides. Subsequent characterization of the reaction products by powder X‐ray diffraction allowed for the determination of alkali metal amide and elemental thallium as products.

Development of a Library of Extremely Bulky Amide Ligands, and their use for the Stabilization of Germanium(I) and Germanium(II) Compounds

AbstractEleven new extremely bulky aryl/silyl substituted secondary amines, L1–11H, have been prepared. These incorporate a combination of one of the bulky aryl groups, C6H2{C(H)Ph2}2R‐2,6,4; R=Me (Ar*), Pri (Ar†); C6H2{C(H)(C6H3But2‐3,5)2}2Me‐2,6,4) (Ar#); or C6H2{C(H)(2‐naphthyl)2}2Me‐2,6,4 (Ar¥), and one of the silyl fragments, SiMe3, SiCy3 (Cy=cyclohexyl), SiPri3, Si(p‐C6H4But)3, or Si(OBor)3 (OBor=[(1S)‐endo]‐(−)‐borneoxy). Amines including the latter silyl group represent the first enantiopure examples of this ligand class. All amines are readily deprotonated with n‐butyllithium or KH. Reactions of five alkali metal amide complexes with GeCl2⋅dioxane have given monomeric amido‐germanium(II) chloride complexes, LxGeCl (x=1–4, 7). Treatment of two of these with KOBut afforded monomeric amido‐germanium(II) tert‐butoxide species, LxGeOBut (x=1 or 3). Reductions of two amido‐germanium(II) chloride systems with a dimagnesium(I) compound afforded amido‐digermyne species, LxGeGeLx (x=3 or 4), the X‐ray crystal structures of which show them to possess very short Ge−Ge bonds, with considerable implied multiple bond character.

Reaction of lithium hexamethyldisilazide (LiHMDS) with water at ultracold conditions.

Alkali metal amides are highly reactive reagents that are broadly applied as strong bases in organic synthesis. Here, we use a combined helium nanodroplet IR spectroscopic and theoretical (DFT calculation) study to show that the reaction of the model compound lithium hexamethyldisilazide (LiHMDS) with water is close to barrierless even at ultra-cold conditions. Upon complex formation of dimeric (LiHMDS)2 with water in helium nanodroplets as ultra-cold nano-reactors (0.37 K) we observed the reaction product (LiOH)2(HMDS)2. This can be rationalized as aggregation induced reation upon stepwise addition of water. With increasing water partial pressure, only the product (LiOH)2(HMDS)2 is observed experimentally. This implies that the large interaction energy (69 kJ mol-1) of (LiHMDS)2 with water is sufficient to overcome the follow-up reaction barriers, in spite of the rapid cooling rates in He nanodroplets.

Alkali Metal Amide–Catalyzed Deuteration and Tritiation of Pharmaceuticals

Alkali Metal Amide–Catalyzed Deuteration and Tritiation of Pharmaceuticals

Progress in ammonothermal crystal growth of indium nitride

Novel synthesis conditions for the ammonothermal synthesis of InN single crystals were tested. All syntheses were conducted using equimolar amounts of alkali metal amide and halide ions, generally providing a near-ammononeutral milieu. InI3 and CsNH2 were used as reactants and mineralizers, which lead to a successful synthesis of InN under rather mild reaction conditions of 423 K and 34 MPa. Moreover, information on the relative solubilities of the reactants in ammonia is obtained, utilizing the mineralizer system InCl3 and KNH2. By spatial separation of InCl3 and KNH2 it is shown that KNH2 dissolves entirely during the process and InN is likely to be formed by reaction of less-soluble InCl3 with the solution.

Reactivity studies and structural outcomes of a bulky dialkylaluminium amide in the presence of the N-heterocyclic carbene, ItBu

Aluminium reagent iBu2Al(TMP) (TMP is 2,2,6,6-tetramethylpiperidide) has previously shown interesting synergistic metallation chemistry when paired with alkali metal amides. Here its structural chemistry and reactivity is explored in the presence of the N-heterocyclic carbene, ItBu, 1,3-di-tert-butylimidazol-2-ylidene. Abnormal aItBu structures are obtained with iBu2Al(TMP) on its own and in the co-presence of LiTMP, NaTMP or KTMP. Reaction with phenol is stoichiometric dependent leading to the diphenolate [ItBu(H)]+ [(PhO)2Al(iBu)2]− and triphenolate [ItBu(H)]+ [(PhO)3Al(iBu)]− ionic complexes. Dinuclear aItBu(Ph)CN[Al(iBu)2NC(TMP)Ph]Al(iBu)2 was the surprising product from reaction with benzonitrile, displaying an imidoC- and (iBu)2Al- disubstituted imidazolium ring as well as a second imido unit made by addition of “non-nucleophilic” TMP across the benzonitrile triple bond. Potential insight into the mechanism of this intriguing complicated reaction was gained through the crystallographic characterisation of the ketamide [iBu2AlNC(Ph)TMP]2, a possible intermediate. Reaction with Ph2CHCN, diphenylacetonitrile, proved more straightforward affording the ionic complex [ItBu(H)]+ [Ph2CCN]−.

Catalytic Enantioselective Alkylation of Prochiral Enolates.

The asymmetric alkylation of enolates is a particularly versatile method for the construction of α-stereogenic carbonyl motifs, which are ubiquitous in synthetic chemistry. Over the past several decades, the focus has shifted to the development of new catalytic methods that depart from classical stoichiometric stereoinduction strategies (e.g., chiral auxiliaries, chiral alkali metal amide bases, chiral electrophiles, etc.). In this way, the enantioselective alkylation of prochiral enolates greatly improves the step- and redox-economy of this process, in addition to enhancing the scope and selectivity of these reactions. In this review, we summarize the origin and advancement of catalytic enantioselective enolate alkylation methods, with a directed emphasis on the union of prochiral nucleophiles with carbon-centered electrophiles for the construction of α-stereogenic carbonyl derivatives. Hence, the transformative developments for each distinct class of nucleophile (e.g., ketone enolates, ester enolates, amide enolates, etc.) are presented in a modular format to highlight the state-of-the-art methods and current limitations in each area.

Facile Synthesis of Cyanide and Isocyanides from CO.

The reaction of K[N(SiMe3 )2 ] with 13 CO proceeds in C6 D6 or THF affording K13 CN and O(SiMe3 )2 under mild conditions as confirmed by crystallographic characterization of K(18-crown-6)CN. Similarly reaction of the alkali metal amides, M[N(SiR3 )R'] (M=Li, K; R=Ph, Me; R'=alkyl, aryl) provides the corresponding 13 C labeled isocyanide RN13 C and MOSiR3 , generally in high yields. In some instances, the use of the sterically bulky Ph3 Si-substituent is required to preclude 1,2-silyl migration affording the silylcarbamoyl salt M[Me3 SiC(O)NR']. These reactions have been used to obtain 19 examples of 13 C labelled isocyanides, and several examples of gram scale reactions are reported. The mechanism of the reactions is probed via reliable DFT calculations.

Facile Synthesis of Cyanide and Isocyanides from CO

AbstractThe reaction of K[N(SiMe3)2] with 13CO proceeds in C6D6 or THF affording K13CN and O(SiMe3)2 under mild conditions as confirmed by crystallographic characterization of K(18‐crown‐6)CN. Similarly reaction of the alkali metal amides, M[N(SiR3)R′] (M=Li, K; R=Ph, Me; R′=alkyl, aryl) provides the corresponding 13C labeled isocyanide RN13C and MOSiR3, generally in high yields. In some instances, the use of the sterically bulky Ph3Si‐substituent is required to preclude 1,2‐silyl migration affording the silylcarbamoyl salt M[Me3SiC(O)NR′]. These reactions have been used to obtain 19 examples of 13C labelled isocyanides, and several examples of gram scale reactions are reported. The mechanism of the reactions is probed via reliable DFT calculations.

Review of the Decomposition of Ammonia to Generate Hydrogen

Because of the problems associated with the generation and storage of hydrogen in portable applications, the use of ammonia has been proposed for on-site production of hydrogen through ammonia decomposition. First, an analysis of the existing systems for ammonia decomposition and the challenges for this technology are presented. Then, the state of the art of the catalysts used to date for ammonia decomposition is described considering the catalysts composed of noble and non-noble metals and their combinations, as well as novel materials such as alkali metal amides and imides. The effect of the supports and promoters used is analyzed in detail, and the catalytic activity obtained is compared. An analysis of the kinetics of the reaction obtained with different catalysts is also presented and discussed, including the reaction mechanism, the determining step of the reaction, and the apparent activation energy. Finally, the structured reactors used to date for the decomposition reaction of ammonia are explored, as well as the possibilities offered by catalytic membrane reactors, which allow the on-site simultaneous production and separation of hydrogen.

Pyrrole‐based pincer ligands containing iminophosphorane moieties and their coordination chemistry with group 1 metals and magnesium

AbstractThe Staudinger reaction of 2,5‐bis((di‐tert‐butylphosphaneyl)methyl)‐1H‐pyrrole (tBuPNP)H; tBuPNP=C4H2N‐2,5‐CH2PtBu2) with 2 equiv. of Me3SiN3 cleanly furnishes 1,1′‐((1H‐pyrrole‐2,5‐diyl)bis(methylene))bis(1,1‐di‐tert‐butyl‐N‐(trimethylsilyl)‐λ5‐phosphanimine) (1; (NPNPN)H, NPNPN=C4H2N‐2,5‐CH2PtBu2NSiMe3) in excellent yield. Pyrrole 1 is easily deprotonated by alkali metal amides, [MN(SiMe3)2] (M=Li, Na, K, Cs) to yield the corresponding alkali metal pyrrolides, 1‐M. Compound 1‐Li is features a κ‐N,N,N coordination whereby both iminophosphorane side‐arms are coordinated to the lithium cation (with additional short Li⋅⋅⋅H contacts, whereas the heavier congeners form dimeric structures. This results in κ‐N,N coordination within one [(NPNPN)M] (M=Na, Cs) unit, and the dimeric structure is then completed by additional η5‐coordination of the pyrrolyl ligand to the neighbouring alkali metal. Furthermore, heteroleptic magnesium alkyl complexes, 1‐MgR, are isolated from the reaction of [MgR2] (R= CH2SiMe3, CH2CMe3, CH2CMe2Ph) with (PNP*)H (1 equiv).

Rare-Earth Metal Boroxide with Formal Triple Metal–Oxygen Orbital Interaction: Synthesis from B(C 6 F 5 ) 3 ·H 2 O and Radical-Anion Ligated Rare-Earth Metal Amides

Rare-earth metal boroxides are not only rare and of great synthetic challenge but also important theoretically due to their unrevealed bonding characteristics. In this paper, we report the synthesi...

Isolable Diaminophosphide Boranes.

Metalation of secondary diaminophosphine boranes by alkali metal amides provides a robust and selective access route to a range of metal diaminophosphide boranes M[(R2N)2P(BH3)] (M=Li, Na, K; R=alkyl, aryl) with acyclic or heterocyclic molecular backbones, whereas reduction of a chlorodiaminophosphine borane gave less satisfactory results. The metalated species were characterized in situ by NMR spectroscopy and in two cases isolated as crystalline solids. Single‐crystal XRD studies revealed the presence of salt‐like structures with strongly interacting ions. Synthetic applications of K[(R2N)2P(BH3)] were studied in reactions with a 1,2‐dichlorodisilane and CS2, which afforded either mono‐ or difunctional phosphine boranes with a rare combination of electronegative amino and electropositive functional disilanyl groups on phosphorus, or a phosphinodithioformate. Spectroscopic studies gave a first hint that removal of the borane fragment may be feasible.

Ambient Moisture Accelerates Hydroamination Reactions of Vinylarenes with Alkali-Metal Amides under Air.

A straightforward alkali-metal-mediated hydroamination of styrenes using biorenewable 2-methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions.