Trialkylammonium salt degradation: implications for methylation and cross-coupling.

Trialkylammonium (most notably N,N,N-trimethylanilinium) salts are known to display dual reactivity through both the aryl group and the N-methyl groups. These salts have thus been widely applied in cross-coupling, aryl etherification, fluorine radiolabelling, phase-transfer catalysis, supramolecular recognition, polymer design, and (more recently) methylation. However, their application as electrophilic methylating reagents remains somewhat underexplored, and an understanding of their arylation versus methylation reactivities is lacking. This study presents a mechanistic degradation analysis of N,N,N-trimethylanilinium salts and highlights the implications for synthetic applications of this important class of salts. Kinetic degradation studies, in both solid and solution phases, have delivered insights into the physical and chemical parameters affecting anilinium salt stability. 1H NMR kinetic analysis of salt degradation has evidenced thermal degradation to methyl iodide and the parent aniline, consistent with a closed-shell SN2-centred degradative pathway, and methyl iodide being the key reactive species in applied methylation procedures. Furthermore, the effect of halide and non-nucleophilic counterions on salt degradation has been investigated, along with deuterium isotope and solvent effects. New mechanistic insights have enabled the investigation of the use of trimethylanilinium salts in O-methylation and in improved cross-coupling strategies. Finally, detailed computational studies have helped highlight limitations in the current state-of-the-art of solvation modelling of reaction in which the bulk medium undergoes experimentally observable changes over the reaction timecourse.

Molecular Manipulations of a Utility Nitrogen-Heterocyclic Carbene by Sodium Magnesiate Complexes and Transmetallation Chemistry with Gold Complexes.

Expanding the scope and applications of anionic N-heterocyclic carbenes (NHCs), a novel series of magnesium NHC complexes is reported using a mixed sodium-magnesium approach. Sequential reactivity of classical imidazol- 2-ylidene carbene IPr with NaR and MgR2 (R=CH2 SiMe3 ) affords [(THF)3 Na(µ-IPr- )MgR2 (THF)] (2) [IPr- =:C{[N(2,6-iPr2 C6 H3 )]2 CHC] containing an anionic NHC ligand, whereas surprisingly sodium magnesiate [NaMgR3 ] fails to deprotonate IPr affording instead the redistribution coordination adduct [IPr2 Na2 MgR4 ] (1). Compound 2 undergoes selective C2-methylation when treated with MeOTf furnishing novel abnormal NHC complex [{aIPrMe MgR2 }2 ] (3). Dissolving 3 in THF led to the dissociation of this complex into MgR2 and aIPrMe with the latter isomerizing to the olefinic NHC IPr=CH2 . The ability of 2 and 3 to transfer their anionic and abnormal NHC ligands, respectively to AuI metal fragments has been investigated allowing the isolation and structural characterization of [RAu(µ-IPr- )MgR(THF)2 ] (4) and [aIPrMe AuR] (5) respectively. In both cases transfer of an alkyl R group is observed. However while 3 can also transfer its abnormal NHC ligand to give 5, in 4 the anionic NHC still remains coordinated to Mg via its C4 position, whereas the {AuR} fragment occupies the C2 position previously filled by a donor-solvated {Na(THF)3 }+ cation.

Assessing the reactivity of sodium alkyl-magnesiates towards quinoxaline: single electron transfer (SET) vs. nucleophilic alkylation processes.

By exploring the reactivity of sodium butyl-magnesiate (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}(2-) (Ar* = 2,6-iPr2-C6H3) towards Quinoxaline (Qx), the ability of this bimetallic system to effectively promote SET processes has been disclosed. Thus 1 executes the single-electron reduction of Qx affording complex (2) whose structure in the solid state contains two quinaxolyl radical anions Qx˙ stabilised within a dimeric magnesiate framework. Combining multinuclear NMR and EPR measurements with DFT calculations, new insights into the constitution of 2 in solution and its magnetic behaviour have been gained. Further evidence on the SET reactivity of 1 was found when it was reacted with nitroxyl radical TEMPO which furnished contacted ion pair sodium magnesiate [(Ph2Si(NAr*)2)Mg(TEMPO(-))Na(THF)3] (4) where both metals are connected by an alkoxide bridge, resulting from reduction of TEMPO. The role that the different ligands present in 1 can play in these new SET reactions has also been assessed. Using an amination approach, the Bu group in 1 can be replaced by the more basic amide TMP allowing the isolation of (3) which was characterised by multinuclear NMR and X-ray crystallography. (1)H NMR monitoring of the reaction of 3 with Qx showed its conversion to 2, leaving the hydrogen atoms of the heterocycle untouched. Contrastingly, using sodium homoalkyl magnesiate [NaMg(CH2SiMe3)3] (5) led to the chemoselective C2 alkylation of this heterocycle, suggesting that the presence of the steric stabiliser {Ph2Si(NAr*)2}(2-) on the mixed-metal reagent is required in order to facilitate the Qx reduction.

Potassium-alkyl magnesiates: synthesis, structures and Mg-H exchange applications of aromatic and heterocyclic substrates.

Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg-H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes.

New lithium-zincate approaches for the selective functionalisation of pyrazine: direct dideprotozincation vs. nucleophilic alkylation.

Comparing the reactivity of the related lithium zincates [(THF)LiZn(TMP)(t)Bu(2)] (1) and [(PMDETA)LiZn(t)Bu(3)] (2) towards pyrazine discloses two new bimetallic approaches for the selective 2,5-dideprotonation and room temperature C-H alkylation of this sensitive heterocycle.

A new polymeric alkyl/alkoxide magnesium-sodium inverse crown complex.

Poly[bis(µ(3)-trimethylsilylmethanolato)tetrakis(µ(2)-trimethylsilylmethyl)dimagnesiumdisodium], [Na(2)Mg(2)(C(4)H(11)OSi)(2)(C(4)H(11)Si)(4)](n), was obtained from the controlled exposure to oxygen of the unsolvated sodium magnesate [NaMg(CH(2)SiMe)(3)](n). Exhibiting a centrosymmetric (Z' = 1/2) dimeric core of a heterobimetallic eight-membered cationic ring, hosting two alkoxide ligands at its core, the title compound forms a two-dimensional coordination polymer in the crystallographic bc plane through Na···Me contacts. These contacts from Na to formally uncharged groups are only 0.06 longer than those between Na and the formally charged CH(2)R anions. The coordination polymers stack along the a direction to give a layer structure with alternating hydrophobic and hydrophilic regions.

Synthesis and characterization of an infinite sheet of metal-alkyl bonds: unfolding the elusive structure of an unsolvated alkali-metal trisalkylmagnesiate.

The study of co-complexation reactions between NaCH(2)SiMe(3) and Mg(CH(2)SiMe(3))(2) has allowed the isolation and structural elucidation of the first solvent-free alkali-metal alkylmagnesiate [{NaMg(CH(2)SiMe(3))(3)}(∞)] (1) as well as the related solvent-free sodium alkyl [{(NaCH(2)SiMe(3))(4)}(∞)] (3).