Diastereotopic Protons Research Articles

Primary α-Phosphino- and α-Arseno-Nitriles, Analogues of α-Aminonitriles.

More than 170 years after the synthesis of α-aminonitriles by the reaction of Strecker, α-phosphinonitriles, and α-arsenonitriles have been prepared and characterized by NMR and IR spectroscopy. For the simplest derivatives, the reaction was carried out by reaction of cyanomethyltributylstannane with phosphorus or arsenic trichloride, followed by a chemoselective reduction of the dichlorophosphine and dichloroarsine formed to the corresponding primary phosphine and arsine. The phosphinoacetonitrile can be stored at -80 °C for months in its pure state, but arsenoacetonitrile decomposes at this temperature. Chiral compounds can be synthesized from C-substituted cyano-1-alkyltributylstannanes. In 1H NMR spectroscopy, these chiral phosphines and arsines display diastereotopic protons for the PH2 and AsH2 groups, a property never observed for the NH2 group of α-aminonitriles. This work paves the way for further studies on the chemistry of these compounds, including a comparative chemistry of these phosphorus and arsenic derivatives with the well-known α-aminonitriles.

Butyl (2,2-Dibutoxybutanoyl)-ʟ-Tryptophanate

The multicomponent reaction between ʟ-tryptophan 1, 2-oxobutanoic acid 2, and 1-butanol in the presence of SiMe3Cl was studied using microwave irradiation conditions. The main product was identified as an unreported acetal-containing compound, namely, butyl (2,2-dibutoxybutanoyl)-ʟ-tryptophanate (3), yielding 89%. NMR experiments demonstrated that the adjacent methylene protons of the acetal group appeared as two signals exhibiting their behavior as diastereotopic protons. DFT/B3LYP calculations revealed an asymmetric molecular structure with specific angles, leading to an explanation of the NMR results. The calculated chemical shifts showed slight differences with the experimental values and suggested magnetic anisotropy and inductive deprotection around the methylene hydrogen atoms in the acetal location. The reaction mechanism was proposed in which SiMe3Cl plays a crucial role by promoting water removal through key steps.

Assignment of NMR spectral data of diastereomeric tetrahydrofuranyl acetals directly from their mixture by spectral simulation

In this study, an NMR spectral analysis of the mixture of diastereomeric acetals, synthesized from 2,3-dihydrofurane and a racemic mixture of citronellol, was performed. 1H-NMR full spin analysis was achieved by manually adjusting ?H and J values (previously calculated using the Spartan software) to fit the experimentally available values, followed by further optimization using MestreNova software. The simulated 1H- and 13C-NMR spectra of individual diastereomers, as well as their superimposed and summed spectra, were compared with the obtained experimental spectra. Spin simulation of proton signals was particularly useful for the assignment of the diastereotopic protons of tetrahydrofuranyl moiety and diastereomer discrimination. The NMR spectral data of individual diastereomers ? chemical shifts, coupling constants, HMBC and NOESY interactions were systematized in appropriate tables and schemes. To the best of our knowledge, this is for the first time that the complete assignment of tetrahydrofuranyl moiety was performed, and the data obtained herein may be of great importance for the utilization of this protecting group in the future.

High-resolution NMR spectroscopy for measuring complex samples based on chemical-shift-difference selection.

NMR spectroscopy serves as an immensely powerful tool for component assignments and molecular structure elucidations. However, proton NMR spectra are generally trapped with spectral congestion caused by limited frequency differences and complex multiplets. 2D NMR can effectively relieve spectral congestion, but its resolution and acquisition efficiency are restricted by the broad spectral bandwidth. Herein, we introduce an NMR method based on chemical-shift-difference selection by chirp excitation to record high-resolution 2D NMR spectra for extracting coupling correlation networks and multiplet structures, suitable for measurements on complex samples. The performance of the proposed method is illustrated in determining diastereotopic methylene protons, small frequency-difference coupled proton pairs of furanose, pyranose and benzene rings. This study is expected to benefit molecular structure elucidation and composition analysis of complex samples in chemistry, biochemistry and metabonomics.

N-heterocyclic carbenes with three and six fluorous ponytails and their highly fluorophilic Rh and Ir complexes

Reactions of 1-methylimidazole and 1-(1-methylethyl)imidazole with (3-iodopropyl)tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane gave the corresponding 1-alkyl-3-(3-(tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) silyl) propyl) imidazolium iodides 1 and 2. Reaction of imidazole in excess with (3-iodopropyl)tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane afforded 1-(3-(tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) silyl) propyl) imidazole 3 which was further reacted with (3-iodopropyl)tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane to produce the doubly tagged 1,3-bis[3-(tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) silyl) propyl] imidazolium iodide 4 and by anion exchange a tetrafluoroborate salt 5. The prepared imidazolium iodides 1,2, and 4 were then used as precursors in synthesis of chlorido(cycloocta-1,5-diene)rhodium or -iridium complexes bearing Nheterocyclic carbenes with one 3-[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]propyl-substituent and methyl-, 1-methylethyl-and another 3-[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]propyl-substituent on nitrogens, 6 – 11. The metal complexes were equimolar mixtures of conformational enantiomers as was best documented by the 1H NMR signals of diastereotopic CH2 protons next to nitrogen. Fluorophilicity fi as the natural logarithm of partition coefficient Pi between fluorous and organic phase of the complexes was determined in the standard solvent system (perfluoro)methylcyclohexane/toluene. All the complexes are fluorophilic with variation of fi between 0.96 and 4.06, the complexes with high values may be classified as highly fluorophilic (heavy fluorous).

Ruthenium-Locked Helical Chirality: A Barrier of Inversion and Formation of an Asymmetric Macrocycle.

Upon coordination to metal centers, tetradentate ligands based on the 6,6′-bis(2″-aminopyridyl)-2,2′-bipyridine (bapbpy) structure form helical chiral complexes due to the steric clash between the terminal pyridines of the ligand. For octahedral ruthenium(II) complexes, the two additional axial ligands bound to the metal center, when different, generate diastereotopic aromatic protons that can be distinguished by NMR. Based on these geometrical features, the inversion barrier of helical [RuII(L)(RR′SO)Cl]+ complexes, where L is a sterically hindered bapbpy derivative and RR′SO is a chiral or achiral sulfoxide ligand, was studied by variable-temperature 1H NMR. The coalescence energies for the inversion of the helical chirality of [Ru(bapbpy)(DMSO)(Cl)]Cl and [Ru(bapbpy)(MTSO)(Cl)]Cl (where MTSO is (R)-methyl p-tolylsulfoxide) were found to be 43 and 44 kJ/mol, respectively. By contrast, in [Ru(biqbpy)(DMSO)(Cl)]Cl (biqbpy = 6,6′-bis(aminoquinolyl)-2,2′-bipyridine), increased strain caused by the larger terminal quinoline groups resulted in a coalescence temperature higher than 376 K, which pointed to an absence of helical chirality inversion at room temperature. Further increasing the steric strain by introducing methoxy groups ortho to the nitrogen atoms of the terminal pyridyl groups in bapbpy resulted in the serendipitous discovery of a ring-closing reaction that took place upon trying to make [Ru(OMe-bapbpy)(DMSO)Cl]+ (OMe-bapbpy = 6,6′-bis(6-methoxy-aminopyridyl)-2,2′-bipyridine). This reaction generated, in excellent yields, a chiral complex [Ru(L″)(DMSO)Cl]Cl, where L″ is an asymmetric tetrapyridyl macrocycle. This unexpected transformation appears to be specific to ruthenium(II) as macrocyclization did not occur upon coordination of the same ligand to palladium(II) or rhodium(III).

Acetylene Derivatives of Cationic Diazaoxatriangulenes and Diaza [4]Helicenes ‐ Access to Red Emitters and Planar Chiral Stereochemical Traits

Cationic triangulenes, and related helicenes, constitute a rich class of dyes and fluorophores, usually absorbing and emitting light at low energy, in the orange to red domains. Recently, to broaden the scope of applications, regioselective late‐stage functionalizations on these core moieties have been developed. For instance, with the introduction of electron‐donating groups (EDGs), important bathochromic shifts are observed pushing absorptions towards or in the near‐infrared (NIR) spectral domain while emissive properties disappear essentially completely. Herein, to upset this drawback, acetylene derivatives of cationic diazaoxa triangulenes (DAOTA) and [4]helicenes are prepared (16 examples). Contrary to other EDG‐functionalized derivatives, C≡C− functionalized products remain broadly fluorescent, with red‐shifted absorptions (Δλ abs up to 25 nm) and emissions (Δλ em up to 73 nm, Φ PL up to 51 %). Quite interestingly, a general dynamic stereoisomerism phenomenon is evidenced for the compounds derived from achiral DAOTA cores. At low temperature in 1H NMR spectroscopy (218 K), N−CH2 protons become diastereotopic with chemical shifts differences (Δδ) as high as +1.64 ppm. The signal coalescence occurs around 273 K with a barrier of ∼12 kcal mol−1. This phenomenon is due to planar chiral conformations (S p and R p configurations), induced by the geometry of the alkyl (n‐propyl) side‐chains next to the acetylenic substituents. Ion pairing studies with Δ‐TRISPHAT anion not only confirm the occurrence of the chiral conformations but evidence a moderate but definite asymmetric induction from the chiral anion onto the cations. Finally, DFT calculations offer a valuable insight on the geometries, the corresponding stereodynamics and also on the very large difference in NMR for some of the diastereotopic protons.

Front Cover: Interconversion of tetrahedral [(M)4∩{Mg4(L1)6}]/[In4(L2)4] and cyclic [In6Cl6(L3)6]. Enantiotopization of diastereotopic protons monitored by means of VT 1H NMR spectroscopy (Eur. J. Inorg. Chem. 4/2022)

The Front Cover shows the enantiotopization of diastereotopic groups via enantiomerization using isopropyl-COT as an example. This fundamental phenomenon is the common thread running through the manuscript. Impressively, this is also shown by the dynamic temperature dependent (VT) 1H NMR spectrum for the diastereotopic methylene protons (green) of meso-[In4(L)4)] 1. Because of the helitopic ligands (L)3−, all signals are triplicated. Due to mesomerization (Bailar twist/helitopization) of the identical twins (2Δ,2Λ)(2P,2 M)-1 ⇌ (2Λ,2Δ)(2 M,2P)-1′ all signals coalesce. More information can be found in the Minireview by R. W. Saalfrank and co-workers.

Bulky Selenium Ligand Stabilized Trans-Palladium Dichloride Complexes as Catalyst for Silver-Free Decarboxylative Coupling of Coumarin-3-Carboxylic Acids.

This report describes the syntheses of three new trans-palladium dichloride complexes of bulky selenium ligands. These complexes possess a Cl-Pd-Cl rotor spoke attached to a Se-Pd-Se axle. The new ligands and palladium complexes (C1-C3) were characterized with the help of NMR, HRMS, UV-Vis., IR, and elemental analysis. The single-crystal structure of metal complex C2 confirmed a square planar geometry of complex with trans-orientation. The X-ray structure revealed intramolecular secondary interactions (SeCH-Cl) between chlorine of PdCl2 and CH2 proton of selenium ligand. Variable-temperature NMR data shows coalescence of diastereotopic protons, which indicates pyramidal inversion of selenium atom at elevated temperature. The relaxed potential energy scan of C2 suggests a rotational barrier of ∼12.5 kcal/mol for rotation of chlorine atom through Cl-Pd-Cl rotor. The complex C3 possesses dual intramolecular secondary interactions (OCH2 -Cl and SeCH2 -Cl) with stator ligand. Molecular rotor C2 was found to be a most efficient catalyst for the decarboxylative Heck-coupling under mild reaction conditions. The protocol is applicable to a broad range of substrates with large functional group tolerance and low catalyst loading (2.5 mol %). The mechanism of decarboxylative Heck-coupling reaction was investigated through experimental and computational studies. Importantly the reaction works under silver-free conditions which reduces the cost of overall protocol. Further, the catalyst also worked for decarboxylative arylation and decarboxylative Suzuki-Miyaura coupling reactions with good yields of the coupled products.

Interconversion of tetrahedral [(M)4∩{Mg4(L1)6}]/[In4(L2)4] and cyclic [In6Cl6(L3)6]. Enantiotopization of diastereotopic protons monitored by means of VT 1H NMR spectroscopy

AbstractIn this review we report on the enantiomerization of tetrahedral racemic‐[(NH4)4∩{Mg4(L1)6}] monitored by means of variable temperature (VT) 1H NMR spectroscopy. The enantiotopization of the diastereotopic protons is due to simultaneous Bailar twists at the four octahedrally coordinated magnesium centres, synchronized with atropisomerization of the six edge‐bridging ligands (L1)2‐.The VT 1H NMR spectrum of tetrahedral meso‐[In4(L2)4] is coined through the helicity of the four face‐centred tripodal hexadentate ligands (L2)3‐ and can, alike the 1H NMR of cyclic meso‐[In6Cl6(L3)6], be explained by the enantiotopization of the diastereotopic protons via mesomerization.

Sustainable Synthesis, NMR and Computational Study of Isobutylmesitylphosphine

AbstractThe alkyl‐aryl‐substituted secondary phosphines i‐Bu(Mes)PH and Cy(Mes)PH are obtained from the reaction of the electrochemically generated organonickel sigma‐complex [NiBr(Mes)(bpy)] (Mes=2,4,6‐trimethylphenyl; bpy=2,2′‐bipyridine) with primary phosphines i‐BuPH2 and CyPH2, respectively. Detailed multinuclear NMR spectroscopy and quantum‐chemical calculations were used to assign the diastereotopic protons of i‐Bu(Mes)PH.

Computational 1 H and 13 C NMR of the trimeric monoterpenoid indole alkaloid strychnohexamine: Selected spectral updates.

Very large trimeric indole alkaloid strychnohexamine, with empirical formula C59 H60 N6 O (66 second-row atoms and 60 protons), has been subjected to the state-of-the-art computation of the 1 H and 13 C nuclear magnetic resonance (NMR) chemical shifts of its configurational isomers at each of the 14 asymmetric centers. Several spectral reassignments and corrections of 1 H and 13 C NMR spectra of this alkaloid were suggested based on the PBE0/pcSseg-2//pcseg-2 calculation of its NMR chemical shifts. Thus, all pairs of diastereotopic protons were assigned together with four aromatic carbon resonances of C-9 and C-11, C-9″, and C-11″. In addition, the unassigned chemical shifts of carbon C-23″ and proton at C-3' in, accordingly, 13 C and 1 H NMR spectra were predicted.

1H NMR and conformational analysis of diastereotopic methylene protons in achiral flexible molecules

Unlike diastereotopic -CH2- protons from chiral compounds, the diastereotopic protons from achiral compounds may not be easily predictable. For molecules with flexible chain this task is even more problematic. Additionally, the assignment from the experimental 1H NMR spectrum of chemical shifts and coupling constants is very frequently uncertain. Nevertheless, computationally, for both chiral and achiral molecules the -CH2- protons diastereotopic nature is evident as well as NMR parameters assignments. In the present paper we examine the NMR parameters calculated as a sum of Boltzmann weighted average of the lowest conformations that fits a window less than 10 kJ/mole. A Spartan20 six steps protocol was chosen to select the lower energy conformations. The NMR conformationally averaged parameters obtained for 2-ethyl-2-hyroxybutanoic acid (EHB) and citric acid (CA), both achiral molecules, and the chiral malic acid (MA) fit acceptable well with the experimental data, although the calculation is done for gas phase (conformations dominated by intermolecular hydrogen bonding) and the experiment was carried out in D2O (conformations controlled by intermolecular hydrogen bonding of highly decorated molecules with OH and COOH that can interact with the solvent). In addition, in the present paper we have examined EHB, CA and MA the lowest energy conformer geometry, Atom in Molecules (AIM) and Natural Bond Orbital protocols to identify the intramolecular hydrogen bonds.

An ingenious method for the determination of the relative and absolute configurations of compounds containing aryl-glycerol fragments by 1H NMR spectroscopy.

A concise method was established to determine the relative and absolute configurations of aryl-glycerols that depend on the chemical shift differences (Δδ) of the diastereotopic methylene protons (H-3) by 1H NMR spectroscopy. When using DMSO-d6 as the preferred solvent, the threo configuration corresponded to a larger ΔδH3a–H3b value (>0.15 ppm), whereas the erythro configuration (<0.07 ppm) corresponded to a smaller value. Furthermore, the absolute configurations were determined with the aid of a simple acylation reaction through camphanoyl chloride. In the threo enantiomers, the Δδ value of the 1R,2R configuration was <0.15 ppm, and that of the 1S,2S configuration was >0.20 ppm. In the erythro enantiomers, the Δδ value of 1R,2S was >0.09 ppm, and that of 1S,2R was <0.05 ppm. Remarkably, this empirical rule is invalid in CDCl3. In addition, this method was also verified by a quantum 1H NMR calculation.

Assignment of 1H and 13C NMR spectral data of diastereomeric acetals directly from their mixture by spectral simulation

Herein, an NMR spectral analysis was performed of a mixture of diastereomeric acetals synthesized from 2-fluorobenzaldehyde and a racemic mixture of 4-methylpentan-2-ol. The simulated 1H- and 13C-NMR spectra of individual diastereomers, as well as their superimposed and summed spectra, were compared with the obtained experimental spectra. Spin simulation of proton signals was particularly useful for the assignment of the aromatic part of the molecules and of the diastereotopic protons of the methylene groups. The isomer NMR spectral data - chemical shifts, coupling constants, HMBC and NOESY interactions were systematized in appropriate tables and schemes.

Pure shift HMQC: Resolution and sensitivity enhancement by bilinear rotation decoupling in the indirect and direct dimensions

The heteronuclear multiple-quantum coherence in the indirect dimension of the two-dimensional HMQC experiment evolves under the passive 1H-1H J-couplings leading to multiplet structures in the F1 dimension. Besides, 1H-1H J-multiplets appear in the direct dimension as well. Thus, multiplets along both dimensions lower the resolution and sensitivity of this technique, when high resolution is required along both dimensions. An efficient broadband homodecoupling scheme along the F1 dimension of the HMQC experiment has not been realized to date. We have implemented broadband homonuclear decoupling using bilinear rotation decoupling (BIRD) by adding a 1H SQ evolution period followed by BIRD before the 1H-13C multiple-quantum evolution period in the HMQC. In the direct time domain, BIRD is implemented using a real-time or single-scan scheme, which further improves resolution and sensitivity of this technique. The resulting pure shift HMQC provides singlet peak per chemical site along F1 as well as F2 axes and, hence, better resolution and sensitivity than conventional HMQC spectrum for all peaks except diastereotopic methylene protons. Due to the incorporation of the BIRD, the indirect time domain becomes double in length compared to the conventional HMQC. However, slow relaxation of small molecules favors better sensitivity for ps-HMQC relative to conventional HMQC under all conditions. We also found that the sensitivity of ps-HMQC is only slightly less than ps-HSQC for small molecules.

Reactions of α-haloacroleins with azides: highly regioselective synthesis of formyl triazoles

A metal-free route to 1,4-disubstituted and 1,4,5-trisubstituted formyl triazoles was developed. One 1,2,3-triazole containing diastereotopic protons was identified.

Cobalt(II), copper(II), and zinc(II) isostructural, pseudotetrahedral, racemic complexes of pyrrolo[2,3-b]quinoxaline with bis(2-thienylmethyl)propylenediamine chain: Synthesis, crystal structure, spectroscopy

Cobalt(II), copper(II), and zinc(II) cations all have similar effective ionic radii so they form with (E)-1-phenyl-3-{N-[N′,N′-bis(thiophen-2-ylmethyl)-3-aminopropyl]aminophenylmethylidene}-1,3-dihydro-2H-pyrrolo[2,3-b]quinoxalin-2-one (1) isostructural, pseudotetrahedral complexes 2a, 2b, and 2c, respectively. Single crystal X-ray analysis of the synthesized complexes reveals that they are chiral (Λ-M-pS, pS; Δ-M-pR, pR) and crystalize as racemates in P 21/c space group. There is axial chirality connected with tetrahedrally substituted metal center and crystallization induced planar chirality of two symmetry independent ligand molecules (different conformers). In solution only metal center chirality is maintained due to the conformational lability of the 3-[N,N-bis(thien-2-ylmethyl)amino]propyl group. Chirality of zinc complex 2c in solution was confirmed by the analysis of 1D and 2D NMR spectra. NMR data show diastereotopic protons of aliphatic chain and the restriction of phenyl ring rotation at C(30) carbon atom. Complex 2c is fluorescent in solid state as well as in solution (fluorescence quantum yield in acetonitrile, ϕ = 0.1). The NMR titration at room temperature shows that the major product of zinc coordination is not 2c but the complex with a tautomeric form of the ligand having proton located at N(4) nitrogen atom (enamine-imine tautomerism). UV–Vis data for 2a, 2b, and 2c both in solid and in solution are discussed.

Novel iron(II)-N-heterocyclic carbene catalysts for efficient transfer hydrogenations under mild condition

Four novel N-heterocyclic carbene (NHC) based Fe(II) complexes, [Fe(L1)Cp(CO)]I (1), [L1 = 3-methyl-1-(pyridin-2-ylmethyl)-benzimidazol-2-ylidene], [Fe(L2)Cp(CO)]Br (2) [L2 = 3-benzyl-1-(pyridin-2-ylmethyl)-benzimidazol-2-ylidene], [Fe(L3)Cp-(CO)]Br (3), [L3 = 3-(4-tert-butyl-benzyl)-1-(pyridin-2-ylmethyl)-benzimidazol-2-ylidene] and [Fe(L4)Cp(CO)]I (4), L4 = 1,3-di-(2- methylenepyridyl methyl)-benzimidazol-2-ylidene] have been synthesized and characterized as efficient catalysts for transfer hydrogenation of carbonyl compounds. The disappearance of 1H NMR signals at 10.09–11.78 ppm of NHC ligand confirms the complex formation via carbene coordination to low spin Fe(II) center and it is further supported by the two distinct doublets for two diastereotopic protons of the methylene group connects pyridine and benzimidazole rings. The IR spectra show νstr, 1939–1958 cm−1 for the coordinated CO, which are virtually independent of the wingtip substituents and possibly this limits the influence of those groups on the electronic properties of iron(II) center. The molecular structure of the complexes 1, 2 and 4 reveals the coordination of NHC ligand, cyclopentadiene (Cp) and CO to low spin FeII center (S = 0). The bonds Fe-Ccarbene (1.907–1.934 Å), Fe-NPy (1.995–2.019 Å), Fe−CO (1.743–1.762 Å) and Fe-Cp (2.058–2.097 Å) are almost identical in all the complexes. The bite angles CO-Fe-Ccarbene (90.9°– 113.8°) are higher than Cp-Fe-Ccarbene (92.6°–93.2°) but the bite angle CO-Fe-Npy are merely indentical in all complexes (89.7°). All the complexes showed two redox couples at 1.050 - 1.080 V and 0.560 – 0.585 V corresponds to FeII/FeIII and ligand-based redox couples respectively. The complexes exhibited the excellent transfer hydrogenation for aldehydes up to yield of 99% with the turnover frequency (TOF) of 13,680 h−1 at room temperature. The ketone substrates showed conversion of alcohols with the yield and TOF of 98% and 2264 h−1 respectively at 60 °C.

Synthesis, characterization, and catalytic application in aldehyde hydrosilylation of half-sandwich nickel complexes bearing (κ1-C)- and hemilabile (κ2-C,S)-thioether-functionalised NHC ligands.

Neutral nickel-N-heterocyclic carbene complexes, (κ1-C)-[NiCpBr{R-NHC-(CH2)2SR'}] [Cp = η5-C5H5; R-NHC-(CH2)2SR' = 1-mesityl-3-[2-(tert-butylthio)ethyl]- (1a), 1-mesityl-3-[2-(phenylthio)ethyl]- (1b), 1-benzyl-3-[2-(tert-butylthio)ethyl]- (1c), 1-benzyl-3-[2-(phenylthio)ethyl]-imidazol-2-ylidene (1d)], which bear a N-bound thioether side arm, were prepared by the reaction of nickelocene with the corresponding imidazolium bromides [R-NHC-(CH2)2SR'·HBr] (a-d), via conventional or microwave heating. The 1H NMR spectra of the benzyl-substituted species 1c and 1d showed signals for diastereotopic NCH2CH2S protons at room temperature. However, structural studies established the absence of coordination of the sulphur atom in the solid state, and solvent DFT calculations showed that bromide displacement by sulphur is an unfavourable process (ΔG = +13.5 kcal mol-1 for 1d), thereby suggesting that the observed disatereotopicity is more likely due to significant steric congestion rather than to a possible C,S-chelation in solution. Treatment of these complexes with KPF6 in tetrahydrofuran (THF) led to bromide abstraction to afford the cationic complexes [NiCp{R-NHC-(CH2)2SR'}](PF6) (2a-c). Alternatively, 2a-c could also be prepared by the direct reaction of nickelocene with the corresponding imidazolium hexafluorophosphate salts [R-NHC-(CH2)2SR'·HPF6]. Inversely to the neutral species, whereas X-ray crystallography established C,S-chelation in the solid state, the 1H NMR spectra (CDCl3, CD2Cl2, or thf-d8) at room temperature showed no diastereotopic NCH2CH2S protons, thus suggesting the possible displacement of the sulphur atom by the respective solvents and/or very fast sulphur inversion. DFT calculations established a low energy inversion process in all cases (+9 ≤ΔG‡≤ +13 kcal mol-1) as well as a favourable solvent coordination process (ΔG‡≈ +11 kcal mol-1; ΔG≈-7 kcal mol-1) with a solvent such as THF, thus suggesting that sulphur inversion and/or solvent coordination can both account for the absence of diastereotopy at room temperature, depending on the solvent. While all complexes catalysed the hydrosilylation of benzaldehyde in the absence of any additive, the cationic C,S-chelated complexes 2 proved more active than the sterically constrained neutral species 1. In particular, 2c proved to be the most active pre-catalyst and its catalytic charge could be lowered down to 2 mol% with PhSiH3 as the hydrogen source.