Bispidine Platform as a Tool for Studying Amide Configuration Stability

In this work, the solution conformations of seventeen 3,7-diacyl bispidines were studied by means of NMR spectroscopy including VT NMR experiments. The acyl groups included alkyl, alkenyl, aryl, hetaryl, and ferrocene moieties. The presence of syn/anti-isomers and their ratios were estimated, and some reasons explaining experimental facts were formulated. In particular, all aliphatic and heterocyclic units in the acylic R(CO) fragments led to an increased content of the syn-form in DMSO-d6 solutions. In contrast, only the anti-form was detected in DMSO-d6 and CDCl3 in the case when R = Ph, ferrocenyl, (R)-myrtenyl. In the case of a chiral compound derived from the natural terpene myrtene, a new dynamic process was found in addition to the expected inversion around the amide N-C(O) bond. Here, rotation around the CO-C=C bond in the acylic R fragment was detected, and its energy was estimated. For this compound, ΔG for amide N-C(O) inversion was found to be equal to 15.0 ± 0.2 kcal/mol, and for the rotation around the N(CO)–C2′ bond, it was equal to 15.6 ± 0.3 kcal/mol. NMR analysis of the chiral bispidine-based bis-amide was conducted for the first time. Two X-ray structures are reported. For the first time, the unique syn-form was found in the crystal of an acyclic bispidine-based bis-amide. Quantum chemical calculations revealed the unexpected mechanism for amide bond inversion. It was found that the reaction does not proceed as direct N-C(O) bond inversion in the double-chair (CC) conformation but rather requires the conformational transformation into the chair–boat (CB) form first. The amide bond inversion in the latter requires less energy than in the CC form.

Positional Effect of π-extension in Triple Helicenes

The targeted application of multiple helicenes in photo-optical applications requires their rational design. Toward this goal, we report on the synthesis of pyrene-based triple helicene 1 and investigate the positional effect of extension of the π-conjugated system on the photo-chemical and chiro-optical properties of triple helicenes. The conformational and aggregatory behavior of 1 were studied both experimentally using VT NMR spectroscopy and computationally using high-level DFT computations. Although π-extension was observed to have a marked effect on the spectroscopic properties of triple helicenes, comparison with other known π-extended helicenes reveals that the position at which π-extension is introduced is only of nominal importance. Our results thus suggest that the presence of a particular helicene motif is dominant in dictating the physico-chemical properties of triple helicenes.

Positional Effect of π-extension in Triple Helicenes

Application of multiple helicenes in photo‐optical applications requires their rational design. We therefore here report on the synthesis of pyrene‐based triple helicene 1, to study the positional effect of extension of the π‐conjugated system on the photo‐chemical and chiro‐optical properties of triple helicenes. The conformational and aggregatory behavior of 1 were studied both experimentally using VT NMR spectroscopy and computationally using high‐level DFT computations. Although π‐extension was observed to have a marked effect on the spectroscopy properties of triple helicenes, comparison with other known π‐extended helicenes reveals that the position at which π‐extension is introduced is only of nominal importance. Our results thus suggest that the presence of a particular helicene motive is dominant in dictating the physico‐chemical properties of triple helicenes.

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.

Asymmetric Bis-PNP Pincer Complexes of Zirconium and Hafnium - a Measure of Hemilability

Asymmetrically-bound pyrrollide-based bis-PNP pincer complexes of zirconium and hafnium<br>have been formed. The [κ2-PNPPh][κ3-PNPPh]MCl2 species are in direct contrast to previous<br>zirconium PNP pincer complexes. The pincer ligands are fluxional in their binding and the<br>energy barrier for exchange has been approximated using VT-NMR spectroscopy and the<br>result validated by DFT calculations.

Asymmetric Bis-PNP Pincer Complexes of Zirconium and Hafnium - a Measure of Hemilability

Asymmetrically-bound pyrrollide-based bis-PNP pincer complexes of zirconium and hafnium<br>have been formed. The [κ2-PNPPh][κ3-PNPPh]MCl2 species are in direct contrast to previous<br>zirconium PNP pincer complexes. The pincer ligands are fluxional in their binding and the<br>energy barrier for exchange has been approximated using VT-NMR spectroscopy and the<br>result validated by DFT calculations.

Softening the Donor-Set: From [Cu(P^P)(N^N)][PF6] to [Cu(P^P)(N^S)][PF6]

We report the synthesis and characterization of [Cu(P^P)(N^S)][PF6] complexes with P^P = bis(2-(diphenylphosphino)phenyl) ether (POP) or 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (xantphos) and N^S = 2-(iso-propylthio)pyridine (iPrSpy) or 2-(tert-butylthio)pyridine (tBuSpy). The single crystal structures of [Cu(POP)(iPrSPy)][PF6] and [Cu(POP)(tBuSPy)][PF6] have been determined and confirm a distorted tetrahedral copper(I) centre and chelating P^P and N^S ligands in each complex. Variable temperature (VT) 1H and 31P{1H} NMR spectroscopy reveals dynamic behavior with motion of the POP backbone in [Cu(POP)(iPrSPy)][PF6] and [Cu(POP)(tBuSPy)][PF6] frozen out at 238 K. VT NMR spectroscopic data including EXSY peaks in the ROESY spectrum of [Cu(xantphos)(tBuSPy)][PF6] at 198 K reveal that two conformers exist in an approximate ratio of 5:1. Replacing bpy by the N^S ligands shifts the Cu+/Cu2+ oxidation to a higher potential. The copper(I) compounds are weak emitters in the solid state with PLQY values of <2%. These values are similar to those for [Cu(POP)(bpy)][PF6] and [Cu(xantphos)(bpy)][PF6] in the solid state.

Variable-Temperature Multinuclear Solid-State NMR Study of Oxide Ion Dynamics in Fluorite-Type Bismuth Vanadate and Phosphate Solid Electrolytes

<p>In this study, we employ a multinuclear, variable-temperature NMR spectroscopy approach to characterise and measure oxide ionic motion in the V- and P-substituted bismuth oxide materials Bi0.913V0.087O1.587, Bi0.852V0.148O1.648 and Bi0.852P0.148O1.648, previously shown to have excellent ionic conduction properties. Two main ¹⁷O NMR resonances are distinguished for each material, corresponding to O in the Bi–O and V–O/P–O sublattices. Using variable-temperature (VT) measurements ranging from room temperature to 923 K, the ionic motion experienced by these different sites has then been characterised, with coalescence of the two environments in the V-substituted materials clearly indicating a conduction mechanism facilitated by exchange between the two sublattices. The lack of this coalescence in the P-substituted material indicates a different mechanism, confirmed by ¹⁷O T1 (spin-lattice relaxation) NMR experiments to be driven purely by vacancy motion in the Bi–O sublattice. ⁵¹V and ³¹P VT-NMR experiments show high rates of tetrahedral rotation even at room temperature, increasing with heating. An additional VO4 environment appears in ¹⁷O and ⁵¹V NMR spectra of the more highly V-substituted Bi0.852V0.148O1.648, which we ascribe to differently distorted VO4 tetrahedral units that disrupt the overall ionic motion, consistent both with linewidth analysis of the 17O VT-NMR spectra and experimental results of Kuang <i>et al.</i> showing a lower oxide ionic conductivity in this material compared to Bi0.913V0.087O1.587 (<i>Chem. Mater. </i>2012, 24, 2162). This study shows solid-state NMR is particularly well suited to understanding connections between local structural features and ionic mobility, and can quantify the evolution of oxide-ion dynamics with increasing temperature.</p>

Variable-Temperature Multinuclear Solid-State NMR Study of Oxide Ion Dynamics in Fluorite-Type Bismuth Vanadate and Phosphate Solid Electrolytes

<p>In this study, we employ a multinuclear, variable-temperature NMR spectroscopy approach to characterise and measure oxide ionic motion in the V- and P-substituted bismuth oxide materials Bi0.913V0.087O1.587, Bi0.852V0.148O1.648 and Bi0.852P0.148O1.648, previously shown to have excellent ionic conduction properties. Two main ¹⁷O NMR resonances are distinguished for each material, corresponding to O in the Bi–O and V–O/P–O sublattices. Using variable-temperature (VT) measurements ranging from room temperature to 923 K, the ionic motion experienced by these different sites has then been characterised, with coalescence of the two environments in the V-substituted materials clearly indicating a conduction mechanism facilitated by exchange between the two sublattices. The lack of this coalescence in the P-substituted material indicates a different mechanism, confirmed by ¹⁷O T1 (spin-lattice relaxation) NMR experiments to be driven purely by vacancy motion in the Bi–O sublattice. ⁵¹V and ³¹P VT-NMR experiments show high rates of tetrahedral rotation even at room temperature, increasing with heating. An additional VO4 environment appears in ¹⁷O and ⁵¹V NMR spectra of the more highly V-substituted Bi0.852V0.148O1.648, which we ascribe to differently distorted VO4 tetrahedral units that disrupt the overall ionic motion, consistent both with linewidth analysis of the 17O VT-NMR spectra and experimental results of Kuang <i>et al.</i> showing a lower oxide ionic conductivity in this material compared to Bi0.913V0.087O1.587 (<i>Chem. Mater. </i>2012, 24, 2162). This study shows solid-state NMR is particularly well suited to understanding connections between local structural features and ionic mobility, and can quantify the evolution of oxide-ion dynamics with increasing temperature.</p>

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

The inexpensive room temperature ionic liquid (RTIL), [bmim][Br] has been found to be a superior medium for the Bi-mediated Barbier-type allylation of aldehydes compared to other conventional solvents. It plays the dual role of a solvent and a metal activator enabling higher yields of the products in a shorter reaction time using stoichiometric/near-stoichiometric amounts of reagents. Plausibly, [bmim][Br] activates Bi metal by a charge transfer mechanism. The 1H VT-NMR studies suggested that both the allylating species, allylbismuth dibromide and diallylbismuth bromide, are generated in situ.