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Helicene-derived 2,2'-bipyridine N -monoxide was evaluated as a Lewis base catalyst for the enantioselective propargylation of N -acylhydrazones with allenyltrichlorosilane. The helicene-derived catalyst provided moderate-to-good reactivity and enantioselectivity for a range of acylhydrazones. This study represents the first example of the catalytic asymmetric propargylation of non-activated acylhydrazones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The synthesis and structures of nitrile complexes of V(N[ t Bu]Ar) 3 , 2 (Ar = 3,5-Me 2 C 6 H 3 ), are described. Thermochemical and kinetic data for their formation were determined by variable temperature Fourier transform infrared (FTIR), calorimetry, and stopped-flow techniques. The extent of back-bonding from metal to coordinated nitrile indicates that electron donation from the metal to the nitrile plays a less prominent role for 2 than for the related complex Mo(N[ t Bu]Ar) 3 , 1 . Kinetic studies reveal similar rate constants for nitrile binding to 2 , but the activation parameters depend critically on the nature of R in RCN. Activation enthalpies range from 2.9 to 7.2 kcal·mol -1 , and activation entropies from -9 to -28 cal·mol -1 ·K -1 in an opposing manner. Density functional theory (DFT) calculations provide a plausible explanation supporting the formation of a π-stacking interaction between a pendant arene of the metal anilide of 2 and the arene substituent on the incoming nitrile in favorable cases. Data for ligand binding to 1 do not exhibit this range of activation parameters and are clustered in a small area centered at Δ H ‡ = 5.0 kcal·mol -1 and Δ S ‡ = -26 cal·mol -1 ·K -1 . Computational studies are in agreement with the experimental data and indicate a stronger dependence on electronic factors associated with the change in spin state upon ligand binding to 1 .

A new strategy to effectively lock the conformation of substituents at the 3,3'-positions of axial-chiral biisoquinoline N , N' -dioxides was developed based on the strong dipole-dipole interaction between 1,2,3-triazole and pyridine N -oxide rings. The crystal structure and the DFT calculations of 3,3'-bis(1-benzyl-1 H -1,2,3-triazole-4-yl)-1,1'-biisoquinoline N , N' -dioxide ( 3a ) provided strong support for this strategy. Furthermore, we successfully demonstrated that readily available 4-trimethylsilyl-1,2,3-triazoles are viable nucleophiles for Hiyama cross-coupling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The rate and mechanism of the elimination of N 2 O from trans -R 3 Sn-O-N═N-O-SnR 3 (R = Ph ( 1 Ph ) and R = Cy ( 1 Cy )) to form R 3 Sn-O-SnR 3 (R = Ph ( 2 Ph ) and R = Cy ( 2 Cy )) have been studied using both NMR and IR techniques to monitor the reactions in the temperature range of 39-79 °C in C 6 D 6 . Activation parameters for this reaction are Δ H ⧧ = 15.8 ± 2.0 kcal·mol -1 and Δ S ⧧ = -28.5 ± 5 cal·mol -1 ·K -1 for 1 Ph and Δ H ⧧ = 22.7 ± 2.5 kcal·mol -1 and Δ S ⧧ = -12.4 ± 6 cal·mol -1 ·K -1 for 1 Cy . Addition of O 2 , CO 2 , N 2 O, or PPh 3 to sealed tube NMR experiments did not alter in a detectable way the rate or product distribution of the reactions. Computational DFT studies of elimination of hyponitrite from trans -Me 3 Sn-O-N═N-O-SnMe 3 ( 1 Me ) yield a mechanism involving initial migration of the R 3 Sn group from O to N passing through a marginally stable intermediate product and subsequent N 2 O elimination. Reactions of 1 Ph with protic acids HX are rapid and lead to formation of R 3 SnX and trans -H 2 N 2 O 2 . Reaction of 1 Ph with the metal radical •Cr(CO) 3 C 5 Me 5 at low concentrations results in rapid evolution of N 2 O. At higher •Cr(CO) 3 C 5 Me 5 concentrations, evolution of CO 2 rather than N 2 O is observed. Addition of 1 atm or less CO 2 to benzene or toluene solutions of 2 Ph and 2 Cy resulted in very rapid reaction to form the corresponding carbonates R 3 Sn-O-C(═O)-O-SnR 3 (R = Ph ( 3 Ph ) and R = Cy ( 3 Cy )) at room temperature. Evacuation results in fast loss of bound CO 2 and regeneration of 2 Ph and 2 Cy . Variable temperature data for formation of 3 Cy yield Δ H o = -8.7 ± 0.6 kcal·mol -1 , Δ S o = -17.1 ± 2.0 cal·mol -1 ·K -1 , and Δ G o 298K = -3.6 ± 1.2 kcal·mol -1 . DFT studies were performed and provide additional insight into the energetics and mechanisms for the reactions.

Ball milling of sodium oxides and alkali metal halide salts under a pressure of 2 atm nitrous oxide at temperatures of 38 ± 4 °C is reported. After 2.5 h of ball milling, FTIR data for both 14 N 2 O and 15 N 2 O additions show conclusively that cis -Na 2 N 2 O 2 is formed based on excellent agreement with data reported earlier by Jansen and Feldmann who prepared pure crystalline cis -Na 2 N 2 O 2 by reaction of sodium oxide and nitrous oxide for 2 h at 360 °C in a tube furnace. Continued ball milling under nitrous oxide leads to slow buildup of NaNO 3 with yields on the order of 24% achieved in 20 h. Production of nitrate only occurs during active ball milling. Studies over the first 10 h reveal a trend among potassium halide salts: KBr ≅ KCl > KI ≫ KF. Ball milling of sodium oxide alone under an atmosphere of N 2 O gives much lower yields than ball milling in the presence of added alkali metal halide salt. Ball milling of sodium oxide and nitrous oxide in fluorocarbon oil, silicone oil, calcium fluoride, clinoptilolite, molecular sieves, and silica gel does not lead to significant yields of either cis -Na 2 N 2 O 2 or NaNO 3 ., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The catalytic enantioselective ketimine Mannich and its related reactions provide direct access to chiral building blocks bearing an α-tertiary amine stereogenic center, a ubiquitous structural motif in nature. Although ketimines are often viewed as challenging electrophiles, various approaches/strategies to circumvent or overcome the adverse properties of ketimines have been developed for these transformations. This review showcases the selected examples that highlight the benefits and utilities of various ketimines and remaining challenges associated with them in the context of Mannich, allylation, and aza-Morita-Baylis-Hillman reactions as well as their variants., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

While oxidized pillar[5]arenes with 1-5 benzoquinone units are known, very few examples of oxidized pillar[6]arenes have been reported. We describe here the synthesis, characterization and electrochemical behavior of a series of macrocyclic hosts prepared by the stepwise oxidation of 1,4-diethoxypillar[6]arene, resulting in high-yield and high-purity isolation of two constitutional isomers for each macrocycle, in which two, three or four 1,4-diethoxybenzene units are replaced by benzoquinone residues. A careful structural comparison with their counterparts in the pillar[5]arene framework indicates that the geometries of the macrocycles are better described as non-Euclidean hyperbolic hexagons and elliptic pentagons, respectively. A comprehensive computational study to determine anisotropic induced current density (ACID) allows us to visualize and quantify through-space and through-bond communication pathways along the macrocyclic belt. Experimental and simulated voltammetric data, as well as UV-vis spectra, of the new macrocycles afford insights into the various electronic communication pathways in these compounds., (© 2020. The Author(s).)

A borondipyrromethene (BODIPY) chromophore is connected to a benzoxazole, benzothiazole, or nitrobenzothiazole heterocycle through an olefinic bridge with trans configuration. Rotation about the two [C-C] bonds flanking the olefinic bridge occurs with fast kinetics in solution, leading to the equilibration of four conformational isomers for each compound. Ensemble spectroscopic measurements in solutions fail to distinguish the coexisting isomers. They reveal instead averaged absorption and emission bands with dependence of the latter on the excitation wavelength. Using high-throughput single-molecule spectroscopy, two main populations of single molecules with distinct spectral centroids are observed for each compound on glass substrates. Computational analyses suggest the two populations of molecules to be conformational isomers with antiperiplanar and periplanar arrangements of the BODIPY chromophores about its [C-C] bond to the olefinic bridge. Thus, statistical analysis of multiple single-molecule emission spectra can discriminate stereoisomers that would otherwise be impossible to distinguish by ensemble measurements alone.

As the inhibitory γ-aminobutyric acid-ergic (GABAergic) transmission has a pivotal role in the central nervous system (CNS) and defective forms of its synapses are associated with serious neurological disorders, numerous versions of caged GABA and, more recently, photoswitchable ligands have been developed to investigate such transmission. While the complementary nature of these probes is evident, the mechanisms by which the GABA receptors can be photocontrolled have not been fully exploited. In fact, the ultimate need for specificity is critical for the proper synaptic exploration. No caged allosteric modulators of the GABA A receptor have been reported so far; to introduce such an investigational approach, we exploited the structural motifs of the benzodiazepinic scaffold to develop a photocaged version of diazepam (CD) that was tested on basolateral amygdala (BLa) pyramidal cells in mouse brain slices. CD is devoid of any intrinsic activity toward the GABA A receptor before irradiation. Importantly, CD is a photoreleasable GABA A receptor-positive allosteric modulator that offers a different probing mechanism compared to caged GABA and photoswitchable ligands. CD potentiates the inhibitory signaling by prolonging the decay time of postsynaptic GABAergic currents upon photoactivation. Additionally, no effect on presynaptic GABA release was recorded. We developed a photochemical technology to individually study the GABA A receptor, which specifically expands the toolbox available to study GABAergic synapses., Competing Interests: The authors declare no competing interest.

A mechanism to photoactivate far-red/near-infrared fluorescence with infinite contrast and under mild visible illumination was designed around the photophysical properties of borondipyrromethene (BODIPY) dyes and the photochemical behavior of oxazine heterocycles. Specifically, the photoinduced and irreversible cleavage of an oxazine ring with a laser line at 405 nm extends the electronic conjugation of a BODIPY chromophore over a 3 H-indole auxochrome with a 2-(4-methoxyphenyl)ethenyl substituent in position 5. This structural transformation shifts bathochromically the main absorption band of the BODIPY component to allow the selective excitation of the photochemical product with a laser line of 633 nm and produce fluorescence between 600 and 850 nm. This combination of activation, excitation, and emission wavelengths permits the visualization of the cellular blastoderm of developing Drosophila melanogaster embryos with optimal contrast and essentially no autofluorescence from the biological specimen. Furthermore, the sequential acquisition of images, after the photoactivation event, enables the tracking of individual cells within the embryos in real time. Thus, our structural design and operating principles for the photoactivation of far-red/near-infrared fluorescence can evolve into invaluable probes to monitor cellular dynamics in vivo.

Reaction of [Pd(IPr) 2 ] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and O 2 leads to the surprising discovery that at low temperature the initial reaction product is a highly labile peroxide complex cis-[Pd(IPr) 2 (η 2 -O 2 )]. At temperatures ≳ -40 °C, cis-[Pd(IPr) 2 (η 2 -O 2 )] adds a second O 2 to form trans-[Pd(IPr) 2 (η 1 -O 2 ) 2 ]. Squid magnetometry and EPR studies yield data that are consistent with a singlet diradical ground state with a thermally accessible triplet state for this unique bis-superoxide complex. In addition to reaction with O 2 , cis-[Pd(IPr) 2 (η 2 -O 2 )] reacts at low temperature with H 2 O in methanol/ether solution to form trans-[Pd(IPr) 2 (OH)(OOH)]. The crystal structure of trans-[Pd(IPr) 2 (OOH)(OH)] is reported. Neither reaction with O 2 nor reaction with H 2 O occurs under comparable conditions for cis-[Pd(IMes) 2 (η 2 -O 2 )] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The increased reactivity of cis-[Pd(IPr) 2 (η 2 -O 2 )] is attributed to the enthalpy of binding of O 2 to [Pd(IPr) 2 ] (-14.5 ± 1.0 kcal/mol) that is approximately one-half that of [Pd(IMes) 2 ] (-27.9 ± 1.5 kcal/mol). Computational studies identify the cause as interligand repulsion forcing a wider C-Pd-C angle and tilting of the NHC plane in cis-[Pd(IPr) 2 (η 2 -O 2 )]. Arene-arene interactions are more favorable and serve to further stabilize cis-[Pd(IMes) 2 (η 2 -O 2 )]. Inclusion of dispersion effects in DFT calculations leads to improved agreement between experimental and computational enthalpies of O 2 binding. A complete reaction diagram is constructed for formation of trans-[Pd(IPr) 2 (η 1 -O 2 ) 2 ] and leads to the conclusion that kinetic factors inhibit formation of trans-[Pd(IMes) 2 (η 1 -O 2 ) 2 ] at the low temperatures at which it is thermodynamically favored. Failure to detect the predicted T-shaped intermediate trans-[Pd(NHC) 2 (η 1 -O 2 )] for either NHC = IMes or IPr is attributed to dynamic effects. A partial potential energy diagram for initial binding of O 2 is constructed. A range of low-energy pathways at different angles of approach are present and blur the distinction between pure "side-on" or "end-on" trajectories for oxygen binding.

Fluorescent 3H-indolium cations are valuable components for the realization of activatable fluorophores for bioimaging applications. Their relatively poor fluorescent quantum yields in organic solvents, however, appear to be in contradiction to their good performance in analytical methods based on single-molecule detection. The elucidation of the structural factors governing the excitation dynamics of these compounds is, therefore, essential to rationalize these effects and possibly guide the future design of activatable probes with improved performance. In this context, the structural, photochemical and photophysical properties of a model compound, consisting of coumarin and 3H-indolium heterocycles separated by a [C-C[double bond, length as m-dash]C-C] bridge, were characterized with a combination of experimental and theoretical analyses. These studies demonstrate that the fast rotation about the [C-C] bond adjacent to the coumarin component competes with the radiative deactivation of the excited state in nonviscous environments. This geometrical change dislodges the coumarin and 3H-indolium cations out of planarity to allow the population of a weakly-emissive twisted intramolecular charge-transfer (TICT) state and produce fluorescence with low quantum yield. In viscous environments, the conformational change is slow and cannot compete effectively with the radiative deactivation of the excited state, which instead produces fluorescence with high quantum yield. These results indicate that structural modifications aimed at the restriction of the rotation of this [C-C] bond are essential to improve considerably the fluorescence quantum yield of this chromophoric platform. Should a synthetic strategy for the implementation of these design guidelines be identified, activatable fluorophores, based on the 3H-indolium platform, with improved brightness will ultimately emerge.

The kinetics of the reaction of Ph 3 SnH with excess •Cr(CO) 3 C 5 Me 5 = •Cr, producing HCr and Ph 3 Sn-Cr, was studied in toluene solution under 2-3 atm CO pressure in the temperature range of 17-43.5 °C. It was found to obey the rate equation d[Ph 3 Sn-Cr]/dt = k[Ph 3 SnH][•Cr] and exhibit a normal kinetic isotope effect (k H /k D = 1.12 ± 0.04). Variable-temperature studies yielded ΔH ‡ = 15.7 ± 1.5 kcal/mol and ΔS ‡ = -11 ± 5 cal/(mol·K) for the reaction. These data are interpreted in terms of a two-step mechanism involving a thermodynamically uphill hydrogen atom transfer (HAT) producing Ph 3 Sn• and HCr, followed by rapid trapping of Ph 3 Sn• by excess •Cr to produce Ph 3 Sn-Cr. Assuming an overbarrier of 2 ± 1 kcal/mol in the HAT step leads to a derived value of 76.0 ± 3.0 kcal/mol for the Ph 3 Sn-H bond dissociation enthalpy (BDE) in toluene solution. The reaction enthalpy of Ph 3 SnH with excess •Cr was measured by reaction calorimetry in toluene solution, and a value of the Sn-Cr BDE in Ph 3 Sn-Cr of 50.4 ± 3.5 kcal/mol was derived. Qualitative studies of the reactions of other R 3 SnH compounds with •Cr are described for R = n Bu, t Bu, and Cy. The dehydrogenation reaction of 2Ph 3 SnH → H 2 + Ph 3 SnSnPh 3 was found to be rapid and quantitative in the presence of catalytic amounts of the complex Pd(IPr)(P(p-tolyl) 3 ). The thermochemistry of this process was also studied in toluene solution using varying amounts of the Pd(0) catalyst. The value of ΔH = -15.8 ± 2.2 kcal/mol yields a value of the Sn-Sn BDE in Ph 3 SnSnPh 3 of 63.8 ± 3.7 kcal/mol. Computational studies of the Sn-H, Sn-Sn, and Sn-Cr BDEs are in good agreement with experimental data and provide additional insight into factors controlling reactivity in these systems. The structures of Ph 3 Sn-Cr and Cy 3 Sn-Cr were determined by X-ray crystallography and are reported. Mechanistic aspects of oxidative addition reactions in this system are discussed.