Preparation and Photochemistry of Parent Triplet Vinylarsinidene.

Vinyl pnictinidenes are an elusive family of molecules that have been suggested as key intermediates in multiple chemical reactions and commonly display a predisposition toward open-shell electronic ground states (as is evident from quantum chemical computations). However, owing to their expected extremely high reactivity, no vinyl pnictinidene has ever been isolated and characterized spectroscopically. Here, we report the synthesis and spectroscopic characterization of vinylarsinidene, a higher congener of vinylnitrene. As we demonstrate, triplet vinylarsinidene can be prepared through the low-temperature photolysis of diazidovinylarsine at 10 K in an argon matrix. The title compound can also be generated through high-vacuum flash pyrolysis of the diazide at 700 °C and trapped analogously. Triplet vinylarsinidene was characterized by IR and UV/vis spectroscopy and displayed remarkably rich unimolecular photochemistry. Upon selective photoirradiation, it rearranges to vinylidenearsine, 2H-arsirene, triplet ethynylarsinidene or an arsinidene (H-As) acetylene complex. The formation mechanisms of these products were rationalized with DFT and CASPT2 computations.

Leveraging Limited Experimental Data with Machine Learning: Differentiating a Methyl from an Ethyl Group in the Corey-Bakshi-Shibata Reduction.

We present a case study on how to improve an existing metal-free catalyst for a particularly difficult reaction, namely, the Corey-Bakshi-Shibata (CBS) reduction of butanone, which constitutes the classic and prototypical challenge of being able to differentiate a methyl from an ethyl group. As there are no known strategies on how to address this challenge, we leveraged the power of machine learning by constructing a realistic (for a typical laboratory) small, albeit high-quality, data set of about 100 reactions (run in triplicate) that we used to train a model in combination with a key-intermediate graph (of substrate and catalyst) to predict the differences in Gibbs activation energies ΔΔG‡ of the enantiomeric reaction paths. With the help of this model, we were able to select and subsequently screen a small selection of catalysts and increase the selectivity for the CBS reduction of butanone to 80% enantiomeric excess (ee), the highest possible value achieved to date for this substrate with a metal-free catalyst, thereby also exceeding the best available enzymatic systems (64% ee) and the selectivity with Corey's original catalyst (60% ee). This translates into a >50% improvement in relative ΔG‡ from 0.9 to 1.4 kcal mol-1. We underscore the transformative potential of machine learning in accelerating catalyst design because we rely on a manageable small data set and a key-intermediate graph representing a combination of catalyst and substrate graphs in lieu of a transition-state model. Our results highlight the synergy of synthetic chemistry and data-centric approaches and provide a blueprint for future catalyst optimization.

Experimentally Delineating the Catalytic Effect of a Single Water Molecule in the Photochemical Rearrangement of the Phenylperoxy Radical to the Oxepin-2(5H)-one-5-yl Radical.

Catalysis plays a pivotal role in both chemistry and biology, primarily attributed to its ability to stabilize transition states and lower activation free energies, thereby accelerating reaction rates. While computational studies have contributed valuable mechanistic insights, there remains a scarcity of experimental investigations into transition states. In this work, we embark on an experimental exploration of the catalytic energy lowering associated with transition states in the photorearrangement of the phenylperoxy radical-water complex to the oxepin-2(5H)-one-5-yl radical. Employing matrix isolation spectroscopy, density functional theory, and post-HF computations, we scrutinize the (photo)catalytic impact of a single water molecule on the rearrangement. Our computations indicate that the barrier heights for the water-assisted unimolecular isomerization steps are approximately 2-3 kcal mol-1 lower compared to the uncatalyzed steps. This decrease directly coincides with the energy difference in the required wavelength during the transformation (Δλ = λ546 nm - λ579 nm ≡ 52.4-49.4 = 3.0 kcal mol-1), allowing us to elucidate the differential transition state energy in the photochemical rearrangement of the phenylperoxy radical catalyzed by a single water molecule. Our work highlights the important role of water catalysis and has, among others, implications for understanding the mechanism of organic reactions under atmospheric conditions.

Quantifying Intermolecular Interactions in Asymmetric Peptide Organocatalysis as a Key toward Understanding Selectivity.

The kinetic resolution of trans-cyclohexane-1,2-diol with a lipophilic oligopeptide catalyst shows extraordinary selectivities. To improve our understanding of the factors governing selectivity, we quantified the Gibbs free energies of interactions of the peptide with both enantiomers of trans-cyclohexane-1,2-diol using nuclear magnetic resonance (NMR) spectroscopy. For this, we use advanced methods such as transverse relaxation (R2), diffusion measurements, saturation transfer difference (STD), and chemical shift (δ) analysis of peptide-diol mixtures upon varying their composition (NMR titrations). The methods employed give comparable and consistent results. The molecular recognition by the catalyst is approximately 3 kJ mol-1 in favor of the preferentially acetylated (R,R)-enantiomer in the temperature range studied. Interestingly, the difference of 3 kJ mol-1 is also confirmed by results from reaction monitoring of the acylation step under catalytic conditions, indicating that this finding is true regardless of whether the investigation is performed on the acetylated species or on the free catalyst. To arrive at these conclusions, the self-association of both the catalyst and the substrate in toluene was found to play an important role and thus needs to be taken into account in reaction screening.

Hydrogen Tunneling Exhibiting Unexpectedly Small Primary Kinetic Isotope Effects.

Probing quantum mechanical tunneling (QMT) in chemical reactions is crucial to understanding and developing new transformations. Primary H/D kinetic isotopic effects (KIEs) beyond the semiclassical maximum values of 7-10 (room temperature) are commonly used to assess substantial QMT contributions in one-step hydrogen transfer reactions, because of the much greater QMT probability of protium vs. deuterium. Nevertheless, we report here the discovery of a reaction model occurring exclusively by H-atom QMT with residual primary H/D KIEs. 2-Hydroxyphenylnitrene, generated in N2 matrix, was found to isomerize to an imino-ketone via sequential (domino) QMT involving anti to syn OH-rotamerization (rate determining step) and [1,4]-H shift reactions. These sequential QMT transformations were also observed in the OD-deuterated sample, and unexpected primary H/D KIEs between 3 and 4 were measured at 3 to 20 K. Analogous residual primary H/D KIEs were found in the anti to syn OH-rotamerization QMT of 2-cyanophenol in a N2 matrix. Evidence strongly indicates that these intriguing isotope-insensitive QMT reactivities arise due to the solvation effects of the N2 matrix medium, putatively through coupling with the moving H/D tunneling particle. Should a similar scenario be extrapolated to conventional solution conditions, then QMT may have been overlooked in many chemical reactions.

Structure of [18]Annulene Revisited: Challenges for Computing Benzenoid Systems.

For cyclic conjugated structures, erratic computational results have been obtained with Hartree-Fock (HF) molecular orbital (MO) methods as well as density functional theory (DFT) with large HF-exchange contributions. In this work, the reasons for this unreliability are explored. Extensive computations on [18]annulene and related compounds highlight the pitfalls to be avoided and the due diligence required for such computational investigations. In particular, a careful examination of the MO singlet-stability eigenvalues is recommended. The appearance of negative eigenvalues is not (necessarily) problematic, but near-zero (positive or negative) eigenvalues can lead to dramatic errors in vibrational frequencies and related properties. DFT approaches with a lower HF admixture generally appear more robust in this regard for the description of benzenoid structures, although they may exaggerate the tendency toward planarity and C-C bond-equalization. For the iconic [18]annulene, the results support a nonplanar equilibrium structure. The density-fitted frozen natural orbital coupled-cluster singles and doubles with perturbative triples [DF-FNO CCSD(T)] method of electron correlation with an aug-pVQZ/aug-pVTZ basis set places the C2 global minimum 1.1 kcal mol-1 below the D6h stationary point.

Sterically controlled mechanochemistry under hydrostatic pressure.

Mechanical stimuli can modify the energy landscape of chemical reactions and enable reaction pathways, offering a synthetic strategy that complements conventional chemistry. These mechanochemical mechanisms have been studied extensively in one-dimensional polymers under tensile stress using ring-opening and reorganization, polymer unzipping and disulfide reduction as model reactions. In these systems, the pulling force stretches chemical bonds, initiating the reaction. Additionally, it has been shown that forces orthogonal to the chemical bonds can alter the rate of bond dissociation. However, these bond activation mechanisms have not been possible under isotropic, compressive stress (that is, hydrostatic pressure). Here we show that mechanochemistry through isotropic compression is possible by molecularly engineering structures that can translate macroscopic isotropic stress into molecular-level anisotropic strain. We engineer molecules with mechanically heterogeneous components-a compressible ('soft') mechanophore and incompressible ('hard') ligands. In these 'molecular anvils', isotropic stress leads to relative motions of the rigid ligands, anisotropically deforming the compressible mechanophore and activating bonds. Conversely, rigid ligands in steric contact impede relative motion, blocking reactivity. We combine experiments and computations to demonstrate hydrostatic-pressure-driven redox reactions in metal-organic chalcogenides that incorporate molecular elements that have heterogeneous compressibility, in which bending of bond angles or shearing of adjacent chains activates the metal-chalcogen bonds, leading to the formation of the elemental metal. These results reveal an unexplored reaction mechanism and suggest possible strategies for high-specificity mechanosynthesis.

Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry.

London dispersion (LD) interactions are the main contribution of the attractive part of the van der Waals potential. Even though LD effects are the driving force for molecular aggregation and recognition, the role of these omnipresent interactions in structure and reactivity had been largely underappreciated over decades. However, in the recent years considerable efforts have been made to thoroughly study LD interactions and their potential as a chemical design element for structures and catalysis. This was made possible through a fruitful interplay of theory and experiment. This review highlights recent results and advances in utilizing LD interactions as a structural motif to understand and utilize intra- and intermolecularly LD-stabilized systems. Additionally, we focus on the quantification of LD interactions and their fundamental role in chemical reactions.

Preparation and Spectroscopic Identification of the Cyclic CO2 Dimer 1,2-Dioxetanedione.

We report the preparation and infrared spectroscopic identification of 1,2-dioxetanedione, which is one of the two possible cyclic dimers of carbon dioxide. We prepared this hitherto experimentally incompletely characterized species in a solid nitrogen matrix at 3 K from the reaction of oxalyl dichloride with the urea·hydrogen peroxide complex. Surprisingly, irradiation at 254 nm does not lead to its dissociation into carbon dioxide but rather yields cyclic carbon trioxide. We further assert our spectroscopic assignments by 18O isotopic labeling and high-level N-electron valence state perturbation theory and coupled-cluster computations. The successful isolation of 1,2-dioxetanedione supports its viability as the postulated high-energy intermediate in the well-known and ubiquitously exploited "peroxyoxalate" chemiluminescent system.

Triplet Phenylarsinidene and Its Oxidation to Dioxophenylarsine.

Carbenes and nitrenes are key intermediates involved in numerous chemical processes, and they have attracted considerable attention in synthetic chemistry, biochemistry, and materials science. Even though parent arsinidene (H-As) has been characterized well, the high reactivity of subsituted arsinidenes has prohibited their isolation and characterization to date. Here, we report the preparation of triplet phenylarsinidene through the photolysis of phenylarsenic diazide isolated in an argon matrix and its subsequent characterization by infrared and UV/vis spectroscopy. Doping matrices containing phenylarsinidene with molecular oxygen leads to the formation of hitherto unknown anti-dioxyphenylarsine. The latter undergoes isomerization to novel dioxophenylarsine upon 465 nm irradiation. The assignments were validated by isotope-labeling experiments and agree very well with B3LYP/def2-TZVP computations.

Exploring the Limits of Intramolecular London Dispersion Stabilization with Bulky Dispersion Energy Donors in Alkane Solution.

We present an experimental study of a cyclooctatetraene-based molecular balance disubstituted with increasingly bulky tert-butyl (tBu), adamantyl (Ad), and diamantyl (Dia) substituents in the 1,4-/1,6-positions for which we determined the valence-bond shift equilibrium in n-hexane (hex), n-octane (oct), and n-dodecane (dod). Computations including implicit and explicit solvation support our temperature-dependent NMR equilibrium measurements indicating that the more sterically crowded 1,6-isomer is always favored, irrespective of solvent, and that the free energy is quite insensitive to substituent size.

Insights into molecular cluster materials with adamantane-like core structures by considering dimer interactions.

A class of adamantane-like molecular materials attracts attention because they exhibit an extreme non-linear optical response and emit a broad white-light spectrum after illumination with a continuous-wave infrared laser source. According to recent studies, not only the nature of the cluster molecules, but also the macroscopic structure of the materials determines their non-linear optical properties. Here we present a systematic study of cluster dimers of the compounds AdR4 and [(RT)4 S6 ] (T = Si, Ge, Sn) with R = methyl, phenyl or 1-naphthyl to gain fundamental knowledge about the interactions in the materials. For all compounds, a similar type of dimer structures with a staggered arrangement of substituents was determined as the energetically most favorable configuration. The binding energy between the dimers, determined by including London dispersion interactions, increases with the size of the core and the substituents. The cluster interactions can be classified as substituent-substituent-dominated (small cores, large substituents) or core-core-dominated (large cores, small substituents). Among various possible dimer conformers, those with small core-core distances are energetically preferred. Trimer and tetramer clusters display similar trends regarding the minimal core-core distances and binding energies. The much lower energy barrier determined for the rotation of substituents as compared to the rotation of the cluster dimers past each other indicates that the rotation of substituents more easily leads to different conformers in the material. Thus, understanding the interaction of the cluster dimers allows an initial assessment of the interactions in the materials.

Site-Selective Acylation of Pyranosides with Immobilized Oligopeptide Catalysts in Flow.

We report the site-selective acetylation of partially protected monosaccharides using immobilized oligopeptide catalysts, which are readily accessible via solid-phase peptide synthesis. The catalysts are able to invert the intrinsic selectivity, which was determined using N-methylimidazole, for a variety of pyranosides. We demonstrate that the catalysts are stable for multiple reaction cycles and can be easily reused after separation from the reaction solution. The catalysts can also be used in flow without loss of reactivity and selectivity.

Probing the Size Limit of Dispersion Energy Donors with a Bifluorenylidene Balance: Magic Cyclohexyl.

We report the synthesis of 14 2,2'-disubstituted 9,9'-bifluorenylidenes as molecular balances for the quantification of London dispersion interactions between various dispersion energy donors. For all balances, we measured ΔGZ/E at 333 K using 1H NMR in seven organic solvents. For various alkyl and aryl substituents, we generally observe a preference for the "folded" Z-isomer due to attractive London dispersion interactions. The cyclohexyl-substituted system shows the largest Z-preference in this study with ΔGZ/E = -0.6 ± 0.05 kcal mol-1 in all solvents, owing to the rotational freedom of cyclohexyl groups paired with their large polarizability that maximizes London dispersion interactions. On the other hand, rigid and sterically more demanding substituents like tert-butyl unexpectedly favor the unfolded E-isomer. This is a result of the close relative position in which the functional groups are positioned in this molecular balance. This close proximity is the reason for the increase of Pauli repulsion in the Z-isomers with large rigid substituents (tert-butyl, adamantyl, and diamantyl) which leads to an equilibrium shift toward the unfolded E-form. While we were able to reproduce most of our experimental trends qualitatively using contemporary computational chemistry methods, quantitative accuracy of the employed methods still needs further improvement.

Synthesis and Functionalization of Isomeric Sesquihomodiamantenes.

anti- and syn-sesquihomodiamantenes (SDs) were prepared and structurally characterized. anti-SD and parent sesquihomoadamantene were CH-bond functionalized by utilizing a phase-transfer protocol. The density functional theory-computed ionization potentials of unsaturated diamondoid dimers correlate well with the experimental oxidation potentials obtained from cyclic voltammetry. Similar geometries ensue for both the reduced and ionized SD states, whose persistence is supported by the ß-hydrogen's spatial sheltering. This makes SDs promising building blocks for the construction of diamond materials with high stability and carrier mobility.

Rethinking Chemistry.

The German Chemical Society (GDCh) Board of Directors chose the motto "Rethinking Chemistry" last year to address challenges connected to climate change, loss of natural resources, and geopolitical conflicts as the guiding principle of all our endeavors and actions. Rethinking Chemistry indicates the Board's desire to encourage scientists to approach chemistry in a new way, with a focus on reconsidering the field from many different angles. By taking a holistic approach, the Board intends to foster innovative, sustainable, and effective ways to use chemistry. Rethinking Chemistry is also the motto of the GDCh Science Forum Chemistry (WiFo) 2023, and a Special Collection on the homepage of Angewandte Chemie is dedicated to this event and its motto. Rethinking Chemistry means something different in each area of chemistry, and the WiFo 2023 as well as this Special Collection of Angewandte Chemie showcase its many facets.

Glycine Imine-The Elusive α-Imino Acid Intermediate in the Reductive Amination of Glyoxylic Acid.

Simple unhindered aldimines tend to hydrolyze or oligomerize and are therefore spectroscopically not well characterized. Herein we report the formation and spectroscopic characterization of the simplest imino acid, namely glycine imine, by cryogenic matrix isolation IR and UV/Vis spectroscopy. Glycine imine forms after UV irradiation of 2-azidoacetic acid by N2 extrusion in anti-(E,E)- and anti-(Z,Z)-conformation that can be photochemically interconverted. In matrix isolation pyrolysis experiments with 2-azidoacetic acid, glycine imine cannot be trapped as it further decarboxylates to aminomethylene. In aqueous solution glycine imine is hydrolyzed to hydroxy glycine and hydrated glyoxylic acid. At higher concentrations or in the presence of FeII SO4 as a reducing agent glycine imine undergoes self-reduction by oxidative decarboxylation chemistry. Glycine imine may be seen as one of the key reaction intermediates connecting prebiotic amino acid and sugar formation chemistry.

Selective Preparation of Phosphorus Mononitride (P≡N) from Phosphinoazide and Reversible Oxidation to Phosphinonitrene.

The interstellar candidate phosphorus mononitride PN, a metastable species, was generated through high-vacuum flash pyrolysis of (o-phenyldioxyl)phosphinoazide in cryogenic matrices. Although the PN stretching band was not directly detected because of its low infrared intensity and possible overlaps with other strong bands, o-benzoquinone, carbon monoxide, and cyclopentadienone as additional fragmentation products were clearly identified. Moreover, an elusive o-benzoquinone-PN complex formed when (o-phenyldioxyl)phosphinoazide was exposed to UV irradiation at λ=254 nm. Its recombination to (o-phenyldioxyl)-λ5 -phosphinonitrile was observed upon irradiation with the light at λ=523 nm, which demonstrates for the first time the reactivity of PN towards an organic molecule. Energy profile computations at the B3LYP/def2-TZVP density functional theory level reveal a concerted mechanism. To provide further evidence, UV/Vis spectra of the precursor and the irradiation products were recorded and agree well with time-dependent DFT computations.

On-Surface Synthesis and Real-Space Visualization of Aromatic P3 N3.

On-surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on-surface synthesis of the structurally elusive cyclotriphosphazene (P3 N3 ), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e., voltage pulse-induced sextuple dechlorination of an ultra-small (about 6 Å) hexachlorophosphazene P3 N3 Cl6 precursor by the tip of a scanning probe microscope. Real-space atomic-level imaging of cyclotriphosphazene reveals its planar D3h -symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3 N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy.

Assessing the Experimental Hydrogen Bonding Energy of the Cyclic Water Dimer Transition State with a Cyclooctatetraene-Based Molecular Balance.

We have conducted an experimental and computational study of cyclooctatetraene-1,4/1,6-dimethanol (1,4 and 1,6) as a molecular balance with the goal in mind to determine the otherwise inaccessible hydrogen bonding energy (HBE) of the cyclic water dimer, which constitutes a transition state. The 1,4/1,6 folding equilibrium is governed by an intramolecular hydrogen bond in the folded 1,6-isomer, in which the OH groups adopt a cyclic planar geometry, akin to the structure of the cyclic water dimer transition state. We characterized hydrogen bonding in 1,6 and reference complexes utilizing SAPT2 + (3)δMP2/aug-cc-pVTZ and selected quantum theory of atoms in molecule descriptors at M06-2XD3(0)/ma-def2-TZVPP. Additionally, we computed HBEs at the DLPNO-CCSD(T)/aug-cc-pVQZ level of theory. We find that hydrogen bonding in 1,6 is very similar to the interaction in the Ci symmetric cyclic water dimer TS, both in magnitude and character. We experimentally determined the Gibbs free energy of the folding process (ΔGeq) in a variety of organic solvents via nuclear magnetic resonance spectroscopy measurements at room temperature. By combining experimentally obtained ΔGeq values with corrections derived from accurate computational methods, we provide estimates for the HBE of cyclic water dimers and the cyclic water dimer TS, as the most stable cyclic water dimer.