"Hydridic Hydrogen-Bond Donors" Are Not Hydrogen-Bond Donors.

Herein, we dismiss a recent proposal by Civis, Hobza, and co-workers to modify the IUPAC definition of hydrogen bonds in order to expand the scope from protonic Y-Hδ+ to hydridic Y-Hδ- hydrogen-bond donor fragments [J. Am. Chem. Soc. 2023, 145, 8550]. Based on accurate Kohn-Sham molecular orbital (KS-MO) analyses, we falsify the conclusion that interactions involving protonic and hydridic hydrogens are both hydrogen bonds; they are not. Instead, our quantitative KS-MO, energy decomposition, and Voronoi deformation density analyses reveal two fundamentally different bonding mechanisms for protonic Y-Hδ+ and hydridic Y-Hδ- fragments which go with charge transfer in opposite directions. On one hand, we confirm the IUPAC definition for regular hydrogen bonds in the case of protonic Y-Hδ+ fragments. On the other hand, complexes involving Y-Hδ- fragments are, in fact, acceptors in other well-known families of Lewis-acid/base interactions, such as halogen bonds, chalcogen bonds, and pnictogen bonds. These mechanisms lead to the same spectroscopic phenomenon in both the Y-Hδ+ and Y-Hδ- fragments, that is, the redshift in the Y-H stretching frequency, which is, thus, not an exclusive indicator for hydrogen bonding.

Retro-Cope elimination of cyclic alkynes: reactivity trends and rational design of next-generation bioorthogonal reagents.

The retro-Cope elimination reaction between dimethylhydroxylamine (DMHA) and various cyclic alkynes has been quantum chemically explored using DFT at ZORA-BP86/TZ2P. The purpose of this study is to understand the role of the following three unique activation modes on the overall reactivity, that is (i) additional cycloalkyne predistortion via fused cycles, (ii) exocyclic heteroatom substitution on the cycloalkyne, and (iii) endocyclic heteroatom substitution on the cycloalkyne. Trends in reactivity are analyzed and explained by using the activation strain model (ASM) of chemical reactivity. Based on our newly formulated design principles, we constructed a priori a suite of novel bioorthogonal reagents that are highly reactive towards the retro-Cope elimination reaction with DMHA. Our findings offer valuable insights into the design principles for highly reactive bioorthogonal reagents in chemical synthesis.

Origin of the Felkin-Anh(-Eisenstein) model: a quantitative rationalization of a seminal concept.

Quantum chemical calculations were carried out to quantitatively understand the origin of the Felkin-Anh(-Eisenstein) model, widely used to rationalize the π-facial stereoselectivity in the nucleophilic addition reaction to carbonyl groups directly attached to a stereogenic center. To this end, the possible approaches of cyanide to both (S)-2-phenylpropanal and (S)-3-phenylbutan-2-one have been explored in detail. With the help of the activation strain model of reactivity and the energy decomposition analysis method, it is found that the preference for the Felkin-Anh addition is mainly dictated by steric factors which manifest in a less destabilizing strain-energy rather than, as traditionally considered, in a lower Pauli repulsion. In addition, other factors such as the more favorable electrostatic interactions also contribute to the preferred approach of the nucleophile. Our work, therefore, provides a different, more complete rationalization, based on quantitative analyses, of the origin of this seminal and highly useful concept in organic chemistry.

The nature of metallophilic interactions in closed-shell d8-d8 metal complexes.

We have quantum chemically analyzed the closed-shell d8-d8 metallophilic interaction in dimers of square planar [M(CO)2X2] complexes (M = Ni, Pd, Pt; X = Cl, Br, I) using dispersion-corrected density functional theory at ZORA-BLYP-D3(BJ)/TZ2P level of theory. Our purpose is to reveal the nature of the [X2(CO)2M]⋯[M(CO)2X2] bonding mechanism by analyzing trends upon variations in M and X. Our analyses reveal that the formation of the [M(CO)2X2]2 dimers is favored by an increasingly stabilizing electrostatic interaction when the M increases in size and by more stabilizing dispersion interactions promoted by the larger X. In addition, there is an overlooked covalent component stemming from metal-metal and ligand-ligand donor-acceptor interactions. Thus, at variance with the currently accepted picture, the d8-d8 metallophilicity is attractive, and the formation of [M(CO)2X2]2 dimers is not a purely dispersion-driven phenomenon.

What defines electrophilicity in carbonyl compounds.

The origin of the electrophilicity of a series of cyclohexanones and benzaldehydes is investigated using the activation strain model and quantitative Kohn-Sham molecular orbital (MO) theory. We find that this electrophilicity is mainly determined by the electrostatic attractions between the carbonyl compound and the nucleophile (cyanide) along the entire reaction coordinate. Donor-acceptor frontier molecular orbital interactions, on which the current rationale behind electrophilicity trends is based, appear to have little or no significant influence on the reactivity of these carbonyl compounds.

Correction: Pericyclic reaction benchmarks: hierarchical computations targeting CCSDT(Q)/CBS and analysis of DFT performance.

Correction for 'Pericyclic reaction benchmarks: hierarchical computations targeting CCSDT(Q)/CBS and analysis of DFT performance' by Pascal Vermeeren et al., Phys. Chem. Chem. Phys., 2022, 24, 18028-18042, https://doi.org/10.1039/D2CP02234F.

Solvent-induced dual nucleophiles and the α-effect in the SN2 versus E2 competition.

We have quantum chemically investigated how microsolvation affects the various E2 and SN2 pathways, their mutual competition, and the α-effect of the model reaction system HOO-(H2O)n + CH3CH2Cl, at the CCSD(T) level. Interestingly, we identify the dual nature of the α-nucleophile HOO- which, upon solvation, is in equilibrium with HO-. This solvent-induced dual appearance gives rise to a rich network of competing reaction channels. Among both nucleophiles, SN2 is always favored over E2, and this preference increases upon increasing microsolvation. Furthermore, we found a pronounced α-effect, not only for SN2 substitution but also for E2 elimination, i.e., HOO- is more reactive than HO- in both cases. Our activation strain and quantitative molecular orbital analyses reveal the physical mechanisms behind the various computed trends. In particular, we demonstrate that two recently proposed criteria, required for solvent-free nucleophiles to display the α-effect, must also be satisfied by microsolvated HOO-(H2O)n nucleophiles.

Nature and strength of group-14 A-A' bonds.

We have quantum chemically investigated the nature and stability of C-C and Si-Si bonds in R3A-AR3 (A = C, Si; R3 = H3, Me3, Me2Ph, MePh2, Ph3, t-Bu3) using density functional theory (DFT). Systematic increase of steric bulk of the substituents R has opposite effects on C-C and Si-Si bonds: the former becomes weaker whereas the latter becomes stronger. Only upon going further, from R = Ph to the bulkiest R = t-Bu, the R3Si-SiR3 bond begins to weaken. Our bonding analyses show how different behavior upon increasing the steric bulk of the substituents stems from the interplay of (Pauli) repulsive and (dispersion) attractive steric mechanisms. Extension of our analyses to other model systems shows that C-Si bonds display behavior that is in between that of C-C and Si-Si bonds. Further increasing the size of the group-14 atoms from C-C and Si-Si to Ge-Ge, Sn-Sn and Pb-Pb leads to a further decrease in the sensitivity of the bond strength with respect to the substituents' bulkiness. Our findings can be used as design principles for tuning A-A and A-A' bond strengths.

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

The front cover artwork is provided by the TheoCheM group at the Vrije Universiteit Amsterdam. The image shows how, in X- •••H3 C-Y complexes, the Lewis base X- tetrel-binds to the central C while sterically pushing the H atoms towards C; hence, the compression and blueshift of the H-C bonds. Read the full text of the Research Article at 10.1002/cphc.202300480.

Stabilization of Diborynes versus Destabilization of Diborenes by Coordination of Lewis Bases: Unravelling the Dichotomy.

We have quantum chemically investigated the boron-boron bonds in B2 , diborynes B2 L2 , and diborenes B2 H2 L2 (L=none, OH2 , NH3 ) using dispersion-corrected relativistic density functional theory at ZORA-BLYP-D3(BJ)/TZ2P. B2 has effectively a single B-B bond provided by two half π bonds, whereas B2 H2 has effectively a double B=B bond provided by two half π bonds and one σ 2p-2p bond. This different electronic structure causes B2 and B2 H2 to react differently to the addition of ligands. Thus, in B2 L2 , electron-donating ligands shorten and strengthen the boron-boron bond whereas, in B2 H2 L2 , they lengthen and weaken the boron-boron bond. The aforementioned variations in boron-boron bond length and strength become more pronounced as the Lewis basicity of the ligands L increases.

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

We have quantum chemically investigated the origin of the atypical blueshift of the H-C bond stretching frequency in the hydrogen-bonded complex X- •••H3 C-Y (X, Y=F, Cl, Br, I), as compared to the corresponding redshift occurring in Cl- •••H3 N and Cl- •••H3 C-H, using relativistic density functional theory (DFT) at ZORA-BLYP-D3(BJ)/QZ4P. Previously, this blueshift was attributed, among others, to the contraction of the H-C bonds as the H3 C moiety becomes less pyramidal. Herein, we provide quantitative evidence that, instead, the blueshift arises from a direct and strong X- •••C interaction of the HOMO of A- with the backside lobe on carbon of the low-lying C-Y antibonding σ* LUMO of the H3 C-Y fragment. This X- •••C bond, in essence a tetrel bond, pushes the H atoms towards a shorter H-C distance and makes the H3 C moiety more planar. The blueshift may, therefore, serve as a diagnostic for tetrel bonding.

More Electropositive is More Electronegative: Atom Size Determines C=X Group Electronegativity.

Opposite to what one might expect, we find that the C=X group can become effectively more, not less, electronegative when the Pauling electronegativity of atom X decreases down Groups 16, 15, and 14 of the Periodic Table. Our quantum-chemical analyses, show that, and why, this phenomenon is a direct consequence of the increasing size of atom X down a group. These findings can be applied to tuning and improving the hydrogen-bond donor strength of amides H2 NC(=X)R by increasingly withdrawing density from the NH2 group. A striking example is that H2 NC(=SiR2 )R is a stronger hydrogen-bond donor than H2 NC(=CR2 )R.

Cobalt-Catalyzed Enantio- and Regioselective C(sp3 )-H Alkenylation of Thioamides.

An enantioselective cobalt-catalyzed C(sp3 )-H alkenylation of thioamides with but-2-ynoate ester coupling partners employing thioamide directing groups is presented. The method is operationally simple and requires only mild reaction conditions, while providing alkenylated products as single regioisomers in excellent yields (up to 85 %) and high enantiomeric excess [up to 91 : 9 enantiomeric ratio (er), or up to >99 : 1 er after a single recrystallization]. Diverse downstream derivatizations of the products are demonstrated, delivering a range of enantioenriched constructs. Extensive computational studies using density functional theory provide insight into the detailed reaction mechanism, origin of enantiocontrol, and the unusual regioselectivity of the alkenylation reaction.

Unraveling the Bürgi-Dunitz Angle with Precision: The Power of a Two-Dimensional Energy Decomposition Analysis.

Understanding the geometrical preferences in chemical reactions is crucial for advancing the field of organic chemistry and improving synthetic strategies. One such preference, the Bürgi-Dunitz angle, is central to nucleophilic addition reactions involving carbonyl groups. This study successfully employs a novel two-dimensional Distortion-Interaction/Activation-Strain Model in combination with a two-dimensional Energy Decomposition Analysis to investigate the origins of the Bürgi-Dunitz angle in the addition reaction of CN- to (CH3)2C═O. We constructed a 2D potential energy surface defined by the distance between the nucleophile and carbonylic carbon atom and by the attack angle, followed by an in-depth exploration of energy components, including strain and interaction energy. Our analysis reveals that the Bürgi-Dunitz angle emerges from a delicate balance between two key factors: strain energy and interaction energy. High strain energy, as a result of the carbonyl compound distorting to avoid Pauli repulsion, is encountered at high angles, thus setting the upper bound. On the other hand, interaction energy is shaped by a dominant Pauli repulsion when the angles are lower. This work emphasizes the value of the 2D Energy Decomposition Analysis as a refined tool, offering both quantitative and qualitative insights into chemical reactivity and selectivity.

Understanding chemistry with the symmetry-decomposed Voronoi deformation density charge analysis.

The symmetry-decomposed Voronoi deformation density (VDD) charge analysis is an insightful and robust computational tool to aid the understanding of chemical bonding throughout all fields of chemistry. This method quantifies the atomic charge flow associated with chemical-bond formation and enables decomposition of this charge flow into contributions of (1) orbital interaction types, that is, Pauli repulsive or bonding orbital interactions; (2) per irreducible representation (irrep) of any point-group symmetry of interacting closed-shell molecular fragments; and now also (3) interacting open-shell (i.e., radical) molecular fragments. The symmetry-decomposed VDD charge analysis augments the symmetry-decomposed energy decomposition analysis (EDA) so that the charge flow associated with Pauli repulsion and orbital interactions can be quantified both per atom and per irrep, for example, for σ, π, and δ electrons. This provides detailed insights into fundamental aspects of chemical bonding that are not accessible from EDA.

SN 2 versus E2 Competition of Cyclic Ethers.

We have quantum chemically studied the influence of ring strain on the competition between the two mechanistically different SN 2 and E2 pathways using a series of archetypal ethers as substrate in combination with a diverse set of Lewis bases (F- , Cl- , Br- , HO- , H3 CO- , HS- , H3 CS- ), using relativistic density functional theory at ZORA-OLYP/QZ4P. The ring strain in the substrate is systematically increased on going from a model acyclic ether to a 6- to 5- to 4- to 3-membered ether ring. We have found that the activation energy of the SN 2 pathway sharply decreases when the ring strain of the system is increased, thus on going from large to small cyclic ethers, the SN 2 reactivity increases. In contrast, the activation energy of the E2 pathway generally rises along this same series, that is, from large to small cyclic ethers. The opposing reactivity trends induce a mechanistic switch in the preferred reaction pathway for strong Lewis bases from E2, for large cyclic substrates, to SN 2, for small cyclic substrates. Weak Lewis bases are unable to overcome the higher intrinsic distortivity of the E2 pathway and, therefore, always favor the less distortive SN 2 reaction.

Origin of the Bürgi-Dunitz Angle.

The Bürgi-Dunitz (BD) angle plays a pivotal role in organic chemistry to rationalize the nucleophilic addition to carbonyl groups. Yet, the origin of the obtuse trajectory of the nucleophile remains incompletely understood. Herein, we quantify the importance of the underlying physical factors quantum chemically. The obtuse BD angle appears to originate from the concerted action of a reduced Pauli repulsion between the nucleophile HOMO and carbonyl π bond, a more stabilizing HOMO-π*-LUMO(C=O) interaction, as well as a more favorable electrostatic attraction.

Insertion of CO2 and CS2 into Bi-N bonds enables catalyzed CH-activation and light-induced bismuthinidene transfer.

The uptake and release of small molecules continue to be challenging tasks of utmost importance in synthetic chemistry. The combination of such small molecule activation with subsequent transformations to generate unusual reactivity patterns opens up new prospects for this field of research. Here, we report the reaction of CO2 and CS2 with cationic bismuth(iii) amides. CO2-uptake gives isolable, but metastable compounds, which upon release of CO2 undergo CH activation. These transformations could be transferred to the catalytic regime, which formally corresponds to a CO2-catalyzed CH activation. The CS2-insertion products are thermally stable, but undergo a highly selective reductive elimination under photochemical conditions to give benzothiazolethiones. The low-valent inorganic product of this reaction, Bi(i)OTf, could be trapped, showcasing the first example of light-induced bismuthinidene transfer.

Probing Polar-π Interactions Between Tetrazoles and Aromatic Rings.

The heterocyclic tetrazole, a well-established bioisosteric replacement of carboxylic acid, plays an important role in medicinal chemistry. To deepen the functional understanding of tetrazoles in chemical sciences, it is essential to investigate the noncovalent interactions between the tetrazole ring and aromatic rings. Here, we report synthetic, spectroscopic, structural and quantum chemical analyses on specially designed 2-arylphenyl-1H-tetrazoles to study the underlying noncovalent interactions between the tetrazole ring and the neighboring aromatic ring possessing substituents at para/meta position. pKa values and proton affinities of 2-arylphenyl-1H-tetrazoles correlate well with Hammett sigma values of para-substituents at the flanking aromatic ring. Molecular orbital and energy decomposition analyses reveal that through-space NH-π interactions and π-π interactions contribute to the trend of pKa values and proton affinities of 2-arylphenyl-1H-tetrazoles. The electrostatic interaction between tetrazole/tetrazolide interacting with the aromatic rings appears responsible for the observed acidity trends. These results will be helpful for the rational design of tetrazole-based drugs and materials.