On the mechanism of the dyotropic expansion of hydrindanes into decalins.

A combined computational/experimental approach has revealed key mechanistic aspects in a recently reported dyotropic expansion of hydrindanes into decalins. While computer simulations had already anticipated the need for acid catalysis for making this reaction feasible under the mild conditions used in the laboratory, this work places the dyotropic step not into the reaction flask but at a later step, during the work up instead. With this information in hand the reaction has been optimized by exploring the performance of different activating agents and shown to be versatile, particularly in steroid related chemistry due to the two scaffolds that this reaction connects.

Enantioselective CO Fixation Via a Heck-Coupling/Carboxylation Cascade Catalyzed by Nickel.

A novel asymmetric nickel-based procedure has been developed in which CO fixation is achieved as a second step of a truncated Heck coupling. For this, a new chiral ligand has been prepared and shown to achieve enantiomeric excesses up to 99 %. The overall process efficiently furnishes chiral 2,3-dihydrobenzofuran-3-ylacetic acids, an important class of bioactive products, from easy to prepare starting materials.

The effect of solvation in torquoselectivity: ring opening of monosubstituted cyclobutenes.

The paradigmatic electrocyclic ring opening of monosubstituted cyclobutenes has been used to diagnose possible solvation effects tuning the torquoselectivity observed in these reactions. This kind of selectivity in electrocyclic reactions is mostly due to strong orbital interactions, particularly when they involve powerful electron donors and acceptors, which also combine with usually milder steric effects. Orbital interactions are established between the cleaving C-C bond and the HOMO/LUMO of the EDG/EWG substituent.

On the Use of Popular Basis Sets: Impact of the Intramolecular Basis Set Superposition Error.

The magnitude of intramolecular basis set superposition error (BSSE) is revealed via computing systematic trends in molecular properties. This type of error is largely neglected in the study of the chemical properties of small molecules and it has historically been analyzed just in the study of large molecules and processes dominated by non-covalent interactions (typically dimerization or molecular complexation and recognition events). In this work we try to provide proof of the broader prevalence of this error, which permeates all types of electronic structure calculations, particularly when employing insufficiently large basis sets.

Rational Design of Efficient Environmental Sensors: Ring-Shaped Nanostructures Can Capture Quat Herbicides.

The viability of using []-cycloparaphenylenes (CPPs) of different sizes to encapsulate diquat (DQ) pesticide molecules has been tested analyzing the origin of the host-guest interactions stabilizing the complex. This analysis provides rational design capabilities to construct ad hoc capturing systems tailored to the desired pollutant. All CPPs considered ( = 7-12) are capable of forming remarkably stable complexes with DQ, though [9]-CPP is the best candidate, where a fine balance is established between the energy penalty due to the deformation + repulsion of the pesticide molecule inside the cavity (larger in smaller CPPs) and the maximization of the favorable dispersion, electrostatic and induction contributions (which also decrease in larger rings).

Gold-Catalyzed Homogeneous (Cyclo)Isomerization Reactions.

Gold is currently one of the most used metals in organometallic catalysis. The ability of gold to activate unsaturated groups in different modes, together with its tolerance to a wide range of functional groups and reaction conditions, turns gold-based complexes into efficient and highly sought after catalysts. Natural products and relevant compounds with biological and pharmaceutical activity are often characterized by complex molecular structures.

Phosphine-Catalyzed Stereoselective Dearomatization of 3-NO-Indoles with Allenoates.

The stereoselective phosphine-catalyzed (( pMeOCH)P, 10-20 mol %) dearomatization of 3-NO-indoles with allenoates is described. A range of densely functionalized indolines (18 examples) is obtained in high yields (up to 96%) under mild reaction conditions (rt, air, reagent-grade solvent). Computational simulations and labeling experiments revealed a stepwise [3 + 2]-type mechanism involving a water-assisted hydrogen shift and accounted for the diastereoselection recorded.

Lennard-Jones Intermolecular Potentials for the Description of 6-Membered Aromatic Heterocycles Interacting with the Isoelectronic CO and CS.

We have generated Lennard-Jones potentials for the interaction between CX (X = O, S) and 11 nitrogen-doped benzene derivatives in different orientations at the M06-2X/def2-tzvpp level as tools to parametrize accurate force fields and to better understand the interaction of these greenhouse gases with heterocyclic building blocks used in the design of capture and detection systems. We find that the most favorable interactions are found between the carbon in CO and the main heterocycle in the ring in a parallel orientation, whereas the preferred interaction mode of CS is established between sulfur and the π density of the aromatic ring. The fact that the preferences for interaction sites and orientations of CO and CS are most of the times opposite helps in terms of ensuring the selectivity of these systems in front of these two isoelectronic compounds.

Pushing the limits of concertedness. A waltz of wandering carbocations.

Among the array of complex terpene-forming carbocation cyclization/rearrangement reactions, the so-called "triple shift" reactions are among the most unexpected. Such reactions involve the asynchronous combination of three 1,-shifts into a concerted process, , a 1,2-alkyl shift followed by a 1,3-hydride shift followed by a second 1,2-alkyl shift. This type of reaction so far has been proposed to occur during the biosynthesis of diterpenes and the sidechains of sterols.

Mechanism of the Molybdenum-Mediated Cadogan Reaction.

Oxygen atom transfer reactions are receiving increasing attention because they bring about paramount transformations in the current biomass processing industry. Significant efforts have therefore been made lately in the development of efficient and scalable methods to deoxygenate organic compounds. One recent alternative involves the modification of the Cadogan reaction in which a Mo(VI) core catalyzes the reduction of -nitrostyrene derivatives to indoles in the presence of PPh.

Nitrogen doped nanohoops as promising CO capturing devices.

The impact of climate change in the face of steady or increasing emissions has made the capture and storage of CO2 a priority issue. Supramolecular chemistry is one of the tools that can be used for this task, due to the possibility of tuning intermolecular interactions for the capture of this gas in a selective and efficient way. In this context, this work presents a novel approach for the capture of CO2 based on n-cycloparaphenylenes ([n]-CPPs) doped with nitrogen atoms.

Lennard-Jones Potentials for the Interaction of CO with Five-Membered Aromatic Heterocycles.

We used M06-2X/Def2-TZVPP to calculate a broad set of rigid interaction profiles between CO and 30 different aromatic heterocycles, based on pyrrole, furan, and thiophene with ring positions subsituted with up to four nitrogens. For each system, several orientations of the fragments were explored to both find the preferred interaction mode and have information about other interaction modes that can contribute to the binding energy when CO is captured by complex systems. From these data, Lennard-Jones potentials were obtained, which can be used for the parametrization of force fields that correctly describe the multipolar and dispersion interactions at play between these kinds of fragments.

CO Complexes with Five-Membered Heterocycles: Structure, Topology, and Spectroscopic Characterization.

In a first step toward the rational design of macrocyclic structures optimized for CO capture, we systematically explored the potential of 30 five-membered aromatic heterocycles to establish coordinating complexes with this pollutant. The interactions between the two moieties were studied in several orientations, and the obtained complexes were analyzed in terms of electron density and vibrational fingerprint. The former is an aid to provide an in-depth knowledge of the interaction, whereas the latter should help to select structural motifs that have not only good complexation properties but also diagnostic spectroscopic signals.

Gold-Catalyzed Synthesis of 1-(Indol-3-yl)carbazoles: Selective 1,2-Alkyl vs 1,2-Vinyl Migration.

Gold(III)-catalyzed cycloisomerization of α-bis(indol-3-yl)methyl alkynols selectively affords 1-(indol-3-yl)carbazoles, in a transformation that takes place through a selective 1,2-alkyl vs 1,2-vinyl migration step in the vinyl-gold intermediate generated from the initial 5-endo-spirocyclization. The reaction proceeds well with either tertiary or secondary starting alkynols as well as with a wide variety of alkyne substituents. The key role of the other indol-3-yl substituent for the unexpected selectivity in the 1,2 rearrangement has also been supported by DFT calculations that reveal a low barrier, two-step mechanism in the alkyl migration path where the second indole significantly stabilizes a carbocationic intermediate.

[MoO]-Mediated Oxygen Atom Transfer via an Unusual Lewis Acid Mechanism.

Density functional theory is applied to the study of the oxygen atom transfer reaction from sulfoxide (DMSO) to phosphine (PMe) catalyzed by the [MoO] active core. In this work, two fundamentally different roles are explored for this dioxometal complex in the first step of the catalytic cycle: as an oxidizing agent and as a Lewis acid. The latter turns out to be the favored pathway for the oxygen atom transfer.

Governing effects in the mechanism of the gold-catalyzed cycloisomerization of allenic hydroxylamine derivatives.

The formation of chiral heterocycles via cycloisomerization reactions of allene derivatives has gained relevance due to their associated efficiency and atom-economy. The only drawback that keeps these reactions away from being routine synthetic strategies is the control in the regioselectivity (most often 5-endo vs. 6-endo).

From Hydrindane to Decalin: A Mild Transformation through a Dyotropic Ring Expansion.

An unexpected ring expansion converting hydrindane cores into decalins has been observed. The process occurs under very mild conditions and with exquisite transfer of chiral information. The ring expansion provides access to decorated decalins with complete stereocontrol.

Dynamic Effects Responsible for High Selectivity in a [3,3] Sigmatropic Rearrangement Featuring a Bispericyclic Transition State.

Bispericyclic transition states appear when two independent pericyclic transition states merge into one. They are a particular case of the more general ambimodal concept applied to a transition state that connects reactants with two or more products involving reaction path bifurcations through valley-ridge inflections. In the present computational work, the first example of a bifurcating sigmatropic reaction featuring a bispericyclic transition state is reported for a cyclohexane featuring opposing methylene and a vinylidene fragments.

Cycloreversion of the CO trimer: a paradigmatic pseudopericyclic [2 + 2 + 2] cycloaddition reaction.

Very recently, the CO trimer has been experimentally synthesized, isolated and characterized. This process opens new ways for the withdrawal and storage of this greenhouse gas. The trimer is reported to be stable up to -40 °C, with a lifetime of about 40 min at this temperature.

A Radical Mechanism for the Vanadium-Catalyzed Deoxydehydration of Glycols.

We propose a novel mechanism for the deoxydehydration (DODH) reaction of glycols catalyzed by a [BuN][VO(dipic)] complex (dipic = pyridine-2,6-dicarboxylate) using triphenylphosphine as a reducing agent. Using density functional theory, we have confirmed that the preferred sequence of reaction steps involves reduction of the V(V) complex by phosphine, followed by condensation of the glycol into a [VO(dipic)(-O-CHCH-O-)] V(III) complex (6), which then evolves to the alkene product, with recovery of the catalyst. In contrast to the usually invoked closed-shell mechanism for the latter steps, where 6 suffers a [3+2] retrocycloaddition, we have found that the homolytic cleavage of one of the C-O bonds in 6 is preferred by 12 kcal/mol.

Assessing the attractive/repulsive force balance in axial cyclohexane C-H ···Y contacts: A combined computational analysis in monosubstituted cyclohexanes.

The interactions of axial substituents in monosubstituted cyclohexane rings are studied in this work using an array of different computational techniques. Additionally, the anomalous axial preference for some bulky substituents is related to stabilizing dispersion interactions. We find that the C-H ···Y contacts for various substituents with distances ranging from 2 to ∼5 Å may include attractive dispersion forces that can affect the conformational equilibrium; these forces co-exist with Pauli repulsive forces effected by Y group due to van der Waals sphere penetration.

Exploring the Reactivity of α-Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]-Wittig Rearrangement and the Mechanistic Proposal Revisited.

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α-lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]-Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α-lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups.

Rational Design in Catalysis: A Mechanistic Study of β-Hydride Eliminations in Gold(I) and Gold(III) Complexes Based on Features of the Reaction Valley.

β-Hydride eliminations for ethylgold(III) dichloride complexes are identified as reactions with an unusually long prechemical stage corresponding to the conformational preparation of the reaction complex and spanning six phases. The prechemical process is characterized by a geared rotation of the L-Au-L group (L = Cl) driving methyl group rotation and causing a repositioning of the ligands. This requires more than 28 kcal/mol of the total barrier of 34.

Solving the Pericyclic-Pseudopericyclic Puzzle in the Ring-Closure Reactions of 1,2,4,6-Heptatetraene Derivatives.

The ongoing controversy whether cyclization reactions of conjugated allenes or ketenes follow a pericyclic or a pseudopericyclic mechanism has triggered dozens of investigations, which have led to new valuable synthetic routes. In this work, the mechanism of 10 representative cyclization reactions of hepta-1,2,4,6-tetraenes with different terminal groups is investigated utilizing the unified reaction valley approach that registers all electronic structure changes of the target molecule along the entire reaction pathway. A clear differentiation between a purely pericyclic and a purely pseudopericyclic mechanism is established.

Normal-to-Abnormal NHC Rearrangement of Al(III) , Ga(III) , and In(III) Trialkyl Complexes: Scope, Mechanism, Reactivity Studies, and H2 Activation.

The present contribution reports experimental and theoretical mechanistic investigations on a normal-to-abnormal (C2-to-C4-bonded) NHC rearrangement processes occurring with bulky group 13 metal NHC adducts, including the scope of such a reactivity for Al compounds. The sterically congested adducts (nItBu)MMe3 (nItBu=1,3-di-tert-butylimidazol-2-ylidene; M=Al, Ga, In; 1 a-c) readily rearrange to quantitatively afford the corresponding C4-bonded complexes (aItBu)MMe3 (4 a-c), a reaction that may be promoted by THF. Thorough experimental data and DFT calculations were performed on the nNHC-to-aNHC process converting the Al-nNHC (1 a) to its aNHC analogue 4 a.