Computational Study of Gold-Catalyzed Homo- and Cross-Coupling Reactions

The role of gold as the organizing metal in homo- and cross-coupling reactions is explored in this paper combining DFT calculations with QTAIM, NBO, and the energetic span model analysis. For the gold­(III) complex 7, a key intermediate in the experimental oxidative coupling scheme by Zhang et al., we describe the mechanisms corresponding to a cross-coupling after transmetalation with boron compounds and to a homocoupling after transmetalation with the original gold­(I) complex 6, a new example of dual role of this metal in homogeneous catalysis. We predict for the first path a two-step transmetalation with a low energy rate-limiting step characterized by a four-center transition structure, where fluorine plays an essential role, followed by a reductive elimination where the C–C bond formation is coupled to the departure of fluorine from the gold center. The homocoupling path follows a similar mechanism, with a two-step transmetalation with interesting changes in bonding around the Au­(I) center and a rate-limiting reductive elimination. Our findings on the competition between mechanisms, and the effect of ligands and solvent, agree with the experimental results and provide new insights into the mechanism of gold-catalyzed cross-coupling reactions

Computational Study of Gold-Catalyzed Homo- and Cross-Coupling Reactions

The role of gold as the organizing metal in homo- and cross-coupling reactions is explored in this paper combining DFT calculations with QTAIM, NBO, and the energetic span model analysis. For the gold­(III) complex 7, a key intermediate in the experimental oxidative coupling scheme by Zhang et al., we describe the mechanisms corresponding to a cross-coupling after transmetalation with boron compounds and to a homocoupling after transmetalation with the original gold­(I) complex 6, a new example of dual role of this metal in homogeneous catalysis. We predict for the first path a two-step transmetalation with a low energy rate-limiting step characterized by a four-center transition structure, where fluorine plays an essential role, followed by a reductive elimination where the C–C bond formation is coupled to the departure of fluorine from the gold center. The homocoupling path follows a similar mechanism, with a two-step transmetalation with interesting changes in bonding around the Au­(I) center and a rate-limiting reductive elimination. Our findings on the competition between mechanisms, and the effect of ligands and solvent, agree with the experimental results and provide new insights into the mechanism of gold-catalyzed cross-coupling reactions

Lennard-Jones Intermolecular Potentials for the Description of 6‑Membered Aromatic Heterocycles Interacting with the Isoelectronic CO₂ and CS₂

We have generated Lennard-Jones potentials for the interaction between CX2 (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 CO2 and the main heterocycle in the ring in a parallel orientation, whereas the preferred interaction mode of CS2 is established between sulfur and the π density of the aromatic ring. The fact that the preferences for interaction sites and orientations of CO2 and CS2 are most of the times opposite helps in terms of ensuring the selectivity of these systems in front of these two isoelectronic compounds. The existence of very good linear correlations (R2 values very close to one) between the number of nitrogen atoms in the heterocyclic ring and the depth of the interaction potential wells opens the door to the use of these results in generating coarse-grained potentials or models with predictive power for use in the design of larger systems

On the Memory of Chirality in Gold(I)-Catalyzed Intramolecular Carboalkoxylation of Alkynes

A computational study of the mechanism of the intramolecular carboalkoxylation of alkynes reported by Toste et al. allows the characterization of the chirality transfer process that makes this reaction enantioselective. Memory of chirality is preserved up until the stereocenter-generating iso-Nazarov cyclization through the synergy between the helicity of a pentadienyl cation intermediate and the control in the conformation of the allyl group, both elements defined upon alkoxy migration. The high barriers to conformational scrambling relative to those corresponding to chemical steps ensure the robustness of the chirality transfer mechanism and result in an unusual importance of conformational changes in reactivity that seems to be common in gold-catalyzed transformations

Sulfoxide-Induced Stereoselection in [1,5]-Sigmatropic Hydrogen Shifts of Vinylallenes. A Computational Study

The sulfoxide-induced preference for a migrating trajectory in the vinylallene [1,5]-H sigmatropic shift (resulting in stereodefined trienes in the conceptual equivalent of torquoselectivity in electrocyclizations), originally reported by Okamura, has been computationally studied at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31++G(d,p) level. The face selectivity this group induces in the [1,5]-H shift is enhanced by bulky geminal substituents and is not reproduced by any of the other (more than 20) substituents tested. Analysis of transition-state geometries or charges and evaluation of steric effects did not show any correlation with the preferences. The origin of this selectivity is thought to lie in a secondary orbital interaction (SOI) involving the termini of the pericyclic array and the sulfinyl group which is only observed for this substituent. This secondary orbital interaction, arising from the favorable energies of the orbitals involved, is enhanced in the transition structure due to a better orbital overlap (πC2-C3 → ), which correlates with a πC2-C3 → SOI, which is more important in the transition structure, that weakens the C−H bond, thus lowering the energy of the corresponding transition structure

Characterization of the Switch in the Mechanism of an Intramolecular Diels−Alder Reaction

Changing the dienophile moiety of an intramolecular Diels−Alder (IMDA) cycloaddition from an allyl ether to an allenyl ether can dramatically change the regioselectivity. We hereby show by density functional theory computations that such unprecedented divergence is produced by an underlying change in the mechanism of the reaction. The allyl ether yields a fused tetrahydrofuran through a classical Diels−Alder reaction, whereas the allenyl ether yields a (methylidene)tetrahydropyran through a stepwise process. The latter reaction involves an extreme asynchronism in the bond-forming events with a diradicaloid intermediate that is stabilized by conjugation and synergistic (captodative) effects. Comparison with intermolecular model D−A reactions, which are concerted processes with various degrees of asynchrony, helps explain the change in regioselectivity for the IMDA reaction of allyl systems and the shift in mechanism for the IMDA reaction of the allenyl derivatives studied

Computational Study and Analysis of the Kinetic Isotope Effects of the Rearrangement of <i>cis</i>-Bicyclo[4.2.0]oct-7-ene to <i>cis,cis</i>-Cycloocta-1,3-diene

On the basis of KIE experiments, the ring opening of cis-bicyclo[4.2.0.]oct-7-ene has been suggested as an anti-Woodward−Hoffmann reaction candidate. We hereby report the results of a high-level computational study of the alternate reaction pathways which proves that the energy profiles show a clear preference for the conrotatory (W−H allowed) ring opening followed by double-bond isomerization. Computed KIE values for the aforementioned mechanism are in good agreement with the experimental values

Electrocyclic Ring Opening of Charged <i>cis</i>-Bicyclo[3.2.0]heptadiene and Heterocyclic Derivatives. The Anti-Woodward−Hoffmann Quest (II)

The ring opening reactions of fused cyclobutenes have been the subject of mechanistic debate for decades. Some reports have been published recently suggesting that, in some heterocyclic derivatives, the disrotatory anti-Woodward−Hoffmann mechanism might be responsible for the ring opening. We hereby show that the conrotatory pathway is still the lowest energy alternative for all cases examined, including push−pull substituted 2-thia-4-azabicyclo[3.2.0]hepta-3,6-dienes. Actually, we found that the disrotatory transition state exchanges roles with a double-bond isomerization depending on the substituents around the bicyclic structure

Associative Transmetalation in the Stille Cross-Coupling Reaction to Form Dienes: Theoretical Insights into the Open Pathway

The open transmetalation mechanism for the Stille cross-coupling of vinylbromide and vinyl triflate with trimethylvinylstannane catalyzed by Pd(PMe3)2 as well as the roles of a coordinating solvent molecule (DMF) and additive (LiCl) have been theoretically studied using density functional theory (DFT). The cyclic mechanism seems to be favored for vinyl bromides. In contrast, the open alternative is likely followed by triflates. An oxidative addition mechanism involving a rearrangement of the triflate group on the Pd(PMe3)2(η2-vinyl triflate) complex has been characterized. The open transmetalation pathway for vinyl triflate involves the more electrophilic palladium species generated by the substitution of the triflate by a ligand Y (PMe3, DMF) on the oxidative addition intermediate. Moreover, LiCl as additive is shown to favor the oxidative addition step of triflates by forming an anionic trivalent species, [Pd(PMe3)2Cl]−. The square-planar trans-[Pd(PMe3)2(vinyl)Cl] complex generated by reaction with vinyl triflate corresponds formally to the product of direct oxidative addition of vinyl chloride to Pd(PMe3)2, which then would follow the cyclic transmetalation pathway

Allenyl Azide Cycloaddition Chemistry: Exploration of the Scope and Mechanism of Cyclopentennelated Dihydropyrrole Synthesis through Azatrimethylenemethane Intermediates

Detailed studies of the thermal conversion of 1-azidohepta-3,4,6-trienes into cyclopentennelated dihydropyrroles are presented. High levels of diastereoselectivity and regioselectivity are documented. A mechanistic proposal that accounts for all of the diverse results is developed through the use of density functional calculations. These calculations provide support for the intervention of unexpected mechanistic subtleties, such as the planarity of an azatrimethylenemethane diyl intermediate and an apparent Woodward−Hoffmann-type electrocyclization of a five-atom diyl array