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Compounds with dibenzannelated heterocycles with eight π-electrons are found in a range of applications. These molecules often adopt a bent structure in the ground state (S0 ) but can become planar in the first excited states (S1 and T1 ) because of the cyclically conjugated 4nπ central ring, which fulfils the requirements for excited state aromaticity. We report on a quantum chemical investigation of the aromatic character in the S1 and T1 states of dibenzannelated seven- and six-membered heterocycles with one, two, or three heteroatoms in the 8π-electron ring. These states could have ππ* or nπ* character. We find that compounds with one or two heteroatoms in the central ring have ππ* states as their S1 and T1 states. They are to a significant degree influenced by excited state aromaticity, and their optimal structures are planar or nearly planar. Among the heteroatoms, nitrogen provides for the strongest excited state aromaticity whereas oxygen provides for the weakest, following the established trend of the S0 state. Yet, dibenzannelated seven-membered-ring compounds with N=N bonds have non-aromatic nπ* states with strongly puckered structures as their S1 and T1 states.

Summary Haloaromatic drug molecules of the amiloride family are plagued by photodegradation with associated toxicity. Herein, we report on the photodegradation of analogs of amiloride, which are known to undergo photosubstitution in water. Model compounds built on the same scaffold undergo clean photosubstitution also in alcoholic solvent, where a certain amount of photodehalogenation is normally expected. Available evidence points to a mechanism starting with photoexcitation followed by photoionization to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment, as well as to a class of increasingly popular synthetic photoredox methods.

Summary Efficient functionalization of C−H bonds can be achieved using transition metal catalysts, such as Pd(OAc)2. To better control the regioselectivity in these reactions, some functional groups on the substrate may be used as directing groups, guiding the reactivity to an ortho position. Herein, we describe a methodology to score the relative strength of such directing groups in palladium-catalyzed aromatic C−H activation. The results have been collected into a scale that serves to predict the regioselectivity on molecules with multiple competing directing groups. We demonstrate that this scale yields accurate predictions on over a hundred examples, taken from the literature. In addition to the regioselectivity prediction on complex molecules, the knowledge of the relative strengths of directing groups can also be used to work with new combinations of functionalities, exploring uncharted chemical space., Graphical Abstract, Highlights • Directing group strength for ortho-palladation can be predicted quantum chemically • Correlation with fragments allow regioselectivity predictions in complex molecules • Directing strength is enhanced by deprotonation under the reaction conditions • Palladation in between two directing groups is disfavored sterically; no synergy, Catalysis; Computational Molecular Modelling; Organic Reaction

The mechanism for the iridium-catalyzed asymmetric hydrogenation of prochiral imines has been investigated for an experimentally relevant ligand substrate combination using DFT calculations. The possible stereoisomers of the stereodetermining hydride transfer transition state were considered for four possible hydrogenation mechanisms starting from the recently disclosed active catalyst consisting of iridium phosphine-oxazoline with cyclometalated imine substrate. The hydrogenation was found to proceed via an outer sphere pathway. The transition state accurately describes the experimental observations of the active catalyst and provides a structural rationale for the high stereoinduction despite the lack of direct interaction points in the outer-sphere mechanism. The predicted enantioselectivity was consistent with experimental observations. Experimental studies support the hypothesis that the iridacycle forms spontaneously and functions as the active catalyst in the hydrogenation.

Under optimised conditions, the Trost modular ligand (TML) series induces high levels of asymmetric induction in an extraordinarily wide range of reactions involving palladium π-allyl intermediates. Prior mechanistic investigations into reactions involving Pd-η3-C6H9 intermediates have focussed on the monomeric 13-membered ring formed via P,P-chelation of the ligand to Pd. However, it is also recognised that ring-opening oligomerisation provides a pool of high nuclearity Pd-η3-C6H9 species that, by affording a low level, or even the opposite sense, of asymmetric induction relative to the mononuclear species, are responsible for a reduction in selectivity under non-optimised conditions. Herein we describe an investigation by NMR spectroscopy, molecular mechanics, molecular dynamics, and small-angle neutron scattering (SANS), of a Pd-η3-C6H9 cation bearing the 1,2-diaminocyclohexane TML ligand (2). Using both nondeuterated and perdeuterated (D47) isotopologues of the resulting complexes, we show that a two-stage oligomerisation-aggregation process forms self assembled cylindrical aggregates of very high nuclearity (up to 56 Pd centres). We also investigate how concentration, solvent and counter-anion all modulate the extent of oligomerisation.

η3-Allyl palladium complexes are key intermediates in Tsuji–Trost allylic substitution reactions. It is well known that (η3-1-aryl-3-alkyl substituted allyl)Pd intermediates result in nucleophilic attack at the alkyl substituted terminus. In contrast, the chemistry of (η3-1,2,3-trisubstituted allyl)Pd intermediates is relatively unexplored. Herein we probe the regioselectivity with 1,2,3-trisubstituted allylic substrates in Tsuji–Trost allylic substitution reactions. DFT investigation of cationic (η3-1-Ph-2-B(pin)-3-alkyl-allyl)Pd(PPh3)2 intermediates predict that nucleophilic attack should occur preferentially on anti-allyls rather than the syn-isomers to generate benzylic substitution products under Curtin–Hammett conditions. Experimentally, systematic studies with 1,2,3-trisubstituted allylic substrates revealed that a Linear Free Energy Relationship (LFER) is observed when Charton steric parameters of the C-2 substituents are plotted against the log of the ratio of regioisomers. Bulkier C-2 substituents in 1,2,3-trisubstituted η3-allyl palladium intermediates provide stronger preference for nucleophilic attack at anti-oriented benzylic termini. Additionally, the geometry of 1,4-elimination products supports the presence of anti-allyl palladium intermediates.

A new efficient protocol for the nickel-catalyzed Heck reaction of aryl triflates with vinyl ethers is presented. Mild reaction conditions that equal those of the corresponding palladium-catalyzed Heck reaction are applied, representing a practical and more sustainable alternative to the conventional regioselective arylation of vinyl ethers. A catalytic system comprised of Ni(COD)2 and 1,1′-bis(diphenylphosphino)ferrocene (DPPF) in combination with the tertiary amine Cy2NMe proved effective in the olefination of a wide range of aryl triflates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination and base promoted catalyst regeneration. Although these elementary reactions are normally considered challenging, DFT calculations suggested this pathway to be favorable under the applied reaction conditions.

The formation of an atypical, saturated, diarylated, Heck/Suzuki, domino product produced under oxidative Heck reaction conditions, employing arylboronic acids and a chelating vinyl ether, has been investigated by DFT calculations. The calculations highlight the crucial role of 1,4-benzoquinone (BQ) in the reaction. In addition to its role as an oxidant of palladium, which is necessary to complete the catalytic cycle, this electron-deficient alkene opens up a low-energy reaction pathway from the post-insertion σ-alkyl complex. The association of BQ lowers the free-energy barrier for transmetallation of the σ-alkyl complex to create a pathway that is energetically lower than the oxidative Heck reaction pathway. Furthermore, the calculations showed that the reaction is made viable by BQ-mediated reductive elimination and leads to the saturated diarylated product.

The mechanism of the recently developed palladium-catalyzed ene-yne coupling has been evaluated by DFT methods. The calculations validate the previously proposed reaction mechanism and explain the stereoselectivity of the reaction (exclusive formation of the E isomer of the disubstituted alkene). Concerning chemoselectivity, the calculations also clarify why the ene-yne coupling is able to dominate over plausible alternative reaction pathways such as alkene homocoupling and alkyne polymerization. The role of the phosphine ligand at various stages of the catalytic cycle has also been delineated.

International audience; DFT calculations at the B3P86/6-31G** level have been carried out to derive the bond dissociation energies (BDE) and free energies for a number of R−X systems (X = Cl, Br, I, N3, and S2CNMe2) that have been or can potentially be used as initiators for atom transfer radical polymerization (ATRP). For selected systems, a conformational search was carried out for R−X and R by using semiempirical (PM3) and molecular mechanics (MM+ augmented with appropriately optimized parameters for the radical systems) methods. The MM+ technique is more suited to search for the most stable conformations. The computed energies are in good agreement with the experimentally available BDEs and reveal a small weakening effect caused by the substitution of an α-H atom with a CH3 group. The free energies are used to derive the relative equilibrium constant for the ATRP activation/deactivation process. These are compared with the equilibrium constants that have been determined from ATRP polymerization rates and from model studies of activation−deactivation−termination processes in the absence of monomer. These comparisons reveal the effectiveness of the DFT-computed BDEs for predicting polymerization rates for new monomers in ATRP processes.