The concerted metalation-deprotonation mechanism predicts relative reactivity and regioselectivity for a diverse set of arenes spanning the entire spectrum of known palladium-catalyzed direct arylation coupling partners. An analysis following an active strain model provides a more complete portrayal of the important arene/catalyst parameters leading to a successful coupling. The breadth of arenes whose reactivity can be predicted by the CMD mechanism indicates that it may be far more widespread than previously imagined.

Directing groups that can act as internal oxidants have recently been shown to be beneficial in metal-catalyzed heterocycle syntheses that undergo C-H functionalization. Pursuant to the rhodium(III)-catalyzed redox-neutral isoquinolone synthesis that we recently reported, we present in this article the development of a more reactive internal oxidant/directing group that can promote the formation of a wide variety of isoquinolones at room temperature while employing low catalyst loadings (0.5 mol %). In contrast to previously reported oxidative rhodium(III)-catalyzed heterocycle syntheses, the new conditions allow for the first time the use of terminal alkynes. Also, it is shown that the use of alkenes, including ethylene, instead of alkynes leads to the room temperature formation of 3,4-dihydroisoquinolones. Mechanistic investigations of this new system point to a change in the turnover limiting step of the catalytic cycle relative to the previously reported conditions. Concerted metalation-deprotonation (CMD) is now proposed to be the turnover limiting step. In addition, DFT calculations conducted on this system agree with a stepwise C-N bond reductive elimination/N-O bond oxidative addition mechanism to afford the desired heterocycle. Concepts highlighted by the calculations were found to be consistent with experimental results.

Reaction thermodynamics and potential energy surfaces are calculated using density functional theory to investigate the mechanism of the reductive cleavage of the N-O bond by the mu(4)-sulfide-bridged tetranuclear Cu(Z) site of nitrous oxide reductase. The Cu(Z) cluster provides an exogenous ligand-binding site, and, in its fully reduced 4Cu(I) state, the cluster turns off binding of stronger donor ligands while enabling the formation of the Cu(Z)-N(2)O complex through enhanced Cu(Z) --> N(2)O back-donation. The two copper atoms (Cu(I) and Cu(IV)) at the ligand-binding site of the cluster play a crucial role in the enzymatic function, as these atoms are directly involved in bridged N(2)O binding, bending the ligand to a configuration that resembles the transition state (TS) and contributing the two electrons for N(2)O reduction. The other atoms of the Cu(Z) cluster are required for extensive back-bonding with minimal sigma ligand-to-metal donation for the N(2)O activation. The low reaction barrier (18 kcal mol(-)(1)) of the direct cleavage of the N-O bond in the Cu(Z)-N(2)O complex is due to the stabilization of the TS by a strong Cu(IV)(2+)-O(-) bond. Due to the charge transfer from the Cu(Z) cluster to the N(2)O ligand, noncovalent interactions with the protein environment stabilize the polar TS and reduce the activation energy to an extent dependent on the strength of proton donor. After the N-O bond cleavage, the catalytic cycle consists of a sequence of alternating protonation/one-electron reduction steps which return the Cu(Z) cluster to the fully reduced (4Cu(I)) state for future turnover.

A comprehensive understanding of the C-H bond cleavage step by the concerted metalation-deprotonation (CMD) pathway is important in further development of cross-coupling reactions using different catalysts. Distortion-interaction analysis of the C-H bond cleavage over a wide range of (hetero)aromatics has been performed in an attempt to quantify the various contributions to the CMD transition state (TS). The (hetero)aromatics evaluated were divided in different categories to allow an easier understanding of their reactivity and to quantify activation characteristics of different arene substituents. The CMD pathway to the C-H bond cleavage for different classes of arenes is also presented, including the formation of pre-CMD intermediates and the analysis of bonding interactions in TS structures. The effects of remote C2 substituents on the reactivity of thiophenes were evaluated computationally and were corroborated experimentally with competition studies. We show that nucleophilicity of thiophenes, evaluated by Hammett σ(p) parameters, correlates with each of the distortion-interaction parameters. In the final part of this manuscript, we set the initial equations that can assist in the development of predictive guidelines for the functionalization of C-H bonds catalyzed by transition metal catalysts.

Ammonia borane (AB), which has a very high hydrogen content by weight (19.6%), is attracting attention as a means of achieving efficient chemical hydrogen storage.1,2 Heating AB in the solid state, 3 ionic liquids 4 or the presence of acid 5 has been shown to induce the release of >1.0 equiv of H 2 over the course of several hours, and transition metal complexes of Rh, 6 Ni, 7 and Ir 8 have been shown to catalyze H 2 release under mild conditions. Notably, the Ni catalysts described by Baker release up to 2.8 equiv of H 2 , 7 an observation that has prompted a more detailed evaluation of their reaction mechanism.9a When considering strategies for dehydrogenation, AB is often compared to ethane.10 Computational predictions provide little mechanistic support for this analogy, however, 9,11 and in terms of local dipoles and reactivity AB may better be compared to methanol. Drawing from this analogy, we have discovered that ruthenium catalysts, originally developed for alcohol redox processes, 12 will induce the release of 1 equiv of H 2 from AB (up to 1.0 system wt %) within 5 min at room temperature with as little at 0.03 mol% Ru. Furthermore, 2 equiv of H 2 is rapidly released from highly concentrated (11 M) MeAB solutions at 22°C (ambient temperature), providing 3.0 system wt % hydrogen release. We have also found that by using an AB/MeAB mixture at 50°C, up to 3.6 system wt % H 2 can be released with 0.1 mol % Ru.An evaluation of several alcohol oxidation/reduction catalysts provided promising leads with complexes 1 to 6 (Figure 1). 13 In these studies, the precatalysts (0.1 mol%) were activated via treatment with KO t Bu (3 mol%) 13c in THF under inert atmosphere to generate the active ruthenium amide species prior to the addition of AB to the reaction vessel.14 Complexes 1 and 2 are particularly reactive even at 0.03 mol% Ru.14 Optimal outcomes are observed at high [AB] (5.0 M), an important parameter for maximal gravimetric H 2 density. In reactions with AB, we note the formation of an insoluble precipitate, which has been identified as the same polymeric aminoborane species obtained by Goldberg 8 and Manners. 15 The dehydrogenation of methylammonia-borane (MeAB) was also evaluated. 6 Under conditions similar to those employed for AB dehydrogenation, 0.5 mol% 1 induced the release of up to 2.0 equiv of H 2 from MeAB in ∼10 min (Figure 2). 16 These reactions are characterized by a very rapid release of the first equivalent of H 2 (occurring in less than 10 s), generating poly(N-methylaminoborane).15 This is followed by a slower release of the second equivalent over ∼10 min. 17 Since no insoluble precipitate is observed, more concentrated conditions (11 M [MeAB]) may be employed, increasing the system % H 2 to 3% (1.9 equiv of H 2 released). To further maximize the gravimetric H 2 density, AB-MeAB mixtures were evaluated.18 Initial results using a 1:1 AB/MeAB mixture at 50°C indicate that 3.6 system wt % H 2 release can be achieved with 0.1 mol% 1 under solvent-free conditions. 16As a preliminary probe i...