An efficient one-pot synthesis of carbazole fused benzoquinolines and pyridocarbazoles

Cobalt­(II), in the presence of acetate and nitrate, quantitatively adds to the manganese–cobalt oxido cubane Mn^IVCo^III₃O₄(OAc)₅(py)₃ (<b>1</b>) to furnish the pentametallic dangler complex Mn^IVCo^III₃Co^IIO₄(OAc)₆(NO₃)­(py)₃ (<b>2</b>). Complex <b>2</b> is structurally reminiscent of photosystem II’s oxygen-evolving center, and is a rare example of a transition-metal “dangler” complex. Superconducting quantum interference device magnetometry and density functional theory calculations characterize <b>2</b> as having an <i>S</i> = 0 ground state arising from antiferromagnetic coupling between the Co^II and Mn^IV ions. At higher temperatures, an uncoupled state dominates. The voltammogram of <b>2</b> has four electrochemical events, two more than that of its parent cubane <b>1</b>, suggesting that addition of the dangler increases available redox states. Structural, electrochemical, and magnetic comparisons of complexes <b>1</b> and <b>2</b> allow a better understanding of the dangler’s influence on a cubane

Synthetic and Computational Studies on the Rhodium-Catalyzed Hydroamination of Aminoalkenes

The influence of ligand structure on rhodium-catalyzed hydroamination has been evaluated for a series of phosphinoarene ligands. These catalysts have been evaluated in a set of catalytic intramolecular Markovnikov hydroamination reactions. The mechanism of hydroamination catalyzed by the rhodium­(I) complexes in this study was examined computationally, and the turnover-limiting step was elucidated. These computational studies were extended to a series of theoretical hydroamination catalysts to compare the electronic effects of the ancillary ligand substituents. The relative energies of intermediates and transition states were compared to those of intermediates in the reaction catalyzed by the unsubstituted catalyst. The experimental difference in the reactivities of electron-rich and electron-poor catalysts was compared to the computational results, and it was found that the activity for the electron-poor catalysts predicted from the reaction barriers was overestimated. Thus, the analysis of the catalysts in this study was expanded to include the binding preference of each ligand, in comparison to that of the unsubstituted ligand. This information accounts for the disparity between observed reactivity and the calculated overall reaction barrier for electron-poor ligands. The ligand-binding preferences for new ligand structures were calculated, and ligands that were predicted to bind strongly to rhodium generated catalysts for the experimental catalytic reactions that were more reactive than those predicted to bind more weakly

Quantum chemical modeling of the reaction path of chorismate mutase based on the experimental substrate/product complex

Chorismate mutase is a well‐known model enzyme, catalyzing the Claisen rearrangement of chorismate to prephenate. Recent high‐resolution crystal structures along the reaction coordinate of this enzyme enabled computational analyses at unprecedented detail. Using quantum chemical simulations, we investigated how the catalytic reaction mechanism is affected by electrostatic and hydrogen‐bond interactions. Our calculations showed that the transition state (TS) was mainly stabilized electrostatically, with Arg90 playing the leading role. The effect was augmented by selective hydrogen‐bond formation to the TS in the wild‐type enzyme, facilitated by a small‐scale local induced fit. We further identified a previously underappreciated water molecule, which separates the negative charges during the reaction. The analysis includes the wild‐type enzyme and a non‐natural enzyme variant, where the catalytic arginine was replaced with an isosteric citrulline residue

Understanding Precatalyst Activation in Cross-Coupling Reactions: Alcohol Facilitated Reduction from Pd(II) to Pd(0) in Precatalysts of the Type (η³‑allyl)Pd(L)(Cl) and (η³‑indenyl)Pd(L)(Cl)

Complexes of the type (η³-allyl)­Pd­(L)­(Cl) (L = PR₃ or NHC), have been used extensively as precatalysts for cross-coupling and related reactions, with systems containing substituents in the 1-position of the η³-allyl ligand, such as (η³-cinnamyl)­Pd­(L)­(Cl), giving the highest activity. Recently, we reported a new precatalyst scaffold based on an η³-indenyl ligand, (η³-indenyl)­Pd­(L)­(Cl), which typically provides higher activity than even η³-cinnamyl supported systems. In particular, precatalysts of the type (η³-1-^tBu-indenyl)­Pd­(L)­(Cl) give the highest activity. In cross-coupling reactions using this type of Pd­(II) precatalyst, it is proposed that the active species is monoligated Pd(0), and the rate of reduction to Pd(0) is crucial. Here, we describe detailed experimental and computational studies which explore the pathway by which the Pd­(II) complexes (η³-allyl)­Pd­(IPr)­(Cl) (IPr = 1,3-bis­(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene), (η³-cinnamyl)­Pd­(IPr)­(Cl), (η³-indenyl)­Pd­(IPr)­(Cl) and (η³-1-^tBu-indenyl)­Pd­(IPr)­(Cl) are reduced to Pd(0) in alcoholic solvents, which are commonly used in Suzuki–Miyaura and α-arylation reactions. The rates of reduction for the different precatalysts are compared and we observe significant variability based on the exact reaction conditions. However, in general, η³-indenyl systems are reduced faster than η³-allyl systems, and DFT calculations show that this is in part due to the ability of the indenyl ligand to undergo facile ring slippage. Our results are consistent with the η³-indenyl systems giving increased catalytic activity and provide fundamental information about how to design systems that will rapidly generate monoligated Pd(0) in the presence of alcohols

DFT Investigation of Suzuki–Miyaura Reactions with Aryl Sulfamates Using a Dialkylbiarylphosphine-Ligated Palladium Catalyst

Aryl sulfamates are valuable electrophiles for cross-coupling reactions because they can easily be synthesized from phenols and can act as directing groups for C–H bond functionalization prior to cross-coupling. Recently, it was demonstrated that (1-^tBu-Indenyl)­Pd­(XPhos)­Cl (XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) is a highly active precatalyst for room-temperature Suzuki–Miyaura couplings of a variety of aryl sulfamates. Herein, we report an in-depth computational investigation into the mechanism of Suzuki–Miyaura reactions with aryl sulfamates using an XPhos-ligated palladium catalyst. Particular emphasis is placed on the turnover-limiting oxidative addition of the aryl sulfamate C–O bond, which has not been studied in detail previously. We show that bidentate coordination of the XPhos ligand via an additional interaction between the biaryl ring and palladium plays a key role in lowering the barrier to oxidative addition. This result is supported by NBO and NCI-Plot analysis on the transition states for oxidative addition. After oxidative addition, the catalytic cycle is completed by transmetalation and reductive elimination, which are both calculated to be facile processes. Our computational findings explain a number of experimental results, including why elevated temperatures are required for the coupling of phenyl sulfamates without electron-withdrawing groups and why aryl carbamate electrophiles are not reactive with this catalyst

Cp* Iridium Precatalysts for Selective C–H Oxidation via Direct Oxygen Insertion: A Joint Experimental/Computational Study

A series of Cp*Ir complexes are active precatalysts in C–H oxidation of <i>cis</i>-decalin, cyclooctane, 1-acetylpyrrolidine, tetrahydrofurans, and γ-lactones. Moderate to high yields were achieved, and surprisingly, high selectivity for mono-oxidation of cyclooctane to cyclooctanone was observed. Kinetic isotope effect experiments in the C–H oxidation of ethylbenezene to acetophenone yield <i>k</i>_H/<i>k</i>_D = 15.4 ± 0.8 at 23 °C and 17.8 ± 1.2 at 0 °C, which are consistent with C–H oxidation being the rate-limiting step with a significant tunneling contribution. The nature of the active species was investigated by TEM, UV–vis, microfiltration, and control experiments. DFT calculations showed that the C–H oxidation of <i>cis</i>-decalin by Cp*Ir­(ppy)­(Cl) (ppy = <i>o</i>-phenylpyridine) follows a direct oxygen insertion mechanism on the singlet potential energy surface, rather than the radical rebound route that would be seen for the triplet, in good agreement with the retention of stereochemistry observed in this reaction

Insight into the Efficiency of Cinnamyl-Supported Precatalysts for the Suzuki–Miyaura Reaction: Observation of Pd(I) Dimers with Bridging Allyl Ligands During Catalysis

Despite widespread use of complexes of the type Pd­(L)­(η³-allyl)Cl as precatalysts for cross-coupling, the chemistry of related Pd^I dimers of the form (μ-allyl)­(μ-Cl)­Pd₂(L)₂ has been underexplored. Here, the relationship between the monomeric and the dimeric compounds is investigated using both experiment and theory. We report an efficient synthesis of the Pd^I dimers (μ-allyl)­(μ-Cl)­Pd₂(IPr)₂ (allyl = allyl, crotyl, cinnamyl; IPr = 1,3-bis­(2,6-diisopropylphenyl)­imidazol-2-ylidene) through activation of Pd­(IPr)­(η³-allyl)Cl type monomers under mildly basic reaction conditions. The catalytic performance of the Pd^II monomers and their Pd^I μ-allyl dimer congeners for the Suzuki–Miyaura reaction is compared. We propose that the (μ-allyl)­(μ-Cl)­Pd₂(IPr)₂-type dimers are activated for catalysis through disproportionation to Pd­(IPr)­(η³-allyl)Cl and monoligated IPr–Pd⁰. The microscopic reverse comproportionation reaction of monomers of the type Pd­(IPr)­(η³-allyl)Cl with IPr–Pd⁰ to form Pd^I dimers is also studied. It is demonstrated that this is a facile process, and Pd^I dimers are directly observed during catalysis in reactions using Pd^II precatalysts. In these catalytic reactions, Pd^I μ-allyl dimer formation is a deleterious process which removes the IPr–Pd⁰ active species from the reaction mixture. However, increased sterics at the 1-position of the allyl ligand in the Pd­(IPr)­(η³-crotyl)Cl and Pd­(IPr)­(η³-cinnamyl)Cl precatalysts results in a larger kinetic barrier to comproportionation, which allows more of the active IPr–Pd⁰ catalyst to enter the catalytic cycle when these substituted precatalysts are used. Furthermore, we have developed reaction conditions for the Suzuki-Miyaura reaction using Pd­(IPr)­(η³-cinnamyl)Cl which are compatible with mild bases

Distortional Effects of Noncovalent Interactions in the Crystal Lattice of a Cp*Ir(III) Acylhydroxamic Acid Complex: A Joint Experimental–Computational Study

[Cp*Ir­(μ-OH)₃IrCp*]­OH reacts with PhCONHOH to give [Cp*Ir­(η²-ONCOPh)], in which the doubly deprotonated −NHOH unit binds side-on via N and O, an otherwise unrecorded binding mode. The X-ray structure shows pyramidalization at Ir together with secondary bonding between the carbonyl oxygen and Ir (<i>d</i>_Ir···O = 2.873(8) Å). The related <i>o</i>-hydroxyphenyl­hydroxamic acid gives a conventional chelate structure in which both sp³ O atoms are bound in deprotonated form. In contrast, PhSO₂NHOH reacts with S–N cleavage to give the nitrosyl, [Cp*Ir­(NO)­(SO₂Ph)]. A detailed computational analysis identifies noncovalent interactions in the crystal lattice (crystal-packing effects) as responsible for the distortion in [Cp*Ir­(η²-ONCOPh)]

Insight into the Efficiency of Cinnamyl-Supported Precatalysts for the Suzuki–Miyaura Reaction: Observation of Pd(I) Dimers with Bridging Allyl Ligands During Catalysis

Despite widespread use of complexes of the type Pd­(L)­(η³-allyl)Cl as precatalysts for cross-coupling, the chemistry of related Pd^I dimers of the form (μ-allyl)­(μ-Cl)­Pd₂(L)₂ has been underexplored. Here, the relationship between the monomeric and the dimeric compounds is investigated using both experiment and theory. We report an efficient synthesis of the Pd^I dimers (μ-allyl)­(μ-Cl)­Pd₂(IPr)₂ (allyl = allyl, crotyl, cinnamyl; IPr = 1,3-bis­(2,6-diisopropylphenyl)­imidazol-2-ylidene) through activation of Pd­(IPr)­(η³-allyl)Cl type monomers under mildly basic reaction conditions. The catalytic performance of the Pd^II monomers and their Pd^I μ-allyl dimer congeners for the Suzuki–Miyaura reaction is compared. We propose that the (μ-allyl)­(μ-Cl)­Pd₂(IPr)₂-type dimers are activated for catalysis through disproportionation to Pd­(IPr)­(η³-allyl)Cl and monoligated IPr–Pd⁰. The microscopic reverse comproportionation reaction of monomers of the type Pd­(IPr)­(η³-allyl)Cl with IPr–Pd⁰ to form Pd^I dimers is also studied. It is demonstrated that this is a facile process, and Pd^I dimers are directly observed during catalysis in reactions using Pd^II precatalysts. In these catalytic reactions, Pd^I μ-allyl dimer formation is a deleterious process which removes the IPr–Pd⁰ active species from the reaction mixture. However, increased sterics at the 1-position of the allyl ligand in the Pd­(IPr)­(η³-crotyl)Cl and Pd­(IPr)­(η³-cinnamyl)Cl precatalysts results in a larger kinetic barrier to comproportionation, which allows more of the active IPr–Pd⁰ catalyst to enter the catalytic cycle when these substituted precatalysts are used. Furthermore, we have developed reaction conditions for the Suzuki-Miyaura reaction using Pd­(IPr)­(η³-cinnamyl)Cl which are compatible with mild bases

Distortional Effects of Noncovalent Interactions in the Crystal Lattice of a Cp*Ir(III) Acylhydroxamic Acid Complex: A Joint Experimental–Computational Study

[Cp*Ir­(μ-OH)₃IrCp*]­OH reacts with PhCONHOH to give [Cp*Ir­(η²-ONCOPh)], in which the doubly deprotonated −NHOH unit binds side-on via N and O, an otherwise unrecorded binding mode. The X-ray structure shows pyramidalization at Ir together with secondary bonding between the carbonyl oxygen and Ir (<i>d</i>_Ir···O = 2.873(8) Å). The related <i>o</i>-hydroxyphenyl­hydroxamic acid gives a conventional chelate structure in which both sp³ O atoms are bound in deprotonated form. In contrast, PhSO₂NHOH reacts with S–N cleavage to give the nitrosyl, [Cp*Ir­(NO)­(SO₂Ph)]. A detailed computational analysis identifies noncovalent interactions in the crystal lattice (crystal-packing effects) as responsible for the distortion in [Cp*Ir­(η²-ONCOPh)]