Mechanism and origins of cobalt-catalyzed ligand-controlled regiodivergent C-H functionalization of aldehydes with enynes.

The influence of the P-M-P bite angle in diphosphine ligands on selectivity has been observed in various catalytic reactions. A better understanding of the ligand bite angle concept is important for the rational design of efficient catalytic systems. In the present work, the mechanism of cobalt-catalyzed C-H functionalization of aldehydes with enynes and how the diphosphine ligands alter regioselectivity were investigated by density functional theory (DFT) calculations. The catalytic cycle is initiated by the oxidative cyclization of enynes rather than the oxidative addition of aldehydes. Regioselectivity arises from competing σ-bond metathesis and migratory insertion steps, in which the steric effects of diphosphine ligands are the dominant factors influencing the activation barriers. The calculations indicate that σ-bond metathesis is more challenging and its feasibility is highly dependent on the ligand bite angle. The improved mechanistic understanding will enable further design of transition-metal-catalyzed selective cyclization reactions.

Cobalt-catalyzed radical-mediated carbon-carbon scission via a radical-type migratory insertion.

Migratory insertions of alkenes into metal-carbon (M-C) bonds are elementary steps in diverse catalytic processes. In the present work, a radical-type migratory insertion that involves concerted but asynchronous M-C homolysis and radical attack was revealed by computations. Inspired by the radical nature of the proposed migratory insertion, a distinct cobalt-catalyzed radical-mediated carbon-carbon (C-C) cleavage mechanism was proposed for alkylidenecyclopropanes (ACPs). This unique C-C activation is key to rationalizing the experimentally observed selectivity for the coupling between benzamides and ACPs. Furthermore, the C(sp2)-H activation in the coupling reaction occurs via the proton-coupled electron transfer (PCET) mechanism rather than the originally proposed concerted metalation-deprotonation (CMD) pathway. The ring opening strategy may stimulate further development and discovery of novel radical transformations.

Exploration of Ligand-Centered Hydride Transfer in La/Y-Catalyzed Deoxygenative Reduction of Tertiary Amides with Pinacolborane.

A number of rare-earth metals and actinides have proven to be active in a wide variety of atom-efficient transformations. As compared to the related organometallic catalysts, the detailed mechanisms for the rare-earth metal-catalyzed reactions remain largely unexplored. Herein, the detailed catalyst activation process and reaction mechanisms of deoxygenative reduction of amides with pinacolborane (HBpin) catalyzed by Y[N(TMS)2]3 and La[N(TMS)2]3 complexes as well as a La4(O)acac10 cluster are investigated by density functional theory calculations. The M(III)-hemiaminal complex is disclosed to be the active catalyst for both the complexes and the cluster. During catalyst activation for both the Y and La complexes, the H-B bond polarity results in the formation of a transient M(III)-hydride intermediate, which is converted into an on-cycle M(III)-hemiaminal complex via facile migratory insertion. However, this kind of La(III)-hydride species cannot be formed for the La cluster. Starting from the M(III)-hemiaminal complex, the reaction proceeds via the ligand-centered hydride transfer mechanism that involves B-O bond formation, hydride transfer to B, C-O cleavage within the hemiaminal borane, hydride transfer to C, and σ-bond metathesis. The additional HBpin molecule is vital for the first hydride transfer that leads to the formation of [H2Bpin]- species. Our calculations reveal several important cooperative effects of the HBpin component during the hydride transfer processes. The improved mechanistic insights will be helpful for further development of selective C═O reduction.

Origins of Stereospecificity and Divergent Reactivity of Pd-Catalyzed Cross Coupling with α,α-Disubstituted Alkenyl Hydrazones.

This article presents an exploration of stereospecificity and divergent reactivity of Pd-catalyzed α,α-disubstituted alkenyl hydrazones to synthesize 1,4-dienes in the Z configuration and vinylcyclopropane. We calculated the energy profiles of four α,α-disubstituted alkenyl hydrazones. The results show that the energy profiles of the whole catalytic cycle are basically the same before the syn-carbopalladation step. Subsequent syn-ß-C elimination yields skipping dienes, or direct ß-H elimination yields vinylcyclopropane. Current theoretical calculations reveal that the stereospecificity and the divergent reactivity of reactions result from the competition between syn-ß-C elimination and ß-H elimination. The C-C bond rotation and subsequent syn-ß-C elimination step control the stereospecificity of the reaction by changing the olefin stereostructure from E to Z configuration. The steric factor of α-substituted groups mediates the transformation between syn-ß-C elimination and ß-H elimination. The results are of great significance for the scientific design of substrates to achieve accurate synthesis of target products.

A Computational Mechanistic Study of Cp*Co(III)-Catalyzed Three-Component C-H Bond Addition to Terpenes and Formaldehydes: Insights into the Origins of Regioselectivity.

Transition metal-catalyzed three-component reactions of arenes, dienes, and carbonyls enable the convergent synthesis of homoallylic alcohols. Controlling regioselectivity is a central challenge for the difunctionalization of substituted 1,3-dienes in which multiple unbiased C═C bonds exist. Here, the mechanisms of Cp*Co(III)-catalyzed three-component C-H bond addition to terpenes and formaldehydes were investigated by density functional theory calculations. The reaction proceeds via sequential C(sp2)-H activation, migratory insertion, ß-hydride elimination, hydride reinsertion, and C-C bond formation to yield the final product. The migratory insertion is the rate- and regioselectivity-determining step of the overall reaction. We employed an energy decomposition approach to quantitatively dissect the contributions of different types of interactions to regioselectivity. For the 2-alkyl substituted 1,3-dienes, the orbital interactions in the 3,4-insertion are intrinsically more favorable as compared to that in the 4,3-insertion, while the stronger steric effects between metallacycle and 1,3-diene override the intrinsic electronic preference. However, the steric effects failed to rationalize the unfavorable 1,2-insertion that is analogous to 4,3-insertion and even bears smaller steric effects. The donor-acceptor interaction analysis indicates that orbital interactions between σCo-C and πC═C decreased significantly in the 1,2-insertion transition state, which leads to higher activation energy barriers. These insights into the dominant effects controlling regioselectivity will enable rational design of new catalysts for selective functionalization of dienes.

Understanding the unique reactivity patterns of nickel/JoSPOphos manifold in the nickel-catalyzed enantioselective C-H cyclization of imidazoles.

The 3d transition metal-catalyzed enantioselective C-H functionalization provides a sustainable strategy for the construction of chiral molecules. A better understanding of the catalytic nature of the reactions and the factors controlling the enantioselectivity is important for rational design of more efficient systems. Herein, the mechanisms of Ni-catalyzed enantioselective C-H cyclization of imidazoles are investigated by density functional theory (DFT) calculations. Both the π-allyl nickel(ii)-promoted σ-complex-assisted metathesis (σ-CAM) and the nickel(0)-catalyzed oxidative addition (OA) mechanisms are disfavored. In addition to the typically proposed ligand-to-ligand hydrogen transfer (LLHT) mechanism, the reaction can also proceed via an unconventional σ-CAM mechanism that involves hydrogen transfer from the JoSPOphos ligand to the alkene through P-H oxidative addition/migratory insertion, C(sp2)-H activation via σ-CAM, and C-C reductive elimination. Importantly, computational results based on this new mechanism can indeed reproduce the experimentally observed enantioselectivities. Further, the catalytic activity of the π-allyl nickel(ii) complex can be rationalized by the regeneration of the active nickel(0) catalyst via a stepwise hydrogen transfer, which was confirmed by experimental studies. The calculations reveal several significant roles of the secondary phosphine oxide (SPO) unit in JoSPOphos during the reaction. The improved mechanistic understanding will enable design of novel enantioselective C-H transformations.

Mechanism and origins of ligand-controlled Pd(ii)-catalyzed regiodivergent carbonylation of alkynes.

Transition-metal-catalyzed carbonylation provides a useful approach to synthesize carbonyl-containing compounds and their derivatives. Controlling the regio-, chemo-, and stereoselectivity remains a significant challenge and is the key to the success of transformation. In the present study, we explored the mechanism and origins of the ligand-controlled regiodivergent carbonylation of alkynes with competitive nucleophilic amino and hydroxy groups by density functional theory (DFT) calculations. The proposed mechanism involves O(N)-cyclization, CO insertion, N-H(O-H) cleavage, C-N(C-O) reductive elimination and regeneration of the catalyst. The chemoselectivity is determined by cyclization. Instead of the originally proposed switch of competitive coordination sites, a new type of concerted deprotonation/cyclization model was proposed to rationalize the ligand-tuned chemoselectivity. The electron-deficient nitrogen-containing ligand promotes the flow of electrons during cyclization, and so it favors the O-cyclization/N-carbonylation pathway. However, sterically bulky and electron-rich phosphine controls the selectivity by a combination of electronic and steric effects. The improved mechanistic understanding will enable further design of selective transition-metal-catalyzed carbonylation.

A Computational Mechanistic Study of Pd(II)-Catalyzed Enantioselective C(sp3)-H Borylation: Roles of APAO Ligands.

A computational mechanistic study has been performed on Pd(II)-catalyzed enantioselective reactions involving acetyl-protected aminomethyl oxazolines (APAO) ligands that significantly improved reactivity and selectivity in C(sp3)-H borylation. The results support a mechanism including initiation of C(sp3)-H bond activation generating a five-membered palladacycle and ligand exchange, followed by HPO42--promoted transmetalation. These resulting Pd(II) complexes further undergo sequential reductive elimination by coordination of APAO ligands and protonation to afford the enantiomeric products and deliver Pd(0) complexes, which will then proceed by oxidation and deprotonation to regenerate the catalyst. The C(sp3)-H activation is found to be the rate- and enantioselectivity-determining step, in which the APAO ligand acts as the proton acceptor to form the two enantioselectivity models. The results demonstrate that the diverse APAO ligands control the enantioselectivity by differentiating the distortion and interaction between the major and minor pathways.

Polarizable force field parameterization and theoretical simulations of ThCl4 -LiCl molten salts.

Recycle of thorium is an essential process in the thorium-uranium closed fuel cycle of molten salt reactor (MSR). Pyrochemical treatment of spent nuclear fuel using chloride molten salts as medium has been considered as a promising method. In this article, we performed molecular dynamics simulations on the ThCl4 LiCl molten salts using a polarizable force field parameterized by us from first-principles calculations. The microscopic structures and macroscopic properties at different compositions were investigated using the developed force field to understand the structure/property relationship in the mixture. The differences between ThCl4 LiCl and ThF4 LiF MSs are compared to understand the behaviors of Th4+ in the fluoride-chloride mixed media. In the molten fluorides, the coordination number of Th4+ is larger, and the resulting more shared anions lead to lower ThF dissociation barrier and shorter lifetime of the Th4+ first solvation shell. Our results also indicate the Pauling's structural rules for crystals can be used to rationalize the local structures in molten salts. © 2018 Wiley Periodicals, Inc.

Mechanistic Exploration of Cp*CoIII/RhIII-Catalyzed Carboamination/Olefination of N-Phenoxyacetamides with Alkenes.

A computational study of Cp*CoIII/RhIII-catalyzed carboamination/olefination of N-phenoxyacetamides with alkenes was carried out to elucidate the catalyst-controlled chemoselectivity. The reaction of the two catalysts shares a similar process that involves N-H and C-H activation as well as alkene insertion. Then the reaction bifurcates at the generated seven-membered metallacycle. For Cp*CoIII catalyst, the resulting metallacycle undergoes oxidation addition, reductive elimination, and protonation to yield the carboamination product exclusively. However, the Cp*RhIII catalyst could promote the subsequent olefination pathway via sequential ß-H elimination, reductive elimination, oxidation addition, and protonation, which enables the experimentally observed mixtures of both carboamination and olefination products. Our results uncover that the higher propensity for the ß-H-elimination of the Cp*RhIII than the Cp*CoIII catalyst in the olefination pathway could be responsible for the different selectivity and reactivity of the two catalysts.

A computational mechanistic study of Pd(ii)-catalyzed γ-C(sp3)-H olefination/cyclization of amines: the roles of bicarbonate and ligand effect.

The detailed mechanism of palladium-catalyzed γ-C(sp3)-H olefination/cyclization of triflyl-protected amines was investigated by density functional theory (DFT) calculations. The olefinated intermediate was initially formed in the first catalytic cycle involving ligand exchange, bicarbonate-assisted C(sp3)-H bond cleavage, alkene insertion and 'reductive ß-hydride elimination'. The following syn-addition and reductive elimination furnish the aza-Wacker product. The first step of reductive elimination is the rate-determining step. The mechanism unveils the important roles of bicarbonate: aiding the C-H activation and abstracting the ß-proton in the second step of reductive elimination. The parallel bridging mode in the metal-olefin intermediate facilitates the syn-addition, explaining the experimentally observed stereoselectivity. The effect of the monodentate pyridine-based ligands is also discussed.

Mechanistic Exploration of the Competition Relationship between a Ketone and C═C, C═N, or C═S Bond in the Rh(III)-Catalyzed Carbocyclization Reactions.

The introduction of a C═O, C═C, C═S, or C═N bond has emerged as an effective strategy for carbocycle synthesis. A computational mechanistic study of Rh(III)-catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or α-carbonyl-nitrones was carried out. Our results uncover the roles of dual directing groups in the three substrates and confirm that the ketone acts as the role of the directing group while the C═C, C═N, or C═S bond serves as the cyclization site. By comparing the coordination of the ketone versus the C═C, C═N, or C═S bond, as well as the chemoselectivity concerning the six- versus five-membered formation, a competition relationship is revealed within the dual directing groups. Furthermore, after the alkyne insertion, instead of the originally proposed direct reductive elimination mechanism, the ketone enolization is found to be essential prior to the reductive elimination. The following C(sp2)-C(sp2) reductive elimination is more favorable than the C(sp3)-C(sp2) formation, which can be explained by the aromaticity difference in the corresponding transition states. The substituent effect on controlling the selectivity was also discussed.

Multicomponent Synthesis of Isoindolinone Frameworks via RhIII -Catalysed in situ Directing Group-Assisted Tandem Oxidative Olefination/Michael Addition.

A RhIII -catalysed three-component synthesis of isoindolinone frameworks via direct assembly of benzoyl chlorides, o-aminophenols and activated alkenes has been developed. The process involves in situ generation of o-aminophenol (OAP)-based bidentate directing group (DG), RhIII -catalysed tandem ortho C-H olefination and subsequent cyclization via aza-Michael addition. This protocol exhibits good chemoselectivity and functional group tolerance. Computational studies showed that the presence of hydroxyl group on the N-aryl ring could enhance the chemoselectivity of the reaction.

Tandem Synthesis of Pyrrolo[2,3-b]quinolones via Cadogen-Type Reaction.

A tandem [3 + 2] cycloaddition/reductive cyclization of nitrochalcones with activated methylene isocyanides for the efficient synthesis of pyrrolo[2,3-b]quinolones is reported. In this reaction, the in situ generated dihydropyrroline acts as the internal reductant to convert the nitro into an electrophilic nitroso group, which undergoes subsequent C-N bond formation. Transition-metal-free, simple experimental procedure and ready accessibility of starting materials characterize the present transformation.

The underlying factors controlling the Pd-catalyzed site-selective alkenylation of aliphatic amines.

The Pd(ii)-catalyzed site-selective δ-C(sp3)-H alkenylation in the presence of more accessible γ-C(sp3)-H bonds is investigated by DFT calculations. Migratory insertion is found to be both the rate-limiting and the selectivity-determining step. The origin of the unusual site-selectivity is originally attributed to the different steric repulsion between the alkyne and palladacycle; however, our theoretical results reveal that the inherent electronic effect instead of steric repulsion determines the site-selectivity. The proposal is further validated by model calculations involving the less sterically hindered 1,2-dimethyl acetylene and acetylene. In addition, a novel HCO3--assisted N-H activation mechanism is reported, and the origin of the regioselectivity of an unsymmetrical alkyne is also studied.

Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and Alkenes.

Recently, a new synthetic methodology of rhodium-catalyzed carboamination/cyclopropanation from the same starting materials at different reaction conditions has been reported. It provides an efficient strategy for the stereospecific formation of both carbon- and nitrogen-based functionalities across an alkene. Herein we carried out a detailed theoretical mechanistic exploration for the reactions to elucidate the switch between carboamination and cyclopropanation as well as the origin of the chemoselectivity. Instead of the experimentally proposed RhIII-RhI-RhIII catalytic mechanism, our results reveal that the RhIII-RhV-RhIII mechanism is much more favorable in the two reactions. The chemoselectivity is attributed to a combination of electronic and steric effects in the reductive elimination step. The interactions between alkene and the rhodacycle during the alkene migration insertion control the stereoselectivity in the carboamination reactions. The present results disclose a dual role of the methanol solvent in controlling the chemoselectivity.

Bonding trends across the series of tricarbonato-actinyl anions [(AnO2)(CO3)3]4- (An = U-Cm): the plutonium turn.

Actinyl-tricarbonato anions [(AnO2)(CO3)3]4- (An = U-Cm) in various environments were investigated using theoretical approaches of quantum-mechanics, molecular-mechanics and cluster-models. Cations and solvent molecules in the 2nd coordination sphere affect the equatorial An←Oeq bonds more than the axial An[triple bond, length as m-dash]Oax bonds. Common actinide contraction is found for calculated and experimental axial bond lengths of 92U to 94Pu, though no longer for 94Pu to 96Cm. The tendency of U to Pu forming actinyl(vi) species dwindles away toward Cm, which already features the preferred AnIII/LnIII oxidation state of the later actinides and all lanthanides. The well known change from d-type to typical U-Pu-Cm type and then to f-type behavior is labeled as the plutonium turn, a phenomenon that is caused by f-orbital energy-decrease and f-orbital localization with increase of both nuclear charge and oxidation state, and a non-linear variation of effective f-electron population across the actinide series. Both orbital and configuration mixing and occupation of antibonding 5f type orbitals increase, weakening the AnOax bonds and reducing the highest possible oxidation states of the later actinides.

Copper-Catalyzed Radical-Promoted Aminocyclization of Acrylamides with N-Fluorobenzenesulfonimide.

A facile copper-catalyzed radical aminoarylation of acrylamide with N-fluorobenzenesulfonimide (NFSI) is described. In the presence of copper acetate and 1,10-phenanthroline, a range of isoquinoline-1,3-diones can be constructed in moderate to good yields using NFSI as the amination reagent. Mechanistic studies demonstrated the reaction went through a sequential radical addition and cyclization pathway, which was supported by DFT calculations.

Computational Mechanistic Study of Redox-Neutral Rh(III)-Catalyzed C-H Activation Reactions of Arylnitrones with Alkynes: Role of Noncovalent Interactions in Controlling Selectivity.

The mechanism of redox-neutral Rh(III)-catalyzed coupling reactions of arylnitrones with alkynes was investigated by density functional theory (DFT) calculations. The free energy profiles associated with the catalytic cycle, involving C(sp2)-H activation, insertion of alkyne, transfer of O atom, cyclization and protodemetalation, are presented and analyzed. An overwhelming preference for alkyne insertion into Rh-C over Rh-O is observed among all pathways, and the most favorable route is determined. The pivalate-assisted C-H activation step is turnover-limiting, and the cyclization step determines the diastereoselectivity of the reaction, with the stereoselectivity arising mainly from the difference of noncovalent interactions in key transition states. The detailed mechanism of O atom transfer, RhIII-RhI-RhIII versus RhIII-RhV-RhIII cycle, is discussed.

Nanoscale UiO-MOF-based luminescent sensors for highly selective detection of cysteine and glutathione and their application in bioimaging.

We report a practical approach, the first of its kind, to construct nanoscale UiO-type metal-organic framework (Mi-UiO-66 and Mi-UiO-67) fluorescent probes for the detection of Cys and GSH. They showed high sensitivity (10(-11) M) and selectivity for Cys and GSH, and their fluorescence imaging of Cys and GSH in living cells was well demonstrated.