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The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here, we report how the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum mechanical calculations were used to develop a predictive model for substrate scope, site selectivity and stereoselectivity of PikC-mediated C-H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions, where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds. [ABSTRACT FROM AUTHOR]

The mechanisms underlying copper-mediated trifluoromethylation of benzylic C(sp 3 )-H bonds were investigated using density functional theory (DFT) calculations. Two distinct pathways were identified: radical recombination/reductive elimination and single-electron transfer (SET). In the radical recombination/reductive elimination pathway, the Cu II species recombines with benzyl radicals to generate a Cu III intermediate, which subsequently undergoes reductive elimination. Conversely, the SET pathway involves single-electron transfer from benzyl radicals to Cu II species, forming a cationic benzylic intermediate and Cu I species, followed by coupling with a CF 3 group coordinated to Cu. DFT calculations revealed that the radical recombination/reductive elimination pathway is favoured for trifluoromethylation of primary and secondary benzylic C(sp 3 )-H bonds, with the reductive elimination step being rate-determining. In contrast, the SET pathway exhibits preference for trifluoromethylation of tertiary benzylic C(sp 3 )-H bonds. These mechanistic insights have significant implications for enhancing the selectivity of copper-mediated trifluoromethylation reactions.

Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures., (© 2024. The Author(s).)

Machine learning is becoming a preferred method for the virtual screening of organic materials due to its cost-effectiveness over traditional computationally demanding techniques. However, the scarcity of labeled data for organic materials poses a significant challenge for training advanced machine learning models. This study showcases the potential of utilizing databases of drug-like small molecules and chemical reactions to pretrain the BERT model, enhancing its performance in the virtual screening of organic materials. By fine-tuning the BERT models with data from five virtual screening tasks, the version pretrained with the USPTO-SMILES dataset achieved R 2 scores exceeding 0.94 for three tasks and over 0.81 for two others. This performance surpasses that of models pretrained on the small molecule or organic materials databases and outperforms three traditional machine learning models trained directly on virtual screening data. The success of the USPTO-SMILES pretrained BERT model can be attributed to the diverse array of organic building blocks in the USPTO database, offering a broader exploration of the chemical space. The study further suggests that accessing a reaction database with a wider range of reactions than the USPTO could further enhance model performance. Overall, this research validates the feasibility of applying transfer learning across different chemical domains for the efficient virtual screening of organic materials.Scientific contributionThis study verifies the feasibility of applying transfer learning to large language models in different chemical fields to help organic materials perform virtual screening. Through the comparison of transfer learning from different chemical fields to a variety of organic material molecules, the high precision virtual screening of organic materials is realized., (© 2024. The Author(s).)

Photoreduction of CO 2 with water into chemical feedstocks of fuels provides a green way to help solve both the energy crisis and carbon emission issues. Metal-organic frameworks (MOFs) show great potential for CO 2 photoreduction. However, poor water stability and sluggish charge transfer could limit their application. Herein, three water-stable MOFs functionalized with electron-donating methyl groups and/or electron-withdrawing trifluoromethyl groups are obtained for the CO 2 photoreduction. Compared with UiO-67- o -CF 3 -CH 3 and UiO-67- o -(CF 3 ) 2 , UiO-67- o -(CH 3 ) 2 achieves excellent performance with an average CO generation rate of 178.0 μmol g -1 h -1 without using any organic solvent or sacrificial reagent. The superior photocatalytic activity of UiO-67- o -(CH 3 ) 2 is attributed to the fact that compared with trifluoromethyl groups, methyl groups could not only elevate CO 2 adsorption capacity and reduction potential but also promote photoinduced charge separation and migration. These are evidenced by gas physisorption, photoluminescence, time-resolved photoluminescence, electrochemical impedance spectroscopy, transient photocurrent characteristics, and density functional theory calculations. The possible working mechanisms of electron-donating methyl groups are also proposed. Moreover, UiO-67- o -(CH 3 ) 2 demonstrates excellent reusability for the CO 2 reduction. Based on these results, it could be affirmed that the strategy of modulating substituent electronegativity could provide guidance for designing highly efficient photocatalysts.

Transition metal-peroxide complexes play a crucial role as intermediates in oxidation reactions. To unravel the mechanism of benzaldehyde oxidation by the Co-peroxo complex, we conducted density functional theory (DFT) calculations. The identified competing mechanisms include nucleophilic attack and hydrogen atom transfer (HAT). The nucleophilic attack pathway involves Co-O cleavage and nucleophilic attack, leading to the formation of the benzoate product. And the HAT pathway comprises O-O cleavage and HAT, ultimately resulting in the benzoate product. DFT calculations revealed that the formation of the end-on Co-superoxo complex 2 through Co-O cleavage, starting from the side-on Co-peroxo complex 1 , is much more favorable than the formation of the two-terminal oxyl-radical intermediate 3 through O-O cleavage. Compared with the nucleophilic attack of benzaldehyde by 2 , the abstraction of a hydrogen atom from benzaldehyde by 3 requires higher energy. The nature of the nucleophilicity of 2 and 3 accounts for the reactivity of the reaction.

This study presents the rare examples of S-heteroaryl tetradentate Pt(S^C^N^O) luminescent complexes ( PtSZ and PtSZtBu ) containing a Pt-S bond. The presence of the Pt-S bond allows the novel Pt(S^C^N^O) complexes to exhibit temperature-dependent phosphorescent emission behavior. The PtSZtBu exhibits dual-emission phenomena and biexponential transient decay spectra above 250 K, indicating the presence of two minimal excited states in the potential energy surface (PES) of the T 1 state. Through complementary experimental and computational studies, we have identified changes in orbital composition between Pt(d xy )-S(p x ) and Pt(d yz )-S(p z ) in excited states with increasing temperature. This results in two energy minima, enabling the excited states to decay selectively and radiatively at different temperatures. Consequently, this leads to remarkable steady-state and transient emission spectra changes. Our work not only provides valuable insights for the development of novel Pt-S bond-based tetradentate Pt(II) complexes but also enhances our understanding of the distinctive properties governed by the Pt-S bond.

An enantioselective Pd-catalyzed intramolecular dearomative reductive Heck reaction of N -( o -bromoaryl) indole-3-carboxamide is developed. By employing Pd(dba) 2 /SPINOL-based phosphoramidite as the chiral catalyst and HCO 2 Na as the hydride source, a series of enantioenriched spiro indolines bearing vicinal stereocenters were afforded in moderate to good yields with excellent enantioselectivities. The reductive Heck reaction of formal tetrasubstituted alkene bearing β-hydrogens is therefore realized by inhibiting β-H elimination.

A demethylenative En-Yne radical cyclization of 1,7-enynes has been successfully developed to chemoselectively afford 3,4-dihyroquinolin-2-ones or quinolin-2-ones under the catalysis of Cu(I) photosensitizers PS3 and PS6 with different redox potentials. The preliminary mechanistic experiments revealed that the reaction underwent an unprecedented olefin-α-amino radical metathesis-type process. A reasonable mechanism was proposed to illustrate the catalyst-controlled chemoselectivity of the reaction based on preliminary mechanistic experiments and DFT calculations.

Two novel six-membered perimidocarbene (PIC)-based tetradentate Pt(II) complexes were designed and successfully synthesized. Systematical experimental and theoretical studies suggest that the PIC moiety greatly affects the frontier orbitals, as well as the photophysical and excited-state properties of the Pt(II) complexes. PtYK2 has a broad emission spectrum peaking at 576 nm with a shoulder band at 620 nm, along with a full width at half-maximum (FWHM) value of 100.0 nm at 77 K in 2-MeTHF; however, the emission spectrum is slightly red-shifted with a dominant peak at 610 nm and a FWHM value of 125.0 nm at room temperature in a poly(methyl methacrylate) (PMMA) film. Time-dependent-density functional theory and natural transition orbital analyses reveal that PtYK2 has a 3 LC ( 3 π PIC * → π PIC )-dominated character with an unexpectedly negligible contribution of 3 MLCT transition (0.68%) in the T 1 state, which results in a broad emission spectrum and a relatively low quantum efficiency of 7.4% in the PMMA film.

Ultraviolet organic light-emitting diodes (UV OLEDs) have attracted increasing attention because of their promising applications in healthcare, industry, and agriculture; however, their development has been hindered by the shortage of robust UV emitters. Herein, we embedded double boron-oxygen units into nonlinear polycyclic aromatic hydrocarbons (BO-PAHs) to regulate their molecular configurations and excited-state properties, enabling novel bent BO-biphenyl ( BO-bPh ) and helical BO-naphthyl ( BO-Nap ) emitters with hybridized local and charge-transfer (HLCT) characteristics. They could be facilely synthesized in gram-scale amounts via a highly efficient two-step route. BO-bPh and BO-Nap showed strong UV and violet-blue photoluminescence in toluene with full width at half-maximum values of 25 and 37 nm, along with quantum efficiencies of 98 and 99%, respectively. A BO-bPh -based OLED showed high color purity UV electroluminescence peaking at 394 nm with Commission Internationale de l'Eclairage (CIE) coordinates of (0.166, 0.021). Moreover, the device demonstrated a record-high maximum external quantum efficiency (EQE) of 11.3%, achieved by successful hot exciton utilization. This work demonstrates the promising potential of double BO-PAHs as robust emitters for future UV OLEDs.

An efficient one-pot strategy for the facile synthesis of double boron-oxygen-fused polycyclic aromatic hydrocarbons (dBO-PAHs) with high regioselectivity and efficient skeletal editing is developed. The boron-oxygen-fused rings exhibit low aromaticity, endowing the polycyclic aromatic hydrocarbons with high chemical and thermal stabilities. The incorporation of the boron-oxygen units enables the polycyclic aromatic hydrocarbons to show single-component, low-temperature ultralong afterglow of up to 20 s. Moreover, the boron-oxygen-fused polycyclic aromatic hydrocarbons can also serve as ideal n-type host materials for high-brightness and high-efficiency deep-blue OLEDs; compared to single host, devices using boron-oxygen-fused polycyclic aromatic hydrocarbons-based co-hosts exhibit dramatically brightness and efficiency enhancements with significantly reduced efficiency roll-offs; device 9 demonstrates a high color-purity (Commission International de l'Eclairage CIE y  = 0.104), and also achieves a record-high external quantum efficiency (28.0%) among Pt(II)-based deep-blue OLEDs with Commission International de l'Eclairage CIE y  < 0.20; device 10 achieves a maximum brightnessof 27219 cd/m 2 with a peak external quantum efficiency of 27.8%, which representes the record-high maximum brightness among Pt(II)-based deep-blue OLEDs. This work demonstrates the great potential of the double boron-oxygen-fused polycyclic aromatic hydrocarbons as ultralong afterglow and n-type host materials in optoelectronic applications., (© 2023. The Author(s).)

The vision-inspired artificial neural network based on optical synapses has drawn a tremendous amount of attention for emulating biological senses. Although photoexcitation-induced synaptic functionalities have been widely studied, optical habituation via the photoinhibitory pathway is yet to be demonstrated for sophisticated biomimetic visual adaptive systems. Here, the first optical neuromorphic block copolymer (BCP) phototransistor is demonstrated as an all-optical operation responding to various wavelengths, fulfilling photoassisted dynamic learning/forgetting cycles via optical potentiation without gate bias. The polyfluorene BCPs were precisely designed to enable wavelength-adaptive responses, benefiting from interfacial semiconductor/electret morphology and the crystallinity/electron affinity of the BCPs. Notably, this is the first work to simultaneously exhibit fully light-controlled short- and long-term memory based on organic material systems. The device presents a high current contrast above 100-fold and long-term retention over 10 4 s. As a proof-of-concept for neural networks, a 6 × 6 array of photosynapses performed outstanding visual pattern learning/forgetting with high accuracy. This study exploits the design strategy of a conjugated BCP electret to unleash the full potential of wavelength-adaptive visual neuroplasticity transitions. It provides an effective architecture for designing high-performance and high-storage capacity required applications in next-generation neuromorphic systems.

A series of novel tetradentate 6/6/6 Pt(II) complexes containing an 8-phenylquinoline-benzo[ d ]imidazole-carbazole ligand was designed; the Pt(II) complexes could be synthesized by metalizing the corresponding ligand with K 2 PtCl 4 in high isolated yields of 60-90%. Experimental and theoretical studies suggested that the ligand modification of the quinoline moieties of the Pt(II) complexes could tune their electrochemical, photophysical, and excited-state properties. Notably, all the Pt(II) complexes exhibited highly electrochemical stabilities with reversible redox processes except the quasi-reversible reduction of PtYL3 . The large π-conjugation of the ligand together with increased metal-to-ligand charge-transfer ( 3 MLCT) characters in T 1 states enabled the Pt(II) complexes to show broad Gaussian-type NIR emission spectra with high photoluminescence quantum efficiencies of 1.2-1.5% and short τ of 0.8-1.5 μs in dichloromethane at room temperature. This work should provide a valuable reference for the design and development of monomer NIR emitters.

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N -hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp 3 ) activation changes from a Ni-mediated process when benzyl chlorides and Mn 0 are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a Ni II -alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

The Fe III (OH)(Cl) complex resembles the key intermediate proposed for the non-heme iron halogenases. Goldberg and co-workers reported that the Fe III (OH)(Cl) RC reacts with triphenylmethyl radical 1 to give an exclusive hydroxylation product. To understand the chemoselectivity of the reaction of RC with 1, density functional theory (DFT) calculations have been conducted. From RC, the competing pathways were identified as the OH-transfer, Cl-transfer, and isomerization pathways. The direct Cl-transfer is more favorable than direct OH-transfer by 2.8 kcal/mol. The hydrogen bonding interactions between the hydroxyl group and the pendent amine ligand impede the direct OH-transfer from RC. Compared with the direct Cl-transfer pathway, the isomerization pathways require lower barriers. In isomer RC iso2 , the equatorial hydroxyl group, which has smaller diabatic bond dissociation energy, prefers to transfer to form the hydroxylation product. In Fe III (Cl) 2 RC2 and RC2 iso , the equatorial chloride group also prefers to transfer to give the chlorination product., (© 2023 Wiley-VCH GmbH.)

We report here a regiospecific [3 + 2] annulation between aminocyclopropanes and various functionalized alkynes enabled by a P / N -heteroleptic Cu(I) photosensitizer under photoredox catalysis conditions. Thus, a divergent construction of 3-aminocyclopentene derivatives including methylsulfonyl-, arylsulfonyl-, chloro-, ester-, and trifluoromethyl-functionalized aminocyclopentenes could be achieved with advantages of high regioselectivity, broad substrate compatibility, and mild and environmentally benign reaction conditions.

The synthesis and photophysical characterization of a series of tetradentate cyclometalated M( tzp Ph-O-CzPy-R) complexes and their analogues are reported, where M is palladium or platinum and a tetradentate cyclometalating ligand contains tzp Ph (3-phenyl-[1,2,4]triazolo[4,3- a ]pyridine) and CzPy (carbazolylpyridine) moieties linked with an oxygen atom. Variations of the σ-electron-donating group R on the ligand significantly affect the photophysical properties of the complexes. By using the strong electron-withdrawing tzp portion as an acceptor and the carbazole portion as a donor, a series of Pd(II)-based metal-assisted delayed fluorescence (MADF) materials was developed. Electrochemical analysis demonstrates the irreversible reduction process occurs on the tzp ring and the irreversible oxidation process mainly occurs on the metal-phenyl moiety. This is in agreement with the HOMO and LUMO distributions by the DFT calculations, which also shows that the Pt(II) complex has more metal orbital character than those of the Pd(II) complexes. Most of the Pd(II) complexes reported here are highly emissive at 77 K in 2-MeTHF with luminescent lifetimes in the millisecond range (τ = 1.96-2.36 ms) and λ max = 488-499 nm; however, the luminescent lifetimes are shortened to the microsecond range (τ = 26.7-152.9 μs in solution and 57.0-109.9 μs in thin film respectively) at room temperature. The quantum efficiency of the Pd(II) complexes can be increased by more than 8-fold through structure modification with σ-donating groups on the ligand. Especially, the Pd( tzp -3) has a small Δ E ST of 0.228 eV and exhibits strong typical MADF in PMMA film. The Pt(II) complex Pt( tzp -2) exhibits high thermal stability (Δ T 0.5% = 440 °C) and high quantum efficiency (Φ = 50.1%) in dichloromethane solution with τ of 15.8 μs. The Pt( tzp -2) based bright green OLED achieved a peak EQE of 8.7% and a maximum brightness of 28280 cd/m 2 using an unoptimized device structure.

C-H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C-H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C-H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C-H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C-H bonds with high levels of site selectivity and enantioselectivity.

The mechanisms of Diels-Alder reactions between 1,2,3-triazines and enamines have been explored with density functional theory computations. The focus of this work is on the origins of the different reactivities and mechanisms induced by substituents and by hexafluoroisopropanol (HFIP) solvent. These inverse electron-demand Diels-Alder reactions of triazines have wide applications in bioorthogonal chemistry and natural product synthesis. Both concerted and stepwise cycloadditions are predicted, depending on the nature of substituents and solvents. The nature of zwitterionic intermediates and the mechanism by which HFIP accelerates cycloadditions with enamines are characterized. Our results show the delicate nature of the concerted versus stepwise mechanism of inverse electron-demand Diels-Alder reactions of 1,2,3-triazines, and that these mechanisms can be altered by electron-withdrawing substituents and hydrogen-bonding solvents.

C-H activation and functionalization are on the forefront of modern synthetic chemistry. Imagine if any C-H bond of a molecule could be converted to a C-X bond, where X is the target functionality-this would alter the synthetic blueprints for complex target molecules since it would provide novel disconnections in retrosynthetic analysis. Collaborations between many experimental and computational groups have led to rapid developments of new C-H functionalization methods. Our groups represent an example of this; we were brought together as part of the NSF-supported Center for Selective C-H Functionalization. Many examples of experimental-computational synergy for selective Pd(II)-catalyzed C-H activation of aryl and alkyl groups are described in this Account. We describe computations by the Houk group made in response to experimental stimuli by the Yu group. The first section discusses the experimental and computational investigations of oxazoline-directed stereoselective Pd(II)-catalyzed C(sp 3 )-H bond activation that occurs through the concerted metalation-deprotonation (CMD) pathway involving a monomeric Pd(II) complex. The second section involves two types of bidentate ligands, mono-N-protected amino acid (MPAA) and acetyl-protected aminoethyl quinoline (APAQ) ligands that promote the C-H activation reactions with the ligand as the internal base. In the MPAA-assisted remote C-H bond activation, the basic dianionic amidate ligand participates in the deprotonation of a specific C-H bond. This mechanism accounts for the improved reactivity and selectivity in C-H activation reactions with MPAA ligands. The chiral APAQ ligands enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. The dianionic amidate of the APAQ ligand acts as an intramolecular base to deprotonate the methylene C-H asymmetrically and facilitate chiral Pd-C bond formation. The origins of the dramatic differences of five-membered (relatively inactive) and six-membered (highly active) chelation in β-methylene C(sp 3 )-H activation reactions by a Pd(II) catalyst were explained with density functional theory (DFT) calculations. This is mainly due to the steric repulsions between the Ar F group of the substrate and the quinoline group of the ligand. The steric repulsion between the Ar F group of the substrate and the quinoline group of the APAQ ligand destabilizes the five-membered chelate transition structure, increasing the energy of the transition state. The third section discusses a mechanism involving a Pd-Ag heterodimeric complex intermediate in the template-directed, Pd(II)-catalyzed remote meta functionalization of toluene derivatives and benzoic acid derivatives. The nitrile directing group of the template coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in the transition state, leading to the observed high meta selectivity. The selective activation of remote meta-C-H bonds at various distances can be achieved by tuning the template. The dual role of AgOAc as both an oxidant and part of the heteronuclear active species in the mechanism involving PdAg(OAc) 3 was determined by DFT calculations and is in accord with literature information about complexes. For the systems discussed in these three sections, the similarity is that they all proceed via the CMD mechanism. The differences lie in the proton acceptors and the active Pd species. Common CMD involves a monomeric Pd mechanism with acetate as the proton acceptor. Both MPAA and APAQ ligands react via monomeric Pd mechanisms with a ligand moiety (the amidate oxygen) as the proton acceptor. Nitrile-containing template-mediated meta-C-H activations proceed via a Pd-Ag heterodimeric mechanism, still with acetate as the proton acceptor. The interaction between our two groups, experts in experiment and computation, and the discoveries made possible by that interplay are highlighted in this Account.

The origin of the unique effectiveness of six-membered chelates on the β-methylene C(sp 3 )-H activation reactions by Pd(II) catalyst was explained with density functional theory. The Pd(II) catalysts that involve five-membered chelates are inactive in this transformation. Computational studies suggest that the C(sp 3 )-H bond activation is the rate-limiting step in both cases. The C(sp 3 )-H bond activation with a five-membered chelate is unfavorable by 7.7 kcal/mol compared to the corresponding six-membered chelate with Pd(II). Two factors cause the difference: (1) the dimeric Pd species with five-membered chelation square-planar structure is more stable than that with six-membered chelation by 2.0 kcal/mol; (2) steric repulsion between the Ar F group of the substrate and the quinoline group of the acetyl-protected aminomethyl quinoline ligand destabilizes the five-membered chelate transition structure by 5.7 kcal/mol. The six-membered chelate of Pd(II) with an acetyl-protected aminoethyl quinoline ligand orients the ligand away from the Ar F group of the substrate and alleviates the steric repulsion.

We report the first observed Pd-catalyzed isomerization ("cage-walking") of B(9)-bromo-meta-carborane during Pd-catalyzed cross-coupling, which enables the formation of B-O and B-N bonds at all boron vertices (B(2), B(4), B(5), and B(9)) of meta-carborane. Experimental and theoretical studies suggest this isomerization mechanism is strongly influenced by the steric crowding at the Pd catalyst by either a biaryl phosphine ligand and/or substrate. Ultimately, this "cage-walking" process provides a unique pathway to preferentially introduce functional groups at the B(2) vertex using B(9)-bromo-meta-carborane as the sole starting material through substrate control.

Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C-H bonds in aliphatic amides. Using bidentate ligands to accelerate C-H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C-H activation is also demonstrated by enantioselective β-C-H arylation of simple carboxylic acids without installing directing groups., (Copyright © 2016, American Association for the Advancement of Science.)

We report the first catalytic method for activating the acyl C-O bonds of methyl esters through an oxidative-addition process. The oxidative-addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, to understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and the Al(OtBu)3 additive on the kinetics and thermodynamics of the reaction., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Copper-catalyzed reactions of glycine ester arylimines and methacrylonitrile provide selective access to either the endo or exo pyrrolidine cycloadducts. DFT calculations have elucidated the origins of ligand-controlled diastereoselectivity.

We report the generation of the first 3,4-piperidyne and its use as a building block for the synthesis of annulated piperidines. Experimental and computational studies of this intermediate are disclosed, along with comparisons to the well-known 3,4-pyridyne. The distortion/interaction model is used to explain the observed regioselectivities.

Density functional theory investigations have elucidated the mechanism and origins of meta-regioselectivity of Pd(II)-catalyzed C-H olefinations of toluene derivatives that employ a nitrile-containing template. The reaction proceeds through four major steps: C-H activation, alkene insertion, β-hydride elimination, and reductive elimination. The C-H activation step, which proceeds via a concerted metalation-deprotonation (CMD) pathway, is found to be the rate- and regioselectivity-determining step. For the crucial C-H activation, four possible active catalytic species-monomeric Pd(OAc)2, dimeric Pd2(OAc)4, heterodimeric PdAg(OAc)3, and trimeric Pd3(OAc)6-have been investigated. The computations indicated that the C-H activation with the nitrile-containing template occurs via a Pd-Ag heterodimeric transition state. The nitrile directing group coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in the transition state, leading to the observed high meta-selectivity. The Pd2(OAc)4 dimeric mechanism also leads to the meta-C-H activation product but with higher activation energies than the Pd-Ag heterodimeric mechanism. The Pd monomeric and trimeric mechanisms require much higher activation free energies and are predicted to give ortho products. Structural and distortion energy analysis of the transition states revealed significant effects of distortions of the template on mechanism and regioselectivity, which provided hints for further developments of new templates.

Density functional theory calculations (B3LYP) have been carried out to investigate the 4π-electron systems of 2,4-disila-1,3-diphosphacyclobutadiene (compound 1) and the tetrasilacyclobutadiene dication (compound 2). The calculated nucleus-independent chemical shift (NICS) values for these two compounds are negative, which indicates that the core rings of compounds 1 and 2 have a certain amount of aromaticity. However, deep electronic analysis reveals that neither of these two formal 4π-electron four-membered ring systems is aromatic. Compound 1 has very weak, almost negligible antiaromaticity, and the amidinate ligands attached to the Si atoms play an important role in stabilizing this conjugated 4π-electron system. The monoanionic bidentate ligand interacts with the conjugated π system to cause π-orbital splitting. This ligand-induced π-orbital splitting effect provides an opportunity to manipulate the gap between occupied and unoccupied π orbitals in conjugated systems. Conversely, compound 2 is nonaromatic because its core ring does not have a conjugated π ring system and does not fulfill the requirements of a Hückel system., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)