Understanding the Reaction Mechanism of Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Enamines: Chemoselectivity of (Bi-oxazoline)NiH.

This density functional theory study explores the detailed mechanism of nickel-catalyzed hydroalkylation of the C═C bond of N-Cbz-protected enamines (Cbz = benzyloxycarbonyl) with alkyl iodides to give chiral α-alkyl amines. The active catalyst (biOx)NiH, a chiral bioxazoline (biOx)-chelated Ni(I) hydride, exhibits chemoselectivity that favors single electron transfer to the alkyl iodide over C═C hydrometalation with the enamine. This generates an alkyl radical and a Ni(II) intermediate, which takes up the enamine substrate CbzNHCH═CH2CH3 via a regio- and enantioselective C═C insertion into the NiII-H bond. The resulting Ni(II) alkyl complex combines with the alkyl radical, forming a Ni(III) intermediate, from which the alkyl-alkyl reductive elimination delivers the chiral amine product. The regioselectivity arises from a combination of orbital and noncovalent interactions, both of which are induced by the Cbz group. Thus, Cbz plays an additional role in controlling regioselectivity. The enantioselectivity stems from the differing distortion energies of CbzNHCH═CH2CH3. The reductive elimination is the rate-determining step (ΔG⧧ = 18.7 kcal/mol). In addition, the calculations show a noninnocent behavior of the biOx ligand induced by the insertion of CbzNHCH═CH2CH3 into the Ni-H bond of (biOx)NiH. These computationally gained insights can have implications for developing new Ni(I)-catalyzed reactions.

Enantioselective Hydroxylation of Dihydrosilanes to Si-Chiral Silanols Catalyzed by In Situ Generated Copper(II) Species.

Catalytic enantioselective hydroxylation of prochiral dihydrosilanes with water is expected to be a highly efficient way to access Si-chiral silanols, yet has remained unknown up to date. Herein, we describe a strategy for realizing this reaction: using an alkyl bromide as a single-electron transfer (SET) oxidant for invoking CuII species and chiral multidentate anionic N,N,P-ligands for effective enantiocontrol. The reaction readily provides a broad range of Si-chiral silanols with high enantioselectivity and excellent functional group compatibility. In addition, we manifest the synthetic potential by establishing two synthetic schemes for transforming the obtained products into Si-chiral compounds with high structural diversity. Our preliminary mechanistic studies support a mechanism involving SET for recruiting chiral CuII species as the active catalyst and its subsequent σ-metathesis with dihydrosilanes.

Linker Engineering toward Full-Color Emission of UiO-68 Type Metal-Organic Frameworks.

Luminescent metal-organic frameworks (LMOFs) demonstrate strong potential for a broad range of applications due to their tunable compositions and structures. However, the methodical control of the LMOF emission properties remains a great challenge. Herein, we show that linker engineering is a powerful method for systematically tuning the emission behavior of UiO-68 type metal-organic frameworks (MOFs) to achieve full-color emission, using 2,1,3-benzothiadiazole and its derivative-based dicarboxylic acids as luminescent linkers. To address the fluorescence self-quenching issue caused by densely packed linkers in some of the resultant UiO-68 type MOF structures, we apply a mixed-linker strategy by introducing nonfluorescent linkers to diminish the self-quenching effect. Steady-state and time-resolved photoluminescence (PL) experiments reveal that aggregation-caused quenching can indeed be effectively reduced as a result of decreasing the concentration of emissive linkers, thereby leading to significantly enhanced quantum yield and increased lifetime.

Mechanistic Insights into Formation of All-Carbon Quaternary Centers via Scandium-Catalyzed C-H Alkylation of Imidazoles with 1,1-Disubstituted Alkenes.

This density functional theory (DFT) study reveals a detailed plausible mechanism for the Sc-catalyzed C-H cycloaddition of imidazoles to 1,1-disubstituted alkenes to form all-carbon quaternary stereocenters. The Sc complex binds the imidazole substrate to enable deprotonative C2-H bond activation by the Sc-bound α-carbon to afford the active species. This complex undergoes intramolecular cyclization (C═C into Sc-imidazolyl insertion) with exo-selectivity, generating a ß-all-carbon-substituted quaternary center in the polycyclic imidazole derivative. The Sc-bound α-carbon deprotonates the imidazole C2-H bond to deliver the product and regenerate the active catalyst, which is the rate-determining step. Calculations illuminate the electronic effect of the ancillary Cp ligand on the catalyst activity and reveal the steric bias caused by using a chiral catalyst that induce the enantioselectivity. The insights can have implications for advancing rare-earth metal-catalyzed C-H functionalization of imidazoles.

Activation of Aryl Carboxylic Acids by Diboron Reagents towards Nickel-Catalyzed Direct Decarbonylative Borylation.

The Ni-catalyzed decarbonylative borylation of (hetero)aryl carboxylic acids with B2 cat2 has been achieved without recourse to any additives. This Ni-catalyzed method exhibits a broad substrate scope covering poorly reactive non-ortho-substituted (hetero)aryl carboxylic acids, and tolerates diverse functional groups including some of the groups active to Ni0 catalysts. The key to achieve this decarbonylative borylation reaction is the choice of B2 cat2 as a coupling partner that not only acts as a borylating reagent, but also chemoselectively activates aryl carboxylic acids towards oxidative addition of their C(acyl)-O bond to Ni0 catalyst via the formation of acyloxyboron compounds. A combination of experimental and computational studies reveals a detailed plausible mechanism for this reaction system, which involves a hitherto unknown concerted decarbonylation and reductive elimination step that generates the aryl boronic ester product. This mode of boron-promoted carboxylic acid activation is also applicable to other types of reactions.

Tuning and Directing Energy Transfer in the Whole Visible Spectrum through Linker Installation in Metal-Organic Frameworks.

While limited choice of emissive organic linkers with systematic emission tunability presents a great challenge to investigate energy transfer (ET) over the whole visible light range with designable directions, luminescent metal-organic frameworks (LMOFs) may serve as an ideal platform for such study due to their tunable structure and composition. Herein, five Zr6 cluster-based LMOFs, HIAM-400X (X=0, 1, 2, 3, 4) are prepared using 2,1,3-benzothiadiazole and its derivative-based tetratopic carboxylic acids as organic linkers. The accessible unsaturated metal sites confer HIAM-400X as a pristine scaffold for linker installation. Six full-color emissive 2,1,3-benzothiadiazole and its derivative-based dicarboxylic acids (L) were successfully installed into HIAM-400X matrix to form HIAM-400X-L, in which the ET can be facilely tuned by controlling its direction, either from the inserted linkers to pristine MOFs or from the pristine MOFs to inserted linkers, and over the whole range of visible light. The combination of the pristine MOFs and the second linkers via linker installation creates a powerful two-dimensional space in tuning the emission via ET in LMOFs.

Radical Dehydroxylative Alkylation of Tertiary Alcohols by Ti Catalysis.

Deoxygenative radical C-C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10-g-scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C-OH bond.

Ni-Catalyzed Reductive Coupling of Electron-Rich Aryl Iodides with Tertiary Alkyl Halides.

This work illustrates the reductive coupling of electron-rich aryl halides with tertiary alkyl halides under Ni-catalyzed cross-electrophile coupling conditions, which offers an efficient protocol for the construction of all carbon quaternary stereogenic centers. The mild and easy-to-operate reaction tolerates a wide range of functional groups. The utility of this method is manifested by the preparation of cyclotryptamine derivatives, wherein successful incorporation of 7-indolyl moieties is of particular interest as numerous naturally occurring products are composed of these key scaffolds. DFT calculations have been carried out to investigate the proposed radical chain and double oxidative addition pathways, which provide useful mechanistic insights into the part of the reaction that takes place in solution.

Enantioselective Tandem Cyclization of Alkyne-Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis.

Reported is the enantioselective synthesis of tetracyclic indolines using silver(I)/chiral phosphoric acid catalysis. A variety of alkyne-tethered indoles are suitable for this process. Mechanistic studies suggest that the in situ generated silver(I) chiral phosphate activates both the alkyne and the indole nucleophile in the initial cyclization step through an intermolecular hydrogen bond and the phosphate anion promotes proton transfer. In addition, further modifications of the cyclization products enabled stereochemistry-function studies of a series of bioactive indolines.

Computational design of organometallic oligomers featuring 1,3-metal-carbon bonding and planar tetracoordinate carbon atoms.

Density functional theory computations (B3LYP) have been used to explore the chemistry of titanium-aromatic carbon "edge complexes" with 1,3-metal-carbon (1,3-MC) bonding between Ti and planar tetracoordinate Cß . The titanium-coordinated, end-capping chlorides are replaced with OH or SH groups to afford two series of difunctional monomers that can undergo condensation to form oxide- and sulfide-bridged oligomers. The sulfide-linked oligomers have less molecular strain and are more exergonic than the corresponding oxide-linked oligomers. The HOMO-LUMO gap of the oligomers varies with their composition and decreases with growing oligomer chain. This theoretical study is intended to enrich 1,3-MC bonding and planar tetracoordinate carbon chemistry and provide interesting ideas to experimentalists. Organometallic complexes with the TiE2 (E = OH and SH) decoration on the edge of aromatic hydrocarbons have been computationally designed, which feature 1,3-metal-carbon (1,3-MC) bonding between titanium and planar tetracoordinate ß-carbon. Condensation of these difunctional monomers by eliminating small molecules (H2O and H2S) produce chain-like oligomers. The HOMO-LUMO gaps of the oligomers decreases with growing oligomer chain, a trend that suggests possible semiconductor properties for oligomers with longer chains.

The degree of π electron delocalization and the formation of 3D-extensible sandwich structures.

DFT B3LYP/6-31G(d) calculations were performed to examine the feasibility of graphene-like C42H18 and starbenzene C6(BeH)6 (SBz) polymers as ligands of 3D-extensible sandwich compounds (3D-ESCs) with uninterrupted sandwich arrays. The results revealed that sandwich compounds with three or more C42H18 ligands were not feasible. The possible reason may be the localization of π electrons on certain C6 hexagons due to π-metal interactions, which makes the whole ligand lose its electronic structure basis (higher degree of π electron delocalization) to maintain the planar structure. For comparison, with the aid of benzene (Bz) molecules, the SBz polymers can be feasible ligands for designing 3D-ESCs because the C-Be interactions in individual SBz are largely ionic, which will deter the π electrons on one C6 ring from connecting to those on neighbouring C6 rings. This means that high degree of π electron delocalization is not necessary for maintaining the planarity of SBz polymers. Such a locally delocalized π electron structure is desirable for the ligands of 3D-ESCs. Remarkably, the formation of a sandwich compound with SBz is thermodynamically more favourable than that found for bis(Bz)chromium. The assembly of 3D-ESCs is largely exothermic, which will facilitate future experimental synthesis. The different variation trends on the HOMO-LUMO gaps in different directions (relative to the sandwich axes) suggest that they can be developed to form directional conductors or semiconductors, which may be useful in the production of electronic devices.

Ultrashort Beryllium-Beryllium Distances Rivalling Those of Metal-Metal Quintuple Bonds Between Transition Metals.

Chemical bonding is at the heart of chemistry. Recent work on high bond orders between homonuclear transition metal atoms has led to ultrashort metal-metal (TM-TM) distances defined as dM-M <1.900 Å. The present work is a computational design and characterization of novel main group species containing ultrashort metal-metal distances (1.728-1.866 Å) between two beryllium atoms in different molecular environments, including a rhombic Be2 X2 (X=C, N) core, a vertical Be-Be axis in a 3D molecular star, and a horizontal Be-Be axis supported by N-heterocyclic carbene (NHC) ligands. The ultrashort Be-Be distances are achieved by affixing bridging atoms to attract the beryllium atoms electrostatically or covalently. Among these species are five global minima and one chemically viable diberyllium complex, which provide potential targets for experimental realization.

The mechanism of a ligand-promoted C(sp3)-H activation and arylation reaction via palladium catalysis: theoretical demonstration of a Pd(II)/Pd(IV) redox manifold.

Density functional theory (DFT) computations (BP86 and M06-L) have been utilized to elucidate the detailed mechanism of a palladium-catalyzed reaction involving pyridine-type nitrogen-donor ligands that significantly expands the scope of C(sp(3))-H activation and arylation. The reaction begins with precatalyst initiation, followed by substrate binding to the Pd(II) center through an amidate auxiliary, which directs the ensuing bicarbonate-assisted C(sp(3))-H bond activation producing five-membered-ring cyclopalladate(II) intermediates. These Pd(II) complexes further undergo oxidative addition with iodobenzene to form Pd(IV) complexes, which proceed by reductive C-C elimination/coupling to give final products of arylation. The base-assisted C(sp(3))-H bond cleavage is found to be the rate-determining step, which involves hydrogen bond interactions. The mechanism unravels the intimate involvement of the added 2-picoline ligand in every phase of the reaction, explains the isolation of the cyclopalladate intermediates, agrees with the observed kinetic hydrogen isotope effect, and demonstrates the Pd(II)/Pd(IV) redox manifold.

CBe5Hn((n-4)) (n = 2-5): Hydrogen-Stabilized CBe5 Pentagons Containing Planar or Quasi-Planar Pentacoordinate Carbons.

The diagonal relationship between beryllium and aluminum and the isoelectronic relationship between BeH unit and Al atom were utilized to design a new series ppC- or quasi-ppC-containing species C5v CBe5H5(+), Cs CBe5H4, C2v CBe5H3(-), and C2v CBe5H2(2-) by replacing the Al atoms in previously reported global minima planar pentacoordinate carbon (ppC) species D5h CAl5(+), C2v CAl4Be, C2v CAl3Be2(-), and C2v CAl2Be3(2-) with BeH units. The three-center two-electron (3c-2e) bonds formed between Be and bridging H atoms were crucial for the stabilization of these ppC species. The natural bond orbital (NBO) and adaptive natural density partitioning (AdNDP) analyses revealed that the central ppCs or quasi-ppCs possess the stable eight electron-shell structures. The AdNDP analyses also disclosed that these species are all 6σ+2π double-aromatic in nature. The aromaticity was proved by the calculated negative nucleus-independent chemical shifts (NICS) values. DFT and high-level CCSD(T) calculations revealed that these ppC- or quasi-ppC species are the global minimum or competitive low-lying local minimum (Cs CBe5H4) on their potential energy surfaces. The Born-Oppenheimer molecular dynamic (BOMD) simulations revealed that the H atoms in C2v CBe5H3(-) and C2v CBe5H2(2-) can easily rotate around the CBe5 cores and the structure of quasi-planar C5v CBe5H5(+) will become the planar structure at room temperature; however, these interesting dynamic behaviors did not indicate the kinetic instability as the basic ppC structures were maintained during the simulations. Therefore, it would be potentially possible to realize these interesting ppC- or quasi-ppc-species in future experiments.

A computational mechanistic study of an unprecedented Heck-type relay reaction: insight into the origins of regio- and enantioselectivities.

Density functional theory (DFT) calculations (B3LYP and M06) have been utilized to study a newly reported Heck-type reaction that uses an allylic or alkenyl alcohol as substrate and palladium as catalyst in the form of a chelate with a chiral pyridine oxazoline (PyrOx) ligand. The reaction not only controls the regio- and enantioselectivities of arylation of the C═C bond, but also forms the carbonyl functionality up to four bonds away from the aryl substituent via tandem C═C bond migration and enol-to-keto conversion. Computations performed on representative reaction systems allow us to propose a detailed mechanism with several key steps. Initial oxidation of palladium(0) by aryldiazonium generates active arylpalladium(II) species that bind the C═C bond of an allylic or alkenyl alcohol. The activated C═C bond inserts into the palladium-aryl moiety to attain aryl substitution and a chiral carbon center, and the resulting complex undergoes ß-hydride elimination to give a new C═C bond that can repeat the insertion/elimination process to move down the carbon chain to form an enol that tautomerizes to a highly stable carbonyl final product. The calculations reveal that the C═C bond migratory insertion step determines both the regioselectivity and the enantioselectivity of arylation, with the former arising mainly from the electronic effect of the hydroxyl group on the charge distribution over the C═C bond and the latter originating from a combination of steric repulsion, trans influence, and C-H/π dispersion interactions.

Building an emission library of donor-acceptor-donor type linker-based luminescent metal-organic frameworks.

Luminescent metal-organic frameworks (LMOFs) have been extensively studied for their potential applications in lighting, sensing and biomedicine-related areas due to their high porosity, unlimited structure and composition tunability. However, methodical development in systematically tuning the emission properties of fluorescent organic linker-based LMOFs to facilitate the rational design and synthesis of target-specific materials has remained challenging. Herein we attempt to build an emission library by customized synthesis of LMOFs with targeted absorption and emission properties using donor-acceptor-donor type organic linkers. By tuning the acceptor groups (i.e. 2,1,3-benzothiadiazole and its derivatives), donor groups (including modification of original donors and use of donors with different metal-linker connections) and bridging units between acceptor and donor groups, an emission library is developed for LMOFs with their emissions covering the entire visible light range as well as the near-infrared region. This work may offer insight into well controlled design of organic linkers for the synthesis of LMOFs with specified functionality.

Mechanistic insights into Ni-catalyzed hydrogen atom transfer (HAT)-triggered hydrodefluorination of CF3-substituted alkenes.

We report the first computational study on a nickel hydride HAT-initiated catalytic reaction, a novel hydrodefluorination of CF3-substituted aryl alkenes to afford gem-difluoroalkenes. This study provides detailed mechanistic insights into the reaction, including HAT from NiH to C[double bond, length as m-dash]C, a carbon radical rebound to nickel to facilitate chemoselective defluorination, and a two-state reactivity of Ni(ii) enabling σ-bond metathesis with PhSiH3 to regenerate the catalyst. The findings can have implications for developing new metal hydride HAT-initiated reactions.

Understanding Methyl Salicylate Hydrolysis in the Presence of Amino Acids.

Methyl salicylate, the major flavor component in wintergreen oil, is commonly used as food additives. It was found that amino acids can unexpectedly expedite methyl salicylate hydrolysis in an alkaline environment, while the detailed mechanism of this reaction merits investigation. Herein, the role of amino acid, more specifically, glycine, in methyl salicylate hydrolysis in aqueous solution was explored. 1H NMR spectroscopy, combined with density functional theory calculations, was employed to investigate the methyl salicylate hydrolysis in the presence and absence of glycine at pH 9. The addition of glycine was found to accelerate the hydrolysis by an order of magnitude at pH 9, compared to that at pH 7. The end hydrolyzed product was confirmed to be salicylic acid, suggesting that glycine does not directly form an amide bond with methyl salicylate via aminolysis. Importantly, our results indicate that the ortho-hydroxyl substituent in methyl salicylate is essential for its hydrolysis due to an intramolecular hydrogen bond, and the carboxyl group of glycine is crucial to methyl salicylate hydrolysis. This study gains a new understanding of methyl salicylate hydrolysis that will be helpful in finding ways of stabilizing wintergreen oil as a flavorant in consumer food products that also contain amino acids.

Mechanism of nickel-catalyzed direct carbonyl-Heck coupling reaction: the crucial role of second-sphere interactions.

We present a detailed DFT mechanistic study on the first Ni-catalyzed direct carbonyl-Heck coupling of aryl triflates and aldehydes to afford ketones. The precatalyst Ni(COD)2 is activated with the phosphine (phos) ligand, followed by coordination of the substrate PhOTf, to form [Ni(phos)(PhOTf)] for intramolecular PhOTf to Ni(0) oxidative addition. The ensuing phenyl-Ni(ii) triflate complex substitutes benzaldehyde for triflate by an interchange mechanism, leaving the triflate anion in the second coordination sphere held by Coulomb attraction. The Ni(ii) complex cation undergoes benzaldehyde C[double bond, length as m-dash]O insertion into the Ni-Ph bond, followed by ß-hydride elimination, to produce Ni(ii)-bound benzophenone, which is released by interchange with triflate. The resulting neutral Ni(ii) hydride complex leads to regeneration of the active catalyst following base-mediated deprotonation/reduction. The benzaldehyde C[double bond, length as m-dash]O insertion is the rate-determining step. The triflate anion, while remaining in the second sphere, engages in electrostatic interactions with the first sphere, thereby stabilizing the intermediate/transition state and enabling the desired reactivity. This is the first time that such second-sphere interaction and its impact on cross-coupling reactivity has been elucidated. The new insights gained from this study can help better understand and improve Heck-type reactions.