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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Preparation of α-amino acids via Ni-catalyzed reductive vinylation and arylation of α-pivaloyloxy glycine.

This work emphasizes easy access to α-vinyl and aryl amino acids via Ni-catalyzed cross-electrophile coupling of bench-stable N-carbonyl-protected α-pivaloyloxy glycine with vinyl/aryl halides and triflates. The protocol permits the synthesis of α-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine α-carbon (Gly) radicals to Ni(0) and Ar-Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp2) electrophile to the resultant Gly-Ni(i) intermediate gives a key Gly-Ni(iii)-Ar intermediate. The auxiliary chelation of the N-carbonyl oxygen to the Ni center appears to be crucial to stabilize the Gly-Ni(i) intermediate.

Mechanism of C-P bond formation via Pd-catalyzed decarbonylative phosphorylation of amides: insight into the chemistry of the second coordination sphere.

We report on the basis of DFT computations a plausible and detailed reaction mechanism for the first Pd-catalyzed decarbonylative phosphorylation of amides forming C-P bonds, which reveals, among other things, crucial events in the second coordination sphere, including ion pair and hydrogen bonding interactions as well as proton transfer.

Neutral nano-polygons with ultrashort Be-Be distances.

Ultrashort metal-metal distances (USMMDs, dM-M < 1.900 Å) have been realized computationally between the main group metal beryllium. However, due to their ionic charge state and the insufficient stability of their electronic structures and/or thermodynamic stabilities, the known species with ultrashort Be-Be distances are unsuitable for synthesis in the condensed phase, which deters the applications of these interesting structures from being explored. In the present study, using our previously reported global minima species [XH3-Be2H3-XH3]+ (X = N and P) with ultrashort Be-Be distances and well-defined electronic structures as their parent molecules, we designed a series of neutral polygons retaining ultrashort Be-Be distances. These polygons also possess well-defined electronic structures and good thermodynamic stabilities, which are demonstrated by their large HOMO-LUMO gaps of 6.20-7.68 eV, very high vertical detachment energies (VDEs) of 8.96-11.29 eV, rather low vertical electron affinities (VEAs) of -1.21 to +1.78 eV, and unexpectedly high formation energies relative to the building blocks of E- and Be2H3+ (-105.2 to -153.2 kcal mol-1 for the formation of an E-Be bond). The good stability with regard to their electronic structures and thermochemistry reveal their high feasibility to be synthesized in the condensed phase. Thus, we anticipate experimental studies on these interesting nano-polygons to realize structures with USMMDs between main group metals and explore their possible application.

Computational design of species with ultrashort Be-Be distances using planar hexacoordinate carbon structures as the templates.

A current project in metal-metal bonding chemistry is to achieve ultrashort metal-metal distances (USMMDs, denoted by dM-M < 1.900 Å) between main group metal beryllium atoms. A valid way for achieving such USMMDs is the substitution of a carbon atom in a planar pentacoordinate environment with the isoelectronic Be2 moiety. In the present work, we report our recent findings that a similar substitution can be applied to the carbon atom in a planar hexacoordinate environment. Using species CN3Be3+ and CO3Li3+ and related analogues as the templates, the Be2N3M3+ (M = Be, Mg, Ca) and Be2O3M3+ (M = Li, Na, K) species with axial ultrashort Be-Be distances of 1.627-1.870 Å were designed computationally. The ultrashort Be-Be distances in these species represent a balance between the lengthening effect of axial Be-Be electrostatic interactions and the shortening effects of the strong X-Be bonding and repulsive X-X-X electrostatic interactions. In addition, the shorter axial Be-Be distances were determined firstly by the smaller size of the bridging electronegative X atoms and secondly by the lower electronegativity of the peripheral M atoms, while the stabilities of the newly designed species were closely related to the types of valence electron pairs, whereby the localized two-center two-electron bonds were better for stabilization than the non-bonding valence lone pairs. Among the newly designed species, Be2N3Be3+ and Be2N3Mg3+ were characterized to be the kinetically stable global minima, thereby providing promising targets for the experimental realization of species with USMMDs between main group metals.

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.

Simulating the effect of a triple bond to achieve the shortest main group metal-metal distance in diberyllium complexes: a computational study.

The subject of metal-metal bonding interactions in molecular systems continues to attract research interest. Chromium heretofore has been the only element known to afford metal-metal distances shorter than 1.700 Å in the form of Cr-Cr multiple bonds. In this computational study, the effect of a triple bond on reducing interatomic distances is simulated through forming three non-classical bonding orbitals between two beryllium atoms, thereby realizing the remarkably short Be-Be distances (1.692-1.735 Å) in kinetically stable global minimum species [L → Be2H3 ← L]+ (L = NH3, PH3, and noble gases Ne-Xe). Such diberyllium complexes make promising candidates for experimental realization. In particular, the Be-Be distance of 1.692 Å in [Ne → Be2H3 ← Ne]+ represents the first example of global minimum having a main group metal-metal distance under 1.700 Å. [TEA → Be2H3 ← TEA]+, which contains the bulky triethylamine (TEA) ligands, is designed as a more promising target for synthesis and isolation in condensed states.

Stabilization of beryllium-containing planar pentacoordinate carbon species through attaching hydrogen atoms.

The diagonal relationship between beryllium and aluminum and the isoelectronic relationship between BeH unit and Al atom were utilized to design nine new planar and quasi-planar pentacoordinate carbon (ppC) species CAl n Be m H x q (n + m = 5, q = 0, ±1, x = q + m - 1) (1a-9a) by attaching H atoms onto the Be atoms in CAl4Be, CAl3Be2 -, CAl2Be3 2-, and CAlBe4 3-. These ppC species are σ and π double aromatic. In comparison with their parents, these H-attached molecules are more stable electronically, as can be reflected by the more favourable alternative negative-positive-negative charge-arranging pattern and the less dispersed peripheral orbitals. Remarkably, seven of these nine molecules are global energy minima, in which four of them are kinetically stable, including CAl3Be2H (2a), CAl2Be3H- (4a), CAl2Be3H2 (5a), and CAlBe4H4 + (9a). They are the promising target for the experimental realization of species with a ppC.

Aluminum(i) ß-diketiminato complexes activate C(sp2)-F and C(sp3)-F bonds by different oxidative addition mechanisms: a DFT study.

DFT computations reveal different reaction mechanisms for the oxidative addition of C(sp2)-F and C(sp3)-F bonds to the Al(i) complexes: a concerted mechanism for C(sp2)-F and a stepwise mechanism for C(sp3)-F involving fluoride transfer and the formation and recombination of an ion pair.

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.