Photocatalytic Dehydrogenative Cross‐Coupling of Alkenes with Alcohols or Azoles without External Oxidant

Direct cross‐coupling between alkenes/R‐H or alkenes/RXH is a dream reaction, especially without external oxidants. Inputting energy by photocatalysis and employing a cobalt catalyst as a two‐electron acceptor, a direct C−H/X−H cross‐coupling with H₂ evolution has been achieved for C−O and C−N bond formation. A new radical alkenylation using alkene as the redox compound is presented. A wide range of aliphatic alcohols—even long chain alcohols—are tolerated well in this system, providing a new route to multi‐substituted enol ether derivatives using simple alkenes. Additionally, this protocol can also be used for N ‐vinylazole synthesis. Mechanistic insights reveal that the cobalt catalyst oxidizes the photocatalyst to revive the photocatalytic cycle.     

Tuned C?H Functionalization to Construct Aza‐Podophyllotoxin/Aza‐Conidendrin Derivatives by Means of Domino Cyclization

An efficient domino cyclization method for the construction of aza‐podophyllotoxin/aza‐conidendrin derivatives has been established. Reactions of different dienes with aryl halides in the presence of a palladium catalytic system produced different kinds of podophyllotoxin derivatives through a highly regioselective C? H functionalization. Treatment of dienes with aryl halides that have electron‐withdrawing substituents on the phenyl ring created aza‐podophyllotoxin derivatives by means of the functionalization of the C? H bonds ortho to the C? halide bonds of the incoming aryl halides. The reaction of dienes with 1‐iodobenzene or aryl halides that incorporate electron‐donating groups produced aza‐conidendrin derivatives by means of the functionalization of both sp³ C? H and sp² C? H bonds. The regioselective C? H functionalization for the formation of different pseudo‐podophyllotoxin/‐conidendrin derivatives is proven by analyses of the ¹H NMR spectra of the products and selective X‐ray analyses of the structures of the products. Thus, the palladium‐catalyzed domino cyclization of 1,6‐dienes for the preparation of aza‐podophyllotoxin/aza‐conidendrin derivatives can be controlled by selectively controlling the C? H functionalization.     

Nickel/NHC‐Catalyzed Asymmetric C−H Alkylation of Fluoroarenes with Alkenes: Synthesis of Enantioenriched Fluorotetralins

Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C?H alkylation of polyfluoroarenes with alkenes is described. The reaction employs bulky chiral N‐heterocyclic carbene (NHC) ligands for nickel catalysts to enable exclusive activation of C?H bonds over C?F bonds and complete endo‐selective C?H annulation and excellent enantioselectivity. A wide variety of chiral fluorotetralins, compounds otherwise difficultly accessed but serve as important bioisosteric analogs of both tetralin and heterocycle units for drug design, are expediently synthesized from easily available substrates. To our knowledge, this is the first example of catalytic enantioselective C?H functionalization of polyfluoroarenes.     

Strategies for Synthesis of Imidazo[1,2‐a]pyridine Derivatives: Carbene Transformations or C−H Functionalizations

The imidazo[1,2‐a]pyridines are an important target in organic synthetic chemistry and have attracted critical attention of chemists mainly due to the discovery of the interesting properties exhibited by a great number of imidazo[1,2‐a]pyridine derivatives. Although lots of synthetic methods of imidazo[1,2‐a]pyridines have been developed in the past years, the chemistry community faces continuing challenges to use green reagents, maximize atom economy and enrich the functional group diversity of product. Undoubtedly, with its low cost and lack of environmentally hazardous byproducts, cascade reactions and C?H functionalizations are ideal strategies for this field. In this record we highlight some of our progress toward the goal to synthesis of imidazo[1,2‐a]pyridine derivatives through carbene transformations or C?H functionalizations.     

Theoretical study of mechanism of extraction reaction between germylene carbene and its derivatives and thiirane

The mechanism of the sulfur extraction reaction between singlet germylene carbene and its derivatives [X₂Ge?C: (X = H, F, Cl, CH₃)] and thiirane has been investigated with density functional theory, including geometry optimization and vibrational analyses for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by B3LYP/6‐311G(d,p) method. From the potential energy profile, it can be predicted that the reaction pathway of this kind consists two steps: (1) the two reactants firstly form an intermediate (INT) through a barrier‐free exothermic reaction; (2) the INT then isomerizes to a product via a transition state (TS). This kind reaction has similar mechanism, when the germylene carbene and its derivatives [X₂Ge?C: (X = H, F, Cl, CH₃)] and thiirane get close to each other, the shift of 3p lone electron pair of S in thiirane to the 2p unoccupied orbital of C in X₂Ge = C: gives a p → p donor–acceptor bond, leading to the formation of INT. As the p → p donor–acceptor bond continues to strengthen (that is the C? S bond continues to shorten), the INT generates product (P + C₂H₄) via TS. It is the substituent electronegativity that mainly affects the extraction reactions. When the substituent electronegativity is greater, the energy barrier is lower, and the reaction rate is greater. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Structure elucidation,complete NMR assignment and PM5 theoretical studies of new hydroxy‐aminoalkyl‐α,β‐unsaturated derivatives of the macrolide antibiotic josamycin

Four new hydroxy‐aminoalkyl derivatives of α,β‐unsaturated macrolide‐josamycin (2–5) have been synthesised and their structures have been studied by means of ¹H and ¹³C NMR and FT‐IR methods. Complete assignment of resonances in the ¹H and ¹³C NMR spectra has been made on the basis of ¹H? ¹³C HSQC, ¹H? ¹³C HMBC, ¹H? ¹H COSY, ¹H? ¹H NOESY 2D experiments. Spectroscopic data indicated that for the derivatives 3 and 4 some equilibrium between two different structures exists in contrast to derivatives 2 and 5. The lowest‐energy structures of the new derivatives of josamycin have been calculated and visualised by PM5 method at semi‐empirical level of theory, taking into account the NMR and FT‐IR data. The most significant differences between the structures of josamycin and its newly synthesised derivatives' were found in the conformation of the macrolide aglycone part and in the mutual orientation of the 4‐O‐isovalerylmycarosylmycaminose moiety relative to the aglycone part. PM5 semi‐empirical calculations indicated that the structures of the new macrolide derivatives are stabilised by rather weak intramolecular hydrogen bonds in agreement with spectroscopic data. Antimicrobial properties of the new derivatives 2–5 as well as those having an acetate group at C‐3 (6 and 7) were determined and compared to that of the parent macrolide antibiotic josamycin (1). Copyright © 2010 John Wiley & Sons, Ltd.     

Site‐Selective Late‐Stage Aromatic [18F]Fluorination via Aryl Sulfonium Salts

Site‐selective functionalization of C?H bonds in small complex molecules is a long‐standing challenge in organic chemistry. Herein, we report a broadly applicable and site‐selective aromatic C?H dibenzothiophenylation reaction. The conceptual advantage of this transformation is further demonstrated through the two‐step C?H [¹⁸F]fluorination of a series of marketed small‐molecule drugs.     

Reinvestigation of intramolecular hydrogen bond in malonaldehyde derivatives: An ab initio,AIM and NBO study

The RAHB systems in malonaldehyde and its derivatives at MP2/ 6‐311++G(d,p) level of theory were studied and their intramolecular hydrogen bond energies by using the related rotamers method was obtained. The topological properties of electron density distribution in O? H···O intramolecular hydrogen bond have been analyzed in term of quantum theory of atoms in molecules (QTAIM). Correlations between the H‐bond strength and topological parameters are probed. The results of QTAIM clearly showed that the linear correlation between the electron density distribution at HB critical point and RAHB ring critical point with the corresponding hydrogen bond energies was obtained. Moreover, it was found a linear correlation between the electronic potential energy density, V(r_cp), and hydrogen bond energy which can be used as a simple equation for evaluation of HB energy in complex RAHB systems. Finally, the similar linear treatment between the geometrical parameters, such as O···O or O? H distance, and Lp(O)→σ*_OH charge transfer energy with the intramolecular hydrogen bond energy is observed. © 2010 Wiley Periodicals, Inc., Int J Quantum Chem, 2011     

Nickel‐Catalyzed Insertion of Alkynes and Electron‐Deficient Olefins into Unactivated sp3 CH Bonds

Insertion of unsaturated systems such as alkynes and olefins into unactivated sp³ C?H bonds remains an unexplored problem. We herein address this issue by successfully incorporating a wide variety of functionalized alkynes and electron‐deficient olefins into the unactivated sp³ C?H bond of pivalic acid derivatives with excellent syn‐ and linear‐ selectivity. A strongly chelating 8‐aminoquinoline directing group proved beneficial for these insertion reactions, while an air‐stable and inexpensive Ni^II salt has been employed as the active catalyst.     

Hydrogen Bonding of Fluorinated Saccharides in Solution: F Acting as H‐Bond Acceptor in a Bifurcated H‐Bond of 4‐Fluorinated Levoglucosans

4‐Fluorinated levoglucosans were synthesised to test if OH???F H‐bonds are feasible even when the O???F distance is increased. The fluorinated 1,6‐anhydro‐β‐D ‐glucopyranoses were synthesised from 1,6 : 3,4‐dianhydro‐β‐D ‐galactopyranose ( 8 ). Treatment of 8 with KHF₂ and KF gave 43% of 4‐deoxy‐4‐fluorolevoglucosan ( 9 ), which was transformed into the 3‐O‐protected derivatives 13 by silylation and 15 by silylation, acetylation, and desilylation. 4‐Deoxy‐4‐methyllevoglucosan ( 19 ) and 4‐deoxylevoglucosan ( 21 ) were prepared as reference compounds that can only form a bivalent H‐bond from HO? C(2) to O? C(5). They were synthesised from the ⁱPr₃Si‐protected derivative of 8 . Intramolecular bifurcated H‐bonds from HO? C(2) to F? C(4) and O? C(5) of the 4‐fluorinated levoglucosans in CDCl₃ solution are evidenced by the ¹H‐NMR scalar couplings ^h1J(F,OH) and ³J(H,OH). The OH???F H‐bond over an O???F distance of ca. 3.0 Å is thus formed in apolar solvents, at least when favoured by the simultaneous formation of an OH???O H‐bond.     

Mononuclear Nonheme High‐Spin (S=2) versus Intermediate‐Spin (S=1) Iron(IV)–Oxo Complexes in Oxidation Reactions

Mononuclear nonheme high‐spin (S=2) iron(IV)–oxo species have been identified as the key intermediates responsible for the C?H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C?H bond activation of hydrocarbons by a synthetic mononuclear nonheme high‐spin (S=2) iron(IV)–oxo complex occurs through an oxygen non‐rebound mechanism, as previously demonstrated in the C?H bond activation by nonheme intermediate (S=1) iron(IV)–oxo complexes. We also report that C?H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high‐spin (HS) and intermediate‐spin (IS) iron(IV)–oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)–oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters.     

α‐Halogenoacetanilides as Hydrogen‐Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine

α‐Halogenoacetanilides (X=F, Cl, Br) were examined as H‐bonding organocatalysts designed for the double activation of C?O bonds through NH and CH donor groups. Depending on the halide substituents, the double H‐bond involved a nonconventional C?H???O interaction with either a H?CX_n (n=1–2, X=Cl, Br) or a H?C_Ar bond (X=F), as shown in the solid‐state crystal structures and by molecular modeling. In addition, the catalytic properties of α‐halogenoacetanilides were evaluated in the ring‐opening polymerization of lactide, in the presence of a tertiary amine as cocatalyst. The α‐dichloro‐ and α‐dibromoacetanilides containing electron‐deficient aromatic groups afforded the most attractive double H‐bonding properties towards C?O bonds, with a N?H???O???H?CX₂ interaction.     

1,2‐Thiazines: One‐Pot Syntheses Utilizing Mono and Diaza Analogs of Sulfones

A one‐pot Michael addition/cyclization/condensation reaction sequence for the regioselective synthesis of 1,2‐thiazines, starting from propargyl ketones and NH‐sulfoximines or NH‐sulfondiimines, has been developed. Under mild and operationally simple reaction conditions previously unprecedented 1,2‐thiazine 1‐imide and 1‐oxide derivatives are formed in good to excellent yields. The products represent heterocyclic building blocks, readily modifiable by a regioselective C?H bond functionalization, classical cross‐coupling reactions, and deprotection.     

On the role of substituent in noncovalent functionalization of graphene and organophosphor recognition: IQA and SAPT perspective

Despite importance of integrating organic molecules with graphene to fabricate graphene‐based electronic devices, the role of substituents and interface stabilizing forces are poorly understood. In this work, the interactions of 7,7,8,8‐tetracyanoquinodimethane (TCNQ), 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4TCNQ), hydroquinone (Q), and tetrafluorohydroquinone (TFQ) with graphene have been investigated by means of interacting quantum atoms and SAPT(DFT). In addition, in context of potential design of a graphene‐based sensor for detection of the nerve agent sarin, we studied the interaction of graphene and the organic molecules with the dimethyl methylphosphonate (DMMP)—the molecule that mimics sarin. The results show that the organic molecules attach to graphene via C(sp²)?C(sp²), C(sp²)?C(sp) and H?π bonds. In addition, they trap DMMP via various linkages such as hydrogen, lonepair?π and H?π . The quantum effects play a significant role. The Pauli repulsion is responsible for p‐doping of graphene. The substituents are stabilized on graphene by the exchange‐correlation energy. The fluorination of the benzenoid ring raises the electron‐sharing . The through space and through bond effects of the fluorine atoms (‐F) increase the classical attraction of the cyano groups and benzenoid ring with graphene, respectively. When comparing performance of the ab initio and DFT methods, MP2 predicts too much attraction due to well‐known overestimation of the dispersion energy by the uncoupled dispersion component for benzene rings, while ω B97xD functional and SAPT(DFT) provide weaker interaction energies, in good agreement with each other.     

Theoretical study of interaction of heteroaromatic compounds with a cluster model of kaolinite tetrahedral surface

Heteroaromatic hydrocarbons (including thiophene [TH], benzothiophene [BT], and dibenzothiophene [DBT]) do not have apparent functional groups capable of interacting with the silica‐oxide tetrahedral surface of kaolinite. Thus, question remains concerning what would be the driving forces for the adsorption. Here, the Si₁₃O₃₇H₂₂ cluster model for the surface is constructed, and the interactions of the surface with three heteroaromatic compounds are studied at the MP2/6‐31G(d,p)//B3LYP/6‐31G(d) level. The computed properties characterizing the complexes include optimized structural parameters, electron density characteristics (the ρ and ? ²ρ values for C? H…O bonds), adsorption energies, vibration frequencies and electrostatic potential maps. The results suggest that the C? H…O hydrogen bonding interactions between the heteroaromatic compounds and tetrahedral surface are likely among the important interactions for the adsorption. The order of the stability of the cluster model of kaolinite complexed with the heteroaromatic compounds is found to be 3Si? O? DBT > 3Si? O? BT > 3Si? O? TH based on the calculations.     

Biologically Inspired C−H and C=C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes

The development of catalysts for the selective oxidation of readily available hydrocarbons or organic precursors into oxygenated products is a long‐standing goal in organic synthesis. In the last decade, some iron coordination complexes have shown the potential to fit this role. These catalysts can mimic the O?O activation mode of far more sophisticated iron oxygenase enzymes, generating powerful yet selective oxidants. In this review, we report state‐of‐the‐art C?H and C=C oxidations catalyzed by non‐heme iron complexes and H₂O₂ as the oxidant. Finally, we briefly describe some novel oxidative reactivity and the perspectives of this chemistry.     

1H and 13C NMR spectral characterization of some antimalarial in vitro 2,4‐diamino‐10‐methylpyrimido[4,5‐b]‐5‐quinolone derivatives

We report the ¹H NMR and ¹³C NMR chemical shifts and J(H,H), J(H,F) and J(C,F) coupling constants of 13 2,4‐diamino‐10‐methylpyrimido[4,5‐b]‐5‐quinolone derivatives, some of them with moderate activity against Plasmodium falciparum in vitro. They were characterized and assigned on the basis of ¹H, ¹³C and ¹³C–¹H (short‐ and long‐range) correlated spectra. Copyright © 2002 John Wiley & Sons, Ltd.     

Decorating Tetrathiafulvalene (TTF) with Fluorinated Phenyls through Sulfur Bridges: Facile Synthesis,Properties, and Aggregation through Fluorine Interactions

Tetrathiafulvalene derivatives ( TTF1 – TTF9 ) bearing fluorinated phenyl groups attached through the sulfur bridges have been synthesized by employing a copper‐mediated C–S coupling reaction of C₆H_5?xF_xI (x=1, 2, 5) and a zinc‐thiolate complex, (TBA)₂[Zn(DMIT)₂] (TBA=tetrabutyl ammonium, DMIT=1,3‐dithiole‐2‐thione‐4,5‐dithiolate), as the key step. Particularly, the selective synthesis of C₆F₅‐substituted ( TTF8 ) and C₆F₄‐fused ( TTF9 ) TTFs from C₆F₅I is disclosed. The physicochemical properties and crystal structures of these TTFs are fully investigated by UV/Vis absorption spectra, cyclic voltammetry, molecular orbital calculation, and single‐crystal X‐ray diffraction. The exchange of hydrogen versus fluorine on the peripheral phenyl groups show a notable influence on both the electronic and crystallographic natures of the resulting TTFs: 1) lowering both the HOMO and the LUMO energy levels, 2) modulating the electrochemical properties by regioselective and/or the degree of fluorination, 3) enhancing the driving forces of stacking by multiple fluorine interactions (F???S, C?F???π/π_F, C?F???F?C, and C?F???H). This work indicates that the decoration with fluorinated phenyls holds promise to produce functional TTFs with novel electronic and aggregation features.     

Tracing the Fingerprint of Chemical Bonds within the Electron Densities of Hydrocarbons: A Comparative Analysis of the Optimized and the Promolecule Densities

The equivalence of the molecular graphs emerging from the comparative analysis of the optimized and the promolecule electron densities in two hundred and twenty five unsubstituted hydrocarbons was recently demonstrated [Keyvani et al. Chem. Eur. J. 2016 , 22, 5003]. Thus, the molecular graph of an optimized molecular electron density is not shaped by the formation of the C?H and C?C bonds. In the present study, to trace the fingerprint of the C?H and C?C bonds in the electron densities of the same set of hydrocarbons, the amount of electron density and its Laplacian at the (3, ?1) critical points associated with these bonds are derived from both optimized and promolecule densities, and compared in a newly proposed comparative analysis. The analysis not only conforms to the qualitative picture of the electron density build up between two atoms upon formation of a bond in between, but also quantifies the resulting accumulation of the electron density at the (3, ?1) critical points. The comparative analysis also reveals a unified mode of density accumulation in the case of 2318 studied C?H bonds, but various modes of density accumulation are observed in the case of 1509 studied C?C bonds and they are classified into four groups. The four emerging groups do not always conform to the traditional classification based on the bond orders. Furthermore, four C?C bonds described as exotic bonds in previous studies, for example the inverted C?C bond in 1,1,1‐propellane, are naturally distinguished from the analysis.     

Cu‐Catalyzed Intramolecular Amidation of Unactivated C(sp3)−H Bonds To Synthesize N‐Substituted Indolines

A copper‐catalyzed intramolecular amidation of unactivated C(sp³)?H bonds to construct indoline derivatives has been developed. Such an amidation proceeded well at primary C?H bonds preferred to secondary C?H bonds. The transformation owned a broad substrate scope. The corresponding indolines were obtained in good to excellent yields. N‐Formal and other carbonyl groups were suitable and were easily deprotected and transformed into methyl or long‐chained alkyl groups. Preliminary mechanistic studies suggested a radical pathway.