Palladium-catalyzed silyl C(sp3)-H bond activation

The first transition-metal-catalyzed activation of silyl C(sp(3))-H bond was realized and synthetically applied. A variety of organic skeletons substituted with SiMe(3) groups could undergo the Pd-catalyzed intramolecular coupling reaction, resulting in an unprecedented synthetic method for yielding six-membered silacycles. It was found that the adjacent Si atom played an essential role for the activation of the C(sp(3))-H bond of the SiMe(3) group; no activation reaction of the C(sp(3))-H bond of the CMe(3) group took place under the same reaction conditions.     

Determination of the C4-H bond dissociation energies of NADH models and their radical cations in acetonitrile

Heterolytic and homolytic bond dissociation energies of the C4-H bonds in ten NADH models (seven 1,4-dihydronicotinamide derivatives, two Hantzsch 1,4-dihydropyridine derivatives, and 9,10-dihydroacridine) and their radical cations in acetonitrile were evaluated by titration calorimetry and electrochemistry, according to the four thermodynamic cycles constructed from the reactions of the NADH models with N,N,N',N'-tetramethyl-p-phenylenediamine radical cation perchlorate in acetonitrile (note: C9-H bond rather than C4-H bond for 9,10-dihydroacridine; however, unless specified, the C9-H bond will be described as a C4-H bond for convenience). The results show that the energetic scales of the heterolytic and homolytic bond dissociation energies of the C4-H bonds cover ranges of 64.2-81.1 and 67.9-73.7 kcal mol(-1) for the neutral NADH models, respectively, and the energetic scales of the heterolytic and homolytic bond dissociation energies of the (C4-H)(.+) bonds cover ranges of 4.1-9.7 and 31.4-43.5 kcal mol(-1) for the radical cations of the NADH models, respectively. Detailed comparison of the two sets of C4-H bond dissociation energies in 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch 1,4-dihydropyridine (HEH), and 9,10-dihydroacridine (AcrH(2)) (as the three most typical NADH models) shows that for BNAH and AcrH(2), the heterolytic C4-H bond dissociation energies are smaller (by 3.62 kcal mol(-1)) and larger (by 7.4 kcal mol(-1)), respectively, than the corresponding homolytic C4-H bond dissociation energy. However, for HEH, the heterolytic C4-H bond dissociation energy (69.3 kcal mol(-1)) is very close to the corresponding homolytic C4-H bond dissociation energy (69.4 kcal mol(-1)). These results suggests that the hydride is released more easily than the corresponding hydrogen atom from BNAH and vice versa for AcrH(2), and that there are two almost equal possibilities for the hydride and the hydrogen atom transfers from HEH. Examination of the two sets of the (C4-H)(.+) bond dissociation energies shows that the homolytic (C4-H)(.+) bond dissociation energies are much larger than the corresponding heterolytic (C4-H)(.+) bond dissociation energies for the ten NADH models by 23.3-34.4 kcal mol(-1); this suggests that if the hydride transfer from the NADH models is initiated by a one-electron transfer, the proton transfer should be more likely to take place than the corresponding hydrogen atom transfer in the second step. In addition, some elusive structural information about the reaction intermediates of the NADH models was obtained by using Hammett-type linear free-energy analysis.     

Original palladium pincer complexes deriving from 1,3-bis(thiophosphinoyl)indene proligands: C(sp3)-H versus C(sp2)-H bond activation

A series of original 2-indenylidene palladium pincer complexes {PdL[Ind(Ph(2)P==S)(2)]} (L = HNCy(2), PPh(3), Cl(-)) have been prepared by double C-H activation of a 1,3-bis(thiophosphinoyl)indene proligand. Crystallographic analyses and DFT calculations indicate that the bonding situation of the {Pd[Ind(Ph(2)P==S)(2)]} fragment is essentially governed by the conjugated and rigid nature of the dianionic pincer ligand, the nature of the coligand having little influence. The formation of the 2-indenylidene complexes involves either a 2-indenyl pincer or a four-membered cyclometalated complex as an intermediate, suggesting that C(sp(2))-H or C(sp(3))-H bond activation takes place. However, deuterium labelling experiences show that in all cases, C(sp(3))-H bond activation occurs followed eventually by a Pd/H exchange. Nevertheless, evidence for direct C(sp(2))-H bond activation under mild conditions is obtained when a methyl group is introduced at the indene proligand to prevent C(sp(3))-H bond activation. The ensuing dissymmetrical 2-indenyl palladium pincer complex has been fully characterized.     

Aza-oxindole synthesis by oxidative coupling of C(sp2)-H and C(sp3)-H centers

A Cu(II) mediated oxidative C(sp(2))-H and C(sp(3))-H coupling protocol gives access to aza-oxindoles in good to excellent yield in the presence of NaOtBu as base and toluene as solvent.     

Theoretical analysis of the hydrogen bond of imidazolium C(2)-H with anions

The intermolecular interaction energies of ion pairs of imidazolium-based ionic liquids were studied by MP2/6-311G level ab initio calculations. Although the hydrogen bond between the C(2) hydrogen atom of an imidazolium cation and anion has been regarded as an important interaction in controlling the structures and physical properties of ionic liquids as in the cases of conventional hydrogen bonds, the calculations show that the nature of the C(2)-H...X interaction is considerably different from that of conventional hydrogen bonds. The interaction energies of the imidazolium cation with neighboring anions in the four crystals of ionic liquids were calculated. The size of the interaction is determined mainly by the distance between the imidazolium ring and anion. The calculated interaction energy is nearly inversely proportional to the distance, which shows that the charge-charge interaction is the dominant interaction in the attraction. The orientation of the anion relative to the C(2)-H bond does not greatly affect the size of the interaction energy. Calculated interaction energy potentials of 1,3-dimethylimidazolium tetrafluoroborate ([dmim][BF(4)]) complexes show that the C(2)-H bond does not prefer to point toward a fluorine atom of the BF(4). This shows that the C(2)-H...X hydrogen bond is not essential for the attraction.     

Palladium-catalyzed amidation by chemoselective C(sp3)-H activation: concise route to oxindoles using a carbamoyl chloride precursor

Quite select: a new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad(2)PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp(3))-H activation proceeded in the presence of a C(sp(2))-H bond. Ad=adamantyl.     

Sequential protocol for C(sp)-H carboxylation with CO_2:KO~tBu-catalyzed C(sp)-H silylation and KO~tBu-mediated carboxylation

CO_2 incorporation into C-H bonds is an important and interesting topic. Herein a sequential protocol for C(sp)-H carboxylation by employing a metal-free C-H activation/catalytic silylation reaction in conjunction with KO~tBu-mediated carboxylation with CO_2 was established, in which KO~t Bu catalyzes silylation of terminal alkynes to form alkynylsilanes at low temperature, and simultaneously mediates carboxylation of the alkynesilanes with atmospheric CO_2. Importantly, the carboxylation further promotes the silylation, which makes the whole reaction proceed very rapidly. Moreover, this methodology is simple and scalable, which is characterized by short reaction time, wide substrate scope, excellent functional-group tolerance and mild reaction conditions,affording a range of corresponding propiolic acid products in excellent yields in most cases. In addition, it also allows for a convenient ~(13)C-labeling through the use of ~(13)CO_2.     

Sequential protocol for C(sp3)-H carboxylation with CO2: transition-metal-catalyzed benzylic C-H silylation and fluoride-mediated carboxylation

One of the most challenging transformations in current organic chemistry is the catalytic carboxylation of a C(sp(3))-H bond using CO(2) gas, an inexpensive and ubiquitous C1 source. A sequential protocol for C(sp(3))-H carboxylation by employing a nitrogen-directed, metal-assisted, C-H activation/catalytic silylation reaction in conjunction with fluoride-mediated carboxylation with CO(2) was established. The carboxylation proceeded only at the benzylic C(sp(3))-Si bond, not at the aromatic C(sp(2))-Si, which is advantageous for further manipulations of the products.     

Efficient alkyl ether synthesis via palladium-catalyzed, picolinamide-directed alkoxylation of unactivated C(sp3)-H and C(sp2)-H bonds at remote positions

We report the efficient synthesis of alkyl ethers by the functionalization of unactivated sp(3)- and sp(2)-hybridized C-H bonds. In the Pd(OAc)(2)-catalyzed, PhI(OAc)(2)-mediated reaction system, picolinamide-protected amine substrates undergo facile alkoxylation at the γ or δ positions with a range of alcohols, including t-BuOH, to give alkoxylated products. This method features a relatively broad substrate scope for amines and alcohols, inexpensive reagents, and convenient operating conditions. This method highlights the emerging value of unactivated C-H bonds, particularly the C(sp(3))-H bond of methyl groups, as functional groups in organic synthesis.     

Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl

The regioselective carbonylation of unactivated C(sp(3))-H bonds of aliphatic amides was achieved using Ru(3)(CO)(12) as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru(3)(CO)(12) gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.     

甘氨酸衍生物C(sp3)―H官能团化反应在喹啉类化合物合成中的应用

The direct oxidative C(sp³)-H functionalization reaction has long been considered as one of the most efficient and straightforward synthetic protocol for the construction of C-C bonds. Recently, the synthesis of substituted quinolines via C(sp³)-H functionalization of glycine derivatives has gained widespread attention from the chemists. Recent progresses on the C(sp³)-H functionalization of glycine derivatives and their applications in the synthesis of substituted quinolines are described in this paper. The aims are to broaden students' vision and stimulate their interest in scientific research through the introduction of innovative scientific research.     

Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected C(sp3)-H activation

A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp(3))-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.     

Organocatalytic deprotonative functionalization of C(sp(2))-H and C(sp(3))-H bonds using in situ generated onium amide bases

Onium amides, generated in situ from the combination of aminosilanes and onium fluorides (R(4)PF, R(4)NF), are employed for the first time as bases for catalytic deprotonative functionalization of C(sp(2))-H and activated C(sp(3))-H bonds under mild conditions.     

Collision induced complex formation following electron capture of SO2-H2O complex interacting with argon atoms

Electron capture dynamics of SO(2)-H(2)O(Ar)(n) complexes (n = 0-2) have been investigated by means of direct ab initio molecular dynamics (MD) method in order to elucidate the effects of solvent argon on the reaction dynamics of SO(2)-H(2)O. The neutral complex of SO(2)-H(2)O has a C(s) symmetry, and the sulfur of SO(2) interacts with the oxygen of H(2)O with an eclipsed form. In the SO(2)-H(2)O(Ar)(n) complexes, the dipole of H(2)O interacts with the argon atoms in the most stable structure. Following the electron capture of the complex SO(2)-H(2)O, the complex anion SO(2)(-)(H(2)O) is dissociated directly into SO(2)(-) + H(2)O. On the other hand, the electron capture of SO(2)(H(2)O)(Ar)(n) argon complex (n = 1-2) leads to the anion-water complex SO(2)(-)(H(2)O) because the collision of H(2)O with the Ar atom causes a rebound of H(2)O from Ar atom to the SO(2)(-) anion. The argon solvent enhanced the SO(2)(-)(H(2)O) complex formation. The reaction mechanism of SO(2)(H(2)O) in the participation of argon atoms was discussed on the basis of the present results.     

Palladium-Catalyzed Cascade Process Consisting of Isocyanide Insertion and Benzylic C(sp(3))-H Activation: Concise Synthesis of Indole Derivatives

Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It was found that slow addition of isocyanide is effective for reducing the amount of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation. The construction of the tetracyclic carbazole skeleton was also achieved by a Pd-catalyzed domino reaction incorporating alkyne insertion.     

Cu-catalyzed oxidative C(sp2)-H cycloetherification of o-arylphenols for the preparation of dibenzofurans

A new process involving copper-catalyzed aerobic C(sp(2))-H activation, followed by cycloetherification, has been developed. This reaction serves as a direct method for the preparation of multisubstituted dibenzofurans starting with o-arylphenols. The presence of a strong para-electron-withdrawing group (e.g., NO(2)) on the phenol is essential for the success of the reaction.     

Synthesis of novel palladium OCN-pincer complexes: unprecedented sequential C(sp3)-H activation and aerobic oxidation in the reaction of N,N-dialkyl-3-[(N,N-dimethylamino)methyl]-2-iodoanilines with Pd2(dba)3

The reaction of N,N-dialkyl-3-[(N,N-dimethylamino)methyl]-2-iodoanilines with Pd2(dba)3 under O2 gives palladium OCN-pincer complexes by means of an unprecedented process that involves the formal aerobic oxidation of C(sp3)-H bonds at the alpha position of the aniline N atom.     

Ligand-accelerated cross-coupling of C(sp2)-H bonds with arylboron reagents

A ligand-accelerated Pd(II)-catalyzed C(sp(2))-H/arylboron cross-coupling reaction of phenylacetic acid substrates is reported. Using Ac-Ile-OH as the ligand and Ag(2)CO(3) as the oxidant, a fast, high-yielding, operationally simple, and functional group-tolerant protocol has been developed for the cross-coupling of phenylacetic acid substrates with aryltrifluoroborates. This ligand scaffold has also been shown to improve catalysis using 1 atm O(2) as the sole reoxidant, which sheds light on the path forward in developing optimized ligands for aerobic C-H/arylboron cross-coupling.     

Synthesis of polycyclic molecules by double C(sp2)-H/C(sp3)-H arylations with a single palladium catalyst

Polycyclic molecules were obtained in good yields by double C(sp(2))-H/C(sp(3))-H arylations mediated by a single palladium/phosphine catalyst. Both double intermolecular/intramolecular and intramolecular/intramolecular C-C couplings were performed successfully, which indicates that this concept has a broad applicability for the rapid construction of molecular complexity.     

N-heterocyclic carbene enabled rhodium-catalyzed ortho C(sp2)-H borylation at room temperature

We report a rhodium-catalyzed ortho C(sp²)-H borylation of 2-phenylpyridines using commercially available N-heterocyclic carbenes (NHCs) as ligand and pinacolatodiboron (B₂pin₂) as borylating reagent. The reaction could take place at room temperature, tolerating a wide range of functionalities and affording ortho borylated products in moderate to excellent yields. The current method is also applicable to gram-scale reaction with reduced catalyst loading.