Synthesis of isoindolinones via palladium-catalyzed C-H activation of N-methoxybenzamides

The synthesis of isoindolinones from N-methoxybenzamides and alkenes has been achieved by Pd-catalyzed ortho sp(2) C-H activation and intramolecular oxidative amidation, which involve the cleavage of four bonds and formation of two bonds.     

Catalytic addition of C-H bonds to multiple bonds with the aid of ruthenium complexes

Ruthenium complexes, e.g., RuH2(CO)(PPh3)3, have been found to catalyze the direct addition of ortho carbon-hydrogen bonds of aromatic ketones to olefins and acetylenes with high efficiency and selectivity. The C-H/olefin coupling reaction is applicable to not only C-H bonds in aromatic ketones but also to those in a,b-enones and aro-matic esters. Catalytic addition of ortho carbon-hydrogen bonds of aromatic imines to olefins is found to be catalyzed by Ru3(CO)12.     

Hydrofluoroarylation of alkynes with fluoroarenes

A combination of Ni(cod)(2) and PCyp(3) is found to be an effective catalyst for chemoselective activation of the C-H bond of fluoroarenes over C-F bonds followed by insertion of alkynes to allow direct alkenylation of the electron-deficient arenes. The characteristics of the reactions are: a C-H bond ortho to a fluorine substituent is selectively activated; the reactivity of fluorobenzenes is roughly proportional to the number of fluorine atoms. The reaction conditions tolerate a broad range of both alkynes and fluoroarenes containing both electron-withdrawing and -donating groups, thus allowing efficient synthesis of a variety of substituted ethenes containing a fluoroaryl motif in high regio- and stereoselective manners. Mechanistic studies including both labeling experiments and stoichiometric reactions reveal that oxidative addition of C-H bonds in fluoroarenes to nickel(0) is kinetically highly facile whereas that of C-F bonds is thermodynamically favoured.     

Pd(II)-catalyzed ortho trifluoromethylation of arenes and insights into the coordination mode of acidic amide directing groups

A Pd(II)-catalyzed trifluoromethylation of ortho C-H bonds with an array of N-arylbenzamides derived from benzoic acids is reported. N-Methylformamide has been identified as a crucial promoter of C-CF(3) bond formation from the Pd center. X-ray characterization of the C-H insertion intermediate has revealed a rare coordination mode of acidic amides as directing groups and the origin of their capacity in directing C-H activation.     

Nickel-catalyzed alkenylation and alkylation of fluoroarenes via activation of C-H bond over C-F bond

Nickel/P(c-C(5)H(9))(3) (PCyp(3)) catalyst effects the addition reactions of fluoroarenes across alkynes, 1,3-dienes, and vinylarenes via the activation of C-H bonds over C-F bonds. The acidic C-H bonds located ortho to fluorine are exclusively activated to afford a range of alkenylated and alkylated fluoroarenes.     

Synthesis of polycyclic heterocycles via a one-pot ortho alkylation/direct heteroarylation sequence

[reaction: see text] Polycyclic thiophenes and furans were synthesized using a one-pot ortho alkylation/direct heteroarylation reaction sequence. Under the optimized reaction conditions, aryl iodides were coupled with 3-(bromoalkyl)thiophenes or -furans, affording six- and seven-membered annulated ring products via formation of two C-C bonds from two aryl C-H bonds.     

Outer-sphere direction in iridium C-H borylation

The NHBoc group affords ortho selective C-H borylations in arenes and alkenes. Experimental and computational studies support an outer sphere mechanism where the N-H proton hydrogen bonds to a boryl ligand oxygen. The regioselectivities are unique and complement those of directed ortho metalations.     

Remote C-H bond functionalization reveals the distance-dependent isotope effect

Iodination of remote aryl C-H bonds has been achieved using palladium acetate as the catalyst and iodoacetate (IOAc) as the oxidant. Systematic kinetic isotope studies imply a mechanistic regime shift as the number of bonds separating the directing heteroatom and the target C-H bond increases. Both isotope and electronic effects observed in remote C-H bond activation are consistent with an electrophilic palladation pathway in which the initial palladation is slower than the C-H bond cleavage.     

Ruthenium-catalyzed C-H/CO/Olefin coupling reaction of N-arylpyrazoles. Extraordinary reactivity of N-arylpyrazoles toward carbonylation at C-H bonds

The reaction of 1-arylpyrazoles with CO and ethylene in the presence of Ru(3)(CO)(12) resulted in regioselective carbonylation at the ortho C-H bonds. While it is found that the pyrazole ring also functions as the directing group for C-H bond cleavage, the efficiency of the reaction depends on the position of the pyrazole ring.     

Control of product selectivity by a styrene additive in ruthenium-catalyzed C-H arylation

A unique effect of styrene additive on product selectivity was observed for RuH(2)(CO)(PPh(3))(3)-catalyzed C-H arylation of acetophenone derivatives bearing two ortho C-H bonds. Without styrene, the C-H arylation with arylboronates gives diarylation products as the major products throughout the reaction, but the use of styrene as an additive switches the product selectivity and leads to selective formation of monoarylation products.     

Rhodium-catalyzed selective olefination of arene esters via C-H bond activation

A new catalytic procedure of ortho-olefination of benzoates and benzaldehydes has been developed. Ester and carboxaldehyde units were revealed to be effective chelating groups in focusing the activation of aryl C-H bonds ortho to the directing moieties under the Rh-catalyzed oxidative conditions. The reaction is highly regioselective with a range of benzoates and benzaldehydes enabling the efficient olefination with acrylates, acrylic acid, and styrenes.     

Oxidative coupling of NH isoquinolones with olefins catalyzed by Rh(III)

Rh(III)-catalyzed oxidative coupling reactions between isoquinolones with 3-aryl groups and activated olefins have been achieved using anhydrous Cu(OAc)(2) as an oxidant to give tetracyclic products. The nitrogen atom acts as a directing group to facilitate ortho C-H activation. This reaction can be one-pot starting from methyl benzohydroxamates, without the necessity of the isolation of isoquinolone products. A broad scope of substrates has been demonstrated, and both terminal and internal activated olefins can be applied. In the coupling of N-methylmaleimide, a Wacker-like mechanism was proposed, where backside attack of the NH group in isoquinolones is suggested as a key step. Selective C-H activation has also been achieved at the 8-position of 1-naphthol, leading to an olefination product.     

Low-valent niobium-mediated double activation of C-F/C-H bonds: fluorene synthesis from o-arylated alpha,alpha,alpha-trifluorotoluene derivatives

By the treatment of 0.3 molar amount of NbCl5 and LiAlH4, o-arylated alpha,alpha,alpha-trifluorotoluenes afforded fluorene derivatives in good yields. C-F bonds of the CF3 group and the neighboring ortho C-H bond were doubly activated to give the coupling products.     

Amide-directed arylation of sp C-H bonds using Pd(II) and Pd(0) catalysts

Protocols to effect β-arylation of sp³ C-H bonds via Pd(II)/(IV) and Pd(0)/(II) catalytic cycles have been achieved using a newly developed monodentate CONHC₆F₅ directing group. These reactions provide an unprecedented means to functionalize sp³ C-H bonds in aliphatic carboxylic acid-derived substrates.     

Ruthenium- and rhodium-catalyzed direct carbonylation of the ortho C-H bond in the benzene ring of N-arylpyrazoles

The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon monoxide and ethylene in the presence of Ru(3)(CO)(12) or Rh(4)(CO)(12) resulted in the site-selective carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones. A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher reactivities than would be expected, based on the pK(a) values of the conjugate acid of pyrazole. The choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best result.     

Ligand-controlled gold catalyzed highly site-selective carbene transfer in C-H bond formation

A ligand-controlled gold-catalyzed highly site-selective insertion of a carbene into carbonhydrogen bonds has been achieved.This new gold-catalyzed direct C-H bond functionalization opens up new exciting opportunities for the functionalization of C-H bond.     

C-H键选择性直接电氧化研究

C-H键是有机化合物中最基本的化学键,C-H键的活化和直接转化避免了反应物的预先官能化,是最终实现烷烃类化合物转化为不同种类有机化合物最直接、高效的转换方式,通过C-H键构建C-X键（X=O、C、N）是非常重要和具有挑战性的研究. C-H键直接电氧化活化过程中以“电子”参与反应,不需要加入额外的催化剂,并可通过选择合适的电极材料、支持电解质、溶剂和反应温度,通过恒电流或者恒电位电解,进行具有特定的反应选择性和区域选择性的C-H键电氧化活化,从而获得含其他活性基团的目标产物.     

CH...O and CH...F links form the cage structure of dioxane-trifluoromethane

The molecular beam Fourier transform microwave spectrum of 1,4-dioxane-trifluoromethane has been assigned and measured. The two subunits form a cage stabilized by one C-H...O and two C-H...F weak hydrogen bonds. The C-H...O link involves the axial lone pair of one of the two equivalent ring oxygens, while the two C-H...F bridges connect trifluoromethane to the two axial hydrogens in positions 3 and 5. The dissociation energy has been estimated from the D(J) centrifugal distortion parameter to be approximately 6.8 kJ/mol.     

Copper-mediated chelation-assisted ortho nitration of (hetero)arenes

A novel copper-mediated chelation-assisted ortho C-H nitration of (hetero)arenes has been developed for the first time, which used dioxygen as terminal oxidant and 1,2,3-TCP as solvent, leading to the synthesis of nitroaromatics with excellent regioselectivity and in good yields. Mechanistic investigations indicate a mechanism involving a four-centered transition state, with simultaneous cleavage of an ortho C-H bond and a N-O bond of the nitrate anion on the 2-arylpyridine-coordinated copper(II) complex.     

Chelation-assisted Rh(I)-catalyzed ortho-alkylation of aromatic ketimines or ketones with olefins

Described herein is the Rh(I)-catalyzed ortho-alkylation of aromatic ketimines or ketones with olefins. This method showed high reactivity and selectivity to monoalkylation for a variety of olefins including 1-alkenes with an allylic proton, alpha,omega-dienes, and internal olefins. For a mechanistic study, H/D exchange experiments were carried out, which demonstrated that the ortho C-H bond could be easily cleaved even at the low temperature of 45 degrees C. The key step of this reaction is the formation of a stable five-membered metallacycle by a chelation-assisted ortho C-H bond activation. Furthermore, the direct ortho-alkylation of aromatic ketones with the Rh(I) complex was successfully achieved by adding 50 mol % of benzylamine as a chelation-assistant tool.