Intermolecular amidation of unactivated sp2 and sp2 C-H bonds via palladium-catalyzed cascade C-H activation/nitrene insertion

This communication describes the Pd(OAc)2-catalyzed intermolecular amidation reactions of unactivated sp2 and sp3 C-H bonds using primary amides and potassium persulfate. The substrates containing a pendent oxime or pyridine group were amidated with excellent chemo- and regioselectivities. It is noteworthy that reactive C-X bonds were well-tolerated and a variety of primary amides can be effective nucleophiles for the Pd-catalyzed C-H amidation reactions. For the reaction of unactivated sp3 C-H bonds, beta-amidation of 1 degrees sp3 C-H bonds versus 2 degrees C-H bonds is preferred. The catalytic reaction is initiated by chelation-assisted cyclopalladation involving C-H bond activation. Preliminary mechanistic study suggested that the persulfate oxidation of primary amides should generate reactive nitrene species, which then reacted with the cyclopalladated complex.     

Ru催化的C-H键的活化反应

概述了Ru催化的碳氢键的活化反应，包括C-H/烯烃，C-H/炔径和C-H/CO/烯烃 偶联反应，加氢酰化反应，硅化反应。     

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.     

C-H bond activation of hydrocarbons by an imidozirconocene complex

Monomeric imidozirconocene complexes of the type Cp2(L)Zr=NCMe3 (Cp = cyclopentadienyl, L = Lewis base) have been shown to activate the carbon-hydrogen bonds of benzene, but not the C-H bonds of saturated hydrocarbons. To our knowledge, this singularly important class of C-H activation reactions has heretofore not been observed in imidometallocene systems. The M=NR bond formed on heating the racemic ethylenebis(tetrahydro)indenyl methyl tert-butyl amide complex, however, cleanly and quantitatively activates a wide range of n-alkane, alkene, and arene C-H bonds. Mechanistic experiments support the proposal of intramolecular elimination of methane followed by a concerted addition of the hydrocarbon C-H bond. Products formed by activation of sp2 C-H bonds are generally more thermodynamically stable than those formed by activation of sp3 C-H bonds, and those resulting from reaction at primary C-H bonds are preferred over secondary sp3 C-H activation products. There is also evidence that thermodynamic selectivity among C-H bonds is sterically rather than electronically controlled.     

Palladium-catalyzed oxidative allylic C-H silylation

Palladium-catalyzed allylic C-H silylation was performed with use of hexamethyldisilane as the silyl source. These C-H functionalization reactions occur only in the presence of hypervalent iodine reagents or other strong oxidants and proceed with excellent regioselectivity, providing the linear allylic isomer of the allylsilane products. In demonstrating the first oxidative allylic C-H silylation of alkenes, this study marks an important advance for the catalytic C-H functionalization method.     

Intermolecular Ritter-type C-H amination of unactivated sp3 carbons

Intermolecular Ritter-type C-H amination of unactivated sp(3) carbons has been developed. This new reaction proceeds under mild conditions using readily available reagents and an inexpensive source of nitrogen (acetonitrile). A broad scope of substrates can be aminated with this method since many functional groups are tolerated. This reaction also allows for the direct, innate C-H amination of a variety of hydrocarbons such as cyclohexane without the need of prefunctionalization or installation of a directing group.     

Investigation on the regioselectivities of intramolecular oxidation of unactivated C-H bonds by dioxiranes generated in situ

We found that dioxiranes generated in situ from ketones 1-6 and Oxone underwent intramolecular oxidation of unactivated C-H bonds at delta sites of ketones to yield tetrahydropyrans. From the trans/cis ratio of oxidation products 1a and 2a as well as the retention of the configuration at the delta site of ketone 5, we proposed that the oxidation reaction proceeds through a concerted pathway under a spiro transition state. The intramolecular oxidation of ketone 6 showed the preference for a tertiary delta C-H bond over a secondary one. This intramolecular oxidation method can be extended to the oxidation of the tertiary gamma' C-H bond of ketones 9 and 10. For ketone 11 with two delta C-H bonds and one gamma' C-H bond linked respectively by a sp(3) hydrocarbon tether and a sp(2) ester tether, the oxidation took place exclusively at the delta C-H bonds. Finally, by introducing proper tethers, regioselective hydroxylation of steroid ketones 12-14 have been achieved at the C-17, C-16, C-3, and C-5 positions.     

Propargylation of 1,3-dicarbonyl compounds with 1,3-diarylpropynes via oxidative cross-coupling between sp3 C-H and sp3 C-H

A highly efficient oxidative-coupling reaction between diarylpropargylic sp(3) C-H and active methylenic sp(3) C-H was achieved with DDQ as oxidant. The reaction afforded a direct method for the propargylation of 1,3-dicarbonyl compounds, thus providing a concise synthesis of the corresponding products.     

Catalytic allylic alkylation via the cross-dehydrogenative-coupling reaction between allylic sp3 C-H and methylenic sp3 C-H bonds

A catalytic allylic alkylation was developed via the cross-dehydrogenative-coupling reaction of allylic sp3 C-H and methylenic sp3 C-H catalyzed by copper bromide and cobalt chloride in the presence of an oxidizing reagent, t-BuOOH. This methodology provides a direct way to use allylic sp3 C-H bonds for forming C-C bonds.     

Ru3(CO)12-catalyzed C-H/CO/olefin coupling of N-pyridylindolines. Direct carbonylation at a C-H bond delta to the pyridine nitrogen

The reaction of N-pyridylindolines with CO and ethylene in the presence of Ru3(CO)12 results in direct carbonylation at a C-H bond delta to the pyridine sp2 nitrogen, which represents a new type of C-H/CO/olefin coupling. The presence of a pyridine ring as a directing group on the substrates is essential for the reaction to proceed. The choice of N,N-dimethylacetamide (DMA) as the solvent is crucial for the reaction to proceed efficiently.     

Highly efficient copper-catalyzed nitro-Mannich type reaction: cross-dehydrogenative-coupling between sp3 C-H bond and sp3 C-H bond

A novel C-C bond formation method was developed via the cross-dehydrogenative-coupling (CDC) reaction catalyzed by using copper bromide in the presence of an oxidizing reagent, tert-BuOOH. The CDC reaction provides a simple and efficient catalytic method to construct beta-nitroamine via the reaction between sp3 C-H and sp3 C-H bonds.     

Acylation of five-membered N-heteroaromatic compounds by ruthenium carbonyl-catalyzed direct carbonylation at a C-H bond

The ruthenium-catalyzed carbonylation at the C-H bond of five-membered N-heteroaromatic compounds is described. The reaction of imidazoles with CO and olefins in toluene in the presence of a catalytic amount of Ru(3)(CO)(12) results in carbonylation of the C-H bond at the 4-position (adjacent to the sp(2)-nitrogen) of the imidazole ring to give acylated imidazoles in good to high yields. A wide range of olefins can be utilized in the carbonylation reaction, and a variety of functional groups are compatible under the reaction conditions. Other five-membered N-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can also be used for the carbonylation reaction, and in all cases, carbonylation takes place exclusively at a C-H bond alpha to the sp(2) nitrogen. The reactivity of the five-membered heterocycles corresponds to the pK(a) of the conjugate acid of these heterocycles. The higher the pK(a) of the substrate, the higher is the reactivity. This indicates that the pK(a) values are related to the ability of the nitrogen atom in the substrates to coordinate to a ruthenium center. The coordination of the substrates to the ruthenium center in the catalyst complex is a necessary prerequisite for the carbonylation to proceed.     

Heterocycle synthesis via direct C-H/N-H coupling

A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)(2) oxidant, and toluene solvent at 80-120 °C. Cyclization is effective for sp(2) as well as aliphatic and benzylic sp(3) C-H bonds.     

Solvent-controlled switch of selectivity between sp2 and sp3 C-H bond activation by platinum(II)

By merely changing the solvent, two different cyclometalated platinum complexes resulted from either sp(2) or sp(3) C-H bond activation can be prepared selectively. For example, the reaction of L1 with K(2)PtCl(4) in MeCN gave exclusively kinetic product 1a, while the reaction in AcOH was thermodynamically controlled and produced predominantly 1b.     

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.     

CuBr-catalyzed direct indolation of tetrahydroisoquinolines via cross-dehydrogenative coupling between sp3 C-H and sp2 C-H bonds

A novel and efficient C-C bond formation method was developed via the cross-dehydrogenative coupling (CDC) reaction of indoles and tetrahydroisoquinolines catalyzed by copper bromide in the presence of an oxidizing reagent, tert-BuOOH. The CDC reaction provides a simple and efficient catalytic method to construct indolyl tetrahydroisoquinolines via a combination of sp3 C-H bond and sp2 C-H bond followed by C-C bond formation.     

Intermolecular and intramolecular, platinum-catalyzed, acceptorless dehydrogenative coupling of hydrosilanes with aryl and aliphatic methyl C-H bonds

Intermolecular acceptorless dehydrogenative coupling of silanes with arene C-H bonds and intramolecular coupling of silanes with aryl and alkyl C-H bonds occur in good yield in the presence of 5 mol % of TpMe2PtMe2H (TpMe2 = hydridotris(3,5-dimethylpyrazolyl)borate) and related platinum(IV) complexes. The intermolecular reactions of arenes occurred with both trialkyl and dialkylaryl silanes. Intramolecular reactions of dialkylsilylalkylarenes occurred at aryl C-H bonds, and reactions of tributylsilane or dibutylphenylsilane occurred intramolecularly at the aliphatic, primary C-H bond. The reactions of arenes occurred preferentially at the least sterically hindered C-H bonds and preferentially with more electron-poor arenes. Crossover experiments and the lack of reactivity of the arylsilanes with H2 imply that the dehydrogenative silylation of arenes can be irreversible, even in a closed reaction vessel.     

Revealing Silylation of C(sp2)/C(sp3)–H Bonds in Arylphosphines by Ruthenium Catalysis

The first aromatic C−H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho-selectivity results from a four-membered metallacyclic intermediate involving phosphorus chelation. The developed system can be extended to the benzylic C−H silylation of arylphosphines. Diverse silylated arylphosphines are produced, exhibiting broad functional group compatibility. Further functionalization of the products under mild conditions renders the formed compounds useful building blocks.     

Revealing Silylation of C(sp2)/C(sp3)–H Bonds in Arylphosphines by Ruthenium Catalysis

The first aromatic C?H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho‐selectivity results from a four‐membered metallacyclic intermediate involving phosphorus chelation. The developed system can be extended to the benzylic C?H silylation of arylphosphines. Diverse silylated arylphosphines are produced, exhibiting broad functional group compatibility. Further functionalization of the products under mild conditions renders the formed compounds useful building blocks.     

C-H Bond activation and C-C bond formation in the reaction of 2,5-dimethylthiophene with TpMe2Ir compounds

The bulky 2,5-dimethylthiophene (2,5-Me2T) reacts at 60 degrees C with TpMe2Ir(C2H4)2 to give a mixture of two TpMe2Ir(III) hydride products, 3 and 4, that contain in addition a thienyl (3) or a thienyl-derived ligand (4). For the generation of 3 only sp2 C-H activation is needed, but the formation of 4 requires also the activation of an sp3 C-H bond and the formation of a new C-C bond (between vinyl and thienyl fragments). In the presence of 2,5-Me2T, compound 4 reacts further to produce a complex thiophenic structure (5, characterized by X-ray methods) that derives formally from two molecules of 2,5-Me2T and a vinyl fragment. Compounds 3-5 can be readily protonated by [H(OEt2)2][BAr'4](Ar'= 3,5-C6H3(CF3)2), with initial generation of carbene ligands (in the case of 3 and 5) as a consequence of H+ attack at the beta-carbon of the Ir-thienyl unit. Free, substituted thiophenes, derived from the original 2,5-Me2T, may be isolated in this way.