Palladium-catalyzed direct ortho-alkynylation of aromatic carboxylic acid derivatives

The palladium-catalyzed direct alkynylation of C-H bonds in aromatic carboxylic acid derivatives is described. The use of 8-aminoquinoline as a directing group facilitates the alkynylation of an electronically diverse range of C(sp(2))-H bonds.     

Catalytic enantioselective alkynylation of prochiral sp3 C-H bonds adjacent to a nitrogen atom

[reaction: see text] The construction of chiral carbon centers via the first catalytic asymmetric alkynylation of prochiral CH2 groups was developed by using a copper-catalyzed double activation of sp3 and sp C-H bonds. Optically active 1-alkynylated tetrahydroisoquinolines were obtained by this method.     

Electrophilic alkynylation: the dark side of acetylene chemistry

In addition to the well-established nucleophilic alkynylation, the use of electrophilic alkynes can expand tremendously the scope of acetylene transfer reactions. The use of metal catalysis has recently led to a rebirth of this research area. Halogenoalkynes, hypervalent alkynyliodoniums, acetylene sulfones and in situ oxidized terminal acetylenes are the most often used reagents for electrophilic alkynylation. Heteroatoms such as N, O, S and P can be now efficiently alkynylated. For C-C bond formation, electrophilic acetylenes can be coupled with different organometallic reagents. Recently, the first breakthrough in direct C-H and C[double bond, length as m-dash]C bond alkynylation has also been reported. Finally, sulfonyl acetylenes are efficient for alkyne transfer on carbon-centered radicals.     

Silver-catalyzed decarboxylative alkynylation of aliphatic carboxylic acids in aqueous solution

C(sp(3))-C(sp) bond formations are of immense interest in chemistry and material sciences. We report herein a convenient, radical-mediated and catalytic method for C(sp(3))-C(sp) cross-coupling. Thus, with AgNO(3) as the catalyst and K(2)S(2)O(8) as the oxidant, various aliphatic carboxylic acids underwent decarboxylative alkynylation with commercially available ethynylbenziodoxolones in aqueous solution under mild conditions. This site-specific alkynylation is not only general and efficient but also functional group compatible. In addition, it exhibits remarkable chemo- and stereoselectivity.     

Copper-catalyzed coupling of tertiary aliphatic amines with terminal alkynes to propargylamines via C-H activation

We have developed a convenient and efficient method for coupling of tertiary aliphatic amines with terminal alkynes to propargylamines via C-H activation. The protocol uses CuBr as the catalyst, NBS as the free radical initiator, CH(3)CN as the solvent, and the alkynylation was selectively performed on the methyl of tertiary aliphatic amines at 80 degrees C. This is an economical and practical method for the synthesis of propargylamines.     

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.     

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.     

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.     

Recent advances in the transition metal-catalyzed twofold oxidative C-H bond activation strategy for C-C and C-N bond formation

The direct functionalization of heterocyclic compounds has emerged as one of the most important topics in the field of metal-catalyzed C-H bond activation due to the fact that products are an important synthetic motif in organic synthesis, the pharmaceutical industry, and materials science. This critical review covers the recent progresses on the regioselective dehydrogenative direct coupling reaction of heteroarenes, including arylation, olefination, alkynylation, and amination/amidation mainly utilizing transition metal catalysts (113 references).     

CuBr-catalyzed efficient alkynylation of sp3 C-H bonds adjacent to a nitrogen atom

A simple and effective catalytic method to construct propargylamine was developed by using copper bromide and tert-BuOOH via a combination of sp3 C-H bond and sp C-H bond activations followed by C-C bond formation.     

交叉脱氢偶联反应*

发现高效高选择性的有机合成反应是有机合成化学研究中一个重要的发展方向。传统的有机合成化学是建立在官能团相互转化基础上的,又称官能团化学。非活泼化学键（如C-H键）的直接官能团化省去了一步甚至多步制备官能团化的反应底物,因此,非活泼化学键活化是提高有机合成反应效率的一个重要发展方向。交叉脱氢偶联（Cross-Dehydrogenative-Coupling,CDC）反应就是直接利用不同反应底物中的C-H键,在氧化条件下,进行脱氢偶联反应形成C-C键。交叉脱氢偶联反应实现了更短的合成路线和更高的原子利用效率,为直接利用简单的原料进行高效的复杂的有机合成任务提供了一种新的思路和手段。     

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.     

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.     

Direct C2-alkylation of azoles with alcohols and ethers through dehydrogenative cross-coupling under metal-free conditions

A metal-free novel, simple, and highly efficient method for the direct C2-alkylation of azoles with alcohols and ethers has been developed on the basis of an oxidative C-H activation process. The dehydrogenative C-C cross-coupling reactions of α-position sp(3) C-H in alcohols and ethers with the 2-position sp(2) C-H in azoles proceeded smoothly in the presence of tert-butyl hydroperoxide (TBHP) under neat reaction conditions, which generated the corresponding products in good yields.     

Highly regioselective arylation of sp3 C-H bonds catalyzed by palladium acetate

A new palladium-catalyzed arylation process based on C-H activation has been developed. The utilization of pyridine-containing directing groups allows the beta-arylation of carboxylic acid derivatives and gamma-arylation of amine derivatives. Both primary and secondary sp3 C-H bonds, as well as sp2 C-H bonds, are reactive.     

The first Cu- and amine-free Sonogashira-type cross-coupling in the C-6-alkynylation of protected 2′-deoxyadenosine

The Sonogashira cross-coupling reaction offers a convenient route to C(sp)-C(sp²) bond formation. Although the Sonogashira reaction has traditionally been carried out in the presence of Pd catalyst and a co-catalyst of Cu(I) salt, the use of Cu(I) salt is often not efficient because it leads to the formation of unwanted side-products. This has prompted interest in recent years in the development of Cu-free Sonogashira cross-coupling reaction conditions. In addition, the development of Cu-free Sonogashira cross-coupling conditions for the alkynylation of nucleoside derivatives remains largely unexplored. Herein, we demonstrate that Cu- and amine-free Sonogashira-type cross-coupling lead to successful alkynylation of aryl bromides and heteroaryl bromides. For the first time, we have extended this method for the alkynylation of protected 2′-deoxyadenosine at the C-6 position.     

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.     

Synthesis of new class of alkyl azarene pyridinium zwitterions via iodine mediated sp3 C-H bond activation

An efficient and conceptually different approach toward C-H bond activation by using iodine mediated sp(3) C-H functionalization for the synthesis of alkyl azaarene pyridinium zwitterions is described. This work has the interesting distinction of being the first synthesis of a new class of alkyl azaarene pyridinium zwitterion via transition-metal-free sp(3) C-H bond activation of an alkyl azaarene.     

C-H...N and C-H...S hydrogen bonds--influence of hybridization on their strength

Simple complexes connected through C-H...S and C-H...N interactions are investigated: CH4...NH3, C2H4...NH3, C2H2...NH3, CH4...SH2, C2H4...SH2, and C2H2...SH2. Ab initio and DFT calculations are performed (SCF, MP2, B3LYP) using different basis sets up to the MP2/aug-cc-pVQZ//MP2/aug-cc-pVDZ level of approximation. The Bader theory is applied since MP2/6-311++G(d,p) wave functions are used to find and to characterize bond critical points in terms of electron densities and their Laplacians. The influence of hybridization on the properties of C-H...S and C-H...N systems is also studied showing that the strength of such interactions increases in the following order: C(sp3)-H...Y, C(sp2)-H...Y, C(sp)-H...Y, where Y = S, N--it is in line with the previous findings on C-H...O hydrogen bonds. The results also show that CH4...SH2 and C2H4...SH2 complexes should be rather classified as van der Waals interactions and not as hydrogen bonds. The frequency associated with the C-H stretch of C(sp3)-H...S is blue-shifted.     

An oxidative cross-dehydrogenative-coupling reaction in water using molecular oxygen as the oxidant: vanadium catalyzed indolation of tetrahydroisoquinolines

An aerobic oxidative cross-dehydrogenative coupling reaction between sp(3) C-H and sp(2) C-H bonds is developed by employing a vanadium catalyst (10 mol%) in an aqueous medium using molecular oxygen as the oxidant. This environmentally benign strategy exhibits larger substrate scope and shows high regioselectivity.