From C(sp(2))-H to C(sp(3))-H: systematic studies on transition metal-catalyzed oxidative C-C formation

In this tutorial review, we will summarize our recent efforts in transition metal-catalyzed oxidative coupling via C-H functionalization of aromatic, benzylic and allylic C-H bonds. Related works from other laboratories will be cited where suitable, aiming to give the readers a flavor of this field. Special emphasis is placed on the reaction design and development.     

Copper-catalyzed direct thiolation of azoles with aliphatic thiols

Cu(II)-catalyzed direct thiolation of azoles with thiols is described via intermolecular C-S bond formation/C-H functionalization under oxidative conditions. Both aryl thiols and aliphatic thiols are used as coupling partners, and furnished the thiolation products in moderate to good yields. The reaction is compatible with a wide range of heterocycles including oxazole, thiazole, imidazole and oxadiazole.     

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).     

稀土金属催化的碳氢官能团化反应

过渡金属催化的碳氢官能团化反应具有原子经济性高、区域选择性好和合成路线简短等优点,近年来得到了化学家们的广泛关注,是当前有机合成化学的热门研究领域之一.近几年来,稀土金属催化剂也逐渐被开发应用于该领域,得到优异的结果,同时也表现出一些独特的催化活性.本文综述了稀土金属络合物催化的碳氢官能团化反应,主要包括C-H烷基化反...     

An easy synthetic approach to 1,2,3-triazole-fused heterocycles

A convenient synthesis of 1,2,3-triazole-fused isoindolines and dihydroisoquinolines in good to excellent yield is reported, starting from easily available terminal alkynes and (2-haloaryl)alkylazides. The method is based upon a cycloaddition reaction, via click chemistry, followed by a transition metal-catalyzed functionalization of a C-H bond.     

Catalytic C-H functionalization by metalloporphyrins: recent developments and future directions

Metalloporphyrins are a class of versatile catalysts with the capability to functionalize saturated C-H bonds via several well-defined atom/group transfer processes, including oxene, nitrene, and carbene C-H insertions. The corresponding hydroxylation, amination, and alkylation reactions provide direct approaches for the catalytic conversion of abundant hydrocarbons into value-added functional molecules through C-O, C-N, and C-C bond formations, respectively. This tutorial review describes metalloporphyrin-based catalytic systems for the functionalization of different types of sp(3) C-H bonds, both inter- and intramolecularly, including challenging primary C-H bonds. Additional features of metalloporphyrin-catalyzed C-H functionalization include unusual selectivities and high turnover numbers.     

Copper-catalyzed enantioselective intramolecular alkene amination/intermolecular Heck-type coupling cascade

Enantioselective copper-catalyzed cyclization of γ-alkenylsulfonamides and a δ-alkenylsulfonamide in the presence of a range of vinyl arenes results in variously functionalized 2-substituted chiral nitrogen heterocycles via a formal alkene C-H functionalization process. Application of this reaction to the concise synthesis of a 5-HT(7) receptor antagonist is demonstrated.     

Catalytic C-H amination for the preparation of substituted 1,2-diamines

Rhodium-catalyzed C-H insertion of hydroxylamine-derived sulfamate esters makes possible the synthesis of unique oxathiadiazinane heterocycles, which upon mild reduction furnish differentially substituted 1,2-diamine products. This highly chemo- and diastereoselective transformation underscores the power of catalytic C-H functionalization as a general approach to C-N bond construction.     

Efficient metal-catalyzed hydroarylation of styrenes

[reaction: see text] A highly efficient metal-catalyzed hydroarylation of various styrenes has been developed. This new bismuth-catalyzed C-H functionalization provides straightforward access to a series of valuable 1,1-diarylalkane products.     

Quinuclidine and its derivatives as hydrogen-atom-transfer catalysts in photoinduced reactions

Hydrogen-atom-transfer(HAT) is an efficient way for direct C-H functionalization of inert C-H bonds,therefore it has attracted great interests in recent years. So far, various HAT catalysts have been developed. Among them, quinuclidine and its derivatives show different characters toward other HAT catalysts as they tend to abstract electron-rich and hydridic hydrogens in the presence of weak and neutral C-H bonds. These features enable direct C-H functionalization of compounds with various groups which are unable or difficult by other methods. This review summarizes recent advance of photoinduced reactions with quinuclidine and its derivatives as HAT catalysts and exhibits powerful synthetic potential by using quinuclidine and its derivatives as HAT catalysts.     

Pd-Catalyzed C-3 functionalization of indolizines via C-H bond cleavage

New transition metal-catalyzed methods for the arylation of indolizines by the direct cleavage of C-H bonds have been developed. A wide range of aryltrifluoroborate salts react with indolizines in the presence of Pd(OAc)(2) catalyst and AgOAc oxidant to give the arylated indolizines in high yields. Both electron-donating and electron-withdrawing groups perform smoothly while bromide and chlorine substituents are tolerated. In addition, the indolizines display similar reactivities in the Pd-catalyzed reaction with 3-phenylpropiolic acid to afford the corresponding C-3 alkynylated indolizines. These methods allow the direct functionalization of indolizines in one step.     

Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization

Chromone and flavone are both central backbones of natural products and clinical medicines. Synthesis of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional materials. The direct C-H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone derivatives. Considering the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C-H activation or functionalization, we review herein the research advances in the C-H bond activation and functionalization reactions of chromone and flavones, in hope of showing the current states and promise of the research domain.     

Reaching Green: Heterocycle Synthesis by Transition Metal-Catalyzed C−H Functionalization in Sustainable Medium

Catalytic C−H functionalization has emerged as an efficient alternative to traditional coupling reactions. However, some of these reactions depend on environmentally harmful solvents, weakening the overall green nature of these methods. As organic processes consume large amount of solvents, the use of less harmful solvents enhance the sustainability of these reactions. Herein, we present an overview of transition metal-catalyzed C−H functionalization reactions for the synthesis of heterocycles in sustainable solvents based on CHEM21 solvent selection guide.     

Palladium-catalyzed annulation of aryl heterocycles with strained alkenes

[reaction: see text] An annulation reaction proceeding by the intermolecular addition of an arylpalladium(II) halide across a strained alkene, followed by an intramolecular C-H functionalization of a pendant heterocycle is described. A variety of polycyclic heterocycles have been prepared from readily accessible haloaryl heterocycles by annulation with a range of strained alkene partners.     

Catalytic C-H functionalization driven by CO as a stoichiometric reductant: application to carbazole synthesis

[reaction: see text] A palladium-catalyzed regioselective C-H bond functionalization driven by CO as the stoichiometric reductant is described. Nitrogen heterocycles, e.g., carbazoles, are accessible in good to excellent yields with use of palladium acetate and 70 psig of carbon monoxide at 140 degrees C.     

C-H bond functionalization in the synthesis of fused 1,2,3-triazoles

A highly modular approach to fused 1,2,3-triazoles has been developed featuring a one-pot procedure combining copper(I) catalyzed azide-alkyne cycloaddition and palladium-catalyzed C-H bond functionalization. A class of structurally unique heterocycles was synthesized in good yields.     

A general procedure for the synthesis of alkyl- and arylethynyl-1,2,3-triazole-fused dihydroisoquinolines

A general procedure for the synthesis of the title compounds has been devised starting from the available 2-halophenylethyl azides, by means of click reactions with trimethylsilylacetylene or 1-trimethylsilyl-1,3-butadiyne followed by a transition metal-catalyzed functionalization of C-H bond. A further extension of this procedure led us to devise the synthesis of more complex 4,4'-bitriazole-fused dihydroisoquinolines.     

Metal catalysts: applications in higher-membered <Emphasis Type="Italic">N</Emphasis>-heterocycles synthesis

In recent decades, a large number of reports related to synthesis of N-, O- and S-containing heterocycles have appeared owing to a wide variety of their biological activity. The metal-catalyzed synthesis of heterocycles is becoming an important and highly rewarding protocol in organic synthesis. This review focuses on the use of metal as a catalyst for the synthesis of nitrogen-containing heterocycles. It describes the formation of higher-membered heterocyclic rings.     

Directing group assists in transition metal-catalyzed site-selective C-H bond activation/transformations

In the review paper, we attempt to point out the importance of the directing group in the transition metal-catalyzed C-H bond activation/transformations, especially in the site-selectivity and reactivity. The employment of the directing groups in the type of reaction can enable a chemist to straightforwardly approach the desired molecular skeletons. Thus, understanding the role of the directing groups in the C-H bond activation/transformations would benefit chemists to design better auxiliary groups and develop more efficient and practical synthetic methodologies. We believe that the synthetic strategy based on the utility of the directing group to assist in the transition metal-catalyzed C-H bond activation/transformations will keep playing as a mainstream role in the research field.     

Iron-facilitated direct oxidative C-H transformation of allyl arenes to alkenyl aldehydes

A direct oxidative approach to alkenyl aldehydes from allyl arenes via allyl sp³ C-H functionalization was disclosed. An inexpensive iron catalyst was employed to facilitate this transformation. The mechanistic studies indicate that the cleavage of the allyl sp³ C-H bond is involved in the rate-determining step.