Consecutive C–F bond activation and C–F bond formation of heteroaromatics at rhodium: the peculiar role of FSi(OEt)3

C–F activation of 2,3,5,6-tetrafluoropyridine at [Rh{Si(OEt)₃}(PEt₃)₃] (1) yields [Rh{2-(3,5,6-C₅F₃HN)}(PEt₃)₃] (2) and FSi(OEt)₃, but in an unprecedented consecutive reaction FSi(OEt)₃ acts as a fluoride source to give [Rh(4-C₅F₄N)(PEt₃)₃] (4) by regeneration of the C–F bond and C–H activation. Analogous refluorination steps were observed for other 2-pyridyl rhodium complexes. NMR spectroscopic studies revealed a delicate balance between the feasibility for C–F bond formation accompanied by a C–H activation and the occurrence of competing reactions such as hydrodefluorinations induced by the intermediary presence of H₂.     

Synthesis of (diarylmethyl)amines using Ni-catalyzed arylation of C(sp3)–H bonds

The first nickel catalyzed deprotonative cross coupling between C(sp³)–H bonds and aryl chlorides is reported, allowing the challenging arylation of benzylimines in the absence of directing group or stoichiometric metal activation. This methodology represents a convenient access to the (diarylmethyl)amine moiety, which is widespread in pharmaceutically relevant compounds.     

Mechanism,reactivity, and selectivity of the iridium-catalyzed C(sp3)–H borylation of chlorosilanes

The iridium-catalyzed C(sp³)–H borylation of methylchlorosilanes is investigated by means of density functional theory, using the B3LYP and M06 functionals. The calculations establish that the resting state of the catalyst is a seven-coordinate Ir(v) species that has to be converted into an Ir(iii)tris(boryl) complex in order to effect the oxidative addition of the C–H bond. This is then followed by a C–B reductive elimination to yield the borylated product, and the catalytic cycle is finally completed by the regeneration of the active catalyst over two facile steps. The two employed functionals give somewhat different conclusions concerning the nature of the rate-determining step, and whether reductive elimination occurs directly or after a prior isomerization of the Ir(v) hydride intermediate complex. The calculations reproduce quite well the experimentally-observed trends in the reactivities of substrates with different substituents. It is demonstrated that the reactivity can be correlated to the Ir–C bond dissociation energies of the corresponding Ir(v) hydride intermediates. The effect of the chlorosilyl group is identified to originate from the α-carbanion-stabilizing effect of the silicon, which is further reinforced by the presence of an electron-withdrawing chlorine substituent. Furthermore, the source of selectivity for the borylation of primary over secondary C(sp³)–H can be explained on a steric basis, by repulsion between the alkyl group and the Ir/ligand moiety. Finally, the difference in the reactivity between C(sp³)–H and C(sp²)–H borylation is investigated and rationalized in terms of distortion/interaction analysis.     

DDQ-mediated oxidation of sp C–H bond for the direct synthesis of vicinal tricarbonyl compounds

A facile and direct synthetic method was developed for the construction of vicinal tricarbonyl compounds (VTCs) in moderate to excellent yields (46–92%), by treating the readily available 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reaction pathway involves the DDQ-mediated oxidative activation of sp³ C–H bond and subsequent coupling to TEMPO to form the key intermediate TEMPO-substrate adduct, which can be further converted to VTC products promoted by DDQ.     

Iodine-catalyzed efficient synthesis of azaarene substituted 3-hydroxy-2-oxindole derivatives through sp3 C–H functionalization

Iodine-catalyzed benzylic sp³ C–H bond functionalization of lutidines or picolines to isatins is described. This synthetic method provides a rapid entry towards biologically interesting 3-azaarene substituted 3-hydroxy-2-oxindole derivatives.     

Sulfonylation of C(sp3)–H bond for synthesis of 2-sulfolmethyl azaarenes catalyzed by TBAI in water

Research on Chemical Intermediates - A tetrabutylammonium iodide (TBAI)-catalyzed method for synthesis of 2-sulfolmethyl quinolone has been developed. Using water as solvent, a wide range of...     

Friedlander synthesis of highly functionalized isoxazolyl quinoline libraries via addition of C(sp3)–H bond to aldehydes

A novel protocol for ionic liquid (IL)-mediated C(sp³)–H bond functionalization of 3,5-dimethyl-4-nitroisoxazoles 4 to substituted o-amino benzaldehydes 5 was developed in excellent yields. Isoxazolyl aryl ethanones 7 have been synthesized from isoxazolyl aryl ethanol synthon 6. Furthermore, utilizing the later as synthons for IL promoted Friedlander synthesis of highly functionalized isoxazole substituted quinoline libraries 9. The merit of this synthesis is easily available and economical starting materials, effective utilization of all the reactants, and simple workup procedure. It is noteworthy that ionic liquid used in C(sp³)–H bond functionalization and Friedlander synthesis reactions can be recycled and reused five times without significant decrease in activity.     

Asymmetric C–H functionalization of cyclopropanes using an isoleucine-NH2 bidentate directing group

The systematic investigation of substrate-bound α-amino acid auxiliaries has resulted in catalytic asymmetric C–H functionalization of cyclopropanes enabled by amino acid amides as chiral bidentate directing groups. The use of an Ile-NH₂ auxiliary embedded in the substrate provided excellent levels of asymmetric induction (diastereomeric ratio of up to 72 : 1) in the Pd(ii)-catalyzed β-methylene C(sp³)–H bond activation of cyclopropanes and cross-coupling with aryl iodides.     

Oxidation-induced ortho-selective C–H bond functionalization of 2-naphthylamine derivative

Selective C–H bond functionalization has been emerged as a versatile strategy for the construction of new chemical bonds. In the past decades, the directing group(DG)-assisted C–H bond activation has been developed as one of the most efficient methods for selective C–H functionalization. Although a great progress has been made by utilizing this traditional method, developing new strategy for selective C–H bond functionalization is still highly demanded. Hence, a novel oxidation-induced C–H bond functionalization method was demonstrated in this work. By this new method, ortho-C(sp2)–H chlorination of N-substituted 2-naphthylamine was realized in a highly selective manner.     

Indium trichloride catalyzed sp C–H bond functionalization of 2-alkyl azaarenes under microwave irradiation

Microwave promoted indium trichloride (10 mol %) catalyzed sp³ C–H bond functionalization of 2-alkyl azaarenes 1 or 4 has been observed to construct C–C bond either with but-2-ene-1,4-diones 2 or (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one (6) giving access to 2-((quinolin-2-yl)methyl)butane-1,4-diones 3, 2-((pyridin-2-yl)methyl)butane-1,4-diones 5, or 3-(quinolin-2-yl)propan-2-yl)indolin-2-ones 7 in good yields using 1,4-dioxane as solvent.     

Enantioselective cis-β-lactam synthesis by intramolecular C–H functionalization from enoldiazoacetamides and derivative donor–acceptor cyclopropenes

β-Lactam derivatives are produced through intermediate donor–acceptor cyclopropene intermediates in high yield, exclusive cis-diastereoselectivity, and high enantiocontrol in a chiral dirhodium carboxylate catalyzed intramolecular C–H functionalization reaction of enoldiazoacetamides.     

Synthesis of 3-(quinolin-2-yl)indolizines through iodine-mediated sp3C–H functionalization of azaarenes

An efficient approach toward C–H bond activation using iodine-mediated sp³C–H bond functionalization for the synthesis of dialkyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylates and dialkyl 3-(quinolin-2-yl)pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylates through 1,3-dipolar cycloaddition reaction of nitrogen ylides with acetylenic esters is described.     

A catalytic asymmetric total synthesis of (–)-perophoramidine

We report a catalytic asymmetric total synthesis of the ascidian natural product perophoramidine. The synthesis employs a molybdenum-catalyzed asymmetric allylic alkylation of an oxindole nucleophile and a monosubstituted allylic electrophile as a key asymmetric step. The enantioenriched oxindole product from this transformation contains vicinal quaternary and tertiary stereocenters, and is obtained in high yield along with high levels of regio-, diastereo-, and enantioselectivity. To install the second quaternary stereocenter in the target, the route utilizes a novel regio- and diastereoselective allylation of a cyclic imino ether to deliver an allylated imino ether product in near quantitative yield and with complete regio- and diastereocontrol. Oxidative cleavage and reductive amination are used as final steps to access the natural product.     

Catalytic asymmetric α-C(sp)–H functionalization of amines

In this digest review, we aim to give a brief overview of catalytic asymmetric α-C(sp³)–H functionalization of amines, mainly via internal tert-aminocyclization, intermolecular C–H oxidative couplings, and redox neutral metal insertion C–H bond.     

Mini-review on the functionalization of C–H bond to C-X linkage via metalla-electrocatalyzed tool

To date, the C–H activation protocol and its functionalization of bonds via transition metal have witnessed major attention in coordination chemistry as they eliminate the pre-functionalization of the substrate. Conventional approaches use a stoichiometric amount of chemical oxidants which are toxic under mild conditions. This will create a major problem in C–H functionalization reactions that involve a selective issue of reductive elimination from metal center to form a significant amount of by-product (waste) in large amount which is difficult to separate and thus reduce atom economy and sustainability of the reaction medium. This will limit catalyst turnover and thus, decreases the reaction rate. To avoid this, there is an urgent need for renewable resources which bring about the functionalization of the C–H bond. Metalla-electro catalyzed is the cleanest tool on the platform of C–H activation chemistry. Here, electricity was being involved as a clean surrogate of chemical oxidant and holds unleashed potential for an oxidative protocol of C–H activation with unmet site selectivity. This mini-review pay attention to the C–H functionalization of the bond to C–C, C–N, and C-Miscellaneous (P, O, and S) bond linkage by employing different transition metal {precious (Pd, Rh, Ru, and Ir)} and {earth-abundant (Mn, Ni, Co, and Cu)} using the electrochemical tool. Such metalla-electro catalyzed tools are helpful to those who were not being trained electrochemists but can unleash this potential benefit in various sustainable organic transformations.     

Iron(III) catalyzed direct C–H functionalization at the C-3 position of chromone for the synthesis of fused chromeno-quinoline scaffolds

This communication describes an iron-catalyzed route for the synthesis of 6-substituted chromeno[3,2-c]quinolin-7-one. The method developed does not require any pre-functionalization to execute the pivotal coupling reaction at the C-3 position of flavones. The final step involves the consecutive application of imine formation, C_sp²-C_sp² coupling and oxidation reaction, with aromatic aldehydes and 2-(2-aminophenyl)-4H-chromen-4-one as the reactants. Presence of electron donating/withdrawing groups was well tolerated in the aldehydes and the method developed could also be extended to other substituted 2-(2-aminophenyl)-4H-chromen-4-one’s. This is the first report of synthesis of 6-substituted chromeno[3,2-c]quinolin-7-one’s via direct functionalization of the C-3 site of flavones.     

When C–H bond functionalization meets visible-light photoredox catalysis

In recent years, visible-light-mediated C–H bond functionalization has become an emerging field at the forefront of organic synthesis. It is of considerable interest to academic and industrial chemists owing to the atom/step economical features as well as the overall sustainability. In this Letter, we mainly discussed the recent typical examples in sp² and sp³ C–H bond functionalization by means of visible-light photoredox catalysis.     

Acid ionic liquid promoted addition of C(sp)–H bond to aldehyde

A novel protocol for acid ionic liquid promoted C(sp³)–H bond functionalization of alkyl azaarenes and nucleophilic addition to aldehydes was developed in good to excellent yields, which provides an efficient approach for the synthesis of alkyl-substituted azaarene derivatives. It is worthwhile to note that acid ionic liquid used for this reaction can be recycled and reused six times without a significant decrease in activity.     

Carbon–hydrogen (C–H) bond activation at PdIV: a Frontier in C–H functionalization catalysis

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a Pd^II/Pd^IV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a Pd^II centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at Pd^IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd^II. This mini review highlights proposed examples of C–H activation at Pd^IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.