Palladium-catalyzed method for the synthesis of carbazoles via tandem C-H functionalization and C-N bond formation

The development of a new method for the assembly of unsymmetrical carbazoles is reported. The strategy involves the selective intramolecular functionalization of an arene C-H bond and the formation of a new arene C-N bond. The substitution pattern of the carbazole product can be controlled by the design of the biaryl amide substrate, and the method is compatible with a variety of functional groups. The utility of the new protocol was demonstrated by the concise synthesis of three natural products from commercially available materials.     

Palladium-catalyzed C-N bond formation via direct C-H bond functionalization. Recent developments in heterocyclic synthesis

The formation of carbon-nitrogen bonds by reaction between a nitrogen atom and an unactivated carbon-hydrogen bond is a highly atom-economical process that attracted the attention of the chemists in the last two decades. The widely useful amination and hydroamination reactions, which furnish acyclic or cyclic products, give access to various nitrogen-containing basic and fine chemicals. This review highlights recent progress in the development of palladium-catalyzed reactions that occur by direct functionalization of simple carbon-hydrogen bonds to give heterocyclic products. Pd(0)- and Pd(II)-catalyzed reactions are described separately, emphasizing the different behavior of the metal in these two oxidation states.     

Combined C-H functionalization/C-N bond formation route to carbazoles

A new method in which a series of substituted carbazoles is efficiently produced by the combination of an amide and an arene is described. The key feature of this method is the palladium-catalyzed tandem directed C-H functionalization and amide arylation. The method tolerates substitution on either ring of the biaryl amide substrates, and the products can be assembled in a simple two-step protocol from readily available reagents. The Pd(0) species generated are reoxidized to Pd(II) in the presence of Cu(OAc)2 and an atmosphere of oxygen.     

Fe-catalysed oxidative C-H functionalization/C-S bond formation

Iron was used as the catalyst for the direct C-H functionalization/C-S bond formation under mild conditions. Various substrates could afford benzothiazoles in moderate to excellent yields. Preliminary mechanistic studies revealed that pyridine played a crucial role for the high yields and selectivities.     

Copper-mediated synthesis of substituted 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles via C-H functionalization/C-N/C-O bond formation

An efficient method for the transformation of N-benzyl bisarylhydrazones and bisaryloxime ethers to functionalized 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles is described. The protocol involves a copper(II)-mediated cascade C-H functionalization/C-N/C-O bond formation under neutral conditions. Substrates having either electron-donating or -withdrawing substituents undergo the cyclization to afford the target heterocycles at moderate temperature.     

C-C, C-O and C-N bond formation via rhodium(III)-catalyzed oxidative C-H activation

Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene substrates bearing nitrogen and oxygen directing groups are covered in their coupling with unsaturated partners such as alkenes and alkynes. The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials. Comparisons and contrasts between rhodium(III) and palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of structures accessible is demonstrated with various recent examples, with a proposed mechanism for each transformation being briefly summarized (critical review, 138 references).     

Highly efficient synthesis of quinoxalinone-N-oxide via tandem nitrosation/aerobic oxidative C-N bond formation

An efficient method for constructing quinoxalinone-N-oxides from cyanoacetanilides has been developed. This transformation can be achieved using inexpensive reagents and molecular oxygen under mild conditions, thus offering a practical pathway to quinoxalinone-containing pharmaceuticals such as ataquimast and opaviraline.     

Palladium-catalyzed synthesis of cyclopentane-fused benzocyclobutenes via tandem directed carbopalladation/C-H bond functionalization

A new Pd-catalyzed reaction for the stereoselective synthesis of cyclopentane-fused benzocyclobutenes is described. These transformations likely proceed via carbamate-directed carbopalladation followed by intramolecular C-H activation of an alkylpalladium intermediate. The mechanistic relationship between these transformations and Pd-catalyzed reactions of gamma-(n-Boc-amino)alkenes with aryl bromides that afford pyrrolidines is discussed. Differences in reactivity between Pd-amino and Pd-amido complexes appear to play a key role in the outcome of these transformations.     

4-Aryl-2-quinolones from 3,3-diarylacrylamides through intramolecular copper-catalyzed C-H functionalization/C-N bond formation

Free NH 3,3-diarylacrylamides are cyclized to substituted 2-quinolones in the presence of CuI, PPh(3), and KO-t-Bu in o-xylene at 100 °C. The reaction proceeds through a C-H functionalization/C-N bond formation process. With unsymmetrical 3,3-diarylacrylamides, high selectivity is observed using substrates where the aromatic ring trans to the amide group bears o-methyl, -chloro, or -bromo substituents.     

Metal-free synthesis of 2-aminothiadiazoles via TBHP-Mediated oxidative C-S bond formation

An efficient one-pot synthesis of 2-amino-1,3,4-thiadiazoles from easily available aldehydes and thiosemicarbazide using TBHP as an oxidant has been described. Notably, these reactions were carried out at room temperature using ethanol as solvent. This is the first example for one-pot synthesis of 2-amino-1,3,4-thiadiazole derivatives from aldehydes. This new synthetic methodology provides a simple procedure utilizing a safer oxidizing system that affords the target products in mild reaction condition with satisfactory yields and wide substrate scope.     

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).     

Concerted C-N and C-H bond formation in a magnesium-catalyzed hydroamination

Coordinatively saturated To(M)MgMe (1; To(M) = tris(4,4-dimethyl-2-oxazolinyl)phenylborate) is an active precatalyst for intramolecular hydroamination/cyclization at 50 °C. The empirical rate law of -d[substrate]/dt = k'(obs)[Mg](1)[substrate](1) and Michaelis-Menten-type kinetics are consistent with a mechanism involving reversible catalyst-substrate association prior to cyclization. The resting state of the catalyst, To(M)MgNHCH(2)CR(2)CH(2)CH═CH(2) [R = Ph, Me, -(CH(2))(5)-], is isolable, but isolated magnesium amidoalkene does not undergo unimolecular cyclization at 50 °C. However, addition of trace amounts of substrate allows cyclization to occur. Therefore, we propose a two-substrate, six-center transition state involving concerted C-N bond formation and N-H bond cleavage as the turnover-limiting step of the catalytic cycle.     

Arylation of heterocycles via rhodium-catalyzed C-H bond functionalization

[reaction: see text] A new method for the rhodium-catalyzed arylation of a variety of heterocycles has been developed. The reaction provided moderate to good yields of the arylated products. A preliminary mechanistic investigation of this reaction revealed the intermediacy of an isolable N-heterocyclic carbene complex.     

C-C bond formation via double C-H functionalization: aerobic oxidative coupling as a method for synthesizing heterocoupled biaryls

The aerobic oxidative coupling of arenes such as benzofuran and N-substituted indoles with benzene and derivatives thereof is described. The reaction is shown to take place in both inter- and intramolecular scenarios.     

Metal-free N-iodosuccinimide-catalyzed mild oxidative C-H bond amination of benzoxazoles

A facile, efficient, and mild protocol for the synthesis of aminobenzoxazoles has been developed using direct oxidative C-H bond amination of benzoxazoles with secondary or primary amines. The reaction was performed using catalytic amount of N-iodosuccinimide and aqueous hydrogen peroxide as a green oxidant and in the absence of transition metals. Reaction proceeds smoothly at ambient temperature and requires shorter reaction time to furnish excellent yield of the desired products. Various cyclic, acyclic, and functionalized aliphatic amines were well tolerated under optimized reaction conditions and provided good to excellent yield of the respective aminobenzoxazoles.     

Metal-free oxidative C-C bond formation of active methylenic sp C-H bonds with benzylic sp C-H and allylic sp C-H bonds mediated by DDQ

An efficient and simple method for the oxidative coupling of benzylic and allylic sp³ C-H bonds with active methylenic sp³ C-H bonds under metal-free conditions was developed by employing 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. The reaction was shown to proceed smoothly for various 1,3-dicarbonyl compounds with a range of benzylic and allylic substrates in good to excellent yields.     

Metal-free direct oxidative intermolecular diarylation of anilides at ambient temperature assisted by cascade selective formation of C-C and C-N bonds

A new atom-economical process of direct oxidative intermolecular functionalization of aniline derivatives by simple arenes was developed. The products were formed in a highly regioselective manner under metal-free conditions at ambient temperature.     

Ruthenium-catalyzed oxidative synthesis of 2-pyridones through C-H/N-H bond functionalizations

An inexpensive ruthenium catalyst enabled oxidative annulations of alkynes by acrylamides with ample scope, which allowed for the preparation of 2-pyridones employing various electron-rich and electron-deficient acrylamides as well as (di)aryl- and (di)alkyl-substituted alkynes.