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.     

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.     

Metal-free intermolecular oxidative C-N bond formation via tandem C-H and N-H bond functionalization

The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both a N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.     

Copper-catalyzed synthesis of five-membered heterocycles via double C-N bond formation: an efficient synthesis of pyrroles, dihydropyrroles, and carbazoles

An efficient copper-catalyzed double C-N bond forming reaction using diiodides and nitrogen-centered nucleophiles including amides and carbamates is reported. The reactions proceed to afford di- or tri-substituted N-acylpyrroles, dihydropyrroles, and carbazoles in good to excellent yields when different diiodides such as 1,4-diiodo-1,3-butadienes, 1,4-dihalobut-1-enes, and 2,2′-diiodobiphenyls were employed, respectively. It is crucial to use CuI as the catalyst with the assistance of proper base and diamine ligand.     

Synthesis of new tetracyclic azaheteroaromatic cores via auto-tandem Pd-catalyzed and one-pot Pd- and Cu-catalyzed double C-N bond formation

Inter- and intramolecular transition metal-catalyzed amination of 2-chloro-3-iodopyridine and 2,3-dibromopyridine, respectively, with benzodiazinamines yielded six hitherto unknown tetracyclic azaheteroaromatic cores. C-N bond formation was achieved via auto-tandem (Pd-catalyst) as well as one-pot (sequential use of a Pd- and Cu-catalyst) catalysis.     

Palladium catalyzed C-N bond formation in the synthesis of 7-amino-substituted tetracyclines

A facile synthesis of 7-alkylamino- and 7-cycloalkylaminotetracycline derivatives has been accomplished using an in situ generated aminostannane precursor. This procedure is advantageous in that it allows the concise synthesis of a number of unreported tetracycline derivatives that are cumbersome to prepare through traditional methods. These compounds are crucial to understanding structure activity relationships in the D-ring of tetracycline-type antibiotics and the acquired efflux resistance mechanism to this class of antibiotics.     

A sequential metal-catalyzed C-N bond formation in the synthesis of 2-amido-indoles

A sequential metal-catalyzed C-N bond formation employing ortho-haloaryl acetylenic bromides is described. The initial amidation is highly selective for C (sp)-N bond formation, leading to o-haloaryl-substituted ynamides that can be useful building blocks, while the overall sequence provides a facile construction of 2-amido-indoles.     

Palladium-catalyzed tandem allenyl and aryl C-N bond formation: efficient access to N-functionalized multisubstituted indoles

An efficient palladium-catalyzed synthesis of N-functionalized multisubstituted indoles from easily accessible ortho-haloarylallenes and primary amines has been developed. A wide range of electronically and structurally varied nitrogen fragments could be introduced through this tandem C-N bond-forming process by tuning the reaction conditions.     

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.     

Copper-catalyzed, one-pot, three-component synthesis of benzimidazoles by condensation and C-N bond formation

Benzimidazoles were synthesized by the copper-catalyzed, one-pot, three-component reaction of 2-haloanilines, aldehydes, and NaN(3). The reaction was optimized when 2-iodo- or 2-bromoanilines (1.0 equiv), aldehydes (1.2 equiv), NaN(3) (2.0 equiv), 5 mol% of CuCl, and 5 mol % of TMEDA were reacted in DMSO at 120 °C for 12 h. Good yields resulted, and the reaction showed tolerance toward functional groups such as ester, nitro, and chloro. Aliphatic and heteroaromatic aldehydes also afforded the desired products in moderate to good yields.     

DBU-promoted tandem Michael-addition/cyclization for the synthesis of polysubstituted pyrroles

An efficient and transition-metal-free method for the synthesis of the structurally diversified pyrroles is described. Various α,β-unsaturated ynones reacted with N-substituted ethyl glycine ethyl ester hydrochlorides in the presence of DBU to form the corresponding products in good yields. This protocol has the advantages of readily available starting materials, mild reaction conditions and a wide scope of substrates, which provides a practical route for the synthesis of polysubstituted pyrroles.     

Photochemical electrocyclization of the indolinylphenylethenes involving a C-N bond formation

[reaction: see text] A novel oxidative photodehydrocyclization of indolinylphenylethenes to a polycyclic heteroaromatic cation with good yields was described. Starting from the trans derivative, the phototransformation is a multistep process. The process includes two photochemical reactions and a trans-cis isomerization reaction, followed by an 1-aza-1,3,5-hexatrienic electrocyclic reaction involving the formation of a C-N bond. The cyclized product gives the stable heteroaromatic cations from hydride elimination with oxygen from air or iodine.     

Copper-catalyzed intramolecular C-N bond formation: a straightforward synthesis of benzimidazole derivatives in water

A straightforward, efficient, and more sustainable copper-catalyzed method has been developed for intramolecular N-arylation providing the benzimidazole ring system. With Cu(2)O (5 mol %) as the catalyst, DMEDA (10 mol %) as the ligand, and K(2)CO(3) as the base, this protocol was applied to synthesize a small library of benzimidazoles in high yields. Remarkably, the reaction was exclusively carried out in water, rendering the methodology highly valuable from both environmental and economical points of view.     

Ligand-free CuCl-catalyzed C-N bond formation in aqueous media

CuCl-catalyzed N-arylation of alkyl amines and N-heterocycles with substituted aryl iodides and bromides can be carried out in 40% ⁿBu₄N⁺OH⁻ aqueous solution without any ligands.     

Intramolecular oxidative C-N bond formation for the synthesis of carbazoles: comparison of reactivity between the copper-catalyzed and metal-free conditions

New synthetic procedures for intramolecular oxidative C-N bond formation have been developed for the preparation of carbazoles starting from N-substituted amidobiphenyls under either Cu-catalyzed or metal-free conditions using hypervalent iodine(III) as an oxidant. Whereas iodobenzene diacetate or bis(trifluoroacetoxy)iodobenzene alone undergoes the reaction to provide carbazole products in moderate to low yields, combined use of copper(II) triflate and the iodine(III) species significantly improves the reaction efficiency, giving a more diverse range of products in good to excellent yields. On the basis of mechanistic studies including kinetic profile, isotope effects, and radical inhibition experiments, the copper species is proposed to catalytically activate the hypervalent iodine(III) oxidants. The synthetic utility of the present approach was nicely demonstrated in a direct synthesis of indolo[3,2-b]carbazole utilizing a double C-N bond formation.     

Two coordination polymers created via in situ ligand synthesis involving C-N and C-C bond formation

We report the synthesis and crystal structures of two transition metal-based coordination polymers comprising ligand molecules not included in the original reaction mixtures but instead formed in situ during hydrothermal treatment. Zinc meso-iminodisuccinate hydrate (I), Zn(2)(C(8)H(7)NO(8)).0.57H(2)O, formed from zinc acetate and L-aspartic acid, and tetraaquanickel(II) 5,10-dioxo-5,10-dihydro-4,9-dioxa-pyrene-2,7-dicarboxylate (II), Ni(H(2)O)(4)(C(16)H(4)O(8)), formed from nickel acetate and 5-hydroxyisophthalic acid. We show that the formation of I takes place via a fumaric acid intermediate, while the formation of II requires the formation of a new C-C bond. The structure of I consists of weakly interacting sheets, while the structure of II consists of strongly hydrogen-bonded chains. Crystal data: for I, P2(1)/n (14), a = 10.073 A, b = 9.894 A, c = 12.053 A, beta = 105.605 degrees, V = 1156.87(13) A(3), Z = 4; for II, P1 (2), a = 5.011 A, b = 6.526 A, c = 12.305 A, alpha = 76.868 degrees, beta = 84.988 degrees, gamma = 87.619 degrees, V = 390.3(4) A(3), Z = 1.     

Copper-mediated C-N bond formation via direct aminolysis of dithioacetals

Mediated by copper acetate, an efficient approach to the C-N bond formation via direct aminolysis of dithioacetals 2 and 5 with ammonia, primary or secondary amines are developed under mild conditions. Enaminones 3 and 6 were thus obtained in high to excellent yields with high chemoselectivity. This type of aminolysis reaction presents a new synthetic application of the dithioacetal functionality. [reaction: see text]