Catalytic C-H amination with aromatic amines

Aniline joins the club: A β-diketiminato copper(I) catalyst enables C-H amination of anilines employing low catalyst loadings to preclude oxidation to the diazene ArN=NAr. Electron-poor anilines are particularly resistant towards diazene formation and participate in the amination of strong and unactivated C-H bonds. N-alkyl anilines also take part in C-H amination.     

Amination of aromatic olefins with anilines: a new domino synthesis of quinolines

A new catalytic amination of aromatic olefins with anilines is presented. In a domino reaction, substituted quinoline derivatives are obtained in the presence of cationic rhodium complexes, such as [Rh(cod)2]BF4, and PPh3. Ethylbenzene is formed as a by-product in this new oxidative reaction. The first transition metal catalyzed anti-Markovnikov hydroamination of styrene with anilines occurs as a side reaction. Mechanistic investigations strongly support the regioselective oxidative amination of styrene as the key reaction step.     

Direct amination of γ-halo-β-ketoesters with anilines

The direct amination of α-haloacetoacetates with anilines is described. Compared to existing methods, this simple protocol provides an attractive strategy to prepare diverse γ-anilino-β-ketoesters in one step. Good to excellent yields of the amination products were obtained under robust conditions, providing versatile and useful scaffolds.     

IMINO DIELS-ALDER REACTIONS CATALYZED BY OXALIC ACID DIHYDRATE. SYNTHESIS OF TETRAHYDROQUINOLINE DERIVATIVES

Oxalic acid dihydrate is found to catalyze the Imino Diels-Alder reaction of schiff bases derived from substituted anilines with cyclopentadiene, results in the formation of Tetrahydroquinoline derivatives in moderate yields.     

Synthesis of 2,3-dihydroindoles, indoles, and anilines by transition metal-free amination of aryl chlorides

Aliphatic and aromatic amines react with 2- and 3-chlorostyrene in the presence of potassium tert-butoxide to give N-substituted 2,3-dihydroindoles in good yields. The combination of this domino-amination protocol with a suitable dehydrogenation reaction gives access to pharmacologically interesting indoles in a one-pot procedure. Overall product yields of N-substituted indoles >50% are obtained by this method starting from commercially available substrates. In addition to the intramolecular base-promoted amination of aromatic C-Cl bonds, metal-free intermolecular aminations of aryl chlorides with primary and secondary amines are described. The use of potassium tert-butoxide as base allows the synthesis of various anilines in good to excellent yields. Due to the formation of aryne intermediates, either N-substituted anilines or meta-substituted anilines are produced with excellent selectivities.     

A novel catalytic one-pot synthesis of carbazoles via consecutive amination and C-H activation

Sequential palladium catalysed amination and C-H activation reactions occur between 2-chloro-N-alkylated anilines and aryl bromides to give carbazoles in one pot.     

Selective palladium-catalyzed amination of β-chloroacroleins by substituted anilines

β-Chloroacroleins can undergo a selective amination on their chloro position under palladium catalysis; in those conditions, no imine formation was observed. Their coupling with anilines carrying electron-donating or electron-withdrawing substituents proceeds in moderate to good yields and steric hindrance does not seem to be a limitation as o-substituted anilines react readily.     

Regioselective copper-catalyzed amination of chlorobenzoic acids: synthesis and solid-state structures of N-aryl anthranilic acid derivatives

[reaction, structure: see text] A chemo- and regioselective copper-catalyzed cross-coupling reaction for effective amination of 2-chlorobenzoic acids with aniline derivatives has been developed. The method eliminates the need for acid protection and produces a wide range of N-aryl anthranilic acid derivatives in up to 99% yield. The amination was found to proceed with both electron-rich and electron-deficient aryl chlorides and anilines and also utilizes sterically hindered anilines such as 2,6-dimethylaniline and 2-tert-butylaniline. The conformational isomerism of appropriately substituted N-aryl anthranilic acids has been investigated in the solid state. Crystallographic analysis of seven anthranilic acid derivatives showed formation of two distinct supramolecular architectures exhibiting trans-anti and unprecedented trans-syn dimeric structures.     

2-(Trimethylsilyl)ethanesulfonyl amide as a new ammonia equivalent for palladium-catalyzed amination of aryl halides

2-(Trimethylsilyl)ethanesulfonyl amide (SES-NH₂) is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that anilines and anilines with sensitive functional groups can be readily prepared.     

Palladium‐Catalyzed Amination of Aryl Sulfides with Anilines

A combination of a palladium–NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho‐substituted aryl sulfides. This amination can be applied to the modular synthesis of N‐aryl carbazoles from the corresponding ortho‐bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho‐substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2‐anilinobenzothiophene and an indole as proof‐of‐principle of the utility of the extended Pummerer reaction/amination cascade.     

Direct, metal-free amination of heterocyclic amides/ureas with NH-heterocycles and N-substituted anilines in POCl3

A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.     

Palladium-catalyzed amination of aryl nonaflates

The first detailed study of the palladium-catalyzed amination of aryl nonaflates is reported. Use of ligands 2-4 and 6 allows for the catalytic amination of electron-rich and -neutral aryl nonaflates with both primary and secondary amines. With use of Xantphos 5, the catalytic amination of a variety of functionalized aryl nonaflates resulted in excellent yields of anilines; even 2-carboxymethyl aryl nonaflate is effectively coupled with a primary alkylamine. Moderate yields were obtained when coupling halo-aryl nonaflates with a variety of amines, where in most cases the aryl nonaflate reacted in preference to the aryl halide. Overall, aryl nonaflates are an effective alternative to triflates in palladium-catalyzed C-N bond-forming processes due to their increased stability under the reaction conditions.     

An inexpensive cyclodiphosphazane as an efficient ligand for the palladium-catalyzed amination of aryl bromides and chlorides

An economic and novel ligand, cyclodiphosphazane [ClPN(t-Bu)]₂ (1), was introduced in the palladium-catalyzed amination of unactivated aryl halides. The catalyst allows for the amination of aryl chlorides and bromides with secondary cyclic amines and anilines in good yields.     

Copper-catalyzed direct amination of electron-deficient arenes with hydroxylamines

The C-H amination of electron-deficient arenes such as polyfluoroarenes and azole compounds with O-acylated hydroxylamines effectively proceeds in the presence of a copper catalyst even at room temperature to provide the corresponding anilines and aminoazoles in good yields.     

Selective ruthenium-catalyzed double reductive aminations using hydrosilane to access tertiary amines and piperidine derivatives

A highly selective double reductive aminations of aldehydes with anilines to give tertiary amines, in the presence of [RuCl₂(p-cymene)]₂ catalyst and PhSiH₃, was performed under neat conditions. Piperidine derivatives were successfully synthesized by a double reductive amination followed by cyclisation from glutaric dialdehyde with anilines.     

Direct reductive amination of aldehydes and ketones using phenylsilane: catalysis by dibutyltin dichloride

A procedure for direct reductive amination of aldehydes and ketones was developed which uses phenylsilane as a stoichiometric reductant and dibutyltin dichloride as a catalyst. Suitable amines included anilines and dialkylamines but not monoalkylamines.     

Towards Uniform Iodine Catalysis: Intramolecular C−H Amination of Arenes under Visible Light

A photochemical catalytic amination of arenes is presented. The reaction proceeds under benign iodine catalysis in the presence of visible light as the initiator and provides access to a range of differently substituted arylamines. A total of 29 examples demonstrate the broad applicability of this mild oxidation method. The scope of the reaction could further be expanded to silyl‐tethered derivatives, which undergo intramolecular amination upon formation of seven‐membered heterocycles. Cleavage of the silicon tether provides access to the corresponding 3‐substituted anilines.     

Metal-based Heterogeneous Catalysts for One-Pot Synthesis of Secondary Anilines from Nitroarenes and Aldehydes

Recently, N-substituted anilines have been the object of increasing research interest in the field of organic chemistry due to their role as key intermediates for the synthesis of important compounds such as polymers, dyes, drugs, agrochemicals and pharmaceutical products. Among the various methods reported in literature for the formation of C–N bonds to access secondary anilines, the one-pot reductive amination of aldehydes with nitroarenes is the most interesting procedure, because it allows to obtain diverse N-substituted aryl amines by simple reduction of nitro compounds followed by condensation with aldehydes and subsequent reduction of the imine intermediates. These kinds of tandem reactions are generally catalyzed by transition metal-based catalysts, mainly potentially reusable metal nanoparticles. The rapid growth in the last years in the field of metal-based heterogeneous catalysts for the one-pot reductive amination of aldehydes with nitroarenes demands for a review on the state of the art with a special emphasis on the different kinds of metals used as catalysts and their recyclability features.     

Stereoselective synthesis of fused heterocycles from substituted o-Benzoquinones and anilines

The reaction of trisubstituted o-benzoquinones with substituted anilines gives unstable o-benzoquinone imines which undergo intramolecular cyclization to 4aH-phenoxazine derivatives. Dimerization of the latter according to Diels-Alder yields complex heterocyclic systems, 7a,14a,15a,15b-tetrahydro-14,16-dioxa-5,9-diaza-8,15-ethenohexaphenes. Effective shielding of the carbonyl groups in 3,6-di-tert-butyl-4-isopropyl-o-benzoquinone makes it inactive toward substituted anilines.     

Synthesis of the himandrine skeleton

The hexacyclic himandrine skeleton 5, which is present in the most complex alkaloids of the tropical rain forest tree Galbulimima belgraveana, has been prepared for the first time. The synthesis begins from the known [3.2.1]benzobicyclooctene intermediate 10. Key steps include a Diels-Alder cycloaddition, Curtius rearrangement, Birch reduction, an intramolecular nucleophilic amination, and a palladium-mediated alkene amination. [reaction: see text]