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.     

A versatile synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones

A mild and general strategy for the synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. The seven-membered lactam is prepared by intramolecular amide bond formation from the intermediate amino acid, which is obtained either by reductive alkylation of a variety of amines with N-Boc,N-Me-ortho-formyl-Phe and Phth-ortho-formyl-Phe, or by reductive amination of a variety of aldehydes with N-Boc-ortho-aminomethyl-Phe.     

Intramolecular Heck reaction: A facile sequential one-pot synthesis of 1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines

A simple and convenient sequential one-pot synthesis of 1,2,3,4-tetrahydrobenzo[b][1,6] naphthyridines has been developed. The reductive amination of 2-chloro-3-formylquinolines with various amines in the presence of sodium borohydride provided the corresponding secondary amines in high yields. Further, a sequential one-pot reaction involving N-allylation and intramolecular Heck type 6-exo-trig cyclization was performed on the secondary amines to afford a range of desired 1,2,3,4-tetrahydrobenzo[b][1,6]-naphthyridine derivatives in good to high yields.     

A novel palladium catalyst for the amination of electron-rich indole derivatives

The palladium-catalyzed amination of a 3-silyloxy-substituted bromo-indole with primary and secondary amines is described for the first time. In the presence of the novel catalyst system of Pd(OAc)₂/N-phenyl-2-(di-1-adamantylphosphino)pyrrole potentially bioactive amino-functionalized indole derivatives are obtained in a general manner in high yield.     

N-(3-Trimethylsilyl)propargyl amino esters via reductive amination

N-Propargyl amino esters are useful starting materials in a variety of settings. General reductive amination conditions for N-(3-trimethylsily)propargylation of amino esters have been developed. These conditions demonstrated greater tolerance for nucleophilic side chains (amines and alcohols) than has been previously reported. This procedure produced a variety of N-(3-trimethylsilyl)propargyl amino esters in good to excellent yield.     

Development of one-pot benzylic amination reactions of azine N-oxides

An efficient one-pot synthetic methodology has been developed for the benzylic amination reactions of methyl-substituted azine N-oxides that operate under mild conditions. The reaction was found to tolerate quinoline and isoquinoline N-oxides with electron donating and withdrawing substituents as the electrophilic reaction partners as well as a broad range of nucleophilic primary, secondary and aromatic amines, affording the benzylic amination products in up to 82% yield.     

Metal catalyst-free amination of meso-bromoporphyrins: an entry to supramolecular porphyrinoid frameworks

meso-Bromoporphyrins can be conveniently substituted by primary and secondary amines in a metal catalyst-free reaction which gives access to a large variety of meso-N-substituted derivatives. In some cases, considerable acceleration of this amination can be effected under microwave irradiation. The amino anchor on the porphyrin skeleton is useful for constructing novel self-assembling porphyrinoids as demonstrated by a single crystal X-ray analysis as well as stationary absorption and fluorescence spectroscopies.     

A highly chemoselective Boc protection of amines using sulfonic-acid-functionalized silica as an efficient heterogeneous recyclable catalyst

A facile and versatile method for the chemoselective Boc protection of amines has been developed by a treatment with (Boc)₂O in the presence of sulfonic-acid-functionalized silica as a catalyst. The method is general for the preparation of N-Boc derivatives of aliphatic (acyclic and cyclic), aromatic, and heteroaromatic amines; primary and secondary amines; aminols, amino-esters; and sulfonamides. The catalyst works under heterogeneous conditions and can be recycled.     

Development of a new linker for the solid-phase synthesis of N-hydroxylated and N-methylated secondary amines

Merrifield resin was modified by the introduction of an ortho-nitrophenylethanal group that served as a linker moiety to attach amines to the resin by reductive amination. Resin-bound tertiary amines were shown to be readily transferred into the respective liberated N-hydroxylated or N-methylated derivatives by either an oxidation/Cope elimination or a permethylation/Hofmann elimination protocol. With these two divergent liberation/derivatization options, the new resin offers new flexibility in the solid phase synthesis of N-modified secondary amines, for instance in spider toxin synthesis.     

Synthesis of some alkylaminothiophene derivatives from 3,4-dibromothiophene and their theoretical calculations

In this study, the copper catalyzed amination reactions of 3,4-dibromothiophene with some primary, cyclic and acyclic secondary amines were investigated to prepare novel electron rich-thiophenes which are expected to be used as novel N-containing donor type monomer candidates for conductive polymers. In order to obtain better yields, this S_NAr type amination reaction was optimized by studying the reaction conditions, such as the copper catalyst, the type of copper source, the presence of a base and the type of the solvent on the model reaction between 3,4-dibromothiophene and n-butylamine. A variety of 3,4-(N,N′-dialkylamino)thiophenes and 3-(N-alkylamino)thiophenes were synthesized in moderate yields under the optimized reaction conditions. In addition, two new heterocyclothiophene derivatives were successfully prepared from the cyclization reaction of 3,4-bis(N-butylamino)thiophene. The characterization of the isolated alkylaminothiophenes was performed by FTIR, ¹H and ¹³C NMR, GCMS and elemental analysis. The theoretical calculations for all alkylaminothiophenes were executed by using the DFT/B3LYP/6-311+G(2d,p) approach.     

N-(2-formyl-1-methylimidazol-4-yl)-2,2-dimethylpropanamide: a versatile reagent for preparing imidazole-amine ligands with variable second-coordination spheres

Two synthetic pathways to N-(2-formyl-1-methylimidazol-4-yl)-2,2-dimethylpropanamide from 1-methyl-2-carboxaldehyde are described. The reagent serves as a useful synthon for reductive amination reactions with primary and secondary amines in the presence of sodium cyanoborohydride to yield a series of ligands with second coordination sphere functional groups. Protocols for the syntheses of related imidazole synthons functionalized in the 4-position with amino acids, Schiff bases, and other amides are also reported.     

Perfluoro alkyl 1,3-diketonates of cyclic and acyclic secondary amines

Cyclic and acyclic secondary amines were quaternized with perfluoroalkyl 1,3-diketones to form secondary ammonium perfluoroalkyl 1,3-diketonates in good yields. Saturated cyclic secondary amines, including morpholine, N-acetylmorpholine, 3-methyl-N-acetylpiperidine, 2,2,6,6-tetramethyl-4-aminopiperidine, 4,4-dimethylimidazoline, 1,3-bispiperidine propane, and acyclic secondary amines, di(n-propyl) amine, di(isopropyl) amine, di(n-butyl) amine, and di(isobutyl) amine were reacted with various fluorine-containing 1,3-diketones (1-5) to yield the corresponding 1,3-diketonates (6-29). The compounds were characterized by ¹H, ¹⁹F, and ¹³C NMR, electrospray MS, and elemental analyses. Melting points and T_g values were obtained by DSC. Thermal decomposition data (5% weight loss temperature) were recorded by TGA. X-ray single-crystal structures show that 9 and 26 crystallize in monoclinic space group P2(1)/c.     

Well-defined NHC–Pd(II)–Im (NHC=N-heterocyclic carbene; Im=1-methylimidazole) complex catalyzed C–N coupling of primary amines with aryl chlorides

We report herein a well-defined NHC–Pd(II)–Im (NHC=N-heterocyclic carbene; Im=1-methylimidazole) complex catalyzed C–N coupling of primary amines with aryl chlorides. Under the optimal reaction conditions, a variety of primary amines can be coupled with aryl chlorides to give the amination products in good to high yields within 4 h. It is worthy of noting here that the NHC–Pd(II)–Im complex showed especially high catalytic activity toward challenging sterically hindered substrates including both of aryl amines and aryl chlorides. In addition, alkyl amines were also proved to be suitable reaction partners to give the corresponding amination products in good to high yields.     

An efficient route from coumarins to highly functionalized N-phenyl-2-quinolinones via Buchwald-Hartwig amination

Multiple substituted N-phenyl-2-quinolinones were obtained in a convenient four-step route from a variety of commercially available coumarins, utilizing customised Buchwald-Hartwig amination protocols for the key reaction. Whereas simple aminolysis of coumarins is limited to non-electron-deficient, sterically unhindered derivatives of aniline under harsh conditions, the present method allows for conversions with multiple substituted aromatic amines, as demonstrated by the example of chlorinated aminosalicylates.     

Palladium-catalysed allylic amination for the direct synthesis of epi-4-alkylamino-N-acetylneuraminic acid derivatives

A simple and efficient procedure has been developed for the direct formation of epi-4-alkylamino-N-acetylneuraminic acid derivatives as potential inhibitors of influenza neuraminidases. The allylic amination of oxazoline 6 has been effected with a series of primary and secondary amines in the presence of catalytic Pd(π-allyl)₂(Et₃P)₂ to give the corresponding 4-epi-alkylamino products in a stereoselective and regiospecific manner.     

Atom-efficient synthesis of 2,6-diazacyclophane compounds through alcoholysis/reduction of 3-nitroarylmethylene-2,5-piperazinediones

Readily available cyclic dehydrodipeptides are convenient starting materials for atom-efficient synthesis of different compounds. A one-pot ring-opening/alcoholysis/hydrolysis process with 3-nitroarylmethylene-2,5-piperazinediones yielded N-3-nitroarylpyruvoylamino esters, which gave the corresponding amines by reduction of the nitro group. In the case of 2-nitroaryl compounds, an intramolecular reductive amination afforded N-indole-2-carbonylamino esters, while the intermolecular reductive amination of 3- and 4-nitroaryl derivatives allowed the synthesis of 2,6-diazacyclophanes. The amino compounds may be coupled with amino acids to get peptide-like derivatives.     

Arylation of adamantanamines: VI. Palladium-catalyzed arylation of amines and diamines of the adamantane series with 3-bromopyridine

Palladium-catalyzed amination of 3-bromopyridine with amines of the adamantane series in the presence of Pd(dba)₂/L [L = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or 2-dimethylamino-2′-dicyclohexylphosphinobiphenyl] gave the desired N-(pyridin-3-yl)-substituted amines in 74–97% yields. Diamines of the adamantane series reacted with 2 equiv of 3-bromopyridine in a complicated fashion to produce mono- and triaryl-substituted derivatives as by-products, while the yields of N,N′-diarylation products were 18–56%.     

Synthesis and Crystal Structure Determination of [H2‐cryptand 222](Br3)2: A Unique Tribromide Catalyst for the Catalytic Chemoselective N‐Boc Protection of Amines

The organic tribromide, [H₂‐cryptand 222](Br₃)₂ was synthesized and characterized by X‐ray crystallography, and was utilized as an active catalyst for the N‐boc protection of amines. The method is general for the preparation of N‐boc derivatives of aliphatic (acyclic and cyclic), aromatic, primary and secondary amines. We also applied our new reaction protocols for the N‐boc protection of some new amines and spectral and physical data for the obtained products are reported.     

2,4-DINITROPHENYLHYDROXYLAMINE: AN EFFICIENT AND MORE GENERAL REAGENT FOR IRON-CATALYZED ALLYLIC AMINATION

2,4-Dinitrophenylhydroxylamine (1) is an efficient reagent for the iron-catalyzed regioselective allylic amination of olefins. Moderate to excellent yields of N-DNP-N-allyl amines (2) are obtained resulting from introduction of the N-DNP group at the less substituted vinylic carbon with accompanying double bond transposition. N-alkylation of 2 and subsequent treatment with MeNH₂ affords secondary N-alkyl-N-allyl amines (5) in good overall yield.     

Ultra-small cobalt nanoparticles from molecularly-defined Co–salen complexes for catalytic synthesis of amines

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions. In the presence of ammonia and hydrogen, cobalt–salen complexes such as cobalt(ii)–N,N′-bis(salicylidene)-1,2-phenylenediamine produce ultra-small (2–4 nm) cobalt-nanoparticles embedded in a carbon–nitrogen framework. The resulting materials constitute stable, reusable and magnetically separable catalysts, which enable the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds and ammonia. The isolated nanoparticles also represent excellent catalysts for the synthesis of primary, secondary as well as tertiary amines including biologically relevant N-methyl amines.

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions.