Tandem Amination Research Articles

Visible-Light-Mediated Aerobic Tandem Dehydrogenative Povarov/Aromatization Reaction: Synthesis of Isocryptolepines.

A metal‐free, photoinduced aerobic tandem amine dehydrogenation/Povarov cyclization/aromatization reaction between N‐aryl glycine esters and indoles leads to tetracyclic 11H‐indolo[3,2‐c]quinolines under mild conditions and with high yields. The reaction can be performed by using molecular iodine along with visible light, or by combining an organic photoredox catalyst with a halide anion. Mechanistic studies reveal that product formation occurs through a combination of radical‐mediated oxidation steps with an iminium ion or N‐haloiminium ion [4+2]‐cycloaddition, and the N‐heterocyclic products constitute new analogues of the antiplasmodial natural alkaloid isocryptolepine.

Photo-generated reactive oxygen species assisted tandem amine homocoupling and amine-alcohol cross-coupling reaction on mesoporous spinel cobalt oxide

Mesoporous spinel cobalt oxide (Co3O4) with fine-tuned pore size distributions (9.6–17.6 nm) and different surface areas (33–85 m2/g) were synthesized using a series of nonionic surfactants. A direct influence of the chemical composition of the surfactants and calcination temperature on crystallite size, morphology, pore size/volume, surface area, valance band edge, and Co2+/Co3+ ratio was recognized. Correlation between the aforementioned factors, transition metal ion incorporation and benzylamine homocoupling reaction was discussed. Shape-specific binding of amine on the cobalt oxide active sites was proposed based on substrate scope study. Tandem synthesis strategy to selectively synthesize amine (aliphatic/aromatic) homo-coupled imines and amine-alcohol cross-coupled imines was introduced. Low-intensity light-induced singlet oxygen and hydroxyl radical-mediated reaction mechanism was proposed based on the EPR, XPS, photoreactor, and reactive oxygen species scavenger tests. Selective and switchable synthesis of homo-coupled (yield 85%) and cross-coupled (yield 87%) products was achieved with sodium azide and mannitol additives.

Oxidative Asymmetric Formal Aza-Diels⁻Alder Reactions of Tetrahydro-β-carboline with Enones in the Synthesis of Indoloquinolizidine-2-ones.

Ru-catalyzed tandem amine oxidative dehydrogenation/formal aza-Diels–Alder reaction for enantio- and diastereoselective synthesis of indoloquinolizidine-2-ones from tetrahydro-β-carbolines and α,β-unsaturated ketones is described. The reaction proceeds via tandem ruthenium-catalyzed amine dehydrogenation using tert-butyl hydroperoxide (TBHP) as the oxidant and a chiral thiourea-catalyzed formal aza-[4 + 2] cycloaddition, providing a step-economical strategy for the synthesis of these valuable heterocyclic products.

Synthesis of primary amines via linkage of hydroaminomethylation of olefins and splitting of secondary amines

An elegant method capable of synthesising primary amines from olefins is presented by a new orthogonal tandem amination reaction. Rh/Ru-catalysed bis-hydroaminomethylation of dienes towards secondary amines 10 and primary amines 13 is implemented. The obtained secondary amines 10 intermediates are then converted in a second reaction step to primary amines 13via splitting of amines through subsequent addition of ammonia. Influences on the orthogonal catalytic system towards the formation of primary amines are discussed and point towards a novel N-dealkylation and alkylation mechanism. For the model substrate dicyclopentadiene (tricyclo[5.2.1.02,6]deca-3,8-diene, dcpd 1) yields of up to 29% of the primary diamine (3(4),8(9)-bis(aminomethyl)tricycle-[5.2.1.02,6]decane, TCD-diamine 13) were achieved under optimized conditions, with a primary amine 13 to secondary amine 10 ratio of 5.8. The reverse reaction towards secondary amines was revealed as the limiting factor in the selective reaction towards primary amines 13 caused by the equilibrium of the reaction. In this equilibrium, however, a slight tendency towards the primary amine 13 was identified.

Open-Flask Synthesis of Amine–Boranes via Tandem Amine–Ammonium Salt Equilibration–Metathesis

An amine-ammonium salt equilibration-metathesis sequence provides high-purity amine-boranes in excellent yields from sodium borohydride in refluxing reagent-grade tetrahydrofuran in an open flask.

Tandem amine and ruthenium-catalyzed hydrogenation of CO2 to methanol.

This Communication describes the hydrogenation of carbon dioxide to methanol via tandem catalysis with dimethylamine and a homogeneous ruthenium complex. Unlike previous examples with homogeneous catalysts, this CO2-to-CH3OH process proceeds under basic reaction conditions. The dimethylamine is proposed to play a dual role in this system. It reacts directly with CO2 to produce dimethylammonium dimethylcarbamate, and it also intercepts the intermediate formic acid to generate dimethylformamide. With the appropriate selection of catalyst and reaction conditions, >95% conversion of CO2 was achieved to form a mixture of CH3OH and dimethylformamide.

Synthesis of Monoazaphenoxazine Derivatives via Buchwald-Hartwig Tandem Amination Protocol

Synthesis of Monoazaphenoxazine Derivatives via Buchwald-Hartwig Tandem Amination Protocol

Allylic amination of Passerini adducts. Application to the selective synthesis of chromone-substituted α-and γ-amino acid peptidic and retropeptidic units

The first allylic amination of Passerini acetates is described, where both α and γ-substitution products are obtained regioselectively from chromone derived adducts. While α-substitution occurs in THF, CuCl in methanol catalyses a tandem amination followed by a rearrangement leading to γ-amino acid-derived chromones.

An Efficient Synthesis of 1-Alkyl-2-phenyl-4-quinolones from 2-Halobenzoic Acids

1-Methyl-2-phenyl-4-quinolones are naturally occurring alkaloids isolated from the leaves and stems of the plant family Rutaceae. They have drawn considerable interest because of their potent pharmacological activities that include antifungal and antitumor activity, inhibition of acetylcholinesterase (AChE), and antimutagenic effect. Several methods have been developed to synthesize 1alkyl-2-phenyl-4-quinolones from 2'-substituted acetophenones, anilines, and 2-halobenzoyl chlorides as starting materials. The reaction of N-methylisatoic anhydride with the lithium enolate of an 4'-methoxyacetophenone afforded the 1-methyl-2-phenyl-4-quinolone in a short sequence, but the yield was low. N-(2-Acetylphenyl)benzamides, prepared by Friedel-Crafts acylation of N-phenyl benzamides with acetyl chloride or benzoylation of 2'-aminoacetophenones with benzoyl chlorides, were cyclized with potassium tbutoxide to yield 2-aryl-4-quinolones, which were further alkylated with alkyl iodides to give 1-alkyl-2-aryl-4-quinolones. However, acylation was accompanied by formation of the regioisomer and alkylation yielded a mixture of Nalkylquinolones as the main products together with 4alkoxyquinolines as minor products. On the other hand, Nmethylated (2-acetylphenyl)benzamides, prepared from 2'(N-methylamino)acetophenones and benzoyl chlorides, could be cyclized with sodium hydride in DMF to afford the 1-methyl-2-phenyl-4-quinolones in moderate yields. 2'-(N-Alkylamino)chalcones, prepared by aldol condensation of 2'-aminoacetophenones and benzaldehydes followed by N-alkylation with alkyl halides, upon treatment with polystyrene-supported selenenyl bromide in the presence of ZnCl2 afforded 2,3-dihydro-3-polystyrene-supported selenenyl-4-quinolones. These compounds were subsequently oxidized with H2O2 and eliminated to give 1-alkyl-2-phenyl4-quinolones. Palladium-catalyzed carbonylative coupling of 2-iodo-N-ethylaniline with phenylacetylene occurred smoothly to give a mixture of the corresponding enamine and the desired cyclic quinolone. Further cyclization of the enamine intermediate with sodium hydride in refluxing THF led to 1-ethyl-2-phenyl-4-quinolone. Palladium-catalyzed tandem amination of 2-bromoalkynones, obtained by Sonogashira cross-coupling of arylacetylenes and 2-bromobenzoyl chlorides, with arylamines in refluxing dioxane was effective for the synthesis of 1-aryl-2-phenyl-4-quinolones. Similarly, treatment of 2-halophenyl alkynones with arylamines afforded the corresponding 3-(N-arylamino) α,βunsaturated ketones by conjugate addition. These compounds were then cyclized with K2CO3 in refluxing DMF for 52 h 13

ChemInform Abstract: One‐Pot Synthesis of Pentasubstituted Pyrroles from Propargylic Alcohols, Amines, and Dialkyl Acetylenedicarboxylates; Tandem Amination, Propargylation and Cycloisomerization Catalyzed by Molecular Iodine.

AbstractThe methodology offers a simple synthesis of a variety of fully substituted pyrroles.

One-Pot Synthesis of Pentasubstituted Pyrroles from Propargylic Alcohols, Amines, and Dialkyl Acetylenedicarboxylates; Tandem Amination, Propargylation and Cycloisomerization Catalyzed by Molecular Iodine

A multicomponent one-pot synthesis of fully substituted pyrroles has been developed by the tandem reaction of amines, dialkyl acetylenedicarboxylates, and propargylic alcohols using iodine as a catalyst. The reaction was complete in three hours and afforded the products in high yields (75–88%). The method is simple, efficient, cost-effective, and metal-free.

Catalytic enantioselective synthesis of atropisomeric 2-aryl-4-quinolinone derivatives with an N–C chiral axis

In the presence of an (R)-MOP-Pd2(dba)3 catalyst, the reaction of ortho-tert-butylaniline with 2-bromophenyl arylethynyl ketone proceeded via a tandem amination (1,4-addition of aniline to an ynone and subsequent intramolecular Buchwald–Hartwig amination) to afford axially chiral N-(2-tert-butylphenyl)-2-aryl-4-quinolinone derivatives with moderate enantioselectivity (up to 72% ee).

ChemInform Abstract: Synthesis of N‐Alkyl‐Substituted 4‐Quinolones via Tandem Alkenyl and Aryl C—N Bond Formation.

N-Alkyl-substituted 4-quinolones are present as the key structural motif in many marketed drugs. An efficient one-step tandem amination approach was developed to afford N-alkyl-substituted 4-quinolones in high yields from easily accessible o-chloroaryl acetylenic ketones and functionalized alkyl amines. The approach complements and extends our previous work. Compared with other reported methods, the current method provides a very simple and convenient route.

ChemInform Abstract: Biobased Synthesis of Secondary Arylamines from (‐)Shikimic Acid.

AbstractA tandem amination—aromatization reaction of dehydroshikimate (I) with aromatic and aliphatic amines provides title arylamines in good yields.

Synthesis of N-Alkyl-Substituted 4-Quinolones via Tandem Alkenyl and Aryl C-N Bond Formation

<i>N</i>-Alkyl-substituted 4-quinolones are present as the key structural motif in many marketed drugs. An efficient one-step tandem amination approach was developed to afford <i>N</i>-alkyl-substituted 4-quinolones in high yields from easily accessible <i>o</i>-chloroaryl acetylenic ketones and functionalized alkyl amines. The approach complements and extends our previous work. Compared with other reported methods, the current method provides a very simple and convenient route.

ChemInform Abstract: Palladium‐Catalyzed Tandem N‐Vinylation and Cyclization of Anilines and Haloenynes: An Efficient Approach to Substituted Quinolines.

AbstractThe reaction can be performed successfully with bromo‐ and iodoenynes.

Efficient [5 + 1]-strategy for the assembly of 1,8-naphthyridin-4(1H)-ones by domino amination/conjugate addition reactions of 1-(2-chloropyridin-3-yl)prop-2-yn-1-ones with amines

A facile synthetic approach for the synthesis of 1,8-naphthyridine-4(1H)-one derivatives via a catalyst free and Pd-supported tandem amination sequence is developed and described. In a case of aliphatic amines reaction proceeds in a catalyst free mode, however anilines demand Pd-supported reaction conditions.

Synthesis of substituted amines and isoindolinones: catalytic reductive amination using abundantly available AlCl3/PMHS

AlCl3 has been employed for highly chemoselective reductive amination of carbonyl compounds in ethanol using polymethylhydrosiloxane as an inexpensive, stable and safe reducing agent without an inert atmosphere. A large range of functional groups such as nitro, carboxylic acid, acetyl, nitrile, halogen, methoxy, alkene and heterocycles were well tolerated. AlCl3 also catalyzed tandem amination–amidation of 2-carboxybenzaldehyde with different amines to afford N-substituted isoindolinones. The catalyst can be recycled at least three times without any significant effect on activity and selectivity.

Palladium‐Catalyzed Tandem N‐Vinylation and Cyclization of Anilines and Haloenynes: An Efficient Approach to Substituted Quinolines

AbstractThe palladium‐catalyzed tandem amination of haloenynes and intramolecular cyclization has been developed. The reaction provides a novel route for the synthesis of quinoline derivatives with high yields.

ChemInform Abstract: Organocatalytic Synthesis of Terminal Propargylamine Derivatives by Tandem Amination—Alkynylation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.