Secondary Propargylamines Research Articles

Noble metal free double helix binuclear Cu(I) complex as catalyst for carboxylative cyclization of propargylamines with atmospheric carbon dioxide toward oxazolidinones synthesis under mild conditions

The application of economically abundant, renewable and C1-feedstock, carbon dioxide into organically important compounds is considered as the hot topic in modern aspects. In this prospective, a binuclear double helix copper (I) complex (1) was synthesized through insitu reaction between quinolone-2-carbaldehyde and succino-hydrazide with copper (II) nitrate hexahydrate. Single crystal X-ray analysis of complex 1, clearly explained that both tetra co-ordinated Cu(I) ions are in tetrahedral geometric environment, having suprmolecular network arrangement via weak interaction of H-bonding, π…π stacking and CH…π stacking. The complex 1 was found to be effectively active catalyst in carboxylative cyclization reaction of propargylic amines with carbon dioxide towards oxazolidinones synthesis under atmospheric pressure and mild reaction conditions. Due to the initiation of side reaction by –NH2 group of primary propargyliamines, which reduces the yield percentage of respective oxazolidinones as a result the carboxylative cyclization reaction of primary propargylic amines, was rarely developed. In this work both primary and secondary propargylamines smoothly undergoes through this catalytic reaction and produced high percentage of desired oxazolidinones product. Again neat condition for this catalytic reaction makes the methodology more environmentally benign and sustainable. The complex 1 showed luminescent property. Moreover DFT methods were utilized in order to explain the probable mechanistic pathway of carboxylative cyclization reaction.

Diastereoselective Synthesis of Secondary Propargylamines Exploiting CuI-Based Promoters and Determination of Their Relative Configuration by DFT-GIAO Conformational Analysis

AbstractThe stereoselective synthesis of several secondary propargylamines by the copper-promoted A3-coupling reaction of aliphatic and aromatic aldehydes with phenylacetylene and (R)-(+)-phenylethylamine is here reported. Two different synthetic methodologies have been investigated in this study, involving CuSO4/NaI and ­CeCl3·7H2O/CuI promoting systems. The reported methodologies were compared in terms of efficiency, diastereoselectivity, and toxicity, both showing advantages with respect to the current methodologies. The relative configurations of each of the obtained propargylamines, previously unknown in the literature, were assigned by comparison of the 1H NMR experimental chemical shifts with those theoretically predicted via the DFT-GIAO method.

Catalysis-free synthesis of thiazolidine-thiourea ligands for metal coordination (Au and Ag) and preliminary cytotoxic studies.

The reaction of propargylamines with isothiocyanates results in the selective formation of iminothiazolidines, aminothiazolines or mixed thiazolidine-thiourea compounds under mild conditions. It has been observed that secondary propargylamines lead to the selective formation of cyclic 2-amino-2-thiazoline derivatives, while primary propargylamines form iminothiazoline species. In addition, these cyclic thiazoline derivatives can further react with an excess of isothiocyanate to give rise to thiazolidine-thiourea compounds. These species can also be achieved by reaction of propargylamines with isothiocynates in a molar ratio of 1 : 2. Coordination studies of these heterocyclic species towards silver and gold with different stoichiometries have been carried out and complexes of the type [ML(PPh3)]OTf, [ML2]OTf (M = Ag, Au) or [Au(C6F5)L] have been synthesised. Preliminary studies of the cytotoxic activity in lung cancer cells have also been performed in both ligands and complexes, showing that although the ligands do not exhibit anticancer activity, their coordination to metals, especially silver, greatly enhances the cytotoxic activity.

Synthetic Access to Secondary Propargylamines via a Copper-Catalyzed Oxidative Deamination/Alkynylation Cascade.

A novel and selective cascade reaction of primary amines and alkynes for the synthesis of the corresponding secondary propargylamines is described. This protocol proceeds with a CuBr2/TBHP system through a process of oxidative deamination of primary amines to imine and alkynylation, featuring a wide scope of substrates with good functional-group tolerance and operational simplicity. Additionally, the use of two different primary amines could also work smoothly using this protocol.

Activation of Primary Amines by Copper(I)-Based Lewis Acid Promoters in the Solventless Synthesis of Secondary Propargylamines

Primary amines are activated by copper(I)-based Lewis acid promoters in an A3-coupling one-pot solventless reaction with aldehydes and phenylacetylene for the synthesis of secondary propargylamines. The reaction is promoted by a CuSO4/NaI system, a practical precursor of the in situ generated effective CuI/I2 system, that worked well, but only in a restricted number of examples. Substitution of I2 with CeCl3·7H2O in a one-pot two-step reaction provided good yields and a wider applicability, with the added value given by a safer procedure.

Front Cover: Copper‐Catalyzed Reaction of Secondary Propargylamines with Ethyl Buta‐2,3‐dienoate for the Synthesis of 1,6‐Dihydropyridines (Eur. J. Org. Chem. 10/2019)

Front Cover: Copper‐Catalyzed Reaction of Secondary Propargylamines with Ethyl Buta‐2,3‐dienoate for the Synthesis of 1,6‐Dihydropyridines (Eur. J. Org. Chem. 10/2019)

Copper‐Catalyzed Reaction of Secondary Propargylamines with Ethyl Buta‐2,3‐dienoate for the Synthesis of 1,6‐Dihydropyridines

A copper(I) bromide‐catalyzed reaction of A3‐coupling‐derived propargylamines with ethyl buta‐2,3‐dienoate for the fast assembly of a 1,6‐dihydropyridine core is described. The developed protocol was tested on a variety of secondary propargylamines and the possibility of a one‐pot synthesis of 1,6‐dihydropyridine through the A3‐coupling and subsequent ethyl buta‐2,3‐dienoate incorporation was investigated.

Cooperative N-heterocyclic carbene Au and amino catalysis for continuous synthesis of secondary propargylamines in a fiber supported hydrophilic microenvironment

A series of reusable and tunable polyacrylonitrile fiber supported catalysts that make use of the cooperative interplay between N-heterocyclic carbene (NHC) Au(III) and amino groups have been developed for synthesis of secondary propargylamines. The yield using immobilized NHC-Au(III) as catalyst is twice as much as that of its small molecule counterpart. Moreover, implementation of a flow system with polyacrylonitrile fiber supported NHC-Au(III) as catalyst leads to a short retention time of 3.3 min and an efficient productivity of 27 mmol/h. The highly catalytic activity of this catalyst is ascribed to the unique hydrophilic microenvironment consisting of NHC-Au(III), -NH2 and -CN groups in the surface of fiber catalyst. In this microenvironment, the adjacent NHC-Au(III) and amino groups promote the formation of gold-acetylide complex cooperatively with turnover numbers (TON) up to 5200.

Metal Acetylide Elimination: The Key Step in the Cascade Decomposition and Transformation of Metalated Propargylamines

Metal acetylide elimination facilitates a novel one-pot cascade metalation and elimination/addition route to a series of unsymmetrical secondary amines from the reaction of secondary propargylamines with organometallic reagents. Spectroscopic evidence suggests a dimetalated amido intermediate rather than an allene.

Reactions of secondary propargylamines with heteroallenes for the synthesis of diverse heterocycles.

This focused review aims to summarize recent developments in the processes involving additions of secondary propargylamines to various heteroallenes and subsequent transition metal-catalyzed or electrophile-mediated cyclizations. The utility of this convenient and tunable strategy spans from the carbon dioxide fixation and target-oriented synthesis of complex natural and biologically active products to the generation of extended synthetic libraries of diverse oxygen-, nitrogen- and sulfur-containing heterocycles. For comparative purposes, the analogous transformations of propargylic alcohols are also highlighted in this account.

Urea derivatives from carbon dioxide and amines by guanidine catalysis: Easy access to imidazolidin-2-ones under solvent-free conditions

A novel methodology to easily access imidazolidin-2-ones from propargylamines, primary amine and CO2 with TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) or MTBD (7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene) as catalysts under solvent-free conditions is here reported. Bicyclic guanidines, able to catalyze the formation of oxazolidinones from secondary propargylamines and CO2, are now presented for the first time as effective organocatalysts for the chemical fixation of CO2 into linear and cyclic ureas. Plausible reaction pathways are proposed on the basis of experimental findings.

Valorization of CO2: Preparation of 2-Oxazolidinones by Metal–Ligand Cooperative Catalysis with SCS Indenediide Pd Complexes

The capture and utilization of CO2 to prepare high-value compounds is very attractive chemically and highly desirable socially. Indenediide-based Pd SCS pincer complexes are shown here to promote the carboxylative cyclization of propargylamines leading to 2-oxazolidinones under mild conditions (0.5–1 bar of CO2, DMSO, 40–80 °C, 1–5 mol % Pd loading). The indenediide Pd complex is competitive with known catalysts. It proved successful for a wide range of propargylamines, including hitherto challenging substrates such as secondary propargylamines bearing tertiary alkyl groups at nitrogen, primary propargylamines, and propargylanilines. Thorough experimental (NMR) and computational (DFT) investigations were undertaken to gain mechanistic insights. Accordingly, (i) the resting state of the catalytic cycle is a Pd DMSO complex; (ii) the indenediide backbone and Pd center act in concert to activate the carbamic acid intermediate and promote its cyclization; (iii) proton shuttling is essential to lower the activ...

Efficient Rhodium-Catalyzed Multicomponent Reaction for the Synthesis of Novel Propargylamines.

[{Rh(μ-Cl)(H)2 (IPr)}2 ] (IPr = 1,3-bis-(2,6-diisopropylphenyl)imidazole-2-ylidene) was found to be an efficient catalyst for the synthesis of novel propargylamines by a one-pot three-component reaction between primary arylamines, aliphatic aldehydes, and triisopropylsilylacetylene. This methodology offers an efficient synthetic pathway for the preparation of secondary propargylamines derived from aliphatic aldehydes. The reactivity of [{Rh(μ-Cl)(H)2 (IPr)}2 ] with amines and aldehydes was studied, leading to the identification of complexes [RhCl(CO)IPr(MesNH2 )] (MesNH2 = 2,4,6-trimethylaniline) and [RhCl(CO)2 IPr]. The latter shows a very low catalytic activity while the former brought about reaction rates similar to those obtained with [{Rh(μ-Cl)(H)2 (IPr)}2 ]. Besides, complex [RhCl(CO)IPr(MesNH2 )] reacts with an excess of amine and aldehyde to give [RhCl(CO)IPr{MesNCHCH2 CH(CH3 )2 }], which was postulated as the active species. A mechanism that clarifies the scarcely studied catalytic cycle of A3 -coupling reactions is proposed based on reactivity studies and DFT calculations.

ChemInform Abstract: Facile and Diverse Microwave‐Assisted Synthesis of Secondary Propargylamines in Water Using CuCl/CuCl2.

AbstractThe novel protocol provides a wide range of secondary propargylamines equipped with diverse substituents in generally high yields.

ChemInform Abstract: Propargylamine—Isothiocyanate Reaction: Efficient Conjugation Chemistry in Aqueous Media.

A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC under mild conditions using this method.

ChemInform Abstract: Unexpected Regio‐ and Chemoselectivity of Cationic Gold‐Catalyzed Cycloisomerizations of Propargylureas: Access to Tetrasubstituted 3,4‐Dihydropyrimidin‐2(1H)‐ones.

Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.

Unexpected regio- and chemoselectivity of cationic gold-catalyzed cycloisomerizations of propargylureas: access to tetrasubstituted 3,4-dihydropyrimidin-2(1H)-ones

Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.

Tetrasubstituted 2-Imidazolones via Ag(I)-Catalyzed Cycloisomerization of Propargylic Ureas

A one-pot protocol based on a Ag(I)-catalyzed cycloisomerization of propargylic ureas, derived from secondary propargylamines and isocyanates, was developed for the generation of the 2-imidazolone core.

Diversity-Oriented Silver(I)-Mediated Synthesis of Spiro-2-aminoimidazoles

A diversity-oriented protocol giving access to a novel class of spiro-cyclic guanidine derivatives is described. The copper(I)-catalyzed, three-component coupling of a ketone, an alkyne and a primary amine (KA²-coupling) provides the required secondary propargylamines and assures the generation of diversity. The key step of the protocol, a silver(I)-mediated tandem guanylation of secondary propargylamines followed by an intramolecular heterocyclization, provides the target bis-Boc-protected-2-iminoimidazolines spiro-fused with a five-, six- or seven-membered (heterocyclic) ring, which could, in most cases, be further deprotected to the spiro-2-aminoimidazoles.

Silver-Catalyzed Synthesis of 2-Amino-imidazole Alkaloids

Reported is the silver-mediated synthesis of 1,4,5-trisubstituted 2-aminoimidaz­oles 4 starting from secondary propargylamines 1 and thioureas 2. Silver nitrate in acetonitrile was found to be the most efficient catalyst. The guanylation and the cyclization steps can be carried out either in a stepwise manner using EDCl and the Hünig base, or in a one-pot manner using triethyl­amine as a base and a recoverable silver(I) salt as promoter and catalyst. Thus, using the Boc- and Cbz-protected S-methylthioureas 2b, a variety of secondary propargylamines 1 were converted in a single step into Boc- and Cbz-protected 2-imino­imidazolines 3 under mild conditions, in very short reaction times, and in good to excellent yields. Boc-protected products 3 were deprotected by treatment with TFA to afford the corresponding 2-aminoimidazoles 4. A mechanism involving a carbodiimide intermediate was proposed without evidence.