Propargylic Amines Research Articles

N-Heterocyclic Silylene-Cu(I) Complexes as Efficient Catalysts for Three-Component Coupling Reactions.

We have explored NHSi-supported copper(I) complexes as active and highly efficient catalysts for A3 (aldehyde-alkyne-amine) and KA2 (ketone-alkyne-amine) three-component coupling reactions to synthesize propargyl amines in excellent yields with high TOF under solvent-and additive-free conditions.

A Precise Route to Tetrasubstituted Allyl Amines via Regioselective Dicarbofunctionalization of Masked Propargyl Amines.

Allyl amines are vital components in various biologically important molecules and play a significant role in their function. Presently, most methods are geared toward the preparation of di- and trisubstituted allyl amines, leaving a gap for the development of more versatile approaches. We herein describe an approach to yield tetrasubstituted allyl amines through palladium (Pd)-catalyzed regioselective dicarbofunctionalization of masked N-phthalimide-protected propargyl amines. The cationic Pd-intermediate in conjunction with the masked amine exerts collective control for the reaction regioselectivity. This method accommodates a wide range of alkynes, aryl boronic acids, and aryl diazonium salts offering direct access to a wide range of unusual tetrasubstituted allyl amines.

Efficient paddle-wheel copper cluster-based metal-organic framework for catalytic conversion of CO2 to oxazolidinones under mild conditions

Efficient utilization of CO2 and its conversion into high-value-added products contribute to mitigating environmental issues such as the greenhouse effect. Among these methods, the carboxylation cyclization of CO2 with propargylic amine represents a green and atom-economical approach. Developing cost-effective catalyst that can promote this reaction under mild condition is desirable but challenging. Herein, a unique two-dimensional (2D) metal–organic framework (MOF) {[Cu(QCA)2]∙0.5DMF∙0.5H2O}n (1) (QCA =6-quinolinecarboxylic acid, DMF = N,N-dimethylformamide) have been synthesized and thoroughly characterized. Compound 1 was constructed from paddle-wheel dinuclear copper clusters [Cu2(COO)4] and carboxylate ligands, presenting a two-dimensional framework with new topology. Stability tests indicate that compound 1 undergoes reversible structural changes in different solvents and exhibits good thermal stability. 1 as heterogeneous catalyst enabled the transformation of CO2 and propargylic amine into oxazolidinones under mild conditions with broad substrate generality. In addition, 1 could maintain its catalytic performance with five continuous reactions. This work presents an infrequent example of a 2D noble metal free MOF-based catalyst that shows high catalytic efficiency under mild conditions.

Two Sustainable Pathways of MOF-Catalyzed Room Temperature Chemical Fixation of CO2 inside Alkynes under Atmospheric Pressure.

The rising atmospheric CO2 levels necessitate the development of effective materials for its mitigation. Utilization of adsorbent materials for the reversible physisorption of CO2 has a significantly less impact. Recognizing this need, herein, we present a nitrogen-rich, aqua-stable, Ag(0)-nanoparticle-doped metal-organic framework (MOF) designed for the irreversible chemical conversion of CO2 into valuable fine chemicals. We demonstrate two sustainable pathways for CO2 fixation, utilizing the catalyst, 1'@Ag NPs. The designed catalyst facilitates the cyclization of propargylic amines and alcohols under ambient temperature and pressure conditions. Remarkably, this is the first MOF-based catalyst that allows for quantitative conversion of propargylic amines into 2-oxazolidinones at room temperature with atmospheric CO2 pressure. The process successfully transforms various propargylic amines and alcohols into 2-oxazolidinones and α-alkylidene cyclic carbonates under the CO2 atmosphere. Additionally, the catalyst shows excellent recyclability, maintaining its activity and structural integrity across multiple reuse cycles. Control experiments revealed that the catalytic efficiency of 1'@Ag NPs is attributed to the highly exposed alkynophilic Ag(0) sites on its pore walls. Computational studies further elucidate the mechanistic pathway for CO2 fixation. This work highlights the potential of 1'@Ag NPs to enhance environmental sustainability by converting CO2 into valuable bioactive chemicals under mild conditions.

Conversion of atmospheric CO2 catalyzed by thiolate-based ionic liquids under mild conditions: efficient synthesis of 2-oxazolidinones.

Thiolate-based ionic liquids, specifically the catalyst [TBP][2-Tp], have demonstrated their efficiency in catalyzing the reaction of CO2 with propargylic amine. This novel synthetic method can be used to synthesize various 2-oxazolidinone derivatives with high yields. The catalyst can be easily regenerated and reused without any decline in its catalytic activity. Experimental and spectroscopic investigations have confirmed that the high activity of [TBP][2-Tp] is attributed to the synergistic effect of its S and N sites in activating CO2, rather than depending solely on basicity to activate the amino group of propargylic amine. These findings highlight the significant potential of thiolate-based ionic liquids for applications in CO2 activation and conversion.

Non-Noble Metal Anchored 2D Covalent Organic Framework for Ambient CO2 Fixation to High-Value Compounds.

The catalytic functionalization of CO2 into high-value compounds comprises a promising approach to mitigate its atmospheric content and sustainable generation of fine chemicals. Herein, we report application of a crystalline, nano-porous 2D COF (ET-BP-COF) for utilization of CO2. The ET-BP-COF features a unique 2D kagome (kgm) topology composed of hexagonal and triangular 1D channels decorated with bipyridine sites, which were exploited for covalent anchoring of eco-friendly Cu(I) by post-synthetic method. The Cu(I) engrafted COF was applied as a recyclable catalyst for coupling CO2 with alkynes to generate two high-value compounds, α-alkylidene cyclic carbonates (α-ACCs) and 2-oxazolidinones. Notably, Cu(I)@ET-BP-COF demonstrated excellent catalytic performance for transforming propargylic amine and CO2 to 2-oxazolidinone, an essential building block for antibiotics. Besides, an efficient transformation of propargylic alcohols to generate α-ACCs, valuable commodity chemicals, has been achieved by utilizing carbon dioxide. Further, detailed theoretical simulations disclosed the insight mechanistic path of Cu(I) catalyzed coupling of CO2 with alkynes to produce 2-oxazolidinones and α-ACCs. Significantly, Cu(I)@COF was reusable for multiple cycles without losing framework rigidity and catalytic performance. This study showcases the potential application of ET-BP-COF for stable anchoring of eco-friendly metals as catalytic sites for effective utilization of CO2 to produce two high-value products.

Egg shell powder mediated Cu catalyst: A biowaste based catalytic approach for the synthesis of quinazolin-4(3H)-ones and propargyl amines

A novel and efficient approach for a tandem oxidative synthesis of quinazolin-4(3H)-one from 2-aminobenzonitrile and benzyl alcohol has been unveiled via Cu2(CO3)(OH)2. Herein CuSO4.5H2O accompanied by egg shell powder is used for the easy preparation of Cu2(CO3)(OH)2. The reported method portrays a wide range of substrate scope with good to excellent yield and the given reaction proceed at room temperature within 12 h. Single crystal of one of the synthesized quinazolin-4(3H)-ones was analysed through single crystal X-ray diffraction (SC-XRD). Some of the compounds reported here are also known to possess various pharmaceutical activities. Eventually the newly prepared catalyst was applied for propargylamine synthesis via a multi component reaction. Perceiving all the advantages, present protocol is conceivably considered as clean, cost-effective and sustainable over reported procedures used for synthesis of quinazolin-4(3H)-ones and propargyl amines.

Cu(II)-Organic Framework for Carboxylative Cyclization of Propargylic Amines with CO2.

Effective CO2 transformations hold essential significance for carbon neutrality and sustainable energy development. Carboxylative cyclization of propargylic amines with CO2 serves as an atom-economic reaction to afford oxazolidinones, showing broad applications in organic synthesis and pharmaceutical fields. However, most catalysts involved noble metals, exhibited low efficiency, or required large amounts of base. Hence, it is imperative to explore alternative noble-metal-free catalysts in order to achieve efficient conversion while minimizing the use of additives. Herein, a novel nanopore-based Cu(II)-organic framework (1) based on a new imidazole carboxylic ligand was successfully constructed and exhibited excellent stability. Catalytic investigations revealed that the combination of 1 with 1,4-diaza[2.2.2]bicyclooctane (DABCO) efficiently catalyzed the carboxylative cyclization of propargylic amines with CO2, achieving turnover numbers of 142 based on the catalyst and 7.1 based on DABCO. 1 as a heterogeneous catalyst maintained high catalytic performance even after being reused at least 5 cycles, with its structure remaining stable. The strong activation of Cu(II) cluster nodes of catalyst 1 toward -NH- groups within organic substrates, as demonstrated by mechanism experiments, along with excellent CO2 adsorption performance and the presence of regular 1D channels, synergistically facilitates the reaction rate. This research presents the first instance of a Cu(II)-organic framework achieving this cyclization reaction, offering wide prospects for novel catalyst design and CO2 utilization.

Cu(I)-Glutathione Assembly Supported on ZIF-8 as Robust and Efficient Catalyst for Mild CO2 Conversions.

The Cu-glutathione (GSH) redox system, essential in biology, is designed here as a supramacromolecular assembly in which the tetrahedral 18e Cu(I) center loses a thiol ligand upon adsorption onto ZIF-8, as shown by EXAFS and DFT calculation, to generate a very robust 16e planar trigonal single-atom Cu(I) catalyst. Synergy between Cu(I) and ZIF-8, revealed by catalytic experiments and DFT calculation, affords CO2 conversion into high-value-added chemicals with a wide scope of substrates by reaction with terminal alkynes or propargyl amines in excellent yields under mild conditions and reuse at least 10 times without significant decrease in catalytic efficiency.

Cu(I)‐Glutathione Assembly Supported on ZIF‐8 as Robust and Efficient Catalyst for Mild CO2 Conversions

AbstractThe Cu‐glutathione (GSH) redox system, essential in biology, is designed here as a supramacromolecular assembly in which the tetrahedral 18e Cu(I) center loses a thiol ligand upon adsorption onto ZIF‐8, as shown by EXAFS and DFT calculation, to generate a very robust 16e planar trigonal single‐atom Cu(I) catalyst. Synergy between Cu(I) and ZIF‐8, revealed by catalytic experiments and DFT calculation, affords CO2 conversion into high‐value‐added chemicals with a wide scope of substrates by reaction with terminal alkynes or propargyl amines in excellent yields under mild conditions and reuse at least 10 times without significant decrease in catalytic efficiency.

Tandem Condensation-Cycloaddition of Propargylic Amines with α-Azido Ketones and β-Alkoxy-γ-Azido Enones.

α-Azido ketones and their vinylogous relatives β-alkoxy-γ-azido enones are versatile building blocks for constructing diverse heterocyclic products, but are prone to azide decomposition. Here, we report their condensation with propargylic amines and investigate the fate of the intermediate azido-enamine condensation products, both experimentally and theoretically. Efficient intramolecular cycloaddition was observed for electron-poor azide substrates, and a range of diversely substituted [1,2,3]triazolo[1,5-a]pyrazine products is reported. For electron-rich substrates, azide decomposition predominated. Computational modeling of possible pathways from the azido-enamine intermediates revealed two alternative mechanisms for azide decomposition, which were consistent with observed side products.

Design of efficient benzimidazole-derived N-heterocyclic carbene Ag(I) catalysts for aldehyde–amine–alkyne coupling

A mild catalytic protocol for aldehyde, amine, and alkyne coupling (A3-coupling) allows for the selective synthesis of propargyl amines using 5,6-dimethylbenzimidazole-derived N-heterocyclic carbene (BNHC) silver(I) catalysts. A series of BNHC Ag(Ⅰ) halide complexes were synthesized and their structures have been elucidated through the use of multinuclear NMR and FT-IR spectroscopy. Furthermore, the pseudo-linear geometry of two different compounds was substantiated by single-crystal X-ray diffraction. Silver-based A3-coupling was achieved for both acyclic and cyclic secondary amines using a diverse set of alkynes to afford propargyl amines with yields of up to 95 %. The present approach is environmentally benign and water is generated as the sole byproduct.

Conversion of Propargylic Amines with CO2 Catalyzed by a Highly Stable Copper(I) Iodide Thorium-Based Heterometal-Organic Framework.

The conversion of CO2 to generate high-value-added chemicals has become one of the hot research topics in green synthesis. Thereinto, the cyclization reaction of propargylic amines with CO2 is highly attractive because the resultant oxazolidinones are widely found in pharmaceutical chemistry. Cu(I)-based metal-organic frameworks (MOFs) as catalysts exhibit promising application prospects for CO2 conversion. However, their practical application was greatly limited due to Cu(I) being liable to disproportionation or oxidization. Herein, the solid copper(I) iodide thorium-based porous framework {[Cu5I6Th6(μ3-O)4(μ3-OH)4(H2O)10(L)10]·OH·4DMF·H2O}n (1) (HL = 2-methylpyridine-4-carboxylic acid) constructed by [Th6] clusters and [CuxIy] subunits was successfully prepared and structurally characterized. To our knowledge, this is the first copper(I) iodide-based actinide organic framework. Catalytic investigations indicate that 1 can effectively catalyze the cyclization of propargylic amines with CO2 under ambient conditions, which can be reused at least five times without a remarkable decline of catalytic activity. Importantly, 1 exhibits excellent chemical stability and the oxidation state of Cu(I) in it can remain stable under various conditions. This work can provide a valuable strategy for the synthesis of stable Cu(I)-MOF materials.

Silver Complex Bearing N-Heterocyclic Carbene Bidentate Chelating Ligand as an Efficient Catalyst in Solvent-Free KA2 Coupling.

We report a synthesis of silver complexes bearing chelating bidentate N-heterocyclic carbene, with various substitutions at the terminal positions of the imidazole moiety of the NHC units. The long aliphatic substituents proved to be beneficial in terms of the synthetic efficiency of the complexes, compared to previously reported methyl substitution. The complexes demonstrated excellent suitability for the KA2 coupling reaction, providing quaternary carbon-containing propargylic amines in yields up to 95 %, under solvent-free conditions. The method showed high tolerance for a wide range of substrates, including naturally occurring ketones, underscoring its practicality. To our knowledge, this represents the first use of a well-defined silver species in KA2 coupling, marking an advancement in the field.

Incorporation of CO2 in efficient oxazolidinone synthesis at mild condition by covalent triazine framework designed with Ag nanoparticles

We have synthesized a new hybrid material, Ag0@CTFN in which small-sized Ag-nanoparticles (Ag-NPs) are anchored on the surface of covalent triazine framework nanosheet (CTFN). Here, CTFN works as the support as well as the capping agent for the small-sized Ag-NPs. Ag0@CTFN has been synthesized in a one pot method where Ag-NPs attach with the nitrogen atoms present in the triazin units. This as synthesized Ag0@CTFN material has been characterized by FTIR, XRD, N2 adsorption desorption analysis, SEM, TEM and XPS analysis. All these characterizations reveal that around 4.97 nm sized Ag-NPs are anchored on the surfaces of layer-like CTFN nanosheets. Ag0@CTFN samples have shown their excellent catalytic activity for the selectively oxazolidinone formation from propargyl alcohol and amine by fixing CO2 under mild reaction condition. Moreover, this is the first report on Ag0@CTFN hybrid material which catalyze the oxazolidinone synthesis by fixing CO2. Again, this catalyst has shown their recyclability for oxazolidinone synthesis reaction up to sixth cycle by keeping their activity almost intact. There is no metal or catalyst leaching noticed up to sixth cycle for this reaction.

Propargyl amines by aldehyde-amine-acetylene coupling mediated by Ag(I) and Cu(I) complexes of super bulky N-heterocyclic carbenes: Unveiling the role of the super bulky ligands in the coupling reaction

The copper (1–2)a and the silver (1–2)b complexes of the super bulky N-heterocyclic carbene (NHC) variants namely, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]MX [where, M = Cu; X = Cl (1a), Br (2a): M = Ag; X = Cl (1b), Br (2b)] effectively facilitated the A3 coupling reaction of diverse amine, aldehyde, and acetylene substrates yielding a wide array of propargylamines in moderate to good (ca. 24−89 %) yields. A metal bound acetylide species, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]M(CCPh) [where, M = Cu (A), Ag (B)] has been identified as a key catalytic species by mass spectrometric studies. The Density functional theory (DFT) studies further revealed the rate-limiting step as the formation of the C-C coupling transition state (TS2) from the silver-acetylide species (Int2). The super bulky ligand framework plays a pivotal role in this step by anchoring the protonated Schiff's base imine in the vicinity of the alkyne through several non-covalent-interactions, including a strong C–H•••O interaction, thereby reducing the corresponding kinetic barrier leading to an efficient catalytic transformation as reflected in the high propargylamine yields. Furthermore, the catalytic utility of the coupling reaction was further extended by synthesising pargyline, which is a monoamine oxidase B (MAO-B) inhibitor drug molecule, in a one-pot manner and that to in a gram-scale synthesis.

Access to 4‐Membered Heterocycles via Visible‐Light Triggered Intramolecular Cyclization from Alkynes: Bypassing Unfavorable 4‐endo‐dig Cyclization

AbstractWe describe a catalyst, oxidant, and coupling‐reagent free strategy to access 4‐membered heterocycles, representing a unique example of visible‐light triggered intramolecular cyclization of propargylic alcohols and amines to access oxetanones and azetidinones respectively. Despite the direct 4‐endo‐dig cyclization from these starting materials has proven to be unfavorable, the formation of key p‐quinone methide intermediacy allows an efficient bypass for regioselective 4‐exo‐trig cyclization, resulting in the formation of the desired 4‐membered heterocycles. This mild and operationally simple protocol facilitates the synthesis of products with distinct substitution patterns such as quaternary α‐carbons, and enables late‐stage functionalization.

An Attractive and Efficient Method for Preparation of Propargyl Amines: Presentation of a Novel Magnetically Reusable Manganese Nanocatalyst for C-N Bond Formation

An Attractive and Efficient Method for Preparation of Propargyl Amines: Presentation of a Novel Magnetically Reusable Manganese Nanocatalyst for C-N Bond Formation

Synthesis of Quinolones from Propargylic Chlorides and Amines

Synthesis of Quinolones from Propargylic Chlorides and Amines

Enantioselective propargylic amination and related tandem sequences to α-tertiary ethynylamines and azacycles.

Chiral α-tertiary amines and related azacycles are sought-after compounds for drug development. Despite progress in the catalytic asymmetric construction of aza-quaternary stereocentres, enantioselective synthesis of multifunctional α-tertiary amines remains underdeveloped. Enantioenriched α-disubstituted α-ethynylamines are attractive synthons for constructing chiral α-tertiary amines and azacycles, but methods for their catalytic enantioselective synthesis need to be expanded. Here we describe an enantioselective asymmetric Cu(I)-catalysed propargylic amination (ACPA) of simple ketone-derived propargylic carbonates to give both α-dialkylated and α-alkyl-α-aryl α-tertiary ethynylamines. Sterically confined pyridinebisoxazoline (PYBOX) ligands, with a C4 shielding group and relaying groups, play a key role in achieving excellent enantioselectivity. The syntheses of quaternary 2,5-dihydropyrroles, dihydroquinines, dihydrobenzoquinolines and dihydroquinolino[1,2-α]quinolines are reported, and the synthetic value is further demonstrated by the enantioselective catalytic total synthesis of a selective multi-target β-secretase inhibitor. Enantioselective Cu-catalysed propargylic substitutions with O- and C-centred nucleophiles are also realized, further demonstrating the potential of the PYBOX ligand.