Propargylic Amines Research Articles

A [Cu2I2] cluster-based lanthanide metal–organic framework (MOF) catalyst for the highly efficient conversion of CO2 with propargylic alcohols and aziridines

A new metal–organic framework (MOF) with the formula [Eu2Cu2I2(IN)6(DMF)4]·4DMF (1) (HIN = isonicotinic acid, DMF = N,N-dimethylformamide) based on lanthanide ions and copper iodide clusters (Cu2I2) have been successfully constructed and characterized. Structural analysis indicates that the [Cu2I2] cluster-based lanthanide MOF 1 displays a two-dimensional plane with sql topology. Catalytic study indicates that MOF 1 can efficiently catalyze the propargylic alcohols or aziridines with CO2 under mild conditions. What's more, 1 as a heterogeneous catalyst can be recycled at least five times without obvious loss of catalytic performance. To our best knowledge, it is a rare example of a [Cu2I2] cluster-based lanthanide MOF catalyst that can catalyze both aziridines and propargylic amines with CO2 simultaneously under mild conditions.

Enantioselective Alkynylation of 2-Aryl-3H-indol-3-ones via Cooperative Catalysis of Copper/Chiral Phosphoric Acid.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)-CPA catalysis is described. The strategy of the alkynylation of 2-aryl-3H-indol-3-one directly to chiral propargylic amines containing indolin-3-one moiety in good yields and enantioselectivities. Moreover, gram-scale synthesis of chiral propargylamines based C2-quaternary indolin-3-ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity.

Low-cost and high-performance acetylglucose-based imidazolium salts for copper-catalyzed cyclization of propargylic amines and CO2

The rise of carbon dioxide (CO2) in atmosphere is considered as a major cause of global warming. Therefore, CO2 utilization has attracted increasing attention. Among those, using CO2 as C1-feedstock for “value carbon” in advanced chemicals provides a solution. Here, we show an acetylglucose-based imidazolium salt for Cu-catalyzed cyclization of propargylic amines and CO2 with an excellent turnover frequency value of 400 h−1. To the best of our knowledge, it is the first example of acetylglucose-based imidazolium salts for a noble-metal-free Cu catalytic system for the cyclization of propargylic amines and CO2.

HAuCl4 Catalyzed and Dibenzyl amine Centered A3 coupling reaction: Synthesis, Spectroscopic Proofing and Anti‐microbial Efficacy

AbstractThis research suggests an ideal method for synthesizing propargyl amine adducts by a three‐component condensation of dibenzyl amine (DBA), aldehyde, and phenylacetylene (known as A3 coupling reactions). The aimed synthesis was carried out using a gold catalyst, chlouro auric acid (HAuCl4) and compared with Cu(I) systems to check the involvement of metals to generate enantiomerically pure compounds (4 a–4 j). No major deactivation of the catalyst was observed after repeated use in a similar reaction system (>10 times). The derived motifs′ spectroscopic profiling (1H NMR, 13C NMR, APT, IR and MS) has confirmed the structural fragments in a single core. Moreover, the applications of the derived motifs confirmed the comparable antimicrobial activity in some selected Gram‐positive and Gram‐negative bacterial; and fungi strains. Our consequences show that the scaffolds 4 d and 4 i having 4‐F and 4‐NMe2 substitution in the araldehyde system exhibited potent antimicrobial activity in most used bacterial and fungi strains.

Elemental Selenium in the Synthesis of Selenaheterocycles

An overview of the known methods of introducing selenium under the action of elemental selenium into the structures of various saturated, unsaturated, and heteroaromatic selenacycles containing C–Se, N–Se, B–Se, Ge–Se and P–Se bonds is presented. These methods include metal, iodine, bromine or chlorine exchange for selenium and the direct cyclization of 1-(2-bromoaryl)benzimidazoles, polyunsaturated hydrocarbons, acetylenes, propargylic amines, 3-halogenaryl amides, aryl amides, diazo-compounds, 2-aminoacetophenone, and the annulation of ethynyl arenes. Three- and four-component reactions utilizing elemental selenium as one of the components and leading to selenium-containing heterocycles are presented as well.

Copper and In Situ-Generated Triflic Acid Relay-Promoted Four-Component Cascade Reaction for the Construction of Polysubstituted Cycloguanidines

An unprecedented copper and in situ-generated triflic acid relay-promoted four-component cascade reaction of cyanamides, diaryliodonium triflates, propargylic amines, and H2O was established for rapid and concise construction of diverse five-membered cycloguanidines. Copper-catalyzed guanidination/intramolecular hydroamination and in situ-generated HOTf-accelerated hydration proceeded sequentially with high level of chemoselectivity and regioselectivity, and six new bonds were simultaneously built in high yields. Thus, diaryliodonium triflates served not only as an arylation reagent but also as an internal acid promoter, establishing an alternative strategy for highly efficient utilization of diaryliodonium trifates.

UVA LED Light Promoted Cross‐Coupling of Tertiary α‐Silylamines with 1‐Iodoalkynes

AbstractA synthetic strategy that exploits the formation of an electron donor‐acceptor (EDA) complex between a tertiary α‐silylamine and 1‐iodoalkyne under UVA LED (light emitting diode) light (λmax=365 nm) to prepare propargyl amines is described. The site‐ and chemoselective synthetic method was shown to tolerate a wide range of functional groups to give the α‐alkynylation product in good to excellent yields. The usefulness of the C(sp)–C(sp3) bond formation protocol was also exemplified by the late‐stage functionalisation of a variety of natural products and bioactive compounds.

Enantioselective aminomethylation of 1-(benzyloxy)propan-2-one with an aromatic C-ethyl substituted propargyl amine ether

Enantioselective aminomethylation of 1-(benzyloxy)propan-2-one with an aromatic propargyl amino ether in the presence of a chiral pseudoephedrine catalyst in an aqueous medium gave anti / syn products with high yields and optical purity.

Cu/Ag-Mediated One-Pot Enantioselective Synthesis of Fully Decorated 1,2,3-Triazolo[1,5-a]pyrazines.

The synthesis of chiral triazole-fused pyrazine scaffolds from readily available substrates in a step-economical asymmetric catalytic way is highly appealing. We herein report that an efficient Cu/Ag relay catalyzed protocol employing cascade asymmetric propargylic amination, hydroazidation, and [3 + 2] cycloaddition reaction with high efficiency to access the target enantioenriched 1,2,3-triazolo[1,5-a]pyrazine has been accomplished by applying a novel N,N,P-ligand. The one-pot reaction of three components exhibits high functional group tolerance, excellent enantioselectivities, and a broad substrate scope with readily available starting materials.

Gold nanoparticle decorated post-synthesis modified UiO-66-NH2 for A3-coupling preparation of propargyl amines

In this report, the novel UiO‑66‑NH2 based-MOF(Zr) catalytic system which further modified with nitrogen-rich organic ligand (5-aminotetrazole) using post synthetic modification (PSM) approach has been prepared here as an efficient catalyst to promote the A3-coupling preparation of propargyl amines in green aquatic media. This newly highly efficient catalyst was synthesized upon Zr-based MOF (UiO‑66‑NH2) which successfully functionalized with 2,4,6‑trichloro‑1,3,5‑triazine (TCT) and 5‑aminotetrazole, following through stabilization of gold metal (Au) nanopartilces. The addition of N-rich organic ligand through post-synthesis modification which can be assisted to stabilize the bister and stable gold nanoparticles caused to unique structure of the final composite in favor of the progress of the A3 coupling reaction. Also several strategies comprising XRD, FT-IR, SEM, BET, TEM, TGA, ICP, EDS and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@ Cyanuric Chloride@ 5-amino tetrazole/Au-NPs. The results of productivity catalyst are accomplished in good to excellent yields for all sort of reactions under mild conditions which is a proof of superior activity heterogeneous catalyst containing Au-nanoparticles. In addition, the suggested catalyst represented excellent reusability with no remarkable loss in activity up 9 sequential runs.

Genetically encoded photocatalytic protein labeling enables spatially-resolved profiling of intracellular proteome

Mapping the subcellular organization of proteins is crucial for understanding their biological functions. Herein, we report a reactive oxygen species induced protein labeling and identification (RinID) method for profiling subcellular proteome in the context of living cells. Our method capitalizes on a genetically encoded photocatalyst, miniSOG, to locally generate singlet oxygen that reacts with proximal proteins. Labeled proteins are conjugated in situ with an exogenously supplied nucleophilic probe, which serves as a functional handle for subsequent affinity enrichment and mass spectrometry-based protein identification. From a panel of nucleophilic compounds, we identify biotin-conjugated aniline and propargyl amine as highly reactive probes. As a demonstration of the spatial specificity and depth of coverage in mammalian cells, we apply RinID in the mitochondrial matrix, capturing 477 mitochondrial proteins with 94% specificity. We further demonstrate the broad applicability of RinID in various subcellular compartments, including the nucleus and the endoplasmic reticulum (ER). The temporal control of RinID enables pulse-chase labeling of ER proteome in HeLa cells, which reveals substantially higher clearance rate for secreted proteins than ER resident proteins.

Theoretical studies on the mechanisms and origins of substituent effects in CuBr-catalyzed three-component tandem reactions of terminal propargyl alcohols, aldehydes and amines

The CuBr-catalyzed A3-coupling-based tandem reactions of terminal propargyl alcohols, aldehydes and amines to synthesize five-membered dihydrofuran P1, disubstituted furan P2 and six-membered pyrone P3 have been developed. In this work, density functional theory (DFT) calculations have been performed to uncover the detailed reaction mechanisms and the substituent effects on the transformation of dihydrofuran P1 to pyrone P3. Computational results suggest that the catalytic cycle of dihydrofuran P1 is divided into three main processes: A3-coupling, isomerization and intramolecular cyclization. The generation of disubstituted furan P2 from dihydrofuran P1 proceeds via N-methylation and deprotonation steps. The transformation of five-membered dihydrofuran P1 to six-membered pyrone P3 is affected by the substituents R on substrate aldehyde 2. When R = OEt this transformation proceeds smoothly, undergoing the favorable OEt departure pathway. In contrast, the departure pathway is unworkable for Ph- and Me-substituted aldehydes due to the lack of hydrogen-bonding stabilization. They could only follow 1,2-R migration pathways. However, the high activation barriers in the migration pathways for the two aldehydes render the transformation infeasible. The results also reveal that silica gel acts as a significantly important hydrogen bond partner to stabilize the complexes in the transformation process. The theoretical research contributes to deeper insights into the mechanisms and the origins of substituent effects on the transformation between different heterocycles of the title reaction, which would promote the further development and design of the five- and six-membered oxygen-containing heterocycles.

Cyclization of Propargyl Amines with CO2 Catalyzed by MOF-Supported Cu2O and DABCO

Key words metal-organic frameworks - copper catalysis - carbon dioxide - propargyl amines - oxazolidinones - cyclization

Design, Synthesis, Molecular docking, and Antibacterial Study of Aminomethyl Triazolo Substituted Analogues of Benzimidazolo [1,4]-benzodiazepine

Sternbach-Reeder rearrangement of 2-chloromethyl substituted derivatives of benzimidazolo annulated analog of quinazoline 4(a-e) with propargyl amine (5) proceeded through a one-pot domino reaction leading to a concomitant opening of quinazoline ring followed by its intramolecular ring expansion to produce the corresponding 2-propargyl amino substituted derivatives of benzimidazolo [1,2]-benzodiazepine 6(a-e), which underwent a facile domino click copper-catalyzed cyclo-condensation reaction with NaN3 to form the 2-aminomethyl triazole substituted analogs of benzimidazolo [1,2]-benzodiazepine 7(a-e). Molecular docking and antibacterial properties of the synthesized compounds have also been reported.

Regioselective anti-Silyllithiation of Propargylic Amines

AbstractThe regioselective anti-silyllithiation of propargylic amines is developed to facilitate the efficient synthesis of alkenylsilanes. This reaction generates an alkenyllithium intermediate that is stabilized by the formation of a five-membered cyclic structure through intramolecular coordination of the nitrogen functional group. Upon subsequent treatment with an electrophile, the alkenyllithium intermediate is further functionalized to afford tetrasubstituted allylic amines bearing a β-silicon substituent.

Modular Divergent Synthesis of Functionalized Indoles via TFA-Promoted Amino-Claisen Rearrangement at Room Temperature.

A conceptually novel approach for the modular and divergent synthesis of highly functionalized indoles via trifluoroacetic acid-promoted amino-Claisen rearrangement is reported. This metal-free protocol could be performed at room temperature with wide functional group tolerance. The substitution type of the resultant indoles could be easily adjusted by the variation of the starting propargyl amines. The resultant products could be easily transformed into different value-added indole derivatives with simple experimental operations.

Synthesis of Polysubstituted Furan Frameworks via [3 + 2] Annulation of N-Enoxyimides with Chelated Alkynes Initiated by Rh(III)-Catalyzed C–H Activation

A variety of 2,3,5-trisubstituted furans were synthesized by virtue of a Rh(III)-catalyzed vinylic C-H coupling of N-enoxyimides with propargyl alcohols or amines. In this protocol, N-enoxyimides served as a one-oxygen and two-carbon synthon and the -OH/-NHR moiety in the alkynes was found to be crucial for realizing the desired chemo-/regioselectivity. Detailed experimental mechanistic studies together with DFT calculations clarified the sequential C-H activation/regioselective alkyne insertion/simultaneous O-N bond cleavage and hydrogen transfer/intramolecular nucleophilic addition/aromatization reaction path, which involved a distinctive Rh(V) carbene species as the active intermediate.

Lewis Acid-Catalyzed 1,4-Addition and Annulation of 4-Hydroxy-coumarins with o-Hydroxyphenyl Propargyl Amines: Entry to Regio-Selective Synthesis of Furano[3,2-c]coumarins and Pyrano[3,2-c]coumarins.

A facile and regioselective Lewis acid-catalyzed cascade annulation of o-hydroxyphenyl propargyl amines with 4-hydroxycoumarin to afford furano[3,2-c]coumarin and pyrano[3,2-c]coumarin derivatives is reported. The reaction presumably proceeds by the conjugate addition of 4-hydroxycoumarin to the in situ-generated alkynyl o-quinone methide and is followed by intramolecular 5-exo-dig and 6-endo-dig annulation to form furano[3,2-c]coumarins and pyrano[3,2-c]coumarins, respectively. The prepared o-hydroxyl substituted pyrano[3,2-c]coumarins could be readily transformed into the corresponding coumarin-derived dioxabicycles by acid-mediated cyclization.

Intramolecular Cyclization of N-Propargylic Amides without Transition-Metal Catalysis for Synthesis of Fluoroalkylated Oxazoles: Using Carboxylic Acid Anhydrides as the Fluoroalkyl Source

AbstractSynthesis of 2-fluoroalkylated oxazoles was developed by transition-metal-free intramolecular cyclization of N-propargylic amides, which are prepared from propargylic amines by employing a small excess of commercially available fluorocarboxylic acid anhydrides as fluoroalkyl­ sources, under basic conditions. Oxazoles bearing a trifluoro­methyl, pentafluoroethyl, or heptafluoropropyl group at the C2 position and functional groups on the C4 and/or C5 positions are obtained in moderate to high yields by controlling the reaction conditions.

Synthesis of 2‑Boryl Allylboronates by a Bimetallic Platinum/Zinc-Promoted Diborylation of Propargylic Amines

Abstract2‑Boryl allylboronates, which contain both a C(sp2)–B bond and a C(sp3)–B bond, are attractive synthetic intermediates due to their diverse reactivity profiles toward a wide range of organic transformations. We report a facile approach to (Z)-2‑boryl allylboronates through a Pt/Zn-promoted diborylation reaction of readily available propargylic amines. An array of valuable (Z)-2‑boryl allylboronates were obtained in up to 73% yield in the presence of 2.5 mol% of Pt(PPh3)4 and 50 mol% of ZnBr2.