Propargylic Amines Research Articles

Copper-Catalyzed Aerobic Oxidative Alkynylation of 3,4-Dihydroquinoxalin-2-ones

Herein, we described a ligand-free copper-catalyzed aerobic oxidative functionalization of 3,4-dihydroquinoxalin-2(1H)-ones with terminal alkynes using visible-light and oxygen as terminal oxidant to give 3-ethynyl-3,4-dihydroquinoxalin-2(1H)-one, cyclic propargylic amines, in moderate to good yields. Moreover, we demonstrate the versatility of the 3-ethynyl-3,4-dihydroquinoxalin-2(1H)-ones obtained by preparing several 3,4-dihydroquinoxalin-2-one derivatives.

Development of a Telescoped Flow Process for the Safe and Effective Generation of Propargylic Amines.

Propargylic amines are important multifunctional building blocks that are frequently exploited in the synthesis of privileged heterocyclic entities. Herein we report on a novel flow process that achieves the safe and effective on-demand synthesis of propargylic amines in a telescoped manner. This process minimizes exposure to hazardous azide intermediates and renders a streamlined route into these building blocks. The value of this approach is demonstrated by the rapid generation of a small selection of drug-like thiazolines that result from a high-yielding reaction cascade between propargylic amines with different aryl isothiocyanates.

Concise design and synthesis of pyridine-fused heterocycles via 6π-Azaelectrocyclization process of iminoalkyne derivatives

A concise and regioselective approach to the synthesis of pyridine-fused heterocycles and benzoxazepine derivatives was developed. Propargyl imines derived from aromatic aldehydes and propargyl amine underwent 6π-electrocyclization reactions at high temperatures in high yields to form pyridine-fused heterocycles. Application of the same methodology to aromatic imines having a hydroxyl group in the ortho position resulted in the formation of (benz)oxazepine derivatives. The formation mechanism of the products was discussed.

Regioselective single-step synthesis of 2-aminoimidazole derivatives

A convenient single-step strategy for the regioselective assembly of 2-aminoimidazole derivatives is herein described. Through a transition metal-free domino addition/cyclization process, the reactions of unsymmetrical carbodiimides with propargylic amines mediated by Cs2CO3 selectively afforded the corresponding polysubstituted 2-aminoimidazoles in moderate to good yields under very mild conditions. The regioselectivity was reversed in the presence of TEA at a higher temperature. The obtained 2-(o-iodoaryl)amino imidazoles could be easily converted to 2-(2-biphenyl)amino imidazole, 2-(o-alkynylphenyl)amino imidazole, benzoimidazo[1,2-a]imidazole and N-(imidazol-2-yl)indole derivatives.

Carboxylative Cyclization of Propargylic Amines with Carbon Dioxide­ Catalyzed by Poly(amidoamine)-Dendrimer-Encapsulated Gold Nanoparticles

We prepared gold nanoparticles encapsulated in poly(amidoamine) (PAMAM) dendrimers as templating agents. The resulting gold nanoparticles were used as catalysts for the carboxylative cyclization of propargylic amines with carbon dioxide to afford the corresponding 1,3-oxazolidin-2-ones in yields of up to 99%.

Synthesis of Thiazolo[3,2‐b] [1,2,4]triazoles through Pd‐Catalyzed Copper‐Free Sonogashira Coupling Reaction

AbstractThe synthesis of 2‐substituted thiazolo[3,2‐b] [1,2,4]triazoles is accomplished copper‐free, Pd‐catalyzed Sonogashira reaction of 6‐(iodomethyl)‐2‐methylthiazolo[3,2‐b][1,2,4]triazole with terminal alkynes in DMF at 70 °C. The coupling reaction of phenylacetylene and 4‐ethynyltoluene gave the desired products in high yields. While, the Sonogashira reaction of alkynes such as 1‐hexyne, 1‐octyne, propargyl alcohols, and propargyl amines afforded the products in good yields.

Cu doped ZIF Catalyzed Synthesis of Propargyl Amines with Quaternary Carbon Center Under Solvent Free Conditions

AbstractHere we report catalytic application of Cu doped ZIF‐8 in synthesis of propargylamines bearing a quaternary center. The developed solvent free protocol has shown good substrate scope and the catalyst has performed well in the recyclability experiment with negligible loss in catalytic efficiency after four catalytic cycles.

Snail shell-shaped chiral substituted helical polyacetylene: preparation, characterization and infrared emissivity performance

The first snail shell-shaped helical polyacetylenes (SHPAs) were synthesized from the copolymerization between l-serine-grafted propargylamine (LSA) and propargylamine (PA). The novel structure was obtained at the monomer input proportion of 50%. The monomer (LSA) and copolymers (poly(LSAm-co-PAn)) were characterized by 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, ultraviolet visible spectroscopy, circular dichroism and transmission electron microscopy. The infrared emissivity of poly(LSA50-co-PA50) investigated at 8–14 μm was 0.451, which was much lower than the other copolymers. This was because the poly(LSA50-co-PA50) could form the obvious intramolecular interaction and self-assembled to a snail-shell shape by intermolecular hydrogen bonding in MeOH solution. Meanwhile, the conjugation performance of the main chain was enhanced. Consequently, the abundant hydrogen bonds formed through N–H and C=O bonding and the strong conjugate properties both could decrease the unsaturation degree, as well as change the heat conduction mode in the molecules, thereby reducing the infrared emissivity. This strategy provided a new direction to achieve the controllable infrared stealth.

Cobalt-based catalysis for carboxylative cyclization of propargylic amines with CO2 at atmospheric pressure

A cobalt-bicyclic guanidine catalytic system consisting of CoBr2 and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) for the carboxylative cyclization of terminal propargylic amines with CO2 was firstly developed in this work to produce 2-oxazolinones efficiently. The existence of induction period urged us to understand the reaction mechanism of cobalt catalysis. Investigation on the roles of CoBr2 and TBD was conducted using control experiments and density functional theory (DFT) calculation. TBD presumably acts as a base to activate propargylic amine for favorable CO2 capture, and a ligand to coordinate with CoBr2 via forming bulkier CoBr2(TBD) in the same time. This bulkier complex can enhance the O-nucleophility of the in situ formed carbamate intermediate and then promote subsequent intramolecular cyclization to generate 2-oxazolinone, accounting for the high activity of cobalt catalysis. This protocol enables the synthesis of various 2-oxazolinones from propargylic amines and CO2 under atmospheric pressure in good to excellent yields, representing a simple, cost-effective and practical route for CO2 fixation to 2-oxazolinones under mild conditions.

Gold-Catalyzed Hydrophenoxylation of Propargylic Alcohols and Amines: Synthesis of Phenyl Enol Ethers.

A practical method for the synthesis of phenyl enol ethers is reported. The combination of a gold(I) catalyst and potassium carbonate selectively mediates the addition of phenols to propargylic alcohols/amines in a chemo-, regio-, and stereoselective fashion in high yield. The resulting enol ethers are formed exclusively with a Z-configuration and can be obtained from a wide array of phenols and propargylic alcohols or amines with the reaction showing excellent functional group tolerance.

Palladium‐Catalyzed Carboxy‐Alkynylation of Propargylic Amines Using Carbonate Salts as Carbon Dioxide Source

A palladium‐catalyzed multicomponent reaction of propargylic amines, alkynyl bromides and cesium hydrogen carbonate to access oxazolidinones is reported. In contrast to previous reports, only a slight excess of cesium hydrogen carbonate is used as a surrogate of carbon dioxide. The reaction gives access to oxazolidinones bearing alkyl‐ and aryl polysubstituted enynes in good yield and very high E stereoselectivity.

Epoxide-Mediated Stevens Rearrangements of α-Amino-Acid-Derived Tertiary Allylic, Propargylic, and Benzylic Amines: Convenient Access to Polysubstituted Morpholin-2-ones.

A new strategy has been established for the synthesis of polysubstituted morpholin-2-ones through Stevens rearrangements of tertiary amines via in situ activation with epoxides. A range of α-amino acid-derived tertiary allylic, propargylic, and benzylic amines reacted with epoxides in the presence of zinc halide catalysts to afford structurally diverse allyl-, allenyl-, and benzyl-substituted morpholin-2-ones, respectively, in moderate-to-good yields with high regioselectivity. The process involves [2,3]- and [1,2]-Stevens rearrangements of quaternary ammonium ylide intermediates and constitutes a very convenient method to prepare polysubstituted morpholin-2-ones through tandem formation of C-N, C-O, and C-C bonds. Moreover, replacing epoxides with aziridines permitted the synthesis of polysubstituted piperazin-2-ones.

Design and Synthesis of a Cyclic Double-Grafted Polymer Using Active Ester Chemistry and Click Chemistry via A "Grafting onto" Method.

Combing active ester chemistry and click chemistry, a cyclic double-grafted polymer was successfully demonstrated via a “grafting onto” method. Using active ester chemistry as post-functionalized modification approach, cyclic backbone (c-P2) was synthesized by reacting propargyl amine with cyclic precursor (poly(pentafluorophenyl 4-vinylbenzoate), c-PPF4VB6.5k). Hydroxyl-containing polymer double-chain (l-PS-PhOH) was prepared by reacting azide-functionalized polystyrene (l-PSN3) with 3,5-bis(propynyloxy)phenyl methanol, and further modified by azide group to generate azide-containing polymer double-chain (l-PS-PhN3). The cyclic backbone (c-P2) was then coupled with azide-containing polymer double-chain (l-PS-PhN3) via CuAAC reaction to construct a novel cyclic double-grafted polymer (c-P2-g-Ph-PS). This research realized diversity and complexity of side chains on cyclic-grafted polymers, and this cyclic double-grafted polymer (c-P2-g-Ph-PS) still exhibited narrow molecular weight distribution (Mw/Mn < 1.10).

Palladium-Catalyzed Carbo-Oxygenation of Propargylic Amines using in Situ Tether Formation.

1,2-Amino alcohols and α-aminocarbonyls are frequently found in natural products, drugs, chiral auxiliaries, and catalysts. This work reports a new method for the palladium-catalyzed oxyalkynylation and oxyarylation of propargylic amines. The reaction is perfectly regioselective based on the in situ introduction of a hemiacetal tether derived from trifluoroacetaldehyde. cis-Selective carbo-oxygenation was achieved for terminal alkynes, whereas internal alkynes gave trans-carbo-oxygenation products. The obtained enol ethers could be easily transformed into 1,2-amino alcohols or α-amino ketones using hydrogenation or hydrolysis, respectively.

Ternary hybrid TiO2-PANI-AuNPs for photocatalytic A3-coupling of aldehydes, amines and alkynes: First photochemical synthesis of propargyl amines

The present paper describes the successful synthesis and application of a ternary hybrid consists of gold nanoparticles decorated on titania-polyaniline (TiO2-PANI-AuNPs) for A3-coupling between aldehydes, terminal alkynes and amines under visible irradiation. The synthesis of ternary hybrid involved the coating of PANI on TiO2 via an oxidative polymerization method followed by the deposition of AuNPs on TiO2-PANI using trisodium citrate as a reducing agent. The synthesized photocatalyst was characterized by various techniques like FT-IR, SEM, HR-TEM, XRD, UV-VIS, ICP-AES, TGA, XPS and PL spectroscopy. The synthesized photocatalyst exhibited higher efficiency which was presumed due to the suppressed electron-hole recombination and better electron mobility at the surface of the photocatalyst. In the hybrid, polyaniline was found to enhance the activity as well as stability of the photocatalyst owing to its chemical interaction with titania and gold. Furthermore, after the reaction, the photocatalyst could readily be recovered and recycled for several runs with consistent photoactivity.

Intramolecular azavinyl carbene-triggered rearrangement of furans.

An intramolecular rhodium-catalyzed reaction of 1-tosyl-1,2,3-triazoles with furans has been explored. The tosylimino functionality was found to play a significant chemical role participating in the subsequent domino-transformations of a key reaction intermediate. One of the reaction pathways leads to valuable 2-formyl- and 2-acetylpyridine building blocks, which could be obtained in one-pot starting from easily accessible (furan-2-ylmethyl)propargyl amines. An original method for the synthesis of highly functionalized indolizines from the obtained pyridines has been proposed.

Ag NPs decorated on a COF in the presence of DBU as an efficient catalytic system for the synthesis of tetramic acids via CO2 fixation into propargylic amines at atmospheric pressure.

CO2 fixation reactions by inserting it in reactive organic compounds are very challenging for the utilization of this abundant and harmful gas present in air and thus to mitigate this greenhouse gas responsible for global warming. This can be achieved by appropriate design of functionalized porous nanocatalysts having high surface areas and porosity and good CO2 uptake capacity. Herein, we first report the decoration of silver nanoparticles (NPs) over the surface of a covalent organic framework (COF) material TpPa-1 synthesized through the polycondensation of 2,4,6-triformylphloroglucinol (TFP) and p-phenylenediamine. The resulting material Ag@TpPa-1 was thoroughly characterized by N2 adsorption/desorption, powder X-ray diffraction (PXRD), FE-SEM, TEM, UV-Vis, FT IR and thermogravimetric techniques. This Ag NP decorated porous COF in the presence of DBU exhibited excellent catalytic activity for the synthesis of tetramic acids from a variety of propargylic amine derivatives at 60 °C under atmospheric pressure of carbon dioxide via formation of oxazolidinones, where CO2 acts as a C1 reagent. The Ag@TpPa-1 catalyst exhibited excellent recycling efficiency for the synthesis of tetramic acid with no leaching of Ag from the catalyst surface.

Silver(i)-catalysed carboxylative cyclisation of primary propargylic amines in neat water using potassium bicarbonate as a carboxyl source: an environment-friendly synthesis of Z-5-alkylidene-1,3-oxazolidin-2-ones

An environment-friendly synthesis of Z-5-alkylidene-1,3-oxazolidin-2-ones in water under gas-free conditions.

Novel ferrocene-labeled propargyl amines via CuI multicomponent amination/alkynylation

An efficient synthesis of ferrocene-tagged propargyl amine derivatives via one-pot three-component domino amination/alkynylation in water is reported.

Facile Synthesis of Pyridines from Propargyl Amines: Concise Total Synthesis of Suaveoline Alkaloids.

A general and efficient protocol was developed for the synthesis of polysubstituted pyridines from propargyl amines and unsaturated carbonyl compounds through a tandem condensation/alkyne isomerization/6π 3-azatriene electrocyclization sequence. This process was found to be applicable to a wide range of readily available substrates (30 examples, up to 95 % yield) and could be readily performed on a preparative (20 g) scale. By taking advantage of this method for late-stage pyridine incorporation, we successfully completed the collective total synthesis of suveoline, norsuveoline, and macrophylline.