Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• , generated from the tetranuclear complex, as the catalytically active species. 2.4 A3 reactions In recent years, the three component reaction of an aldehyde, a secondary amine and a terminal alkyne, known as A3 reaction to afford chiral propargylamines 140 has received much attention. The latter compounds

• resulting propargylamines to give allylamines 144 and alkylamines 145 in quantitative yields (Scheme 57). This system is made up of a silica support that has been modified with a covalently linked NHC–Cu complex for the A3 coupling, as well as RuNPs for hydrogenation. Detailed investigations revealed that

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• University, Kaliningrad 236016, Russian Federation 10.3762/bjoc.18.175 Abstract The previously described α-acetyl-α-diazomethanesulfonamide was employed in a three-component reaction with azide-containing benzaldehydes and propargylamines. Besides the initial formation of the triazole core, the reaction

• benzaldehydes and propargylamines. Besides the initial formation of the triazole core, the reaction proceeded further, in uncatalyzed fashion at room temperature and yielded structurally intriguing bistriazoles whose structure was unequivocally confirmed by single-crystal X-ray analysis. Compounds are non

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• trifluoromethylpropargylamine is of general research interest [28][29][30][31][32]. The asymmetric Ru/(R)-CPA-catalyzed chemoselectivie biomimetic reduction [33] and the organocatalytic transfer hydrogenation [34] of fluorinated alkynylketimines have been developed for the synthesis of fluorinated propargylamines in good

• yields and high enantioselectivities by the groups of Zhou and Peng, respectively (Scheme 1a). It should be mentioned that the Qing group also reported a method for the synthesis of α-trifluoromethylated α-propargylamines via a Ti-promoted addition reaction between acetylide and chiral CF3-ketimines

• synthesis of chiral α-trifluoromethylated propargylamines. In order to determine the absolute configuration of the chiral addition products, we successfully performed a crystallographic analysis of the minor product 3a. The structure is shown in Figure 2, the absolute configuration of the newly generated

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• reaction of trifluoroacetaldehyde hemiaminals with enolizable carbonyl compounds in the presence of a strong base [23], the reaction of aldiminium salts with (trifluoromethyl)trimethylsilane/Lewis base [24], and the preparation of secondary α-(trifluoromethyl)propargylamines from imines CF3CH=NR and

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• multicomponent reaction of rare-earth metal amides [28], the reaction of CO2 with propargylamines or aziridines [29][30] and the cycloaddition reaction of epoxides with isocyanates [31][32]. On the other hand, for the synthesis of five-membered cyclic carbonates, the cycloaddition of CO2 to epoxides, the

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• -alkynylbenzamides, affording indoles bearing an alkylidene-iminoisobenzofurane moiety, has been reported [40]. Results and Discussion The starting N-propargyl-2-iodobenzamides 2 were easily obtained by the reaction of the readily available [41] propargylamines 1 with 2-iodobenzoyl chloride in CH2Cl2 at room

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• propargylureas (leading to 2-imidazolones) and extend the range of Lewis acid-catalyzed azole syntheses based on N-carbonyl propargylamines. Keywords: alkyne hydroamination; cyclocondensation; Lewis acid catalysis; multicomponent reactions; propargylurea; Introduction The pioneering publications of Beller and

• imidazoles 2 from tertiary propargylamides and ammonium chloride under conventional heating [3]. More recently, we applied the Beller protocol to the synthesis of 2-substituted 5-methyloxazoles 3 from secondary propargylamides [4]. Being curious to explore more variants of N-carbonyl propargylamines, we

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• confirm the present interest in the chemistry of terminal alkynes, e.g., in the synthesis of sulfinamides and isothiazoles [4], 1,3-enynes [5], α-monosubstituted propargylamines [6], 2-substituted pyrazolo[5,1-a]isoquinolines [7], etc. Terminal alkynes can be prepared by dehydrohalogenation of vicinal

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• , we investigated the effect of the substitution pattern on the propargylamine 2. For this, we chose easily available propargylamines 2b and 2c which gave moderate to good yields (60 and 40%, respectively) of diketopiperazine-fused triazolobenzodiazepine 7e and 7f. Furthermore, halogen substituents

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24 N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman’s chiral

• sulfinamide provides chiral N-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pure N-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cα of amino acids. Whereas propargylamines

• substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• only key structural units in a wide variety of natural products but they also constitute important building blocks in medicinal chemistry. Therefore, the synthesis of these compounds using new protocols is always interesting. It is well known that N-propargylamines can undergo a number of cyclization

• reactions to produce various nitrogen-containing heterocycles. In this review, we highlight the most important developments on the synthesis of thiazole and its derivatives starting from N-propargylamines. This review will be helpful in the development of improved methods for the synthesis of natural and

• biologically important compounds. Keywords: 6-endo-dig cyclization; 5-exo-dig cyclization; N-heterocycles; N-propargylamines; thiazoles; Introduction Thiazoles are an important class of azole compounds that have attracted considerable attention due to the fact that they exhibit a wide variety of

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• Sujit Ghosh Kinkar Biswas Suchandra Bhattacharya Pranab Ghosh Basudeb Basu Department of Chemistry, University of North Bengal, Darjeeling 734013, India 10.3762/bjoc.13.53 Abstract The synthesis of propargylamines via A3 coupling mostly under metal-catalyzed procedures is well known. This work

• salicylaldehyde has been explored, which presumably activates the Csp–H bond of the terminal alkyne leading to the formation of propargylamines in good to excellent yields, thus negating the function of the metal catalyst. This observation is hitherto unknown, tested for a variety of salicylaldehyde, amine and

• acetylene, established as a general protocol, and is believed to be of interest for synthetic chemists from green chemistry. Keywords: A3 coupling; metal-catalyst-free; propargylamine; salicylaldehyde; terminal alkyne; Introduction Propargylamines are important synthetic intermediates for the preparation

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• Zachary L. Palchak Paula T. Nguyen Catharine H. Larsen Department of Chemistry, University of California, Riverside, CA 92521, USA 10.3762/bjoc.11.154 Abstract Propargylamines are popular substrates for triazole formation, but tetrasubstituted variants have required multistep syntheses involving

• stoichiometric amounts of metal. A recent cyclohexanone–amine–silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection–triazole formation reported herein offers rapid access to alpha-tetrasubstituted

• relationships [10][14][15][16][17][18][19]. Propargylamines are a popular choice for the terminal alkyne component and form highly selective inhibitors (Figure 1) [2]. Due to the difficulty of forming tetrasubstituted propargylamines, the incorporation of deprotectable variants into triazoles is extremely rare

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• ions, generated from the condensation of amines and aldehydes, represents the most convenient method to access propargylamines [4]. Although numerous examples of the A3-coupling reaction have been reported, there are still many challenges and opportunities for this multicomponent coupling reaction. The

• aldehydes and amines to give the corresponding propargylamines 1 (Scheme 1). As Li and Van der Eycken reported in their valuable reviews, some other silver salts (e.g., Ag3PW12O40 [6], AgX [7]), complexes [8], zeolites [9] and nanoparticles [10][11] have been explored to catalyze the A3-coupling, but only

• , and under a nitrogen atmosphere. The in situ generated polymer-supported complexes 2 were claimed to be more active than the parent NHC–silver halides. The reactions afforded the corresponding propargylamines 1 in excellent yields starting from aromatic and aliphatic aldehydes, a wide range of

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• the synthesis of spiroindolines with propargylamines as an alkyne source (Scheme 1). Results and Discussion The use of benzoic acid as an acid component in the Ugi-4CR did not produce the Ugi-adduct in good yield even after a prolonged reaction time. Therefore, we switched to phenylacetic acid. The

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• ][13]. In addition, the three-component aldehyde–alkyne–amine (A3) coupling and asymmetric aldehyde–alkyne–amine (AA3) coupling reactions have received increasing attention due to the easy formation of high-value product propargylamines [14][15][16]. Notably, the A3 coupling reaction has also been

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• ]. A simple combination of amino acid and copper catalyst provided an easily tunable system for synthesizing a range of propargylamines with high enantioselectivity. A key element of the elevate enantioselectivity was the hydrogen bonding between the chiral amino acid and the substrate, while high

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• Michela Martinelli Thierry Milcent Sandrine Ongeri Benoit Crousse Laboratoire BioCIS-CNRS, Faculté de Pharmacie, Univ. Paris-Sud, rue J. B. Clément, F-92296 Châtenay-Malabry, France. Fax: +33 1 46 83 57 40. 10.3762/bjoc.4.19 Abstract Trifluoromethyl propargylamines react with various azide

• trifluoromethyl groups on the conformation of peptidomimetics, we decided to explore the preparation of trifluoromethyl triazole derivatives. Herein we turn our attention to the synthesis of new triazoles from trifluoromethyl propargylamines using the Huisgen 1,3-dipolar cycloaddition [27][28][29]. Results and

• Discussion The synthetic approach depicted in Scheme 1 shows that the desired compounds could be easily obtained via a 1,3-dipolar cycloaddition from the corresponding propargylamines which are obtained using an efficient procedure from the trifluoromethyl imines previously described by our group [30][31][32