Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• ][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis. Keywords: alkoxy; azabenzotriazole; benzotriazole; peptide-coupling; phosphonium; Introduction Benzotriazole derivatives are of importance in diverse contexts. As examples, in medicinal chemistry substituted benzotriazoles

• complexes from allylic benzotriazolyloxy products described herein should be feasible. In this context, N-allylbenzotriazole derivatives undergo reaction with preformed enamines, in the presence of Pd(OAc)2 and PPh3 [37]. Super-stoichiometric ZnBr2 was necessary for these reactions, in the absence of which

• no reaction was observed [37]. With these data in mind, we decided to evaluate a few reactions of cinnamyloxy benzotriazolyl derivative 1g. However, instead of using preformed enamines, we chose to utilize a combination of metal- and organocatalysis, wherein the enamine is formed in situ [38

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• -en-1-ylideneindolones are essentially nonemissive in films or in the solid state. TD-DFT computations rationalize the charge-transfer nature of the characteristic broad long-wavelength absorptions bands. Keywords: alkynes; cross coupling; enamines; fluorescence; heterocycles; multicomponent

• ][40] and pyranoindoles [41] via domino sequences. Interestingly, our versatile three-component enaminone synthesis [42][43] could be readily extended in a vinylogous fashion with enamines furnishing orange or deep red diene chromophores 2 and 3 that display aggregation induced emission [31]. In

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

• several substituents and enolates 33 can be generated from methyl- or ethyl vinyl ketone, the corresponding α,β-unsaturated esters being unreactive. Enamines 34 arise from cyclic or linear C3–C5 ketones, acetophenones and β-diketones. It is noteworthy, that the reactions are highly regiospecific for

• (enamines and carbanions) or be involved in cycloaddition reactions affording tricyclic compounds by cascade processes. An unprecedented, co-catalyzed reaction involving enamines 51 as nucleophilic partners, also yields the H-pyrazolo[5,1-a]isoquinoline nucleus 48, in the presence of silver triflate and

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• dimethyl acetal (DMF-DMA) [34]. Previous attempts to synthesize the nicotinonitriles via enamines resulted in poor yields due to dimerization of the starting alkylidene malononitrile [35][36][37]. A high yield enamine approach allows us to begin the synthesis from the commodity chemicals (acetone and

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• under solvent-free conditions (Scheme 1, present work). Results and Discussion Recently, we have reported that the enamines 3 generated from acetylacetone (1) and amines 2 react with ninhydrin to form the cyclic hemiaminal dihydroxyindenopyrroles 4. Subsequently intermediates 4 produce the pyrrole-fused

• some acetylated amines were always produced as byproducts. Besides, the formation of 4 from 3 did not proceed significantly when the enamines of ethyl acetoacetate were employed, because under acidic conditions, the enamines of ethyl acetoacetate readily hydrolyze and the free amines react with

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• (Scheme 26) [93]. Functionalization of the sp3 C–H bond α to the nitrogen atom in tetrahydroquinolines and indolines via iminium ions is challenging because the corresponding iminium ions are enolizable and thus tend to tautomerize to enamines [94][95] and/or aromatize [96][97]. The authors adopted a

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• synthesis and no 2,3,4-trisubstituted pyridine 16 was formed (Scheme 5). This supported earlier findings [49] by Bohlmann and Rahtz and highlights a reactivity trend of 3-substituted propargyl aldehydes in reaction with enamines. A comparable process in EtOH in the absence of AcOH failed to provide complete

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• Julien Lefranc Alberto Minassi Jonathan Clayden School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK 10.3762/bjoc.9.70 Abstract N-Alkenyl ureas and N-alkenyl carbamates, like other N-acyl enamines, are typically nucleophilic at their β-carbon. However, by

• products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the

• reversed when N-acylenamines (especially N-vinyl ureas [8]) meet organolithium nucleophiles. N-Carbamoyl enamines bearing α-aryl substituents (in other words, α-acylaminostyrenes), may undergo reaction as electrophiles, with the carbon atom β to nitrogen succumbing to attack by organolithium nucleophiles

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• dienophiles, vinyl enol ethers, vinyl enamides, vinyl sulfides, cyclopentadienes, indenes, alkynes and enamines have been mostly used in this method [12][13][14][15][16][17][18][19][20][21][22]. β-Enamino esters [23][24][25][26], which may be readily generated in situ by the addition of a primary amine to

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• expected to proceed with nucleophiles of 2 < N < 14, because such nucleophiles are strong enough to react with iminium ions but weak enough not to react with their precursor aldehydes. With the N parameters of enamines derived from phenylacetaldehyde and MacMillan’s imidazolidinones one can rationalize why

• -nucleophiles, which are listed in Figure 12 [61]. Figure 12 shows that the nucleophilicities N of the enamides 17 are comparable to those of silylated enol ethers, in between those of allylsilanes and enamines. Accordingly, we expected them to react readily with the iminium ions 3 at room temperature. However

• needs the reactivity parameters N and sN for the enamines 28 and the electrophilicity parameter E for the electrophiles 29. The electrophilicity parameters for the Michael acceptors, stabilized carbenium ions, and azodicarboxylates shown in Figure 18 have been derived from the kinetics of their

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• FCAA reaction toward α,β-unsaturated aldehydes through iminium intermediates [32][37], and an asymmetric α-oxyamination of aldehydes via enamines [33], they are expected to be suitable for a one-pot sequential reaction to make the chiral indoles mentioned above. Herein, we report on an enantioselective

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• triazines (9, R1 = NO2, CONH2), but due to the electron withdrawing nature of the isatin substituents, subsequent sulfonylations were not successful (not shown). The intermolecular IEDDA reactions of 8a with various electron-rich dienophiles, including ethyl ethynyl ether, the enamines (E)-1-N

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• ][28][29], reduction of unsaturated heterocycles [30][31][32], ring closure via intramolecular nucleophilic substitution [33][34][35][36][37], cascade reactions of enamines/imines and aldehydes [38][39][40][41], and ring-closing metathesis followed by hydrogenation [42][43][44][45][46][47][48

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• %, respectively. In the absence of a gold catalyst, a similar result was obtained (Scheme 5) confirming that Selectfluor itself can react with 6 and 7 to give 3a and 5a, which is consistent with Shreeve’s study on the fluorination of enamines [29]. However, the formation of 5a may also be ascribed to the

• could be explained as outlined in Scheme 6. The cationic Au(I) catalyst would promote the cyclization of 1a to the mixture of enamines 6 and 7 as previously observed with cationic Au(III) species (Scheme 4). Activation of the electron rich double bond of 6 or 7 by the cationic Au(I) complex could

• ), 39.2 (CH2), 27.7 (CH2), 26.6 (CH3), 22.7 (CH2), 21.7 (CH3), 21.6 (CH3); IR (neat) 1452, 1332, 1154, 1089, 1000, 811, 655 cm−1; HRMS (m/z): [M + Na]+ calcd for C24H30N2O4S2, 497.1539; found, 497.1517. Synthesis of cyclic enamines Cyclic enamines were synthesized in 59% yield (endo/exo 2:3) according to

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• substituted by one nitrogen at the central carbon (C=C(N)–C) has scarcely been studied [38][39][40]. Deprotonation of simple enamines or allylamines employing n-BuLi and t-BuLi/t-BuOK produced nitrogen-substituted allylic anions which undergo protonation, alkylation, trimethylsilylation and reaction with

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• through the Povarov MCR (the interaction of anilines, aldehydes and activated olefin inputs under acid catalysis) [4][5][6][7][8]. Interestingly, this process allows cyclic enol ethers and enamines to be used as electron-rich alkenes, leading to heterocycle-fused tetrahydroquinolines, usually as a mixture

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• , carbamates, N-heterocycles, enamines and intramolecular N-arylation reactions [45]. We compare here the success of the different C–N-arylation reactions as applied to the synthesis of more complex structures and discuss selected examples of palladium- and copper-mediated reactions for the synthesis of

Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

• Lisa K. Thalén and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2010, 6, 823–829, doi:10.3762/bjoc.6.97

• for their preparation that are applicable on multigram scale. They can be prepared by resolution of amines, hydrogenation of prochiral imines and enamines [1][2], alkylation of prochiral imines [3], aminohydroxylation of alkenes [4], transamination of prochiral ketones [5][6][7], and reductive

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• , enamines, and thiolate anions with these reagents, albeit in low to moderate yields [28]. Neutral hypervalent iodine(III)–CF3 reagent Initial attempts by Yagupolskii and Umemoto to synthesize iodonium salts with a trifluoromethyl group were unsuccessful. Whilst iodonium salts including p

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• ). Functionalisation of the N-sulfonyl enamines 5a and 5b was subsequently studied with the ultimate aim of introducing substituents, in a stereoselective fashion, to the masked pyrrolidine ring. Thus, epoxidation of 5a and 5b (Scheme 3) using m-CPBA proceeded smoothly for both substrates and as hoped, occurred under

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• structure, including radical cyclisations [3]; nucleophilic addition to imines [5][14][15]; electrophilic alkylation of pyrroles [7][13]; alkylation of enamines [6], β-amino esters [8] and pyrrolidinyllithiums [12]; stereoselective reduction of enamines [4][9] and pyridinium salts [11]; and titanium