Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• reaction to yield 5-aryl-3,4-dihydro-1,8-naphthyridin-2(1H)-ones by an efficient synthetic route. Keywords: inverse-electron-demand Diels–Alder reaction; microwave irradiation; naphthyridin-2(1H)-ones; Sonogashira cross-coupling; 1,2,4-triazine; Introduction 1,8-Naphthyridine derivatives are an important

• -demand Diels–Alder reaction under microwave irradiation [22][23][24]. The use of 1,2,4-triazines in inverse electron-demand Diels–Alder reactions proved to be an efficient strategy for the construction of various heterocyclic compounds [25][26][27], such as azacarbazoles [28][29][30][31][32][33

• ], polycyclic condensed pyrazines [34][35], dihydropyrrolopyridines [36][37], thienopyridines and thiopyranopyridines [38][39], as well as furo- and pyranopyridines [22][23][24][40][41][42]. Reactions with microwave irradiation are well-known for their ability to reduce reaction times, increase product yields

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• acid, I2, Br2·SMe2 and BF3·OEt2, at temperatures ranging from rt to 80 °C. The transformations were tested under standard heating or microwave irradiation, with reaction times lasting form 30 min to 48 h. The imine 1a was generated in situ, using MS 4 Å, or previously prepared by condensation of the

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• tripeptide byproduct. Nucleophilic aromatic substitution (SNAr) chemistry contributes to creating useful materials. In 2005, Comer and Organ reported SNAr reactions of 2-fluoronitrobenzene using a flow microreactor system with microwave irradiation (Scheme 9) [69]. Toward making compound-libraries, Schwalbe

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• )3]}, are also well soluble in organic solvents and do thus allow for homogeneous CuAAC reactions. They were first applied in the synthesis of neoglycoconjugates in the presence of DIPEA or DBU under microwave irradiation in toluene solution [137]. However, a recent study by Díez-González has shown

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

•  2, entry 6). Meanwhile, reactions in THF or ethyl acetate resulted in marginally lower yields (Table 2, entries 8 and 9). Switching to water with assistance by microwave irradiation or performing the reaction in ethanol provided even unacceptable yields (Table 2, entries 10 and 11). Further, when

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• were accessed by intramolecular addition in excellent yields (Scheme 8b). The combined use of more electrophilic phosphite-gold complexes [41][42] and enabling techniques such as microwave irradiation [43] led to consistent improvement in efficiency of the catalytic system. In particular when (Ph3O

• )PAuOTf was employed under microwave irradiation with a catalyst loading as low as 0.05 mol %, the condensation of TsNH2 to norbornene was realized in quantitative yield. In addition, the introduction of carbene ligands [44] allowed performing the intramolecular hydroamination of N-alkenyl ureas

• obtained from moderate to good yields under microwave irradiation (DCE, Scheme 17c) [54]. Additionally, the stronger Lewis acid AuCl3/AgSbF6 was documented to catalyze the Markovnikov selective hydroarylation of aryl- and alkyl olefins with less-nucleophilic benzene derivatives and thiophene in good yields

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• synthesize 5,6-dihydroindolo[1,2-a]quinoxaline derivatives by CuI-catalyzed intramolecular N-arylation under microwave irradiation. This method rapidly afforded the tetracyclic products with good to excellent yields (83–97%) in short reaction times (45–60 min). Keywords: copper; 5,6-dihydroindolo[1,2-a

• ]quinoxaline; intramolecular N-arylation; microwave irradiation; Introduction The indole scaffold is considered as a privileged structure because of its ubiquitous presence in a large number of natural products and pharmaceutical agents [1][2][3][4][5][6]. In particular, indole-fused heterocycles have

• technology to conduct the intramolecular N-arylation. As a result, a similar yield was obtained under the same catalytic conditions when 1a was subjected to microwave irradiation for just one hour (Table 1, entry 2). Then, we tried to optimize the reaction conditions under microwave heating. At first

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute. Keywords

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• -methylpyrrolidone (8:8:1) was used. The reaction was performed in a sealed vial at 120 °C under microwave irradiation for 3–5 h. The unusual combination of Pd(PPh3)4 and (t-Bu)3PH·BF4 as an additional ligand proved beneficial for the transformation of long-chained dialkynes. The domino reaction proceeded smoothly

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• . aChlorogold precursor (0.32–0.37 mmol), 2 equiv arylboronic acid, 2 equiv Cs2CO3, 50 °C, 20 min, iPrOH (1.5 mL), microwave irradiation. bIsolated yields. cTHF was used as the solvent. Hydrophenoxylation of alkynesa,b. aAlkyne (0.28 mmol), phenol (0.56 mmol), 130 °C, 20 min, no solvent. bIsolated yields

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

• . Strauss first demonstrated in 1994 that by combining microwave-heating technology with continuous flow processing, problems with the limited penetration depth of microwave irradiation and the physical restrictions of a standing wave cavity could be overcome [14]. A continuous flow reactor has the

• that this cyclocondensation proceeds in a similar fashion and high efficiency under microwave irradiation [48], and that we have previously demonstrated that pyridines and pyrimidines can both be formed rapidly and efficiently from ethynyl ketones using microwave dielectric heating, the transfer of

• continuous flow reactor examined the cyclodehydration of Bohlmann–Rahtz aminodienone intermediates in the presence of a Brønsted acid catalyst [44][45]. This relatively simple cyclization reaction was utilized previously as we had already established its facility under microwave irradiation and so it

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• pyrimidine core toward subsequent substitution. The usage of very harsh reaction conditions (prolonged heating for hours or days, high pressure or microwave irradiation of the reaction mixtures) is required to carry out the second SNAr reaction (Scheme 1) [9][10][11][12][13][14]. In 2012 we published a

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• diastereoselectivity around 10:1, with further enhancement following silyl protection and purification. Although the silylated compound 60 proved to be reluctant to form the Weinreb amide, microwave irradiation allowed this process to proceed on a reasonable time scale. Grignard addition to the Weinreb amide afforded

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• undergo cycloaddition with diene 4 to tricycle 2, which represents the ABC-ring system of beticolin 0 (1) and other beticolins [10]. We found that dienophile 3 and diene 4 can undergo a cycloaddition by applying either thermal conditions or microwave irradiation to these both compounds (Table 1) [9

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• ] annulation reaction is described here. Use of piperidinium trifluoroacetate salt as the catalyst and toluene as the solvent appears to be critical for a successful annulation. We also demonstrated for the first time that microwave irradiation can accelerate aza-[3 + 3] annulation reactions. An attempt to

• 87%, while lowering the catalyst loading from 500 mol % to 50 mol %, although the reaction temperature was raised to 150 °C. Lastly, we also examined the use of microwave irradiation [66][67] and observed a distinct rate enhancement (Table 1, entry 9). The observed reactivity difference of the

• intramolecular aza-[3 + 3] annulation reaction. Use of piperidinium trifluoroacetate salt as the catalyst and toluene as the solvent appears to be critical for a successful annulation. We also demonstrated for the first time that microwave irradiation can accelerate aza-[3 + 3] annulation reactions. An attempt

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• advantageous compared to microwave irradiation (up to 50 W for 7 min, 75 °C (CH3CN), 100 °C (DMF)). Higher labelling yields were achieved when the nosyl precursor 4 was used instead of tosylate 3 (75–85% (n = 12) versus 45–55% (n = 9), respectively; Figure 3). Notably, employing DMF as solvent resulted in

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• microwave irradiation the time was drastically reduced to 2 h. Both procedures are simple and involve a low-cost catalytic system. This methodology was also applied to the “one-pot” synthesis of target heterocycles, such as 3H-benzo[c][1,2]dithiol-3-one and 2-methylbenzothiazole, alkyl aryl sulfides, diaryl

• the reactions of KSCOMe (1) with aryl iodides under a Cu/ligand/base-free system to afford S-aryl thioacetates 2 as thiol surrogates in good to excellent yields, under conventional heating and microwave irradiation as an efficient access to a variety of sulfur compounds. Results and Discussion

• yield. As a result, the simple methodology here presented could be an attractive alternative for the synthesis of polysulfides and other sulfur relevant materials (Table 3, entries 10–12). In a comparative fashion we have also performed these reactions under microwave irradiation in order to improve

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• % isolated yield (Table 1, entry 17). Thus, under microwave irradiation conditions, not only the isolated yield of 6a increased from 60% under conventional heating to 71%, but the duration of reaction was also reduced from 15 h to 1.5 h. Switching the solvent from DMSO to DMF under microwave conditions

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• heating under reflux (Method A), in methanol under microwave irradiation at 120 °C (Method B), or by ultrasonication at ambient temperature in acetic acid (Method C). In all these cases triazolopyrimidine 7 was isolated as the sole reaction product (Scheme 2, Table 1). In most cases the best results from

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• amine counterpart under high reaction temperatures, preferably under heating to more than 180 °C or through the use of microwave irradiation, results in the amino-7-azaindole in moderate to low yield [5][7]. Primary alkylamines or anilines under similar reaction conditions provided the displacement

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• -chloroacetoacetate did not take place, and a gummy mass was obtained as product. In this context, Muscia et al. [39] described the synthesis of ethyl 6-chloro-2-(chloromethyl)-4-phenylquinoline-3-carboxylate by the Friedländer reaction employing microwave irradiation (MW) in the presence of a catalytic amount of

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• short, Fmoc-protected amino acids were coupled in a solid-state synthesis scheme using HOBt, TBTU, and DiPEA under microwave irradiation. Using suitably protected amino acids, i.e., Fmoc-Arg(Pbf)-OH, Fmoc-Trp(Boc)-OH, and Fmoc-Lys(Boc)-OH, and polystyrene-based resin decorated with Fmoc-protected Rink

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• hydroamination of the allenes 39, easily accessible by prototropic isomerization of the corresponding propargylamides (Scheme 20) [78]. The selective 5-exo-allylic hydroamination occurs in mild conditions in the presence solely of Pd(PPh3)4 under microwave irradiation by an initial coordination of the Pd(0

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• ) for the retro-inverso peptides. All cycles for the synthesis of the glycosylated peptides and aglycons follow a published procedure [16][23]. The automated synthesis of the aglycons was performed under microwave irradiation at a maximum of 78 °C at 35 W, whereas for the glycopeptides lower

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• was the solvent of choice, and microwave irradiation was used for a shorter reaction time. The scope of the reactions was broad allowing different indoles and a variety of N,N-(dialkylamino)benzaldehydes to be employed, and the products 3 were obtained in good to excellent yields (Scheme 4) [16]. For

• -membered lactols, δ-hydroxypyrroles 8 were achieved as the products in good yields (Scheme 6). Later, Pan and Seidel independently extended this methodology to indolines using benzoic acid as the catalyst, conducting the reaction under reflux and microwave irradiation conditions, respectively, to generate

• aromatic and enolisable aldehydes and ketones to their reaction and the desired N-alkylpyrrole products 7 were formed in moderate to good yields (42–73%) under microwave irradiation [23]. Both groups suggested azomethine ylide as the intermediate in their reactions (Scheme 9). Asymmetric variants The first