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

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• and temperature) were examined to identify the optimal conditions. Our initial attempt gave a good yield of 94% with 4.4 equiv of amine, an absence of base, at a concentration of 0.1 M of DMSO, and under microwave irradiation at 150 °C for 20 min (Table 1, entry 2). However, when a hindered amine was

• concentration of solvent, temperature and reaction time were increased. Finally, the optimal results were obtained in the absence of base, with 5 equiv of amine, at a concentration of 0.5 M in DMSO, and under 50 min of microwave irradiation at 180 °C (Table 1, entry 10). All reactions were performed under

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• ). Synthesis of racemic samples The mixture of Selectfluor (0.057 g, 0.16 mmol) and ethyl benzoylacetate (0.031 g, 0.16 mmol) in CH3CN (1 mL) was stirred at 90 °C under microwave irradiation for 40 min. The reaction was quenched by water. The mixture was extracted with ethyl acetate (3 mL). The organic layer

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

• Chunhui Dai,
• Bo Liang and
• Corey R. J. Stephenson

Beilstein J. Org. Chem. 2012, 8, 986–993, doi:10.3762/bjoc.8.111

• , spiro [1,3]oxazino compounds having a diene moiety within their molecular framework are susceptible to Diels–Alder (D–A) reactions [22]. Scheme 2 highlights three examples in which compound 3a was exposed to N-substituted maleimides in toluene at 150 °C under microwave irradiation for 0.5 h, and D–A

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

• efficient turnover. The intramolecular cycloaddition of 13a, the alkyne-tethered triazine, was studied under various conditions (Scheme 4, Table 3). Ultimately, it was found that the IEDDA reaction proceeded smoothly under microwave irradiation, in diglyme (120 °C, 20 min; Table 3, entry 3) to give the γ

• 5). Little reaction occurred in toluene under microwave irradiation (Table 3, entry 6) unless silicon carbide chips were added as a microwave facilitator (Table 3, entry 7) [87]. Upon further exploration of the reaction conditions, it was discovered that the amidation/cycloaddition sequence could be

• ), under the optimized cycloaddition conditions (diglyme, microwave irradiation, 120 °C, 20 min), producing the desired α-carbolines in excellent yields (96–98%). However, propargyl amide 13f with the internal alkyne (Table 4, entry 6) required a longer reaction time (40 min) for the cycloaddition to be

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• provoked without any workup procedure by the addition of tris(benzyltriazolylmethyl)amine [55] (TBTA), sodium ascorbate, and the propargyl glycoside 1 [56] of N,N’-diacetylchitobiose and heating of the mixture to 80 °C by microwave irradiation, until TLC showed complete consumption of the intermediate

Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene

• Sabine Leber,
• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2012, 8, 738–743, doi:10.3762/bjoc.8.83

• 11. Reductions with NaBH4 and sulfur [13] or with ammonium formate and Pd/C under microwave irradiation [14] were unsuccessful. However, compound 8 was completely reduced to the diamine 9 by using the classical reduction with Sn and HCl (Scheme 2). The reaction was complete in 1 h. Under the same

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• synthesized using solid-phase peptide synthesis, followed by esterification and subsequent cleavage from the resin, deprotection and cyclization to yield 1, assisted by microwave irradiation at every stage with the exception of the esterification (Scheme 1). In detail, a preloaded 2-chlorotrityl chloride

• hexafluorophosphate (HBTU) in dimethylformamide (DMF) and N,N-diisopropylethylamine (DIEA) in N-methylpyrrolidone (NMP), assisted by microwave irradiation. After the final Fmoc-deprotection with 20% piperidine in DMF, the N-terminus was formylated with para-nitrophenyl formate (pNPF) in the presence of N

• % hexafluoroisopropanol (HFIP) in dichloromethane (DCM) in order to preserve the side-chain protecting group. Following this, the peptide was cyclized in solution by using O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) and DIEA in DMF, assisted by microwave irradiation. Afterwards, the