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

Enaminones in a multicomponent synthesis of 4-aryldihydropyridines for potential applications in photoinduced intramolecular electron-transfer systems

• Nouria A. Al-Awadi,
• Maher R. Ibrahim,
• Mohamed H. Elnagdi,
• Elizabeth John and
• Yehia A. Ibrahim

Beilstein J. Org. Chem. 2012, 8, 441–447, doi:10.3762/bjoc.8.50

• % yield by microwave irradiation with R-1-phenylethylamine in this three-component reaction. The bis(dihydropyridines) 5a,b were obtained in 75–92% yield with ethylenediamine and 1,3-diaminopropane as the primary amines, respectively. The 4-(1-naphthyl)dihydropyridines 6a–f and 4-(phenanthren-9-yl

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• diseases [4]. Halocoumarins also exhibit insecticidal and fungicidal properties [5]. A few methods have been documented for regioselective bromination of coumarins, which include CuBr2/Al2O3 in bromobenzene under reflux [5], Br2 in glacial AcOH [6], Br2/Al2O3 under microwave irradiation [7], NBS in CHCl3

• ], and for the selective synthesis of α-bromo and α,α-dibromoalkanones supported on silica gel under solvent-free conditions and microwave irradiation [13]. As a part of our endeavor to develop novel solvent-free protocols for important organic transformations, we have reported the efficient synthesis of

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• -3-methyl-pyrazole, aromatic aldehydes and dimedone under controlled microwave irradiation at 150 °C involves the participation of C3-H of the pyrazole ring in such a cyclocondensation reaction, this is not favoured in our case. In addition two signals were assigned to two CH2 groups and three methyl

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• was considered in order to compare the contribution of this moiety to the potential antiplasmodial activity with that of a diethylamino group. This objective was achieved by treatment of aziridines 15 with 20 equiv of Me2NH·HCl in CH3CN at 140 °C for 2 h under microwave irradiation, resulting in

• . In order to drive the reaction to completion, and to avoid competition between chloride- and diethylamine-induced ring opening, a large excess of Et2NH·HCl (20 equiv) and an additional amount of diethylamine (10 equiv) was used. Thus, heating of the aziridines 15 at 140 °C in CH3CN under microwave

• irradiation resulted in full and selective conversion to the desired new triaminopropanes 16a–e after 2 h (Scheme 3), which were purified by column chromatography (SiO2) in order to obtain analytically pure samples. Furthermore, in addition to the use of diethylamine, the introduction of a dimethylamino group

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• into the reactor. By means of a peristaltic pump the reagents were continuously pumped through the reaction vessel under microwave irradiation (50 W). The product solution was collected from the outlet tube, which was connected to a 250 psi backpressure regulator of the commercial flow microwave system

• ). However, the best result was achieved when the reaction was conducted under solvent-free conditions (Table 1, entry 4). To probe the influence of microwave heating on this transformation, we examined the same transformation under batch conditions and without microwave irradiation. As shown in Table 1

• mixture of alkyne 1 and aldehyde 2 was constantly pumped into the flow cell, filled with the solid acid catalyst and solvent, at the flow rate of 0.5 mL min−1 under microwave irradiation. This was followed by a washing procedure with 100 mL of solvent and then the next substrate was introduced

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• initial investigation towards the synthesis of 3a according to reported methods under solvent-free [49] or solvent-free, microwave-irradiation conditions [50]. Unfortunately, it was found that the Rap–Stoermer reaction did not occur or gave intractable, complex mixtures (as observed by TLC), according to

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride

• Sergio Pascual,
• Christophe Bour,
• Paula de Mendoza and
• Antonio M. Echavarren

Beilstein J. Org. Chem. 2011, 7, 1520–1525, doi:10.3762/bjoc.7.178

• demonstrated to be amongst the best catalysts in many gold(I)-catalyzed cyclizations [6][58]. No reaction was observed with complex 5 after heating for 5 min at 70 °C in CH2Cl2 under microwave irradiation (Table 1, entry 1), whereas the more electrophilic 6, bearing a less donating phosphite ligand, led almost

Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• opened reaction vessel overnight at rt. After the addition of sodium sulfide nonahydrate (960 mg, 4 mmol), potassium hydroxide (224 mg, 4 mmol), and methanol (5 mL) the vessel was heated to 120 °C under microwave irradiation for 2 h. After cooling to rt the mixture was adsorbed on neutral aluminium oxide

Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine

• Jessica Baiget,
• Sabin Llona-Minguez,
• Stuart Lang,
• Simon P. MacKay,
• Colin J. Suckling and
• Oliver B. Sutcliffe

Beilstein J. Org. Chem. 2011, 7, 1407–1411, doi:10.3762/bjoc.7.164

• of 54% being achieved for this one-pot tandem process under these conditions (Table 1, entry g). Disappointingly, although it lowered the time required to carry out the reaction, the use of microwave irradiation led to a lower isolated yield of β-carboline 6 (Table 1, entries f and g), showing that

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• no competition between the Sonogashira coupling with these substrates and iodoanilides is observed. A variety of 2,3-disubstituted indoles 59 were obtained under mild conditions in good yields (Scheme 26). A similar three-component reaction was further developed under microwave irradiation by Larock

Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S_NAr reaction

• Charlotte Wiles and
• Paul Watts

Beilstein J. Org. Chem. 2011, 7, 1360–1371, doi:10.3762/bjoc.7.160

• ] describing the use of scCO2, and Moseley et al. [15] employing microwave irradiation as a means of efficiently heating the reaction mixture in order to significantly reduce reaction times (Scheme 1). Although microwaves have found widespread application in the research laboratory, their implementation at a

• ) any energy savings made as a result of using microwave irradiation were attributable to the reduction in reaction time achieved through the use of sealed vessels, and not because microwave irradition is a more energy efficient method of heating. When considering large-scale reactors [18], multimode

• steady state. Effect of reaction solvent: When performing reactions under microwave irradiation, it is important to select a solvent that is not transparent to microwave radiation in order to ensure efficient heating of the reaction mixture. With this in mind, the method reported in the literature

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• ], acetonitrile as a solvent, and under microwave irradiation at 120 °C for 20 min. This optimized condition was developed after other solvents, including water, EtOH and toluene, and different microwave reaction temperatures (100–130 °C) and times (10–20 min) were explored. The Biginelli products were separated

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• time can be dramatically decreased by means of microwave irradiation. Under these conditions, the zincation is complete within 1 h at 120 °C (Scheme 10). Similarly, the functionalized pyridine 61 is zincated within 1 h at 80 °C under microwave irradiation leading to 62. The success of this procedure is

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• , because of the extended reaction times needed for complete consumption of the starting materials, we developed an alternative protocol under microwave irradiation that shortens the time required for the coupling to a few minutes (method D), and the final products were obtained in similar yields to those

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• -functionalized monoliths in a flow microreactor, is the achievement of an efficient coupling of the microwave energy, which will be a function of both the absorbing species present and of the penetration depth of microwave irradiation into the reaction zone [17]. This is especially important in flow systems