Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• yields. The intermediate 4,5-dihydroisoxazolines were isolated as trans isomers during the reaction of (E)-β-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of β-azolyl enamines with hydroxamoyl chlorides were considered and studied

• chlorides proceeds in a regio- and stereospecific manner. In contrast to the reactions of these β-azolyl enamines, similar reactions of β-alkyl enamines as reported by Bujak et al. [24] are regioselective and not stereospecific and therefore not concerted. We could propose stepwise (path 1) and concerted

• . Investigation of the stepwise mechanism’s pathway allowed locating the only transition state (1a_1−7), which is appropriate to the addition of nitrile oxide 2a onto the double bond of enamine 1a_1, and the respective product – oxime 7. However, the intermediate 7 was found to cyclize to isoxazoline 3a through

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• + 2] annulation between 5H-thiazol-4-ones and nitroalkenes [10]. In this stepwise process, the use of 3,5-dichlorophenyl as the substituent group of the urea in catalyst V would remarkably increase the free energy difference between R- and S-selection in the first Michael addition step, and also

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• ; tetrahydroquinazoline; Introduction The synthesis of new molecules with potential biological activity through pot, atom and step-economic (PASE) reactions is an attractive green organic technique [1][2][3][4][5]. By the combination of multicomponent reactions (MCR) [6][7][8][9][10][11] with stepwise one-pot reactions

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• performed in a stepwise manner (step 1 and step 2) in a one-pot operation without any intermediate isolation. These results are given in Table 6. To elaborate, firstly we carried out the preparation of 2-aryl-3-bromobenzofuran in step 1 and it was followed by a second arylation at the 3-position as part of

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• extracted repeatedly with EtOAc (3 × 15 L) to afford a residue (4.3 g), which was subjected to silica gel chromatography using a VLC column with a stepwise gradient of a mixture of petroleum ether (PE)−ethyl acetate (EtOAc) (from 5:1 to 1:1), and then by CHCl3−MeOH (20:1 and 10:1) to provide 7 fractions (1

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics

• Forrest S. Etheridge,
• Roshan J. Fernando,
• Sandra Pejić,
• Matthias Zeller and
• Geneviève Sauvé

Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182

• cleaned stepwise in each of the following under ultra-sonication for 15 minutes: detergent, deionized water, acetone, and isopropanol. From a 0.25 M ZnO precursor solution, the ZnO layer was spun coat. For all of the devices fabricated, the total concentration of the active layer was 20 mg/mL with varying

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• alternative stepwise process involves the C–OR bond spontaneously cleaving at a rate similar to that of RO− protonation by H3O+. The latter describes a spontaneous uncatalysed hydrolysis. In the case of 1,3-dioxolanes, the concerted mechanism is believed to dominate [25]; however Guthrie [9] asserts that

• orthoesters are in fact delicately poised between stepwise and concerted processes; depending upon the substituent, both mechanisms are operational for aryl dimethyl orthoformates [21]. Stage 2 sees reaction of B with H2O to afford 2-hydroxy-1,3-dioxolane C (i.e., k2) with the overall equilibrium constant K2

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• -methanides led to mixtures of 2-CH2 and 5-CH2 isomers with the major component being the sterically more crowded 2-CH2 isomers. The preferred formation of the latter products is explained by the assumption that the formal [3 + 2]-cycloadducts were formed via a stepwise reaction mechanism with a stabilized

• -dithiolanes, supports the proposed stepwise radical reaction mechanism via a stabilized 1,5-diradical as an intermediate. Finally, in the case of ferrocenyl methyl thioketone used as a dipolarophile, the concerted [3 + 2]-cycloaddition dominated due to the reduced stabilizing effect of the methyl group

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• avoided by the assumption of a concerted process from A1+ to H1+, but it will be very difficult, if not impossible, to distinguish experimentally between a stepwise and the alternative concerted mechanism. Both PMA119 and PMA119(179) point to a formation of the ion m/z = 119 from the C1–C6 + C15 portion

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• , dehydropiperidine or piperidine is consistent with a [4 + 2] cycloaddition across two dehydrated serine residues [79][80]. Genetic disruption of tclM from the thiocillin pathway showed that TclM was responsible for this transformation [81], although the precise cyclisation mechanism (concerted or stepwise) could

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• . Therefore, a stepwise approach towards 19 was pursued instead. This involved either a coupling of 12 first with isocyanate to give 16 followed by a cross-metathesis or starting with the cross-metathesis to 18 and subsequent installment of the urea motif. As shown in the table inserted in Scheme 3 for

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied. Keywords: arylation; cationic palladium; C–H functionalization; green chemistry; olefination; Introduction Transition metal-catalyzed, direct functionalization of aryl C–H bonds has made

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• acceleration of the dehaloganation process of 3 into monophenylpyridine 2 was observed. This phenomenon can be assigned to the stepwise slow decomposition of the catalytic complex into palladium metal. The effectiveness of commercially available Pd(PPh3)4 was verified in systems containing various bases and

• monoarylated intermediate. Two alternative approaches were based on a one-pot reaction concept, which is advantageous from the point of view of costs (solvents, adsorbents etc.) and work-up procedure. Route 2 is based on the stepwise diarylation of 1 without isolation of the monoarylated product. We also

• less than 5%) due to practical problems associated with chromatographic purification. Their structures were therefore proposed on the basis of GC–MS analysis. Since a stepwise transformation of 1 according to route 2 led to a similar inseparable mixture of symmetrical and unsymmetrical diarylpyridines

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• (5'S)-configuration, contrary to the results of MIC value determination. Further studies were then carried out with (5'R)-derivatives only, i.e., with 5'-epimers of the parent natural products. The influence of protecting groups was examined applying a strategy of stepwise deprotection. This led to

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• , discussions on the mechanism contribute significantly to the development of fundamental concepts in organic chemistry [3][4][5][6][7]. The first general concept of concerted [3 + 2]-cycloadditions was formulated by Huisgen [4]. However, some time later, Huisgen and co-workers reported stepwise [3 + 2

• , respectively, were obtained as sole products. The obtained results can be explained by the assumption that in the case of hetaryl thioketones 1 stepwise mechanisms via diradical intermediates govern the formation of the isolated 1,3-dithiolanes 10 (Scheme 3). Based on earlier studies, the stability of 1,3,4

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• preparation of the macrocycle (Figure 5e). To this day, the stepwise procedure [6] we currently use to make triazolophanes still largely follows the path he set for it. Anion binding to triazolophane macrocycles. At the time when the triazolophane was drawn on the notepad, the central cavity clearly beckoned

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• distinct modules reduce the keto group in a stepwise manner to the hydroxy group and the C=C double bond. Subsequently, the KR present in the terminal module catalyzes the reduction of the β-keto group to an L-hydroxy group. This hydroxy is then further reduced by the catalytic activity of the DH in the

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• rearrangements Generation of carbocations via protonated alcohols – the concerted vs stepwise spectrum The seminal work of Dupuis and co-workers in running dynamics simulations to elucidate the nature of the dehydration-rearrangement mechanism of protonated pinacolyl alcohol (Figure 5, R = CH3) was instrumental

• in bringing the issue of dynamic effects to a wide audience [46]. The question addressed in this work was ostensibly simple: is the mechanism of dehydration/alkyl migration of a protonated alcohol a concerted or stepwise process? The IRC for the process revealed a concerted mechanism (Figure 5, blue

• ), with no secondary carbocation found as a stationary point on the PES. However, molecular dynamics simulations initiated from the reactant revealed trajectories that predominantly followed a stepwise mechanism (Figure 5, green), with a lifetime of the secondary carbocation of up to 4000 fs. This is the

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• . The stepwise preparation of unsymmetrical 4,4'-bitriazoles. The synthesis of 5,5'-bitriazoles. The synthesis of bistriazoles and cyclic 5,5’-bitriazoles under different catalytic systems. The double CuAAC reaction between helicenequinone and 1,1’-diazidoferrocene. The synthesis of 1,2,3-triazoles and

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• vacuum liquid chromatography using silica gel with a stepwise gradient eluent from 100:0 to 80:20 (CH2Cl2/MeOH, v/v). The two fractions eluting with 97:3 and 94:6 (CH2Cl2/MeOH, v/v) were further purified by HPLC and yielded the three new bromotyrosine derivatives 14-debromo-11-deoxyfistularin-3 (1

• partitioned between EtOAc and H2O. The EtOAc fraction was further purified by vacuum liquid chromatography using silica gel eluting with stepwise gradient from 100:0 to 80:20 (CH2Cl2/MeOH, v/v). The fraction eluted with 97:3 (CH2Cl2/MeOH, v/v) was concentrated and further purified by HPLC using an RP C18

• column (stepwise gradient 60:40, 40:60, and 20:80 H2O/MeCN, v/v) to yield 5 (198.0 mg), 11 (263.0 mg), 12 (445.0 mg), 13 (55.0 mg), 14 (7.9 mg), 16 (15.0 mg), 17 (9.1 mg), and two other fractions. The first fraction was purified using reversed-phase HPLC [52:48 H2O (0.1% TFA)/MeCN (0.1% TFA), v/v] to

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• synthesis of various polycyclic structured quinazolinones 86 via corresponding starting materials 85 which were synthesized before by stepwise preparation (Scheme 22). Based on a similar strategy of combining an Ullmann C–N bond formation and C–H amidation, Fu and Xu [79] also achieved the cascade reactions

Synthesis, structure, and mechanical properties of silica nanocomposite polyrotaxane gels

• Kazuaki Kato,
• Daisuke Matsui,
• Koichi Mayumi and
• Kohzo Ito

Beilstein J. Org. Chem. 2015, 11, 2194–2201, doi:10.3762/bjoc.11.238

• gelation occurred without silica. Thus, the modulus tends to increase with the concentration of silica, though the incremental increase of modulus is not proportional to silica concentration but stepwise. This suggests that the cross-linking density becomes higher with increasing silica concentration

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• reaction of 1a with 2 and effective in the reaction of 1b with 2. In this latter case, the reaction outcome could be explained by the formation of two energetically comparable transition states (endo + exo TS) or by the occurrence of a stepwise mechanism. Finally, the results obtained with indole 1i

• occurrence of a stepwise mechanism. Distinction between the two proposed mechanisms cannot be made on the basis of experimental evidences. Therefore, isolation or detection in the reaction mixtures of plausible intermediates were unsuccessful and a computational study devoted to the identification of the

Polythiophene and oligothiophene systems modified by TTF electroactive units for organic electronics

• Alexander L. Kanibolotsky,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1749–1766, doi:10.3762/bjoc.11.191

• polymer thin film revealed the splitting of the first oxidation wave during the cathodic run, which the authors attributed to a stepwise reduction from the aggregated radical cation to an intermediate mixed valence state, then further reduction to the neutral species. To decrease the difference in the

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• tetrasubstituted 40 suggests no intramolecular charge delocalization between the adjacent TTF units. The splitting and broadening of the first oxidation waves in 38 and 42 are considered to be caused by intermolecular interactions between the neutral and cationic TTF units. As shown in Figure 15, the stepwise

• of 40, the changes show several isosbestic points, indicating that each TTF unit is oxidized from the neutral to the radical cation (TTF•+) in a stepwise manner (Figure 15b). On the other hand, for 38 and 42, there are no isosbestic points (Figure 15a,c). For 38, a new broad peak around 1850 nm

• permission from [23]. Copyright 2011 American Chemical Society. Stepwise oxidation of (a) 38 (0.02 mM), (b) 40 (0.05 mM), and (c) 42 (0.03 mM) with incremental addition of Fe(ClO4)3 in a mixture of CH2Cl2–CH3CN (2:1, v/v) at 25 °C. The blue line indicates the neutral absorption spectra, the green line the