Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• phenyl group was proposed to introduce at the 3-position in substituted pyrazinone via regioselective bromination followed by Suzuki coupling with phenylboronic acid. Accordingly, the bromination of 10a was successfully carried out to furnish regioisomers 12a and 12b in 82% yield upon treatment with

• bromodimethylsulfonium bromide (BDMS) [38] in dichloromethane at 0 °C to room temperature. The conventional Suzuki coupling of the regioisomers 12a and 12b with phenylboronic acid furnished the corresponding arylated products 13a and 13b in excellent yield (Scheme 5). To our dismay, the imide 7h did not participate in

• reaction mixture was purified through silica gel column chromatography using ethyl acetate/hexane, 30:70 as eluent to afford 12a and 12b in the ratio 79:21. The regioisomers of bromopyrazinone (12a and 12b) (1.0 mmol), bis(triphenylphosphine)palladium(II) chloride (10 mol %, 7 mg) in dimethylformamide (2

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• treatment with Boc2O afforded the suitable heterocyclic precursor 17 (Scheme 4). The coupling reaction of (+/−)-7 and 17 using the Mitsunobu reaction gave a separable mixture of N9/N7 regioisomers (+/−)-18 and (+/−)-19 with 55% and 5% yield, respectively. After purification, compound (+/−)-18 was treated

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• exclusively at the equatorial 4-OH group presumably due to the bulkiness of the silylated donor. Thus compound 55 (Scheme 9) was formed as the only product out of four possible isomers in 54% yield. When the D-gluco-configured acceptor analogue of 54 was used, a mixture of regioisomers was obtained. However

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• -alkylindole and indazole derivatives 2 that can be obtained from 5-bromoindoles/indazoles (1). The latter compounds were synthesized according to procedures described in the literature [18][19][20]. The regioisomers of N-alkylated 5-bromoindazoles were isolated by column chromatography using a hexane–ethyl

• indazole analogues 7e–k under similar reaction conditions. Based on the same logic of vinylindole, regioisomers of N-alkylvinylindazole were considered. So, this 1,3-dipolar cycloaddition reaction could be well applied to both derivatives which afforded a range of differentially substituted final products

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• –n leading to (±)-5b–n. Reaction conditions: (±)-6b–h (0.4 mmol), TsOH·H2O (20 mol %), toluene (8 mL), 80 °C, 45 min. The numbers in parentheses represent isolated yields after silica gel column chromatography. aYield of isolated mixture of the inseparable regioisomers. ORTEP diagram of 5k

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• -thiouridine (very weak substrate) vs uridine (non-substrate), thymidine (very weak substrate) vs 2-thiothymidine (non-substrate). Shugar and co-workers studied the substrate properties of N-3-regioisomers of adenosine and inosine, N3-(β-D-ribofuranosyl)-adenine (N3-Ado) and -hypoxanthine (N3-Ino

• the PNPs. Noteworthy that phosphorolysis of both N-3-regioisomers proceeds irreversibly. In the present work, we compared the energy minimized structures of N3-Ado and 5-aza-2'-deoxycytidine (14) and found a rather similar stereochemistry of both structures, in particular, a quite similar orientation

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• through celite and partitioned between dichloromethane and 5% aqueous sodium bicarbonate solution (10 mL each). The organic layer was washed twice with 5% aqueous sodium bicarbonate solution (2 × 10 mL), dried over Na2SO4 and evaporated. The regioisomers were separated by flash chromatography (toluene

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• by preparative HPLC to result in regioisomers (±)-2a–d and (±)-3a–d as crystalline powders in a ratio of 43:57, respectively. These data clearly showed that the reaction took place without notable regioselectivity, which was in agreement with the observed 58:42 ratio of natural dracocephins A and B

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

• challenge. We turned our attention to the reaction of enamines with nitrile oxides (or their precursors, hydroxamoyl chlorides). The reaction has been shown to take place regioselectively to form only one of two possible regioisomers [18][19][20][21][22][23][24][25][26]. Therefore, this holds some promise

• around the double bond, and found to be 38.09 kcal∙mol−1 above 1a_1 in free energy. Calculations of the suggested mechanisms (Scheme 3) performed for E-isomer 1a_1 and nitrile oxide 6a allowed localizing a concerted transition state for both, observed and not observed regioisomers 3 and 8, respectively

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

• Katrina Tait,
• Oday Alrifai,
• Rebecca Boutin,
• Jamie Haner and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 2189–2196, doi:10.3762/bjoc.12.209

• the C1 position, the formation of two regioisomers is possible (Scheme 4). The bridgehead-oxygen bond can break in two different directions (a or b), creating either a tertiary or secondary cation which after the nucleophilic ring opening creates two different regioisomers. In all cases, the

• cyclopropanated 8 and its proposed ring-opening mechanisms. Formation of the possible regioisomers for the ring opening of asymmetric C1-substituted cyclopropanated oxabenzonorbornadiene. Effects of palladium catalysts and catalyst equivalency on the ring-opening reaction of oxabicyclic alkene 8a with alcohols

Comparing blends and blocks: Synthesis of partially fluorinated diblock polythiophene copolymers to investigate the thermal stability of optical and morphological properties

• Pierre Boufflet,
• Sebastian Wood,
• Jessica Wade,
• Zhuping Fei,
• Ji-Seon Kim and
• Martin Heeney

Beilstein J. Org. Chem. 2016, 12, 2150–2163, doi:10.3762/bjoc.12.205

• -fluorinated monomer gives an approximate 4:1 mixture of regioisomers [45][46]. Although this mixture of isomers can afford good regularity under certain conditions, it can be expected to have a detrimental effect on regioregularity [47]. For this reason most block co-polymers utilize a regiochemically pure

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• -heteroarene reactants [91]. Nicholas and co-workers investigated the thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine with various dienes [92]. Generally, the cycloaddition of an unsymmetrical diene and nitroso compound will lead to two regioisomers – proximal and distal (Scheme 11

• dichloromethane throughout. When the reaction in solution shown in Scheme 20, giving 1,2-oxazine 97, was performed in MeOH, the ratio of regioisomers was changed from 3:2 (in DCM) to 3:1 (in MeOH) [100]. The comparison between the solution and solid-phase syntheses is possible to do with respect to the

• regioselectivity. On the other hand, its isomer 106 gave two regioisomers in a ratio of 2:1 [88][95] (Scheme 21). This was proposed to be due to an increased steric interaction between the phenyl ring at position 4 on the β-lactam ring in 107 and the nitrosobenzene (47) during the formation of product 108. For the

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• in low yields (40% combined yield, entry 3, Table 1). Alternatively, when 2.5 equivalents of Et3N were used, the two regioisomers 11a and 12a were obtained in an excellent overall yield of 87% (entry 2, Table 1). In addition, the ratio of 11a to 12a was not significantly affected by reaction times

• and temperatures (entries 4–6, Table 1). Although initial attempts to synthesize pyrrolotriazinone 12a regioselectively were not successful, it should be highlighted that the regioisomers oxadiazine 11a and triazinone 12a could be easily prepared under very mild conditions (0 °C for 5 min), whereas

• and triazinones 12 are non-crystalline, their exact structures were assigned by NMR spectroscopy (1H and 13C). With the literature results alone [9][10][11][12] the identity of the regioisomers could not be accurately confirmed; therefore, the NMR studies were required. As shown in Table 4, different

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• several examples of literature reported cases where mixtures of regioisomers had been obtained were wrongly assigned. The process described does have certain limitations. For certain nucleophilic substrates no products were obtained when C–N coupling with 4-methoxyphenylboronic acid (17) was attempted

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

• -Ferrocenyl-5-(selenophen-2-yl)spiro[1,3-dithiolane-4,2’-tricyclo[3.3.1.13,7]decane] (5l); 4-Ferrocenyl-4-(selenophen-2-yl)spiro[1,3-dithiolane-2,2’-tricyclo[3.3.1.13,7]decane] (6l): Isolated as a mixture of regioisomers. Yield: 393 mg (73%; crude product ratio 67:33). Yellow solid; IR (KBr) ν: 3085 (w), 3072

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• the generation of regioisomers. In 2002 Sharpless [2] and Meldal [3] independently reported that the addition of catalytic amounts of copper reagent in the AAC allow the reaction to proceed under milder reaction conditions, and there was also an effect on the regioselectivity for the synthesis of 1,4

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• were obtained which were sterically too crowded for attacking the phosphorus atom of the phosphonates. The use of unsymmetrically substituted diamines led to the corresponding syn-regioisomers as the major product and the anti-regioisomer as the minor product. Some of the synthesized 1,5-benzodiazepin

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• rings was formed selectively from precursor 5a. We also briefly studied the palladium-catalyzed cyclization of p-methoxy-substituted aryl iodide 6a/b that led under the standard conditions to a mixture containing compound 16 (Scheme 7). We cannot exclude that other regioisomers or even primarily formed

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• the 3-position of indoles, while Shi et al. reported that they obtained regioisomers when 3-methylindoles were used (Scheme 49) [66], indicating that the 3-methyl group was important for the observed regioselectivity. Shi et al. established a chiral CPA-catalyzed asymmetric allylation of 3

Separation and identification of indene–C₇₀ bisadduct isomers

• Bolong Zhang,
• Jegadesan Subbiah,
• David J. Jones and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2016, 12, 903–911, doi:10.3762/bjoc.12.88

• separation; electron acceptor; fullerene bisadduct; organic solar cell; regioisomers; Introduction Organic solar cells (OSCs) are an emerging renewable energy technology that has achieved remarkable progress over the past two decades. Compared to traditional inorganic semiconductor solar cells, OSCs promise

• ]. Therefore, bisadducts of C70 usually consist of three major regioisomers, which have been described as the 12 o’clock, 2 o’clock and 5 o’clock isomers (Figure 2b) [10]. Each of these three regioisomers also includes two or three geometric isomers as a result of the conformation of the substituents. Given

• . Among these fractions, all of the major regioisomers as well as some minor regioisomers of IC70BA were identified. The separation process, full characterizations as well as the device performance of these isomers of IC70BA are presented in this work. Results and Discussion The synthesis of the isomeric

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• ] may lead to two possible regioisomers: isomer 2 with the benzene ring fused at C5a–C9a and its regioisomer 3 with the benzene ring fused at C4b–C8a (Figure 1). Additionally, due to the new stereocenters created at positions 4 and 4a, each regioisomer could be expressed as a set of diastereoisomers

• ). However, a slight bathochromic shift could be observed when methylene chloride was used in contrast to a hypsochromic shift in the more polar solvent acetonitrile. The analysis of the absorption spectra revealed some differences between the regioisomers 2''b and 3''b and diastereoisomers 2' and 2'', as

• time, most of the isomer 2'a was recovered and traces of derivative 4a could only be detected in the NMR spectrum. Using the same procedure, the enol-lactone isomeric mixture 2'c/3'c was subjected to the dehydrogenation reaction yielding the regioisomers 4c and 5c (Scheme 2). The 1H NMR spectrum

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

• expected three diastereoisomers. In all cases they belong to the same group of regioisomers. The regioselective formation of products 10 was proved by 13C NMR spectroscopy: the signals attributed to C(2) were found in narrow regions at 54.9–59.4 ppm for 10c, 10f–h and 43.1–45.6 ppm for 10m,n, respectively

Aluminacyclopentanes in the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes

• Vladimir A. D’yakonov,
• Alevtina L. Makhamatkhanova,
• Rina A. Agliullina,
• Leisan K. Dilmukhametova,
• Tat’yana V. Tyumkina and
• Usein M. Dzhemilev

Beilstein J. Org. Chem. 2016, 12, 406–412, doi:10.3762/bjoc.12.43

• regioisomers react in situ with phosphorus dihalides and hydrogen peroxide to afford 1-phenyl(alkyl)-2-arylphospholane oxides 7a–f and 1-phenyl(alkyl)-3-arylphospholane oxides 8a–f in 2:1 ratio in a 69–87% total yield (Table 2). The regioisomers were isolated by column chromatography (hexane/ethyl acetate

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• from medium to low as depicted in Table 1. Despite our chromatographic (column, thin-layer) efforts, additional pure products other than 5 and 6 could not be isolated from the complex final reaction mixtures. The structural determination of the reaction products, the 9- and 4-hydroxyalkoxy regioisomers

• 5 and 6, was easily accomplished by using the habitual analytical and spectroscopic techniques, whereas the distinction between each two regioisomers is basically supported by 1H NMR NOE difference experiments. For the major isomers 5 enhancements of the signals due to the H-C2 and CH2-OAr protons

• monodeuterated acetal-fulvene 20 bearing the deuterium atom at C4. This species converted into a 2:1 mixture of the monodeuterated regioisomers 21 and 22 as the only isolated reaction products (Scheme 6). In both compounds, the deuteration percentage at their respective C4 and C9 positions was determined, by 1H