Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• Centre via http://www.ccdc.cam.ac.uk/data_request/cif. X-ray analysis of 1a–f. Acknowledgements This work was supported in part by JSPS KAKENHI (No. 16H01155, No. 16K05777), and by JST, ACT-C, Japan.

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• conformations around the two respective torsion angles [37][38]. In this case, it is also highly probable that hydrogen bonding will reinforce these conformational preferences. Whilst it was not possible to isolate crystals of 3 that were suitable for X-ray analysis, it was possible to unambiguously establish

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• cyclization product 7a and not the 4-exo-dig-cyclization compound 7a' (Scheme 3). We rationalized, as per Baldwin’s rules, that the 5-endo-dig cyclization of a 1,4-Michael addition was more favorable than the 4-exo-dig-cyclization [50][51]. The structure of compound 7a was definitively confirmed by X-ray

• analysis (Figure 1). We then elected to carry out yield optimization studies of the cyclization reaction using a number of solvents, reagents and reaction temperatures (Table 1) and also to explore the possibility of a possible 4-exo-dig outcome. The study validated that all the reaction conditions, with

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• EtOAc/BrPh 1:1 (v/v). The X-ray analysis revealed a triptycene-type arrangement (Figure 2) which was similar to a pyridazine complex of 9,10-dihydro-9,10-diboraanthracene reported by Wagner and co-workers [19] as well as the phthalazine complex of 5,10-dimethyl-5,10-dihydroboranthrene [17]. The 11B NMR

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• X-ray analysis of a single crystal allowed us to assert the (2R,3S) configuration of 3a (Figure 5). This result allowed for the determination of the absolute configurations of all isolated isoindolinones. Asymmetric synthesis of a new pazinaclone analogue With this handful methodology in hands, we

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• for the electrocatalytic hydrogenation of Ph2CO. Characterisation of Pd/C electrocatalyst. a) TEM micrograph. b) Energy dispersive X-ray analysis (EDX). c) Thermogravimety analysis in N2/O2 (4/1) atmosphere at a heating slope of 10 K min−1 from 298 K to 1023 K. SEM images of (a) Pd0.02/C/T and (b

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• X-ray analysis [24]. Next, we investigated the oxidative cycloaddition reactions of hydroxamic acids 1a–c with various dienes 2 under the optimal conditions (Table 2). Similarly to the benzoyl derivative 1a, the carbamate analogues 1b (R1 = OBn) and 1c (R1 = Ot-Bu) reacted with 1,3-cyclohexadiene

• -alkylammonium periodates. To our delight, the sole use of DIB in a mixed solvent of DCM and methanol gave the endo-cycloadduct 6aa as a single regioisomer in 84% yield starting from hydroxamic acid 1a and guaiacol (5a, Scheme 2). The structure of 6aa was determined by single crystal X-ray analysis [24]. It

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• with β-dicarbonyl compounds. Selected NMR parameters of the ANBF-CH-acid adducts (in DMSO-d6)a. Supporting Information Supporting Information File 426: Experimental section, NMR spectra, HRMS and X-ray analysis data. Acknowledgements This work was supported by the Russian Science Foundation (grant no

• -ray analysis [28] (Figure 3). Compound 15 crystallizes as a solvate with one DMSO molecule connected to the hydrogen atom of the amino fragment by an intermolecular H-bond. Bond lengths and angles in the dearomatized 4-aza-6-nitrobenzofuroxan ring are very similar to those observed in the crystal of

• the chirality of carbon atom C7, the protons HA and HB of the methylene group are diastereotopic and therefore have different chemical shifts (3.34 and 3.74 ppm). The geminal protons and H7 represent a well-resolved AMX system, Figure 2. The structure of compound 15 was additionally studied using X

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• characterization of 6 was achieved by X-ray analysis using a single crystal of 6a (Figure 2), and it was found that the iodoarylation products 6 have a seven-membered carbocycle bearing adjacent difluoromethylene and iodomethylene units. In addition, a selective HI elimination from 6a could be achieved by the

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• diastereomer was assigned by X-ray analysis. Finally, one of the products was selectively reduced to provide a functionalized analogue of streptopyrrolidine, a marine natural product isolated from Streptomyces sp. As shown in Table 1, our studies started with the synthesis of dimer 2a using azlactone 1a in the

• -position relative to both the benzyl substituents [32]. The relative stereochemistry of 6 was assigned by X-ray analysis (Figure 5). Conclusion In summary, we have demonstrated the first diastereoselective dimerization of azlactones mediated by a combination of acetonitrile and potassium or sodium

• trichloroacetate salts, which provides a straightforward and practical access to azlactone dimers with good to excellent yields and good diastereoselectivities. In addition, the relative stereochemistry of major azlactone dimer was assigned as being trans by X-ray analysis. A plausible mechanism was proposed by 1H

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• also confirmed by X-ray analysis (Figure 2). In the 1H NMR spectra of these compounds, the characteristic signals of NH protons are observed in the range of 9.84–9.68 and 7.96–7.80 ppm for 3a–e and 4a–e, respectively. The signals of thiophene H-4 and C-4 atoms in the 1H and 13C NMR spectra of compounds

• diazocyanoester 2d with the thioamides 1a–e gave rise to thiophenes 5b–e in the yields of up to 51%. The structure of the isolated thiophenes 5a–e was established by a regular set of spectroscopic data, whereupon the structure of compound 5c was in addition confirmed by X-ray analysis (Figure 3). In the 1H NMR

• )4 and Rh2(Oct)4 was studied (Scheme 3). The reaction was carried out in methylene chloride at room temperature using a 2-fold excess of thioacetamides 1. It produced almost quantitatively dark green adducts 6a–e, 6b’–e’, which structure was confirmed by analytical methods, X-ray analysis for complex

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• pyrenyl–thymine 2 was confirmed by single-crystal X-ray analysis. Crystal structure Crystals of 2 suitable for X-ray diffraction analysis were obtained by slow diffusion of pentane into a chloroform solution of 2. The oak ridge thermal-ellipsoid plot (ORTEP) with the atom labelling scheme is shown in

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• yields. The X-ray analysis showed that products 53 obtained with primary amines are Z-configured whereas those derived from secondary amines, 54, display E-configuration [58] (Scheme 18). The observed different configurations demonstrate the importance of the intramolecular hydrogen-bond between the NH

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• selective and only one diastereomer was obtained, as supported by analytical data. X-ray analysis of the product confirmed the stereochemistry of the three chiral centres and the structure of 15a. To shed more light on the origin of the selectivity observed in the deprotection–cyclization transformation

• (OH)2/C followed by cyclization provided unprecedented DKP 19 in 52% yield. In this case again, spectral data and X-ray analysis showed the selective formation of diketopiperazine 19 as only one isomer (Scheme 6). Conclusion In summary, we have developed an efficient synthesis of two enantiopure

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• structure of 7a was confirmed by X-ray analysis (Figure 2) [30] and the other derivatives were proposed by analogy. In the same way as for the imidazopyridazines, the structure of 7e was established by X-ray analysis [30] and this was extended to the other derivatives. These results unambiguously

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• by NMR. Only the major isomer of 4ai crystallized from the mixture and thus Z-stereochemistry of the two aroyl groups (ClC6H4CO and PhCO) was confirmed by X-ray analysis (Figure 1) [20]. Electron-donating substituents of ynones 2 gave slightly better yields than electron-withdrawing ones. The yields

• confirmed by X-ray analysis as shown in Figure 2 [20]. Isolation of 10 prompted us to get the monoacylated Breslow intermediate C also as a stable compound. Treatment of benzil 1d with equimolar amounts of 3 and DIPEA at room temperature, followed by non-aqueous work-up and column chromatography gave

• crystalline product 12 in 92% yield (Scheme 6). Although 12 did not provide single crystals suitable for X-ray analysis, its structure was determined by NMR and elemental analysis. 1H NMR spectra of 12 showed eleven protons in the aromatic region, i.e., two ClC6H4, Me3C6H2, and one particular proton at δ 6.68

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• determined by X-ray analysis (see the Supporting Information File 1 for details), and the configurations of all other examples were assigned analogously. Once the optimal conditions for the transformation were established, we next proceeded to explore the substrate scope (Scheme 2). The substrate bearing a

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• -diastereoselectivity of the CCR is well documented in the literature [33] and is, therefore, unsurprising. However, the stereocontrol achieved in this reaction over 3 stereocenters present in 10l (obtained in 81% yield as a single diastereomer) is certainly quite noteworthy and was confirmed by X-ray analysis (Figure

• for syn-isomers. According to the X-ray analysis, the dihedral angle values in the C11H–C11aH fragment lie within the 165–170° and 55–58° range for anti- and syn-diastereomers, respectively (Supporting Information File 1, Table S1). Thus, for most of the 2H-indolenine-derived compounds (except for 10d

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• the catalyst d. The absolute configuration of 3g was determined by X-ray analysis (see Supporting Information File 1, Figure S1). Conclusion We have developed a highly efficient and practical strategy for a single step construction of saturated spirocyclopentaneoxindoles containing four consecutive

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• analysis (Figure 3). In the case of compounds 9 the presence of NOE between the signals of the methyl group and the CH group in the isoxazole moiety allowed to distinguish closely located signals of two CH groups (Figure 4). Ultimately, the structure of compounds 9 was proven by an X-ray analysis of

• correlations between the signals of NH protons and corresponding carbon atoms (through two and three bonds, Figure 2) allowed final distinguishing the shifts of three NH groups signals in 1H NMR spectra. However, the final assignment of the structure A for heterocycles 4 was made with the help of X-ray

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• ) as expected. Finally, the structure of 12c was further confirmed by single-crystal X-ray analysis (Figure 5) [32]. The compound 13c could have the structure 16. However, in a structure like 16 one would expect a correlation between the methylene protons and the pyrrole ring carbon atoms. As we were

• single-crystal X-ray analysis (Figure 7) [32]. The following reaction mechanism was proposed for the formation of 19c (Scheme 6). The reaction starts with the π-activation of the triple bond by iodine to form the intermediate 20, which undergoes an intramolecular addition of the ester oxygen atom to the

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• , substituents located in 4-position of the phenyl ring influence the yield of 9 formed in a competitive reaction with the formal [2 + 3]-cycloaddition of 8 with the starting thioketone 10 leading to the sterically crowded 1,3-dithiolane 11. The structure of the dimer 9, confirmed by an X-ray analysis [13

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• isolated and characterized. Except six compounds, these were new compounds. Furthermore, the reactivity was mapped, and the mechanism was evaluated by B3LYP/6-31G (d,p) calculations. The crystal structure of two α-aminophosphonates was studied by X-ray analysis suggesting centrosymmetric dimers. IR spectra

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• diastereomers of 23–25 were obtained from crystal structure analyses and the correlation of the 13C NMR data. According to an X-ray analysis the minor diastereomer 23b has the configuration (S) at the new formed stereogenic center (Figure 2) [23]. The configuration of the new stereogenic centers in compounds 24

• diastereomers 28a and 29a was determined by X-ray analysis (Figure 4 [23] and Figure 5 [23], hydrogen atoms are left out, except those formed at the new stereogenic centers). The new stereogenic centers in both cases have (2’R,3’R)-configuration. For the diastereomers 26b, 27b, 28b and 29b a set of 1H and 13C