Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• ). Only the meso diastereomer of 1c is predicted by Woodward–Hoffman analyses [18] to deliver anti-6 that is required for facile E2 elimination leading to the desired tetracene 7 under thermal conditions. However, the initially required 1c are typically attained as ca. 1:1 rac/meso mixtures and this might

• either the rac or meso diastereomer could be realised. The meso enriched diastereomer of 8a could be realised by treating rac/meso mixtures of bis-lithium alkoxide of 8a with freshly prepared anhydrous NBu4F (2 equivalents) [23] (Scheme 3). Acid quench of the resultant purple dianion leads to ca. 5:1

• chiral diastereomer while no equivalent splitting in 1H NMR samples of 8a prepared from purple 11 (in line with it being the meso diastereomer). These assignments are in line with the finding of Saá [15]. The chemical shifts of the methine CHOH proton in rac-8a (δH 6.20) and meso-8a (δH 6.33) reflect an

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• linker. This results in the formation of an enormous number of diastereomers that may have different properties, such as nuclease stability and RNase H interactions. Some [5][10] but not all [11][12] of the non-phosphorothioate antisense reagents avoid the diastereomer problem, but the extensive study of

• separated and continuous fractionation of the phosphorus epimers that occurred during repeated chromatographies. However, 10 was ultimately obtained as a white foam. Samples of the fast-moving diastereomer and of a mixture of the two diastereomers of 10 were fully characterized. They exhibited the

• diastereomeric mixtures occurred. Due to the sensitivity of the acyls, chromatography on long columns of silica (with or without 1% NEt3 to deactivate the silica) gave rise to the loss of acyls, without any improvement in diastereomer separation. However, the individual samples of fractionated diastereomers of

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• cyclisation in moderate to good yields. The products were generated in diastereoselective fashion and the configuration of the formed diastereomer could be identified by 1H NMR experiments comparing a mixture of both diastereomers, synthesised by conventional selenoalkoxylation, with the electrochemically

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• intermediate 90 was treated with a Lewis acid and vinylmagnesium bromide to afford the trans-diastereomer after column chromatography. Coupling of 91 and 92 (prepared using conventional chemistry) resulted in the peptide-turn inducing compound 93. The Moeller research group has carried out extensive research

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• reported with diastereoselective ratios of greater than 100:1 in some instances. Notably, it has been found that the opposite diastereomer can be accessed via this approach merely through the choice of an alkyllithium reagent. The inherently chiral oxazoline calix[4]arenes have also been preliminarily

• ortholithiation conditions varying the solvent, alkyllithium and ligand. The results are reported in Table 1, which for the purposes of comparison, also includes data from our previously published work on the isopropyloxazoline calix[4]arenes 1a and 1b [27][28]. The conversion values and diastereomer ratios were

• ortholithiation study.a Results of the Tsuji–Trost reaction. Supporting Information Experimental details and characterization data for all products; determination of enantiomeric ratios and determination of major calix[4]arene diastereomer. Supporting Information File 480: Synthetic procedures and spectral data

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• (Table 1, entry 14) gave corresponding adducts in good yield and single anti-diastereomer only. The stereostructures of the DA adducts 3 and 4 were deduced from the literature established [41] 1H NMR pattern of the downfield shift (δ = ~1.8) for the syn methyl protons in the pentachloro DA adducts 4 and

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• focused on the synthesis of the diastereomer of 1, 2,3-trans-astakolactin (1’), to thoroughly uncover its molecular structure and stereochemistry, starting from the aldehyde 18, which was prepared according to the procedure [11] described in Scheme 2. It was postulated that the precursor 26 (Scheme 4) of

• in the corresponding spectra of the natural product. Similar discrepancies in the spectral data were also found for the diastereomer 1’ (Figure 3; see also Supporting Information File 1). These facts indicate that the proposed eight-membered lactone moiety is not comprised in the naturally occurring

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• sufficiently so that they can be separated chromatographically on silica gel. The major diastereomer 8a is isolated mixing the diastereomeric mixture for several hours in dry ether with some quantity of silica gel. The minor diastereomer 8b is identified and characterized in the NMR spectra of the

• photomixtures. The difference in structures of 8a and 8b is in the orientation of HB (8a) or Hb (8b) protons. In the NOESY spectrum of the diastereomeric mixture the interaction between HB and HF protons can be seen which is a clear proof that the HB is facing the methano bridge in the major diastereomer 8a

• . There is no interaction between Hb and Hf protons in the minor isomer 8b suggesting that Hb proton is opposite to the methano-bridge. The diastereomer in which the HB is oriented towards the methano bridge is the main product in photochemical reactions of either 4- or 5-(2-vinylstyryl)oxazole. The

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• -diastereomer [14][15][50][51]. Based on the published findings, we have also examined the cyclisation reactions incorporating the PdII–PdIV catalytic cycle [52][53] (Scheme 6). The experiments were carried out using Pd(OAc)2 salt as a catalyst, PhI(OAc)2 as reoxidant, AcONa and Me4N+Cl− as buffer in AcOH

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• phosphonamide 28e provided a diastereomer of 32 with the opposite configuration of the newly formed stereocenter. This inversion in asymmetric induction relative to non-heteroatom substituted phosphonamides such as 28a is presumably a result of a chelated intermediate that exposes the opposite face of the anion

• phosphorus center, whereas cis confers to a R-configuration. Degradation of the adducts by ozonolysis yielded oxocycloalkane-3-carboxaldehydes 43, which are useful synthetic intermediates. Diastereomer cis-40b however gave only poor diastereofacial selection, providing the corresponding 1,4-addition adducts

• in 28–64% ee [5]. In a similar fashion, Denmark’s oxazaphosphorinane cis-44a yielded keto esters 46a–c in high optical purities via conjugate addition to enones 41 followed by ozonolysis and oxidative esterification. Using diastereomer trans-44b on the other hand provided ketoesters 46a–c with only

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• -(dimethoxymethyl)benzene enabled the synthesis of syn-1,2-oxazine 4. The conversion of this reaction was high (>80%) giving the two diastereomers of 4 (ca. 1:1), but only one diastereomer was isolated in pure form. The second diastereomer could hardly be separated from the excess of 1-bromo-4-(dimethoxymethyl

• 81:19 mixture of diastereomers in 72% yield (Scheme 5). In contrast, the reduction with L-selectride at −10 °C selectively furnished pure diastereomer 12a in 73% yield. In accordance with previous observations of reductions of related phenylthio-substituted bicyclic compounds [25], a hydride attack

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• )-hydroxy-α-ionone but also the cis-diastereomer (3S,6R)-hydroxy-α-ionone [43]. The identification of the position 286 in CYP154E1 that obviously influences the regioselectivity of the enzyme and subsequent replacing of valine at this position by three other hydrophobic amino acids of different size allowed

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• of configuration as expected and the 1H NMR spectra of the crude reaction mixture only showed the desired diastereomer 17. Several known catalytic systems were tested [29]: Pd(PPh3)4/PPh3 in THF/DMF [33], Pd2(dba)3/diphos in THF/DMF [34], Pd2(dba)3/dppf in THF [35]. The first set of conditions proved

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• acyclic D-serinal derivatives for the addition of nucleophiles to amino acid-derived aldehydes [33][34]. However, Zhu and co-workers have pointed out that Garner’s aldehyde surprisingly furnishes the syn diastereomer as the major product from its reaction with isopropyl magnesium chloride [32], thus

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• preparative HPLC or recrystallization. Nucleophilic substitution of pure diastereomer (RP)-2a with methyllithium afforded the phosphine–borane (S)-4 with 94% enantiomeric excess. The substitution resulted in inversion of the configuration at the phosphorus center. Deboranation of the air stable borane adduct

• excesses were reported. As expected, a mechanistic study suggested that the major enantiomer of product was formed from the major diastereomer of the platinum–phosphido intermediate [63]. Glueck and co-workers also developed an analogous method for the tandem alkylation/arylation of primary phosphines on

• following years, the scope and mechanism were elaborated [202][203][204]. In accordance with the mechanism given in Scheme 10, it was concluded that the major enantiomer of the product 108 was derived from the major diastereomer of the Pd-phosphido intermediate. Korff and Helmchen have prepared several

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• analysis of the partially oxidized derivative of compound S(O)-1 (Figure 2) [75]. The phenothiazine and anthraquinone moieties are aligned by intramolecular π-stacking with an average distance of ~3.9 Å [76][77]. In the unit cell the R- and S-enantiomers of a single diastereomer (S-oxide) are arranged in

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• -galactose-OH 12c was carried out in analogy to the preparation of 12a (Scheme 2). Thus, Michael addition of ammonia to D-galactose derived α,β-unsaturated ester 9c [56] afforded 10c (L-glycero) as a single diastereomer in 91% yield that was identified by spectral data identical to the reported [57

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• diastereomer as a racemic mixture. Under kinetic control, inverse-electron demand aza-Diels–Alder as well as normal Diels–Alder reactions are known to favour endo products since the endo approach maximizes secondary orbital overlap [42]. The “boat-type” transition state favours an endo orientation (“inside of

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• of the new compounds 4a and 5a have clearly distinguishable signals for the methylene protons. Thus, in cis-diastereomer 4а the chemical shifts of the doublet signals for the protons of the CH2-groups differ by more than 2 ppm (3.26, 5.62 ppm), whereas in trans-diastereomer (5а) they represent an AB

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• ) also confirmed the structure. The relative orientations of H-1, H-18, H-19 and H-20 could be determined unambiguously by the single-crystal X-ray diffraction analysis of 10a; the ORTEP diagram is presented in Figure 2. No other diastereomer could be detected. The plausible mechanism of this

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• olefinic protons appearing at δ 4.8–5.2 and δ 5.5–5.8 for the major diastereomer and at δ 4.5–4.8 and δ 5.3–5.5 for the minor diastereomer in the 1H NMR spectra. The signals of the corresponding carbon nuclei are accordingly identified in the 13C NMR spectra as methylene signals at δ 114.7–117.5 for the

• major diastereomer and at δ 118.1–123.5 for the minor diastereomer. Based upon computations (B3LYP functional, 6-31G* basis set) [44] on geometry-optimized diastereomers 2Z,4Z-8a and 2Z,4E-8a the former is energetically favored by 1.5 kcal mol−1 over the latter (Figure 2), nicely reproducing the

• (0.56H), 5.61 (s, 0.56H), 5.78 (s, 0.56H), 6.25 (d, J = 7.8 Hz, 0.56H), 6.40–6.56 (m, 2H), 6.60–6.67 (m, 1H), 6.80–7.29 (m, 11H), 7.32 (d, J = 7.4 Hz, 0.56H); additional signals for the minor diastereomer: δ 4.61 (s, 0.44H), 5.33 (s, 0.44H), 6.73 (d, J = 7.5 Hz, 0.88H), 7.49 (d, J = 7.1 Hz, 0.44H); 13C

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• highly reactive chiral pyrroline 38 and several carboxylic acids and isocyanides (Scheme 13). The disubstituted pyrrolidines were obtained in moderate to high yields, with a small preference for the trans-diastereomer 39 [56][57]. The judicious choice of carboxylic acid substituents allows a subsequent

• , respectively, in moderate to excellent yields. The reaction with the erythro isomer resulted in a single diastereomer 48a whereas no selectivity was observed for the threo isomer. Based on this diastereoselective MCR, the group of Banfi developed an Ugi-Joullié 3-CR with carboxylic acids, chiral bicyclic

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• its (SCRN) absolute configuration. Accordingly, the second product, diastereomer 6b, has (SCSN) configuration. The X-ray structure of 5b revealed the complex is not fully planar as expected. The benzophenone chelate ring system deviates from planarity by 14.4° (0.16 e.s.d.). The torsion angle of Ni2

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• the conclusions drawn from the 1H NMR spectra. Two individual peaks for the two diastereomers can be detected when (rac)-3 is employed for complexation and the intensities of the signals of the racemic homochiral diastereomer are approximately three times as large as those of the signals of the

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• a single diastereomer according to 1H NMR. Importantly for up-scaling, only a slight excess of L-Selectride (1.3 equiv) or Superhydride (1.5 equiv), respectively, was required for the quantitative conversion of 7a–d to the intermediate II. Therefore the deprotonation of the free OH-group of 7 must

• starting material 14a was dissolved in the less polar CH2Cl2 (rather than THF), the dr further increased to >19:1 (entry 6). Moreover, N-Selectride provided the product 9a almost as a pure diastereomer (entry 7, solvent THF), only a very small trace of the syn-diastereomer was visible in the 1H NMR (400

• temperature, immediate L-Selectride reduction (giving intermediate V), HCl quenching and Et3N-induced cyclisation afforded the piperidine trans-11a in an excellent ee (≥99%) and as a single diastereomer according to crude 1H NMR. Although the reduction is performed in the presence of a secondary amino