Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• the C-3 carbon atom. The obtained products were benzoylated with benzoyl chloride/pyridine in the presence of DMAP to give the fully benzoylated isoxazolidine-4,5-diols 6a and 6b, which were subsequently treated with Et3SiH (3 equiv) and TMSOTf (2 equiv) in anhydrous CH2Cl2 at room temperature for 2 h

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• research. In an attempt to overcome this reactivity issue, the same authors decided to use the trimethylsilyl-based Lewis acid TMSOTf in order to allow the covalent activation of the alkenylpyridine via pyridinium formation. This strategy turned out successful, and optimisation studies identified reaction

• conditions that allowed highly enantioselective ACAs of Grignard reagents to alkenylpyridines (Scheme 15) [46]. Using the optimised conditions (Cu/L7/TMSOTf), a large variety of pyridine-based chiral compounds was synthesized. Apart from allowing the introduction of different linear, branched, cyclic, and

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• 8 only affording an unidentifiable mixture of compounds. Similarly, the 2,7-anhydro backbone of 11 was not cleaved under the above conditions and results in either recovered starting material or unidentifiable mixtures. Differently, ring-opening reactions of 6 with BF3⋅OEt2, TMSOTf, and Sc(OTf)3 in

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• described. Glycosylations were performed in CH2Cl2 and TMSOTf catalysis (Scheme 2). Galactofuranosyl iodide 5 was obtained by the treatment of per-O-TBS-β-ᴅ-Galf with a stoichiometric amount of TMSI, and glycosylated in situ by adding the acceptor in the presence of EtN(iPr)2 as acid scavenger (Scheme 3

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• mepivacaine (197a) [107]. The key steps in the synthesis involved the initial anodic oxidation of cyclic N-carbamate 194 bearing an 8-phenylmenthyl group as a chiral auxiliary which generates in situ N-acyliminium ion 195 and this 195 upon reaction with nucleophilic CN− in presence of catalytic TMSOTf and β

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• ). Glycosylation of the known GlcNPhth acceptor 2 [12] and the rhamnosyl donor 3 [13] through the activation of thioglycoside using N-iodosuccinimide (NIS) in the presence of TMSOTf gave the Rha-(1→3)-GlcNPhth disaccharide 4 in 84% yield. The presence of a participating acetate group at the 2-position of the

• using NIS and TMSOTf afforded the trisaccharide 10 in 78% yield. The newly formed 1,2-cis glycosidic linkage was confirmed by the peaks at 4.27 ppm (d, J1′′,2′′ = 1.5 Hz, 1H, H-1′′) in the 1H NMR and at 93.8 ppm (C-1′′) in the 13C NMR spectra. The presence of the participating O-benzoyl group at the 6-O

• thioglycoside using NIS in the presence of TMSOTf at low temperature gave the disaccharide 16a (α) [1H NMR: 5.37 ppm (bs, 1H, H-1′), 13C NMR: 108.2 ppm (C-1′)] and 16b (β) [1H NMR: 5.36 ppm (d, J1′,2′ = 4.0 Hz, 1H, H-1′), 13C NMR: 95.6 ppm (C-1′)] in 89% yield (α:β = 2:1) (Scheme 3). Although the acceptor is

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a diastereoselective and stepwise manner. This novel methodology provides a shorter access to the intermediate 97, which is a key intermediate for the synthesis of triptolide. Recently, photoredox catalysis has emerged as a powerful and high-yielding method

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• spectrometry analysis showed that the pNB group was removed under the Suzuki–Miyaura reaction conditions. To obtain the biaryl bicyclic peptide 1, the Boc group of cyclic peptidyl resin 5 was then removed under mild conditions using trimethylsilyl triflate (TMSOTf) in presence of 2,6-lutidine in CH2Cl2 (Scheme

• -Leu-OH, DIPCDI, Oxyma, DMF. (vi) Fmoc-Ala-OH, DIPCDI, Oxyma, DMF. (vii) Boc-Phe(4-BPin)-OH, DIPCDI, Oxyma, DMF, 3 h. (viii) Pd2(dba)3, P(o-tolyl)3, KF, DME/EtOH/H2O (9:9:2), MW, 120 °C, 30 min. (ix) TFA/H2O/TIS (95:2.5:2.5), 2 h. (x) TMSOTf, 2,6-lutidine, CH2Cl2. (xi) PyOxim, Oxyma, DIPEA, NMP, 24 h

• . (vi) Fmoc-Ala-OH, DIPCDI, Oxyma, DMF. (vii) Boc-Tyr(3-B(OH)2,Me)-OH, DIPCDI, Oxyma, DMF, 3 h. (viii) Pd2(dba)3, SPhos, KF, DME/EtOH/H2O (9:9:2), MW, 120 °C, 30 min. (ix) TFA/H2O/TIS (95:2.5:2.5), 2 h. (x) TMSOTf, 2,6-lutidine, CH2Cl2. (xi) PyOxim, Oxyma, DIPEA, NMP, 24 h. Synthesis of the biaryl

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• with trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a tertiary amine as base a broad range of pyridine derivatives was accessible (Scheme 3). According to its discoverer, we named this reaction Flögel pyridine synthesis [21]. The reaction is very flexible with respect to the employed

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• allow for purification by FSPE of the mannosyl intermediates and to facilitate future automated syntheses to produce α-1,2-trimannose in appreciable quantities similar to previous efforts (Scheme 1) [11][47][51]. To synthesize the oligosaccharide, activation of TCA donor 3 with TMSOTf and glycosylation

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• step reaction arrangement starting from pyranose 4 was set up. Scheme 4 shows this setup of a suitable cascade reaction in which DBU, trichloroacetonitrile and pyranose 4 were pumped through the first flow reactor (R1) followed by the addition of the alcohol and TMSOTf through the second reactor. Table

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -benzylidene-β-D-glucopyranoside (11) in 70% yield. Stereoselective glycosylation of compound 11 with D-mannose-derived ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside (3) [14] in the presence of a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) [22

• couple with the D-mannose-derived thioglycoside acceptor 6 in the presence of TMSOTf [35] to furnish phenyl (4,6-O-benzylidene-2,3-di-O-benzyl-β-D-mannopyranosyl)-(1→4)-(6-O-benzoyl-2,3-di-O-benzyl-α-D-glucopyranosyl)-(1→3)-4,6-O-benzylidene-2-O-benzyl-1-thio-α-D-mannopyranoside (19) in 45% yield. The

• trisaccharide thioglycoside 19 can now act as a glycosyl donor fulfilling the orthogonal glycosylation principle [36]. Stereoselective glycosylation of disaccharide acceptor 13 with the trisaccharide donor 19 in the presence of a combination of NIS and TMSOTf [22][23] resulted in the formation of

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• mixtures [24]. In the Vorbrüggen version of the silyl Hilbert–Johnson method, trimethylsilyl trifluoromethanesulfonate (TMSOTf) is used as a Friedel–Crafts catalyst. The TMSOTf-mediated glycosylation of Nam (1a) with tetra-O-acetyl-β-D-ribofuranose was first proposed by Tanimori et al. in 2002 [29] (Scheme

• glycosylation (Figure 3). This intermediate is subsequently approached by Nam from the less hindered side. Subsequently, Franchetti et al. [30] modified the above TMSOTf-protocol by introducing the preliminary silylation of the amide group of Nam, a procedure based on the chemistry developed by Vorbrüggen [24

• -O-acetyl-β-D-ribofuranose (2a) or 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (2b) in the presence of TMSOTf in 1,2-dichloroethane solution to give protected NR+ derivatives as triflates 9a,b. Critically, a larger excess of TMSCl decreases reaction rates and lowers yields, as the silylation of

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• DBU. The glycosylation reaction with 2-propanol using TMSOTf as Lewis acid at 0 ºC cleanly provided the β-isopropyl glycoside 13 in 65% yield. Interestingly, no α-anomer was detected in the reaction mixture. Finally, cleavage of the levulinyl group using hydrazine monohydrate in pyridine/acetic acid

• buffer afforded compound 2. With the required disaccharide building blocks in hand, the synthesis of tetrasaccharide 14β was attempted using catalytic TMSOTf in CH2Cl2 at 0 ºC (Scheme 4). After F-SPE, two spots were detected in the TLC analysis of the fluorous containing fraction, in addition to

• % of TMSOTf with respect to the donor, 0 ºC, CH2Cl2 as solvent). As mentioned before, it has been reported that cyclic protecting groups like 4,6-O-benzylidene acetals in GalNAc trichloroacetimidates lead to the formation of α/β mixtures in glycosylations involving GlcA acceptors [43][47]. However

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• tricyclic sugars 3α/β were individually reacted with trimethylsilyl trifluoromethanesulfonate (TMSOTf) in order to produce the corresponding glycal 4. Surprisingly, apart from the desired glycal 4 its hydrolysis products 5α/β were produced as main side products. In the case of the α-tricyclic sugar 3α the

• ) TMSCF3, NaI, THF, 70 °C, 2 h, 71%; d) TMSCF3, NaI, THF, 70 °C, 4 h, 75%; e) TMSOTf, 2,6-lutidine, DCM, 0 °C to rt, 2 h, 41% (4), 39% (5α/β); f) TMSOTf, 2,6-lutidine, DCM, 0 °C to rt, 7 h, 58% (4), 29% (5α/β). Synthesis of the thymidine phosphoramidite building block 10. Reagents and conditions: a) i

• building block 16. Reagents and conditions: a) Ac2O, pyridine, 0 °C to rt, 17 h, 87%; b) N-benzoylcytosine, BSA, TMSOTf, ACN, 0 °C to rt, 3.5 h, 41%; c) HF-pyridine, DCM/pyridine 5:1, 0 °C, 15 min, 91%; d) i) CeCl3·7H2O, NaBH4, MeOH, −78 °C, 20 min; ii) Bz2O, DMF, rt, 7 h, 94%; e) DMTr-OTf, DCM/pyridine 1

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• precious” and recoverable acceptor 9, which, however, would result in lower yields when compared to glycosylations using excess of donor. In the initial experiment, using TMSOTf as the catalyst in CH2Cl2 at 0 °C, a pleasingly 8:1 3/4-O ratio and a 10:1 α/β-selectivity with a 57% isolated yield of the

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• , treatment of 25 with TiCl4/Zn did not lead to pinacol cyclization and we have evidence that the aldehyde group stayed in place and the keto group had been reduced. Installation of a TMS group at the tertiary alcohol moiety of 25 (TMSOTf, 2,6-lutidine) formed 26, which was simply reduced at the keto function

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• small yields were obtained by the application of the Vangala protocol (activation of the carbohydrate with TMSOTf in toluene and different nitriles as nucleophiles; see Supporting Information File 1 for details). With slight modifications, however, (BF3·OEt2 as Lewis acid instead of TMSOTf and CH2Cl2 as

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• under sila-Pummerer conditions [29][30]. We found that treatment of 12, obtained by oxidation of 11, with excess persilylated N4-acetylcytosine in the presence of TMSOTf as a Lewis acid gave an inseparable mixture of α- and β-anomers of 4’-thioDMDC derivatives 15 in good yield. Based on the study of the

• 28, by treating with 2,4-bis(trimethylsilyl)uracil (29) and excess diisopropylethylamine (DIPEA) in the presence of TMSOTf, gave 4’-thiouridine derivative 30 in a good yield. The reaction stereoselectively proceeded and resulted the predominant formation of the β-anomer due to steric hindrance of the

• subjected to the Pummerer-type glycosylation mediated by hypervalent iodine. Treatment of 36 with bis(trifluoroacetoxy)iodobenzene (PIFA) and uracil in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine gave a 5:1 mixture of 4’-thiouridine derivative 37 in 55% yield. The

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• different cycloaddition products. According to their original presumption some Lewis acids (TMSOTf < Zn(OAc)2 < MgBr2 < Cu(OTf)2) catalyzed the thermal reaction of phenylsydnone with phenylacetylene to give the expected 1,3-diphenylpyrazole in a ratio >10:1 over the 1,4-diphenyl isomer. Quantum calculations

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• formation and ring opening of aziridinium intermediate 58 elucidate the product formation in this transformation [51]. Wirth et al. successfully employed I(III) reagent 8b in combination with trimethylsilyltriflate (TMSOTf) for the stereoselective oxyamination of 59 to furnish isourea 60 with >99% ee

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• trichloroacetimidate donors (6b, Table 1, entries 5 and 6, and 6c, entry 4); the TMSOTf mediated glycosylation in DCM/Et2O solvent (Table 1, entry 6) was found to be effective in case of donor 6b and acceptor 5 which generated the desired disaccharide 3a in high yield and exclusive α-anomeric selectivity (evidenced

• acceptor 4 in 93% yield. Glycosylation between donor 2 and acceptor 4 was achieved uneventfully in the presence of TMSOTf in dichloromethane/Et2O (4:1) to give the trisaccharide 21 in 70% yield. Successful glycosylation was also carried out between trisaccharide 21 and ribitol acceptor 7 in the presence of

• NIS and TMSOTf in dichloromethane at −20 °C to give the tetrasaccharide derivative 1 in 89% yield, thereby finishing the stepwise synthesis of SPn 6A tetrasaccharide 1 in the protected form (Scheme 4). Having standardized a stepwise synthesis of the tetrasaccharide 1 in the protected form we then

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• -iodoxybenzoic acid) and DMP (Dess–Martin periodinane) (Table 1, entries 7 and 8) gave similar yields to the background reaction. Lastly, a Lewis acid screen (Table 1, entries 9–12) was performed. Among the tested Lewis acids, AlCl3, SnCl4, TiCl4, TMSOTf and BF3·Et2O, the latter was found to be the best choice

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• ][44][45]. More commonly, glycosyl azides are synthesized from per-O-acetylated sugars using trimethylsilyl azide in the presence of a variety of Lewis acids such as SnCl4 [46], TiCl4 [47][48], BF3·OEt2 [49], TMSOTf [50][51], etc. However, at higher concentration Lewis acids can potentially lead to

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• enzymes has therefore become an area of significant interest over the past 15 years [35][36]. The synthesis of N-glycan oxazolines Formation of glycosyl oxazolines Glycosyl oxazolines of monosaccharides can be produced straightforwardly using strong Lewis acids (e.g., FeCl3, SnCl4, or TMSOTf) and a fully

• substrates leads to significant cleavage of interglycosidic linkages, and correspondingly low yields of products. However, two methods that are useful for the production of oligosaccharide oxazolines are treatment of the peracetylated sugar with either TMSOTf in dichloroethane [39], or with TMSBr, BF3·Et2O