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

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• trifluoromethanesulfonate (TMSOTf) and 1.5 equiv triethylamine (Et3N) in dichloromethane for 4 hours. Then the mixture was cooled down to 0 °C and 1 equiv of p-nitrobenzaldehyde and 0.3 equiv of TiCl4 were added under stirring. Stirring at room temperature was continued for 15 hours. Then the reaction was quenched by the

• yield, while the syn/anti-ratio was not changed (Table 1, entry 2). Elongation of the reaction time resulted in the formation of more side products, drop of aldol products’ yield and selectivity (Table 1, entry 3). A lower amount of TMSOTf (1.2 equiv) led to increased yield but lower selectivity (Table

• with benzaldehyde, p-nitro-, and p-methoxybenzaldehyde as described recently by Ponomarenko and Röschenthaler et al. [34]. Considering our earlier results [31] on TMSOTf-mediated Claisen-type rearrangements of SF5-acetates of allyl alcohols, we favor the initial formation of (Z)-enolates (ketene

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• reductive opening of benzylidene acetal using the borane−THF complex in the presence of Bu2BOTf. Regioselective TMSOTf-catalysed glycosylation of the diol 4 by the imidate donor 3 resulted in the formation of a single product, the β(1→6)-linked disaccharide 5. After the 2’-N-Fmoc group in 5 was removed with

• reductive opening of the benzylidene acetal to give the acceptor monosaccharide 63. NIS/TMSOTf-promoted glycosylation of 63 with glycosyl donor 64 furnished desired β(1→6) disaccharide which was subjected to treatment with hydrazine hydrate to remove the phthalimido group. Subsequent acylation of the

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

• -difluoroallyl)biphenyl (1a) as a model substrate. To generate a highly reactive, cationic iodine species, several iodine sources were used with acid or metal activators (Table 1, entries 1–3). Upon treatment with N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a 1:1 mixed

• fluorine substituents in the three-membered iodonium intermediates. Since the combination of NIS and TMSOTf was found to be the best for an iodoarylation of 5, the reactions of a couple of 2-(3,3-difluoroallyl)biaryls 5 were examined under the same conditions (Scheme 4). The iodoarylation of

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• -anhydroGlcNAc was carried out according to Tyrtysh et al. [12]. A suspension of 4 (203 mg, 1.0 mmol) in dichloromethane (10 mL) was treated with collidine (264 µL, 2.0 mmol) at room temperature. Trityl triflate (0.3 M in dichloromethane, 5 mL, generated freshly by mixing equimolar quantities of TMSOTf and TrOH

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• nucleophilic halide anion is another feature of this reaction. Indeed the treatment of TMSOTf on a phosphonate did not induce the dealkylation likely due to the absence of nucleophilic species [161]. It is worth noticing that the nucleophilic attack of bromide only occurs on alkyl chains as exemplified by a

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• of PhSeBr. PhSeBr could react with the remaining donor 4 for quantitative activation of 4. The addition of the acceptor to the reaction mixture upon donor preactivation afforded orthoester 6. The orthoester 6 was rearranged in situ with trimethylsilyl trifluoromethanesulfonate (TMSOTf) to

• disaccharide 7, which could be subjected to bromine-promoted glycosylation for further chain elongation. As an example, preactivation of a monosaccharide 8 with bromine was followed by the addition of a bifunctional disaccharide building block 10 and subsequent TMSOTf-promoted orthoester rearrangement

• /AgOTf [18], N-iodosuccinimide (NIS)/TMSOTf [18], dimethyl(methylthio)sulfonium triflate (DMTST) [18], 1-(benzenesulfinyl)piperidine (BSP)/Tf2O [18][19][49], S-(4-methoxyphenyl)benzene-thiosulfinate (MBPT)/Tf2O [50], Ph2SO/Tf2O [36][51], O,O-dimethylthiophosphonosulfenyl bromide (DMTPSB)/AgOTf [52], and

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• intramolecular glycosylation, probably due to steric interactions. A glycine residue spacer was found necessary to separate the two rigid Hyp bound counterparts. Thus, glycosylation of conjugate 38 in the presence of NIS and TMSOTf resulted in the formation of the (1→4)-linked disaccharide 40 in 80% yield with

• obtained (Scheme 12). Following the NIS/TMSOTf-promoted glycosylation, macrocycle 50 was formed in 55% yield with exclusive α-stereoselectivity. Interestingly, when a similar template was attached to the O-2 position followed by glycosylation with the 3-hydroxy group, the reaction proceeded with high β

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) were employed as co-promoters in solution or automated glycan assembly on solid phase. Keywords: automated glycan assembly; 1,3-dibromo-5,5-dimethylhydantoin; glycosylation; promoter; thioglycosides; Introduction Thioglycosides are versatile glycosylating

• modest yield (43%). When TfOH or TMSOTf (10 mol %) were added as co-promoter, the yield increased to more than 90% (Table 1, entries 2 and 3). Next, the amount of the reagent required for activation was studied (Table 1, entries 3–5). Substoichiometric amounts of DBDMH (0.7 equiv) in the presence of co

• oligosaccharides [20][47]. Ideally, stable and non-toxic reagents should be used on such instruments. The automated synthesis of disaccharide 16 served to assess the suitability of the DBDMH/TMSOTf activation system using functionalized resin 15 [48] as solid support (Scheme 1). After two coupling cycles with

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• anomeric center Davis and colleagues [51] developed a unique glycosylation strategy that employs a 4-bromobutanyl group as a self-activating aglycone on a mannose monomer (Scheme 13) which works even in the absence of any activating agent, such as TMSOTf. The synthesis of the self-activating donor proceeds

• very common and well-studied. Typical Lewis acids employed for anomeric activation are TMSOTf and BF3·Et2O (Scheme 14). The reactions proceed through an oxocarbenium ion that was very recently observed by NMR under cryogenic (−40 °C) conditions stabilized by the HF/SbF5 superacid [52]. The highly

• glycosides: A potentially attractive strategy for a 1,2-cis glycosylation has been described by Baker and colleagues [56] and employs the use of a deprotected thiol glycoside in the presence of a large excess of Lewis acid (TMSOTf) and N-iodosuccinimide (NIS). Although the stereoselectivity of the reaction

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• , 2.2 mmol) in dry MeCN (15 mL) was added BSA (1.36 g, 6.7 mmol). The mixture was heated at 50 °C for 20 min. After cooled to room temperature, a solution of 16 (1.00 g, 1.7 mmol) in dry MeCN (5 mL) along with TMSOTf (1.30 g, 5.9 mmol) were added to the above reaction mixture at 0 °C. The solution was

• conditions: (a) I2, acetone, 0 °C to rt, 88%; (b) K2CO3, MeOH, rt, 93%; (c) 2-iodobenzoyl chloride, pyridine, −10 °C to rt, CH2Cl2, 80%; (d) 1-hexyne, PdCl2(PPh3)3, CuI, Et3N, THF, 50 °C , 78%; (e) 9, DMAP, Et3N, CH2Cl2, 0 °C to rt, 74%; (f) Ac2O, H2SO4, acetic acid, rt, 74%; (g) uracil, BSA, TMSOTf, MeCN

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• + 3] approach (Scheme 1, route A) to the synthesis of the repeating unit hexasaccharide 36 (Scheme 7) was attempted. The union of trisaccharides 2 and 3 using TMSOTf in acetonitrile as the activator did not yield the desired hexasaccharide 36. Instead, trisaccharide acceptor 3 missing its C6 silyl

• 44. Considering a potential “mismatch” [38] between the thioglycoside glycosylating agent and the acceptor [39][40] we explored whether the glucosyl trichloroacetimidate donor 6 (Scheme 1) would be more suitable. Indeed, glycosylation of disaccharide 42 with building block 6 using TMSOTf as the

• basic conditions using methyl iodide in 32% yield over three steps [41]. Next, TMSOTf activation of fucosyl trichloroacetimidate 8 (Scheme 1) catalyzed the glycosylation of methyl uronate 48 to afford pentasaccharide 49 exclusively as the α-isomer by virtue of remote participation of the 3-O-acetate

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

• protective groups on the donor a TES-protected trichloroacetimidate of fucose, 4, was employed by Myers et al. [7] in order to have protective groups compatible with their synthesis of neocarzinostatin. It was found that optimal glycosylation was performed with TMSOTf as a catalyst at low temperature and

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• (1.5:1) in good yield (Scheme 6). Glycosylation of 21 with bis-silylated 2-(N-acetylamino)-6-chloropurine under a variety of reaction conditions was found to be unsuccessful. However, glycosylation of 21 with bis(trimethylsilyl)thymine in the presence of TMSOTf in dichloromethane led to the

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

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• ensure complete glycosylation of the nucleophile (Scheme 1). The glycosyl phosphate building blocks 1 and 2 were activated by stoichiometric amounts of TMSOTf (trimethylsilyl trifluoromethanesulfonate) at −30 °C and reacted at this temperature for 30 min. Then the temperature was raised to −15 °C and

• deletion sequences (7 and 8) were also detected. Glycosylations mediated by the strongly acidic activator TMSOTf were found to be neutral when exiting the reaction vessel. An incomplete removal of the strongly basic deprotection solutions would result in quenching of the next glycosylations. Indeed, test

• ), 254 nm. Attempted assembly of SP3 trisaccharide 5 using glycosyl phosphate building blocks 1 and 2. Reagents and conditions: a) 2 (3 equiv), TMSOTf, CH2Cl2, −30 °C (30 min) to −15 °C (30 min), n = 3; b) Et3N in DMF (10% v/v), 25 °C (15 min), n = 3; c) 1 (3 equiv), TMSOTf, CH2Cl2, −30 °C (30 min) to

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• corresponding β-ketoenamines 2a–e were converted into different β-ketoenamides 3a–g by N-acylation with 2-pyridinecarboxylic acid derivatives. These β-ketoenamides were treated with a mixture of TMSOTf and Hünig’s base to promote the cyclocondensation to 4-hydroxypyridine derivatives. Their immediate O

• compounds that are not accessible by alternative methods. Synthesis of highly functionalized 2,2'-bipyridines 4a and 5b from symmetrical 1,3-diketones 1a and 1b; TMSOTf = trimethylsilyl trifluoromethanesulfonate; DIPEA = N,N-diisopropylethylamine; NfF = nonafluorobutanesulfonyl fluoride. Synthesis of β

• the corresponding N-oxide 8. Suzuki-couplings of 2,2'-bipyrid-4-yl nonaflates 5a and 5b to compounds 9 and 10. Palladium-catalyzed couplings of chloro-substituted 2,2'-bipyrid-4-yl nonaflate 5g leading to compounds 11, 12 and 13. Attempted TMSOTf/DIPEA-promoted cyclocondensations of β-ketoenamides 3a