Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• reaction (Table 1, entries 6, 8, and 9). A slight improvement in the yield of 3a was observed when switching from TMSOTf to TfOH as the activator (Table 1, entry 5 vs entry 10). However, substituting TMSOTf with BF3·OEt2 did not yield any target product 3a (Table 1, entry 3 vs entry 12). In our

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• , and TMSOTf resulted in good chemical yields. In the transformation, the selectivity of the endo or exo cyclization depended on the atom number of the chain between alkene and arene, leading to the formation of 6-, 7-, or 8-membered rings. In addition to N-(thio)phthalimides, benzenesulfenyl chloride

• sulfide molecules 137 (Scheme 58) [90]. The Lewis basicity nature of PhSePh as a catalyst and the presence of Lewis acid TMSOTf improved the chemical yields. It is interesting to note that the reaction carried out at a lower temperature because of the high reactivity of allene 136. When the reaction was

• cyclization transformation involving activation of the electrophilic sulfur reagent by PhSePh with the assistance of TMSOTf to form transition state I. Intermediate II formed through capturing of sulfonium by selenium. Then, II reacted with 136 to give regioselective cyclic thiiranium ion III. Nucleophilic

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• TMSOTf) promoted trapping gave the aldol adducts 4 in good to excellent diastereoselectivity (up to a single diastereomer), but the yields were relatively low (25–44%). To overcome this limitation, the authors used TMSOTf to prepare and isolate the corresponding silyl enol ethers, which were later

• unsaturated amides, the trapping worked also with alkenylheterocycles 103. Interestingly, the corresponding aza-enolates could be generated by two sets of experimental conditions where ACA was promoted either by BF3·OEt2 or TMSOTf (Scheme 27A). Based on the recent Harutyunyan discovery of ACA to unsaturated

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• using acyl chloride 6b with an isobutyl side chain is its low volatility in contrast to the highly volatile compound 6a. The aza-Nazarov product 7b was isolated in 61% yield with 20 mol % of AgOTf at 80 °C (Table 1, entry 5). The use of TMSOTf as a Si-based Lewis acid catalyst with 20 mol % loading

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• produce aporphine natural products, while the use of PIDA or PIFA in the presence of BF3·OEt or TMSOTf in wet CH3CN allows to diverge the synthesis to morphinandienone natural products (e.g., 181, Scheme 15). The flow reaction was performed in a reaction coil at room temperature. Two reaction loops were

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• optimization showed that chiral squaramide 47 developed by Jacobsen’s group significantly accelerated the Mukaiyama reaction compared to TMSOTf or TiCl4 thanks to chiral hydrogen bond-donor effect [35]. After Sakurai cyclization promoted by EtAlCl2, the desired product 48 was obtained with the required

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• (trimethylsilyl)acetamide (BSA) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) afforded nucleosides 13a,b. Further, deacetylation of the triacetylated azidoallofuranosyl nucleosides 13a,b with K2CO3 in methanol/water led to the formation of 3′-azido-3′-deoxy-β-ᴅ-allofuranosyl nucleosides 14a,b in 85

• anomeric triacetylated sugars 19a,b with thymine and uracil in the presence of BSA and TMSOTf in acetonitrile afforded nucleosides 20a,b, respectively in high yields. The deacetylation of these nucleosides was carried out using K2CO3 in a solvent mixture of methanol and water (9:1) to afford nucleoside 21a

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• described in Scheme 2. With the monosaccharide building blocks in hand, the galactosamine donor 6 was coupled with galactose acceptor 7 by activation of the thioglycoside using N-iodosuccinimide (NIS) in the presence of TMSOTf to afford the desired disaccharide β-ᴅ-GalpNHTroc-(1→4)-α-ᴅ-Galp (4) in 85% yield

• , as a single isomer (Scheme 3). Then, the chloroacetyl group was selectively removed using thiourea and 2,4,6-collidine [47] to afford the 3’-OH acceptor 5 in 87% yield. Finally, NIS/TMSOTf-promoted coupling of donor 3 with disaccharide acceptor 5 provided the desired β-linked trisaccharide 2 in 89

• acceptor 9 in the presence of TMSOTf as promoter (Scheme 5). After 1 h of reaction, TLC monitoring indicated the full consumption of the starting materials. Analysis of a small aliquot of the reaction mixture by HRMS confirmed the formation of the desired disaccharide. Then, to the same pot, the second

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• isolated oxathiolane precursor 41, as discussed earlier, by enzymatic resolution of an acetoxy sulfide by a Pseudomonas fluorescens lipase. Using this pure precursor 41, the synthesis of 3TC (1) was accomplished by N-glycosylation with silylated base using trimethylsilyl trifluoromethanesulfonate (TMSOTf

• . [40] described coupling of crude 1,3-oxathiolane precursor 20 with silylated acetylcytosine utilizing TMSOTf as a Lewis acid, which gave a mixture of α- and β-anomers (1:2 ratio) of 81 (Scheme 30). The mixture of anomers was further separated by silica gel column chromatography. (+)-BCH-189 (1a) and

• synthetic procedure to access (−)-BCH-189 (1). Compound 20a was synthesized from ʟ-gulose derivative 3f (Scheme 6). The glycosylation reaction of oxathiolane intermediate 20a with silylated N4-acetylcytosine in dichloroethane using TMSOTf as a catalyst gave 81a as a β/α 2:1 mixture (Scheme 31). Separation

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• trifluoromethanesulfonate (TMSOTf) is superior to BF3⋅OEt2 as a catalyst in both dichloromethane (DCM) and acetonitrile (ACN), while ACN appears to be the better choice as solvent. A particularly good yield was obtained with TMSOTf in ACN. Also, it is evident that an increase in the amount of TMSN3 and Lewis acid did not

• provide any significant change in yield. Myers and co-workers described BF2OTf⋅OEt2 as a powerful Lewis acid formed in situ from BF3⋅OEt2 and TMSOTf, which was especially efficient in ACN [45]. This prompted us to investigate the application of BF2OTf⋅OEt2 in our synthesis (Table 1, entries 9–11). As we

• expected, the reaction in ACN was the most efficient, while in DCM, there were no significant differences between BF2OTf⋅OEt2 and TMSOTf. Lowering reaction temperature in ACN (Table 1, entry 10) increased the yield of the tetrazole 13. Again, an increased amount of TMSN3 and catalyst did not provide any

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• (1–3)-Xyl hexamer, an analogue of xylans found in algae cell-walls [206]. TMSOTf promoted the glycosylation of the Bz-protected disaccharide acceptor with the Bz-protected tetrasaccharide trichloroacetimidate donor. Although not yet reported, the authors suggested that this method can be extended to

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ), which has been shown to display memory-enhancing properties and was also effective for the treatment of cognitive disorders. The reaction of the N-tert-butanesulfinyl imine (SS)-119 with trimethylsilyl enol ether derived from acetophenone 123 in the presence of TMSOTf at low temperature, produced β

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• yields (1–72%) (Scheme 8B) [26]. Another variant using trimethylsilyl trifluoromethanesulfonate (TMSOTf) under classical heating conditions in 1,2-dichloroethane has been recently described by Kim et al. [27] to produce phenformin analogs with variable, but generally fairly good yields (4–100%) (Scheme 9

• alkylcyanoguanidines by TMSOTf was also tested by Kim et al. (Scheme 18) [27]. This method proved highly efficient to produce diversely substituted N1,N5-alkylbiguanides as phenformin derivatives, with yields generally excellent (≥94%). Interestingly, the addition of acetyl hydrazide was also tried and delivered the

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• Sakurai macrocyclization/dimerization strategy to produce 150 in the presence of TMSOTf, as shown in Scheme 35 [70]. Hoye and Hu utilized camphor sulfonic acid (CSA) to construct a cis-2,6-disubstituted tetrahydropyran 153 via an intramolecular Sakurai cyclization reaction between the enal 151 and an

• and trans-2,6-DHP, respectively, was reported by a [4 + 2]-annulation strategy. The authors utilized crotylsilanes syn-170 and anti-170, respectively, with an aldehyde 171 in the presence of TMSOTf to deliver different DHPs 172 (Scheme 41) [76]. For syn-170, the reaction went via the favored boat-like

• hydroxyallylsilane 186 with excellent enantioselectivity (Scheme 45) [83][84][85]. This, upon further reaction with another aldehyde in the presence of TMSOTf, gave 2,6-disubstituted 4-methylenetetrahydropyran 187. This strategy was utilized for the synthesis of bryostatin and (+)-dactyloide analogs [86][87][88

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• have reported the TMSOTf-catalyzed synthesis of highly substituted imidazoles from α-azidochalcones under mild conditions [65]. As a sequel, the synthesis of oxazoles with an arylimino substituent has been accomplished in this work. The biologically important arylimino group [66][67][68][69] integrated

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• ). The 3-hydroxy group in 5 was then protected as a Nap ether through a TMSOTf-catalyzed one-pot reductive naphthylmethylation process [17][18], by which free hydroxy groups were first trimethylsilylated in situ with hexamethyldisiloxane ((TMS)2O) before being naphthylmethylated by treatment with 2

• -naphthaldehyde, trimethylsilyl trifluoromethanesulfonate (TMSOTf), and triethylsilane (Et3SiH) [17][19]. On a 10 g scale, the protected methyl ester 6 could be purified by recrystallization followed by filtration to remove the major byproduct 2-methylnaphthalene. Subsequent saponification of the methyl ester 6

• -protected (R)-3-hydroxytetradecanoic acid (7). Conditions: (a) Meldrum's acid, pyridine, CH2Cl2, 0 °C; (b) CH3OH, reflux, 77% over two steps; (c) (R)-Ru(OAc)2(BINAP), H2, CH3OH, 65 °C, 98%; (d) NapCHO, TMSOTf, (TMS)2O, Et3SiH, THF, 0 °C; (e) LiOH, THF, H2O, 65 °C, 78% (over two steps). Synthesis of

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