The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• trifluoromethanesulfonate (TMSOTf). This synthesis was conducted in a mixture of 2,2,2-trifluoroethanol (TFE) and dichloromethane [78]. The synthesized naproxen-containing diaryliodonium salt 67 was further used to modify the aromatic ring of naproxen methyl ester 68 (Scheme 27). Various functionalization reactions which

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• tumors PRCL PC3M and RXF 631L) with IC50 values of about 2.8 mg mL−1 and IC70 values of >3 mg mL−1. In 2005, our group developed a synthesis of indigo-N-glycosides (Scheme 3) [19]. The TMSOTf-mediated reaction of readily available N-benzylindigo (1b) with tri-O-pivaloyl-α-ʟ-rhamnosyl trichloroacetimidate

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• was significantly enhanced when refluxing in DMF with a catalytic amount of AlCl3 compared to the reaction in clear DMF (Table 1, entries 7–9). Other Lewis acids were not as effective, except for a combination of DMSO/TMSOTf (Table 1, entry 4). The application of AcOH/PPA for the synthesis of 5

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• chromones requires the action of trimethylsilyl trifluoromethanesulfonate (TMSOTf) which is a relatively expensive reagent. In future studies, especially the chemistry of 3-methoxalyl- and 3-nitrochromones should be further explored. In case of the methoxalyl derivatives, so far not many synthetic

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• , t-BuOK), with Hoffer’s chlorosugar (13) in the presence or absence of Lewis acid (TMSOTf, SnCl4) did not result in formation of a reasonable amount of appropriate nucleoside (Scheme 2). Nucleobase 12 could not be converted to the corresponding silylated derivative by using HMDS, TMSCl or a

• , providing a linear nucleoside 17 as a mixture of two anomers, which were successfully separated on a silica gel column. Finally, cyclisation of a linear nucleoside was accomplished in the presence of a catalytic amount of the Lewis acid TMSOTf in 64% yield. Unfortunately, cyclisation was accompanied by

• ) H2, Pd/C, CH2Cl2, rt, 3 h; b) chloroacetyl chloride, Et3N, 0 °C, overnight, 38% yield; iii) 10, HMDS, DCE, 90 °C, 24 h, 32% yield; iv) TMSOTf, ACN, 40 °C, 2.5 h, 64% yield. i) H2, 5% Pd/CaCO3/3% Pb, Et3N, CH2Cl2, rt, 1.5 h, 34% and 21% yield for α- and β-anomer of 18, respectively; ii) H2, 10% Pd/C

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