Unprecedented formation of 8(R),5′-O-cycloribonucleosides through a triflation reaction of purine ribonucleosides

5′-Chloro-5′-deoxy-2′,3′-O-isopropylidene-6-fluoro nebularine

“…In detail, in the 1 H-NMR spectrum the 5 -H a,b protons resonated as two doublets of doublets at 3.81 and 3.70 ppm, whereas in the 13 C-NMR spectrum the 5 C carbon resonated at 43.4 ppm. These data were consistent with the presence of a 5 C-Cl bond [20]. In the HMBC spectrum, the 2-H proton at 8.69 ppm correlated with the C6 purine carbon at 159.9 ppm, which appeared as a doublet with J = 261.8 Hz, as a consequence of the coupling with the F atom.…”

“…As previously observed by Ashton and Scammells [19], we noted (TLC monitoring in n-hexane/AcOEt; 1:1) that the process led not only to the formation of the expected fluorinated product 5a with Rf = 0.48 (Scheme 1), but also to the formation of the bisfluorinated product 5b with Rf = 0.42, as a consequence of the substitution in species 4 of the C6 chlorine atom by a fluoride ion. The main component with Rt = 24.2 min was instead identified as the known 5′-chloro-5′-deoxy-2′,3′-O-isopropylidene-6-chloro nebularine 9 [20].…”

“…The main component with Rt = 24.2 min was instead identified as the known 5 -chloro-5 -deoxy-2 ,3 -O-isopropylidene-6-chloro nebularine 9 [20].…”

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

“…Typically, such reactions require the use of high-boiling, dipolar aprotic solvents and anionic nucleophiles under anhydrous conditions at elevated temperatures (up to 150 °C). Competing intramolecular cyclisation reactions between both purine and pyrimidine nucleobases and (especially) the 5′-position of the (deoxy)ribofuranoside are frequently observed during both activation [7] and subsequent displacement reactions [8–9]. This competition confounds the kind of systematic analysis developed recently by Hale and co-workers for sulfonate displacement from furanosides [10] and convoluted optimisations of reaction conditions and nucleoside substrate (e.g., the leaving group [11] or nucleobase protection [12]) are therefore often required.…”

CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF3SO2Cl

“…Anecdotally, CF 3 SO 2 Cl could also be involved in the chlorination of ortho -lithiated veratrole [ 53 ]. It also allowed the surprising formation of a 5’-chloro nucleoside, when used in an attempt to prepare the corresponding 5’-OTf nucleoside [ 54 ]. Moreover, considering the excellent selectivity of the combination CF 3 SO 2 Cl/Et 3 N towards the chlorination of substrates displaying a hydroxy group, the reaction could be further exploited for cascade chlorination/cyclisation processes.…”