α-C-Glycosides via syn Opening of 1,2-Anhydro Sugars with Organozinc Compounds in Toluene/n-Dibutyl Ether

Abstract

The diastereoselective addition of organozinc species to 1,2-anhydro sugars in toluene/n-dibutyl ether solvent is reported. Compared to the existing methods, the reaction proceeds at 0 °C, and only a slight excess of nucleophile is required to achieve good yields. Scope was assessed with different O-protected glycals along with various nucleophiles (aryl, alkynyl). This methodology was applied to the synthesis of the α-anomer of canagliflozin.

A concise and practical stereoselective synthesis of ipragliflozin L-proline

“…The hydroxy group in 2-position of 8 was protected by pivaloyl chloride to generate 5’ . In the 1 H NMR, the coupling constant of the anomeric proton for 6’ was 4.0 Hz, while the corresponding constant for 6 was 9.6 Hz, which was similar with those of canagliflozin [20]. …”

“…Pure compounds of 5’ and 6’ were prepared for the analytical references (Scheme 4). Compound 4a was converted to the corresponding arylzinc derivative in situ, and the latter coupled with pivaloyl-protected 1,2-anhydroglucal 7 [20] to get the α- C -arylglucoside 8 . After removing the protecting groups in the presence of sodium methoxide, the α-anomer 6’ of ipragliflozin was obtained.…”

Homogeneous Catalysis: A Powerful Technology for the Modification of Important Biomolecules

“…Epoxide derivatives that were derived from glycals were also used as precursors for the synthesis of C ‐aryl glycosides . A highly diastereoselective opening of sugar 1,2‐epoxides with aryl zinc nucleophiles that were derived from the corresponding boronic acids and aryl iodides was demonstrated for the synthesis of C ‐aryl glycosides …”

“…[41] A highly diastereoselective openingo fs ugar 1,2-epoxides with aryl zinc nucleophilest hat were derived from the corresponding boronic acids and aryl iodidesw as demonstrated for the synthesis of C-aryl glycosides. [42] An efficient ruthenium(III)Àchloride-catalyzed synthesis of Cand O-glycosides 42 from the corresponding glycals 40 was recently described by Kashyap and co-workers. [43] The reactivity of the glycal derivatives with variousn ucleophiles, such as TMSÀCN, TMSÀH, TMSÀN 3 ,a llylÀTMS, and heterocycles, was studied (Scheme 11).…”

Ferrier Rearrangement of 1,2-Dihydropyrans with Organozinc Species in Toluene/n-Dibutyl Ether

“…8 We recently reported the catalyst-free diastereoselective synthesis of both α-and β-C-glycosides upon addition of a stoichiometric amount of zinc species in toluene/n-dibutyl ether to either glycoside bromides 9 or glycal epoxides. 10 The choice of solvent was also critical in this instance as the same reactions could not be observed in THF in both cases. Encouraged by these results and the unexpected reactivity of the aryl zinc species, we wished to evaluate the scope of the Ferrier rearrangement in a toluene/ndibutyl ether solvent mixture.…”