Addition of electrophilic radicals to 2-benzyloxyglycals: Synthesis and functionalization of fluorinated α-C-glycosides and derivatives

Abstract

A new method for the synthesis of fluorinated α-C-glycosides is described. The reactions between highly electrophilic radicals (fluorinated or unfluorinated) and a 2-benzyloxyglucal or galactal provide 2-keto-D-arabino- or 2-keto-D-lyxo-hexopyranosides through an addition/fragmentation process. Sodium borohydride mediated or Meerwein-Ponndorf-Verley (MPV) reduction of these compounds provides α-C-glycosides that feature appropriate anchoring groups for further synthetic elaboration. The presence of CF2CO 2iPr or CF2Br groups at the pseudo-anomeric position allows efficient reduction/olefination or Br/Li-exchange/nucleophilic-addition sequences. These transformations open the way for the synthesis of fluorinated C-glycosidic analogues of glycoconjugates. Go radical! The reactions between highly electrophilic radicals and a 2-benzyloxyglucal or galactal provide 2-keto-hexopyranosides. Reduction of these compounds affords substituted α-C-glycosides, featuring groups such as CF2CO2R or CF2Br, which allow further synthetic elaboration (see scheme). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.