The enantioselective synthesis of a[alpha],a[alpha],́b[beta],b[beta]-́tetrafluoroethylidene substituted carbohydrates

Abstract

The syntheses of a number of tetrafluoroethylidene substituted carbohydrates are disclosed. From a commercially available fluorinated building block chirality is introduced by way of an asymmetric dihydroxylation (AD). We also disclose the beginnings of work towards the synthesis of fluorinated chiral ligands designed for use in this AD. The chiral 1,2-diol obtained from the AD is selectively protected at either the primary or secondary alcohol to form the central intermediate our our syntheses. The functionalisation and subsequent cyclisation of these compounds are disclosed. To synthesise compounds with the tetrafluoroethylidene unit proximal to the anomeric centre we utilised a novel halogen-lithium exchange/cyclisation procedure. This reaction is shown to have wide scope being used to synthesise hexoses and pentoses in both their pyranose and hexose forms. The intermediate is also shown to take part in a radical addition/atom transfer/nucleophilic cyclisation sequence to form tetrafluoroethylidene substituted carbohydrates where the fluorinated substituent is remote from the anomeric centre. We also disclose the synthesis of a tetrafluoroethylidene substituted nucleoside and glycal.</p