Synthesis of C-glycosylarenes by way of internal reactions of benzylated and benzoylated carbohydrate derivatives

“Internal” C-glycosylarenes [ e.g., (2 R,3 S,3a S,9b R)-3,3a,5,9b-tetrahydro-3-methoxy- and -3,7-dimethoxy-2-methoxymethyl-2 H-furo[3,2- c][2]benzopyran] were prepared by intramolecular reactions of 2- O-benzyl derivatives of methyl 3,5-di- O-methyl- d-xylofuranoside ( 2) and their conversion into authentic C-glycosylated aromatic systems was investigated. The auxiliary benzylic linkage could not be cleaved by hydrogenolysis; isochroman derivatives { e.g., (3 S)-3,4-dihydro-3-[(1 R,2 R)-2-hydroxy-1,3-dimethoxypropyl]-5- methoxy-1 H-2-benzopyran} were obtained under these conditions. However, oxidation of the primary benzylic position with ruthenium tetraoxide gave the corresponding lactone {a dihydroisocoumarin derivative, e.g., (2 R,3 S,3a S,9b R)-2,3,3a,9b-tetrahydro-3,7-dimethoxy-2-methoxy-methyl-5 H-furo[3,2- c][2]benzopyran-5- one} which could be opened by saponification, thereby leading to a stereochemically unique C-glycosylbenzoic acid derivative. The same type of lactone was obtained directly from a derivative of 2 bearing a sufficiently reactive benzoyl group at O-2 (3,5-dimethoxybenzoyl); this process provides a useful approach to a heterocyclic system present in a variety of natural products. In related studies, the 2- O-phenyl substituent was found to be much less reactive than the 2- O-benzyl group in intramolecular Friedel-Crafts reactions of 2- O-substituted glycofuranosides. The first examples of successful internal C-arylation in the pyranoid series were achieved from 2- O-(3-methoxybenzyl)- d-mannopyranosides; the resulting “internal C-glycosides” {(2 R,3 S,4 S,4a S,10b S)-2,3,4,4a,6,10b-hexahydro-3,4,8-trimethoxy-2-methoxymethylpyrano [3,2- c][2]benzopyran and 3,4-bis(benzyloxy)-2-benzyloxymethyl-8-methoxy analog} contain a heterocyclic skeleton closely related to that of the natural product bergenin.