DOUBLE STEREODIFFERENTIATION IN THE LEWIS-ACID PROMOTED C-GLYCOSIDATION OF ACTIVATED GLYCALS WITH CHIRAL (E)-CROTYLSILANES

Lewis acid promoted C-glycosidation reactions of activated glycals wit h chiral (E)-crotylsilanes were found to be highly regio- and diastere oselective. The reactions of chiral silane reagents proceed with the f ormation of a new C-C bond at C6 of the pyran ring with concomitant mi gration of C5-C6 double bond to the C5-C4 position of the pyran ring. The reactions are highly diastereoface selective as the crotylsilane ( carbon nucleophile) approaches the derived oxonium ion anti to the C2 substituent. The stereochemical relationship between the methyl bearin g stereogenic center at the C2 position and the C6 position of the pyr an is defined by the chirality of the silane reagent as the configurat ion of the C-Si bond determines the stereochemistry of the C1'-methyl group. Our experiments have shown that the pair wise combination of th e glycals with the chiral silane reagents give high levels of selectiv ity resulting from the existence of strong stereochemical control elem ents within each reaction component. The topological bias is principal ly controlled by stereoelectronic effects of the pyran oxonium ion and by the facial bias of the silane reagent. Levels of diastereoselectiv ity ranged from 10 to 30 : 1 (alpha/beta ratio) in the presence of BF3 . OEt2 which was found to be with TMSOTf the most effective Lewis aci ds to promote the reactions. Consistent with the behavior of these sil ane reagents and an anti-S-E' mechanism, of the four possible diastere omers only the two isomers derived from the Cl' stereochemical relatio nship are detectable. (C) 1997 Elsevier Science Ltd.