Platinum-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars with O-Nucleophiles. Convenient Synthesis of 2-C-Branched Carbohydrates

A new reaction is described catalyzed by Zeise's dimer that allows for ring opening of 1,2-cyclopropanated sugars with O-nucleophiles to give 2-C-branched carbohydrates. A number of O-nucleophiles can participate in the ring opening including alcohols, phenols, and water. A wide range of alcohols has been employed giving 2-C-branched glycosides ranging from simple methyl glycosides to more complex disaccharides. A very high diastereoselectivity is obtained at the newly formed C-1 stereocenter. The α-glycoside, favored by the anomeric effect, is always the major product in the ring opening with alcohols regardless of the stereochemistry of the starting cyclopropane. When electron-rich phenols are employed as O-nucleophiles, rearrangement to the glycosyl arene has been observed. In general, the ring opening occurs readily with unsubstituted sugar cyclopropanes to give 2-C-methyl carbohydrates. However, cyclopropanes with ester or alkyl substituents are significantly less reactive and some even completely inert to ring opening. When the ring opening is carried out with PdCl2(PhCN)2 catalyst, a Ferrier-type rearrangement occurs, giving 2,3-unsaturated glycosides containing a 2-C-alkyl substituent.