Journal of Organic Chemistry 2006-04-28

4,6-O-[1-cyano-2-(2-iodophenyl)ethylidene] acetals. improved second-generation acetals for the stereoselective formation of beta-D-mannopyranosides and regioselective reductive radical fragmentation to beta-D-rhamnopyranosides. scope and limitations.

David Crich, Albert A Bowers

Index: J. Org. Chem. 71(9) , 3452-63, (2006)

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Abstract

The [1-cyano-2-(2-iodophenyl)]ethylidene group is introduced as an acetal-protecting group for carbohydrate thioglycoside donors. The group is easily introduced under mild conditions, over short reaction times, and in the presence of a wide variety of other protecting groups by the reaction of the 4,6-diol with triethyl (2-iodophenyl)orthoacetate and camphorsulfonic acid, followed by trimethylsilyl cyanide and boron trifluoride etherate. The new protecting group conveys strong beta-selectivity with thiomannoside donors and undergoes a tin-mediated radical fragmentation to provide high yields of the synthetically challenging beta-rhamnopyranosides. The method is also applicable to the glucopyranosides when high alpha-selectivity is observed in the coupling reaction and alpha-quinovosides are formed selectively in the radical fragmentation step. In the galactopyranoside series, beta-glycosides are formed selectively on coupling to donors protected by the new system, but the radical fragmentation is unselective and gives mixtures of the 4- and 6-deoxy products. Variable-temperature NMR studies for the glycosylation step, which helped define an optimal protocol, are described.