46-O-1-Cyano-2-(2-iodophenyl)ethylidene Acetals. Improved Second Generation Acetals for the Stereoselective Formation of β-d-Mannopyranosides and Regioselective Reductive Radical Fragmentation to β-d-Rhamnopyranosides. Scope and Limitations

摘要

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 presence of a wide variety of other protecting groups by the reaction of the 4,6-diol with triethyl (2-iodophenyl)orthoacetate and trimethylsilyl triflate, followed by trimethylsilyl cyanide and boron trifluoride etherate. The new protecting group conveys strong β-selectivity with thiomannoside donors and undergoes a tin mediated radical fragmentation to provide high yields of the synthetically challenging β-rhamnopyranosides. The method is also applicable to the glucopyranosides when high α-selectivity is observed in the coupling reaction and α-quinovosides are formed selectively in the radical fragmentation step. In the galactopyranoside series, α-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.