Selective mono-Claisen rearrangement of carbohydrate glycals. A chemical consequence of the vinylogous anomeric effect.

The mono-Claisen rearrangement of carbohydrate glycals is demonstrated to be a synthetically useful and mechanistically significant reaction. Addition of per-O-acetyl glycal-tert-butyldimethylchlorosilane mixture to lithium diisopropylamide generated a bis (or tris)ketenesilylacetal which, upon heating, underwent smooth mono-Claisen rearrangement to provide a C-glycosyl compound after methylation. A second apparently similar Claisen rearrangement required significantly higher temperatures in all cases. Thus, similar hydroxy groups were differentiated without resort to selective protection. A stereoelectronic rationale based on the newly-introduced vinylogous anomeric effect (VAE) is put forth to explain the accelerated Claisen rearrangements of these glycals. Molecular orbital and resonance descriptions of the VAE are included, and the VAE is also used to rationalize ground-state conformational preferences of carbohydrate glycals. The C-glycosyl compounds produced by mono-Claisen rearrangement were suitable for Pd(0)-catalyzed allylic alkylations, providing an unusually facile entry into the pseudomonic acid-ring systems. A nine-step synthesis of a known precursor of pseudomonic acid C is reported.