Construction of the DEF-Benzoxocin Ring System of Nogalamycin and Menogaril via a Reductive Heck Cyclization

Construction of the DEF-ring system of nogalamycin and menogaril has been achieved with a novel reductive Heck cyclization approach. Our strategy exploited the stereoelectronic preferences dictated by the anomeric effect for introduction of an O-glycosidic bond in order to direct the introduction of a bridging C-glycosidic bond with the desired stereochemistry. Our strategy relied upon a stereoselective O-aryl glycosylation reaction and a highly efficient selenoxide elimination to provide the key substrate for study of the reductive Heck cyclization reaction. The cyclization proceeded smoothly under the optimized conditions, in a yield comparable to that achieved in our previously reported model study.