Michael Acceptor, Masked Aldehyde and Leaving Group in a Single Intermediate: Unorthodox Approach to Enantiopure Saturated Aza‐Heterocycles from a Multifunctional Glyco‐Substrate

A single carbohydrate-derived molecule consisting of a masked aldehyde, a Michael acceptor and a number of cleavable bonds has been designed. The adducts generated from this Michael acceptor and a series of β-dicarbonyl compounds and related reagents after acid treatment afforded a new class of furo[2,3-c]piperidine, furo[2,3-d]azepine and oxa-aza-tricyclic scaffolds to form up to three fused rings and seven stereocenters. In-built chirality centers of the sugar derivative controlled the diastereoselectivity of formation of all new stereocenters without the requirement of any external reagent for asymmetric induction. Simple variations of reaction conditions and reagents afforded diverse polycyclic aza-ring systems containing six and seven membered nitrogen heterocycles, which are privileged structures in numerous pharmaceuticals. A less known but unique 1,2-sulfone migration generated seven membered skeleton. In essence this work manifests the power of carbohydrate-based synthetic chemistry for generating complex oxa-aza molecular scaffolds with stereochemical diversity.