Abstract
A 2,3,4‐tri‐O‐pivaloylated β‐D‐galactopyranosyl azide bearing a hydroxy‐functionalized spacer unit at the C‐6 position of the galactose was synthesized and immobilized on the solid phase by using a polymer‐bound chlorosilane. The azide was reduced to the corresponding galactopyranosylamine, which served as a versatile chiral auxiliary in highly diastereoselective Ugi four‐component condensation reactions at ambient temperature. Fluoride‐induced cleavage from the polymeric support furnished N‐glycosylated N‐acylated α‐amino acid amides. The reaction of the immobilized galactosylamine with aldehydes gave rise to the corresponding aldimines, which underwent a domino Mannich–Michael condensation reaction with Danishefsky's diene at ambient temperature to yield 2‐substituted 5,6‐didehydropiperidin‐4‐ones on the solid phase. Subsequent cleavage with tetra‐n‐butylammonium fluoride delivered the N‐glycosylated products in high yields, purities, and diastereoselectivities. A chemoselective 1,4‐hydride addition to the polymer‐bound dehydropiperidinones was achieved in the presence of the bulky oxygenophilic Lewis acid methylaluminum [bis(2,6‐di‐tert‐butyl‐4‐methylphenoxide)]. The conjugate addition of cyano‐modified Gilman reagents to the immobilized dehydropiperidinones furnished 2,6‐cis‐substituted piperidine derivatives as the major diastereomers that were isolated after cleavage from the support.