Amphipathic 1,3-oxazolidines from N-alkyl glucamines and benzaldehydes: Stereochemical and mechanistic studies

Construction of enantiopure carbohydrate conjugates incorporating heterocyclic fragments is often hampered by the necessity of protection/deprotection protocols and multistep routes. Here we show the preparation and structural features of a broad series of chiral 1,3-oxazolines and 1,3-oxazines embedded in a hydrophilic chain based on glycamines, which bypass the disadvantages associated with labile anomeric positions. These substances, however, interconvert in solution and show dynamic equilibria that can be altered by crystallization. A variety of substitution patterns at the heterocyclic moiety disclose the structural and stereochemical relationships. Equilibria monitored by NMR experiments and aided by DFT calculations provide data on kinetic and thermodynamic stability. The reaction proceeds via the intermediacy of iminium ions as a unifying element controlling the steric outcome.