文摘
In recent years, our group has reported the highly diastereoselective acid-catalyzed N,O-acetalization/intramolecular transcarbamoylation cascade of reactions between protected 伪-amino acid derivatives (Ser and Thr) and tetramethoxyalkanes. The resulting oligocyclic N,O-acetals have been used as excellent chiral building blocks for asymmetric transformations such as diastereoselective alkylation of the 伪-position. We now evaluate the scope of the reaction with related non-natural 伪-amino acid derivatives. A combined experimental and theoretical study reveals the key influence of the 伪-carbon substitution (serine versus 伪-methylserine) and the relative configuration of 伪-/尾-carbons (threonine versus allo-threonine) in the thermodynamic stability of the products and, as a consequence, the stereochemical outcome of the reaction. Notably, the complete diastereoselectivity achieved with natural amino acid precursors is completely lost with their non-natural analogues.