%0 Generic %A Jiménez-Osés, Gonzalo %A Aydillo, Carlos %A Busto, Jesús H. %A Zurbano, María M. %A Peregrina, Jesús M. %A Avenoza, Alberto %D 2014 %T Influence of Amino Acid Stereocenters on the Formation of Bicyclic N,O‑Acetals %U https://acs.figshare.com/articles/dataset/Influence_of_Amino_Acid_Stereocenters_on_the_Formation_of_Bicyclic_i_N_i_i_O_i_Acetals/2312800 %R 10.1021/jo500015c.s002 %2 https://acs.figshare.com/ndownloader/files/3950434 %K diastereoselective %K chiral building blocks %K acid derivatives %X In recent years, our group has reported the highly diastereoselective acid-catalyzed N,O-acetalization/intramolecular transcarbamoylation cascade of reactions between protected α-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 α-position. We now evaluate the scope of the reaction with related non-natural α-amino acid derivatives. A combined experimental and theoretical study reveals the key influence of the α-carbon substitution (serine versus α-methylserine) and the relative configuration of α-/β-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. %I ACS Publications