title: Influence of amino acid stereocenters on the formation of bicyclic N,O-acetals.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles , Los Angeles, California 90095-1569, United States.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Jiménez-Osés
authors.forename: Carlos
authors.initials: C
authors.lastname: Aydillo
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Busto
authors.forename: María M
authors.initials: MM
authors.lastname: Zurbano
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Peregrina
authors.forename: Alberto
authors.initials: A
authors.lastname: Avenoza
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D012694:Serine / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics; D013912:Threonine / Q000737:chemistry*
chemical_list: D000080:Acetals; D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013912:Threonine; D012694:Serine