jo500015c_si_003.cif (14.69 kB)
Influence of Amino Acid Stereocenters on the Formation of Bicyclic N,O‑Acetals
dataset
posted on 2014-03-21, 00:00 authored by Gonzalo Jiménez-Osés, Carlos Aydillo, Jesús
H. Busto, María M. Zurbano, Jesús M. Peregrina, Alberto AvenozaIn
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.