%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