10.1021/jo500015c.s001
Gonzalo Jiménez-Osés
Gonzalo
Jiménez-Osés
Carlos Aydillo
Carlos
Aydillo
Jesús
H. Busto
Jesús
H.
Busto
María M. Zurbano
María M.
Zurbano
Jesús M. Peregrina
Jesús M.
Peregrina
Alberto Avenoza
Alberto
Avenoza
Influence of Amino Acid Stereocenters
on the Formation
of Bicyclic <i>N</i>,<i>O</i>‑Acetals
American Chemical Society
2014
diastereoselective
chiral building blocks
acid derivatives
2014-03-21 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Influence_of_Amino_Acid_Stereocenters_on_the_Formation_of_Bicyclic_i_N_i_i_O_i_Acetals/2312806
In
recent years, our group has reported the highly diastereoselective
acid-catalyzed <i>N</i>,<i>O</i>-acetalization/intramolecular
transcarbamoylation cascade of reactions between protected α-amino
acid derivatives (Ser and Thr) and tetramethoxyalkanes. The resulting
oligocyclic <i>N</i>,<i>O</i>-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 <i>allo</i>-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.