Influence of Amino Acid Stereocenters
on the Formation
of Bicyclic <i>N</i>,<i>O</i>‑Acetals
Gonzalo Jiménez-Osés
Carlos Aydillo
Jesús
H. Busto
María M. Zurbano
Jesús M. Peregrina
Alberto Avenoza
10.1021/jo500015c.s001
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.
2014-03-21 00:00:00
diastereoselective
chiral building blocks
acid derivatives