The well-known epoxide-Ritter reaction
generally affords oxazolines
with poor to average regioselectivity. Herein, a mechanism-based study
of the less known diol-Ritter reaction has provided a highly regioselective
procedure for the synthesis of 1-vic-amido-2-esters
from either terminal epoxides or 1,2-diols via Lewis acid-catalyzed
monoesterification. When treated with a stoichiometric Lewis acid
catalyst (BF3), these diol monoesters form dioxonium cation
intermediates that are ring-opened with nitrile nucleophiles to form
nitrilium intermediates, which undergo rapid and irreversible hydration
to give the desired amidoesters. Diester byproduct formation is irreversible
and appears to occur through disproportionation of diol monoester.
With chiral epoxide starting materials, the formation of amidoester
occurs with retention of configuration and no apparent erosion of
optical purity as determined by single-crystal X-ray analyses and
chiral chromatography, respectively. The direct access to chiral vic-amidoesters is especially practical with regard to the
synthesis of antibacterial oxazolidinone analogues of the Zyvox antimicrobial
family.