jo7b03176_si_001.pdf (4.08 MB)
Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides: A Synthetic and Mechanistic Study
journal contribution
posted on 2018-01-22, 00:00 authored by Béla Mátravölgyi, Tamás Hergert, Erika Bálint, Péter Bagi, Ferenc FaiglAn efficient synthesis has been developed
for the preparation of
9H-pyrrolo[1,2-a]indol-9-ones (fluorazones)
from readily available anthranilic acid derivatives via a one-pot
amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration.
The cyclodehydration process is mediated by the activation of aromatic
tertiary amides by triflic anhydride (Tf2O). Comparison
of various benzo-substituents is shown to demonstrate the high functional
group tolerance of this transformation. In addition, study of the
reaction mechanism is also presented to unfold the exact role of the
applied base additive. Herein, as a first example, we report our findings
that Tf2O-mediated amide activation is obstructed by the
easy protonation of amides by the formed triflic acid during the activation
step. Additionally, it has been also proven that the base additive
is not involved in the transformation of O-triflyliminium
triflates into reactive species (e.g., nitrilium triflates) and is
only responsible to neutralize the superacid to avoid the protonation
of both the secondary or tertiary amides.