Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides: A Synthetic and Mechanistic Study

Abstract

An 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 (TfO). 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 TfO-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.

Metal-Free Synthesis of 2-Fluoroalkylated Quinolines Using Polyfluoroalkanoic Acids as Direct Fluorine Sources

“…According to the above results, together with previous reports, a tentative pathway for the generation of 2-trifluoroalkylated quinolines was proposed as depicted in Scheme . Initially, trifluoroacetamide 13 was generated in situ from 2-vinylaniline and TFA.…”

A Novel Class of 7‐Membered Heterocyclic Compounds

“…Proton scavengers have been indeed observed to improve the general efficiency of amide activation reactions. [32] With suitable conditions in hand, we investigated if other substrates undergo this unusual reactivity (Scheme 3). First, a range of substituents in the α-position of the amide was investigated.…”

Synthesis and Applications of 9H‐Pyrrolo[1,2‐a]indole and 9H‐Pyrrolo[1,2‐a]indol‐9‐one Derivatives

“…The cyclization of [2‐(1 H ‐pyrrol‐1‐yl)phenyl](pyrrolidin‐1‐yl)methanones 129 could be also promoted by trifluoromethanesulfonic anhydride Tf 2 O (Scheme ) . The reaction scope of this intramolecular cyclization of amido‐pyrrole substrates afforded the corresponding tricyclic products 130 in excellent yields (18 examples, 82–97 % yield).…”