Exploiting the Nucleophilicity of NH Imines: Synthesis of Enamides from Alkyl Azides and Acid Anhydrides

Abstract

The nucleophilicity of N-unsubstituted imines, which were generated from alkyl azides by a ruthenium-catalyzed reaction, was investigated in the reaction with acid anhydrides. The initial products were N-acylimines, which isomerized to the corresponding enamides. Heating or triethylamine facilitated the isomerization of N-acylimines that are stable at room temperature. A wide range of acyclic and cyclic enamides containing various functional groups was successfully synthesized under mild conditions. In addition to acetic anhydride, various acid anhydrides were applicable. From the reaction with cyclic anhydrides, enamides containing carboxylic acid group were obtained.

Synthesis of Enamides by Ruthenium‐Catalyzed Reaction of Alkyl Azides with Acid Anhydrides in Ionic Liquid

“…The yield of 4 a was only 32 % in the first attempt in THF (Table , entry 1). However, considering the scope limitation described in the previous report, it was an unexpected and promising result. This finding supports the idea that the catalytic activity of 2 for the generation of octan‐1‐imine was retained to some extent under conditions for acylation.…”

“…Although this is a one‐pot process under mild conditions, the use of an excess amount of Ti(O i Pr) 4 requires a complicated workup procedure to remove titanium waste from the reaction mixture. As an innovative method overcoming the problem of stoichiometric reductants or additives, our group developed the synthesis of enamides from alkyl azides and acid anhydrides that is based on Ru catalysis to transform alkyl azides into N−H imines (Scheme c) . Diruthenium complex 1 shown in Scheme c needs light to be activated, and the resulting activated species is deactivated by acetic acid.…”

“…The N−H imine is liberated from intermediate C in the presence of an external azide substrate. Then, acetic anhydride reacts with the in situ generated N−H imine to form an N ‐acetyl imine intermediate, which isomerizes to the corresponding enamide with the aid of triethylamine or by heating …”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…[183] Under ruthenium-catalyzed reaction conditions, benzylic azides were in situ converted into aromatic NÀ H ketimines 93. [184][185][186] The generated NÀ H ketimines were further taken for annulation with alkynes in the presence of Rh-catalyst. The reaction conditions were successfully employed on benzyl azides bearing alkyl, aryl, ether, ester, halogen and carbonyl functionalities to obtain yields up to 92%.…”

“…Under ruthenium‐catalyzed reaction conditions, benzylic azides were in situ converted into aromatic N−H ketimines 93 [184–186] . The generated N−H ketimines were further taken for annulation with alkynes in the presence of Rh‐catalyst.…”