Synthesis of bicyclic 2-pyridones by regioselective annulations of heterocyclic ketene aminals with anhydrides

Abstract

An efficient strategy for the synthesis of substituted bicyclic 2-pyridones is developed. The proposed approach is based on the regioselective N-acylation of heterocyclic ketene aminals (HKAs) with methacrylic anhydride or crotonic anhydride.

Amination of Bridging Vinyliminium Ligands in Diiron Complexes: C–N Bond Forming Reactions for Amidine-Alkylidene Species

“…A remarkable difference is that the hydrogen migration observed in the reaction with primary amines is no longer accessible because of deprotonation of NHMe 2 . It is worth underlining the peculiar nature of the organic moiety generated by amine addition: N,N-ketene aminals are a known, but relatively uncommon, species, except for heterocyclic ketene aminals (HKAs), which find application as versatile synthetic building blocks in the construction of heterocyclic compounds …”

Efficient Synthesis of Bicyclic 2‐Pyridinones and 6‐Amino‐2‐pyridinones by the Regioselective Cycloaddition of Nitro Ketene Aminal with 3‐Hydroxy‐2‐aryl‐acrylate

“…Owing to their biological properties and interesting structures, this core skeleton has inspired synthetic chemists to develop various novel synthetic methods. [18][19][20][21] General methods for the synthesis of bicyclic 2pyridinone s are based on the cyclocondensation of ketenaminals, [22] the addition of diamines to 1-halo or thiomethylpyridones, [23] and the addition of diamines to cyanobutenoic esters, [24] and so on. [19,[25][26][27] In organic synthesis, many small molecules containing multiple functional groups are important since they can be used to efficiently construct complex structures.…”

“…[18][19][20][21] General methods for the synthesis of bicyclic 2pyridinone s are based on the cyclocondensation of ketenaminals, [22] the addition of diamines to 1-halo or thiomethylpyridones, [23] and the addition of diamines to cyanobutenoic esters, [24] and so on. [19,[25][26][27] In organic synthesis, many small molecules containing multiple functional groups are important since they can be used to efficiently construct complex structures. One such molecule is 3-hydroxy-2-aryl acrylate (Figure 2), which has one nucleophilic and two electrophilic carbon centers.…”

“…They have been found in a wide range of natural products [15–17] and have shown interesting medicinal properties, such as antitumor (A58365B), pilus inhibitors (FN075), and kinase inhibitors (Duvelisib) (Figure 1). Owing to their biological properties and interesting structures, this core skeleton has inspired synthetic chemists to develop various novel synthetic methods [18–21] . General methods for the synthesis of bicyclic 2‐pyridinone s are based on the cyclocondensation of ketenaminals, [22] the addition of diamines to 1‐halo or thiomethylpyridones, [23] and the addition of diamines to cyanobutenoic esters, [24] and so on [19,25–27] …”