Access to 8-Azachromones via Activation of C–H in N-Oxides

Abstract

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or AcO activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

2-(Substituted amino)-8-azachromones from 4,6-Diaryl-2-pyridones: A Synthetic Strategy toward Compounds of Broad Structural Diversity

“…We took advantage of this insolubility to isolate and characterize 1a as potassium salt 1a-K in a simplified reaction work-up. According to the same procedure, we prepared 3-cyano-2-pyridones 1b-e-K diversely substituted in the para position of the 4-phenyl ring (Table 1, entries [6][7][8][9].…”

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

“…The key intramolecular O ‐heteroarylation reaction was achieved by PyBroP‐ or Ac 2 O‐activated nucleophilic addition of enolates to the C2 position of N ‐oxides 331 (Scheme 99). [132] …”

“…The key intramolecular O-heteroarylation reaction was achieved by PyBroP-or Ac 2 O-activated nucleophilic addition of enolates to the C2 position of N-oxides 331 (Scheme 99). [132] Emery's team reported a method for the metal-free synthesis of furo [2,3-b]pyridines 336 (also known as 7-azabenzofuran) at ambient temperatures (Scheme 100). [133] 3-Ethylcarboxylate pyridine N-oxides 335 react with acyl chloride or anhydride to form ethyl acetoacetate derivatives 337, which undergo carbonyl deprotonation and cyclization to generate 338.…”

One-Pot Selective Saturation and Functionalization of Heteroaromatics Leading to Dihydropyridines and Dihydroquinolines

“…Thanks to the pioneering studies by Buchwald and You, C–C-bond-forming dearomatization without preactivation of the heterocycle has emerged as an attractive alternative to traditional dearomatization. Inspired by the impressive advances, and as a continuation of our research on the efficient synthesis of druglike nitrogen heterocycles, we describe herein a regioselective difunctionalization of pyridines and quinolines, providing convenient access to DHPs and DHQs substituted by a trifluoromethyl ketone under mild conditions and in one pot (Scheme D). Besides, the prepared DHPs and DHQs are trifluoromethyl ketones, which would have great potential in both synthetic and medicinal chemistry …”