Isobutyl Nitrite‐Mediated Synthesis of Quinoxalines through Double C−H Bond Amination of N‐Aryl Enamines

Abstract

An efficient and metal-free double CÀH bond amination of N-aryl enamines using isobutyl nitrite (IBN) has been developed. This method enables the preparation of functionalized quinoxalines in good to excellent yields and tolerates a variety of N-aryl enamines with diverse functional substituents. Mechanistic studies revealed the presence of a key b-imino oxime ester intermediate. A quinoxaline derivative could be prepared from bcarbonyl ester in one-pot sequence on a gram scale. Finally, two important quinoxaline scaffolds were easily prepared in moderate yields over two steps.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…Specifically, Zhang and colleagues in 2014 reported that N -aryl enamines could react with nitromethane through an oxidative tandem nitrosation/cyclization sequence enabled by the KI/TBHP catalytic system, furnishing the metal-free synthesis of 3-trifluoromethylquinoxalines in a single step with high efficiency (Scheme a) . In a related synthesis, Mo, Pan, Su, and their co-workers utilized readily available iso -butyl nitrite (IBN) as a novel nitrogen reagent to construct C–N bonds and reported on a reaction between N -aryl enamines and IBN in the presence of Ac 2 O (Scheme b) . This process presumably involved the generation of the key β-imino oxime ester intermediate and subsequent 6πe-azacyclization.…”

“…637 In a related synthesis, Mo, Pan, Su, and their coworkers utilized readily available iso-butyl nitrite (IBN) as a novel nitrogen reagent to construct C−N bonds and reported on a reaction between N-aryl enamines and IBN in the presence of Ac 2 O (Scheme 393b). 638 This process presumably involved the generation of the key β-imino oxime ester intermediate and subsequent 6πe-azacyclization.…”

Activation of enamine by photoexcited organocatalyst assisted singlet oxygen: synthesis of oxazoles and quinoxalines

“…To confirm the presence of singlet oxygen, control experiments were carried out in the presence of 2.0 equiv. of 1 O 2 scavengers such as DABCO (1,4-diazabicyclo[2.2.2]octane), 26 TEMP (2,2,6,6-tetramethylpiperidine) 26 and NaN 3 27 under identical conditions as shown in Scheme 3. The formation of only a trace amount of the oxazole product 3a in all cases confirms the importance of singlet oxygen.…”

New Pd‐Mediated Cascade Reactions for Synthesis of Novel Functionalized 1,3‐Oxazole‐Linked Quinoxaline Amines

“…Recently, new methods have been developed for the synthesis of quinoxaline derivatives. Diverse functionalized quinoxalines have been synthesized by the reaction of aryl amines with β‐keto oximes or double C−H bond amination of N ‐aryl enamines using isobutyl nitrite (IBN) …”