Copper-catalyzed aerobic oxidation protocol

II. First Generation Copper-Catalyzed Aerobic Oxidation Protocol... 

In this domino process, benzylamine was reacted with 2-halobenzamides through UUman-type coupling to yield the N-arylated intermediate 144 (Scheme 9.26). Then, a copper-catalyzed aerobic oxidation of 144 afforded the intermediate 145, which underwent an intramolecular nucleophilic addition of the amide to provide 146. Under the used reaction conditions, the intermediate 146 was oxidized to provide the desired products 147 in excellent yield. This protocol was also utilized by Fu et al. [80] by employing easily available a-amino adds instead of benzylamines to synthesize similar analogs. Very recently, the same method was applied for the synthesis of pyrimido[4,5-b]carbazoles by Nagarajan et al. [81]. 

Synthesis of 2-Hetarylquinazolin-4(3 -ones. The title compound has been employed in an efficient method for the synthesis of 2-hetarylquinazolin-4(3/f)-ones via a copper-catalyzed aerobic oxidative amination protocol (eq 16). ... 

In 2013, AstraZeneca researchers reported an application of copper-catalyzed aerobic dehydrogenative aromatization in the 120 g scale synthesis of AZD8926, a drug candidate for the treatment of central nervous system disorders (Scheme 5.6) [29]. This aerobic dehydrogenation process was determined to be superior for large-scale implementation over other oxidation methods, such as a benzoquinone-mediated oxidation and various protocols using peroxide-based... 

Copper(I)/TEMPO/NMI-catalyzed Aerobic Oxidation of Alcohols. A novel (bpy)Cu(I)/TEMPO/NMI system has been developed to achieve aerobic oxidation of 1° alcohols and avoid overoxidation. This system gave improved conversion relative to other aerobic oxidation protocols, demonstrating functional group tolerance for a diverse range of substrates bearing aliphatic, aryl, alkenyl, alkynyl, halides, as well as 0-, N-, and 5 -heteroatoms (eq 28). In the presence of unprotected 2° alcohols, 1° alcohols undergo selective oxidation (eq 29). ... 

In 2011, Sanford et al. developed an elegant Pd(II)-catalyzed, pyridine-directed aerobic olefination of C(sp )-H bonds. The use of air as an external oxidant renders this protocol very promising. It constitutes an extremely rare example of Pd(II)-catalyzed aerobic C(sp )-H bond functionalization in the absence of copper salts additives. The resulting cyclic pyridinium salt can easily afford 6,5-iV-fiised bicyclic framework or alkene product under reductive conditions or organic base. 

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