Synthesis of Functionalized Isoquinolin‐1(2H)‐ones by Copper‐Catalyzed α‐Arylation of Ketones with 2‐Halobenzamides

Abstract

Copper is key: A concise route to isoquinolin-1(2H)-ones from simple and readily available starting materials is provided by an efficient copper-catalyzed annulation of ketones with 2-halobenzamides. The method is applicable to a wide range of ketones containing different functional groups furnishing the products in moderate to excellent yields.

From Quinoline to Quinazoline‐Based S. aureus NorA Efflux Pump Inhibitors by Coupling a Focused Scaffold Hopping Approach and a Pharmacophore Search

“…NH 3 in CH 3 CN to give amide 30 [42] in 95 % yield. By slightly modifying a procedure reported from Shi et al ., [43] a copper(I)‐catalyzed α‐arylation followed by C−N bond formation between 30 and 1‐(4‐propoxyphenyl)ethan‐1‐one afforded the isoquinoline derivative 31 , in moderate yield. Chlorination in refluxing POCl 3 gave 32 that immediately was reacted with 2‐(diethylamino)ethan‐1‐ol or 1‐piperidinethanol in presence of NaH and in dry THF to afford target compounds 9 a and 9 b .…”

Recent Developments in Inter- and Intramolecular Enolate Arylation

“…15 The method is compatible with a wide range of ketones containing different functional groups, such as substituted aromatic and heteroaromatic rings, and cyclic or aliphatic ketones, furnishing moderate to excellent yields of the corresponding products. The ability to tolerate halogen substituents (F, Cl, Br, and I) in the products increases the potential for further synthetic transformations.…”

Isoquinolone Syntheses by Annulation Protocols

“…H 2 Ocatalyzed cyclocoupling reaction of N-substituted ortho-iodo-benzamides with malononitrile afforded N-substituted-3-amino-4-cyano-isoquinolones in good to high yields, and malononitrile is used as C2 synthon [26]. The formation of functionalized isoquinolones by copper-catalyzed cyclocondensation of ketones with ortho-halobenzamides [27] or ortho-halobenzonitriles [28] through S N Ar reaction giving α-aryl ketones as the intermediates have also been reported (Scheme 5).…”