Palladium-catalyzed aryl-amidation. Synthesis of non-racemic N-aryl lactams

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

“…In general, there are a wide variety of protocols describing the metal-mediated arylation of amines [17,37,39], amides [38], imides [38], imidazoles [14,37,40], benzimidazoles [40–41], sulfonamides [38], pyrroles [42] and lactams [43]. The three typical methods for N-arylation have been extensively reviewed concerning scope and limitation of these reactions [4,44–48].…”

Studies on pyrrolidinones. On the application of copper-catalyzed arylation of methyl pyroglutamate to obtain a new benzo[de]quinoline scaffold

“…The mixture was stirred under nitrogen atmosphere at 60 C for 15 h. The residue was separated by chromatography on silica gel, eluting EtOAc/nheptane 5/5 to generate pure product 14 as a brilliant white powder in 95% yield; mp 91 C, TLC R f (EtOAc/n-heptane 5/5)¼0. 21 (15). The general procedure was followed using DL-methyl pyroglutamate (2.8 g, 20 mmol), 2-methylbromobenzene (2.3 mL, 20 mmol), cesium carbonate (12.7 g, 39 mmol), copper (I) iodide (1.9 g, 9.7 mmol), and DMEDA (2.1 mL, 20 mmol) in dioxane (50 mL).…”

“…The mixture was stirred under nitrogen atmosphere at 60 C for 8 h. The residue was separated by chromatography on silica gel, eluting EtOAc/n-heptane 5/5 to generate pure product 18 as a white powder in 81% yield; TLC R f (EtOAc/n-heptane 5/5)¼0.18; 1 H NMR (CDCl 3 , (20). The general procedure was followed using DL-methyl pyroglutamate (2.0 g, 14 mmol), 2-bromopyridine (1.6 mL, 17 mmol), cesium carbonate (9.1 g, 28 mmol), copper (I) iodide (1.3 g, 7 mmol), and DMEDA (1.5 mL, 14 mmol) in dioxane (20 mL (21). The general procedure was followed using DL-methyl pyroglutamate (7.0 g, 49 mmol), a-bromonaphthalene (6.1 mL, 49 mmol), cesium carbonate (31.9 g, 98 mmol), copper (I) iodide (4.7 g, 24.5 mmol), and DMEDA (5.3 mL, 49 mmol) in dioxane (70 mL).…”

“…Due to the high cost of palladium which invites to less expensive alternatives, and limitations which still remain in the palladium-catalyzed arylation of amides, 18 we chose to use the copper-catalyzed Ullmann-Goldberg arylation of amides. 17,[19][20][21] While the Ullmann reaction is sometimes performed with a ligand and additive free conditions, 22 success in arylation of amides and lactams is often highly dependent on the right combination of the ligand, the base, and the solvent used. 20 The copper-catalyzed coupling of pyroglutamic derivatives with aromatic halides is scarcely documented (Table 1).…”

N-Aryl Lactams by Regioselective Ozonation of N-Aryl Cyclic Amines

“…N -aryl lactams are important precursors in the synthesis of alkaloids [1] and of various biologically active compounds. [2] Their chemesthetic activity has been also recently demonstrated [3].…”