A New Class of Amide Ligands Enable Cu‐Catalyzed Coupling of Sodium Methanesulfinate with (Hetero)aryl Chlorides

Abstract

((2S,4R)‐4‐Hydroxy‐N‐(2‐methylnaphthalen‐1‐yl)pyrrolidine‐2‐carboxamide (HMNPC), an amide derived from 4‐hydroxy‐L‐proline and 2‐methyl naphthalen‐1‐amine, is a powerful ligand for Cu‐catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing for first time the metal‐catalyzed coupling of (hetero)aryl chlorides and NaSO2Me. A considerable number of (hetero)aryl chlorides worked well, providing the pharmaceutically important (hetero)aryl methylsulfones in good to excellent yields.

A Class of Amide Ligands Enable Cu-Catalyzed Coupling of (Hetero)aryl Halides with Sulfinic Acid Salts under Mild Conditions

“…Initially, we examined (2S,4R)-4-hydroxy-N-(2-methylnaphthalen-1-yl)pyrrolidine-2-carboxamide (L1, HMNPC), 14 the best ligand for Cu-catalyzed coupling reaction of (hetero)aryl chlorides and sodium methanesulfinate. It was found that under the action of 2 mol % CuI and L1, the reaction completed after 24 h at 100 °C to afford 1-methoxy-4-(phenylsulfonyl)benzene (2a) in 99% yield (entry 1).…”

“…Because CuI/ l -proline could not efficiently catalyze the coupling of (hetero)­aryl bromides and relatively bulky sodium benzenesulfinate, we chose the coupling of 4-bromoanisole with sodium benzenesulfinate as a model reaction to screen suitable ligands, and the results are summarized in Table . Initially, we examined (2 S ,4 R )-4-hydroxy- N -(2-methylnaphthalen-1-yl)­pyrrolidine-2-carboxamide ( L1 , HMNPC), the best ligand for Cu-catalyzed coupling reaction of (hetero)­aryl chlorides and sodium methanesulfinate. It was found that under the action of 2 mol % CuI and L1 , the reaction completed after 24 h at 100 °C to afford 1-methoxy-4-(phenyl­sulfonyl)­benzene ( 2a ) in 99% yield (entry 1).…”

“…(2S,4R)-4-Hydroxy-N-(2-methylnaphthalen-1-yl)pyrrolidine-2carboxamide (L1). 14 White solid (6.244 g, 77% yield); mp 163−165 °C; 1 H NMR (500 MHz, CD 3 OD) δ 7. 84 (dd,J = 8.3,2.7 Hz,2H),7.75 (d,J = 8.4 Hz,1H), 7.50 (t, J = 7.1 Hz, 1H), 7.45 (t, J = 7.0 Hz, 1H), 7.39 (d,J = 8.4 Hz,1H),4.49 (t,J = 4.4 Hz,1H),4.27 (t,J = 8.4 Hz,1H) , 3.20 (dd, J = 12.0, 4.1 Hz, 1H), 3.03 (dt, J = 12.0, 1.6 Hz, 1H), 2.41−2.37 (m, 1H), 2.36 (s, 3H), 2.13−2.06 (m, 1H); 13 C NMR (125 MHz, CD 3 OD) δ 176.…”

“…3, 134.2, 132.8, 128.7, 128.2, 126.7, 126.6, 126.6, 126.0, 123.0, 122.6, 60.1, 46.2, 30.3, 24 (2S,4R)-4-Hydroxy-N-(naphthalen-1-yl)pyrrolidine-2-carboxamide (L4). 14 White solid (5.459 g, 71% yield); mp 151−153 °C; 6, 133.5, 129.6, 128.8, 127.4, 127.1, 126.9, 126.6, 122.2, 121.5, 73.8, 61.5, 56.0, 40.8 13 C NMR (125 MHz, DMSO-d6) δ 172. 9, 135.1, 134.9, 127.6, 126.1, 60.4, 46.8, 30.7, 25.8, 18. 13 C NMR (125 MHz, DMSO-d6) δ 166.…”

“…Recently, we reported the first metal-catalyzed coupling reaction of (hetero)­aryl chlorides with sodium methanesulfinate by combining CuI and a new class of amide ligands with hybrid structures of 4-hydroxy- l -proline and oxalic diamides (Figure ). During our studies on copper salt/oxalic diamide catalyzed coupling reactions, we found that when ligands that were suitable for Cu-catalyzed coupling reactions with (hetero)­aryl chlorides were applied for coupling reactions with more reactive (hetero)­aryl bromides and iodides, both catalytic loadings and reaction temperatures could be greatly reduced. Accordingly, we explored the possibility of a more practical method for preparing aryl sulfones could be discovered by using these newly developed amide ligands.…”