Platinum-Catalyzed Double Acylation of 2-(Aryloxy)pyridines via Direct C–H Activation

Abstract

A unique, platinum-catalyzed, direct C-H acylation of 2-(aryloxy)pyridines with acyl chlorides is discovered. The reaction requires neither an oxidant nor other additives. When both ortho positions of the aryl group are accessible, the double acylation occurs readily to produce the diacylated products. Aliphatic, aromatic, and α,β-unsaturated acyl groups can all be introduced. The acylation reaction may proceed through an analogous aromatic electrophilic substitution triggered by the nucleophilic attack of the platinum at the acyl chloride.

Platinum in Chemistry: An Adventure from Phosphorescent Materials to Catalytic C−H Functionalization

“…3‐Nitrobenzoyl chloride was found to be more reactive than the 4‐methoxybenzoyl chloride (formation of 111 vs 112 ). This difference in reactivity is further confirmed by a competing acylation, which shows that the ratio of products 111 and 112 is 90 : 10 (Scheme ) . The acylation of 2‐(2‐naphthalenoxy)pyridine occurred at the 3‐position of the naphthalene ( 115 ); apparently the 1‐position is more sterically hindered.…”

“…When either one of the ortho positions or the meta position of 2‐phenoxypyridine was substituted, only monoacylated products 110 – 114 were formed under the same conditions (Figure ) . 3‐Nitrobenzoyl chloride was found to be more reactive than the 4‐methoxybenzoyl chloride (formation of 111 vs 112 ).…”

“…Simply by running the reaction at a higher temperature in benzonitrile (10 mol % K 2 PtCl 4 ) or 1,2‐dichlorobenzene [10 mol % Pt(PhCN) 2 Cl 2 ], both mono and di‐acylated products were formed. Specifically, the reaction of 91 with benzoyl chloride (5 equivalents) in 1,2‐dichlorobenzene at 140 °C for 24 h gave predominately the monoacylated product 92 in 54 % isolated yield, along with the di‐acylated product 93 in 7 % yield (Scheme ) . When xylene or chlorobenzene were used as the solvent, the reaction under reflux for about 2 days gave predominately diacylated product 93 , with only a trace amount of mono‐acylated product 92 .…”

“…An extensive computational study may be necessary to gain insights into the details of the mechanism. A π‐allyl platinum species 119 has also been proposed to account for a facile double acylation reaction ,…”

“…Finally, the directing pyridyl group can be easily removed by sequential treatments with MeOTf and a base . Thus 93 was converted to 2,6‐dibenzoylphenol 113 in 86 % yield . Substituted 2,6‐dibenzoylphenols have been studied as potent anti‐inflammatory agents and as useful ligands in bioinorganic chemistry .…”