Platinum-Catalyzed Acylation of 2-(aryloxy)pyridines Via Direct Carbon-Hydrogen Activation

Abstract

Carbonyl groups are ubiquitous in pharmaceuticals, biomolecules, and natural products. The traditional means of acylation to introduce carbonyls, such as the Friedel-Crafts acylation, can be limited in scope. More recent methods using transition metals to catalyze direct C-H acylation have opened up new opportunities in synthesis, but often require the use of additives in the form of oxidants or expensive silver salts. In this report, a new reaction was developed in which platinum was used as the catalyst to introduce an acyl group to the ortho position of 2-(aryloxy)pyridines with acyl chlorides as the acylating reagent. This reaction occurs via direct carbon-hydrogen bond activation and does not require the use of additives. The reaction was found to allow for double acylation of the ortho position when both sites are available and not sterically hindered. After optimization of the reaction conditions, double acylated and single acylated compounds were synthesized successfully using aliphatic, aromatic, and [alpha],[beta]-unsaturated acyl chlorides as the acylating reagents.