Platinum Catalyzed Synthesis of Alpha-Ketoester via C-H Functionalization

Abstract

Alpha-ketoesters have proven to be useful in a variety of fields. They have found wide spread applications in pharmaceuticals, photochemistry, and biology. Additionally, they are of great interest in synthetic chemistry and are frequently used as a precursor to many useful organic compounds including alpha-keto acids, alpha-hydroxy acids, and alpha-amino acids. Numerous methods have been reported for synthesizing alpha-ketoesters but they all amount to a few notable drawbacks. Herein reported is a potentially more effective transition metal catalyzed reaction to synthesize alpha-ketoester via C-H functionalization. A series of ligands with structural modifications have been designed, synthesized and acylated to shed light on the scope and limitations of the reaction. An inexpensive and readily accessible reagent namely ethyl chlorooxoacetate was employed as the acylating reagent. Reaction conditions were optimized by screening various solvents and catalysts. A variety of solvents were found useful in this reaction, including chlorobenzene, benzonitrile, toluene, and m-xylene although the best results were obtained when chlorobenzene was used. The reaction showed great tolerance to both electron withdrawing and donating groups on the phenyl ring however some electronic effects were observed and it was found that the presence of electron withdrawing group on the phenyl ring decelerated the acylation reaction. Experimental results of the acylation reaction will be reported and the mechanistic implications of these results will be discussed.