EXPLORATION INTO THE SCOPE AND MECHANISM OF THE PLATINUM-CATALYZED ACYLATION OF 2-(ARYLOXY)PYRIDINES

Abstract

Transition metal catalysts have played a key role in direct C-H bond functionalization. However, one main drawback of these reactions is that oxidants and additives are often required to regenerate the active catalyst, oxidize the substrates, or promote the reaction. These needed reagents can often add significant cost and safety concerns to the synthesis. Recently the Huo group has discovered a unique platinum catalyzed acylation reaction to produce alpha-keto esters via C-H functionalization using ethyl chorooxoacetate, a cheap and readily accessible reagent. This reaction eliminated the need for any oxidants or additives and, more importantly, was free of any decarbonylation side reactions (see below). Further reaction optimization was performed to lower the catalyst loading. It was found that with the addition of potassium carbonate, strong acids that were produced during the C-H activation step (B) were neutralized thus allowing the catalyst to coordinate to the 1a more readily. The range of the overall synthesis was explored using different acylating agents. Finally, Hammett analysis was used to study the substituent effects of this reaction. Experimental results will be reported, and the significance of these findings will be discussed.