Functionalized phenoxypyridines are compounds that have many important applications. They can be used medicinally as an anticonvulsant, and synthetically as a chemical that protects maize from the toxic effects of herbicides. The α-ketoamide moiety is important in medicinal and synthetic chemistry due to multiple reactive sites. With the Platinum-catalyzed C-H acylation method developed in our group, an α-ketoamide functional group can be readily introduced in the <i>ortho</i>-position of 2-aryloxypyridines by using 2-(diethylamino)-2-oxoacetyl chloride as the acylating reagent. In this presentation, we will discuss the scope and limitations of this method. A broad range of substrates with various substituents, including electron-withdrawing and electron-donating groups, will be utilized in this reaction. In addition to the substituent tolerance of this reaction, the use of other related acylating reagents will be reported. Those reagents include other 2-amino-2-oxoacetyl chlorides, chloroformates, and carbamoyl chlorides. The relative activity of different acylation reagents will be compared. The reaction mechanism will be discussed. Finally, the application of this C-H acylation method in late-stage modification of medicinally or biologically active molecules will also be discussed.

Synthesis of α-ketoamide via Pt-catalyzed C-H activation and functionalization

ACS Spring 2022

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