Transition metal-catalyzed cross-coupling using esters as electrophiles has gained significant attention over the past decade due to ester’s availability, robustness, and utility as organic synthesis building blocks. Traditionally, these reactions required elevated temperatures, long reaction times, and/or high catalyst and reagent loadings. Following oxidative-addition of the C(acyl)-O bond, the reaction can diverge into decarbonylative or non-decarbonylative pathways depending on reaction conditions. In this presentation, the non-decarbonylative Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions of aryl-esters to form ketones and amides, using the recently developed (η<sup>3</sup>-1-<sup>t</sup>BuIndenyl)Pd(L)Cl pre-catalyst, will be described. Understanding pre-catalyst activation and solvent system selection were shown to be critical in achieving good to high yields at mild reaction conditions. The application of this method for cross-coupling at the C-terminus or glutamic and aspartic acid side chains of amino acids will be discussed as a means of site-selectively modifying peptides.

Palladium-catalyzed cross-coupling of aryl esters

256th National Meeting (2018)

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