Using ketones as catalyst activators in palladium-catalyzed cross- coupling reactions

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University of Alabama Libraries

PEPPSI-IPr (1) has become a very useful catalyst over the past decade. It has shown to be successful with almost every type of cross-coupling reaction that currently exists. These transformations have been used in catalytic studies and the pharmaceutical industry. This study used PEPPSI-IPr and 3-pentanone to greatly improve the yield of the Buchwald-Hartwig amination of various aryl bromides and aniline. This suggests that the ketone acted as the activator where aniline cannot. The importance of using the ketone as an activator for catalysis will be shown in various ways. This transformation has been successful with both sterically hindered and electronically modified substrates. However, the electron-rich substrates proved to produce higher yields than their electron-deficient counterparts. The transformation showed slight favor of sterically hindered substrates over non-hindered ones. The reaction mechanism for ketone activation remains unknown. The goal of this study was to gain further knowledge of how the ketone affects the reaction to better understand how this mechanism occurs. Other conditions of these reactions include low catalyst loading (PEPPSI-IPr, 1), the use of NaO-t-Bu as the base and dry toluene as the solvent over a range of temperatures, 20-80 °C. This study also demonstrated the importance of reagent addition order, and how it affected the transformation. The culmination of this study showed that without the ketone, the reaction was not very successful, producing 3-12% yields; however, with the ketone, most conditions afford yields between 60-100%. In order to convey the importance of the ketone in this reaction, we studied the affect of increasing ketone concentrations and temperatures on the 4-bromoanisole and 2-bromotoluene substrates in addition to a reaction rate profile for 4-bromoanisole.

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Organic chemistry