Metal-Catalyzed Fluorination and Fluoroalkylation

Metal-Catalyzed Fluorination and Fluoroalkylation

We have developed a simple method to convert aryl halides and ketones, esters, amides, cyanoesters, malonates, nitriles, and related compounds to alpha aryl carbonyl compounds and nitriles in the presence of base and a palladium catalyst. Familiar compounds that can be generated from these products include Ibuprofen, Naproxin and Tamoxifen. The reaction occurs in a general fashion and in many cases with low catalyst loadings.

As part of our studies to understand this process, we have generated both O-bound and C-bound palladium enolate complexes. These complexes undergo reductive elimination of the alpha-aryl ketone, ester, or amide product in good yields. Studies on the effects of changing the enolate electronics on reductive elimination rate are in progress.