Palladium-Catalyzed Arylation of Fluoroalkylamines

We
report the synthesis of fluorinated anilines by palladium-catalyzed
coupling of fluoro­alkyl­amines with aryl bromides and aryl
chlorides. The products of these reactions are valuable because anilines
typically require the presence of an electron-withdrawing substituent
on nitrogen to suppress aerobic or metabolic oxidation, and the fluoro­alkyl
groups have steric properties and polarity distinct from those of
more common electron-withdrawing amide and sulfon­amide units.
The fluoro­alkyl­aniline products are unstable under typical
conditions for C–N coupling reactions (heat and strong base).
However, the reactions conducted with the weaker base KOPh, which
has rarely been used in cross-coupling to form C–N bonds, occurred
in high yield in the presence of a catalyst derived from commercially
available Ad­Bippy­Phos and [Pd­(allyl)­Cl]2. Under
these conditions, the reactions occur with low catalyst loadings (<0.50
mol % for most substrates) and tolerate the presence of various functional
groups that react with the strong bases that are typically used in
Pd-catalyzed C–N cross-coupling reactions of aryl halides.
The resting state of the catalyst is the phenoxide complex, (Bippy­Phos­Pd­(Ar)­OPh);
due to the electron-withdrawing property of the fluoro­alkyl
substituent, the turnover-limiting step of the reaction is reductive
elimination to form the C–N bond.