Steric effects in palladium-catalysed amination of aryl triflates and nonaflates with the primary amines PhCH(R)NH2 (R=H, Me)

A systematic study of the effects of aryl triflate and nonaflate structure on the yield of amination with the primary amines PhCH(R)NH2 (R=H, Me) under palladium catalysis has been carried out. High throughput screening indicated that a catalyst composed of X-Phos/Pd2(dba)3/1,4-dioxane was optimal based on a model reaction of Ar(ORf) [Rf=Tf (SO2CF3), Nf (SO2(CF2)3CF3)] with PhCH2NH2. Comparisons of the reactivity of various ArOTf and ArONf [Ar=4-MePh, 2-naphthyl, 1-naphthyl, 2-PhC6H4] indicated that both ortho substitution in the aryl electrophile and at the α-position on the amine are detrimental to the coupling particularly when they occur in combination. Despite being formally a monodentate ligand use of X-Phos leads to only small degrees of racemisation when using (R)-PhCH(Me)NH2 (typically resulting in a reduction from 97 to 86-94% ee for the amine stereocentre).

Graphical abstractDownload full-size image Only minor racemisation despite being a formal 'monodentate' ligand.