Controlling Solvent Effects on in situ Pd Nanoparticle Synthesis Allows ß-Selective Heck Reactions of Unprotected Cinnamylamines

The control of regioselectivity for insertion reactions of allylamines is almost exclusively biased towards γ-functionalization for internal alkenes. Until recently these reactions also required protecting groups to prevent amine oxidation and other side reactions. To expand the synthetic toolbox to access unique new allylamine structures, we’ve found that by using the free amine, we have discovered a general method to synthesize complex allylamines through β-arylation with superior β-selectivity compared to traditional directing/protecting group-modified allylamine substrates which give preferentially γ-arylation or poor selectivity, demonstrating the orthogonality of free amine-directed methods. A comprehensive examina-tion of both the catalyst structure and role of the amine group is presented, with the proposed selectivity deriving from the amount of surface charge of the in situ-formed catalyst.