Use of (E,E)-Dienoic Acids as Switchable (E,E)- and (Z,E)-Dienyl Anion Surrogates via Ligand-Controlled Palladium Catalysis

Carboxylic acids are not readily applied as carbon-based nucleophiles due to their intrinsic acidic group. Here, we demonstrate that free (E,E)-2,4-dienoic acids form electron-neutral and highest occupied molecular orbital-raised eta(2)-complexes with Pd(0) and undergo Friedel-Crafts-type additions to imines with exclusive alpha-regioselectivity, giving formal dienylated products after decarboxylation. Unusual and switchable (E,E)- and (Z,E)-selectivity, along with excellent enantioselectivity, is achieved via ligand-controlled outer-sphere or inner-sphere reaction modes, respectively, which are well supported by comprehensive density functional theory calculation studies. An unprecedented formal reductive Mannich reaction between (E,E)-dienoic acids and imines is also developed to furnish enantioenriched beta-amino acid derivatives.

Automated summary

This study demonstrates the application limitation of carboxylic acids as carbon-based nucleophiles, and proposes a method using free (E,E)-2,4-dienoic acids to form complexes with Pd(0) and undergo selective addition reactions with imines to produce dienylated products.