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

Shun‐Zhong Tan, Peng Chen, Lei Zhu, Meng‐Qi Gan, Qin Ouyang, Wei Du, Ying‐Chun Chen

2022Journal of the American Chemical Society36 citationsDOI

Abstract

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 η2-complexes with Pd(0) and undergo Friedel–Crafts-type additions to imines with exclusive α-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 β-amino acid derivatives.

Topics & Concepts

ChemistryNucleophileRegioselectivityLigand (biochemistry)PalladiumDecarboxylationDensity functional theoryStereochemistryNucleophilic additionSelectivityIonMedicinal chemistryComputational chemistryOrganic chemistryCatalysisReceptorBiochemistryAsymmetric Synthesis and CatalysisCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and Catalysis
Use of (<i>E</i>,<i>E</i>)-Dienoic Acids as Switchable (<i>E</i>,<i>E</i>)- and (<i>Z</i>,<i>E</i>)-Dienyl Anion Surrogates via Ligand-Controlled Palladium Catalysis | Litcius