Mechanistic Study of the Direct Intramolecular Allylic Amination Reaction Catalyzed by Palladium(II)

DFT calculations (PBE1PBE/6-31G­(d,p), Def2-TZVPPD) were performed to study the intramolecular C–H amination of an unsaturated carbamate catalyzed by [Pd­(LL)­(OAc)₂] (<b>2</b>), where LL is the bis­(sulfoxide) ligand PhS­(O)­(CH₂)₂S­(O)­Ph. The coordination takes place by an associative path over a trigonal-bipyramidal transition state. The LL ligand undergoes a coordination shift from κ²S,S to κ¹S, leaving an open position for binding of the substrate (CC). In the next step, the C–H activation, the transition state for the hydrogen abstraction from the substrate to form the σ-allyl complex has an energy of 124.0 kJ mol^–1, which is the highest energy in the whole mechanism (TOF-determining transition state). The σ-allyl converts easily in the π-allyl, the acetic acid molecule leaving the coordination sphere. The remaining acetate receives the second hydrogen from the NH group, while the newly formed acetic acid molecule is replaced by the pendant arm of the LL ligand, and the cyclization takes place (nucleophilic attack). During these changes, the metal is reduced to Pd(0) in the form of the Pd(0) complex of the oxazolidinone product, the most stable species in the cycle (TOF-determining intermediate). Either the C–H activation or the Pd(0) oxidation may be the step determining the energy span of the reaction, depending on reaction conditions

Palladium-Catalyzed Arylic/Allylic Aminations: Permutable Domino Sequences for the Synthesis of Dihydroquinolines from Morita–Baylis–Hillman Adducts

An efficient palladium-catalyzed synthesis of 1,2-dihydroquinolines has been developed via the reaction between anilines and Morita–Baylis–Hillman adducts derived from <i>o</i>-bromobenzaldehyde. This new Pd(0)-catalyzed pseudo-domino type I sequence involves a Buchwald–Hartwig arylic amination and an allylic amination. When starting from an <i>o</i>-bromo allylic alcohol, the chronology is arylic amination/allylic arylation. However, the sequence reverses when the reaction is performed on the corresponding <i>o</i>-bromo allylic acetate

Pd-Catalyzed Direct C–H Alkenylation and Allylation of Azine <i>N</i>‑Oxides

A Pd-catalyzed direct C₂-alkenylation of azine <i>N</i>-oxides with allyl acetate is disclosed. The products are formed through an allylation/isomerization cascade process. The use of a tri-<i>tert</i>-butylphosphonium salt as the ligand precursor and KF is mandatory for optimal yields. When cinnamyl acetate is used, the same catalytic system promotes C₂-cinnamylation of the azine <i>N</i>-oxide without subsequent isomerization. A mechanism is proposed on the basis of experimental studies and DFT calculations

Opening the Way to Catalytic Aminopalladation/Proxicyclic Dehydropalladation: Access to Methylidene γ‑Lactams

A new aerobic intramolecular palladium­(II)-based catalytic system that triggers aminopalladation/dehydropalladation of <i>N</i>-sulfonyl­alkenylamides to give the corresponding methylidene γ-lactams has been identified. Use of triphenylphosphine and chloride anion as ligands is mandatory for optimal yields, and molecular oxygen can be used as the sole terminal oxidant. Scope and limitations of the methods are described. A mechanism is proposed on the basis of experimental results as well as density functional theory calculations

Opening the Way to Catalytic Aminopalladation/Proxicyclic Dehydropalladation: Access to Methylidene γ‑Lactams

A new aerobic intramolecular palladium­(II)-based catalytic system that triggers aminopalladation/dehydropalladation of <i>N</i>-sulfonyl­alkenylamides to give the corresponding methylidene γ-lactams has been identified. Use of triphenylphosphine and chloride anion as ligands is mandatory for optimal yields, and molecular oxygen can be used as the sole terminal oxidant. Scope and limitations of the methods are described. A mechanism is proposed on the basis of experimental results as well as density functional theory calculations

Palladium-Catalyzed [3 + 2]-C–C/N–C Bond-Forming Annulation

The synthesis of bi- and tricyclic structures incorporating pyrrolidone rings is disclosed, starting from resonance-stabilized acetamides and cyclic α,β-unsaturated-γ-oxycarbonyl derivatives. This process involves an intermolecular Tsuji–Trost allylation/intramolecular nitrogen 1,4-addition sequence. Crucial for the success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. When the newly formed annulation product carries a properly located <i>o</i>-haloaryl moiety at the nitrogen substituent, a further intramolecular keto α-arylation can join the cascade, thereby forming two new cycles and three new bonds in the same synthetic operation