Ligand-Promoted Palladium-Catalyzed Aerobic Oxidation Reactions.

Palladium-catalyzed aerobic oxidation reactions have been the focus of industrial application and extensive research efforts for nearly 60 years. A significant transition occurred in this field approximately 20 years ago, with the introduction of catalysts supported by ancillary ligands. The ligands play crucial roles in the reactions, including promotion of direct oxidation of palladium(0) by O2, bypassing the typical requirement for Cu salts or related redox cocatalysts to facilitate oxidation of the reduced Pd catalyst; facilitation of key bond-breaking and bond-forming steps during substrate oxidation; and modulation of chemo-, regio-, or stereoselectivity of a reaction. The use of ligands has contributed to significant expansion of the scope of accessible aerobic oxidation reactions. Increased understanding of the role of ancillary ligands should promote the development of new synthetic transformations, enable improved control over the reaction selectivity, and improve catalyst activity and stability. This review surveys the different ligands that have been used to support palladium-catalyzed aerobic oxidation reactions and, where possible, describes mechanistic insights into the role played by the ancillary ligand.

Synthesis of Indole-2-carboxylate Derivatives via Palladium-Catalyzed Aerobic Amination of Aryl C-H Bonds.

A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures.

Convergent Synthesis of Diverse Nitrogen Heterocycles via Rh(III)-Catalyzed C-H Conjugate Addition/Cyclization Reactions.

The development of Rh(III)-catalyzed C-H conjugate addition/cyclization reactions that provide access to synthetically useful fused bi- and tricyclic nitrogen heterocycles is reported. A broad scope of C-H functionalization substrates and electrophilic olefin coupling partners is effective, and depending on the nature of the directing group, cyclic imide, amide, or heteroaromatic products are obtained. An efficient synthesis of a pyrrolophenanthridine alkaloid natural product, oxoassoanine, highlights the utility of this method.

Palladium Catalyzed Aryl C-H Amination with O2 via In Situ Formation of Peroxide-Based Oxidant(s) from Dioxane.

(DAF)Pd(OAc)2 (DAF = 4,5-diazafluorenone) catalyzes aerobic intramolecular aryl C-H amination with N-benzenesulfonyl-2-aminobiphenyl in dioxane to afford the corresponding carbazole product. Mechanistic studies show that the reaction involves in situ generation of peroxide species from 1,4-dioxane and O2, and the reaction further benefits from the presence of glycolic acid, an oxidative decomposition product of dioxane. An induction period observed for the formation of the carbazole product correlates with the formation of 1,4-dioxan-2-hydroperoxide via autoxidation of 1,4-dioxane, and the in situ-generated peroxide is proposed to serve as the reactive oxidant in the reaction. These findings have important implications for the palladium-catalyzed aerobic oxidation reactions conducted in ethereal solvents.

Palladium-catalyzed intermolecular aminoacetoxylation of alkenes and the influence of PhI(OAc)2 on aminopalladation stereoselectivity.

A modified protocol has been identified for Pd-catalyzed intermolecular aminoacetoxylation of terminal and internal alkenes that enables the alkene to be used as the limiting reagent. The results prompt a reassessment of the stereochemical course of these reactions. X-ray crystallographic characterization of two of the products, together with isotopic labeling studies, show that the amidopalladation step switches from a cis-selective process under aerobic conditions to a trans-selective process in the presence of diacetoxyiodobenzene.

Enantioselective Pd(II)-catalyzed aerobic oxidative amidation of alkenes and insights into the role of electronic asymmetry in pyridine-oxazoline ligands.

Enantioselective intramolecular oxidative amidation of alkenes has been achieved using a (pyrox)Pd(II)(TFA)(2) catalyst (pyrox = pyridine-oxazoline, TFA = trifluoroacetate) and O(2) as the sole stoichiometric oxidant. The reactions proceed at room temperature in good-to-excellent yields (58-98%) and with high enantioselectivity (ee = 92-98%). Catalyst-controlled stereoselective cyclization reactions are demonstrated for a number of chiral substrates. DFT calculations suggest that the electronic asymmetry of the pyrox ligand synergizes with steric asymmetry to control the stereochemical outcome of the key amidopalladation step.