Pd‐Catalysed Mono‐ and Dicarbonylation of Aryl Iodides: Insights into the Mechanism and the Selectivity

Abstract

The mechanism of the experimentally reported phosphine-free palladium-catalysed carbonylation of aryl iodides with amines in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base was investigated at the DFT level. Paths were identified for both di- and monocarbonylation, and the calculated selectivity for three different substrates was in agreement with experiment. In dicarbonylation yielding α-ketoamides, formation of the second carbon-carbon bond occurs through reductive elimination in the Pd acyl amide intermediate after DBU-assisted nucleophilic attack of an amine at a terminal CO ligand. This path yields the major product with iodobenzene and the almost exclusive product with p-methoxyiodobenzene. Two different possible pathways yield the monocarbonylated amide product. In one of them, which affords the minor product for iodobenzene, base-assisted nucleophilic attack of the amine takes place on a Pd-bound acyl ligand. For substrates with electron-withdrawing substituents, such as p-cyanoiodobenzene, aryl migration to the CO ligand is disfavoured, and this allows base-assisted amine attack at a terminal CO ligand early in the catalytic cycle. From the resulting Pd amide aryl complex, the subsequent reductive elimination occurs easily, and monocarbonylation becomes favoured.

Recent Developments in General Methodologies for the Synthesis of α-Ketoamides

“…Computational studies on the mechanism of the Pd/DBUcatalyzed amino-carbonylation suggested specific reaction pathways for both di-and monocarbonylation processes that could convincingly explain how the observed ketoamide vs amide selectivity was a function of electron density on the aromatic nucleus. 278 Steps toward double-carbonylative amination were very similar to those involved in the corresponding Pd−phosphine catalytic system. Thus, formation of the oxidative addition product NHCs are neutral two-electron σ-donors acting as powerful "phosphine mimics" in transition-metal-complex-catalyzed homogeneous reactions.…”

“…Computational studies on the mechanism of the Pd/DBU-catalyzed amino-carbonylation suggested specific reaction pathways for both di- and monocarbonylation processes that could convincingly explain how the observed ketoamide vs amide selectivity was a function of electron density on the aromatic nucleus …”

“…As stated in the introduction to this subsection, the widely accepted mechanism for the Pd-mediated double-carbonylative amination called for the initial formation of the aroyl–Pd species 175 and CO coordination to the metal giving 176 (Scheme ). Next, amine addition at the terminal CO provided the aroyl-carbamoyl Pd species 178 , eventually taken to the target α-ketoamide by Pd(0) reductive elimination (dashed arrows) (see refs − , , , , , and ). Quite surprisingly, Xia advanced an alternative way for the C­(O)–C­(O) chaining process in the related Pd–NHC complex-catalyzed transformation (solid arrows).…”

One‐Step Synthesis of Dicarboxamides through Pd‐Catalysed Aminocarbonylation with Diamines as N‐Nucleophiles

“…[33,34] With regard to the reduction of the Pd II precursor to Pd 0 , some authors postulate that the phosphine ligand in excess acts as reducing agent, with O=P(Ph) 3 having been identified by NMR spectroscopy. [34] Other authors propose the involvement of water in Pd-catalysed carbonylation reactions, through formation of I-Pd-CO 2 H intermediates, which undergo decarboxylation and successive reductive elimination.…”

In situ generated Pd(0) nanoparticles stabilized by bis(aryl)acenaphthenequinone diimines as catalysts for aminocarbonylation reactions in water

“…Subsequent steps of the reaction occur on the surface of Pd-(Ar 2 -BIAN) NPs and are similar to those proposed in the literature. 74,75 Thus, oxidative addition of iodobenzene followed by migratory insertion of CO lead to the acyl intermediate 2.…”