Bypassing β-Hydride Elimination: Excited-State Pd-Catalyzed C(sp³)-C(sp²) Coupling at Room Temperature

Area of Science:

• Organic Chemistry
• Photochemistry
• Catalysis

Background:

• Palladium-catalyzed C-H bond functionalization is crucial in organic synthesis.
• Transformations involving alkyl-Pd(II) intermediates with beta-hydrogens are hindered by beta-hydride elimination.
• Developing new catalytic systems to overcome these limitations is essential.

Purpose of the Study:

• To achieve selective arylation of sp3 C-H bonds in amides and alcohols using palladium catalysis.
• To explore a non-redox-neutral pathway for C(sp3)-C(sp2) cross-couplings.
• To circumvent common beta-hydride elimination and annulation pathways.

Main Methods:

• Utilizing divalent palladium as an excited-state transition metal species.
• Employing aryl iodides as both hydrogen atom transfer (HAT) and arylating agents.
• Conducting mechanistic investigations using isotope-labeled compounds and density functional theory (DFT) studies.

Main Results:

• Selective arylation of sp3 C-H bonds in amides and alcohols was achieved at room temperature.
• A novel non-redox-neutral pathway involving photo-induced Pd(II)-catalyzed aryl radical generation, HAT, and aryl migration was demonstrated.
• The method effectively bypasses beta-hydride elimination and annulation.

Conclusions:

• The developed Pd-photochemical approach offers an effective strategy for C(sp3)-C(sp2) cross-couplings.
• This work provides new mechanistic insights into palladium-catalyzed transformations.
• The findings open avenues for novel synthetic methodologies in organic chemistry.