Catalyst-Controlled Chemodivergent Carbene Transfer Reactions With Bicyclo[1.1.0]butane-Derived Acceptor...

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Transition-metal-catalyzed carbene transfer reactions are vital in organic synthesis but often rely on hazardous diazo compounds.
• A general, redox-neutral, and atom-economical method for generating metal-carbenes from safer precursors is needed.

Purpose of the Study:

• To develop novel, versatile carbene precursors for metal-catalyzed reactions.
• To achieve catalyst-controlled chemodivergent transformations using these new precursors.
• To demonstrate the synthetic utility in preparing bioactive compound core structures.

Main Methods:

• Utilized carboxamide-functionalized bicyclic compounds (BCBs) as carbene precursors.
• Employed nickel catalysis for cyclopropanation reactions with multisubstituted alkenes.
• Applied copper catalysis for chemoselective C(sp2)─H insertion reactions.
• Conducted computational and experimental studies to elucidate reaction mechanisms.

Main Results:

• Nickel catalysis yielded azabicyclo[n.1.0] architectures with high diastereocontrol via an acceptor-type Ni-carbene.
• Copper catalysis afforded allyl oxindoles through efficient C(sp2)─H insertion.
• Both protocols demonstrated broad substrate scope, high functional group tolerance, and excellent atom economy.
• Mechanistic studies revealed distinct pathways for Ni-carbene (stepwise dual C─C cleavage) and Cu-catalyzed reactions (concerted dual cleavage followed by electrophilic aromatic substitution).

Conclusions:

• Carboxamide-functionalized BCBs serve as effective and safe carbene precursors.
• Catalyst control allows for chemodivergent reactivity, enabling access to diverse molecular scaffolds.
• These methods offer a sustainable and efficient platform for synthesizing complex organic molecules and bioactive compounds.