Quaternary Carbon Editing Enabled by Sequential Palladium Migration

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Peripheral functionalization of quaternary carbons via C(sp3)-H activation is advancing.
• Direct Csp3-Csp3 bond cleavage and refunctionalization of nonstrained acyclic molecules are underexplored.
• Quaternary carbons present significant synthetic challenges in organic chemistry.

Purpose of the Study:

• To develop a new method for editing quaternary carbons through C-C bond cleavage.
• To achieve concurrent functionalization of primary, secondary, and quaternary carbons.
• To enable methyl group migration and oxidation of C-C single bonds to C=C double bonds in acyclic systems.

Main Methods:

• Utilized a palladium acetate catalyst with Selectfluor and sodium carbonate.
• Investigated the reaction of morpholinyl amide of 2,2-dimethyl alkanoic acids.
• Performed control experiments to elucidate the reaction mechanism.

Main Results:

• Successfully converted 2,2-dimethyl alkanoic acid derivatives to 2-methylene-3-methyl alkanoic acid derivatives.
• Demonstrated a domino process involving C(sp3)-H activation, Pd(II)/Pd(IV) oxidation, 1,3-Pd(IV) migration, and dyotropic rearrangement.
• Achieved concurrent functionalization of primary, secondary, and quaternary carbons via palladium migration.

Conclusions:

• Developed an unprecedented reaction for Csp3-Csp3 bond cleavage and functionalization.
• The domino process offers a new strategy for complex molecule synthesis.
• This methodology expands the scope of quaternary carbon functionalization in organic synthesis.