A Rationally Designed Iron(II) Catalyst for C(sp³)-C(sp²) and C(sp³)-C(sp³) Suzuki-Miyaura Cross-Coupling

Area of Science:

• * Organic Chemistry
• * Catalysis
• * Sustainable Chemistry

Background:

• * The Suzuki-Miyaura coupling (SMC) is crucial in organic synthesis and industry.
• * Iron catalysis offers a sustainable alternative but is underdeveloped for sp3-hybridized partners in SMC.
• * Developing efficient iron-catalyzed SMC for sp3-hybridized substrates remains a significant challenge.

Purpose of the Study:

• * To develop a novel, well-defined iron(II) catalyst for Suzuki-Miyaura coupling reactions.
• * To enable iron-catalyzed C(sp3)-C(sp2) and C(sp3)-C(sp3) bond formation using alkyl halide electrophiles.
• * To demonstrate the catalyst's utility in synthesizing pharmaceutically relevant compounds.

Main Methods:

• * Synthesis and characterization of an electron-deficient anilido-aldimine iron(II) complex.
• * Optimization of reaction conditions including base and solvent for Suzuki-Miyaura coupling.
• * Application of the developed methodology to synthesize complex organic molecules and pharmaceutical intermediates.

Main Results:

• * The developed iron(II) catalyst efficiently mediates C(sp3)-C(sp2) and C(sp3)-C(sp3) Suzuki-Miyaura couplings.
• * The methodology exhibits broad substrate scope, tolerating various alkyl halides, boronic esters, and boranes.
• * Mild reaction conditions and excellent functional group compatibility were achieved, including sensitive heterocycles.
• * Mechanistic studies suggest a radical pathway for C(sp3)-C(sp2) couplings and involvement of neutral boronic esters in transmetalation.

Conclusions:

• * A versatile iron(II) catalyst has been established for challenging Suzuki-Miyaura couplings involving sp3-hybridized partners.
• * This work significantly advances the field of iron-catalyzed cross-coupling, offering a sustainable approach.
• * The methodology's direct application to synthesize pharmaceutical intermediates highlights its practical importance.