Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp³)-C(sp²) bond formation

Area of Science:

• Organic Chemistry
• Photochemistry
• Catalysis

Background:

• Developing efficient methods for constructing carbon-carbon bonds is crucial in organic synthesis.
• Nickel-catalyzed cross-coupling reactions are powerful tools, but often require specific conditions or additives.
• Photoredox catalysis offers alternative activation pathways but can necessitate specialized photocatalysts.

Purpose of the Study:

• To disclose a novel dual photochemical/nickel-mediated decarboxylative strategy for C(sp3)-C(sp2) linkage assembly.
• To establish a simplified, net-reductive platform that avoids external photocatalysts and stoichiometric reductants.
• To demonstrate the broad applicability of the method for coupling various C(sp3) radical precursors with (hetero)aryl bromides.

Main Methods:

• Utilizing Hantzsch ester (HE) as a dual-acting organic photoreductant and radical initiator under visible light (390 nm).
• Employing a nickel catalyst to mediate the decarboxylative cross-coupling via single-electron transfer (SET) and electron donor-acceptor (EDA) complex activation.
• Investigating the coupling of diverse C(sp3)-centered radical precursors (primary, secondary, benzylic, α-oxy, α-amino) with (hetero)aryl bromides.

Main Results:

• Successful assembly of C(sp3)-C(sp2) linkages through a dual photochemical/nickel-catalyzed decarboxylative process.
• Demonstrated that Hantzsch ester acts as both a potent organic photoreductant and an efficient mediator for radical generation.
• Achieved broad substrate scope, coupling various C(sp3) radical architectures with diverse (hetero)aryl bromides under mild conditions.
• The protocol tolerates sensitive functional groups and pharmaceutically relevant cores.

Conclusions:

• The developed strategy offers a simplified, homogeneous, and net-reductive platform for C(sp3)-C(sp2) bond formation.
• This approach bypasses the need for external photocatalysts, stoichiometric metal reductants, and additives, making it environmentally benign.
• The method's compatibility with sensitive functional groups and complex molecular scaffolds highlights its potential in synthetic and medicinal chemistry.