Molecules dancing under visible light, conducted by nickel atoms.

Alkyl Carbon-Carbon Bonds: The Future of Sustainable Chemistry?

Elliot Brynn in Science & Nature August 2025 • 4 min read.

"Discover how nickel and photoredox catalysis are revolutionizing carbon-carbon bond formation, paving the way for greener and more efficient chemical processes."

In the realm of modern organic synthesis, the creation of carbon-carbon bonds stands as a pivotal process, essential for assembling complex molecular structures with precision and efficiency. Scientists have long sought methods to forge these bonds in a controlled manner, leading to the development of techniques such as palladium-catalyzed cross-couplings, ruthenium-mediated olefin-metathesis, and C-H functionalization.

Among these transformations, the formation of carbon-carbon bonds at sp³-hybridized centers holds particular significance, offering a gateway to three-dimensional architectures. However, achieving this type of bond formation has often presented challenges, particularly in complex molecular environments. Traditional methods often require harsh conditions or pre-activation of coupling partners, limiting functional group compatibility.

Enter photoredox catalysis, a groundbreaking approach that harnesses visible light to drive chemical reactions under mild conditions. By employing a photoexcitable catalyst, this technique enables the generation of reactive C(sp³)-hybridized radicals in a regulated manner, opening new avenues for carbon-carbon bond formation. The convergence of photoredox and nickel catalysis has sparked a renaissance in radical chemistry and nickel-catalyzed transformations, addressing the long-standing challenge of cross-coupling functionalized alkyl fragments.

Nickel/Photoredox Catalysis: A New Frontier in Carbon-Carbon Bond Formation

Molecules dancing under visible light, conducted by nickel atoms.

The recent surge in interest surrounding the use of nickel in carbon-carbon bond formation stems from its ability to overcome limitations associated with traditional cross-coupling methods. By combining nickel catalysis with photoredox principles, chemists have discovered that photocatalytically generated alkyl radicals can be readily captured by nickel complexes, leading to the realization of entirely new feedstocks for cross-coupling reactions.

This innovative approach cleverly divides the conventional two-electron alkyl cross-coupling into multiple, lower-barrier single-electron steps. These steps are intricately linked within two catalytic cycles: the photoredox cycle and the cross-coupling cycle. The cross-coupling cycle involves the capture of a photoredox-generated radical species by ligated nickel to produce a nickel intermediate. Subsequent oxidative addition of an aryl halide to this intermediate then yields a nickel complex.

Mild Conditions: Enables reactions under gentle conditions, minimizing damage to sensitive functional groups.
Broad Functional Group Tolerance: Compatible with a wide range of chemical functionalities, expanding the scope of potential reactions.
Novel Feedstocks: Allows the use of previously inaccessible starting materials for cross-coupling reactions.
Enhanced Control: Provides precise control over radical generation and reactivity, leading to more selective transformations.
Sustainable Approach: Utilizes visible light as an energy source, promoting greener and more sustainable chemical processes.

Notably, the inherently mild nature of this reaction has unlocked unprecedented retrosynthetic disconnections, enabling chemists to envision new strategies for molecular assembly. The system's modularity is particularly impressive, allowing for the incorporation of radical precursors derived from diverse feedstock chemicals, including organoboron reagents, carboxylic acids, aldehydes, and organosilanes. Even alkyl radicals arising from hydrogen atom transfer (HAT) processes can participate in these cross-couplings, further expanding the possibilities.

The Future of Carbon-Carbon Bond Formation

The rapid development and adoption of nickel/photoredox dual catalysis underscore its transformative potential in organic synthesis. By providing access to previously unattainable bond disconnections, this method empowers chemists to design more efficient and sustainable routes to complex molecules. Continued research efforts focused on expanding the scope of radical precursors, developing general protocols for tertiary centers, achieving enantioselective cross-couplings, and refining alkyl-alkyl couplings will undoubtedly solidify the impact of this burgeoning field.

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Everything You Need To Know

What is the primary advantage of using Nickel/Photoredox Catalysis in carbon-carbon bond formation compared to traditional methods?

The primary advantage of using Nickel/Photoredox Catalysis lies in its ability to facilitate reactions under mild conditions and with broad functional group tolerance, unlike traditional cross-coupling methods. These gentle conditions minimize damage to sensitive functional groups, while the broad tolerance allows the incorporation of a wide range of chemical functionalities, expanding the scope of potential reactions. Furthermore, this approach allows for novel feedstocks, enhancing control over radical generation and reactivity, and promoting sustainable chemical processes by utilizing visible light as an energy source.

How does the combination of photoredox and nickel catalysis revolutionize the process of forming carbon-carbon bonds?

The combination of photoredox and nickel catalysis revolutionizes carbon-carbon bond formation by cleverly dividing the conventional two-electron alkyl cross-coupling into multiple, lower-barrier single-electron steps. Photoredox catalysis uses visible light to generate reactive C(sp³)-hybridized radicals in a regulated manner. These radicals are then captured by nickel complexes in the cross-coupling cycle. This approach allows chemists to design more efficient and sustainable routes to complex molecules. The convergence of photoredox and nickel catalysis has sparked a renaissance in radical chemistry, addressing the long-standing challenge of cross-coupling functionalized alkyl fragments, and overcoming limitations associated with traditional cross-coupling methods.

What are the key benefits of employing Nickel/Photoredox dual catalysis in organic synthesis?

Employing Nickel/Photoredox dual catalysis offers several key benefits. Firstly, it enables reactions under mild conditions, minimizing damage to sensitive functional groups. Secondly, it exhibits broad functional group tolerance, expanding the scope of potential reactions. Thirdly, it allows for novel feedstocks, providing access to previously unattainable bond disconnections. Fourthly, it enhances control over radical generation and reactivity, leading to more selective transformations. Finally, it promotes greener and more sustainable chemical processes by utilizing visible light as an energy source.

Can you explain the role of photoredox catalysis and nickel catalysis within the context of alkyl carbon-carbon bond formation?

In alkyl carbon-carbon bond formation, photoredox catalysis acts as the initial trigger, using visible light to generate reactive C(sp³)-hybridized radicals. This is a crucial first step. Nickel catalysis then steps in to capture these radicals, facilitating the cross-coupling process. The photoredox cycle generates the necessary radicals, and the cross-coupling cycle utilizes nickel complexes to react with them. This division of labor allows for the efficient creation of carbon-carbon bonds under mild conditions, expanding the scope of accessible reactions and materials.

What are the future prospects for Nickel/Photoredox dual catalysis in sustainable chemistry?

The future of Nickel/Photoredox dual catalysis in sustainable chemistry looks very promising. Continued research will likely focus on expanding the scope of radical precursors, developing general protocols for tertiary centers, achieving enantioselective cross-couplings (creating molecules with specific spatial arrangements), and refining alkyl-alkyl couplings (forming bonds between alkyl groups). These advancements will further solidify the impact of this burgeoning field by providing chemists with even more powerful tools to design efficient, sustainable, and selective routes to complex molecules, further contributing to greener chemical processes.