Vitamin B12-Catalyzed Reactions in Organic Synthesis

Vitamin B12, or cobalamin, occupies a unique niche in organic synthesis by harnessing its cobalt centre to mediate radical, nucleophilic and photochemical processes under remarkably mild and sustainable conditions. Drawing inspiration from its biological functions—such as methyl group transfers, radical rearrangements and reductive dehalogenations—synthetic chemists have developed B12-derived catalysts that replicate and extend these transformations. Central to these methodologies is the ability of the cobalt ion to cycle between Co(I), Co(II) and Co(III) oxidation states, enabling reversible bond formation and homolysis of carbon–cobalt linkages. This redox flexibility facilitates atom-efficient radical generation, cross-couplings, ring openings and olefinations without resorting to precious metals or harsh reagents. Recent efforts have expanded the substrate scope to include epoxides, halides and complex electrophiles, while the emergence of light-driven B12 photocatalysis has unlocked new pathways for selective C–C and C–X bond formation. Together, these advances underscore the global significance of vitamin B12-catalysed systems as green, cost-effective alternatives for constructing value-added molecules, pharmaceuticals and materials, and they continue to inspire the design of hybrid and biomimetic catalysts for fine chemical synthesis.

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Vitamin B12-Catalyzed Reactions in Organic Synthesis publication trend

The graph below shows the total number of articles in vitamin b12-catalyzed reactions in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Cobalamin: A cobalt-containing complex of the corrin ring that toggles between Co(I), Co(II) and Co(III) to mediate redox and radical processes.

Hydrogen atom transfer (HAT): A mechanism in which a radical abstracts a hydrogen atom from a donor, generating a new radical species.

Dual catalysis: A strategy combining two distinct catalysts (for example cobalt and nickel) to achieve enhanced reactivity or selectivity.

Photocatalysis: Activation of a catalyst by light to access reactive excited states and drive chemical transformations.

Regioselectivity: The preference for bond formation or cleavage at one position in a molecule over others.

References

1. Learning from B12 enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis. Beilstein Journal of Organic Chemistry (2018).
2. Mild olefin formation via bio-inspired vitamin B 12 photocatalysis. Chemical Science (2021).
3. Vitamin B12 and hydrogen atom transfer cooperative catalysis as a hydride nucleophile mimic in epoxide ring opening. Cell Reports Physical Science (2023).
4. Cobalt Catalyst Determines Regioselectivity in Ring Opening of Epoxides with Aryl Halides. Journal of the American Chemical Society (2021).
5. C–C Bond Forming Reactions Enabled by Vitamin B12Opportunities and Challenges. ACS Catalysis (2022).