Spirocyclic frameworks are polycyclic structures in which two rings share exactly one carbon atom, known as the spiro centre. Because the two ring systems attached to that atom adopt an orthogonal arrangement, perpendicular to one another in space, the resulting molecules are rigid and distinctly three-dimensional. That geometry is not merely an aesthetic curiosity. It underpins the function of optoelectronic and hole-transporting materials, guides the design of ligands for coordination complexes, and appears repeatedly in the architecture of numerous natural products. Controlling how two molecular fragments are joined at a single shared atom is therefore a central problem for chemists working across these fields.

The most direct conceptual strategy for building a spiro skeleton is to introduce a single carbon atom that joins two components, effectively acting as the linchpin of the spiro centre. In practice, however, that has proven remarkably difficult. Previous carbon-atom-transfer approaches have largely relied on the reactivity of π-bonds, the double and triple bonds that are inherently reactive and easy to engage in chemical transformations. Carbon–carbon σ-bonds, the single bonds that form the backbone of essentially all organic molecules, are far more inert. Controlled insertion of a carbon atom into such σ-bonds has remained a stubborn challenge in synthetic chemistry, and the new report directly addresses that gap.

The key to the breakthrough is a combination of two components: a rhodium catalyst and a reagent called N-isocyanoiminophosphorane, abbreviated PINC, which serves as an atomic carbon equivalent. Isocyanide-based reagents of this type have been developed as sources of bare carbon atoms that can be delivered under catalytic control, and the Osaka team harnessed PINC to supply the single carbon atom that becomes the spiro centre. Rather than attacking a π-bond, the reaction engages carbon–carbon σ-bonds through a sequence of C–C bond activation steps orchestrated by the rhodium catalyst.

The substrates at the heart of the study are biphenylenes, strained polycyclic molecules in which two benzene rings are fused in a way that imposes significant angular strain. That strain makes their carbon–carbon bonds unusually susceptible to activation by transition metals, which is precisely why the researchers chose them as the testing ground for σ-bond spirofusion. In the reported reaction, the rhodium catalyst sequentially activates C–C bonds of the biphenylene framework, and the carbon atom delivered from PINC is inserted so that the two molecular units are joined at a newly formed spiro centre. The net result is the conversion of comparatively simple biphenylene substrates into complex spirocyclic structures.

What makes the transformation striking from a bond-counting perspective is its efficiency: a single catalytic sequence forms four new carbon–carbon bonds at the spiro centre. Constructing four C–C bonds in one operation is rare in organic synthesis, and doing so while installing the defining feature of a spiro framework, the shared orthogonal carbon atom, represents an unusually economical way to build molecular complexity. The single carbon atom delivered by PINC acts as the central linchpin around which the entire three-dimensional architecture is assembled.

The versatility of the method extends beyond joining identical partners. The researchers demonstrated both homo-spirofusion, in which two identical biphenylene units are joined, and cross-spirofusion, in which two different biphenylenes are combined at a single spiro centre. The ability to couple unlike partners greatly expands the structural diversity accessible with the reaction, because chemists can mix and match molecular fragments to tune the properties of the resulting spirocyclic product. Cross-couplings of this kind are typically harder to achieve than homocouplings, since the catalyst must discriminate between different substrates, making this aspect of the work particularly significant for practical applications.

The team also showed that the strategy is not confined to σ-bond activation alone. The reaction can be extended to processes that combine σ-bond and π-bond activation, broadening the scope of the chemistry beyond biphenylene–biphenylene coupling. This flexibility suggests that the catalytic carbon-atom-transfer concept could serve as a general platform for spirocycle construction, with the rhodium catalyst and the PINC carbon source operating together to stitch together molecular fragments through whichever bond types are most appropriate for a given target structure.

The significance of the work lies in establishing a catalytic strategy for constructing structurally complex spirocyclic frameworks through C–C σ-bond activation, a mode of reactivity that had long resisted controlled exploitation. Because spirocyclic motifs appear in optoelectronic and hole-transporting materials, in ligand design for coordination complexes, and in numerous natural products, a method that assembles them directly from σ-bonds could influence fields well beyond synthetic methodology. Rigid, orthogonal three-dimensional scaffolds are increasingly valued in molecular design, and the ability to generate them by inserting a single carbon atom between two preformed fragments offers a concise and modular approach.

The research, conducted in the Department of Applied Chemistry at the Graduate School of Engineering of The University of Osaka, with Fujimoto and Tobisu also affiliated with the Innovative Catalysis Science Division of the Institute for Open and Transdisciplinary Research Initiatives, was published as a peer-reviewed article carrying the DOI 10.1038/s41586-026-11242-8. Correspondence for the study is handled by Hayato Fujimoto and Mamoru Tobisu. As with any newly reported catalytic method, the coming years will show how broadly the rhodium-catalysed, PINC-mediated spirofusion can be applied across different substrate classes, but the conceptual advance is clear: carbon–carbon σ-bonds, the most ubiquitous bonds in organic chemistry, can now serve as entry points for catalytic carbon-atom transfer, and a single carbon atom can serve as the linchpin that locks two molecular worlds together at a right angle.

Subject of Research: Rhodium-catalysed insertion of atomic carbon into C–C σ-bonds to construct spirocyclic frameworks

Article Title: Catalytic transfer of carbon atoms enables spirofusion of C–C σ-bonds

Article References: Fujimoto, H., Mizutani, M., Imachi, K., Nishioka, T., Ikeda, R., & Tobisu, M. (2026). Catalytic transfer of carbon atoms enables spirofusion of C–C σ-bonds. Nature. https://doi.org/10.1038/s41586-026-11242-8

Image Credits: AI Generated

DOI: 10.1038/s41586-026-11242-8

Keywords: spirocyclic frameworks, carbon atom transfer, C–C σ-bond activation, rhodium catalysis, biphenylene, N-isocyanoiminophosphorane, homogeneous catalysis, synthetic chemistry methodology, cross-spirofusion, organometallic chemistry, molecular architecture, The University of Osaka