Accessing carbon, boron and germanium spiro stereocentres in a unified catalytic enantioselective approach

Yi-Xuan Cao; Anne-Sophie Chauvin; Shuo Tong; Layth Alama; Nicolai Cramer

doi:10.1038/s41929-025-01352-3

Accessing carbon, boron and germanium spiro stereocentres in a unified catalytic enantioselective approach

Nat Catal. 2025;8(6):569-578. doi: 10.1038/s41929-025-01352-3. Epub 2025 Jun 12.

Authors

Yi-Xuan Cao¹, Anne-Sophie Chauvin², Shuo Tong³, Layth Alama¹, Nicolai Cramer¹

Affiliations

¹ Laboratory of Asymmetric Catalysis and Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnic Fédérale de Lausanne, Lausanne, Switzerland.
² Group of Coordination Chemistry, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³ MOE Key Laboratory of Bioorganic Phosphorus and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.

Abstract

Achieving substrate generality in asymmetric catalysis remains a long-standing goal, particularly for the selective construction of chiral heteroatoms. Compared with carbon, sulfur, phosphorus and silicon stereogenic centres, methods for the construction of their boron and germanium congeners remain very scarce. Chiral (hetero) spirocycles are of relevance in several research domains. Methods effective for constructing carbon-centred chiral spirocycles do not translate to boron and germanium, leaving these chiral centres unexplored. We describe a unified strategy for constructing carbon, boron and germanium-centred chiral spirocyclic skeletons via enantioselective hetero [2+2+2] cycloaddition of a bis-alkyne with a nitrile. A chiral designer Ni(0) N-heterocyclic carbene complex enables the required long-range enantioinduction. The resulting enantio-enriched spirocycles feature a pyridine motif, making them exploitable for ligand design and functional materials featuring attractive photophysical and chiroptical properties.

Keywords: Asymmetric catalysis; Optical materials; Synthetic chemistry methodology.