A new study published in Journal of the American Chemical Society (JACS) reports a significant advancement in the field of skeletal editing, a growing area of organic synthesis. The research is the result of a collaboration between the groups of Prof. Marcos Garcia Suero and Prof. Feliu Maseras at the Institute of Chemical Research of Catalonia (ICIQ). It presents the first example of an enantioselective single-carbon insertion that transforms 3-aryl indoles into atropochiral quinolines.
The work demonstrates a novel atroposelective ring-expansion strategy enabled by a catalytically generated chiral rhodium carbynoid intermediate. This highly selective transformation proceeds with excellent efficiency and enantiocontrol, allowing precise construction of a stereogenic C(sp²)–C(sp²) axis. The methodology represents a rare application of α-diazo halocarbonyl compounds in highly enantioselective processes.
Skeletal editing, which involves the direct modification of molecular frameworks via single atom insertion or deletion, is increasingly seen as a powerful strategy for molecular diversification. This study adds to a growing body of research led by Prof. Suero’s group, which has previously pioneered the use of Rh(II)-carbynoids in bond-forming processes involving single-carbon insertion.
Atropisomers—molecules with restricted rotation around a single bond—play a crucial role in pharmaceuticals, materials science, and catalysis. Despite significant progress in catalytic approaches to atroposelectivity, strategies involving ring expansion had remained largely unexplored. The current work addresses this gap by applying a Ciamician–Dennstedt-type transformation under enantioselective conditions.
Computational studies conducted by Prof. Maseras’ group supported the experimental findings, providing insight into the origin of the atroposelectivity and confirming the role of the chiral Rh-carbynoid intermediate in determining the stereochemical outcome.
“The work reports a Rh-catalyzed atroposelective single-carbon insertion into 3-aryl indoles to generate atropochiral quinolines. This strategy provides a new attempt for the construction of biaryl atropisomers, represents a unique example of a highly enantioselective process through a new chiral Rh(II)-carbynoid platform, and broadens the toolkit for enantioselective skeletal editing in organic synthesis” as explained by Dr. Bowen Li, first author and postdoctoral researcher in the Prof. Suero’s group.
This contribution underlines ICIQ’s continuing leadership in the development of innovative catalytic tools for molecular editing, with potential implications for the synthesis of bioactive molecules and novel materials.
Reference publication
Rh-Catalyzed Atroposelective Single-Carbon Insertion
Li, B.; Alfonso, V. G.; Puggioli, A.; Solé-Daura, A.; Maseras, F.; Suero, M. G.
J. Am. Chem. Soc. 2025
DOI: 10.1021/jacs.5c06139
La entrada ICIQ researchers advance skeletal editing with first enantioselective single-carbon insertion into indoles se publicó primero en ICIQ.