ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers

preprint
submitted on 05.07.2019 and posted on 08.07.2019 by Veit G. Haensch, Toni Neuwirth, Johannes Steinmetzer, Florian Kloss, Rainer Beckert, Stefanie Gräfe, Stephan Kupfer, Christian Hertweck
The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. We report the scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless linker (photosplicing). Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C–C bond is formed by an intramolecular photochemical process that involves an excited singlet state and the traverse of a five-membered transition state, thus warranting consistent ipsoipso‑coupling fidelity. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls.

Funding

Deutsche Forschungsgemeinschaft (Leibniz Prize, for C.H.)

Federal Ministry of Education and Research (BMBF) of Germany within the program InfectControl 2020 (FKZ 03ZZ0803 for F.K.)

History

Email Address of Submitting Author

christian.hertweck@leibniz-hki.de

Institution

Leibniz Institute for Natural Product Research and Infection Biology

Country

Germany

ORCID For Submitting Author

0000-0002-0367-337X

Declaration of Conflict of Interest

No conflict of interest

Version Notes

Version 1.0

Exports