Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations
In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the benzene ring. Here, we report a general scalable reaction between alkyl iodides and propellane that provides bicyclo[1.1.1]pentane iodides in milligram, gram and even kilogram quantities. The reaction is performed in flow and requires just light; no catalysts, initiators or additives are needed. The reaction is clean enough that, in many cases, evaporation of the reaction mixture provides products in around 90% purity that can be directly used in further transformations without any purification. Combined with the subsequent functionalization, >300 bicyclo[1.1.1]pentanes for medicinal chemistry have been prepared. So far, this is the most general and scalable approach towards functionalized bicyclo[1.1.1]pentanes.
Authors
- Yelyzaveta Nikandrova
- Stanislav Y. Veselovych
- Serhii Zhersh (ORCID: https://orcid.org/0000-0002-5357-6017)
- Vitalina Levchenko (ORCID: https://orcid.org/0009-0008-3862-5563)
- Andrey A. Tolmachev
- Iryna V. Sadkova
- Pavel K. Mykhailiuk (ORCID: https://orcid.org/0000-0003-1821-9011)
- Daniil Vysochyn
- Vasyl Ripenko (ORCID: https://orcid.org/0000-0002-9542-9023)
- Yurii V. Dmytriv (ORCID: https://orcid.org/0000-0002-2218-4459)
- Iryna Pishel (ORCID: https://orcid.org/0000-0002-5267-6817)
- Ivan Klymov
- Serhii Holovchuk
- Vadym Sham (ORCID: https://orcid.org/0000-0003-0059-4876)
- Dmytro Kyslyi
- Kateryna Horbatok
- Viktoria Kosach
Institutions
- National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” (UA)
- Enamine (Ukraine) (UA)
Publication Details
- Journal
- Nature Synthesis
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1038/s44160-024-00637-y
- Citations
- 28
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 7.00
Funders
- European Commission