Citation: Mengyu Wu, Kewei Ren, Chengyu Zou, Jiacheng Chen, Rui Ma, Chuan Zhu, Chao Feng. A general synthesis of gem–difluorobicyclo[2.1.1]hexanes[J]. Chinese Chemical Letters, ;2025, 36(5): 110213. doi: 10.1016/j.cclet.2024.110213 shu

A general synthesis of gem–difluorobicyclo[2.1.1]hexanes

Mengyu Wu ^a ,
Kewei Ren ^a ,
Chengyu Zou ^b ,
Jiacheng Chen ^a ,
Rui Ma ^a ,
Chuan Zhu ^{a, *,} ,
Chao Feng ^{a, *,}

a.
Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis (IAS), School of Chemistry and Molecular Engineering, State Key Laboratory of Material-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211816, China
b.
College of Electrical Engineering and Control Science, Nanjing Tech University, Nanjing 211816, China

ias_czhu@njtech.edu.cn

iamcfeng@njtech.edu.cn

Received Date: 21 May 2024
Revised Date: 18 June 2024
Accepted Date: 3 July 2024
Available Online: 22 August 2024

Figures(6)

Bridged bicyclic cores have been recognized as valuable bioisosteres of benzene ring, which are of great value in medicinal chemistry. However, the development of fluorinated bicyclic skeletons, which encompass two privileged elements widely acknowledged for fine tuning the working effect of target molecules, are far less common. Herein, we present a general and practical synthesis of gem–difluorobicyclo[2.1.1]hexanes (diF-BCHs) from readily available difluorinated hexa-1,5-dienes through energy transfer photocatalysis. By taking advantage of an efficient Cope rearrangement, the preparation of both constitutional isomers of diF-BCHs is readily achieved under identical conditions. The operational simplicity, mild conditions and wide scope further highlight the potential application of this protocol. Moreover, computational studies indicated a positive effect of fluorine atoms in lowering either the triplet or FMO energies of the hexa-1,5-diene substrates, thus promoting the present photoinduced [2 + 2] cycloaddition.
- gem-Difluorobicyclo[2.1.1]hexanes,
- Visible-light phototcatalysis,
- Energy transfer,
- [2 + 2] Cycloaddition,
- Fluorine effects
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