Angewandte
Communications
Chemie
Photoredox Catalysis
Radical Fluoroalkylation of Isocyanides with Fluorinated Sulfones by
Visible-Light Photoredox Catalysis
Jian Rong, Ling Deng, Ping Tan, Chuanfa Ni,* Yucheng Gu, and Jinbo Hu*
Abstract: The radical fluoroalkylation of isocyanides with
fluorinated sulfones is enabled by visible-light photoredox
catalysis. A wide range of readily available mono-, di-, and
trifluoromethyl heteroaryl sulfones can thus be used as efficient
radical fluoroalkylation reagents under mild conditions. This
method not only describes a new synthetic application of
fluorinated sulfones, but also provides a new route to
fluoroalkyl radicals.
As the “chemical chameleon” in organic synthesis, the
sulfone functional group is ideal for various types of reactions,
and its electron-withdrawing ability can be easily tuned.[15] In
the past decade, fluorinated sulfones have been developed as
versatile fluoroalkylation reagents and widely used for the
incorporation of diverse fluoroalkyl groups into organic
molecules by us and others.[4e] However, the use of fluoroalkyl
sulfones and their derivatives for radical fluoroalkylation by
À
Rf SO2 (Rf = fluoroalkyl) bond cleavage to form RfC radicals
T
he incorporation of fluorinated moieties into organic
is challenging owing to the limitations of conventional radical
initiators or single-electron-transfer (SET) reductants.[16] In
recent years, visible-light photoredox catalysis has emerged as
a powerful synthetic method for bond activation and con-
struction processes that are usually difficult to achieve with
conventional methods.[5] We envisioned that photoredox
catalysts that can generate highly reactive SET reductants
molecules can often lead to significant changes of their
physical, chemical, or biological properties.[1–3] Consequently,
great efforts have been made to develop efficient strategies,
methods, reagents, and catalysts for the incorporation of
fluorine atoms or fluorinated moieties into organic molecules
by nucleophilic, electrophilic, and radical pathways.[4] In
recent years, radical fluoroalkylation reactions by visible-
light photoredox catalysis have attracted much attention
because of their mild reaction conditions and broad func-
tional-group tolerance,[5,6] and many radical fluoroalkylation
reagents, including fluoroalkyl halides (such as CF3I,[7]
PhSO2CF2I,[8] BrCF2COOEt,[9] and BrCHFCOOEt[9b]), fluo-
À
under mild conditions could be used to activate the Rf SO2
bonds of fluoroalkyl sulfones for radical fluoroalkylation.
Herein, we report the use of mono-, di-, and trifluorinated
heteroaryl sulfones as a new class of readily available, bench-
stable, and reactivity-tunable radical fluoroalkylation
reagents
under
visible-light
photoredox
catalysis
roalkanesulfonyl
halides
(such
as
CF3SO2Cl,[10]
(Scheme 1). The high efficiency of this method is demon-
strated by the radical fluoroalkylation of various isocyanides
as excellent radical acceptors[17] to afford fluoroalkylated
phenanthridine derivatives.
HCF2SO2Cl,[11] and CH2FSO2Cl),[11a] the Umemoto
reagents,[12] the Togni reagents,[4c,13] and the Langlois
reagent,[14] have been used for this purpose. Although great
progress has been made in photoredox fluoroalkylation,[6]
especially trifluoromethylation, the known reagents suffer
from limitations, such as the operational complexity intro-
duced by removal of the activation group and the difficulty
associated with handling some of the gaseous starting
materials required to prepare these reagents. Therefore, it is
still of great significance to develop operationally simple,
easy-to-handle, and practical fluoroalkylation reagents that
are suitable for efficient fluoroalkyl group transfer under
photoredox catalysis.
Scheme 1. Radical fluoroalkylation with fluorinated sulfones.
We first investigated the radical reactivity of a series of
difluoromethyl sulfones 2 by using isocyanide 1a as a model
substrate (Table 1). According to the first reduction potentials
of several difluoromethyl sulfones (2a: À1.80 V; 2b: À1.50 V;
2c: À1.35 V; 2d: À1.17 V versus the saturated calomel
electrode, SCE) that we measured by cyclic voltammetry
(see the Supporting Information), we initially used sulfone
2d, which has the highest reduction potential, for the radical
difluoromethylation of 1a under photoredox conditions with
[Ru(bpy)3]Cl2·6H2O as the catalyst (2 mol%), Na2CO3
(2 equiv) as the base, and CH3CN as the solvent (entry 1).
We were pleased to find that the desired product 3a was
formed in 22% yield. Solvent screening showed that polar
solvents were beneficial to this reaction (entries 1–7). In
[*] J. Rong, L. Deng, P. Tan, Dr. C. Ni, Prof. Dr. J. Hu
Key Laboratory of Organofluorine Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Ling-Ling Road, Shanghai, 200032 (China)
E-mail: nichuanfa@sioc.ac.cn
Dr. Y. Gu
Syngenta, Jealott’s Hill International Research Centre
Bracknell, Berkshire RG42 6EY (UK)
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2016, 55, 2743 –2747
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2743