Tetrahedron Letters
Nucleophilic fluoroalkylation of terminal vinyl triflones with SO CF as a
2
3
removable activating group
a
a
a
b
a,
⇑
Ping-ping Tian , Hong-qing Xiao , Lu Wang , Yingxin Yu , Yangen Huang
a
Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999
North Renmin Lu, Shanghai 201620, China
Guangzhou Key Laboratory Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of
b
Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Terminal vinyl triflones served as excellent Michael addition acceptors which readily reacted with diflu-
Received 11 February 2019
Revised 3 March 2019
Accepted 6 March 2019
Available online xxxx
oromethylene phosphabetaine and di- or mono-fluoroalkyl bromides to afford compounds containing CF
or CF groups. This fluoroalkylation is characterized by mild reaction conditions, ready availability of
reagents and excellent functional-group tolerance.
2
Ó 2019 Published by Elsevier Ltd.
Keywords:
Difluoromethylation
Michael addition
Difluoromethylene phosphabetaine
Vinyl triflones
The introduction of fluorine atoms to organic compounds has
attracted significant attention with the expectation of beneficial
changes in the physical, chemical, and biological properties of
the parent compounds [1]. Since naturally occurring fluorine-con-
taining organic compounds are extremely rare, the development of
synthetic methodology for their preparation has been the focus of
organofluorine chemistry, especially with the growing academia
and industry demands for fluorine-containing organic compounds
access to the corresponding difluoromethylated alkanes (Scheme 1,
a) [6]. Dilman and co-workers reported that a series of arylidene
derivatives of Meldrum’s acid reacted with difluoromethylene
phosphabetaine to produce difluoromethylated carboxylic acids
(Scheme 1, b) [7]. Kumadaki and co-workers showed that ethyl
bromodifluoroacetate reacted with various Michael addition
acceptors to give 1,4-adducts in moderate to good yields when
TMEDA was used as an additive (Scheme 1, c) [8]. Consistent with
our continuing interest in the development of synthetic methodol-
ogy for fluorinated compounds, we have recently reported the
[
2]. Fluorinated compounds are mainly obtained by the fluorina-
tion and fluoroalkylation of organic compounds. During the past
decades, the fluoroalkylation reaction has seen great advances
3 2
iodine-mediated direct CAH triflylation of styrenes with CF SO Na
[
3]. Among them, the fluoroalkylation of alkenes is of particular
as an efficient route for the regioselective synthesis of vinyl tri-
flones [9]. Considering the unique characteristics of the trifluo-
romethanesulfonyl (triflyl, SO CF , Tf) group, such as strong
2 3
electron withdrawing ability and high lipophilicity [10], we dis-
close herein the di- and mono-fluoroalkylation of vinyl triflones
interest for the preparation of fluoroalkyl-substituted alkanes;
therefore, the trifluoromethylation and perfluoro-alkylation of
alkenes have been well studied [4]. Meanwhile, the difluo-
2
romethylene group (CF ), which is regarded as a bioisostere for
an oxygen atom, carbonyl group and methylene group, can dra-
matically improve the biological properties of the corresponding
compounds [3c], and fluoroalkyl addition over C@C and C@N
bonds has become one of the most straightforward methods for
3 2
with different fluoroalkyl nucleophiles to give a series of CF SO -
containing compounds. This protocol provides a new method to
access fluoroalkylated alkanes from readily available substrates
and reagents.
constructing C–CF
disclosed that the visible-light-induced reaction of alkenes with
bromodifluoromethyl-phosphonium bromide as a difluoromethyl
2
bonds [5]. For example, Qing and co-workers
In 2013, Xiao and co-workers reported that the decarboxylation
+
CO-
of difluoromethylene phosphobetaine (Ph
3
P CF
2
2
, PDFA, 1) at
90 °C in p-xylene can give the difluoromethylene ylide, which is
the precursor of difluorocarbene [11]. In 2014, Dilman and co-
workers demonstrated that this difluoromethylene ylide can serve
as an equivalent of the difluoromethyl carbanion to undergo
Michael addition, but only arylidene derivatives of Meldrum’s acid
3 2
source in the presence of PPh , H O, and THF provided efficient
⇑
040-4039/Ó 2019 Published by Elsevier Ltd.
0
2 3
CF as a removable activating