Metal-Free Visible Light Hydroperfluoroalkylation of Unactivated Alkenes Using Perfluoroalkyl Bromides

Article abstract of DOI:10.1021/acs.orglett.8b03596

Organic dye-catalyzed visible light induced hydroperfluoroalkylation of unactivated alkenes is described. Hydroperfluoroalkylation proceeds selectively and is applicable for various perfluoroalkyl bromide and alkenes including internal alkenes. The reaction mechanism is discussed, and it is shown that the hydrogen source varies with reaction conditions.

Full text of DOI:10.1021/acs.orglett.8b03596

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Metal-Free Visible Light Hydroperfluoroalkylation of Unactivated
Alkenes Using Perfluoroalkyl Bromides
Tomoko Yajima* and Satsuki Shigenaga
Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
S
* Supporting Information
ABSTRACT: Organic dye-catalyzed visible light induced hydroperfluoroalkylation of
unactivated alkenes is described. Hydroperfluoroalkylation proceeds selectively and is
applicable for various perfluoroalkyl bromide and alkenes including internal alkenes.
The reaction mechanism is discussed, and it is shown that the hydrogen source varies
with reaction conditions.
reaction using perfluoroalkyl halides;9 however, the Giese-type
he incorporation of perfluoroalkyl groups to organic
Tcompounds can confer unique properties such as reaction is not suitable for the radical perfluoroalkylation,
because the hydrogen donor used for the reaction reacts
preferentially with electron-poor perfluoroalkyl radicals and the
desired adduct is difficult to obtain.10 Furthermore, the
reaction must compete with ATRA or addition−elimination
reactions, and achieving selective hydroperfluoroalkylation is
problematic.11 Recently, iridium-catalyzed visible-light-induced
hydrofluoroalkylations of unactivated terminal olefins using a
Hantzsch ester6m or an amine6i as the hydrogen donor have
been reported. However, in these cases, ATRA or addition−
elimination products are also produced, and the examples of
selective hydroperfluoroalkylation are limited.
In the previous work, we studied organic dye-catalyzed
perfluoroalkylation using perfluoroalkyl iodide and reported
that a Kharasch-type iodoperfluoroalkylation reaction pro-
ceeded with various unactivated terminal alkenes and
alkynes.6n In this study, we have investigated an Eosin Y
catalyzed visible light induced reaction using perfluoroalkyl
bromide and found that the reaction gave the hydro-
perfluoroalkylation product selectively. Herein, we report a
metal-free selective hydroperfluoroalkylation of unactivated
olefins, which is the first example of organic dye-catalyzed
perfluoroalkylation using perfluoroalkyl bromide.
We initially examined the reaction between fluoroalkyl
bromide and decene (1) (Table 1). First, the reaction of
decene with 3.0 equiv of perfluorohexyl bromide using 10 mol
% of Eosin Y (3a) with photoirradiation for 17 h using a 12 W
white LED in CH3CN in the presence of aqueous Na2S2O3 was
tested according to our previous report (Table 1, entry 1).6n As
a result, the corresponding hydroperfluorohexylated product
2a was obtained in 10% yield. We tried the reaction in THF
and found that the reaction yield was increased up to 48%
(Table 1, entry 2). Then we screened organic dyes (Table 1,
entries 3−5). The reactions using Phloxine B (3c) and Rose
increased lipophilicity, high chemical and thermal stability,
high water repellency, and so on.1 Owing to their behavior,
perfluoroalkylated compounds have been widely used not only
for pharmaceuticals but also for materials, and the develop-
ment of efficient perfluoroalkylation reactions is a significant
challenge. Therefore, many general and mild perfluoroalkyla-
tions have been reported,2 among which radical perfluor-
oalkylation is one of the most convenient and direct methods
to introduce perfluoroalkyl groups into organic compounds.3
More specifically, the radical reaction using perfluoroalkyl
halides can provide a general method for the introduction of
many kinds of perfluoroalkyl groups, especially because a
variety of perfluoroalkyl halides are commercially available and
easy to obtain.4 Recently, radical reaction using photoredox
catalysis has emerged as an active, sustainable, and promising
field of research.5 Photoredox-catalyzed perfluoroalkylations
have been reported previously;6 however, there are limited
examples using perfluoroalkyl halides as the perfluoroalkyl
source.
There are two well-known types of reactions for the radical
addition to alkenes: the Kharasch-type reaction,7 which gives
an atom transfer radical addition (ATRA) product, and the
Giese-type reaction,8 which gives a hydrogen transfer product
(Scheme 1). The Kharasch-type reaction is well-known for the
Scheme 1. Perfluoroalkylation of Olefins
Received: November 9, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03596
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Letter
a
Table 1. Optimization of the Reaction Conditions
entry
organic dye (mol %)
RfBr (equiv)
solvent
CH3CN
THF
THF
THF
prod
yield (%)
1
2
3
4
5
6
3a (10)
3a (10)
3b (10)
3c (10)
3d (10)
3a (10)
3a (10)
3a (5)
3a (10)
3a (10)
3a (10)
3a (10)
3a (10)
3a (10)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (3.0)
C6F13Br (2.5)
C6F13Br (3.0)
C4F9Br (3.0)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2d
10
48
4
33
38
82
77
67
69
64
61
82
66
34
THF
b
b
b
b
b
b
b
b
b
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
THF/CH3CN
c
7
8
9
10
d
11
12
13
14
EtCO2CF2Br (3.0)
BrCF2CF2Br (1.5)
BrCF2CF2Br (0.5)
a
Reaction conditions: 1 (0.20 mmol), RfBr, 3, solvent (5 mL), Na2S2O3 aq. (1.00 mmol in 1 mL of H2O) at rt for 17 h irradiated with 12 W white
b
c
d
LED under N2 unless otherwise noted. 1:1 mixture. 8 h irradiation. In the absence of Na2S2O3 aq.
Bengal (3d) also proceeded, but the yields were slightly lower
than that of the reaction with Eosin Y. We then tried the
reaction using a 1:1 mixture of CH3CN/THF as a solvent and
found that the yield improved to 82% (Table 1, entry 6). The
reaction was clean, and no side products were observed (SI,
Figure S1). The reactions having a shorter reaction time or a
reduced amount of catalyst or perfluorohexyl bromide
exhibited lower yields (Table 1, entry 7−9). In the absence
of aqueous Na2S2O3, the reaction proceeded, but the yield was
lower (Table 1, entry 10). The reactions using perfluorobutyl
bromide and ethyl bromodifluoroacetate were investigated and
gave their respective fluoroalkylated products in good yield
(Table 1, entries 11 and 12). The reaction with 1,2-
dibromoperfluoroethane was also tested and gave the 1:1
adduct as a single product (Table 1, entries 13 and 14).
Next, we tried the reaction with various unactivated terminal
olefins with perfluorohexyl bromide under the optimized
reaction conditions (Table 1, entry 8) (Scheme 2). The
substrates containing amide (5a), ester (5b), sulfonyl (5c),
and ether groups (5e) proceeded to give the corresponding
hydroperfluoroalkylated product in moderate yield. The
substrate possessing an amide proton (5d) lowers the yield,
but the reaction proceeded. The reactions with aromatic rings
(5f, 5g) also proceeded, and the perfluoroalkylation of the
phenyl group did not occur. We also attempted the reaction
with styrene,12 but the desired product was not obtained.
Interestingly, perfluoroalkylation also proceeded with
unprotected alcohol 4h; however, the THF adduct 6 was
formed as a major product together with perfluoroalkylated
alcohol 5h (Scheme 3).
Scheme 2. Hydroperfluoroalkylation of Terminal Alkenes
Using internal alkenes in the reaction was also investigated
(Scheme 4). The reaction with cyclohexene did not proceed,
but the reaction with cyclooctene gave the corresponding
hydroperfluoroalkylated product 8a. The reaction in the
absence of water gave a higher yield than in the presence of
water in this case. The reaction with cycloheptene gave the
product 8b in 18% yield, and the reaction with 2-norbornene
gave a 44% yield of 8c. The hydroperfluoroalkylation also
proceeded with distorted internal olefins, although the yield
B
DOI: 10.1021/acs.orglett.8b03596
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Scheme 3. Hydroperfluoroalkylation of 4h
Scheme 6. Labeled Experiment
However, the reaction also proceeded in the absence of
aqueous Na2S2O3. Therefore, the second pathway in which
hydrogen comes from THF has been proposed (Scheme 5,
blue line route). The intermediate radical receives hydrogen
from THF, forming a THF radical. Then the THF radical
reacts with the radical cation of Eosin Y, and the catalytic cycle
of Eosin Y is thereby completed. The reacted THF radical is
converted to a carbocation, and when the substrate is alcohol,
as shown in Scheme 2, the THF cation reacts with the
hydroxyl group of alcohol. In order to verify this route, alcohol
was added to the reaction mixture (Scheme 7). Reaction in the
Scheme 4. Hydroperfluoroalkylation of Internal Alkenes
and Alkynes
Scheme 7. In the Presence of Alcohol
a
In the presence of aq. Na2S2O3 (5.0 equiv).
presence of decanol gave the THF adduct, 10, as we expected.
These experiments demonstrated that the reaction presents
two pathways, wherein the hydrogen is derived from either
water or THF.
was not unsatisfactory. The reaction with a terminal alkyne
gave the corresponding hydroperfluoroalkylated alkene 8d as a
stereoisomeric mixture.
Based on these results, we propose the reaction mechanism
as shown in Scheme 3. The photoexcited Eosin Y reacted with
perfluoroalkyl bromide to give a perfluoroalkyl radical and
bromonium ion. The radical was then added to the olefin to
give the intermediate radical, at which point there are two
possible reaction pathways for the intermediate radical.
The first pathway is possible when the reaction is performed
in the presence of aqueous Na2S2O3 (Scheme 5, red line
In summary, we have developed metal-free Eosin Y-
catalyzed visible light induced perfluoroalkylations of unac-
tivated olefins. Selective hydroperfluoroalkylation was achieved
with the use of perfluoroalkyl bromides. We also revealed that
the reaction can proceed via two different pathways: one in
which the hydrogen is derived from water, and another in
which hydrogen is derived from THF. Furthermore, the
reaction permits various bromides and olefins including
internal olefins, which are inappropriate according to the
previously reported iodoperfluoroalkylation. The reaction is
very sustainable and enables the synthesis of various
perfluoroalkyl compounds.
a
Scheme 5. Proposed Mechanism
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03596.
Experimental procedures, and characterization of all new
products, including 1H, 13C and 19F NMR spectra
(PDF)
a
In the presence of aq. Na2S2O3: red line route. In the presence of
THF: blue line route.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yajima.tomoko@ocha.ac.jp.
ORCID
route). The intermediate radical is reduced to the carbanion by
Na2S2O3 and reacts with water to give a hydroperfluoroalky-
lated product. To confirm that hydrogen originated from
water, a labeled experiment using D2O was performed
(Scheme 6). As expected, the reaction gave a deuterated
product.
Tomoko Yajima: 0000-0001-8376-3465
Notes
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.8b03596
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “Advanced Molecular Trans-
formations by Organocatalysts” (No. 26105717) and Scientific
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DOI: 10.1021/acs.orglett.8b03596
Org. Lett. XXXX, XXX, XXX−XXX