Novel synthesis of fluoroalkylated α,β-unsaturated ketones by the oxygenative perfluoroalkylation of α-chlorostyrenes

Article abstract of DOI:10.1246/cl.2000.804

The photochemical reaction of perfluoroalkyl iodide with α-chlorostyrenes in the presence of hexabutylditin under oxygen atmosphere produced fluoroalkylated α,β-unsaturated ketones in moderate to good yields.

Full text of DOI:10.1246/cl.2000.804

804
Chemistry Letters 2000
Novel Synthesis of Fluoroalkylated α,β-Unsaturated Ketones by the Oxygenative
Perfluoroalkylation of α-Chlorostyrenes
Masato Yoshida,* Masanori Ohkoshi, and Masahiko Iyoda*
Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397
(Received April 21, 2000; CL-000381)
The photochemical reaction of perfluoroalkyl iodide with
and the corresponding ketones (2) were obtained in moderate to
good yields (Table 1). The length of the fluoroalkyl chains and
the substituents on the benzene ring (p-Me and p-Cl) showed
little effect on the yields of 2 (Table 1; entries 1–5). In 2-naph-
thyl, the ketones 2 were obtained in nearly the same yields with
those in phenyl (Table 1; entries 9–11), but the yields in 1-
naphthyl were slightly lower (Table 1; entries 6–8). The present
α-chlorostyrenes in the presence of hexabutylditin under oxy-
gen atmosphere produced fluoroalkylated α,β-unsaturated
ketones in moderate to good yields.
For the synthesis of perfluoroalkylated organic molecules,
the building-block strategy has now become one of the most
convenient approaches, and considerable efforts have been
devoted to the development of the synthesis of the fluorine-con-
taining building blocks. The perfluoroalkylated α,β-unsaturat-
ed ketones 2 are expected to be important building blocks for
various interesting fluoroalkylated heterocyclic compounds.1–3
Now, we have found a novel synthesis of the ketones 2 starting
from α-chlorostyrenes 1 using perfluoroalkyl radicals and
molecular oxygen (Scheme 1).
Previously, we found the photochemical reaction of perflu-
oroalkyl iodide with styrene in the presence of hexabutylditin
under oxygen atmosphere to produce the fluoroalkylated alco-
hol mainly and the ketone 2 as a side product.4 In order to
obtain the ketone 2 selectively, the reaction conditions and
some olefins such as α-halostyrenes and α-trimethylsilyl-
styrenes were examined. Among the various attempts, in the
reactions of α-chlorostyrene 1a with perfluorohexyl iodide, flu-
oroalkylated ketones were obtained in good yield as a mixture
of 2a, 3a and 4a (Scheme 2).5,6 Although three types of
ketones (2a−4a) were produced in this reaction, the treatment
of the reaction mixture consisting of 2a, 3a and 4a with NEt3
and NaHCO3 in ether gave 2a as the sole product in 60% over-
all yield. Thus, a practical one-pot procedure was carried out
for the synthesis of 2a directly from α-chlorostyrene as shown
in Scheme 2.
A solution of perfluoroalkyl iodide (0.40 mmol), α-
chlorostyrene 1a (1.20 mmol), and (Bu3Sn)2 (0.44 mmol) in
benzene (3 mL) was irradiated using a metal halide lamp
(National Sky-beam MT-70) in a Pyrex tube under O2 atmos-
phere for 5 h. In order to consume the perfluoroalkyl iodide
completely, 1.1 eq of (Bu3Sn)2 was required. The reaction
mixture was evaporated and the residue was dissolved in ether
(2 mL). After treatment of the solution with Et3N (0.1 mL) and
NaHCO3 (130 mg) for 2 h at room temperature, the ketone 2a
was isolated in 42% yield using a silica gel column chromatog-
raphy, followed by gel permeation chromatography. Various
α-chlorostyrenes and related compounds were further examined
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
805
reaction was only applicable to the olefins possessing an aro-
matic ring at the α-position; in the reaction with 2-chloro-1-
octene, the desired fluoroalkylated ketone was not produced.
The oxyfluoroalkylation described here is a very unique
example for the formation of fluoroalkylated ketones directly
from olefins using a perfluoroalkyl radical and molecular oxy-
gen; the use of molecular oxygen for the selective oxidation of
organic substrate is very attractive and challenging.7–9 As α-
chlorostyrenes were readily synthesized from styrenes with
PhSeCl3 or acetophenones with PCl5,10,11 this method is very
convenient and practical for the synthesis of various perfluo-
roalkylated α,β-unsaturated ketones.
Interestingly, Et3N is an effective reagent for the conver-
sion of 3a to 2a (Scheme 2). Since Et3N easily added to 3a to
form the Michael adduct 5a, the more thermodynamically sta-
ble isomer 2a was formed almost quantitatively via
addition–elimination reactions (Scheme 3). Further studies on
the reactions of 2a are now in progress.
3
4
5
Q.-F. Wang, B. Hu, B.-H. Luo, and C.-M. Hu, Tetrahedron
Lett., 39, 2377 (1998).
M. Yoshida, M. Ohkoshi, N. Aoki, Y. Ohnuma, and M.
Iyoda, Tetrahedron Lett., 40, 5731 (1999).
In this reaction, the saturated ketone 4a was produced at
first, and then the elimination of HF from 4a occurred to
give the unsaturated ketone 2a. The ketone 3a should be
produced by the photoisomerization of 2a. When the iso-
lated 2a was irradiated in benzene under similar conditions,
the isomerization from 2a to 3a was observed; the ratio of
2a / 3a in photostationary state was 1 / 4.
1
6
Spectral data. 2a: H-NMR (500 MHz: CDCl3) δ 6.73 (d,
1H, JHF= 31.7 Hz), 7.50 (m, 2H, Ph), 7.62 (m, 1H, Ph),
7.89 (m, 2H, Ph); 13C-NMR (125.7 MHz, CDCl3) δ
110.67, 128.73, 129.00, 134.39, 136.23, 151.69 (d, JCF
=
284 Hz), 186.29; 19F-NMR (470.4 MHz, CDCl3) δ (ppm
down field from external CF3COOH) −5.92 (3F), −37.14
(1F), −43.43 (2F), −47.81 (4F), −51.32 (2F); HRMS,
1
Found 418.0224. Calcd for C14H6F12O 418.0226. 3a: H-
NMR (500 MHz: CDCl3) δ 6.85 (d, 1H, JHF = 20.1 Hz),
7.52 (m, 2H, Ph), 7.65 (m, 1H, Ph), 7.93 (m, 2H, Ph); 13C-
NMR (125.7 MHz, CDCl3) δ 116.24, 128.92, 129.14,
134.55, 135.76, 151.68 (d, JCF = 302 Hz), 186.43; 19F-
NMR (470.4 MHz, CDCl3) δ (ppm down field from exter-
nal CF3COOH) −5.92 (3F), −40.13 (2F), −41.36 (1F),
−47.25 (2F), −47.99 (2F), −51.29 (2F). 4a: 1H-NMR (500
MHz: CDCl3) δ 3.78 (t, 2H, JHF = 17.7 Hz), 7.52 (m, 2H,
Ph), 7.65 (m, 1H, Ph), 7.95 (m, 2H, Ph); 13C-NMR (100.4
MHz, CDCl3) δ 38.69 (t, JCCF = 21 Hz), 128.60, 128.93,
134.19, 136.43, 189.58; 19F-NMR (470.4 MHz, CDCl3) δ
(ppm down field from external CF3COOH) −5.92 (3F),
−36.10 (2F), −46.86 (2F), −47.87 (4F), −51.26 (2F);
HRMS, Found 438.0263. Calcd for C14H7F13O 438.0289.
T. Umemoto, Y. Kuriu, and S. Nakayama, Tetrahedron
Lett., 23, 4101 (1981).
Financial support by a Grant-in-Aid for Scientific Research
on Priority Areas from the Ministry of Education, Science,
Sports and Culture, Japan (11119256) is gratefully acknowl-
edged.
7
8
9
C.-M. Hu, Z.-Q. Xu, and F.-L. Quing, Tetrahedron Lett.,
30, 6717 (1989).
Y. Sato, S. Watanabe, and K. Uneyama, Bull. Chem. Soc.
Jpn., 66, 1840 (1993).
References and Notes
1
T. Umemoto, Y. Kuriu, S. Nakayama, and O. Miyano,
Tetrahedron Lett., 23, 1471 (1982).
X.-Q. Tang and C.-M. Hu, J. Chem. Soc., Perkin Trans. 1,
1994, 2161.
10 L. Engman, J. Org. Chem., 52, 4086 (1987).
11 T. L. Jacobs, Org. Reactions, 5, 20 (1949).
2