Fluoride ion-assisted cross-coupling reactions of (α-fluorovinyl)diphenylmethylsilane with aryl iodides catalyzed by Pd(0)/Cu(I) systems

Article abstract of DOI:10.1055/s-2001-10791

The palladium-catalyzed cross-coupling reactions of (αfluorovinyl)diphenylmethylsilane with organic halides in the presence of Cu(I) halide afford good yields of α-fluorovinyl organic compounds.

Full text of DOI:10.1055/s-2001-10791

LETTER
281
Fluoride Ion-Assisted Cross-Coupling Reactions of ( -Fluorovinyl)diphenyl-
methylsilane with Aryl Iodides Catalyzed by Pd(0)/Cu(I) Systems
Takeshi Hanamoto,* Tomoko Kobayashi, Michio Kondo
Department of Chemistry and Applied Chemistry, Saga University, Honjyo-machi 1, Saga 840-8502, Japan
Fax (81)-952-28-8704; E-mail: hanamoto@cc.saga-u.ac.jp
Received 24 November 2000
be a promising way. McCarthy et al. have already report-
Abstract: The palladium-catalyzed cross-coupling reactions of ( -
ed the coupling reaction of ( -fluorovinyl)tributylstan-
fluorovinyl)diphenylmethylsilane with organic halides in the pres-
nane with organic halides, however, the preparation for
ence of Cu(I) halide afford good yields of -fluorovinyl organic
( -fluorovinyl)tributylstannane does not seem to be easy.3
compounds.
We have recently synthesized ( -fluorovinyl)diphenyl-
Key words: cross-coupling reaction, 2-fluorinated terminal olefin,
methylsilane and reported the -fluorovinylation of car-
bonyl compounds.4 We believed that the ( -fluorovi-
nyl)diphenylmethylsilane/F- system would be applicable
for the cross-coupling reaction.5 This report describes the
palladium-catalyzed cross-coupling reactions of ( -fluo-
rovinyl)diphenylmethylsilane with organic halides in the
presence of Cu(I) halide.
( -fluorovinyl)diphenylmethylsilane, palladium catalyst, cuprous
iodide
Fluorinated olefins have recently become an area of active
investigation due to their unique properties and biological
activities.1 Among them, the 2-fluorinated terminal ole-
fins are important moieties for the study of mechanism-
based enzyme inhibitors.2 Although some methods have
been developed for providing a path to monosubstituted 2-
fluoro-1-olefins, we have considered that the coupling re-
action of an unsubstituted 1-fluorovinyl compound would
We examined various systems for the reaction of 4’-io-
doacetophenone 2 with ( -fluorovinyl)diphenylmethylsi-
lane 1. The first experiment revealed that the reaction
produced the desired cross-coupling adduct 3, along with
its byproduct 4, in good combined yields. These results
Table 1 Screening of the reaction conditions
SiPh2Me
+
COMe
+
I
COMe
Ph
COMe
F
F
1
2
3
4
Entry
MF (eq.)
Pd (mol%)
CuX (mol%)
Solv.
Temp/°C Time/h
Yield/%
3
4
20
9
1
2
KF (1.5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(OAc)2 (5)
PdCl2(PPh3)2 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
CuI (150)
CuI (20)
CuI (20)
CuI (10)
CuI (10)
CuCl (10)
CuI (10)
CuI (10)
CuI (5)
DMF
DMF
DMF
DMI
DMI
DMI
DMI
DMI
DMF
DMI
DMI
25
25
25
25
25
25
25
25
25
25
50
25
64
80
40
96
96
144
64
64
24
40
32
2
78
60
66
63
93
70
47
77
67
60
73
92
KF (1.5)
3
CsF (1.5)
KF (1.5)
20
18
4
4
5
CsF (1.5)
CsF (1.5)
CsF (1.5)
CsF (1.5)
CsF (1.5)
CsF (1.5)
CsF (1.5)
CsF (3.7)
6
18
4
7
8
16
7
9
10
11
12
CuI (5)
0
CuI (5)
7
CuI (5)
DMI-THF
= 9/1
0
Synlett 2001 No. 2, 281–283 ISSN 0936-5214 © Thieme Stuttgart · New York

282
T. Hanamoto et al.
LETTER
are summarized in Table 1. After a long optimization
work on the reaction, we picked the best procedure. A typ-
ical experimental procedure is as follows: Pd(PPh3)4 (19.8
mg, 0.02 mmol) was added to a suspension of 1 (122.1
mg, 0.5 mmol), 2 (83.0 mg, 0.34 mmol), and anhydrous
CsF (188.0 mg, 1.24 mmol) in DMI (3.6 mL) and THF
(0.4 mL), and the mixture was stirred at room temperature
for 2 hours. The mixture was then extracted with ether/
hexane = 1/1, dried with Na2SO4, and concentrated. The
residue was purified by silica gel chromatography and af-
forded 3 in 92% yield (50.9 mg) (entry 12).6 A Cu(I) ha-
lide and palladium catalyst are essential for the cross-
coupling reaction.7-9 The catalytic activity of several pal-
ladium complexes decreases in the order Pd(PPh3)4 >
PdCl2(PPh3)2 > Pd(OAc)2. CsF is superior to spray-dried
KF, however, TBAF as an organic fluoride source was in-
effective. CuI is superior to CuCl, and DMF is also effec-
tive for the reaction. An excess amount of Cu(I) halide
increases the byproduct 4. No reaction took place in THF,
however, this solvent plays an important role in reducing
the formation of the byproduct 4 in this reaction. When we
applied these mixed solvent conditions to the reaction of
other aryl halides, we encountered the incomplete con-
sumption of the starting substrates except for the nitro
compound (Table 2, entry 2). However, this problem was
solved by using DMI as the sole solvent.
Table 2 Cross-coupling reaction of ( -fluorovinyl)diphenylme-
thylsilane 1 with various aryl halidesa
Entry
Yield
(%)b
Ar-X
Product
ratioc
1d
MeOC
O2N
Br
I
3
62
84
91
89
84 : 16
2e
9a
9b
9c
99 : 1
99 : 1
98 : 2
3
EtO2C
I
I
4
CO2Me
I
5
9d
9e
9f
86
90
63
98 : 2
99 : 1
93 : 7
MeO
AcO
I
I
6
7f
MeO
aAll reactions were conducted with ( -fluorovinyl)diphenylmethyl-
silane (1.5 equiv.) with aryl halides (1.0 equiv.) in the presence of
CuI (5 mol%), Pd(PPh3)4 (5 mol%) and CsF (2.3 equiv.) in DMI at
room temperature. bIsolated yield. cTarget molecule:Byproduct.
Representative results of the cross-coupling reaction of a
variety of aryl halides are shown in Table 2.10 The aryl
bromide was less effective compared to the aryl iodide. A
wide range of functional groups (nitro, ester, ketone, and
ether) on the aromatic rings could be tolerated under the
given reaction conditions. The yields of the aryl iodide
substituted by an electron-withdrawing group were gener-
ally high, however, that of the aryl iodide substituted by
an electron-donating group were moderate. These obser-
vations are probably due to the sluggish oxidative addition
of the Ar-I bonds in the electron-rich aryl iodides.
e
dCuI (10 mol%) was used. The reaction was conducted in DMI-
THF = 9/1. fThe reaction was conducted at 50 °C.
with regenerating CuI and the Pd(0) catalysts. Subsequent
reductive elimination of the resulting diorganopalladium
species 8 afforded the coupled product 9.
In conclusion, we have demonstrated the cross-coupling
reaction of an aryl iodide with ( -fluorovinyl)diphenyl-
methylsilane 1 catalyzed by the CsF/Pd(0)/CuI systems.
In particular, the reaction of this mono-fluorinated silane
reagent proceeded at room temperature in the presence of
a catalytic amount of CuI. A variety of functional groups
can tolerate these mild conditions.
Although we have not examined the mechanism of the ob-
served palladium-catalyzed cross-coupling reactions in
detail, we propose the following plausible mechanism for
the reaction (Scheme). Initially, the reaction between CuI
and the pentavalent silicate 5 generated from 1 and CsF
would give the vinyl copper(I) reagent 6 which facilitates
the transmetallation with the palladium species 7 along
Ar
F
-
9
SiPh2MeF
Pd-Ar
CuI
F
F
8
5
Pd(0)
Cu
Ph2MeSiF
Ar-Pd-I
F
7
Ar-I
6
Scheme
Synlett 2001, No. 2, 281–283 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Fluoride Ion-Assisted Cross-Coupling Reactions
283
(7) Urata, H.; Fuchikami, T. Tetrahedron Lett. 1991, 32, 91.
(8) For transmetallation from tin to copper see: (a) Chen, C.;
Wilcoxen, K.; Zhu, Y.; Kim, K.; McCarthy, J. R. J. Org.
Acknowledgement
We thank Chemetall Japan Co., Ltd. for a gift of CsF.
Chem. 1999, 64, 3476. (b) Chen, C.; Wilcoxen, K.; Kim, K.;
McCarthy, J. R. Tetrahedron Lett. 1997, 38, 7677.
References and Notes
(9) For transmetallation from silicon to copper see: (a) Lam, P. Y.
S.; Deudon, S.; Averill, K. M.; Li, R.; He, M. Y.; DeShong, P;
Clark, C. G. J. Am. Chem. Soc. 2000, 122, 7600. (b) Nishihara,
Y.; Ikegashira, K.; Hirabayashi, K.; Ando, J.; Mori, A.;
Hiyama, T. J. Org. Chem 2000, 65, 1780.
(1) Hudlicky, M.; Pavlath, A. E. Chemistry of Organic Fluorine
Compounds II; ACS Monogragh 187; Washington, DC, 1995.
(2) (a) Matthews, D. P.; Gross, R. S.; McCarthy, J. R.
Tetrahedron Lett. 1994, 35, 1027. (b) Matthews, D. P.; Miller,
S. C.; Jarvi, E. T.; Sabol, J. S.; McCarthy, J. R. Tetrahedron
Lett. 1993, 34, 3057. (c) Sabol, J. S.; McCarthy, J. R.
Tetrahedron Lett. 1992, 33, 3101. (d) McCarthy, J. R.;
Matthews, D. P.; Stemerick, D. M.; Huber, E. W.; Bey, P.;
Lippert, B. L.; Snyder, R. D.; Sunkara, P. S. J. Am. Chem. Soc.
1991, 113, 7439.
(3) Matthews, D. P.; Waid, P. P.; Sabol, J. S.; McCarthy, J. R.
Tetrahedron Lett. 1994, 35, 5177.
(4) Hanamoto, T.; Harada, S.; Shindo, K.; Kondo, M. Chem.
Commun. 1999, 2397.
(5) (a) Hatanaka, Y.; Hiyama, T. Pure & Appl. Chem. 1994, 66,
1471. (b) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53,
918. (c) Denmark, S. E.; Wang, Z. Synthesis 2000, 999.
(6) 3: white solid, mp 56.2-57.8 °C; 1H NMR (CDCl3) 2.62 (3H,
s), 5.00 (1H, dd, J = 17.6, 3.9 Hz), 5.16 (1H, dd, J = 48.8, 3.9
Hz), 7.65 (2H, d, J = 8.3 Hz), 7.97 (2H, d, J = 8.3 Hz); MS
(m/z) 164 (26, M+), 149 (100), 101 (57), 75 (21); IR (KBr)
cm-1 1679, 830; Anal. calcd. for C10H9FO: C, 73.16; H, 5.53.
Found: C, 73.11; H, 5.62.
(10) 1H NMR spectra (CDCl3) for all products (9a-9f):
9a: 5.11 (1H, dd, J = 17.6, 3.9 Hz), 5.27 (1H, dd, J = 48.6, 3.9
Hz), 7.72 (2H, d, J = 8.3 Hz), 8.25 (2H, d, J = 8.3 Hz); 9b:
1.40 (3H, t, J = 7.3 Hz), 4.39 (2H, q, J = 7.3 Hz), 4.98 (1H, dd,
J = 17.8, 3.4 Hz), 5.17 (1H, dd, J = 49.1, 3.4 Hz), 7.62 (2H, d,
J = 8.3 Hz), 8.05 (2H, d, J = 8.3 Hz); 9c: 3.91 (3H, s), 4.80
(1H, dd, J = 47.4, 3.4 Hz), 4.96 (1H, dd, J = 16.1 Hz, 3.4 Hz),
7.43-7.54 (3H, m), 7.79 (1H, d, J = 6.4 Hz); 9d: 3.40 (3H, s),
4.48 (2H, s), 4.84 (1H, dd, J = 18.1, 3.4 Hz), 5.03 (1H, dd,
J = 49.8, 3.4 Hz), 7.34 (2H, d, J = 8.3 Hz), 7.54 (2H, d, J = 8.3
Hz); 9e: 2.11 (3H, s), 4.88 (1H, dd, J = 18.1, 3.4 Hz), 5.05 (1H,
dd, J = 49.8, 3.4 Hz), 5.11 (2H, s), 7.36 (2H, d, J = 8.3 Hz),
7.55 (2H, d. J = 8.3 Hz); 9f: 3.83 (3H, s), 4.85 (1H, dd,
J = 17.6, 3.4 Hz), 5.03 (1H, dd, J = 49.3, 3.4 Hz), 6.89-7.35
(4H, m).
Article Identifier:
1437-2096,E;2001,0,02,0281,0283,ftx,en;Y19000ST.pdf
There is an erratum or addendum to this paper.
Please check www.thieme.de/chemistry/synthesis/index.html.
Synlett 2001, No. 2, 281–283 ISSN 0936-5214 © Thieme Stuttgart · New York