Angewandte
Chemie
Table 2: Pd0-catalyzed hydroalkoxylation in the presence of dppb.[a]
Pd(OAc)2, the Wacker process, was unsuccessful.[4] However,
we found that Pd catalysts containing phosphane ligands, such
as [PdCl2(PPh3)2] and [PdCl2{P(cHex)3}2], gave the expected
ether CF3CHFCF2OCH2CF3 (3a) in 42% and 49% yield,
respectively, after 72 h at 1508C. Interestingly, the hydro-
alkoxylation of 1 was efficiently catalyzed by the Pd0 complex
[Pd(PPh3)4], even at ambient temperature, provided that HFP
was bubbled continuously through the system (Table 1).[5]
Entry
ROH
t [h]
Product
Yield [%][b]
1
2
3
4
5
CF3CH2OH (2a)
CF3CF2CH2OH (2b)
CH3OH (2e)
CH3CH2OH (2 f)
PhCH2OH (2g)
21
21
24
24
24
3a
3b
3e
3 f
84
86
83
78
82
3g
[a] All reactions of 1 (excess) with 2 (2 mmol) in acetonitrile (15 mL)
were carried out in the presence of 5 mol% of [Pd(PPh3)4] and 10 mol%
of dppb at room temperature. [b] Yields based on alcohols 2 calculated
Table 1: Pd0-catalyzed hydroalkoxylation of HFP (1).[a]
1
from the 19F and H NMR spectra with 1,4-bis(trifluoromethyl)benzene
Entry
ROH
t [h]
Product
Yield [%][b]
as an internal standard.
1
2
3
CF3CH2OH (2a)
CF3CF2CH2OH (2b)
(CF3)2CHOH (2c)
2c
CCl3CH2OH (2d)
CH3OH (2e)
CH3CH2OH (2 f)
PhCH2OH (2g)
C6H5OH (2h)
2h
18
18
18
46
18
24
24
18
18
3
3a
3b
3c
3c
3d
3e
3 f
3g
3h
3h
3i
72
73
99
100
92
67
46
9
76
99
41
100
4[c]
5
6[d]
7[d]
8[e]
9
10[f]
11
12[f]
C6F5OH (2i)
2i
77
18
3i
[a] Unless otherwise specified, reactions of 1 (excess) with 2 (2 mmol) in
acetonitrile (5 mL) were carried out in the presence of 5 mol% of
[Pd(PPh3)4] at room temperature. [b] Yields based on alcohols 2
calculated from the 19F and 1H NMR spectra with 1,4-bis(trifluorome-
thyl)benzene as an internal standard. [c] The reaction was carried out in
the presence of 1 mol% of [Pd(PPh3)4]. [d] Acetonitrile (15 mL) was used
as the solvent. [e] Production of trace amounts of benzaldehyde (3%)
was observed. [f] The reaction was conducted at 40–508C.
Scheme 3. Plausible mechanism for the Pd0-catalyzed hydroalkoxyla-
tion.
addition of a proton from alcohols 2 would give the
intermediate 7. Reductive elimination would then afford
fluoroether 3 and regenerate the Pd0 center. Continuous
addition of 1 and dppb should enhance the formation of 6 and
improve the yield. While acidic, fluorinated alcohols and
phenols would stabilize intermediates 7, the steric bulk of 2c
and 2d might enhance the reductive elimination.
The reaction of an excess of HFP with acidic haloalcohols
proceeded at room temperature to afford the corresponding
ethers in good to excellent yields (Table 1, entries 1 to 5). In
the case of poorly acidic alcohols, the corresponding ethers
were obtained in only moderate yields (Table 1, entries 6 and
7). The reaction with benzyl alcohol (2g) gave ether 3g in low
yield (Table 1, entry 8).
The reaction with phenol (2h) also gave the ether
CF3CHFCF2OC6H5 (3h) in 76% yield (Table 1, entry 9). In
the case of pentafluorophenol (2i), the reaction required a
longer time and the ether CF3CHFCF2OC6F5 (3i) was
obtained in only 41% yield (Table 1, entry 11). At 40–508C
these two phenol derivatives gave the corresponding ethers
3h and 3i in almost quantitative yields (Table 1, entries 10
and 12).
1,4-Bis(diphenylphosphanyl)butane (dppb) proved to be
an effective ligand for the Pd0-catalyzed hydroalkoxylation of
HFP—the [Pd(PPh3)4]/dppb system enhanced the yields of
the hydroalkoxylation with poorly acidic alcohols dramati-
cally (Table 2).
Our results indicate the importance of the ability of the
alcohols to act as a proton source and the electron donation
from electron-rich Pd0 species to HFP, which is enhanced by
dppb. We propose the reaction mechanism for the Pd0-
catalyzed hydroalkoxylation of HFP shown in Scheme 3.[6]
The electron-deficient alkene HFP coordinates to the elec-
tron-rich Pd0 center to generate the h2-complex 6. Subsequent
In summary, we have developed a Pd0-catalyzed hydro-
alkoxylation of a fluorinated alkene with various alcohols.
This is the first example of the synthesis of saturated ethers by
=
the addition of an alcohol to a C C double bond in the
presence of a palladium(0) catalyst. In this process, which is
performed under neutral conditions, saturated hydrofluoro-
ethers are selectively obtained without any formation of vinyl
ethers. This procedure might be the basis for an asymmetric
synthesis of hydrofluoroethers. Studies of the scope and
limitations of this reaction, as well as its mechanistic details,
are in progress.
Received: October 5, 2004
Published online: January 11, 2005
Keywords: alcohols · fluorinated alkenes · green chemistry ·
.
hydroalkoxylation · palladium
[1] A. Sekiya, S. Misaki, J. Fluorine Chem. 2000, 101, 215.
[2] a) A. L. Henne, M. A. Smook, J. Am. Chem. Soc. 1950, 72, 4378;
b) J. D. Park, W. M. Sweeney, S. L. Hopwood, Jr., J. R. Lacher, J.
Am. Chem. Soc. 1956, 78, 1685; c) R. E. A. Dear, E. E. Gilbert, J.
Chem. Eng. Data 1969, 14, 493; d) A. V. Fokin, V. A. Komarov,
A. F. Kolomiets, A. I. Rapkin, O. V. Verenikin, T. M. Potarina,
Izv. Akad. Nauk SSSR Ser. Khim. 1977, 9, 2141 [Chem. Abstr.
Angew. Chem. Int. Ed. 2005, 44, 1128 –1130
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1129
Matsukawa, Yasuhisa
