Copper(II)-catalyzed O-phenylation of tertiary alcohols with organobismuth(V) reagents

Article abstract of DOI:10.1246/cl.2006.612

A new method for the Cu(OAc)₂-catalyzed phenylation of tertiary alcohols under mild basic conditions is described. Triphenylbismuth(V) diacetate and tetraphenylbismuth reagents undergo cross-coupling reactions with α-hydroxycarbonyl compouds efficiently. For non-chelating tertiary alcohols, tetraphenylbismuth fluoride is found suitable as a phenyl donor. Copyright

Full text of DOI:10.1246/cl.2006.612

612
Chemistry Letters Vol.35, No.6 (2006)
Copper(II)-catalyzed O-Phenylation of Tertiary Alcohols with Organobismuth(V) Reagents
Kazuhiro Ikegai,1;2 Kentarou Fukumoto,1 and Teruaki Mukaiyamaꢀ1;3
1Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
2Astellas Pharma Inc., Miyukigaoka Research Center, 21 Miyukigaoka, Tsukuba 305-8585
3Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received March 13, 2006; CL-060302; E-mail: mukaiyam@abeam.ocn.ne.jp)
A new method for the Cu(OAc)2-catalyzed phenylation of
tertiary alcohols under mild basic conditions is described. Tri-
phenylbismuth(V) diacetate and tetraphenylbismuth reagents
undergo cross-coupling reactions with ꢀ-hydroxycarbonyl
compouds efficiently. For non-chelating tertiary alcohols, tetra-
phenylbismuth fluoride is found suitable as a phenyl donor.
Table 1. Effect of copper salts and tertiary aminesa
Ph3Bi(OAc)2
Copper salt, amine
EtO2C
OH
EtO2C
OPh
CH2Cl2, rt, 3 h
1a
2a
Entry
Copper salt
Amine
Yield/%
1
2
3
4
5
6
7
8
9
10
11
12
13
Cu
CuI
CuCl2
CuBr2
Cu(acac)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
i-Pr2NEt
Cy2NMe
TMEDA
Pyridine
DMAP
2
45
44
45
1
64
66
68
0
0
0
0
46
The copper-mediated formation of C(aryl)–O bonds
(Ullmann ether synthesis1,2) is an important and frequently
employed transformation in organic synthesis. O-Arylation of
aliphatic alcohols has been performed by using aryl halides
and aryl metalloid reagents such as organo-boron and -bismuth
compounds as aryl donors.2 Recently, Buchwald demonstrated
that copper(I) iodide promoted the cross coupling of aryl halides
with aliphatic alcohols at elevated temperatures.3 Batey reported
coupling reactions of aliphatic alcohols with aryltrifluoroborate
salts in the presence of catalytic amounts of Cu(OAc)2 and 4-
(dimethylamino)pyridine (DMAP) at room temperature,4 which
is a modified protocol of Chan–Evans’s method for the arylation
of phenols using aryl boronic acids.5 Although these Cu-
catalyzed O-arylation reactions proceed effectively with primary
and secondary alcohols, the synthesis of tert-alkyl aryl ethers
from sterically-hindered tertiary alcohols is still difficult.6
Pd-catalyzed reactions enable the cross coupling of tertiary
alcohols with aryl chlorides or bromides,7 but these etherifica-
tion reactions need strongly basic alkoxides and proceed at
elevated temperatures.
Triarylbismuth reagents such as Ar3Bi(OAc)2 are also
known to transfer their aryl groups to aliphatic alcohols particu-
larly in the presence of a catalytic or stoichiometric amount of
copper salts.2a–2c,8 Moreover, the reactions using these Bi re-
agents were applied to the selective O-arylation of hydroxyl
groups of complex, biologically-active natural products.9 How-
ever, the arylation of tertiary alcohols has not yet been examined
thoroughly despite the above successful results. Dodonov report-
ed the Cu-catalyzed reaction of Ph3Bi(OAc)2 in t-butanol used
as solvent gave t-butyl phenyl ether in a poor yield (based on
the Bi reagent).10 As a part of our study on the organobismuth
chemistry,11 we now report the Cu(OAc)2-catalyzed O-phenyla-
tion of tertiary alcohols with tri- or tetraphenylbismuth reagents
in the presence of a tertiary amine. The reactions can be carried
out under air without exclusion of moisture.
1,10-Phenanthroline
None
aThe reactions were carried out by using 1a (1.0 equiv.),
Ph3Bi(OAc)2 (1.1 equiv.), Cu salt (10 mol %), and amine
(2.0 equiv.).
Table 2. Effect of organobismuth reagentsa
Entry
Bi reagent (equiv.)
Yield/%
1
2
3b
4
5
6
7
8
Ph3Bi(OAc)2 (1.1)
Ph3Bi(OAc)2 (1.6)
Ph3Bi(OAc)2 (1.6)
[Ph4Biþ][BF4ꢀ] (1.6)
Ph4BiF (1.6)
Ph3Bi (1.6)
Ph3BiCl2 (1.6)
Ph3BiCO3 (1.6)
69
89
79
95
93
0
0
0
aThe reactions were carried out by using 1a (1.0 equiv.), Bi
reagent, Cu(OAc)2 (5 mol %), and Cy2NMe (2.0 equiv.) in
CH2Cl2 at rt for 3 h. b1 mol % of Cu(OAc)2 was used.
yield (Entry 6). On the other hand, the use of metallic copper,
CuI, CuCl2, CuBr2, or Cu(acac)2 was less effective. Then, the
combinations of Cu(OAc)2 and several tertiary amines were
screened. The yield of 2a was slightly improved when bulky
aliphatic amines such as dicyclohexylmethylamine (Cy2NMe)
were employed (Entries 7 and 8) although N,N,N0,N0-tetra-
methylethylenediamine (TMEDA) and pyridine derivatives did
not afford 2a at all (Entries 9–12). In the absence of amine,
the yield of 2a decreased down to 46% (Entry 13).
At first, ethyl 2-hydroxy-2-methylpropionate (1a) was
chosen as a model on considering the chelating effect of the sub-
strate,12 and then the O-phenylation of 1a using several copper
salts (10 mol %), triethylamine (2.0 equiv.), and Ph3Bi(OAc)2
(1.1 equiv.) in dichloromethane at room temperature was exam-
ined (Table 1, Entries 1–6). The use of Cu(OAc)2 was the best to
promote the reaction, providing the desired product 2a in 64%
Next, the O-phenylation of 1a was studied further by using
various tri-, or tetraphenylbismuth(V) reagents in the coexis-
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.6 (2006)
613
Table 3. Phenylation of various tertiary alocholsa
substantial amount of phenyl acetate was formed by the decom-
position of the Bi reagent12a (Entries 22 and 25). Also, the use of
Bi reagent
ꢁ
Ph4BiþBF4 did not give the desired products at all (Entires 23
Cu(OAc)2, Cy2NMe
ROH
ROPh
and 26). The results were much better in the reaction with
Ph4BiF, and the O-phenylated products 2i and 2j14,15 were ob-
tained in 88 and 50% yields, respectively (Entries 24 and 27).16
Thus, a new protocol for the synthesis of tertiary alkyl–
phenyl ethers via the Cu(II)-catalyzed coupling of polyphenyl-
bismuth(V) reagents with tertiary alcohols at room temperature
was developed. Both chelating and non-chelating substrates par-
ticipated in the reactions by using Ph4BiF as a phenyl donor, and
various functionalities including ketone, carboxylic ester, amide,
tertiary amine, t-butyldiphenylsilyloxy group, and aryl bromide
were well-tolerated. It is noted that the present reaction appa-
rently extends the scope of the Ullmann-arylation chemistry.
Further investigation on the phenylation of primary and second-
ary alcohols by this method is currently under way in our labo-
ratory.
CH2Cl2, rt, 3 h
Bi reagent
1
2
Entry
Alcohol
Yield/ % Product
1
2
3
Ph3Bi(OAc)2
[Ph4Bi+][BF4
Ph4BiF
46
85
87
−
Me
]
]
2b
2c
OH
1b
O
O
4
5
6
Ph3Bi(OAc)2
92
90
82
Ph
[Ph4Bi+][BF4−
Ph4BiF
OH
1c
Et
7
8
9
Ph3Bi(OAc)2
88
85
85
−
[Ph4Bi+][BF4
]
(S)-2d
BnO2C
OH
Ph4BiF
(S)-1d
Ph
10
11
12
Ph3Bi(OAc)2
[Ph4Bi+][BF4
Ph4BiF
82
89
84
−
]
]
(S)-2e
(S)-2f
EtO2C OH
(S)-1e
This study was supported in part by the Grant of the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
Ph
13
14
15
Ph3Bi(OAc)2
[Ph4Bi+][BF4
Ph4BiF
86
71
86
−
MeO2C
OH
(S)-1f
Et
16
17
18
Ph3Bi(OAc)2
80
94
85
References and Notes
N
O
−
[Ph4Bi+][BF4
]
(S)-2g
OH
(S)-1g
1
2
F. Ullmann, Chem. Ber. 1904, 37, 853.
Ph4BiF
For reviews, see: a) S. V. Ley, A. W. Thomas, Angew. Chem.,
Int. Ed. 2003, 42, 5400. b) J.-P. Finet, A. Y. Fedorov, S. Combs,
G. Boyer, Curr. Org. Chem. 2002, 6, 597. c) G. I. Elliott, J. P.
Konopelski, Tetrahedron 2001, 57, 5683. d) J. Lindley, Tetra-
hedron 1984, 40, 1433.
19
20
21
H
N
Ph3Bi(OAc)2
64
73
89
[Ph4Bi+][BF4
]
]
2h
2i
−
OH
1h
Ph4BiF
O
Br
22
23
24
Ph3Bi(OAc)2
< 22
NDb
88
Ph
N
3
M. Wolter, G. Nordmann, G. E. Job, S. L. Buchwald, Org. Lett.
2002, 4, 973; G. E. Job, S. L. Buchwald, Org. Lett. 2002, 4,
3703.
[Ph4Bi+][BF4
−
OH
1i
Ph4BiF
Ph
4
5
T. D. Quach, R. A. Batey, Org. Lett. 2003, 5, 1381.
D. M. T. Chan, K. L. Monaco, R.-P. Wang, M. P. Winters,
Tetrahedron Lett. 1998, 39, 2933; D. A. Evans, J. L. Katz,
T. R. West, Tetrahedron Lett. 1998, 39, 2937.
25c
26c
27c
Ph3Bi(OAc)2
[Ph4Bi+][BF4
Ph4BiF
3
NDb
50
OSiPh2t-Bu
1j
−
2j
]
OH
aThe reactions were carried out by using alcohol (1.0 equiv.), Bi
reagent (1.6 equiv.), Cu(OAc)2 (5 mol %), and Cy2NMe (2.0
equiv.). bNot detected. c2j was obtained after treating the crude
product with Bu4NF.
6
7
The reaction of stoichiometric amounts of Cu(I) alkoxides
with aryl halides gave t-alkyl aryl ethers. G. M. Whitesides,
J. S. Sadowski, J. Lilburn, J. Am. Chem. Soc. 1974, 96, 2829.
M. Watanabe, M. Nishiyama, Y. Koie, Tetrahedron Lett. 1999,
40, 8837; G. Mann, J. F. Hartwig, J. Am. Chem. Soc. 1996, 118,
13109; Q. Shelby, N. Kataoka, G. Mann, J. F. Hartwig, J. Am.
Chem. Soc. 2000, 122, 10718; C. A. Parrish, S. L. Buchwald,
J. Org. Chem. 2001, 66, 2498; M. Palucki, J. P. Wolfe, S. L.
Buchwald, J. Am. Chem. Soc. 1997, 119, 3395.
OH
OPh
2j
8
9
J.-P. Finet, Chem. Rev. 1989, 89, 1487.
tence of Cu(OAc)2 (5 mol %) and Cy2NMe (2.0 equiv.)
(Table 2). In the case where 1.6 equiv. of Ph3Bi(OAc)2 was used
under the above conditions, the product 2a was obtained in 89%
yield (Entry 2). Interestingly, tetraphenylbismuth reagents
(Ph4BiþBF4ꢁ, Ph4BiF)13 were found effective as phenyl donors,
which also produced 2a in high yields (Entries 4 and 5).
With optimal conditions in hand, the scope and limitations
of this method were examined (Table 3). As expected, ꢀ-hy-
droxy-ketone, -carboxylic esters and -carboxamides were effi-
S. Pietri, T. Liebgott, J.-P. Finet, M. Culcasi, L. Billottet, C.
Bernard-Henriet, Drug Dev. Res. 2001, 54, 191; K. M. J.
Brands, U.-H. Dolling, R. B. Jobson, G. Marchesini, R. A.
Reamer, J. M. Williams, J. Org. Chem. 1998, 63, 6721.
10 V. A. Dodonov, A. V. Gushin, T. G. Brilkina, Zh. Obshch.
Khim. 1985, 55, 2514.
11 K. Ikegai, T. Mukaiyama, Chem. Lett. 2005, 34, 1496.
12 a) G. S. Sheppard, Synlett 1999, 1207. b) D. H. R. Barton,
J.-P. Finet, C. Pichon, J. Chem. Soc., Chem. Commun. 1986, 65.
13 Y. Matano, S. A. Begum, T. Miyamatsu, H. Suzuki, Organo-
metallics 1998, 17, 4332; T. Ooi, R. Goto, K. Maruoka, J.
Am. Chem. Soc. 2003, 125, 10494.
14 The corresponding phenylated product of 1j could not be
separated from Ph3Bi.
15 In the reaction of 1j, the amount of Ph4BiF was not optimized.
16 For experimental procedures and characterization data for the
phenylated products 2, see Supporting Information.
ꢁ
ciently phenylated by the use of Ph3Bi(OAc)2, Ph4BiþBF4
,
and Ph4BiF at room temperature, and the desired O-phenylated
products 2b–2h were obtained in high yields (Entries 1–21).
On the other hand, the O-phenylation of the tertiary alcohols
1i and 1j was more sluggish probably because they are non-
chelating substrates. The desired products 2i and 2j were ob-
tained in poor yields when Ph3Bi(OAc)2 was used because a
Published on the web (Advance View) May 13, 2006; doi:10.1246/cl.2006.612