Copper(II)-catalyzed O-arylation of tertiary alcohols with arylbismuth(III) reagents: A convenient system for aryl transfer

Article abstract of DOI:10.1055/s-0031-1290205

Copper(II)-catalyzed O-arylation of tertiary alcohols with various triarylbismuth reagents was investigated. A convenient and efficient system for aryl ether formation of tertiary alcohols has been developed through the in situ oxidation of stable triaryl

Full text of DOI:10.1055/s-0031-1290205

LETTER
405
Copper(II)-Catalyzed O-Arylation of Tertiary Alcohols with Arylbismuth(III)
Reagents: A Convenient System for Aryl Transfer
C
opper(II)-Ca
y
talyzed
O
-A
r
u
ylationof
T
j
ilcohols
with
H
Arylbismuth(III)
a
Reagents rada,a Daisuke Hayashi,a Itaru Sato,*b Masahiro Hiramaa
a
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Fax +81(22)7956566; E-mail: isato@m.tohoku.ac.jp
b
Received 15 November 2011
atm)4d,e was preferred to attain higher yields. Addition of
molecular sieves 4 Å (MS4A) was necessary to prevent
hydrolytic decomposition of 1. Without molecular sieves,
compound 1 decomposed presumably to phenol due to the
Abstract: Copper(II)-catalyzed O-arylation of tertiary alcohols
with various triarylbismuth reagents was investigated. A convenient
and efficient system for aryl ether formation of tertiary alcohols has
been developed through the in situ oxidation of stable triarylbis-
muth(III) to triarylbismuth(V) species using PhI(OAc)2 as the oxi- presence of water in the solution, which was then arylated
dant in the presence of a catalytic amount of copper(II) acetate.
by 1 to afford biaryl ether 5 as a byproduct. Substitution
of the methyl group at the ortho position (1b and 1h)
slightly hindered the reaction (Table 1, entries 2, 8, and
12),5b whereas the o-methoxymethyloxy (MOM) substit-
uent (1e and 1i) practically inhibited the reaction (Table 1,
entries 5 and 9). This lowered transfer reactivity of 1e and
1i may be explained by their chelation effect on the bis-
muth atom rather than steric hindrance.5b Since O-aryla-
tion is slow, bismuth(V) species 1 decomposed, resulting
in a considerable amount of aryl acetate 6 and triarylbis-
muth(III) 75b as the isolable degradation products
(Figure 1). The bismuth(III) species 7 was likely due to
the disproportionation4d of diarylbismuth(III) acetate,
which was formed as the O-arylation product from 1.
Key words: O-phenylation, O-arylation, arylbismuth, ether, iodo-
benzene diacetate, tertiary alcohol
Aryl ethers are ubiquitous structural constituents in phar-
macologically important molecules.1,2 Arylbismuth(V)
reagents are known to transfer aryl groups to phenols and
alcohols in the presence of copper catalyst.2–7 Copper-cat-
alyzed O-phenylation of tertiary alcohols, 2-hydroxy-2-
methylpropionate (2a) and 2-hydroxy-2-methylbutanoate
(2b), with triphenylbismuth(V) reagents at room temper-
ature has been extensively examined by Mukaiyama et
al.6a We needed an efficient procedure for the transfer of
aryl groups containing electron-donating substituents to 2
under mild conditions in our synthetic studies of complex
aryl ether natural products.1c We herein describe such a
convenient system using a mixture of stable triarylbis-
muth(III), Cu(OAc)2, Cy2NMe, and PhI(OAc)2 at room
temperature.
The formation of 7 under Mukaiyama’s conditions sug-
gested that O-arylation using a smaller amount of triaryl-
bismuth(III) 7 could be possible through the in situ
oxidation2b,7 of 7 by PhI(OAc)2 as the oxidant.12 In fact, as
shown in Table 2, the copper(II)-catalyzed O-phenylation
of 2 using 0.7 mol equivalents of Ph3Bi (7a) proceeded
satisfactorily in the presence of 1.2 mol equivalents of
PhI(OAc)2, although the reaction was somewhat hindered.
Copper-catalyzed arylation of a simple primary 1,3-diol
with tris(polymethoxyphenyl)bismuth(V) diacetates was
reported by Finet and Fedorov.5a However, no examples
of the corresponding transfer reactions of aryl groups con-
taining electron-donating substituents to 2 have been de-
scribed. We first examined the O-arylation of 2 with
various triarylbismuth(V) diacetates 18 using Mukaiyama
protocol6a (Table 1).9–11 The O-phenylation reactions of 2
were carried out under Mukaiyama’s optimum conditions
using 1.6 mol equivalents of triphenylbismuth(V) diace-
tate (1a) to give the products 3a and 4a in good yields
(Table 1, entries 1 and 10) as reported.6a
Then, the copper(II)-catalyzed transfer of aryl groups con-
taining electron-donating substituents from triarylbis-
muth(III) 7b–i to 2 was examined in the presence of
PhI(OAc)2 (Table 3).13 The reactions of triarylbis-
muth(III) with electron-rich aromatic rings 7c,d,f,g
(Table 3, entries 2, 3, 5, 6, and 9) worked in high yields,
but became rather slow. Therefore, 1.5 mol equivalents of
7, which was half the amount of bismuth reagents required
for the previous method as shown in Table 1, as well as
1.9–2.4 mol equivalents of PhI(OAc)2, were required to
obtain the products 3 and 4 in high yields. Under these
conditions, substitution of the methyl group at the ortho
position (7b and 7h) affected the reaction (Table 3, entries
1 and 7) to some extent, and the o-methoxymethyloxy
(OMOM) substituent (7e and 7i) inhibited the reaction
(Table 3, entries 4 and 8).
Since substitution of electron-donating groups hindered
the reaction and lowered the yield of the desired product,
three mol equivalents of triarylbismuth(V) diacetates 1b–
i were used to provide the corresponding products 3b–
d,f–h and 4f,h in high yields. An oxygen atmosphere (1
In conclusion, convenient and efficient copper(II)-cata-
lyzed O-phenylation and O-arylation of tertiary alcohols 2
at ambient temperature have been developed through the
SYNLETT 2012, 23, 405–408
Advanced online publication: 25.01.2012
DOI: 10.1055/s-0031-1290205; Art ID: U67411ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
1
2

406
S. Harada et al.
LETTER
Table 1 Copper(II)-Catalyzed O-Arylation of 2 Using Various Triarylbismuth(V) Diacetates 1
R1
R1
R5
Cu(OAc)2 (5 mol%)
Cy2NMe (2 equiv)
R5
R2
R3
R2
R3
O
OBn
Bi(OAc)2
OBn
+
HO
O
CH2Cl2, MS4A
O2 (1 atm), r.t.
O
R4
R4
3a–i: R5 = Me
4a, f, h: R5 = Et
3
1a–i
(3.0 equiv)
2a: R5 = Me
2b: R5 = Et
Entry
R1
R2
R3
R4
Ar3Bi(OAc)2 Alcohol
Time
Product,
yield (%)a
1b
2
H
H
H
H
H
H
H
H
H
H
1a
1b
1c
1d
1e
1f
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2.5 h
3 d
3a 74
3b 74
3c 98
3d 99
3e <10
3f 78
3g 90
3h 77
3i <5
4a 76
4f 90
4h 74
Me
H
H
3
H
Me
H
13 h
12 h
1 d
4
H
H
Me
5
OMOM
H
H
6
H
OMOM
H
1 d
7
H
H
OMOM
1g
1h
1i
1 d
8
Me
OMOM
H
H
H
H
H
H
H
OMOM
CH2OEt
H
3 d
9
H
1 d
10
11
12
H
1a
1f
4 h
H
OMOM
H
H
2 d
Me
OMOM
1h
3 d
a Isolated yield.
b Conditions: 1.6 mol equiv of Ph3Bi(OAc)2.
in situ oxidation of stable triarylbismuth(III) 7 to bis- the present method to the total synthesis are currently un-
muth(V) species 1 using PhI(OAc)2 as the oxidant in the der way and will be reported in due course.
presence of Cy2NMe. This procedure requires only 0.7–
1.5 mol equivalents of the aryl transfer reagents 7 without
the preparation of often unstable bismuth(V) reagents 1
Acknowledgment
This work was supported financially by a Grant-in-Aid for Special-
ly Promoted Research from the Ministry for Education, Culture,
Sports, Science and Technology (MEXT).
containing electron-donating substituents, prior to the O-
arylation reaction. Further studies on the application of
Table 2 Copper(II)-Catalyzed O-Phenylation of 2a Using Triphe-
nylbismuth(III) (7a) in the Presence of PhI(OAc)2
References and Notes
PhI(OAc)2
Cu(OAc)2 (5 mol%)
Cy2NMe (2.0 equiv)
(1) (a) Evans, D. A.; Wood, M. R.; Trotter, B. W.; Richardson,
T. I.; Barrow, J. C.; Katz, J. L. Angew. Chem. Int. Ed. 1998,
37, 2700. (b) Nicolaou, K. C.; Mitchell, H. J.; Jain, N. F.;
Winssinger, N.; Hughes, R.; Bando, T. Angew. Chem. Int.
Ed. 1999, 38, 240. (c) Cao, B.; Park, H.; Joullié, M. M.
J. Am. Chem. Soc. 2002, 124, 520. (d) Joullié, M. M.;
Richard, D. J. Chem. Commun. 2004, 2011.
OBn
OBn
Ph3Bi
+
PhO
HO
CH2Cl2, MS4A, O2 (1 atm)
3 d
O
O
7a
2a
3a
Entry
Ph3Bi (7a)
(mol equiv)
PhI(OAc)2
(mol equiv)
Product 3a,
yield (%)a
(2) (a) Pietri, S.; Liebgott, T.; Finet, J.-P.; Culcasi, M.; Billottet,
L.; Bernard-Henriet, C. Drug Dev. Res. 2001, 54, 191.
(b) Brands, K. M. J.; Dolling, U.-H.; Jobson, R. B.;
Marchesini, G.; Reamer, R. A.; Williams, J. M. J. Org.
Chem. 1998, 63, 6721. (c) Nicolaou, K. C.; Sarlah, D.; Wu,
T. R.; Zhan, W. Angew. Chem. Int. Ed. 2009, 48, 6870.
(3) For reviews, see: (a) Finet, J.-P. Chem. Rev. 1989, 89, 1487.
(b) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
42, 5400.
1
2
3
4
1.6
1.0
0.7
0.5
1.9
1.2
1.2
1.2
77
92
87
33
a Isolated yield.
Synlett 2012, 23, 405–408
© Thieme Stuttgart · New York

LETTER
Copper(II)-Catalyzed O-Arylation of Tertiary Alcohols with Arylbismuth(III) Reagents
407
Table 3 Copper(II)-Catalyzed O-Arylation of 2 Using Various Triarylbismuth(III) Reagents 7 in the Presence of PhI(OAc)2
R1
R1
Cu(OAc)2 (5 mol%)
Cy2NMe (2 equiv)
R5
R5
R2
R3
Bi
R2
R3
O
OBn
PhI(OAc)2 (1.9–2.4 equiv)
OBn
+
HO
CH2Cl2, MS4A, O2 (1 atm), r.t.
O
O
R4
7b–i
R4
3
2a: R5 = Me
2b: R5 = Et
3b–i: R5 = Me
4f: R5 = Et
(1.5 equiv)
Entry
R1
R2
R3
R4
Ar3Bi
Alcohol
Time
(d)
Product,
yield (%)a
1
2
3
4
5
6
7
8
9
Me
H
H
H
H
H
H
H
H
H
7b
7c
7d
7e
7f
2a
2a
2a
2a
2a
2a
2a
2a
2b
5
2
1
5
4
2
6
5
3
3b 19
Me
H
H
3c 98
H
Me
H
3d 93
OMOM
H
3e 0
H
OMOM
H
3f 83
3g 86
3h 30
H
H
OMOM
7g
7h
7i
Me
H
H
H
H
OMOM
CH2OEt
H
OMOM
H
H
3i
0
OMOM
7f
4f 74
a Isolated yield.
To a mixture of n-BuLi (9.7 mmol, 1.6 M in hexane) and
N,N,N¢,N¢-tetramethylethylenediamine (9.7 mmol) was
added dropwise to a solution of the methoxymethoxy-
benzene (9.1 mmol) in anhyd THF (18 mL) at 0 °C. After
stirring for 6 h at this temperature, a THF solution (9 mL) of
BiCl3 (2.9 mmol) was added slowly at –35 °C. The reaction
mixture was allowed to warm to r.t., quenched with H2O (30
mL), extracted with EtOAc (2 × 20 mL), and the combined
organic layers were washed with brine and dried over
Na2SO4. The solvent was removed under reduced pressure,
and the residue was purified by column chromatography on
silica gel using hexane–EtOAc or recrystallization from
MeOH to give the corresponding triarylbismuth(III).
Method B for the Synthesis of Compounds 7b–d,f–h
To an anhyd THF solution (17 mL) of arylmagnesium
bromide, prepared from Mg (17 mmol) and aryl bromide
(17.5 mmol), was added a THF solution (5 mL) of BiCl3 (5
mmol) at 0 °C. The reaction mixture was allowed to warm to
r.t., quenched with H2O (30 mL), extracted with EtOAc (2 ×
20 mL), and the combined organic layers were washed with
brine and dried over Na2SO4. The solvent was removed
under reduced pressure, and the residue was purified by
column chromatography on silica gel using hexane–EtOAc
or recrystallization from MeOH to give the corresponding
triarylbismuth(III).
Bi
O
OAc
R
R
R
R
3
5a–i
6a–i
7a–i
Figure 1
(4) (a) Barton, D. H. R.; Finet, J.-P.; Khamsi, J.; Pichon, C.
Tetrahedron Lett. 1986, 27, 3619. (b) Barton, D. H. R.;
Charpiot, B.; Motherwell, W. B. Tetrahedron Lett. 1982, 23,
3365. (c) Barton, D. H. R.; Finet, J.-P.; Pichon, C. J. Chem.
Soc., Chem. Commun. 1986, 65. (d) Barton, D. H. R.; Finet,
J.-P.; Khamsi, J. Tetrahedron Lett. 1987, 28, 887. (e) The
reaction can be also carried out under air as long as moisture
is excluded.
(5) (a) Finet, J.-P.; Fedorov, A. Y. J. Organomet. Chem. 2006,
691, 2386. (b) Combes, S.; Finet, J.-P. Tetrahedron 1998,
54, 4313.
(6) (a) Ikegai, K.; Fukumoto, K.; Mukaiyama, T. Chem. Lett.
2006, 35, 612. (b) Mukaiyama, T.; Sakurai, N.; Ikegai, K.
Chem. Lett. 2006, 35, 1140. (c) Sakurai, N.; Ikegai, K.;
Mukaiyama, T. ARKIVOC 2007, (vii), 254.
(7) Sheppard, G. S. Synlett 1999, 1207.
(11) Synthesis of Triarylbismuth Diacetate 1b–i
Method A for the Synthesis of Compounds 1c–f,i
A mixture of NaBO3·H2O (4.2 mmol) and Ar3Bi(III) (1.4
mmol) in AcOH (14 mL) was stirred at r.t. for 30 min. The
resulting mixture was poured into H2O (50 mL) and was
extracted with CH2Cl2 (2 × 30 mL). The combined organic
layers were washed with H2O (2 × 30 mL) and dried over
MgSO4. The solvent was distilled off, and the crude product
was precipitated from a mixture of CH2Cl2 (1 mL)–hexane
(30 mL) to give the corresponding triarylbismuth(V)
diacetate.
(8) (a) Matano, Y.; Aratani, Y.; Miyamatsu, T.; Kurata, H.;
Miyaji, K.; Sasako, S.; Suzuki, H. J. Chem. Soc., Perkin
Trans. 1 1998, 2511. (b) Suzuki, H.; Ogawa, T.; Komatsu,
N.; Matano, Y.; Murafuji, T.; Ikegami, T. Organobismuth
Chemistry; Elsevier: Amsterdam, 2001.
(9) Triphenylbismuth(V) diacetate(1a) is commercially
available from Tokyo Kasei Kogyo, Inc. and used without
purification. Triarylbismuth(V) diacetates 1b–i were readily
prepared from BiCl3 as described below.5a,8a,11,12
(10) Synthesis of Triarylbismuth 7b–i:
Method A for the Synthesis of Compounds 7e,i
© Thieme Stuttgart · New York
Synlett 2012, 23, 405–408

408
S. Harada et al.
LETTER
(14) Spectral Data for the Representative Products 3c,f
Method B for the Synthesis of Compounds 1b,g,h
A mixture of Ar3Bi(III) (1.4 mmol) and PhI(OAc)2 (1.5
mmol) in CH2Cl2 (14 mL) was stirred under argon
atmosphere for 24 h at r.t. The solvent was distilled off, and
the crude product was precipitated from a mixture of CH2Cl2
(1 mL)–hexane (30 mL) to give the corresponding
triarylbismuth(V) diacetate.
Benzyl 2-Methyl-2-(3-methylphenoxy)propionate (3c)
Yield: 60 mg (98%). Colorless oil. IR (neat): 2936, 1733,
1488, 1280, 1175, 1137, 959, 695 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.60 (6 H, s, Me), 2.22 (3 H, s, tolyl), 5.21 (2 H,
s, Bn), 6.57 (1 H, br d, J = 8.0 Hz, H6¢), 6.61 (1 H, br s, H2¢),
6.78 (1 H, br d, J = 7.6 Hz, H4¢), 7.05 (1 H, dd, J = 8.0, 7.6
Hz, H5¢), 7.27–7.33 (5 H, m, Bn). 13C NMR (100 MHz,
CDCl3): d = 21.5, 25.6, 67.1, 79.1, 115.9, 120.0, 123.0,
128.4, 128.5, 128.6, 128.9, 135.6, 139.3, 153.4, 174.3.
HRMS (ESI-FT): m/z calcd for C18H20O3Na: 307.1310 [M +
Na]+; found: 307.1307.
(12) A related one-pot but not in situ copper(II)-catalyzed N-
arylation of anilines was reported by Combes and Finet.5b
Barton et al. found that copper(II)-catalyzed N-phenylation
of amines by Ph3Bi(III) occurs smoothly.4d
(13) Typical Procedure for the O-Arylation of 2 (Table 3,
entry 5)
Benzyl 2-[3-(Methoxymethoxy)phenoxy]-2-methyl-
propanoate (3f)
To a suspension mixture of alcohol 2 (0.22 mmol), Cy2NMe
(0.43 mmol), and powdered MS4A (250 mg) in CH2Cl2 (1
mL) was added Cu(OAc)2 (0.01 mmol). After the mixture
was stirred for 30 min, Ar3Bi (0.33 mmol) and PhI(OAc)2
(0.41 mmol) were added, and the resulting mixture was kept
stirring at r.t. under an oxygen atmosphere (1 atm). Upon
completion of the reaction (monitored by TLC), 10% aq NH3
solution (2 mL) was added to the mixture. The precipitates
were filtered off, and the filtrate was extracted with CH2Cl2
(2 × 10 mL). The combined extracts were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure
to give an oily residue. Purification by column chromatog-
raphy on silica gel using hexane–EtOAc yielded the
corresponding aryl ether 314 or 4.
Yield: 130 mg (83%). Colorless oil. IR (neat): 2938, 1731,
1600, 1486, 1282, 1138, 1017, 851, 696 cm–1. 1H NMR (400
MHz, CDCl3): d = 1.61 (6 H, s, Me), 3.45 (3 H, s, OMe), 5.09
(2 H, s, OCH2O), 5.20 (2 H, s, Bn), 6.40 (1 H, ddd, J = 8.0,
2.3, 0.9 Hz, H6¢), 6.57 (1 H, dd, J = 2.3, 2.3 Hz, H2¢), 6.66
(1 H, ddd, J = 8.3, 2.3, 0.9 Hz, H4¢), 7.06 (1 H, dd, J = 8.3,
8.0 Hz, H5¢), 7.27–7.45 (5 H, m, Bn). 13C NMR (100 MHz,
CDCl3): d = 25.5, 56.1, 67.2, 79.3, 94.6, 107.7, 110.1, 112.2,
128.4, 128.6, 129.6, 135.6, 156.6, 158.3, 174.2. HRMS
(ESI-FT): m/z calcd for C19H22O5Na: 353.1365 [M + Na]+;
found: 353.1361.
Synlett 2012, 23, 405–408
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