Catalytic ethenylation reaction of phenol using SnCl4

Article abstract of DOI:10.1021/ol006888d

equation presented Ethenylation reaction of phenol with silylethyne at the o-position is catalyzed by the SnCl₄-BuLi reagent. While turn over numbers (TONs) in the reactions of m-or p-substituted phenols are 3 to 4, those for o-substituted phen

Full text of DOI:10.1021/ol006888d

ORGANIC
LETTERS
2001
Vol. 3, No. 2
241-242
Catalytic Ethenylation Reaction of
Phenol Using SnCl4
Katsumi Kobayashi and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences
Tohoku UniVersity, Aoba, Sendai 980-8578, Japan
yama@mail.pharm.tohoku.ac.jp
Received November 18, 2000
ABSTRACT
Ethenylation reaction of phenol with silylethyne at the o-position is catalyzed by the SnCl4−BuLi reagent. While turn over numbers (TONs) in
the reactions of m- or p-substituted phenols are 3 to 4, those for o-substituted phenols are 8 to 9.
Previously, we reported the ethenylation reaction of phenol
using the SnCl4-Bu3N reagent system.1 Although this
reaction can directly introduce the ethenyl group to the
o-position of the phenol hydroxy group, it has a drawback
of employing the SnCl4-Bu3N reagent the amount of 2 molar
equiv. We now describe the catalytic version of the reaction
using silylethyne (Scheme 1).
be applied to various p- and m-substituted phenols, giving
the products in high yields. As was the case in the
stoichiometric reaction, m-substituted phenols give compa-
rable amounts of the regioisomers even in the case of m-(tert-
butyl)phenol. The turn over number (TON) based on SnCl4
is between 3 and 4, which implies that the amount of SnCl4
can be reduced to approximately 1/10 of that of the original
stoichiometric procedures.1 Although the reason is not clear,
employment of larger amounts of phenol results in the drastic
Butyllithium (50 mol %) and SnCl4 (25 mol %) were
added successively to phenol in chlorobenzene, and after
addition of silylethyne the mixture was heated at 105 °C for
3 h. â-Silylethenylation of phenol first takes place at the
o-position, which is followed by C-O migration of the
trimethylsilyl group. The reaction is quenched by treatment
with aqueous potassium fluoride in methanol, and the
o-ethenylphenol is isolated after acetylation in 90% yield
(Table 1). The use of butyllithium for the base is essential,
and Bu3N is not effective in the catalytic reaction. More
economically, lithium phenoxide prepared from LiOH and
phenol in methanol can be used provided that the salt is
sufficiently dried at 80 °C (3 Torr) for 3 h. A 1:2 ratio of
SnCl4 and butyllithium is critical. The reaction temperature
of 100 to 105 °C is also important, and the yield decreases
either at higher or at lower temperatures. The reaction can
Scheme 1
(1) (a)Yamaguchi, M.; Hayashi, A.; Hirama, M. J. Am. Chem. Soc. 1995,
117, 1151. (b) Yamaguchi, M.; Arisawa, M.; Kido, Y.; Hirama, M. J. Chem.
Soc., Chem. Commun. 1997, 1663. (c)Yamaguchi, M.; Arisawa, M.; Omata,
K.; Kabuto, K.; Hirama, M.; Uchimaru, T. J. Org. Chem. 1998, 63, 7298.
(d)Yamaguchi, M. Pure Appl. Chem. 1998, 70, 1091.
10.1021/ol006888d CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/09/2000

Again, the C-O silicon migration takes place in the reaction
mixture. The presence of CF3CH2OH is essential, and the
yield decreases to 35% in its absence. Small amounts of
ethanol, methanol, and even water are also effective for
improving the yield, while acetic acid, benzoic acid, am-
monium chloride, or triethylamine hydrochloride inhibits the
reaction. Probably, the acidic compounds participate in the
protodestannylation of the organotin intermediate formed.2
A reaction temperature of 80 °C is essential in this reaction.
This method is applicable to other o-methylated phenols as
well as 1-naphthol under similar reaction conditions. Higher
reaction temperatures give better results in the cases of
o-ethylphenol and o-isopropylphenol. The ethenylation of
o-(tert-butyl)phenol is effectively conducted at 150 °C in
the presence of 10 mol % of p-CF3C6H4COOH in place of
CF3CH2OH. The origin of the higher TON in the ethenylation
of o-substituted phenol is not known at present. Some part
of the mechanism might be different, since addition of CF3-
CH2OH inhibits the reaction of phenol.
Table 1. Catalytic Ethenylation of Phenol
substituent
yield/%a
H
4-Me
90
87
85
91
51
85b
95c
4-(t-Bu)
4-MeO
4-Cl
3-(t-Bu)
3-(t-BuMe2SiO)
a Yields of isolated products are shown. b Ratio of 3-(tert-butyl)-2-
ethenylphenol:3-(tert-butyl)-6-ethenylphenol ) 1:2. c Ratio of 2-ethenyl-
3-(silyloxy)phenol:6-ethenyl-3-(silyloxy)phenol ) 1:3.
The mechanism of this catalytic ethenylation most likely
involves carbostannylation of phenoxytin with silylethyne,
resulting in the â-silylethenylation as was the case in the
stoichiometric reaction.2 In addition, protodestannylation of
the carbostannylated intermediate and silicon migration take
place, and two protons at the terminal carbon atom of the
ethenylphenol are transferred from the phenolic hydroxy
group and the o-position of phenol. Although the actual metal
species responsible for these two processes are unclear, a
schematic presentation of the mechanism can be summarized
as shown in the Scheme 1.3
decrease in the yield. It might be suspected that a TON of
less than 4 does not mean catalysis but is the result of the
involvement of four Sn-Cl bonds in SnCl4. This may be
unlikely since BuSnCl3 and Bu2SnCl2 are not effective for
the present reaction. In addition, the reaction of the
o-substituted phenols (vide infra) demonstrates the catalytic
nature of this reaction.
The ethenylation of o-substituted phenol is conducted
under modified reaction conditions (Table 2). O-Cresol is
Acknowledgment. This work was supported by grants
from JSPS. A fellowship to K.K. from JSPS for young
Japanese scientists is also gratefully acknowledged.
Table 2. Catalytic Ethenylation of o-Substituted Phenol
Supporting Information Available: Experimental details
and spectra data. This material is available free of charge
via the Internet at http://pubs.acs.org.
substituent
yield/%a
OL006888D
2-Me
85
81
84
80
83b
81c
92d
(2) Yamaguchi, M.; Kobayashi, K.; Arisawa, M. Synlett 1998, 1317.
(3) Typical procedures for the ethenylation of o-substituted phenol.
Under an argon atmosphere, to o-cresol (1.08 g, 10.0 mmol) in chloroben-
zene (30 mL) were added 1.6 M butyllithium in hexane (1.25 mL, 2.0 mmol)
and SnCl4 (0.12 mL, 1.0 mmol) at 0 °C. The mixture was stirred for 10
min at room temperature, and 2,2,2-trifluoroethanol (0.073 mL, 1.0 mmol)
and trimethylsilylethyne (1.56 mL, 11.0 mmol) were added. Then, the
mixture was heated at 80 °C for 3 h. Methanol (20 mL), THF (20 mL), and
potassium fluoride (580 mg, 10.0 mmol) were added, and the mixture was
stirred for 30 min. Then water was added, and the organic materials were
extracted with ethyl acetate. The organic layer was dried over MgSO4,
filtered, and concentrated to a small volume under reduced pressure
(concentration to dryness caused the decomposition of the product). Flash
chromatography (hexane:ethyl acetate ) 50:1) over silica gel separated the
product from a small amount of the unreacted starting material. The product
was acetylated with pyridine (3.24 mL) and acetic anhydride (1.92 mL) at
room temperature for 12 h. After pouring the mixture into water, the organic
materials were extracted with ethyl acetate, dried over MgSO4, filtered,
and concentrated. Flash chromatography (hexane:ethyl acetate ) 10:1) over
silica gel gave 2-ethenyl-6-methylphenyl acetate (1.50 g, 85%).
2-Me-4-Cl
2-Me-4-I
1-naphthol
2-Et
2-(i-Pr)
2-(t-Bu)
a Yields of isolated products are shown. b Reaction conducted at 95 °C.
c Reaction conducted at 105 °C. d Reaction conducted at 150 °C in the
presence of p-CF3C6H4COOH (10 mol %).
reacted with silylethyne using 10 mol % of SnCl4, 20 mol
% of butyllithium, and 10 mol % of CF3CH2OH in
chlorobenzene at 80 °C for 3 h, and 2-ethenyl-6-methylphe-
nol is obtained in 85% yield (TON 8.5 based on SnCl4).
242
Org. Lett., Vol. 3, No. 2, 2001