Palladium-Catalyzed Etherification of Allyl Alcohols Using Phenols in the Presence of Titanium(IV) Isopropoxide

Full text of DOI:10.1021/jo970534r

J . Org. Chem. 1997, 62, 4877-4879
4877
Ta ble 1. Rea ction of Allyl Alcoh ol (1a ) w ith p-Cr esol
P a lla d iu m -Ca ta lyzed Eth er ifica tion of Allyl
Alcoh ols Usin g P h en ols in th e P r esen ce of
Tita n iu m (IV) Isop r op oxid e
(2a )a
Tetsuya Satoh, Masahiro Ikeda, Masahiro Miura,* and
Masakatsu Nomura
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565, J apan
Pd(OAc)2:PPh3:Ti(OPri)4
(in mmol)
time
(h)
yield of 3
entry
(%)b
Received March 24, 1997
1
0.025:0.1:0
0.025:0.1:0
20
7
1
1
20
1
34
26
93
0
91
61
93
90
2c
3
Palladium-catalyzed reaction of allylic compounds with
carbon, nitrogen, and oxygen nucleophiles is of genuine
synthetic utility.1 The reaction is usually carried out
using allyl esters or carbonates as substrates. In con-
trast, and in spite of their ready availability, the reaction
with allyl alcohols has been relatively less explored.2 We
have reported that palladium-catalyzed nucleophilic
substitution of allyl alcohols using zinc enolates can
proceed efficiently in the presence of titanium(IV) alkox-
ides and LiCl;3 the alkoxides appear to enhance the
reactivity of allyl alcohols toward palladium(0) species.
We considered that, when phenols are employed as
nucleophiles for the reaction, a convenient method to
prepare allyl aryl ethers could be realized; the ethers are
useful compounds in organic synthesis, particularly as
the substrates of the Claisen rearrangement.4 Conse-
quently, as part of our study of palladium-catalyzed
synthetic reactions using phenols as substrates,5,6 we
have examined the reaction of allyl alcohols with phenols
in the presence of a palladium catalyst and titanium-
(IV) isopropoxide.
0.025:0.1:0.25
0:0.2:0.25
0.025:0.1:0.25
0.01:0.04:0.25
0.01:0.04:0.25
0.01:0.1:0.25
4
5d
6
7c
8
1
1
a
Reaction conditions: 1a (4 mmol), 2a (1 mmol), in C6H6 (5
mL) at 50 °C. Determined by GLC analysis. c Reaction was
b
d
carried out using MS4A (200 mg). Reaction at rt.
Table 1).6 The reaction should be accompanied by
formation of water. Addition of molecular sieves (MS4A)
for its removal, however, showed no positive effect (entry
2). On the contrary to this normal desiccant, addition of
Ti(OPri)4 (0.25 mmol) was found to remarkably enhance
both the reaction rate and yield of 3. Thus, the yield
reached 93% within 1 h (entry 3). The reaction of allyl
alcohols with zinc enolates, mentioned above, required
addition of a chloride source such as LiCl together with
Ti(OR)4 to proceed efficiently.3 However, this was not
necessary for the present reaction. It was confirmed that
the reaction did not occur in the absence of the palladium
species (entry 4). Note that compound 3 could also be
produced in good yield in the reaction at room temper-
ature or using a smaller amount of the palladium catalyst
(1 mol %) (entries 5, 7, and 8). In the latter case, either
addition of MS4A or increase in the amount of PPh3
added was needed to prevent catalyst deactivation which
is probably due to water formed during the reaction.
Treatment of 1a using phenols substituted by both
electron-withdrawing and electron-donating groups (2c-
e) also gave ethers 5-7 in good yields (Table 2). In the
case of 2c, the use of Ti(OPri)4 was essential for the
reaction to proceed catalytically. A phenol bearing a
bulky substituent, But, at 2-position could also be reacted,
whereas a more sterically crowded phenol, 2,6-di-tert-
butylphenol, did not undergo the reaction.
When a mixture of allyl alcohol (1a , 4 mmol) and
p-cresol (2a , 1 mmol) was heated in the presence of Pd-
(OAc)2 (0.025 mmol) and PPh3 (0.1 mmol) in C6H6 (5 mL)
under nitrogen at 50 °C for 20 h, 1-(4-methylphenoxy)-
2-propene (3) was produced in a yield of 34% (entry 1 in
(1) (a) Trost, B. M.; Verhoeven, T. R. in Comprehensive Organome-
tallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Per-
gamon: Oxford, 1982; Vol. 8. (b) Heck, R. F. Palladium Reagents in
Organic Syntheses; Academic Press: New York, 1985. (c) Tsuji, J .
Palladium Reagents and Catalysts; J ohn Wiley & Sons Ltd.: Chi-
chester, 1995.
(2) (a) Atkins, K. E.; Walker, W. E.; Manyik, R. M. Tetrahedron Lett.
1970, 3821. (b) Haudegond, J .-P.; Chauvin, Y.; Commereuc, D. J . Org.
Chem. 1979, 44, 3063. (c) Moreno-Man˜as, M.; Trius, A. Tetrahedron
1981, 37, 3009. (d) Lu, X.; J iang, X.; Tao, X. J . Organomet. Chem. 1988,
344, 109. (e) Bergbreiter, D. E.; Weatherford, D. A. J . Chem. Soc.,
Chem. Commun. 1989, 883. (f) Lumin, S.; Falck, J . R.; Capdevila, J .;
Karara, A. Tetrahedron Lett. 1992, 33, 2091. (g) Stary´, I.; Stara´, I. G.;
Kocˇovsky´, P. Tetrahedron Lett. 1993, 34, 179. (h) Tsay, S.; Lin, L. C.;
Furth, P. A.; Shum, C. C.; King, D. B.; Yu, S. F.; Chen, B.; Hwu, J . R.
Synthesis 1993, 329. (i) Masuyama, Y.; Kagawa, M.; Kurusu, Y. Chem.
Lett. 1995, 1121. (j) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Bull.
Chem. Soc. J pn. 1996, 69, 1065.
When 3,5-dimethoxyphenol (2g) whose aryl moiety
seems to be relatively electron rich7 was employed,
C-allylated products 9 and 10 were obtained,4f,8 no
O-allylated products being detected (Scheme 1). Depend-
ing on the ratio of 1a /2g used, monoallylated product 9
or diallylated product 10 was selectively produced. Since
1-(3,5-dimethoxyphenoxy)-2-propene (11) was found to be
transformed to 9 under the present conditions, the
C-allylated products may also be formed, at least in part,
by isomerization of the ether 11.
(3) Itoh, K.; Hamaguchi, N.; Miura, M.; Nomura, M. J . Chem. Soc.,
Perkin Trans. 1 1992, 2833.
(4) Palladium-catalyzed allyl aryl ether synthesis using allylic esters,
ethers, or carbonates: (a) Takahashi, K.; Miyake, A.; Hata, G. Bull.
Chem. Soc. J pn. 1972, 45, 230. (b) Keinan, E.; Roth, Z. J . Org. Chem.
1983, 48, 1769. (c) Keinan, E.; Sahai, M.; Roth, Z.; Nudelman, A.;
Herzig, J . J . Org. Chem. 1985, 50, 3558. (d) Muzart, J .; Geneˆt, J . P.;
Denis, A. J . Organomet. Chem. 1987, 326, C-23. (e) Deardorff, D. R.;
Linde, R. G., II; Martin, A. M.; Shulman, M. J . J . Org. Chem. 1989,
54, 2759. (f) Goux, C.; Massacret, M.; Lhoste, P.; Sinou, D. Organo-
metallics 1995, 14, 4585.
(5) (a) Itoh, K.; Miura, M.; Nomura, M. Tetrahedron Lett. 1992, 33,
5369. (b) Satoh, T.; Kokubo, K.; Miura, M.; Nomura, M. Organome-
tallics 1994, 13, 4431. (c) Satoh, T.; Ikeda, M.; Miura, M.; Nomura, M.
J . Mol. Catal. A: Chemical 1996, 111, 25. (d) Satoh, T.; Tsuda, T.;
Kushino, Y.; Miura, M.; Nomura, M. J . Org. Chem. 1996, 61, 6476. (e)
Satoh, T.; Itaya, T.; Miura, M.; Nomura, M. Chem. Lett. 1996, 823.
(6) The formation of allyl aryl ethers was also observed in the
reaction medium of palladium-catalyzed carbonylation of allyl alcohols
in the presence of phenols at the early stage: Satoh, T.; Ikeda, M.;
Kushino, Y.; Miura, M.; Nomura, M. J . Org. Chem. 1997, 62, 2662.
(7) Trost, B. M.; Toste, F. D. J . Am. Chem. Soc. 1996, 118, 6305.
(8) Recently, it has been reported that treatment of 1- or 2-naphthol
with allyl alcohols gives the corresponding C-allylated products: Tada,
Y.; Satake, A.; Shimizu, I.; Yamamoto, A. Chem. Lett. 1996, 1021.
S0022-3263(97)00534-3 CCC: $14.00 © 1997 American Chemical Society

4878 J . Org. Chem., Vol. 62, No. 14, 1997
Notes
Ta ble 2. Rea ction of Allyl Alcoh ol (1a ) w ith P h en ols
Ta ble 3. Rea ction of Allyl Alcoh ols 1b-g w ith P h en ol
2b-fa
(2b)a
Sch em e 2
Sch em e 1
same products may suggest that the reaction process
involves a common π-allylpalladium intermediate.
A possible mechanism for the formation of allyl aryl
ethers from 1 and 2 is illustrated in Scheme 2, in which
the substituent on allyl alcohol is omitted. Alcohol 1 or
an allyl titanate, formed by alcohol exchange reaction
between 1 and isopropoxide in Ti(OPri)4,3 reacts with Pd0
species generated in situ9 to afford a π-allylpalladium
intermediate (I). Subsequently, the reaction of I with
phenol 2 followed by reductive elimination gives allyl aryl
ether. Under the present reaction conditions using Ti-
(OPri)4, treatment of cinnamyl alcohol (1c) without
phenols gave dicinnamyl ether quantitatively within 1
Results for etherification of a number of allyl alcohols
1b-g with phenol (2b) using Pd(OAc)2, PPh3, Ti(OPri)4,
and MS4A are summarized in Table 3. All of allyl
alcohols examined underwent etherification smoothly to
give the corresponding phenyl ethers in 71-89% yields,
while mixtures of regioisomeric ethers were formed in
the cases using 1e-g. The fact that 1f and 1g gave the
(9) One of the other possible functions of Ti(OPri)4 may be accelera-
tion of the reduction of Pd(OAc)2 to Pd0 species as was observed in our
previous work: Satoh, T.; Itoh, K.; Miura, M.; Nomura, M. Bull. Chem.
Soc. J pn. 1993, 66, 2121.

Notes
J . Org. Chem., Vol. 62, No. 14, 1997 4879
nitrogen at 50 °C for 4-20 h. After cooling, the reaction mixture
was poured into dilute hydrochloric acid, extracted with ether,
and dried over sodium sulfate. Product was isolated by column
chromatography on silica gel using hexane-ethyl acetate (99:
1) as eluent.
h, while part of this was transformed to cinnamyl
isopropyl ether by elongation of the reaction time. Di-
cinnamyl ether may be formed by the reaction of I with
another cinnamyl titanate molecule.10 In the presence
of phenols, which may be relatively more reactive toward
the palladium center, I should be predominantly trans-
formed to II to afford aryl ether. It would also be possible
that II is formed by ligand exchange between I and
Ti(OAr)n(OR)4-n species generated in the reaction me-
dium
Products 3,4a 4,4f 5,11 6,12 7,13 8,14 12,15 13,4f 14,4f 15,15 16,15
17,4f and 184f are known.
4-Allyl-3,5-d im eth oxyp h en ol (9): mp 85-87 °C; 1H NMR
(DMSO-d6) δ 3.16 (d, 2H, J ) 5.9 Hz), 3.33 (s, 6H), 4.81 (t, 1H,
J ) 1.5 Hz), 4.84 (dt, 1H, J ) 4.4, 1.5 Hz), 5.73-5.83 (m, 1H),
6.05 (s, 2H), 7.29 (s, 1H); MS m/ z 194 (M+). Anal. Calcd for
C
11H14O3: C, 68.02; H, 7.26. Found: C, 67.83; H, 7.21.
4,4-Dia llyl-3,5-d im eth oxy-2,5-cycloh exa d ien -1-on e (10):
mp 71-72 °C; 1H NMR (CDCl3) δ 2.57 (d, 4H, J ) 7.3 Hz), 3.70
(s, 6H), 4.92 (dt, 2H, J ) 5.9, 1.0 Hz), 4.96 (dd, 2H, J ) 13.2, 2.0
Hz), 5.33-5.49 (m, 2H), 5.54 (s, 2H); 13C NMR (CDCl3) δ 40.99,
51.19, 55.79, 103.27, 117.75, 132.20, 172.92, 188.37; MS m/ z 234
(M+). Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C,
71.59; H, 7.76.
Exp er im en ta l Section
1H and 13C NMR spectra were recorded at 400 MHz and 100
MHz, respectively. MS data were obtained by EI. GLC analysis
was carried out using a silicon OV-17 column (i.d. 2.6 mm × 1.5
m) or with a CBP-1 capillary column (i.d. 0.5 mm × 25 m).
J O970534R
1-(3,5-Dimethoxyphenoxy)-2-propene (11) was prepared by the
reaction of allyl chloride with 2g using K2CO3 as base in DMF
at 40 °C. Other starting materials were commercially available.
Solvents were purified by standard methods before use.
(11) Mullen, G. B.; Swift, P. A.; Marinyak, D. M.; Allen, S. D.;
Mitchell, J . T.; Kinsolving, C. R.; Georgiev, V. S. Helv. Chem. Acta 1988,
71, 718.
(12) Maruoka, K.; Sato, J .; Banno, H.; Yamamoto, H. Tetrahedron
Lett. 1990, 31, 377.
(13) Derakumar, C.; Saxena, V. S.; Mukerjee, S. K. Agric. Biol.
Chem. 1985, 49, 725.
Eth er ifica tion of Allyl Alcoh ols Usin g P h en ols. A mix-
ture of 1 (1-4 mmol), 2 (1-2 mmol), Pd(OAc)2 (2.2 mg, 0.01
mmol), PPh3 (10 mg, 0.04 mmol), Ti(OPri)4 (0.075 mL, 0.25
mmol), MS4A (200 mg), and benzene (5 mL) was stirred under
(14) Goto, M.; Hayashi, T. Nippon Kagaku Kaishi 1979, 743; Chem.
Abstr. 1979, 91, 107493u.
(15) Flaud, J . C.; Hibon de Gournay, A.; Larcheveque, M.; Kagan,
H. B. J . Organomet. Chem. 1978, 154, 175.
(10) Itoh, K.; Hamaguchi, N.; Miura, M.; Nomura, M. J . Mol. Catal.
1992, 75, 117.