Palladium(II)-catalyzed oxidative transformation of allylic alcohols and vinyl ethers into 2-alkoxytetrahydrofurans: Catechol as an activator of catalyst

Article abstract of DOI:10.1021/ol052377l

(Chemical Equation Presented) A highly effective synthesis of 2-alkoxytetrahydrofurans from allylic alcohols and vinyl ethers was achieved by using catalytic amounts of Pd(OAc)₂, Cu(OAc)₂, and catechol (1:1:2) under O₂. The use of catechol as an activator of Pd(II)-Cu(II) catalyst has been unprecedented. The 2-alkoxytetrahydrofurans are formed via oxypalladation of allylic alcohols toward vinyl ethers followed by 5-exo cyclization of the resulting oxypalladation intermediate and subsequent β-Pd-H elimination. No 6-endo cyclization of the oxypalladation intermediate occurs.

Full text of DOI:10.1021/ol052377l

ORGANIC
LETTERS
2005
Vol. 7, No. 25
5689-5692
Palladium(II)-Catalyzed Oxidative
Transformation of Allylic Alcohols and
Vinyl Ethers into
2-Alkoxytetrahydrofurans: Catechol as
an Activator of Catalyst
Kimi Minami, Yasufumi Kawamura, Koichi Koga, and Takahiro Hosokawa*
Department of EnVironmental Systems Engineering, Kochi UniVersity of Technology,
185 Miyanokuchi, Tosayamada, Kochi, 782-8502, Japan
hosokawa.takahiro@kochi-tech.ac.jp
Received October 2, 2005
ABSTRACT
A highly effective synthesis of 2-alkoxytetrahydrofurans from allylic alcohols and vinyl ethers was achieved by using catalytic amounts of
Pd(OAc)2, Cu(OAc)2, and catechol (1:1:2) under O2. The use of catechol as an activator of Pd(II) Cu(II) catalyst has been unprecedented. The
2-alkoxytetrahydrofurans are formed via oxypalladation of allylic alcohols toward vinyl ethers followed by 5-exo cyclization of the resulting
oxypalladation intermediate and subsequent -Pd H elimination. No 6-endo cyclization of the oxypalladation intermediate occurs.
−
â
−
Among a variety of Pd(II)-catalyzed oxidative transforma-
tions of alkenes with oxygen nucleophiles,1 the use of allylic
alcohols as the nucleophile has not received much attention
in synthetic chemistry.2-4 A paper in 1987 reported the use
of allylic alcohols as the nucleophile to attack vinyl ethers.2a
The oxypalladation intermediates thus formed undergo
intramolecular 5-exo cyclization to give 2-alkoxytetrahydro-
furans via Pd-H elimination (Scheme 1). This reaction
Scheme 1
(1) (a) Tsuji, J. Palladium Reagents and Catalysts, InnoVation in Organic
Synthesis; John Wiley & Sons: New York, 1995; pp 19-124. (b)
Hosokawa, T.; Murahashi, S.-I. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; John Wiley & Sons:
New York, 2002; Vol. II, pp 2141-2192. (c) Henry, P. M. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; John
Wiley & Sons: New York, 2002; Vol. II, pp 2119-2139. (d) Zeni, G.;
Larock, R. C. Chem. ReV. 2004, 104, 2285-2309. (e) For related studies,
see: Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400-3420. Nishimura,
T.; Uemura, S. Synlett 2004, 201-216.
(2) (a) Fugami, K.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1987,
28, 809-812. Also see: Fugami, K.; Oshima, K.; Utimoto, K. Bull. Chem.
Soc. Jpn. 1989, 62, 2050-2054. (b) Kraus, G. A.; Thurston, J. J. Am. Chem.
Soc. 1989, 111, 9203-9205. (c) Larock, R. C.; Lee, N. H. J. Am. Chem.
Soc. 1991, 113, 7815-7816. (d) Ohshima, M.; Murakami, M.; Mukaiyama,
T. Chem. Lett. 1984, 1535-1536.
appeared to have a high synthetic utility, but it was not
catalytic in Pd(II) except for one example with a large
amount of Cu(II) as the promoter of catalyst. Very recently,
an extension of this reaction to stereoselective synthesis of
4-vinyl-2-alkoxytetrahydrofurans with Pd(OAc)2 catalyst has
been reported, but in this case, a large amount of Cu(OAc)2
(2.5 equiv) was also employed as a stoichiometric oxidant.4
We report herein that the use of catalytic amounts of catechol
and Cu(OAc)2 under O2 remarkably enhances Pd(II) catalysis
of this reaction. This finding is not only of significance in
(3) For the use of allylic alcohols as allylation reagents via π-allyl-
palladium(II) precursors, see: Kinoshita, H.; Shinokubo, H.; Oshima, K.
Org. Lett. 2004, 6, 4085-4088 and references therein.
(4) Evans, M. A.; Morken, J. P. Org. Lett. 2005, 7, 3367-3370 and
3371-3373. See also ref 2b.
10.1021/ol052377l CCC: $30.25
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synthetic chemistry,5 but it is also unique since such an effect
of catechol is unprecedented in the chemistry of palladium.
Previously we reported that a catalyst system of PdCl2,
CuCl, and hexamethylphosphoramide (HMPA) activates O2,
resulting in the ketonization of 1-alkenes.6 The activation
of O2 in this system was thought to occur at the copper site
bearing HMPA as the ligand,7 thereby effecting Pd(II)
catalysis. Copper salts have been known to combine with
catechol,8 and catechols activate O2.9 These led us to assume
that Pd(II) catalysis must be enhanced by an array of Pd(II),
Cu(II), and catechol under O2.
Table 1. Reaction of Allylic Alcohols 1 and Vinyl Ethers 2a
From such a viewpoint, we examined the reaction of (E)-
3-phenyl-2-propen-1-ol (1a) and ethyl vinyl ether (2a) with
Pd(OAc)2-Cu(OAc)2 catalyst under O2 (balloon) in MeCN.
Indeed, as shown in Scheme 2, the presence of catechol (4)
Scheme 2
a Pd(OAc)2 (11.2 mg, 0.05 mmol), Cu(OAc)2 (9.1 mg, 0.05 mmol), and
catechol (4) (11.0 mg, 0.1 mmol) were dissolved in MeCN (0.5 mL) in a
25 mL side-armed round-bottomed flask under O2 (balloon), and the mixture
was stirred for 30 min at room temperature. Vinyl ether 2 (4.0 mmol) was
added to the flask, and a solution of allylic alcohol 1 (1.0 mmol) in MeCN
(0.5.mL) was then added. The mixture was stirred at room temperature
until allylic alcohol 1 was nearly completely consumed. b Isolated yields
based on 1. Parentheses contain yields in the case of not using 4. c Using
0.1 mmol of Pd(OAc)2, Cu(OAc)2, and 4 in each with all other conditions
the same. d The ratio of R*R*/R*S* was 87/13 in 3d and 86/14 in 3e. In
the case of not using 4, the value was 87/13 and 93/7, respectively. e In
this entry, GC yields of 3 based on 1 with anisole as an internal standard
are shown. f The cis/trans ratio was 71/29, and in the case of not using 4,
it was 65/35.
(Pd/Cu/4 ) 1/1/1-2) increased the yield of 3a up to 82-
84% (based on 1a) from 48%.10 An excess use of 4 (4 equiv)
rather decreased the yield (79%). The OAc ligand of catalysts
is essential, since with the use of either a combination of
PdCl2-Cu(OAc)2-4 or Pd(OAc)2-CuCl-4 (Pd/Cu/4 ) 1/1/
2) under the conditions shown in Scheme 2 the yield of 3a
was only 4% or 24% along with not yet identified products.
Note that the product 3a in these reactions was obtained
solely as the (Z)-form.
occurred during the reaction, and the yields became lower
as shown in parentheses. In these experiments, 5 mol % of
Pd(OAc)2 catalyst per 1 was usually employed, but it could
be reduced to 1 mol %. Thus, the reaction of 1a (2.5 mmol)
and 2a (10 mmol) with Pd(OAc)2-Cu(OAc)2 (0.025 mmol
each) and 4 (0.05 mmol) (Scheme 3) gave a 86% yield of
With these results in hand, we examined the reaction of
various substrates 1 and 2. In all cases shown in Table 1,
good yields of 3 (73-96%) resulted in the presence of 4. In
the absence of 4, the precipitation of metallic palladium
Scheme 3
(5) For example, we have recently found that 4-benzylidene-2-butox-
ytetrahydrofuran serves as the apoptosis inducer of U937 human lymphoma
cell: Sazuka, M.; Hosokawa, T. Unpublished results.
(6) (a) Hosokawa, T.; Nakahira, T.; Takano, M.; Murahashi, S.-I. J. Mol.
Catal. 1992, 74, 489-498. (b) Hosokawa, T.; Aoki, S.; Takano, M.;
Nakahira, T.; Yoshida, Y.; Murahashi, S.-I. J. Chem. Soc., Chem. Commun.
1991, 1559-1560.
3a (2.15 mmol), although it took a longer reaction time for
completion (24 h). The turnover number of Pd catalyst
corresponds to 86. The O2 absorption measured in this
reaction showed a monotonic increase, and the O2 uptake
after 24 h reached 1.08 mmol, which correlated with the
amount of 3a (2.15 mmol) formed. Namely, the production
of 1 mol of 3a requires only half a mole of O2 as the
stoichiometric oxidant. In this case, the absence of 4 again
remarkably decreased the yield of 3a (20%, 24 h).
(7) For a related study, see: Hosokawa, T.; Takano, M.; Murahashi, S.-
I. J. Am. Chem. Soc. 1996, 118, 3990-3991.
(8) (a) Berreau, L. M.; Mahapatra, S.; Halfen, J. A.; Houser, R. P.; Young,
V. G., Jr.; Tolman, W. B. Angew. Chem., Int. Ed. 1999, 38, 207-210 and
references cited therein. (b) Kodera, M.; Kawata, T.; Kano, K.; Tachi, Y.;
Ito, S.; Kojo, S. Bull. Chem. Soc. Jpn. 2003, 76, 1957-1964 and references
cited therein.
(9) Inui, T.; Nakahara, K.; Uchida, M.; Miki, W.; Unoura, K.; Kokeguchi,
U.; Hosokawa, T. Bull. Chem. Soc. Jpn. 2004, 77, 1201-1207.
(10) The use of other solvents such as 1,2-dichloromethane or ethyl
acetate under the conditions shown in Scheme 2 (Pd/Cu/4 ) 1/1/2) resulted
in poor yields (∼30%) of 3a. When ethyl orthoformate, which acts as a
scavenger of water, was employed, the yield of 3a was only 42%. Note
that in all these cases, the absence of 4 further decreased the yields of 3a.
The previous paper2a reported that the reaction of 1a and
2a under similar conditions did not give 3a, but that
5690
Org. Lett., Vol. 7, No. 25, 2005

2-ethoxy-4-phenyl-3,6-dihydropyran (5) arising from 6-endo
cyclization of the oxypalladation adduct (Scheme 4) was
Allyl alcohol (1c) itself reacts with 2b to afford a 73%
yield of 2-butoxy-4-methylenetetrahydrofuran (3f) (Table 1,
entry 6), which represents the basic structure of this class of
compounds. This is the first preparation of 3f, as well as for
3d and 3e. 2-Buten-1-ol (1d) reacts with 2b to give a 73%
yield of 4-vinyltetrahydrofuran 3g (cis/trans ) 71/29, entry
7), the cis/trans configuration of which was assigned by 2D-
NOESY experiment in NMR.11 The product 3g is formed
by oxypalladation and cyclization (Scheme 1) followed by
â-hydride elimination from the methyl group (R ) Me) in
the side chain.
Scheme 4
All the products 3 formed have thus the five-membered
furan structure arising from 5-exo cyclization of the oxyp-
alladation intermediate (Scheme 1). The preference of this
pathway, rather than the 6-endo one (Scheme 4), must be
due to conformational compatibility of the oxypalladation
adduct for undergoing the cyclization toward internal alkene,
which must coordinate to Pd(II). The rate of this cyclization
is likely influenced by the R group of the allylic moiety,
and thereby the NO2 substituent on the Ph group retards the
reaction (Table 1, entries 3 and 5).
formed. However, the structural assignment of 5 was not
made in detail. In addition, we could not determine why only
this reaction, among several examples, produces the dihy-
dropyran 5 instead of 3a. Then, we decided to determine its
structure by X-ray analysis. No single crystal was obtained
with 3a itself, but 3c (R ) 4-NO2Ph) (Table 1, entry 3) gave
a crystal suitable for X-ray analysis. The ORTEP drawing
shown in Figure 1 proved 3c to possess the furan structure
Finally, for the role of catechol (4) on catalysis, we would
like to mention the following. In palladium(II)-catalyzed
oxidations, p-benzoquinones have been known to act as
oxidants.12 In addition, the catalysis of Pd(II) can be induced
by a redox couple of p-benzoquinone and hydroquinone
13
under O2 with metal complexes such as Cu(OAc)2 or Co-
(salen).12a However, the use of either hydroquinone (10 mol
%) or p-benzoquinone (10 mol %), in place of 4, under the
conditions given in Table 1 (entry 1) gave 3a only in 7% or
17% yield, respectively. This suggests that a redox couple
between catechol and o-quinone is not operative in the
present system. Thus, the role of 4 would be in (i)
enhancement of catalyst stability by constructing a Pd-Cu
heterometallic species bearing 4 as the ligand of Cu14 and
(ii) effective capture of O2 and its activation by the Cu-
catechol moiety. The catalytic turnover process must involve
Pd-H species formed and O2, the details of which are also
the subject of further study.15
In conclusion, the present study demonstrated the ef-
fectiveness of catechol as the activator of Pd(OAc)2-Cu-
(OAc)2 catalyst under O2. The present reaction produces five-
membered furan derivatives, irrespective of substituents in
substrates. The reaction is environmentally benign, since only
Figure 1. ORTEP drawing of compound 3c.
bearing the (Z)-configuration in exo-methylene moiety. Thus,
the previous structural assignment of 5 was incorrect.
The structure assignment of 3e bearing pyranyl moiety
(Table 1, entries 4 and 5) was also made by X-ray analysis.
The product 3e (or 3d) was obtained as a mixture of two
diastereomers, and each isomer was able to be separated by
TLC. One of the diastereomers in 3e (R ) 4-NO2Ph)
produced a single crystal suitable for X-ray analysis. The
ORTEP drawing in Figure 2 shows the tetrahydrofuran
(11) The details are given in the Supporting Information.
(12) (a) Ba¨ckvall, J.-E.; Hopkins, R. B.; Grennberg, H.; Mader, M. M.;
Awasthi, A. K. J. Am. Chem. Soc. 1990, 112, 5160-5166 and references
therein. (b) Ba¨ckvall, J.-E.; Hopkins, R. B. Tetrahedron Lett. 1988, 29,
2885-2888.
(13) Bystro¨m, S. E.; Larsson, E. M.; Åkermark, B. J. Org. Chem. 1990,
55, 5674-5675.
(14) This view could be supported by the following facts. When either
Pd(OAc)2 alone or a combination of Pd(OAc)2 and 4 was employed as the
catalyst under otherwise the same conditions described in Table 1 (entry
1), the yield of 3a was low (15%) and comparable. Thus, a combination of
Cu(OAc)2 and 4 together with Pd(OAc)2 was evidently required for a higher
production of 3a (Table 1, entry 1). It is possible that o-quinone derived
from 4 could be a candidate as the ligand of Cu in catalytically active
species.
Figure 2. ORTEP drawing of compound 3e.
(15) For the related catalysis, see: (a) Steinhoff, B. A.; Guzei, I. A.;
Stahl, S. S. J. Am. Chem. Soc. 2004, 126, 11268-11278. (b) Mueller, J.
A.; Goller, C. P.; Sigman, M. S. J. Am. Chem. Soc. 2004, 126, 9724-
9734.
structure of 3e bearing the R*R* configuration with respect
to the two chiral centers.
Org. Lett., Vol. 7, No. 25, 2005
5691

molecular oxygen is the stoichiometric oxidant. A higher
turnover of the catalyst and simple manipulations make the
reaction synthetically useful. In addition, since a variety of
vinyl ethers are readily available by procedures recently
reported,16 the synthetic utility of this reaction will undoubt-
edly be expanded.
Acknowledgment. We acknowledge Professor K. Oshi-
ma of Kyoto University for helpful discussions.
Supporting Information Available: Experimental de-
tails, characterization data, and X-ray analysis of compounds
3c and 3e. This material is available free of charge via the
Internet at http://pubs.acs.org.
(16) (a) Okimoto, Y.; Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2002,
124, 1590-159l. (b) Bosch, M.; Schlaf, M. J. Org. Chem. 2003, 68, 5225-
5227.
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