Ruthenium-catalyzed transformation of 3-benzyl but-1-ynyl ethers into 1,3-dienes and benzaldehyde via transfer hydrogen

Article abstract of DOI:10.1021/jo049514x

TpRuPPh₃(CH₃CN)₂PF₆ catalyzed the transformation of various 3-benzyl but-1-ynyl ethers into dienes and benzaldehyde at a catalyst loading of 5 mol %. This process represents an atypical pattern of transfer hydrogenation. This catalytic reaction can be applied to various derivatives of 2-ethynyl tetrahydrofurans and pyrans to cleave their ether rings and gives diene and tethered aldehyde functionalities, respectively.

Full text of DOI:10.1021/jo049514x

Ru th en iu m -Ca ta lyzed Tr a n sfor m a tion of 3-Ben zyl Bu t-1-yn yl
Eth er s in to 1,3-Dien es a n d Ben za ld eh yd e via Tr a n sfer Hyd r ogen
Kuo-Liang Yeh, Bo Liu, Yen-Ting Lai, Chia-Wen Li, and Rai-Shung Liu*
Department of Chemistry, National Tsinh-Hua University, Hsinchu, Taiwan, ROC
rsliu@mx.nthu.edu.tw
Received March 24, 2004
TpRuPPh3(CH3CN)2PF6 catalyzed the transformation of various 3-benzyl but-1-ynyl ethers into
dienes and benzaldehyde at a catalyst loading of 5 mol %. This process represents an atypical
pattern of transfer hydrogenation. This catalytic reaction can be applied to various derivatives of
2-ethynyl tetrahydrofurans and pyrans to cleave their ether rings and gives diene and tethered
aldehyde functionalities, respectively.
SCHEME 1
Metal-catalyzed transfer hydrogenation between two
organic molecules has attracted considerable attention.1-4
This process is considered to be environmentally friendly
because it avoids the use of oxidants and reductants.
Several useful catalytic reactions have been designed on
the basis of this process, and notable examples include
the asymmetric hydrogenation of ketones and imines
from 2-propanol and formic acids using chiral metal
catalysts.1a,2a,b Scheme 1 (eq 1) shows a typical pattern
for most cases of metal-catalyzed transfer hydrogenation
which involves the hydrogenation of C ) X (X ) O, NR,
CR2) or alkyne by alcohols and formic acid.1-3 We sought
to identify a new pathway to broaden the present scope.
Benzyl ethers have been widely used as a protecting
group for organic alcohols,5,6 and the removal of this
functionality relies on an excess (>1.0 equimolar) of
suitable oxidants or reductants. Chemical degradation
of this protecting group using a metal catalyst alone is a
challenging problem in synthetic chemistry.
Recently, we reported an interesting degradation of
ethynyl benzyl ethers via metal-catalyzed transfer hy-
drogenation.7 As shown in Scheme 1 (eq 2), the ethers
are transformed into benzaldehyde and dienes using
TpRuPPh3(CH3CN)2PF6 catalyst (8.0 mol %). We propose
a plausible mechanism on the basis of deuterium-labeling
experiments. The reaction is initiated by formation of
ruthenium-allenylidenium species I,8 which subse-
quently formed ruthenium-oxacarbenium II and ulti-
mately gave diene and benzaldehyde in good yields. This
process provides easy access to organic dienes from
readily available ethynyl alcohols. In this study, we
report an improvement in the catalyst efficiency as well
as the catalytic application to the ring cleavage of
2-ethynyltetrahydrofuran and -pyran derivatives.
(1) For reviews of ruthenium-catalyzed hydrogen transfer reactions,
see: (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97. (b)
Naota, T.; Takaya, H.; Murahashi, S. Chem. Rev. 1998, 98, 2599. (c)
Palmer, M. J .; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045.
(2) For examples of ruthenium-catalyzed hydrogen transfer reaction,
see: (a) Yamada, I.; Noyori, R. Org. Lett. 2000, 2, 3425. (b) Matsumura,
K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J . Am. Chem. Soc. 1997,
119, 8738. (c) Gordon, E. M.; Gaba, D. C.; J ebber, K. A.; Zacharias, D.
M. Organometallics 1993, 12, 5020. (d) Wang, G.-Z.; Backvall, J . E. J .
Chem. Soc., Chem. Commun. 1992, 980. (e) Mizushima, E.; Yamaguchi,
M.; Yamagishi, T. Chem Lett. 1997, 237. (f) Genet, J .-P.; Ratovelo-
manana-Vidal V.; Pinel, C. Synlett 1993, 478.
(3) For examples of an aluminum-catalyzed reaction (Meerwein-
Pondorf-Verley reduction), see: (a) Campbell, E. J .; Zhou, H.; Nguyen,
S. T. Org. Lett. 2001, 3, 2391. (b) Ooi, T.; Miura, T.; Maruoka, K. Angew.
Chem., Int. Ed. 1998, 37, 2347. (c) Ooi, T.; Itagaki, Y.; Miura, T.;
Maruoka, K. Tetrahedron Lett. 1999, 40, 2137. (d) Konishi, K.; Makita,
K.; Aida, T.; Inoue, S. J . Chem. Soc., Chem. Commun. 1988, 643.
(4) For hydrogen transfer reaction catalyzed by non-ruthenium
transition-metal complexes, see: (a) Muller, D.; Umbricht, G.; Weber,
B.; Pfaltz, A. Helv. Chim. Acta 1991, 74, 232. (b) Gamez, P.; Fache, F.;
Lemaire, M. Tetrahedron: Asymmetry 1995, 6, 705. (c) Evans, D. A.;
Nelson, S. G.; Gagne, M. R.; Muci, A. R. J . Am. Chem. Soc. 1993, 115,
9800.
We first examined the catalytic transformation of
benzyl ether 1 with various catalysts, and the results are
summarized in Scheme 1. We selected TpRuPPh3(CH3-
CN)2PF69 catalyst (I) containing a tris(1-pyrazolyl)borate
(7) For a preliminary communication, see: Yeh, K. L.; Liu, B.; Lo,
C. Y.; Huang, H. L.; Liu, R. S. J . Am. Chem. Soc. 2002, 124, 6510.
(8) Only several examples are known for nonmetathesis catalytic
reactions involving ruthenium-allenylidenium intermediates: (a)
Trost, B. M.; Flygare, J . A. J . Am. Chem. Soc. 1992, 114, 5476. (b)
Trost, B. M.; Flygare, J . A. Tetrahedron Lett. 1994, 35, 4059.
(5) (a) Czernecki, S.; Georgoulis, C.; Provelenghio, C. Tetrahedron
Lett. 1976, 3535 (b) Iwashige, T. Saeki, H. Chem. Pharm. Bull. 1967,
15, 1803.
(6) (a) Heathcock, C. H.; Ratcliffe, R. J . Am. Chem. Soc. 1971, 93,
1746. (b) Bindra, J . S.; Grodski, A. J . Org. Chem. 1978, 43, 3240.
10.1021/jo049514x CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/16/2004
4692
J . Org. Chem. 2004, 69, 4692-4694

Ru-Catalyzed Transformation of 3-Benzyl But-1-ynyl Ethers
TABLE 1. Ca ta lytic Tr a n sfor m a tion over Va r iou s Solven ts a n d Ca ta lysts
entry
catalysta
solvent
additive
conditionsb
productsc
1
2
3
4
5
6
7
8
9
A (8%)a
A (8%)
A (8%)
A (8%)
A (8%)
A (5%)
A (5%)
A (5%)
A (5%)
A (5%)
B (5%)
C (5%)
DCE
benzene
CH3CN
ethyl acetate
DME
DCE
DCE
benzene
benzene/DCE (1/3)
benzene/DCE (3/1)
benzene/DCE (3/1)
benzene/DCE (3/1)
80 °C (12 h)
80 °C (12 h)
80 °C (24 h)
80 °C (24 h)
80 °C (24 h)
80 °C (24 h)
80 °C (12 h)
80 °C (12 h)
80 °C (15 h)
80 °C (15 h)
80 °C (15 h)
80 °C (15 h)
1 (1.0%), 2 (83%), BA (81%)
1 (68%), 2 (13%), BA (18%)
no reaction (1, 68%)
1 (82%), 2 (9%), BA (13%)
1 (77%), 2 (13%), BA (15%)
1 (30%), 2 (47%), BA (56%)
1 (8%), 2 (23%), BA (70%)
1 (5%), 2 (78%), BA (87%)
1 (2%), 2 (86%), BA (91%)
1 (2%), 2 (84%), BA (89%)
no reaction (1, 75%)
LiOTf (5%)
LiOTf (5%)
LiOTf (5%)
LiOTf (5%)
LiOTf (5%)
LiOTf (5%)
10
11
12
no reaction (1, 85%)
a
b
Catalyst (mol %): TpRuPPh3(CH3CN)2PF6 (A), TpRuPPh3(CH3CN)Cl (B), (C5Me5)RuPPh3 (CH3CN)2PF6 (C). [substrate] ) 0.80 M.
c Yields were obtained after separation from silica column.
TABLE 2. Ca ta lytic Tr a n sofr m a tion of 3-Ben zyl
Bu t-1-yn yl Eth er s
ligand because it readily reacted with a terminal alkyne
to form vinylidenium species.10,11 Among various solvents
(entries 1-5), only dichloroethane showed good catalytic
activity and gave diene 2 (E/Z ) 7.5) in 83% yield in
addition to benzaldehyde (81% yield) with 8.0 mol %
catalyst A. Entries 6-10 show our efforts to enhance the
catalytic efficiency with less catalyst. In the presence of
LiOTf (5.0 mol %) and 5 mol % catalyst A, diene 2 was
obtained in only 23% in dichloroethane despite nearly
90% conversion: benzaldehyde was obtained in 70%
yield. Diene 2 seemed to be unstable in dichloroethane
in the presence of LiOTf additive. Notably, LiOTf shows
a significant improvement in catalytic efficiency in
benzene, in which diene 2 and benzaldehyde were
obtained in respective yields of 78% and 87% yields (entry
8). The use of a mixture of dichloroethane/benzene
solvents (entries 9 and 10) gave the best results, with
diene 2 obtained in yields as high as 84-86% yields. The
catalysts TpRuPPh3(CH3CN)Cl9 (B) and C5Me5RuPPh3-
(CH3CN)2PF6 (C) were inactive even in the presence of
LiOTf additive. These results indicate that the two vacant
sites and electron-donating ability of the tris(1-pyrazolyl)-
borate ligand around catalyst A are crucial for catalytic
activity (Table 1).
a
Condition I: 8.0 mol % catalyst A in DCE (80 °C, 12 h).
b
II: 5 mol % catalyst A 5.0 mol % LiOTf in DCE (80 °C, 12 h).
c III: 15 mol % catalyt A in DCE (80 °C, 48 h). The yields of
d
diene and benzaldehyde after separation from silica column.
We selected benzyl ethers 3a -h to evaluate the
catalytic efficiency. The transformations were performed
by using either catalyst A (8.0 mol %, condition I) or a
mixture of catalyst A (5.0 mol %) and LiOTf (5.0 mol %
condition II) in hot 1,2-dichloroethane (1.5 M, 80 °C, 12
h). Conditions I and II gave dienes 4a -h and benzalde-
hyde in comparable proportions, as shown in Table 2.
Entries 1-3 show the application of this reaction to the
synthesis of dienes 3a ,b bearing a n-C12H25 and phenyl-
ethynyl group, respectively. We prepared Z- and E-styryl
derivatives 3c and 3d (entries 3 and 4) respectively, and
the products 4c and 4d retained the same configuration.
This catalytic process was also suitable to various oxygen-
and nitrogen-containing molecules 3e-g (entries 5-7)
and gave the corresponding dienes 4e-g and benzalde-
hyde in reasonable yields. The acidic fluorenyl proton of
compound 3h did not inhibit the catalytic activity, and
diene 4h was obtained in yields of 73-76% (entry 8).
We also prepared various 2-ethynyl cyclic ethers to
examine the suitability of this catalytic reaction for
cleavage of the ether rings. These ether substrates 5a -j
may be used as E-(or Z-)isomer or a mixture of two
isomers depending on their purities after separation from
a silica column. As shown in Table 3, these cyclic ethers
can be transformed into organic dienes 6a -j bearing a
ketone or aldehyde functionality using 10 mol % catalyst
A in dichloroethane (80 °C, 12 h). Entries 1-4 show
successful examples for cleavage of a tetrahydrofuranyl
ring via transfer hydrogenation: the products might be
either an unconjugated dienyl ketone R or a conjugated
(9) Chan, W.-C.; Lau, C.-P.; Chen, Y.-Z.; Fang, Y.-Q.; Ng, S.-M.; J ia,
G. Organometallics 1997, 16, 34.
(10) (a) O’Connor, J . M.; Pu, L. J . Am. Chem. Soc. 1990, 112, 9013.
(b) Bianchini, C.; Casares, J . A.; Peruzzini, M.; Romerosa, A.; Zanobini,
F. J . Am. Chem. Soc. 1996, 118, 4585. (c) Knaup, W.; Werner, H. J .
Organomet. Chem. 1991, 411, 471. (d) Chin, C. S.; Chong, D.; Maeng,
B.; Ryu, J .; Kim, H.; Kim, M.; Lee, H. Organometallics 2002, 21, 1739.
(11) (a) Davies, S. G.; McNally, J . P.; Smallridge, A. J . Adv.
Organomet. Chem. 1990, 30, 30. (b) Werner, H.; Lass, R. W.; Gevert,
O.; Wolf, J . Organometallics 1997, 16, 4077. (c) O’Connor, J . M.;
Hiibner, K. J . Chem. Soc., Chem. Commun. 1995, 1209.
J . Org. Chem, Vol. 69, No. 14, 2004 4693

Yeh et al.
TABLE 3. Ca ta lytic Rea ction on 2-Eth yn yl Cyclic
Eth er s
SCHEME 3
Exp er im en ta l Section
Trimethylacetylene, benzyl bromide, and other aliphatic
aldehydes were obtained commercially and used without
purification. 3-Benzyl but-1-ynyl ethers were easily prepared
from but-1-yn-3-ol with benzyl bromide in the presence of
NaH.7 TpRuPPh3(CH3CN)2PF6 were prepared by heating
TpRu(PPh3)2Cl with LiPF6 in CH3CN according to methods
described in the literature.9 The synthetic protocol and spectral
data of compounds 3a -c,e-h have been reported previously.7
Spectral data of compounds 3d , 4d , 5a -j, and 6a -j in
repetitive experiments are provided in the Supporting Infor-
mation.
Exp er im en ta l P r oced u r e for th e Syn th esis of Eth yn yl
Cyclic Eth er 5a . The synthetic scheme is shown in Scheme
3. To a dichloromethane (50 mL) solution of 5-butyldihydro-
furan-2-one (5.0 g, 35 mmol) was slowly added DIBAL (42 mL,
42 mmol) at -78 °C, and the mixture was stirred for 1 h before
the addition of methanol (20 mL). The solution was passed
through a short Al2O3 bed to give crude lactol 5a -1 (3.01 g,
21.0 mmol). Compound 5a -1 was added to a THF (100 mL)
solution of TMS-C≡CLi (53.0 mmol) at -78 °C. The mixture
was stirred for 4 h before being quenched with water (50 mL).
The solution was concentrated to ca. 50 mL, extracted with
diethyl ether, and eluted through a short silica column to give
diol 5a -2 (3.2 g, 13 mmol). To an acetone (40 mL) solution of
diol 5a -2 (3.20 g, 13.0 mmol) and toluenesulfonyl chloride (2.60
g, 14.0 mmol) was added an aqueous solution of potassium
hydroxide (6.60 mL, 5.0 M). The mixture was stirred for 8 h
at 25 °C. The solution was extracted with diethyl ether,
concentrated, and eluted through a silica column to afford 5a
(1.30 g, 8.60 mmol) as a mixture of Z/E isomers.
Exp er im en ta l P r oced u r es for Ca ta lytic Rea ction s.
Syn th esis of Un d eca -1,3-d ien e (2). A long tube containing
TpRu(PPh3)(CH3CN)2PF6 (27 mg, 0.035 mmol) was dried in
vacuo for 2 h before it was charged with benzyl ether 1 (200
mg, 6.9 mmol) and 1,2-dichloroethane (0.50 mL). The mixture
was heated at 80 °C for 12 h before cooling to room temper-
ature. The solution was concentrated and eluted through a
silica column (hexane/diether ) 5/1) to give diene 2 (88 mg,
5.8 mmol, 83%) and benzaldehyde (60 mg, 5.6 mmol, 81%),
respectively: IR (neat, cm-1) 2967 (m), 1658 (w), 1604 (w); 1H
NMR (400 MHz, CDCl3) δ 0.89 (3 H, t, J ) 6.8 Hz), 1.21-1.42
(10 H, m), 2.09 (2 H, q, J ) 7.4 Hz), 4.96 (1 H, d, J ) 10.0 Hz),
5.09 (1 H, d, J ) 16.8 Hz), 5.72 (1 H, dt, J ) 15.2 Hz, 6.8 Hz),
6.05 (1 H, m), 6.32 (1 H, dt, J ) 17.2 Hz, 10.0 Hz); 13C NMR
(100 MHz, CDCl3) δ 14.1, 22.6, 27.7, 29.2, 29.2, 31.8, 32.6,
114.5, 130.8, 135.6, 137.4; HRMS calcd for C11H20 152.1565,
found 152.1559.
a
b
10.0 mol % catalyst, 80 °C, DCE, 12 h. The yields of products
were reported after separation from silica column. c 80 °C, DCE,
d
48 h. The structure of this isomer was not available due to the
overlap of the H2 and H6 NMR resonances. e The structure of ether
5j was not determined.
SCHEME 2
isomer â, with isolated yields exceeding 87%. Interest-
ingly, the transfer of hydrogenation occurs not only for
the benzyl ether derivatives 5b-d , but also to a n-butyl
ether species 5a . A similar pattern was observed for
2-ethynyltetrahydropyranyl species 5e-h bearing a 6-sub-
stituent like a n-pentyl, phenyl, phenylethynyl, or E-
styryl group. These ethers underwent ring cleavage
smoothly to give the corresponding diene ketones 6e-f
in excellent yields. This reaction was also applied to
bicyclic ethers 5i and 5j, which gave aldehydes 6i and 6j
in respective yields of 93% and 91%. In a separate
experiment (Scheme 2), we treated tetrahydrofuranyl
derivative 5e with a better hydrogen donor, p-methoxy-
benzyl alcohol (2.0 equiv), in dichloroethane (80 °C, 12
h). The product consisted mainly of dienyl ketone 6e
rather than dienyl alcohol and p-methoxybenzaldehyde.
This result suggested that product 6e was produced from
its cyclic ether 5e via an intramolecular hydrogen
transfer process.
In summary, we developed a new catalytic reaction for
cleavage of ethynyl benzyl ethers in acyclic and cyclic
structural skeletons. These molecules are transformed
into organic dienes and benzaldehyde (or ketones) via
transfer hydrogen that is beyond the present scope. The
catalytic reaction is compatible with suitable oxygen and
nitrogen functionalities. Further development of new
catalytic reactions on the basis of this pathway is
underway.
Ack n ow led gm en t. We thank the National Science
Council, Taiwan, for supporting this work.
Su p p or tin g In for m a tion Ava ila ble: Spectral data of
compounds 3d , 4d , 5a -j, and 6a -j in repetitive experiments
are provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O049514X
4694 J . Org. Chem., Vol. 69, No. 14, 2004