Pd(II) acts simultaneously as a Lewis acid and as a transition-metal catalyst: Synthesis of cyclic alkenyl ethers from acetylenic aldehydes

Article abstract of DOI:10.1021/ja017366b

The reaction of carbon-tethered acetylenic aldehydes with alcohols in the presence of a catalytic amount of Pd(OAc)₂ in 1,4-dioxane at room temperature gave the 5- or 6-membered acetal products in high yields. The 13C NMR studies suggested that a Pd(II) catalyst exhibited dual roles in the present reaction; the attack of ROH to aldehyde is catalyzed by Lewis acidic Pd(OAc)₂, and the nucleophilic oxygen of the resulting hemiacetal reacts with alkyne complexed by Pd(II), giving the alkenyl ethers. Copyright

Full text of DOI:10.1021/ja017366b

Published on Web 01/09/2002
Pd(II) Acts Simultaneously as a Lewis Acid and as a Transition-Metal
Catalyst: Synthesis of Cyclic Alkenyl Ethers from Acetylenic Aldehydes
Naoki Asao, Tsutomu Nogami, Kumiko Takahashi, and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku UniVersity, Sendai 980-8578, Japan
Received October 23, 2001; Revised Manuscript Received December 4, 2001
Two different types of molecular catalysts, Lewis acids1 and
transition metals,2 are becoming increasingly important in modern
Scheme 1. Principal Role of a Lewis Acid and Transition-Metal
Catalyst
organic reactions. A typical role of Lewis acid MXn to enhance
the reactivity of a substrate is the formation of a complex with
lone pairs of CdY (Y ) O, N, ...) multiple bonds, facilitating the
nucleophilic attack of Nu- to the carbon bearing a positive charge
(Scheme 1). One of the representative roles of transition-metal
Scheme 2
catalysts M′Xn, such as Pd(II)X2, is the formation of a complex
with π-electrons of alkene or alkyne multiple bonds, which makes
feasible the attack of Nu- to an electron-deficient carbon to give
an organopalladium intermediate having a C-Nu bond. To the best
of our knowledge, there is no precedent in which a single-metal
complex (MXn ) M′Xn) exhibits dual roles in a single transforma-
tion although it is known that a combination of a Lewis acid (MXn)
and a transition-metal catalyst (M′Xn) is useful for enhancing certain
organic transformations.3 We report that a Pd(II) catalyst really
exhibits dual roles; Pd(OAc)2 catalyzed the reaction of alkynyl-
aldehydes with ROH to give the alkenyl cyclic ethers in good-to-
high yields (eq 1). Here, the attack of ROH to aldehyde is catalyzed
substituent at the terminal position of alkyne exerts a significant
influence on the product ratio. While the 2:3 ratio decreased in the
reaction of 1b bearing p-tolyl group (entry 4) in comparison with
that of 1a (entry 1), the product 2c was obtained exclusively in the
reaction of 1c having p-trifluorophenyl group (entry 5). These results
clearly indicate that an electron-withdrawing group at the terminal
position is favorable for the formation of the five-membered cyclic
ethers 2. The reaction of 1d, having an alkyl group at the terminal
position, gave the five-membered acetal product 2d in a very low
yield (entry 6). When the reaction of 1a was performed in the
by Lewis acidic Pd(OAc)2, and the nucleophilic oxygen of the
resulting hemiacetal reacts with alkyne complexed by Pd(II), giving
the alkenyl ethers (vide post, Scheme 2).4
The reaction of the carbon-tethered acetylenic aldehydes 1 with
methyl alcohol in the presence of a catalytic amount of palladium
was examined (eq 2, Table 1). The reaction of 1a (R ) Ph) with
absence of Pd(OAc)2 or in the presence of catalytic amounts of
AcOH instead of Pd(OAc)2, any cyclization products were not
obtained at all. These blank tests clearly indicate that Pd(OAc)2 is
an essential catalyst for the present reaction.
Next, we examined the reaction of aryl acetylenic aldehydes 4
in which the carbon-tether is a part of the aromatic ring (eq 3, Table
2). The reaction of 4a proceeded smoothly in the presence of 5
MeOH in the presence of 10 mol % of Pd(OAc)2 and 1 equiv of
benzoquinone in 1,4-dioxane at room temperature gave the five-
membered acetal product 2a in 66% yield together with a small
amount of the six-membered product 3a. On the other hand, only
a trace amount of 2a was obtained in the presence of PdCl2- or
PtCl2-catalyst, and a large amount of 1a was recovered in both
cases. Pd(0) catalysts such as Pd(PPh3)4 and Pd2(dba)3‚CHCl3 were
totally ineffective. Benzoquinone was recovered in 83% yield under
the conditions of entry 1. However, the total yield of 2a and 3a
was dramatically decreased when the reaction was carried out in
the absence of benzoquinone (entry 2). These results suggest that
benzoquinone did not work as an oxidizing agent but as a ligand
for the palladium catalyst. Indeed, the reaction of 1a proceeded
smoothly even in the presence of maleic anhydride, which is known
as a π-acidic ligand (entry 3).5 Interestingly, it was found that the
mol % of Pd(OAc)2 at 10 °C, and the six-membered acetal 5a was
obtained in 90% yield as a sole product.6 In contrast to the reaction
of 1, no five-membered product was obtained (entry 1). Even in
the presence of 1 mol % of Pd(OAc)2, the reaction proceeded well
to afford 5a in 87% yield. It is worth mentioning that 5a was
obtained in a high yield (85%) even in the absence of benzoquinone.
Besides methyl alcohol, ethyl alcohol and isopropyl alcohol worked
well as nucleophiles, and the corresponding products 5b and 5c
9
764 VOL. 124, NO. 5, 2002 J. AM. CHEM. SOC.
10.1021/ja017366b CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Palladium-Catalyzed Cyclization Reaction of Acetylenic
Aldehydes 1a
entry
substrate 1 R
condition
yield of 2 (%)b
yield of 3 (%)b
1
Ph
1a
1a
1a
1b
1c
1d
rt, 2.5 h
rt, 1 d
2a
2a
2a
2b
2c
2d
66
13d
55
46
64
28
3a
9
trace
7
17
0
0
2c
3e
4
Ph
3a
3a
3b
3c
3d
Ph
rt, 2 h
p-MePh
p-CF3Ph
C8H17
rt, 3.5 h
rt, 2 h
rt, 3 h
5
6
The acetal functional group of 5 can be used as a key for further
manipulation. For instance, 5a was converted to 10 and 11 in high
yields, respectively, upon treatment with allyltributyltin and 1-
phenyl-1-(trimethylsilyloxy)ethylene in the presence of BF3‚OEt2
(Scheme 3).
Perhaps, the concept presented here may be applicable to the
reactions of a wide range of nucleophiles other than alcohols and
to the reactions involving C-C multiple bonds other than alkyne;
therefore, there is a possibility that a variety of heterocycles can
be synthesized by similar procedures.
Acknowledgment. This paper is dedicated to Professor Herbert
C. Brown on the occasion of his 90th birthday.
Supporting Information Available: Spectroscopic and analytical
data for 2a-d, 3a-b, 5a-f, 10, 11, and 13, 13C and 1H NMR studies
in THF-d8, and the representative procedure for the synthesis of 5a
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
a Reaction was performed with MeOH (2 equiv) in the presence of Pd
catalyst (10 mol %) and benzoquinone (1 equiv) in 1,4-dioxane at room
temperature unless otherwise noted. b Isolated yield. c Reaction was carried
out in the absence of benzoquinone. d 1a was recovered in 40% yield.
e Reaction was carried out in the presence of maleic anhydride (1 equiv)
instead of benzoquinone.
Table 2. Palladium-Catalyzed Cyclization Reaction of Aryl Acetylenic
Aldehydes 4a
1
2
entry
substrate 4 R
R OH
conditions
yield of 5 (%)b
1
Ph
4a
4a
4a
4b
4c
4d
MeOH
EtOH
iPrOH
MeOH
MeOH
MeOH
10 °C, 0.5 h
10 °C, 0.5 h
rt, 1 h
5a
90
76
81
74
72
22
2
Ph
5b
5c
5d
5e
5f
3
Ph
4c
5d
6d
C4H9
Me3Si
H
rt, 0.5 h
50 °C, 2 h
50 °C, 2 h
a Reaction was performed with R2OH (2 equiv) in the presence of Pd
catalyst (5 mol %) and benzoquinone (1 equiv) in 1,4-dioxane at room
temperature unless otherwise noted. b Isolated yield. c Reaction was carried
out in the absence of benzoquinone. d 20 mol % of Pd(OAc)2 was used.
Scheme 3
References
(1) For reviews, see: (a) Lewis Acids in Organic Synthesis; Yamamoto, H.,
Ed.; Wiley-VCH: Weinheim, 2000; Vol. 1-2. (b) Lewis Acid Reagents;
Yamamoto, H., Ed.; Oxford University Press: New York, 1999.
(2) For reviews, see: (a) Transition Metal Catalysed Reactions; Murahashi,
S.-I., Davies, S. G., Eds.; Blackwell Science: Cambridge, MA, 1999. (b)
Tsuji, J. Transition Metal Reagents and Catalysts: InnoVations in Organic
Synthesis; Wiley: New York, 2000.
(3) For example, see: (a) Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem.
Soc. 1996, 118, 3309-3310. (b) Ikeda, S.-i.; Mori, N.; Sato, Y. J. Am.
Chem. Soc. 1997, 119, 4779-4780.
(4) While the palladium-catalyzed cyclization of 2-alkynylbenzonitriles via
the addition of methyl alcohol to a nitrile group has been reported, sodium
methoxide was needed for activation of the nitrile moiety, see: Wei, L.-
M.; Lin, C.-F.; Wu, M.-J. Tetrahedron Lett. 2000, 41, 1215-1218.
were formed in high yields (entries 2, 3, respectively). The reaction
of 4b, bearing butyl group as R1, proceeded smoothly to give 5d
in 74% yield (entry 4). Similarly, the trimethylsilyl-substituted
alkyne 4c also cyclized in a good yield (entry 5). However, the
reaction of the nonsubstituted alkyne 4d gave only a small amount
of 5f along with unidentified byproducts (entry 6).
(5) For example, see: (a) Doyle, M. J.; McMeeking, J.; Binger, P. J. Chem.
Soc., Chem. Commun. 1976, 376-377. (b) Binger, P.; Doyle, J. H.; Kru¨ger,
C.; Tsay, Y. H. Z. Naturforsch., B: Chem. Sci. 1979, 34, 1289. (c) Kohara,
T.; Komiya, S.; Yamamoto, T.; Yamamoto, A. Chem. Lett. 1979, 1513-
1516. (d) Goliaszewski, A.; Schwartz, J. J. Am. Chem. Soc. 1984, 106,
5028-5030. (e) Goliaszewski, A.; Schwartz, J. Organometallics 1985,
4, 417-419.
A conceivable mechanism of the present reaction is shown in
Scheme 2. Pd(OAc)2 acts as a Lewis acid, forms a complex with
the carbonyl oxygen (1 or 4), and makes feasible the attack of
MeOH (6) to produce the hemiacetal 7.7,8 The coordination of an
alkyne of 7 to palladium(II) would induce an attack of a hydroxyl
moiety to the alkyne from the side opposite to the palladium via
the exo or endo pathway to produce the corresponding vinylpal-
ladium complex 8 or 9. These intermediates would be protonated
by acetic acid, generated in the cyclization step from 7 to 8 or 9,
to give the alkenyl cyclic ethers.9 As mentioned above, the
cyclization of 1c proceeded only via 5-exo-dig mode. This
experimental result is in good agreement with the intervention of
the proposed intermediate 7. A positive charge would be generated
on the internal acetylenic carbon of 7, rather than the terminal one,
since the electron-withdrawing group is present at the R position.
The 13C NMR studies of a 1:1 mixture of 1a and Pd(OAc)2 in
THF-d8 at room temperature were carried out.10 In the absence of
Pd(OAc)2, the aldehyde carbon of 1a appeared at δ 198.85, and
the acetylenic carbons, at δ 88.23 and 80.82 (B), while the
downfield shift of the aldehyde carbon was observed in the presence
of Pd(OAc)2 without any shift change of the acetylenic carbons
(A). On the contrary, the downfield shift of acetylenic carbons of
1-phenyl-1-propyne (δ 85.15, 79.42) was observed (δ 85.18, 79.43)
in the presence of Pd(OAc)2.11 Moreover, a 1:1.5:1 mixture of
heptanal, MeOH, and Pd(OAc)2 gave the corresponding acetal
(Supporting Information). These results clearly indicate that Pd-
(OAc)2 can be coordinated potentially both by aldehyde oxygen
and by alkyne, but complexes preferentially with aldehyde oxygen
in the presence of alkyne.12
(6) The 1H NMR spectrum of 5a was identical to that of the known compound,
see: Padwa, A.; Au, A. J. Am. Chem. Soc. 1976, 98, 5581-5590.
(7) Palladium complexes can be used to effect deacetalization under mild
conditions, see: (a) Lipshutz, B. H.; Pollart, D.; Monforte, J.; Kotsuki,
H. Tetrahedron Lett. 1985, 26, 705. (b) Park, M. H.; Takeda, R.; Nakanishi,
K. Tetrahedron Lett. 1987, 28, 3823. (c) Anthony, N. J.; Clarke, T.; Jones,
A. B.; Ley, S. V. Tetrahedron Lett. 1987, 28, 5755. (d) McKillop, A.;
Taylor, R. J. K.; Watson, R. J.; Lewis, N. Synlett 1992, 1005. (e) Schmeck,
C.; Hegedus, L. S. J. Am. Chem. Soc. 1994, 116, 9927.
(8) Transition metal-catalyzed acetalization of aldehydes and ketones has been
reported, see: (a) Ott, J.; Ramos Tombo, G. M.; Schmid, B.; Venanzi, L.
M.; Wang, G.; Ward, T. R. Tetrahedron Lett. 1989, 30, 6151-6154. (b)
Hudson, P.; Parsons, P. J. Synlett 1992, 867-868. (c) Cataldo, M.; Nieddu,
E.; Gavagnin, R.; Pinna, F.; Strukul, G. J. Mol. Catal. 1999, 142, 305-
316.
(9) When the reaction of 4a with MeOD was examined under the same
reaction condition, the deuterated product 13
was obtained in 85% yield in which D content was 95% and no deuterium
was found in other carbons of the product.
(10) The Pd(OAc)2-catalyzed reaction of 1a with MeOH also proceeded in
THF and 2a was obtained in 53% yield together with 3a in 4% yield.
(11) The downfield shift of aldehyde carbon of heptanal (δ 200.37) was
observed (δ 200.41) in the presence of Pd(OAc)2.
(12) It is reported that coordination of the alkyne to Pd(II) induces attack of
ester oxygen to alkyne. (a) Kataoka, H.; Watanabe, K.; Goto, K.
Tetrahedron Lett. 1990, 31, 4181-4184. (b) Kataoka, H.; Watanabe, K.;
Miyazaki, K.; Tahara, S.; Ogu, K.; Matsuoka, R.; Goto, K. Chem. Lett.
1990, 1705-1708.
JA017366B
9
J. AM. CHEM. SOC. VOL. 124, NO. 5, 2002 765