One-pot synthesis of γ,δ-unsaturated carbonyl compounds from allyl alcohols and vinyl or isopropenyl acetates catalyzed by [IrCl(cod)] 2

Article abstract of DOI:10.1021/jo060860j

One-pot synthesis of γ,δ-unsaturated carbonyl compounds from allyl alcohols and vinyl or isopropenyl acetates was achieved through in situ generation of allyl vinyl ethers by the action of the [IrCl(cod)]₂ complex followed by Claisen rearrangement of the resulting ethers. For instance, the reaction of trans-2-methyl-3-phenyl-2-propen-1-ol with isopropenyl acetate in the presence of [IrCl(cod)]₂ (1 mol %) and Cs₂CO ₃ (5 mol %) at 100 °C for 3 h followed by 140 °C for 15 h afforded 5-methyl-4-phenyl-5-hexen-2-one in 72% yield. When vinyl acetate was employed in place of isopropenyl acetate, 4-methyl-3-phenyl-4-pentenal was obtained in 83% yield.

Full text of DOI:10.1021/jo060860j

TABLE 1. Reaction of 1a with 2a under Various Conditionsa
One-Pot Synthesis of γ,δ-Unsaturated Carbonyl
Compounds from Allyl Alcohols and Vinyl or
Isopropenyl Acetates Catalyzed by [IrCl(cod)]2
yieldb (%)
run
catalyst
base
3aa
4aa
5aa
6aa
1
2
3
4
5
6
7
8c
[IrCl(cod)]2
[IrCl(cod)]2
[Ir(cod)2]+BF4
[Cp*IrCl2]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
Na2CO3
0
0
0
0
0
0
0
30
70
0
58
2
72
68
65
30
10
49
10
1
5
11
9
84
7
6
6
8
Masao Morita, Satoshi Sakaguchi, and Yasutaka Ishii*
-
Na2CO3
Na2CO3
Cs2CO3
NaOAc
KOH
Department of Applied Chemistry, Faculty of Engineering &
High Technology Research Center, Kansai UniVersity, Suita,
Osaka 564-8680, Japan
7
10
10
13
Na2CO3
ishii@ipcku.kansai-u.ac.jp
a 1a (0.5 mmol) was reacted with 2a (6 mmol) in the presence of Ir
complex (2 mol %) and base (5 mol %) in mesitylene (1.5 mL) at 100 °C
for 3 h followed by 140 °C for 15 h. b Based on 1a. c The second step was
also carried out 100 °C for 15 h.
ReceiVed April 25, 2006
allyl homoallyl ethers by etherification between allyl bromide
and homoallyl alcohols derived from carbonyl compounds and
allylmagnesium bromide. Therefore, if allyl vinyl ethers, which
undergo the Claisen rearrangement, can be directly prepared
by the vinylation of allyl alcohols with vinyl compounds such
as vinyl acetate, this method would provide a very attractive
route to γ,δ-unsaturated carbonyl compounds, since allyl
alcohols are easily available from commercial sources. Fortu-
nately, we have recently succeeded in performing the vinylation
of alcohols with vinyl acetate using [IrCl(cod)]2 complex,
although the vinylation was very difficult to carry out by
conventional methods.9 Therefore, if the vinylation of allyl
alcohols with vinyl acetate can be carried out by using [IrCl-
(cod)]2, it may be possible to carry out a one-pot synthesis of
γ,δ-unsaturated carbonyl compounds from allyl alcohols and
vinyl or isopropenyl acetate through tandem reactions involving
vinylation and Claisen rearrangement.
One-pot synthesis of γ,δ-unsaturated carbonyl compounds
from allyl alcohols and vinyl or isopropenyl acetates was
achieved through in situ generation of allyl vinyl ethers by
the action of the [IrCl(cod)]2 complex followed by Claisen
rearrangement of the resulting ethers. For instance, the
reaction of trans-2-methyl-3-phenyl-2-propen-1-ol with iso-
propenyl acetate in the presence of [IrCl(cod)]2 (1 mol %)
and Cs2CO3 (5 mol %) at 100 °C for 3 h followed by 140
°C for 15 h afforded 5-methyl-4-phenyl-5-hexen-2-one in
72% yield. When vinyl acetate was employed in place of
isopropenyl acetate, 4-methyl-3-phenyl-4-pentenal was ob-
tained in 83% yield.
The reaction of trans-2-methyl-3-phenyl-2-propen-1-ol (1a)
with isopropenyl acetate (2a) in the presence of [IrCl(cod)]2 (2
mol %) was chosen as a model reaction and was carried out
under various conditions (eq 1 and Table 1).
The Claisen rearrangement of allyl vinyl ethers is recognized
as an attractive tool for the synthesis of olefins1 in a stereo-
selective manner as well as for the creation of asymmetrical
carbon centers.2 Therefore, there have been several reports on
the in situ generation of allyl vinyl ethers which are precursors
for the Claisen rearrangement, e.g., acid-catalyzed decomposi-
tion of diallyl actates,3 vinylation of haloethers,4 Ru- and Ir-
catalyzed rearrangement of diallyl ethers,5 organoaluminum-
promoted allyl vinyl ethers,6 etc. The reaction of allyl alcohols
with terminal alkynes catalyzed by Rh complexes is reported
to lead to the Claisen rearrangement products.7 Previously, we
reported the rearrangement of allyl homoallyl ethers to γ,δ-
unsaturated aldehydes induced by the [IrCl(cod)]2 complex.8 In
this reaction, however, it is necessary to prepare independently
The reaction of 1a with 2a under the influence of [IrCl(cod)]2
(2 mol %) and a base like Na2CO3 at 100 °C for 3 h followed
by 140 °C for 15 h afforded the desired Claisen rearrangement
(5) Ru: (a) Reuter, J. M.; Salomon, R. G. J. Org. Chem. 1977, 21, 3360.
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Chem. Commun. 2002, 1772. (c) Scmidt, B. Synlett 2004, 1541. Ir: (a)
Swenton, J. S.; Bradin, D.; Gates, B. D. J. Org. Chem. 1991, 56, 6156. (b)
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N. B.; Howard, W. L. J. Org. Chem. 1961, 26, 3112. (c) Sethi, D. S.; Yates.
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1590.
(4) Cresson, P. Bull. Soc. Chim. Fr. 1964, 2629.
10.1021/jo060860j CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/06/2006
J. Org. Chem. 2006, 71, 6285-6286
6285

TABLE 2. Reaction of Various Allyl Alcohols with 2a or 2b under
4-methyl-3-phenyl-4-pentenal (4ab), in 83% yield (run 2).
3-Methyl-2-buten-1-ol (1b) reacted with 2a to produce 4,4-
dimethyl-5-hexen-2-one (4ba) in 74% yield (run 3). Similarly,
the reaction of 1b with 2b afforded3,3-dimethyl-4-pentenal
(4bb) in 67% yield (run 4). Geraniol (1c) underwent isopro-
penylation and vinylation with 2a and 2b followed by re-
arrangement to form the corresponding ketone 4ca (81%) and
aldehyde 4cb (72%), respectively (runs 5 and 6). Nerol (1d)
reacted with 2a and 2b to give the corresponding rearrangement
products, 4da and 4db, in 88% and 69% yields, respectively
(runs 7 and 8).
a
the Influence of [IrCl(cod)]2
run
allyl alcohol
acetate
product (yield/%)
1
1a
1a
1b
1b
2a
2b
2a
2b
2a
2b
2a
2b
4aa (72)
4ab (83)
4ba (74)
4bb (67)
4ca (81)
4cb (72)
4da (88)
4db (69)
2
3b
4b
5b,c
6b,c
7b,c
8b,c
geraniol (1c)
1c
nerol (1d)
1d
a The reaction was carried out using the same method as run 5 in Table
1. b P(OPh3)3 (0.04 mmol) was added in the second step. c The second step
was carried out at 150 °C: 2a, isopropenyl acetate; 2b, vinyl acetate.
In conclusion, we have achieved a one-pot synthesis of γ,δ-
unsaturated carbonyl compounds from allyl alcohols and vinyl
or isopropenyl acetates by the use of Ir complexes.
product, 5-methyl-4-phenyl-5-hexen-2-one (4aa), in 70% yield
along with trans-2-methyl-3-phenyl-2-propenyl acetate (5aa)
(10%) and trans-2-methyl-3-phenyl-2-propenal (6aa) (5%) (run
1). However, when the same reaction was carried out in the
absence of Na2CO3 under these conditions, the normal ester
exchange reaction between 1a and 2a took place as a major
reaction to form 5aa, but not the Claisen rearrangement product
4aa, in 49% yield (run 2). In the present Ir-catalyzed reaction
of 1a with 2a, isopropenylation of 1a forming 3aa competes
with acetylation of 1a forming 5aa. It may be considered that
the initial interaction of an Ir species with 2a in preference to
1a leads to the formation of 3aa, while the Ir species first reacts
with 1a followed by 2a to afford 5aa. Therefore, it seems likely
that an excess amount of 2a with respect to 1a is needed to
obtain 3aa as a major product.
Experimental Section
All starting materials were commercially available and used
without any purification. GLC analysis was performed with a flame
ionization detector using a 0.2 mm × 25 m capillary column (OV-
1). 1H and 13C NMR were measured at 270 or 400 and 67.5 MHz,
respectively, in CDCl3 with Me4Si as the internal standard.
A typical reaction procedure of the reaction of 1a with 2a is as
follows: To a mixture of [IrCl(cod)]2 (0.01 mmol) and Na2CO3
(0.025 mmol) in mesitylene (1.5 mL) were added 1a (0.5 mmol)
and 2a (6 mmol) under Ar. The reaction mixture was stirred at
100 °C for 3 h followed by 140 °C for 15 h. The conversions and
yields of products were estimated from the peak areas based on
the internal standard technique using GC.
The products 4aa,10 4ab,11 4ba,12 4bb,13 4ca and 4da,14 and 4cb
and 4db15 are known compounds and have been reported previously.
A cationic complex, [Ir(cod)2]+BF4-, was less active than
the [IrCl(cod)]2 complex, and 4aa was formed in a slightly lower
yield (58%) (run 3). It is interesting that the [Cp*IrCl2]2 complex
produced dehydrogenation product 6aa in high yield (84%)
rather than the Claisen product 4aa (run 4). In this reaction, 2a
was found to serve as a hydrogen acceptor of 1a. This shows
that the [Cp*IrCl2]2 complex catalyzes the dehydrogenation of
1a to 6aa rather than the vinylation of 1a with 2a to 3aa. Among
the bases examined, Cs2CO3 was found to be the best additive
and gave 4aa in 72% yield (run 5). A strong base, KOH, was
also used as a base for the present tandem Claisen rearrangement
(run 7). When the reaction temperature was lowered to 100 °C,
the rate of the Claisen rearrangement of 3aa to 4aa became
very slow, and a considerable amount of 3aa remained without
rearrangement even after 18 h (run 8).
Acknowledgment. This work was supported by the “High-
Tech Research Center” Project for Private Universities: match-
ing fund subsidy from the Ministry of Education, Culture,
Sports, Science and Technology, 2005-2009, and Daicel
Chemical Industries, Ltd.
Supporting Information Available: Copies of 1H and 13C NMR
spectra of 4aa, 4ab, 4ba, 4ca, and 4da. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO060860J
(10) Muraoka, T.; Matsuda, I.; Itoh, K. Tetrahedron Lett. 2000, 41, 8807.
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On the basis of these results, the reaction between allyl
alcohols and vinyl or isopropenyl acetate was carried out, and
the results are summarized in Table 2.
The reaction of 1a with vinyl acetate (2b) under these
conditions afforded the corresponding rearranged product,
6286 J. Org. Chem., Vol. 71, No. 16, 2006