Rhodium-catalyzed cycloisomerization of allyl propargyl ethers: An efficient synthesis of 3,4-disubstituted furans

Article abstract of DOI:10.3987/COM-05-S(T)27

Cycloisomerization of allyl propargyl ethers was found to be catalyzed by a cationic rhodium complex to give 3,4-disubstituted furans in one step. Addition of carboxylic acids to the reaction improved the yield of the products. Generation of a rhodium hyd

Full text of DOI:10.3987/COM-05-S(T)27

HETEROCYCLES, Vol. 67, No. 1, 2006
101
HETEROCYCLES, Vol. 67, No. 1, 2006, pp. 101 - 105. © The Japan Institute of Heterocyclic Chemistry
Received, 6th July, 2005, Accepted, 22nd August, 2005, Published online, 23rd August, 2005. COM-05-S(T)27
RHODIUM-CATALYZED
PROPARGYL ETHERS:
3,4-DISUBSTITUTED FURANS
CYCLOISOMERIZATION
OF
ALLYL
OF
AN EFFICIENT SYNTHESIS
Hiroshi Kawai, Shuichi Oi,* and Yoshio Inoue*
Department of Biomolecular Engineering, Graduate School of Engineering,
Tohoku University, Sendai 980-8579, Japan
Abstract – Cycloisomerization of allyl propargyl ethers was found to be
catalyzed by a cationic rhodium complex to give 3,4-disubstituted furans in one
step. Addition of carboxylic acids to the reaction improved the yield of the
products. Generation of a rhodium hydride species from a rhodium complex with
the carboxylic acids followed by hydrorhodation of the substrate with the
rhodium hydride species would be involved in the reaction pathway.
Transition metal-catalyzed cyclization of enynes provides an efficient and useful method for the
construction of ring systems. It has been known that 1,6-enynes are highly reactive compounds for
cyclization and effective substrate for five-membered ring compounds.1-3 Cyclization of allyl propargyl
ethers has been reported to give 3,4-dialkylidenetetrahydrofurans,4 3-alkenyl-4-alkylidenetetrahydrofu-
rans,4a,5 or 3-alkenyl-2,5-dihydrofurans.6 If the hydrogen transfer takes place after the cyclization, it
becomes a good synthetic method for functionalized furans. There has been only one example for such
cycloisomerization, in which, however, a furan derivative is obtained as a by-product in low yield.7
Herein we report on a rhodium-catalyzed cycloisomerization of allyl propargyl ethers that provides
3,4-disubstituted furans selectively in one step.
Treatment of allyl 3-phenyl-2-propynyl ether (1a) with 2 mol% of [Rh(cod)(MeCN)2]BF4 in 1,4-dioxane
at 100°C for 16 h gave 3-benzyl-4-methylfuran (2a) in 33% isolated yield (Scheme 1). The choice of the
cationic rhodium complex and appropriate bidentate phosphine ligands such as dppp was essential for the
success of this transformation. It is noteworthy that the exo-methylene type product was not detected at all
in this reaction.
This paper is dedicated to Professor Barry M. Trost on the occasion of his 65th birthday.

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HETEROCYCLES, Vol. 67, No. 1, 2006
2 mol% [Rh(cod)(CH3CN)2]BF4
2 mol% dppp
Ph
Ph
O
O
1,4-Dioxane (2 mL), 100°C, 16 h
1a
[ 1 mmol ]
2a
33%
Scheme 1
On the basis of assumption that a rhodium hydride species is an active catalytic species in this
cycloisomerization, we examined various carboxylic acids as additives, which produce Rh(III)-H species
by oxidative addition to Rh(I).4b,8 The effect of various carboxylic acids in this reaction is shown in Table
1. In all cases examined, improvement of the yield was observed (Entries 1-4). In particular, the yield was
increased to 64% when 10 mol% of acetic acid was added to the reaction (Entry 5). However, the reaction
did not proceed when acetic acid was used as solvent (Entry 6). A large excess of acetic acid appeared to
deactivate the catalyst.
Table 1. Effect of various carboxylic acids
2 mol% [Rh(cod)(CH3CN)2]BF4
Ph
2 mol% dppp
Ph
O
O
4 mol% carboxylic acid
1,4-Dioxane (2 mL), 100°C, 16 h
1a
2a
[ 1 mmol ]
Entry
Yield (%) of 2a
Carboxylic acids
HCOOH
1
2
3
4
5
6
49
61
50
44
64
n.r.
AcOH
PhCOOH
CF3COOH
AcOH (10 mol%)
AcOH (Solvent)
The scope of the rhodium-catalyzed cycloisomerization of allyl propargyl ethers is shown in Table 2. The
cycloisomerization of 1b having a substituent on the propargylic position also proceeded giving the
corresponding 2,3,4-trisubstituted furan (2b) in 35% yield (Entry 1). The reaction of substrate (1c) having
an ethyl group at the alkyne terminal gave the product (2c) in a lower yield of 20% (Entry 2).9 However,
the reaction of substrates (1d) and (1e) having a substituent at the olefin terminal did not give any

HETEROCYCLES, Vol. 67, No. 1, 2006
103
Table 2. Rh-catalyzed cycloisomerization of allyl propargyl ethers
2 mol% [Rh(cod)(CH3CN)2]BF4
2 mol% dppp
10 mol% AcOH
Substrate
Product
1,4-Dioxane (2 mL), 100°C, 16 h
[ 1 mmol ]
Substrate
Ph
Entry
1
Product
Ph
Yield, %
35
1b
1c
2b
O
O
O
O
C2H5
20
2
3
4
2c
2d
2a
Ph
Ph
Ph
1d
1e
0
0
O
O
O
O
Ph
cyclized product. Steric hindrance of the substituent at the olefin terminal would prevent the cyclization
(Entries 3 and 4).
Scheme 2 shows a plausible reaction mechanism for the cycloisomerization. Initially, oxidative addition
of AcOH to Rh(I) complex generates Rh(III)-H species as an active catalytic species. Addition of the
resulting Rh(III)-H species to the triple bond followed by insertion of the olefin moiety to Rh-C bond
generates an intermediate (A). β-Hydride elimination affords an exo-methylene type compound (B). Then
repetition of addition and elimination of Rh(III)-H causes the isomerization of double bond, which finally
results in the formation of the product furan (C). Since we did not observe the formation of the
exo-methylene type product (B), the isomerization of the double bond would proceed much faster than the
cyclization.
The label experiment of 1a was performed using 1.2 equiv. of AcOD (Scheme 3). As a result, deuterized
2a-d (54% D) at the benzylic position was obtained in 62% yield. This result supports the mechanism
involving the generation of Rh-D species from Rh(I) complex and AcOD followed by the
deuteriorhodation of the triple bond.

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HETEROCYCLES, Vol. 67, No. 1, 2006
Rh(I)
R
R
O
O
H
AcOH
C
Rh(III)-H
R
H
H
Rh
R
O
Rh
O
R
R
O
O
Rh-H
Rh
H
A
R
R
Rh-H
O
O
Rh
H
H
B
Scheme 2. Plausible mechanism for Rh-catalyzed cycloisomerization of allyl propargyl ethers
D
2 mol% [Rh(cod)(CH3CN)2]BF4
Ph
2 mol% dppp
Ph
O
O
62%
AcOD (1.2 mmol)
1,4-Dioxane (2 mL), 100°C, 16 h
1a
[ 1 mmol ]
2a-d (54% D)
Scheme 3. Label experiment
In conclusion, cycloisomerization of allyl propargyl ethers catalyzed by the cationic rhodium complex
gave 3,4-disubstituted furans selectively in one step. This method provides a convenient synthetic route to
highly substituted furans.
REFERENCES AND NOTES
1. B. M. Trost, Acc. Chem. Res., 1990, 23, 34.

HETEROCYCLES, Vol. 67, No. 1, 2006
105
2. B. M. Trost and M. J. Krische, Synlett, 1998, 1.
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Trost, D. L. Romero, and F. Rise, J. Am. Chem, Soc., 1994, 116, 4268. (c) J. Le Paih, D. C.
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1
9. 2a: H-NMR (500 MHz, CDCl3):δ(ppm) 7.29-7.26 (m, 2H), 7.20-7.19 (m, 3H), 7.17 (s, 1H), 7.10
(s, 1H), 3.71 (s, 2H), 1.86 (s, 3H). 13C-NMR (100 MHz, CDCl3):δ(ppm) 140.2, 139.9, 139.8, 128.5,
128.3, 126.0, 124.4, 120.3, 29.8, 8.1. IR (neat): 2921, 1451, 1142, 1045, 786, 715, cm-1. K. Inomata,
Y. Nakayama, M. Tsutsumi, and H. Kotake, Heterocycles, 1979, 12, 1467. 2b: 1H-NMR (500 MHz,
CDCl3):δ(ppm) 7.23 (t, J=7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.13 (d, J=7.5 Hz, 2H), 7.06 (s, 1H),
13
3.68 (s, 2H), 2.21 (s, 2H), 1.79 (s, 3H). C-NMR (125 MHz, CDCl3):δ(ppm) 148.5, 140.5, 136.7,
128.3, 128.1, 125.8, 120.9, 117.9, 29.4, 11.8, 8.6. IR (neat): 2920, 1494, 1450, 1123, 738, 713 cm-1.
Y. Fujita and T. Nakai, Synthesis, 1983, 997. 2c: 1H-NMR (500 MHz, CDCl3):δ(ppm) 7.14 (s, 1H),
7.13 (s, 1H), 2.31 (t, J=7.5 Hz, 2H), 1.95 (s, 3H), 1.56 (sext, J=7.5 Hz, 2H), 0.96 (t, J=7.5 Hz, 3H).
13C-NMR (125 MHz, CDCl3):δ(ppm) 139.2, 139.0, 125.4, 120.1, 25.6, 22.5, 14.0, 8.1. IR (neat):
2959, 1459, 1141, 1048, 878, 782 cm-1. HRMS (EI). Calcd for C8H12O 124.0888 (M+). Found
124.0887.