Pd0-catalyzed cyclization reaction of aryl or alk-1-enyl halides with 1,2-dienyl ketones: A general and efficient synthesis of polysubstituted furans

Article abstract of DOI:10.1039/a908627g

Under catalysis by Pd⁰ and Ag₂CO₃, the reaction of 1,2-allenyl ketones and organic halides in PhMe using Et₃N as the base provides a new general access to polysubstituted furans with good to excellent yields.

Full text of DOI:10.1039/a908627g

Pd0-catalyzed cyclization reaction of aryl or alk-1-enyl halides with 1,2-dienyl
ketones: a general and efficient synthesis of polysubstituted furans
Shengming Ma* and Junliang Zhang
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. China. E-mail: masm@pub.sioc.ac.cn
Received (in Cambridge, UK) 29th October 1999, Accepted 30th November 1999
Under catalysis by Pd0 and Ag2CO3, the reaction of
1,2-allenyl ketones and organic halides in PhMe using Et3N
as the base provides a new general access to polysubstituted
furans with good to excellent yields.
substituents at the 3- and/or 4-position of the corresponding
unsubstituted furans is difficult, efficient and general method-
ologies for furans with substituents at some or all of the four
positions are still of current interest. During the course of our
study of functionalized allenes,12,13 we envisioned that a Pd0-
catalyzed cyclization of an organic halide with a 1,2-dienyl
ketone would provide an efficient and general route to
polysubstituted furans with the unique assembly of substituents
at the different positions, depending on the substitution of both
reactants (Scheme 1).14
Furans, one of the most prominent classes of heterocyclic
compounds, can be found in many naturally occurring prod-
ucts,1 commercially important pharmaceuticals, and flavor and
fragrance compounds.2 They are also considered as important
synthetic intermediates for the preparation of numerous cyclic
and acyclic compounds.3 Usually, 3-, 2,3-, 2,4-, 3,4-, 2,3,4- and
2,3,5-substituted furans4 can be synthesized via acyclic pre-
cursors or derivatization of simple furans.5 Owing to its
potential and diversity, much attention has been paid to the
synthesis of furans from acyclic precursors. Some of the most
important and interesting methodologies are as follows: (i)
cyclization of alk-4-yn-1-ols;6 (ii) cyclization of alk-3-yn-
1-ols;7 (iii) AlCl3-catalyzed cyclization of acyl chlorides with
1,2-allenyl silanes;8 (iv) epoxidation and subsequent HgO-
catalyzed cyclization of alk-1-enyl alk-1A-ynyl methanols;9 and
(v) Pd-catalyzed cyclization of (Z)-2-iodoalk-2-enyl ke-
tones.10
1,2-Dienyl ketones with different substitution patterns are
easily available.12c,14b,15 As a starting point, we studied the Pd0-
Scheme 2
Recently, Marshall et al.11 reported the Rh+- or Ag+-
catalyzed direct one-component cyclization of 1,2-dienyl
ketones to afford substituted furans with obvious limitations
(mainly R3 = H, Scheme 1). Since the introduction of
Scheme 1
Scheme 3
Table 1 Efficient synthesis of polysubstituted furansa
Ketone 2
Product
(% yield)c
Entry
R3Xb
R1
R2
R4
T/°C
t/h
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a (2.0) 2a
1b (2.0) 2a
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
Et
H
H
H
H
H
H
H
H
H
H
Me
Me
Bu
H
H
H
H
H
H
C12H25
C12H15
80
80
80
80
80
80
80
80
100
100
100
80
80
80
80
80
80
12
13
14
12
9
3a (75)
3b (90)
3c (94)
3d (73)
3e (92)
3f (85)
3g (71)
3hd (61)
3i (68)
3j (79)
3k (97)
31 (51)
3m (51)
3n (77)
3o (73)
3p (66)
3q (63)
1c
1a
1b
1c
1d
1e
1c
1b
1d
1b
1c
1b
1c
1f
2a
2b
2b
2b
2b
2b
2c
2c
2d
2e
2e
2f
C
12H15
Bu
Bu
Bu
Bu
Bu
H
9
11
11
14
11
17
10
10
12
12
11
11
H
H
Ph
Ph
Ph
Ph
Bu
C7H15
2f
2b
2g
1f
a Generally, the reaction was carried out using 1,2-allenyl ketone (1.5 equiv.), R3X (1.0 equiv.), and 5 mol% of Pd(PPh3)4 in PhMe, unless otherwise stated.
b The numbers in the parenthesis are the equiv. of R3X used. c Isolated yield. d The configuration of the CNC bond in R3 is trans.
Chem. Commun., 2000, 117–118
This journal is © The Royal Society of Chemistry 2000
117

2 Common Fragrance and Flavor Materials, ed. K. Bauer and D. Garbe,
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3 B. H. Lipshutz, Chem. Rev., 1986, 86, 795.
catalyzed cyclization reaction of heptadeca-3,4-dien-2-one 2a
with PhI under various reaction conditions. After some
screening, we found that the Pd(PPh3)4-catalyzed cyclization
reaction of PhI with 2a afforded the expected product 3a in 88%
yield together with the formation of 4a in only 9% yield by
using 5 mol% (Pd(PPh3)4 as the catalyst, toluene as the solvent,
and Et3N (2.0 equiv.)–Ag2CO3 (10 mol%) as the base. Similar
to the cyclization reaction of 1,2-allenic carboxylic acids, we
observed that a catalytic amount of Ag2CO3 is crucial to this
reaction (Scheme 2).
4 For most recent reviews, see: X. Hou, H. Y. Cheung, T. Y. Hon, P. L.
Kwan, T. H. Lo, S. Y. Tong and H. N. C. Wong, Tetrahedron, 1998, 54,
1955; B. A. Keay, Chem. Soc. Rev., 1999, 28, 209.
5 E. Bures, J. A. Nieman, S. Yu, P. G. Spinazze´, J. J. Bontront, I. R. Hunt,
A. Rauk and B. A. Keay, J. Org. Chem., 1997, 62, 8750; E. Bures, P. G.
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6 I. Heilbron, E. R. H. Jones and F. Sondheimer, J. Chem. Soc., 1947,
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Using these standard conditions, we studied this new and
efficient synthetic methodology for the synthesis of poly-
substituted furans with differently substituted 1,2-dienyl ke-
tones as well as different kinds of organic halides (Scheme 3).
The results are summarized in Table 1.
The results in Table 1 show that (i) the yields for this reaction
range from moderate to excellent, with the highest being 97%
(entry 11, Table 1); (ii) both electron-rich and electron-deficient
aryl halides afforded the corresponding furans; (iii) substituents
at different positions of furans could be introduced, depending
on the structure of allenyl ketones and organic halides; and (iv)
the reaction of methyl (Z)-3-iodopropenoate16 yielded the
product 3h, providing an opportunity for further elaboration of
the substitutions at the 4-position (entry 8, Table 1).
8 R. L. Danheiser, E. J. Stoner, H. Koyama, D. S. Yamashita and C. A.
Klade, J. Am. Chem. Soc., 1989, 111, 4407.
In conclusion, we have developed an efficient method for the
synthesis of substituted furans with different substitution
patterns. The study of new methodologies for differently
substituted 1,2-allenyl ketones and the scope of this cyclization
reaction, as well as its application in the synthesis of target
molecules with potential activities, are currently being carried
out in our laboratory.
We are grateful to the National Natural Science Foundation
of China, the Chinese Academy of Sciences and the Shanghai
Municipal Committee of Science and Technology for financial
support. S.M. thanks the Hong Kong Qiu Shi Foundation of
Science and Technology for the 1999 Qiu Shi Award for Young
Scientific Workers (1999–2003).
9 C. M. Marson and S. Harper, J. Org. Chem., 1998, 63, 9223.
10 F.-T. Lou, A. C. Bajji and A. Jeevanandam, J. Org. Chem., 1999, 64,
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11 J. A. Marshall and E. D. Robinson, J. Org. Chem., 1990, 55, 3450; J. A.
Marshall and X. Wang, J. Org. Chem., 1991, 56, 960; J. A. Marshall and
E. M. Wallace, J. Org. Chem., 1995, 60, 796.
12 For the hydrohalogenation reaction of electron-deficient allenes, see: (a)
S. Ma, Z. Shi and L. Li, J. Org. Chem., 1998, 63, 4522; (b) S. Ma and
Q. Wei, J. Org. Chem., 1999, 64, 1028; (c) S. Ma and L. Li, H. Xie,
J. Org. Chem., 1999, 64, 5325.
13 For the Pd0/Ag+-cocatalyzed cyclization of organic halides with
1,2-allenyl carboxylic acids to afford b-butenolides, see: S. Ma and Z.
Shi, J. Org. Chem., 1998, 63, 6387; For the corresponding reaction with
2,3-dienols with organic halides to afford oxiranes, see: S. Ma and S.
Zhao, J. Am. Chem. Soc., 1999, 121, 7943.
14 For the PdII-catalyzed direct cyclization and dimerization of terminal
allenyl ketones to afford a mixture of 2-monosubstituted furans and
2,4-disubstituted furans, see: (a) A. S. K. Hashmi, Angew. Chem., 1995,
107, 1749; Angew. Chem., Int. Ed. Engl., 1995, 34, 1581; (b) A. S. K.
Hashmi, T. L. Ruppert, T. Knofel and J. W. Bats, J. Org. Chem., 1997,
62, 7295. In most cases, the dimerization products are predominant.
15 N. A. Petasis and K. A. Teets, J. Am. Chem. Soc., 1992, 114, 10328.
16 S. Ma, X. Lu and Z. Li, J. Org. Chem., 1992, 57, 709. For a review, see:
X. Lu and S. Ma, Chin. J. Chem., 1998, 16, 388.
Notes and references
1 F. M. Dean, in Comprehensive Heterocyclic Chemistry, ed. A. R.
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M. U. Sargent, p. 599; D. M. X. Donnelly, p. 651; R. Benassi, in
Comprehensive Heterocyclic Chemistry, ed. A. R. Katrizky, C. W. Rees
and E. F. U. Scriven, Pergamon, New York, 1996, vol. 2, p. 259; H.
Heaney, p. 297; B. A. Keay, p. 395; K. Nakanishi, Natural Products
Chemistry, Kodamsha, Tokyo, 1974; M. Shipman, Contemp. Org.
Synth., 1995, 2, 1.
Communication a908627g
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Chem. Commun., 2000, 117–118