A new and efficient synthesis of rosefuran. A general synthesis of furans by palladium-catalysed cycloisomerization of (Z)-2-en-4-yn-1-ols

Article abstract of DOI:10.1039/a701988b

(Z)-3,7-Dimethylocta-2,6-dien-4-yn-1-ol, readily available from (Z)-3-methylpent-2-en-4-yn-1-ol, undergoes cycloisomerization in the presence of catalytic amounts of K₂PdI₄ to give rosefuran in high yield.

Full text of DOI:10.1039/a701988b

View Article Online / Journal Homepage / Table of Contents for this issue
A new and efficient synthesis of rosefuran. A general synthesis of furans by
palladium-catalysed cycloisomerization of (Z)-2-en-4-yn-1-ols
Bartolo Gabriele and Giuseppe Salerno*
Dipartimento di Chimica, Universita` della Calabria, 87030 Arcavacata di Rende, Cosenza, Italy
(Z)-3,7-Dimethylocta-2,6-dien-4-yn-1-ol, readily available
from (Z)-3-methylpent-2-en-4-yn-1-ol, undergoes cyclo-
isomerization in the presence of catalytic amounts of K2PdI4
to give rosefuran in high yield.
vinylpalladium intermediate I and HI (Scheme 3; anionic iodide
ligands are omitted for simplicity). Protonolysis of I followed
by acid-catalysed aromatization leads to the final product with
regeneration of the catalytically active species (path a).
Aromatization of I followed by protonolysis is another
possibility, however (path b).
There are few other methods for synthesis of rosefuran
starting from nonfuranoid substrates.5,6 Very recently, 3 was
obtained in 11% overall yield by a four-step synthesis involving
a [3 + 2] nitrile oxide cycloaddition as the key step.6g Another
approach utilized the acid-catalysed cyclization into furans of
aliphatic b,g-dihydroxy ketones, obtained by Ru-catalysed
addition of allyl alcohols and alkynes followed by dihydroxyl-
ation with OsO4, and afforded 3 in 23% overall yield;
isorosefuran (which contains a terminal double bond) was also
formed (rosefuran:isorosefuran ratio = 4).6f It is noteworthy
that a previously reported synthesis of rosefuran starting from
enynol 1 required a sequence of five steps and afforded a ca.
3:1 mixture of 3 and a b-lactone derivative; the latter had to be
separated and recycled.6e
The Ru-catalysed cycloisomerization of (Z)-2-en-4-yn-1-ols
has been reported, but it could only be applied to terminal
enynols.7 On the other hand, a recently proposed Pd-based
catalytic system suitable for internal enynols did not work with
substrates bearing a triple bond conjugated with a double bond
such as 2.7b The catalytic system here described, in spite of its
simplicity, allows the conversion of (Z)-2-en-4-yn-1-ols with
either internal and terminal triple bonds into the corresponding
furans in high yields and with high catalytic efficiencies, and
can also be applied to the synthesis of fragile biologically active
furan derivatives, such as rosefuran.
We report a new, efficient and selective synthesis of rosefuran
3, a natural product present in the highly prized oil of rose1 and
many other natural sources.2 The synthesis is realized in two
steps with a 60% overall isolated yield, according to Scheme
1.
The key step consists of a Pd-catalysed cycloisomerization of
(Z)-3,7-dimethylocta-2,6-dien-4-yn-1-ol 2, readily obtainable
in 78% yield from the commercially available
(Z)-3-methylpent-2-en-4-yn-1-ol 1 via Pd/Cu-catalysed cou-
pling with 1-bromo-2-methylpropene.3 Thus, by reacting 2
(1.88 g, 12.5 mmol) under nitrogen in 5 ml of dry N,N-
dimethylacetamide (DMA) at 100 °C for 24 h in the presence of
PdI2 (45 mg, 0.125 mmol) and KI (41.5 mg, 0.25 mmol),
rosefuran 3 was obtained in 85% GLC yield. After the usual
work-up, 3 was isolated by transfer distillation (1.44 g, 77%).
The Pd-based catalytic system here reported also works very
well with substrates bearing a terminal triple bond, thus
providing a general method for the synthesis of furans by
cycloisomerization of (Z)-2-en-4-yn-1-ols (Scheme 2).
Terminal enynols are indeed much more reactive than
internal ones, and were easily converted to the corresponding
furans in excellent yields and with high catalytic efficiencies at
20–45 °C. For example, 1 (3.0 g, 31.2 mmol) was allowed to
react under nitrogen at 20 °C† for 18 h without solvent in the
presence of PdI2 (22.5 mg, 0.062 mmol) and KI (20.7 mg, 0.125
mmol) to give, after transfer distillation, 2.6 g of 2,3-di-
methylfuran (87%). GLC yield was higher than 92%.
The cycloisomerization process may involve an anti-exo-dig
intramolecular nucleophilic attack of the hydroxy group to the
triple bond coordinated to palladium(ii)4 with formation of a
I2Pd
R1
R2
–HI
IPd
R2
O
•
O
•
R1
Br
H
i
ii
I
H +
+
b
HO
HO
O
+
O
IPd
R2
HI, –PdI2
a
R1
R1
R1
1
2
3
–H +
Scheme 1 Reagents and conditions: i, Pd(PPh3)2Cl2, CuI, Et2NH, 78%; ii,
K2PdI4, DMA, 77%
IPd
R2
R2
O
O
R1
H +
HI –PdI2
K2PdI4
R
–H +
R
O
HO
+
O
R2
R2
O
R1
R = H, Et, Ph
Scheme 2
Scheme 3
Chem. Commun., 1997
1083

View Article Online
D. R. Gedge and G. Pattenden, Tetrahedron Lett., 1977, 4443;
Z. M. Ismail and H. M. R. Hoffmann, Angew. Chem., 1983, 95, 737;
S. Araki and Y. Butsugan, Bull. Chem. Soc. Jpn., 1983, 56, 1446;
L. Meier and H. D. Scharf, Liebigs Ann. Chem., 1986, 731; W. S. Leal,
Y. Kuwahara, T. Suzuki and H. Nakao, Agric. Biol. Chem., 1989, 53,
3279; S. Araki, S.-J. Jin and Y. Butsugan, J. Chem. Soc., Perkin Trans.
1, 1995, 549; P. Weyerstahl, A. Schenk and H. Marschall, Liebigs Ann.
Chem., 1995, 1849.
6 Reported syntheses of rosefuran from nonfuranoid substrates: (a)
R. Okazaki, Y. Negishi and N. Inamoto, J. Org. Chem., 1984, 49, 3819;
(b) S. Takano, M. Morimoto, S. Satoh and K. Ogasawara, Chem. Lett.,
1984, 1261; (c) H. Tsukasa, Agric. Biol. Chem., 1989, 53, 3091; (d)
R. Iriye, T. Uno, I. Ohwa and A. Konishi, Agric. Biol. Chem., 1990, 54,
1841; (e) J. A. Marshall and W. J. DuBay, J. Org. Chem., 1993, 58, 3602;
(f) B. M. Trost and J. A. Flygare, J. Org. Chem., 1994, 59, 1078; (g)
A. Barco, S. Benetti, C. De Risi, G. P. Pollini and V. Zanirato,
Tetrahedron, 1995, 51, 7721.
Footnotes
* E-mail: g.salerno@unical.it
† The reaction temperature must be controlled with the aid of a water bath
owing to the exothermicity of the reaction.
References
1 K. Bauer, D. Garbe and H. Surburg, Common Fragrance and Flavour
Materials, VCH, Weinheim, 1990.
2 For recent examples, see: A. O. Tucker and M. J. Maciarello, J. Essent.
Oil Res., 1995, 7, 653; O. Nishimura, J. Agric. Food Chem., 1995, 43,
2941; D. Karasawa, S. Shatar, A. Erdenechimeg, Y. Okamoto, H. Tateba
and S. Shimizu, J. Essent. Oil Res., 1995, 7, 255.
3 K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975,
4467.
4 C. Lambert, K. Utimoto and H. Nozaki, Tetrahedron Lett., 1984, 25,
5323.
5 Reported syntheses of rosefuran from furan derivatives: G. Buchi,
E. Sz. Kovats, P. Enggist and G. Uhde, J. Org. Chem., 1968, 33, 1227;
O. P. Vig, A. K. Vig, V. K. Handa and S. D. Sharma, J. Indian Chem.
Soc., 1974, 51, 900; A. J. Birch, J. Slobbe, Tetrahedron Lett., 1976, 2079;
A. Takeda, K. Shinhama and S. Tsuboi, Bull. Chem. Soc. Jpn., 1977, 50,
1903; N. D. Ly and M. Schlosser, Helv. Chim. Acta, 1977, 60, 2085;
7 (a) B. Seiller, C. Bruneau and P. H. Dixneuf, J. Chem. Soc., Chem.
Commun., 1994, 493; (b) B. Seiller, C. Bruneau and P. H. Dixneuf,
Tetrahedron, 1995, 51, 13089; (c) H. Kucukbay, B. Cetinkaya,
S. Guesmi and P. H. Dixneuf, Organometallics, 1996, 15, 2434.
Received in Liverpool, UK, 21st March 1997; Com. 7/01988B
1084
Chem. Commun., 1997