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scale preparation of 2,3-dimethylfuran starting from (Z)-3-
methylpent-2-en-4-yn-1-ol was disclosed some years ago.5b
Base-promoted cyclization of (Z)-enynols was achieved
under strongly basic conditions, i.e., KOBut in ButOH-THF,
in the presence of 18-crown-6, which was not suitable for
the synthesis of base-sensitive furan.5c,e,f A Ru-catalyzed
synthesis of furans by selective cyclization of (Z)-enynols
using Ru(PPh3)(p-cymene)Cl2 as catalyst precursor was
reported by Dixneuf et al., which was only suitable for
terminal alkynes.5g,h,l An excellent K2PdI4-based catalytic
system was reported to accomplish the cycloisomerization
of a wide variety of (Z)-enynols under neutral conditions.5a
This methodology was applicable to different substitution
patterns in the starting materials (e.g., terminal and internal
alkynes) and provided most of the corresponding furans in
good to high yields. However, the reaction usually requires
high temperature (100 °C) in a dipolar aprotic solvent such
as DMA when (Z)-enynols bearing a substituent at C-3 and
an internal triple bond were employed. Thus, the catalytic
version of enynol-cyclization that proceeds at ambient
temperature in combination with the efficient (Z)-enynol
construction from simple, readily available starting materials
would greatly enhance the utility of this reaction. It has
recently been shown that gold(III) salts and gold(I) complex
display considerable catalytic activity under moderate condi-
tions.6 Hashmi et al. reported that this catalyst was superiorly
efficient in the cyclization of 2-methylpent-2-en-4-yn-1-ol
to furans (only one substrate was tested).7 Consequently, the
use of gold catalysis in the conversion of highly substituted
(Z)-enynols to furans remains largely unexplored. Herein,
we report the utilization of gold as catalyst for cyclization
of (Z)-enynols, which offers an efficient and straightforward
route to highly substituted furans or dihydrofurans under
extremely mild reaction conditions (Scheme 1).
alk-1-ynes to vinyl ketones followed by acid-catalyzed allylic
isomerization, and reduction of methyl (Z)-2-en-4-ynoates,
etc.5a,c We recently reported an efficient synthetic approach
to stereodefined (Z)-enynols 1 via zirconium-mediated cross-
coupling reactions of three different components involving
alkyne, ketone, and alkynyl bromide in a one-pot procedure
(Scheme 2).8 The subsequent electrophilic cyclization of the
Scheme 2
thus formed (Z)-enynols affords fully substituted (Z)-5-(1-
iodoylidene)-2,5-dihydrofurans. In addition to ketones, al-
dehydes were also confirmed to be suitable substrates for
this type of reaction.9
Thus, a variety of (Z)-enynols with a tertiary or secondary
alcoholic groups were readily synthesized by this method.
With (Z)-enynols 1 in hand, we were interested in exploring
the feasibility of using 1 in gold-catalyzed cyclization reac-
tions. We began our investigation with enynol 1a (R1 ) Me,
R2 ) o-ClC6H4, R3 ) R4 ) R5 ) Ph) bearing phenyl group
at C-5 and a tertiary alcohol group at C-1 (Scheme 3).
Scheme 3
Scheme 1
Treatment of 1a with 1 mol % of (PPh3)AuCl in refluxing
CH3CN for 5 days afforded (Z)-5-ylidene-2,5-dihydrofuran
The preparation of (Z)-enynols is usually achieved through
multistep transformations involving Pd/Cu-catalyzed coup-
ling of the terminal alkynes with vinylic halides, addition of
(6) (a) Ito, Y.; Sawamura, M.; Hayashi, T. Tetrahedron Lett. 1987, 28,
6215. (b) Sawamura, M.; Nakayama, Y.; Kato, T.; Ito, Y. J. Org. Chem.
1995, 60, 1727. (c) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem.
Soc. 2004, 126, 7458. (d) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650. (e) Dyker, G. Angew.
Chem., Int. Ed. 2000, 39, 4237. (f) Reetz, M. T.; Sommer, K. Eur. J. Org.
Chem. 2003, 3485. For cyclization of enynes, see: (g) Luzung, M. R.;
Markham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858. (h) Nieto-
Oberhuber, C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.; Ca´rdenas, D. J.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402. (i) Bruneau, C.
Angew. Chem., Int. Ed. 2005, 44, 2328. For furan formation from 2-(1-
alkynyl)-2-alken-1-ones, see: (j) Yao, T.; Zhang, X.; Larock, R. C. J. Am.
Chem. Soc. 2004, 126, 11164. (k) Yao, T.; Zhang, X.; Larock, R. C. J.
Org. Chem. 2005, 70, 7679.
(5) (a) Gabriele, B.; Salerno, G.; Lauria, E. J. Org. Chem. 1999, 64,
7687, and the references therein. (b) Ve´gh, D.; Zalupsky, P.; Kova´cˇ, J.
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Chem. 1993, 58, 3435. (d) Marshall, J. A.; Dubay, W. J. J. Org. Chem.
1993, 58, 3602. (e) Marshall, J. A.; Bennett, C. E. J. Org. Chem. 1994, 59,
6110. (f) Marshall, J. A.; Dubay, W. J. J. Org. Chem. 1994, 59, 1703. (g)
Seiller, B.; Bruneau, C.; Dixneuf, P. H. J. Chem. Soc., Chem. Commun.
1994, 493. (h) Ku¨cu¨kbay, H.; Cetinkaya, B.; Guesmi, S.; Dixneuf, P. H.;
Organometallics 1996, 15, 2434. (i) C¸ etinkaya, B.; O¨ zdemir, I.; Bruneau,
C.; Dixneuf, P. H. J. Mol. Catal. 1997, 118, L1-L4. (j) Hashmi, A. S. K.;
Schwarz, L.; Choi, J.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 112, 2285.
For a recent review, see: (k) Brown, R. C. D. Angew. Chem., Int. Ed. 2005,
44, 850. (l) Seiller, B.; Bruneau, C.; Dixneuf, P. H. Tetrahedron 1995, 51,
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(7) Hashmi, A. S. K.; Schwarz, L.; Choi, J.; Frost, T. M. Angew. Chem.,
Int. Ed. 2000, 112, 2285.
(8) Liu, Y. H.; Song, F. J.; Cong, L. Q. J. Org Chem. 2005, 70, 6999-
7002.
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