Gold-catalyzed cyclization of enyne-1,6-diols to substituted furans

Article abstract of DOI:10.1016/j.tetlet.2010.02.026

Treatment of enyne-1,6-diols with 5 mol % Ph₃PAuCl in the presence of 5 mol % AgOTf as a cocatalyst selectively produced trisubstituted furans in good to excellent yields in dichloromethane at room temperature for 5-10 min through cyclization f

Full text of DOI:10.1016/j.tetlet.2010.02.026

Tetrahedron Letters 51 (2010) 1899–1901
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Tetrahedron Letters
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Gold-catalyzed cyclization of enyne-1,6-diols to substituted furans
Sundae Kim a, Dongjin Kang a, Seunghoon Shin b, Phil Ho Lee a,
*
a National Research Laboratory for Catalytic Organic Reaction, Department of Chemistry and Institute for Molecular Science and Fusion Technology,
Kangwon National University, Chuncheon 200-701, Republic of Korea
b Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of enyne-1,6-diols with 5 mol % Ph3PAuCl in the presence of 5 mol % AgOTf as a cocatalyst
selectively produced trisubstituted furans in good to excellent yields in dichloromethane at room tem-
perature for 5–10 min through cyclization followed by isomerization.
Received 31 December 2009
Revised 2 February 2010
Accepted 5 February 2010
Available online 10 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Furan derivatives widely occur as essential structural units in a
variety of natural products which can be applied to pharmaceuti-
cals and flavor and fragrance compounds.1 Because they also repre-
sent versatile building blocks for the synthesis of more elaborate
heterocyclic compounds, development of new synthetic method
of furan compounds is an important and continuing goal of organic
synthesis.2 To date various transition metal-, acid-, and base-cata-
lyzed synthetic methods of furans have been reported.3 Recently, it
has been demonstrated that gold shows efficient catalytic activity
for furan and dihydrofuran synthesis.4 These include the cycliza-
tion of allenyl ketones,5 2-(1-alkynyl)-2-alken-1-ones,6 (Z)-2-en-
4-yn-1-ols,7 1-(1-alkynyl)cyclopropyl ketones,8 alkynyl epoxide9,
or heteroatom-substituted propargyl alcohol10 through nucleo-
philic attack of oxygen atom to a gold-coordinated C–C double or
triple bond.11 Also, Belting and Krause described Au-catalyzed tan-
dem cycloisomerization-hydroalkoxylation of homopropargyl
alcohols.12 Recently, we reported that the treatment of allenyne-
1,6-diols with 15 mol % AuCl3 selectively produced 2,5-di-hydrofu-
rans through the selective activation of terminal double bond in al-
kene (Eq. (1)).13 However, subjecting allenyne-1,6-diols to
15 mol % AgOTf selectively afforded furans through the selective
activation of triple bond (Eq. (2)).13
R
cat. Ag
ð2Þ
HO
R
R
R
O
OH
HO
In pursuit of continuous investigations in this field, we found
that the treatment of enyne-1,6-diols with Au catalyst selectively
gave furans in contrast with the above-mentioned results.13 Here-
in, we report efficient synthetic routes to trisubstituted-furans
through selective cyclization of enyne-1,6-diols catalyzed by gold
followed by isomerization (Scheme 1).
First, a variety of enyne-1,6-diols 1 were prepared from the
reaction of aldehydes with organoindium reagent generated
in situ from indium and 1,6-dibromo-2,4-hexadiyne in the pres-
ence of lithium iodide in THF14 and subsequent allylation (Scheme
2).15 Initially, we examined the cyclization of enyne-1,6-diol 1a by
using Ag and Au catalysts. The results are summarized in Table 1.
Although the treatment of allenyne-1,6-diol with 15 mol % AgOTf
gave selectively furans,13 the reaction of 1a with 5 mol % AgOTf
did not produce the cyclized product (entry 1). Exposure of 1a on
5 mol % TfOH afforded unknown compound (entry 2).
Surprisingly, the treatment of 1a with 5 mol % AuCl3 selectively
provided trisubstituted furan 2a in 40% yield in CH2Cl2 at room
temperature for 12 h (entry 3). The use of 10 mol % AuCl3 did not
increase the yield of 2a (entry 4). When dichloroethane was used
as a solvent, the cyclic compound 2a was obtained in 35% yield
R
HO
cat. Au
ð1Þ
R
R
OH
HO
R
O
4
3
2
5
cat. Au
R
1
6
R
R
HO
R
OH
HO
O
* Corresponding author. Tel.: +82 33 250 8493; fax: +82 33 253 7582.
E-mail address: phlee@kangwon.ac.kr (P.H. Lee).
Scheme 1. Selective cyclization of enyne-1,6-diols catalyzed by Au.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.026

1900
S. Kim et al. / Tetrahedron Letters 51 (2010) 1899–1901
5 mol % Ph3PAuCl
5 mol % AgOTf
Br
In, LiI
THF
Ph
RCHO
+
2
ð3Þ
ð4Þ
CH2Cl2, 25 ºC
5 min
Br
R
R
MeO
Ph
66% 2k
OH
HO
Ph
Ph
1k
O
OMe
HO
Br / In
THF
5 mol % Ph3PAuCl
5 mol % AgOTf
messy
R
R
1
CH2Cl2, 25 ºC
5 min
OH
HO
Ph
Ph
1l
OH
MeO
Scheme 2. Preparation of enyne-1,6-diol.
To demonstrate the efficiency and scope of the present method,
we applied the catalytic system to a variety of enyne-1,6-diols 1
(Table 2). Enyne-1,6-diol 1b obtained from butanal was treated
with 5 mol % Ph3PAuCl and 5 mol % AgOTf in dichloromethane for
5 min to selectively produce trisubstituted furan 2b in 83% yield
at 80 °C for 12 h (entry 5). Reaction of 1a with 3 mol % AuCl3 and
9 mol % AgOTf or 5 mol % AuCl3 and 15 mol % AgOTf gave 2a in
15% and 8% yields, respectively (entries 6 and 7). However, the
exposure of 1a to 5 mol % Ph3PAuCl and 5 mol % AgOTf selectively
produced trisubstituted furan 2a in 89% yield in CH2Cl2 at room
temperature for 5 min through nucleophilic attack of the hydroxyl
oxygen atom on C-1 position to a gold-coordinated C–C triple bond
(entry 8). Treatment of 1a with 5 mol % Ph3PAuCl did not proceed,
indicating that the catalytic system combining with Ph3PAuCl and
AgOTf is essential for cyclization (entry 9). There is no 4,5-dihydro-
furan 3a formed in any entries through nucleophilic attack of the
hydroxyl oxygen atom on C-6 position to a gold-coordinated C–C
triple bond. The use of Au catalysts having other phosphine ligands
such as (C6F5)3PAuCl and (4-MeO–C6H4)3PAuCl gave the desired
product 2a in 64% and 70% yields, respectively (entries 10 and 11).
Table 2
Cyclization of enyne-l,6-diols catalyzed by Au
R1
R1
5 mol % Ph3PAuCl
5 mol % AgOTf
R
CH2Cl2, 25 ºC
5 ~ 10 min
HO
R
O
R
R
2
OH
HO
1
Entry R, R1
Product
Yielda
(%)
OH
OH
2b
1
2
3
n-Propyl, H 1b
C6H11, H 1c
Ph, H 1a
83
71
89
Ph
3a
O
O
Ph
HO
Next, we examined the cyclization of protected alcohols (1k and
1l) obtained from subjecting diol 1a to NaH followed by the treat-
ment of methyl iodide. Although allyl alcohol 1k having methyl-
protected homopropargyl ether gave the cyclized product 2k in
66% yield under the optimum reaction conditions (Eq. (3)), homo-
propargyl alcohol 1l having methyl-protected allyl ether did not
produce the corresponding furan (Eq. (4)). This result indicates that
the presence of double bond on propargylic position is critical to
produce the furan.
2c
O
OH
OH
2a
2d
Ph
Ph
O
4
Ph, Me 1d
81b
Ph
Ph
O
OH
2e
2f
Table 1
5
6
4-CI–C6H4, H 1e
4-Me–C6H4, H 1f
84
83
68
80
89
90
4-Cl-C6H4
4-Me-C6H4
Reaction optimization of Au-catalyzed cyclization of la
C6H4-4-Cl
O
OH
cat. Au
CH2Cl2
25 ºC
Ph
C6H4-4-Me
O
HO
Ph
Ph
Ph
O
OH
HO
OH
2g
2,4,6-Me3–C6H2,
H 1g
1a
2a
7
2,4,6-Me3-C6H2
C6H2-2,4,6-Me3
Entry
Cat. Au
Time
Yielda (%)
O
1
2
3
5 mol % AgOTf
5 mol % TfOH
5 mol % AuCI3
10 mol %AuCI3
5 mol % AuCI3
24 h
2 h
0
OH
3-MeO–C6H4, H
1h
2h
b
8
3-MeO-C6H4
3-HO-C6H4
12 h
12 h
12 h
12 h
12 h
40 (35)
30 (41)
35 (37)
15 (48)
8 (60)
89
0
64
70
C6H4-3-OMe
O
4
5c
6
OH
2i
3 mol % AuCI3/9 mol % AgOTf
5 mol % AuCI3/15 mol % AgOTf
5 mol % Ph3PAuCI/5 mol % AgOTf
5 mol % Ph3PAuCI
5 mol % (C6F5)3PAuCI/5 mol % AgOTf
5 mol % (4-MeO–C6H4)3PAuCI/5 mol % AgOTf
9
3-HO–C6H4, H 1i
7
8
9
10
11
C6H4-3-OH
O
5 min
19 h
5 min
5 min
OH
4-MeO2C–C6H4,
H 1j
2j
C6H4-4-CO2Me
10
4-MeO2C-C6H4
O
a
b
c
Isolated yield. Numbers in parentheses indicate the recovery yield of la.
Unknown was obtained.
Reaction performed in dichloroethane at 80 °C.
a
Isolated yield.
b
Isomeric ratio = 1 (internal alkene):3.2 (terminal alkene).

S. Kim et al. / Tetrahedron Letters 51 (2010) 1899–1901
1901
(entry 1). In the case of compound 1c generated from cyclohexan-
ecarbaldehyde, furan 2c was selectively obtained in 71% yield (en-
try 2). Enyne-1,6-diol 1d having 4-methyl-4-pentenylidene group
at C-2 position turned out to be compatible with the employed
reaction conditions, affording 2d (1:3.2) in 81% (entry 4). This
isomerization may be due to the coordination of gold to the C–C
double bond or acidic conditions. Altering the electron demand
of the substituents on aromatic rings did not diminish the effi-
ciency or selectivity (entries 5–10). Under the optimum reaction
conditions, 3-hexyne-1,6-diol 1e having 4-chlorophenyl group
gave rise to the desired product 2e in 84% yield (entry 5). Enyne-
1,6-diol (1f and 1h) bearing 4-methylphenyl and 3-methoxy-phe-
nyl group were cleanly converted to the desired furans (2f and 2h)
in 83% and 80% yields, respectively (entries 6 and 8). However, eny-
ne-1,6-diol having 2,4,6-trimethyl-phenyl group afforded furan 2g
in 68% yield due to steric hindrance (entry 7). It is noteworthy that
the additional hydroxyl group on substrate did not affect the effi-
ciency of the cyclization reactions, producing furan 2i in 89% yield
(entry 9). Enyne-1,6-diol 1j bearing electron-withdrawing group
such as 4-methoxycarbonyl group was treated with 5 mol %
Ph3PAuCl in the presence of 5 mol % AgOTf as a cocatalyst to result
in the selective formation of functionalized furan 2j in 90% yield
(entry 10).
A plausible reaction pathway is described in Scheme 3. Thus,
coordination of the gold catalyst to triple bond in 3-hexyne-1,6-
diols 1 results in the formation of the intermediate 4 which, upon
nucleophilic attack of the hydroxyl oxygen atom on 1-position to a
gold-coordinated C–C triple bond, is cyclized to the vinylgold com-
plex 5. Release of the proton from 5 followed by protodeauration of
6 affords the 4,5-dihydrofuran derivatives 7 and regenerates the
gold cationic active species. Finally, compounds 7 easily isomerize
to functionalized furans 2. Surprisingly, no other cyclic compound
such as 3 (disubstituted 4,5-dihydrofuran) through nucleophilic at-
tack of the hydroxyl oxygen atom on C-6-position to a gold-coordi-
nated C–C triple bond is formed. Although the reason for selective
attack of the hydroxyl oxygen atom on C1-position to gold-coordi-
nated C–C triple bond has not been established at present, it seems
that geometry and bond distance between triple bond and hydro-
xyl group and bond angle on C-2 and C-5-position might be impor-
tant factors. The elucidation of the detailed reaction mechanism
must wait further study.
In summary, we have developed an efficient synthetic method
of trisubstituted furans from the treatment of enyne-1,6-diols with
5 mol % Ph3PAuCl and 5 mol % AgOTf in CH2Cl2 at room tempera-
ture through selective cyclization followed by isomerization.
Acknowledgments
This work was supported by the KRF Grant funded by the Kor-
ean Government (KRF-2008-314-C00213), by the KOSEF through
the NRL Program funded by the MOST (No. M10600000203-
06J0000-20310), by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (2009-
0087013), and by Korea Sanhak Foundation. This work was sup-
ported by the second phase of the Brain Korea 21 Program in
2009. Dr. Sung Hong Kim at the KBSI (Daegu) is thanked for obtain-
ing the MS data. The NMR data were obtained from the central
instrumental facility in Kangwon National University.
References and notes
1. (a) Dean, F. M. In Naturally Occurring Oxygen Ring Compounds; Butterworth:
London, 1963; (b) Nakanishi, K.; Goto, T.; Ito, S.; Natori, S.; Nozoe, S.. In Natural
Products Chemistry; Kodansha: Tokyo, 1974; Vols. 1–3, (c) Dean, F. M.. In
Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.; Academic Press: New
York, 1983; Vol. 31, p 237; (d) Sargent, M. V.; Dean, F. M.. In Comprehensive
Heterocyclic Chemistry; Bird, C. W., Cheeseman, G. W. H., Eds.; Pergamon Press:
Oxford, 1984; Vol. 3, p 599; (e) Lipshutz, B. H. Chem. Rev. 1986, 86, 795; (f)
Heaney, H.; Ahn, J. S.. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.,
Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press: Oxford, 1996; Vol. 2, p 297;
(g) Faul, M. M.; Huff, B. E. Chem. Rev. 2000, 100, 2407; (h) Fernandez, J. J.; Souto,
M. L.; Norte, M. Nat. Prod. Rep. 2000, 23, 26; (i) Konig, B.. In Maas, G., Ed.;
Science of Synthesis, Houben–Weyl Methods of Molecular Transformations;
Thieme Verlag: Stuttgart, 2001; Vol. 9, p 183; (j) Eicher, T.; Hauptmann, S.. In
The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications;
Wiley-VCH: Weinheim, 2003; (k) Blunt, J. W.; Copp, B. R.; Munro, M. H.;
Northcote, G. P. T.; Prinsep, M. R. Nat. Prod. Rep. 2006, 17, 235.
2. (a) Heaney, H. In Natural Products Chemistry; Nakanishi, K., Ed.; Kodansha:
Tokyo, 1974; p 297; (b) Sundberg, R. J.. In Comprehensive Heterocyclic Chemistry;
Katrizky, A. R., Rees, C. W., Eds.; Pergamon: New York, 1984; Vol. 5, p 313; (c)
Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kwan, P. L.; Lo, T. H.; Tong, S. Y. T.; Wong, H.
N. C. Tetrahedron 1998, 54, 1955; (d) Keay, B. A. Chem. Soc. Rev. 1999, 28, 209;
(e) Shipman, M. Contemp. Org. Synth. 1995, 2, 1; (f) Hou, X. L.; Yang, Z.; Wong, H.
N. C.. In Progress in Heterocyclic Chemistry; Gribble, G. W., Gilchrist, T. L., Eds.;
Pergamon: Oxford, 2002; Vol. 14, p 139.
3. (a) Hashmi, A. S. K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1581; (b) Sromek, A.
W.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2004, 43, 2280; (c) Patil, N.
T.; Wu, H.; Yamamoto, Y. J. Org. Chem. 2005, 70, 4531.
R
4. (a) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896; (b)
Hashmi, A. S. K.; Blanco, M. C.; Fischer, D.; Bats, J. W. Eur. J. Org. Chem. 2006,
1387; (c) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; Gorin, D. J.; Toste, F. D.
Nature 2007, 446, 395; (d) Arcadi, A. Chem. Rev. 2008, 108, 3266; (e) Patil, N.;
Yamamoto, Y. Chem. Rev. 2008, 108, 3395; (f) Li, Z.; Brouwer, C.; He, C. Chem.
Rev. 2008, 108, 3239; (g) Shen, H. C. Tetrahedron 2008, 64, 3885; (h) Muzart, J.
Tetrahedron 2008, 64, 5815; (i) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917;
(j) Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev. 2008, 37, 1766.
5. (a) Hashmi, A. S. K.; Schwarz, L.; Choi, J.; Frost, T. M. Angew. Chem., Int. Ed. 2000,
39, 2285; (b) Dyker, G. Angew. Chem., Int. Ed. 2000, 39, 4237; (c) Sromek, A. W.;
Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500; (d) Zhou, C.-Y.;
Chan, P. W. H.; Che, C.-M. Org. Lett. 2006, 8, 325.
R
HO
O
2
R
HO
R
O
7
LAu+
3
4
2
5
1
6
H+
R
R
OH
HO
1
6. (a) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004, 126, 11164; (b) Yao, T.;
Zhang, X.; Larock, R. C. J. Org. Chem. 2005, 70, 7679.
LAu+
7. Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409.
8. Zhang, J.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2006, 45, 6704.
LAu
R
9. (a) Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 356, 432; (b) Shu, X.-Z.; Liu,
X.-Y.; Xiao, H.-Q.; Ji, K.-G.; Guo, L.-N.; Qi, C.-Z.; Liang, Y.-M. Adv. Synth. Catal.
2007, 349, 2493; (c) Dai, L.-Z.; Shi, M. Tetrahedron Lett. 2008, 49, 6437.
10. Aponick, A.; Li, C.-Y.; Malinge, J.; Marques, E. F. Org. Lett. 2009, 11, 4624.
11. (a) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729; (b) Teles, J. H.; Brode, S.;
Chabanas, M. Angew. Chem., Int. Ed. 1998, 37, 1415; (c) Antoniotti, S.; Genin, E.;
Michelet, V.; Genet, J.-P. J. Am. Chem. Soc. 2005, 127, 9976.
12. Belting, V.; Krause, N. Org. Lett. 2006, 8, 4489.
13. Kim, S.; Lee, P. H. Adv. Synth. Catal. 2008, 350, 547.
14. Kim, S.; Lee, K.; Seomoon, D.; Lee, P. H. Adv. Synth. Catal. 2007, 349, 2449.
15. Kim, S.; Lee, P. H. Eur. J. Org. Chem. 2008, 2262.
R
R
HO
R
O
6
O
H
O
H
4
LAu
R
H+
3
R
O
HO
R
O +
H
R
5
HO
Scheme 3. Plausible mechanism for furan synthesis catalyzed by Au.