Cyclization of allenyne-1,6-diols catalyzed by gold and silver salts: An efficient selective synthesis of dihydrofuran and furan derivatives

Article abstract of DOI:10.1002/adsc.200700471

Treatment of allenyne-1,6-diols with gold and silver catalysts selectively produced 2,5-dihydrofuran and furan derivatives, respectively, in good to excellent yields through the selective activation and differentiation of the double and triple bonds in al

Full text of DOI:10.1002/adsc.200700471

COMMUNICATIONS
DOI: 10.1002/adsc.200700471
Cyclization of Allenyne-1,6-diols Catalyzed by Gold and Silver
Salts: An Efficient Selective Synthesis of Dihydrofuran and Furan
Derivatives
Sundae Kima and Phil Ho Leea,*
a
National Research Laboratory for Catalytic Organic Reaction, Department of Chemistry, and Institute for Basic Science,
Kangwon National University, Chunchon 200-701, Republic of Korea
Fax : (+82)-33-253-7582; e-mail: phlee@kangwon.ac.kr
Received: September 26, 2007; Revised: December 18, 2007; Published online: February 26, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Treatment of allenyne-1,6-diols with gold
and silver catalysts selectively produced 2,5-dihy-
drofuran and furan derivatives, respectively, in good
to excellent yields through the selective activation
and differentiation of the double and triple bonds
in allenyne-1,6-diols. It is noteworthy that the che-
moselectivity is clearly switched by simply changing
the metal from gold to silver.
in the cyclization of 2-methylpent-2-en-4-yn-1-ol to
furans[5a] and the cyclization of allenyl carbinols to di-
hydrofurans[5b] and Krause et al. described that gold-
A
polysubstituted 2,5-dihydrofurans.[6] Although many
examples of the synthesis of dihydrofurans and furans
via the cyclization of alcohols bearing one alkynyl or
allenyl group have been described,[4b,5a,6a,7] the devel-
opment of efficient methods for the synthesis of dihy-
drofuran and furan derivatives having diverse func-
tional groups under mild conditions remains an im-
portant objective. Moreover, as far as we are aware,
no selective synthesis of dihydrofurans and furans
from compounds possessing both one allenol and two
alkynols as a function of catalyst has been reported.
Keywords: cyclization; dihydrofuran; furan; gold;
silver
Dihydrofuran and furan derivatives widely occur as Herein, we report selective synthetic routes to dihy-
important structural units in a variety of natural prod- drofurans and furans from allenyne-1,6-diols through
ucts that can be applied as pharmaceuticals and flavor the selective activation and differentiation of double
and fragrance compounds.[1] Because they are useful and triple bonds catalyzed by gold and silver, respec-
and versatile synthetic intermediates for heterocyclic tively (Scheme 1).
compounds, the development of methodologies for
Our initial study focused on the cyclization of 1,6-
the synthesis of such compounds are of significant in- diphenyl-2-vinylidenehex-3-yne-1,6-diol (1a, dr=1:1)
terest.[2] To date various transition metal-, acid-, and with a variety of gold and silver catalysts. The results
base-catalyzed synthetic methods for dihydrofurans are summarized in Table 1. Treatment of 1a with 3
and furans have been reported.[3] Recently, it has mol% AuCl3 gave 3-(4-hydroxy-4-phenyl-1-butyn-1-
been demonstrated that cationic gold species show ef- yl)-2-phenyl-2,5-dihydrofuran (2a) and 5-(2-hydroxy-
ficient catalytic activity for the cyclization of alkynyl 2-phenylethyl)-2-phenyl-3-vinylfuran (3a) in 38% and
ketones, allenyl ketones, alkynyl epoxides and enyne 31% yields (258C, 10 min), respectively (entry 1). In-
alcohols under mild conditions.[4] In this respect, creasing the catalytic amount of AuCl3 gave a better
Hashmi et al. found that a gold catalyst was efficient selectivity (entries 1–3). The use of 15 mol% AuCl3
Scheme 1. Selective cyclization of allenyne-1,6-diols catalyzed by gold and silver salts.
Adv. Synth. Catal. 2008, 350, 547 – 551
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
547

Sundae Kim and Phil Ho Lee
COMMUNICATIONS
Table 1. Optimization for selective cyclization of allenyne-
Table 2. Synthesis of dihydrofurans from allenyne-1,6-diols
1,6-diol catalyzed by Au and Ag salts.[a]
catalyzed by AuCl3.[a]
[a]
Reactions were carried out with 15 mol% AuCl3 in
CH2Cl2 (0.20M) at 258C.
Isolated yield.
Diastereomeric ratio=1:1.
[b]
[c]
ingly, subjecting 1a to 15 mol% silver triflate exclu-
sively gave 3a in 80% yield (entry 13), indicating that
silver triflate selectively activated the alkynyl group
in allenyne-1,6-diol. It is noteworthy that the chemo-
selectivity is clearly switched by simply changing the
metal from gold to silver. Other silver catalysts such
as AgBF4, AgSbF6, and AgAsF6 failed to produce the
cyclized products. It is noteworthy that no 2-[1-(1-hy-
droxyphenylmethyl)propan-1,2-dienyl-1-yl]-4,5-dihy-
drofuran (4a) formed in these reactions. Dichlorome-
[a]
Diastereomeric ratio of 1a=1:1.
Isolated yield. Diastereomeric ratio of 2a=1:1.
Recovery yield of 1a.
Reaction was carried out at 08C.
MeCN was used as the solvent.
Reaction was carried out in 1,2-DCE at 758C.
[b]
[c]
[d]
[e]
[f]
afforded 2a as a major compound in 60% yield to- thane was the best solvent among several reaction
gether with 3a in 18% yield (entry 3), indicating that media (CH3CN, CH2Cl2 and ClCH2CH2Cl) that were
the gold catalyst preferentially activated the terminal examined.
double bond in the allenyl group of the allenyne-1,6-
Encouraged by above results, the selective cycliza-
diol. The cyclic compounds were obtained in 95% tion of a variety of allenyne-1,6-diols catalyzed by
yield (2a:3a=1.3:1) at 08C (entry 4). Five mol% gold was examined and the results are summarized in
AuCl3-5 mol% AgOTf gave 2a and 3a (1.9:1) in 84% Table 2. Treatment of 1b with 15 mol% AuCl3 gave
yield (entry 7). However, exposure of 1a to 5 mol% 2b and 3b in 64% yield (2b:3b=4.3:1) (entry 1).
Ph3PAuCl in DCE selectively produced 3a in 21% Compound 1c, obtained from cyclohexanecarbalde-
yield despite recovery of 1a in 60% yield (entry 9). hyde, indium, and 1,6-dibromo-2,4-hexadiyne, was
Moreover, 5 mol% AuCl3-15 mol% AgOTf and 5 transformed to dihydrofuran 2c and furan 3c in 71%
mol% Ph3PAuCl-5 mol% AgOTf selectively fur- yield (2c:3c=2.9:1) under the optimum conditions
nished 3a in 51% and 48% yields, respectively (en- (entry 2). In the case of various allenyne-1,6-diols,
tries 8 and 10). With these results, the use of silver electronic variation of substituents such as 4-chloro,
salts (AgOTf, AgBF4, AgSbF6, and AgAsF6) as a co- 3-methoxy, 4-methoxy, and 4-acetyl groups on the ar-
catalyst in combination with cat-gold was applied to omatic ring did not affect the efficiency and selectivi-
the cyclization of 1a, producing selectively the cyclic ty of the reactions (entries 4–7). Subjecting 1f to 15
compound (3a), however in low yields. Therefore, a mol% AuCl3 gave rise to the cyclized product 2f as
variety of silver catalysts were used alone for the cy- the major compound (2f:3f=7.5:1) (entry 6). Allen-
A
G
triflate gave 2a and 3a in 80% yield (1:3.4) (entry 11). acetyl group produced dihydrofuran 2g and furan 3g
Increasing the catalytic amount of silver triflate (5, 7 in 85% yield (2g:3g=4.0:1) in the presence of 15
and 10 mol%) resulted in better selectivity. Surpris- mol% AuCl3 (entry 7). Under the optimum condi-
548
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 547 – 551

Cyclization of Allenyne-1,6-diols Catalyzed by Gold and Silver Salts
COMMUNICATIONS
Table 3. Synthesis of furans from allenyne-1,6-diols cata-
lyzed by AgOTf.[a]
[a]
Reactions were carried out with 15 mol% AgOTf in
CH2Cl2 (0.20M) at 258C.
Isolated yield.
Compound 2e.
[b]
[c]
tions, the selective cyclization of compound 1h de-
rived from 2-furaldehyde provided the dihydrofuran
2h as the major compound (2h:3h=5.4:1) (entry 8).
Next, the selective cyclization of various allenyne-
1,6-diols catalyzed by silver was examined (Table 3).
Exposure of 1b to 15 mol% AgOTf selectively gave
3b in 68% yield (entry 1). That indicates an initial ac-
tivation of the alkynyl moiety, followed by the nucleo-
philic addition of the homoallenyl alcohol onto the re-
Scheme 2. Mechanism of selective cyclization of allenyne-
1,6-diol catalyzed by gold and silver salts.
sulting silver alkynyl complex. The method worked an (4) formed in these reactions, indicating that the
equally well with compound 1c, producing selectively hydroxy group at the C1-position in allenyne-1,6-diol
furan 3c in 86% yield (entry 2). Varying the electron is more nucleophilic than the one at the C6-position
demand of the substituents (4-Cl, 3-MeO, and 4-Ac) because the hydroxy group at the C6-position might
on the aromatic ring did not diminish the efficiency be coordinated to the gold and silver salts. More de-
and selectivity of the cyclization reactions (entries 4– tailed mechanistic studies about the selective forma-
6). Treatment of compound 1e and 1g with 15 mol% tion of dihydrofurans and furans are now in progress.
AgOTf selectively gave furans 3e and 3g in 81% and
85% yields, respectively (entries 5 and 6).
In summary, we have shown that treatment of al-
lenyne-1,6-diols with gold and silver catalysts gave
ACHTREUNG
Although the mechanism of the cyclization reaction 2,5-dihydrofuran and furan derivatives, respectively,
has not been established, a plausible reaction pathway in good to excellent yields through the selective acti-
is described in Scheme 2. The gold catalyst selectively vation and differentiation of the double and triple
activates the allenyl group in 1 and subsequent cycli- bonds in the allenyne-1,6-diol. It is noteworthy that
zation affords 6 to give the vinyl gold intermediate 7. the chemoselectivity is switched by simply changing
Subsequent protonation of the transient the vinyl the metal from gold to silver. These results should im-
gold species 7 produces 2 and regenerates the gold mediately provide more opportunities for the selec-
catalyst to continue the catalytic cycle. However, tive synthesis of dihydrofurans or furans from the
when a catalytic amount of silver triflate is used, the same starting materials as a function of catalyst.
alkynyl group in 1 is selectively activated and subse-
quent cyclization followed by isomerization provides
3 and silver catalyst to continue the catalytic cycle. As
described in Table 1, Au(III) has a higher preference
Experimental Section
A
in the activation of allene over alkyne, while Au(I)
and Ag(I) exhibited the opposite selectivity. It seems
that the difference in selectivity could also originate
from the charge difference of the catalysts rather than
Typical Experimental Procedures for Intramolecular
Cyclization Catalyzed by AuCl3
AuCl3 (9.8 mg, 0.032 mmol) was added to a solution of 1,6-
the identity of the metal itself. There is no dihydrofur- diphenyl-2-vinylidenehex-3-yne-1,6-diol
(63.0 mg,
Adv. Synth. Catal. 2008, 350, 547 – 551
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
549

Sundae Kim and Phil Ho Lee
COMMUNICATIONS
0.217 mmol) in dichloromethane (1.5 mL). After the reac-
tion mixture had been stirred for 10 min, the solvent was re-
moved under reduced pressure. The crude product was puri-
fied by silica gel column chromatography to give 3-(4-hy-
droxy-4-phenyl-1-butyn-1-yl)-2-phenyl-2,5-dihydrofuran (2a)
(yield: 38.0 mg, 60%) using EtOAc/hexane=1/3 (Rf =0.3)
and 5-(2-hydroxy-2-phenylethyl)-2-phenyl-3-vinylfuran (3a)
(yield: 11.4 mg, 18%) using EtOAc/hexane=1/5 (Rf =0.3).
3-(4-Hydroxy-4-phenyl-1-butyn-1-yl)-2-phenyl-2,5-dihy-
drofuran (2a): 1H NMR (400 MHz, CDCl3): d=7.39–7.21
(m, 10H), 6.18 (s, 1H), 5.61 (s, 1H), 4.94 (dd, J=5.99,
5.99 Hz, 1H), 4.83 (d, J=14.4 Hz, 1H), 4.74–4.68 (m, 1H),
2.73–2.60 (m, 2H), 2.12 (s, 1H); 13C NMR (100 MHz,
CDCl3): Isomer A d=142.34, 140.65, 130.80, 128.44, 128.40,
128.21, 127.89, 126.67, 125.61, 125.11, 91.17, 89.09, 75.97,
75.77, 72.30, 30.47; Isomer B d=142.30, 140.69, 130.80,
128.44, 128.40, 128.24, 127.85, 126.67, 125.68, 125.61, 91.11,
89.12, 76.08, 75.77, 72.13, 30.54; IR (film): n=3433, 3062,
3028, 2921, 1972, 1884, 1817, 1601, 1491 cmÀ1; HR-MS (EI):
m/z=290.1309, calcd. for C20H18O2M+: 290.1307.
S. Natori, S. Nozoe), Kodansha, Tokyo, 1974, Vols. 1–3;
c) F. M. Dean, in: Advances in Heterocyclic Chemistry,
(Ed.: A. R. Katritzky), Academic Press, New York,
1983, Vol. 31, p 237; d) M. V. Sargent, F. M. Dean, in:
Comprehensive Heterocyclic Chemistry, (Eds.: C. W.
Bird, G. W. H. Cheeseman), Pergamon Press, Oxford,
1984, Vol. 3, p 599; e) B. H. Lipshutz, Chem. Rev. 1986,
86, 795; f) H. Heaney, J. S. Ahn, in: Comprehensive Het-
erocyclic Chemistry II, (Eds.: A. R. Katritzky, C. W.
Rees, E. F. V. Scriven), Pergamon Press, Oxford, 1996,
Vol. 2, p 297; g) M. M. Faul, B. E. Huff, Chem. Rev.
2000, 100, 2407; h) J. J. Fernandez, M. L. Souto, M.
Norte, Nat. Prod. Rep. 2000, 17, 26; i) B, Kçnig, in: Sci-
ence of Synthesis Houben-Weyl Methods of Molecular
Transformations, (Ed.: G. Maas), Thieme Verlag, Stutt-
gart, 2001, Vol. 9, p 183; j) The Chemistry of Heterocy-
cles: Structure, Reactions, Syntheses, and Applications,
(Eds.: T. Eicher, S. Hauptmann), Wiley-VCH, Wein-
heim, 2003; k) J. W. Blunt, B. R. Copp, M. H. G. Munro,
P. T. Northcote, M. R. Prinsep, Nat. Prod. Rep. 2006, 23,
235.
5-(2-Hydroxy-2-phenylethyl)-2-phenyl-3-vinylfuran (3a):
1H NMR (400 MHz, CDCl3): d=7.55 (d, J=8.58 Hz, 2H),
7.43–7.34 (m, 6H), 7.32–7.27 (m, 2H), 6.84 (dd, J=17.3,
10.8 Hz, 1H), 6.39 (s, 1H), 5.50 (d, J=17.3 Hz, 1H), 5.20 (d,
J=10.8 Hz, 1H), 5.05 (t, J=6.50 Hz, 1H), 3.07 (d, J=
6.5 Hz, 2H), 2.29 (s, 1H); 13C NMR (100 MHz, CDCl3): d=
151.73, 149.39, 143.30, 131.05, 128.57, 128.52, 127.79, 127.65,
127.52, 126.54, 125.78, 121.09, 114.50, 107.35, 72.74, 38.42;
IR (film): n=3419, 3061, 3029, 2923, 1954, 1668, 1598, 1491,
[2] a) M. Maier, in: Organic Synthesis Highlights II, (Ed.:
H. Waldmann), VCH, Weinheim, 1995, p 231; b) R. Be-
nassi, in: Comprehensive Heterocyclic Chemistry II,
(Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven), Per-
gamon Press, Oxford, 1996, Vol. 2, p 259.
[3] a) J. A. Marshall, X.-J. Wang, J. Org. Chem. 1991, 56,
960; b) Y. Fukuda, H. Shiragami, K. Utimoto, H.
Nozaki, J. Org. Chem. 1991, 56, 5816; c) J. A. Marshall,
G. S. Bartley, J. Org. Chem. 1994, 59, 7169; d) R. Vieser,
W. Eberbach, Tetrahedron Lett. 1995, 36, 4405; e) A.
Arcadi, F, Marinelli, E. Pini, E. Rossi, Tetrahedron
Lett. 1996, 37, 3387; f) A. Arcadi, E. Rossi, Tetrahedron
1998, 54, 15253; g) C. D. Brown, J. M. Chong, L. Shen,
Tetrahedron 1999, 55, 14233; h) S. Cacchi, J. Organomet.
Chem. 1999, 576, 42; i) A. V. Kel’in, V. Gevorgyan, J.
Org. Chem. 2002, 67, 95; j) G. Balme, D. Bouyssi, T.
Lomberget, N. Monteiro, Synthesis 2003, 2115; k) F.
Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104,
3079; l) G. Zeni, R. C. Larock, Chem. Rev. 2004, 104,
2285; m) I. Nakamura, Y. Yamamoto, Chem. Rev. 2004,
104, 2127; n) G. Kirsch, S. Hesse, A. Comel, Curr. Org.
Synth. 2004, 1, 47; o) G. Zeni, R. C. Larock, Chem. Rev.
2006, 106, 4644.
1261 cmÀ1
;
HR-MS (EI): m/z=290.1308, calcd. for
C20H18O2M+: 290.1307.
Typical Experimental Procedures for Intramolecular
Cyclization Catalyzed by AgOTf
AgOTf (8.4 mg, 0.032 mmol) was added to a solution of 1,6-
diphenyl-2-vinylidenehex-3-yne-1,6-diol
(63.0 mg,
0.217 mmol) in dichloromethane (1.5 mL). After the reac-
tion mixture had been stirred for 1.5 h, the solvent was re-
moved under reduced pressure. The crude product was puri-
fied by silica gel column chromatography (EtOAc/hexane=
1/5, Rf =0.3) to give 5-(2-hydroxy-2-phenylethyl)-2-phenyl-3-
vinylfuran (3a); yield: 51.0 mg (80%).
[4] a) T. Yao, X. Zhang, R. C. Larock, J. Am. Chem. Soc.
2004, 126, 11164; b) A. S. K. Hashmi, P. Sinha, Adv.
Synth. Catal. 2004, 346, 432; c) Y. Liu, F. Song, Z. Song,
M. Liu, B. Yan, Org. Lett. 2005, 7, 5409; d) T. Yao, X.
Zhang, R. C. Larock, J. Org. Chem. 2005, 70, 7679;
e) C.-Y. Zhou, P. W. H. Chan, C.-M. Che, Org. Lett.
2006, 8, 325; f) J. Zhang, H.-G. Schmalz, Angew. Chem.
2006, 118, 6856; Angew. Chem. Int. Ed. 2006, 45, 6704;
g) X. Liu, Z. Pan, X. Shu, X. Duan, Y. Liang, Synlett
2006, 1962; h) A. Buzas, F. Istrate, F. Gagosz, Org. Lett.
2006, 8, 1957.
Acknowledgements
This work was supported by the Korea Science and Engineer-
ing Foundation (KOSEF) through the National Research
Lab. Program funded by the Ministry of Science and Tech-
nology (No. M10600000203–06J0000–20310), by the CMDS
at KAIST, and by the Korea Science and Engineering Foun-
dation (KOSEF, R01–2006–000–11283–0). The NMR and
mass data were obtained from the central instrumental facility
in Kangwon National University.
[5] a) A. S. K. Hashmi, L. Schwarz, J. Choi, T. M. Frost,
Angew. Chem. 2000, 112, 2382; Angew. Chem. Int. Ed.
2000, 39, 2285; b) A. S. K. Hashmi, M. C. Blanco, D.
Fischer, J. Bats, Eur. J. Org. Chem. 2006, 1387;
c) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180.
References
[1] a) F. A. Dean, in: Naturally Occurring Oxygen Ring
Compounds, Butterworth, London, 1963; b) Natural
Products Chemistry, (Eds.: K. Nakanishi, T. Goto, S. Ito,
[6] a) A. Hoffmann-Rçder, N. Krause, Org. Lett. 2001, 3,
2537; b) N. Morita, N. Krause, Org. Lett. 2004, 6, 4121.
550
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 547 – 551

Cyclization of Allenyne-1,6-diols Catalyzed by Gold and Silver Salts
COMMUNICATIONS
[7] a) G. Dyker, Angew. Chem. 2000, 112, 4407; Angew.
Chem. Int. Ed. 2000, 39, 4237; b) A. S. K. Hashmi, T. M.
Frost, J. W. Bats, J. Am. Chem. Soc. 2000 122, 11553;
c) A. S. K. Hashmi, Gold Bull. 2003, 36, 3; d) V.
Mamane, T. Gress, H. Krause, A. Fꢁrstner, J. Am.
Chem. Soc. 2004, 126, 8654; e) A. S. K. Hashmi, Gold
Bull. 2004, 37, 51; f) A. S. K. Hashmi, G. J. Hutchings,
Angew. Chem. 2006, 118, 8064; Angew. Chem. Int. Ed.
2006, 45, 7896.
Adv. Synth. Catal. 2008, 350, 547 – 551
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
551