Mechanistic studies and improvement of coinage metal-catalyzed transformation of alkynyloxiranes to furans: An alcohol addition-cyclization- elimination cascade

Article abstract of DOI:10.1021/jo9008172

(Chemical Equation Presented) In the presence of alcohol Ag or Au salts or complexes catalyze the conversion of alkynyloxiranes to substituted furans. Both catalysts are effective, and a large furan diversity can be obtained in high yield with one or the

Full text of DOI:10.1021/jo9008172

pubs.acs.org/joc
Mechanistic Studies and Improvement of Coinage Metal-Catalyzed
Transformation of Alkynyloxiranes to Furans: An Alcohol
Addition-Cyclization-Elimination Cascade
ꢀ
Aurelien Blanc, Katharina Tenbrink, Jean-Marc Weibel, and Patrick Pale*
ꢁ
ꢀ
ꢀ
ꢀ
Laboratoire de Synthese et Reactivite Organiques associe au CNRS, Institut de Chimie,
Universiteꢀ de Strasbourg 4 rue Blaise Pascal, 67000 Strasbourg, France
ppale@chimie.u-strasbg.fr
Received April 21, 2009
In the presence of alcohol Ag or Au salts or complexes catalyze the conversion of alkynyloxiranes to
substituted furans. Both catalysts are effective, and a large furan diversity can be obtained in high yield
with one or the other catalyst. Mechanistic studies revealed that a cascade pathway and not the
sometimes reported direct intramolecular nucleophilic addition of oxirane oxygen atom to inter-
mediate acetylene-metal π-complex occurs. Under the defined conditions, the intermediate forma-
tion of epoxide opening products has been identified. Depending on the catalyst, one or
both of the latter cyclized to dihydrofurans, and further elimination of the alcohol led to the corres-
ponding furans. These results highlight the duality between oxophilicity and alkynophilicity of Ag or Au
salts.
Introduction
Most of these new methodologies were based on the
alkeno- and alkynophilicity of silver or gold ions,3 especially
for the cyclization of allenyl, alkenyl, or alkynyl alcohols
or acids. However, silver and gold ions are Lewis acids
and calculations revealed that they also exhibit mild oxophi-
licity.4 This property of Ag or Au species has so far been less
investigated and applied than alkynophilicity. Nevertheless,
a few publications highlight the dual role of late transition
metals such as Au or Pd as catalysts.5
Reasoning that alkynyloxiranes would be ideal sub-
strates for studying such dual behavior with Ag or Au species,
we already studied the transformation of acyloxylated alkyny-
loxiranes in divinyl ketones through a gold(I)-catalyzed
In the past few years, silver and more certainly gold salts and
complexes have gained increasing interest from the synthetic
organic chemist community. Acting as mild catalysts, they
offer a wide variety of new and mild conditions for known
reactions as well as new methods in organic synthesis.1,2
(1) For recent reviews on silver chemistry, see: (a) Weibel, J.-M.; Blanc,
A.; Pale, P. Chem. Rev. 2008, 108, 3149–3173. (b) Alvarez-Corral, M.;
Munoz-Dorado, M.; Rodriguez-Garcia, I. Chem. Rev. 2008, 108, 3174–
3198. (c) Yamamoto, Y. Chem. Rev. 2008, 108, 3199–3222. (d) Halbes-
Letinois, U.; Weibel, J.-M.; Pale, P. Chem. Soc. Rev. 2007, 36, 759–769.
(2) For selected recent reviews on gold chemistry, see: (a) Li, Z.;
Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239–3265. (b) Arcadi, A. Chem.
ꢀ
Rev. 2008, 108, 3266–3325. (c) Jimenez-Nunez, E.; Echavarren, A. M. Chem.
Rev. 2008, 108, 3326–3350. (d) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem.
Rev. 2008, 108, 3351–3378. (e) Hashmi, A. S. K.; Rudolph, M. Chem. Soc.
Rev. 2008, 37, 1766–1775. (f) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180–
(4) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817–7831.
(5) (a) Jin, T.; Yamamoto, Y. Org. Lett. 2008, 10, 3137–3139. (b) Jin, T.;
Yamamoto, Y. Org. Lett. 2007, 9, 5259–5262. (c) Georgy, M.; Boucard, V.;
Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 14180–14181. (d) Asao, N.;
Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,
764–765. (e) Asao, N.; Ohishi, T.; Sato, K.; Yamamoto, Y. J. Am. Chem. Soc.
2001, 123, 6931–6932. (f) Asao, N.; Asano, T.; Ohishi, T.; Yamamoto, Y. J.
Am. Chem. Soc. 2000, 122, 4817–4818.
ꢀ
ꢀ~
3211. (g) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Commun. 2007, 333–
346. (h) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45,
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€
(3) (a) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403. (b) Pyykko,
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Pitzer, K. S. Chem. Phys. Lett. 1975, 33, 408–411.
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Published on Web 07/02/2009
DOI: 10.1021/jo9008172
r
2009 American Chemical Society

Blanc et al.
JOCArticle
SCHEME 1. Gold(I)-Catalyzed Cascade Initiated by Intramo-
lecular Nucleophilic Addition
or alkoxyallenyl alcohols, which could then be cyclized
(Scheme 3, route b).
In the present contribution, we report a comparison of Ag
and Au salts or complexes as catalysts for the formation of
furans from alkynyloxiranes in the presence of alcohol. We
also provided evidence revealing that such reactions did not
proceed through the usually proposed intramolecular nu-
cleophilic addition of the oxirane oxygen atom on an inter-
mediate acetylene-metal π-complex7,9 (Scheme 3, route a)
but through a cascade of events promoted by external
hydroxy nucleophiles, including adventitious water or alco-
hol (Scheme 3, route b). These silver- and gold-catalyzed
reactions offered a very convergent and mild method for the
preparation of highly substituted furans from simple and
easily available alkynyloxiranes in the presence of methanol.
The silver- and especially the gold-catalyzed transformations
described herein clearly improved the few other known
methods (see Scheme 2). These reactions also complemented
the known late-transition-metal-catalyzed furan formations
from allene or alkyne derivatives.11-14
SCHEME 2. Late Transition-Metal-Catalyzed Formation of
Substituted Furans from Alkynyloxiranes
Results and Discussion
The role of silver or gold species in the reaction of
alkynyloxiranes with alcohols was first examined with the
readily available 1-(hex-1-ynyl)-1,2-epoxycyclohexane15
1a as starting material and methanol as external nucleo-
phile.8 Except for comparison experiments, dichloro-
methane was used as solvent, due to its low coordinative
ability, allowing us to enhance the Lewis acid character of
silver or gold ions.
rearrangement (Scheme 1).6 In the latter reaction, the acyloxy
group served as the internal nucleophile. It is noteworthy that
no trace of side reaction and especially no furan product were
observed during these reactions even if gold salts are known to
catalyze the formation of furans from alkynyloxiranes
(Scheme 2, eq 1).7 Based on this observation, we focused our
attention on the mechanism of this furan formation and we
very recently showed that silver salts were able to promote such
reaction in the presence of an external nucleophile (Scheme 2,
eq 2).8 In parallel, platinum chloride also proved to be an
efficient catalyst for this so-called rearrangement (Scheme 2,
eq 3).9 It is worth noting that such a reaction has already
been mentioned decades ago with mercury salts as catalysts
(Scheme 2, eq 4).10
Silver-Catalyzed Reaction. In this solvent at room tem-
perature and with silver triflate as catalyst, 1a was con-
verted to the corresponding furan 2a, although no external
(11) (a) Brown, R. C. D. Angew. Chem., Int. Ed. 2005, 44, 850–852. (b)
Dudnik, A. S.; Gevorgyan, V. Angew. Chem., Int. Ed. 2007, 46, 5195–5197.
(c) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395–3442.
(12) For selected references on cyclization approaches to substituted
furans catalyzed by silver, see: (a) Marshall, J. A.; Robinson, E. D. J. Org.
Chem. 1990, 55, 3450–3451. (b) Marshall, J. A.; Sehon, C. A. J. Org. Chem.
1995, 60, 5966–5968. (c) Dalla, V.; Pale, P. Tetrahedron Lett. 1996, 37, 2781–
2784. (d) Arimitsu, S.; Hammond, G. B. J. Org. Chem. 2007, 72, 8559–8567.
By palladium, see: (e) Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H.
J. Org. Chem. 1991, 56, 5816–5819. (f) Hashmi, A. S. K. Angew. Chem., Int.
Ed. 1995, 34, 1581–1583. (g) Seiller, B.; Bruneau, C.; Dixneuf, P. H.
Tetrahedron 1995, 51, 13089–13102. (h) Arcadi, A.; Cacchi, S.; Rosario,
M. D.; Fabrizi, G.; Marinelli, F. J. Org. Chem. 1996, 61, 9280–9288. (i) Ma, S.
M.; Zhang, J. L.; Lu, L. H. Chem.;Eur. J. 2003, 9, 2447–2456. By platinum,
see: (j) Nakamura, I.; Mizushima, Y.; Yamamoto, Y. J. Am. Chem. Soc.
Particularly noteworthy are the reaction conditions in this
series. The mercury and platinum versions required ethanol
and water, respectively. The role of the latter could not
be ascribed. Although not pointed out by the authors, the
Au-catalyzed version seemed efficient only when the starting
material carried a free hydroxyl group. These observa-
tions suggested a key role of water or alcohol on the rate
and efficiency of the reaction and led us to investigate
an Ag-8 and an Au-catalyzed versions in the presence of
external hydroxy nucleophiles as well as to investigate the
mechanism of these Ag and Au-catalyzed reactions. Hydroxy
nucleophiles were expected to add to alkynyloxirane through
€
2005, 127, 15022–15023. (k) Furstner, A.; Davies, P. W. J. Am. Chem. Soc.
€
2005, 127, 15024–15025. (l) Furstner, A.; Heilmann, E. K.; Davies, P. W.
Angew. Chem., Int. Ed. 2007, 46, 4760–4763. By gold, see: (m) Hashmi, A. S.
K.; Schwarz, L.; Choi, J. H.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 34,
2285–2288. (n) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004,
126, 11164–11165. (o) Yao, T.; Zhang, X.; Larock, R. C. J. Org. Chem. 2005,
70, 7679–7685.
(13) For selected references on rearrangement approaches to substituted
furans catalyzed by gold, see: (a) Suhre, M. H.; Reif, M.; Kirsch, S. F. Org.
Lett. 2005, 7, 3925–3927. (b) Zhang, J.; Schmalz, H.-G. Angew. Chem., Int.
Ed. 2006, 45, 6704–6707.
2
20
(14) For gold-catalyzed transformation of alkynyloxiranes, see: (a) Dai,
L.-Z.; Qi, M.-J.; Shi, Y.-L.; Liu, X.-G.; Shi, M. Org. Lett. 2007, 9, 3191–3194.
(b) Shu, X.-Z.; Liu, X.-Y.; Ji, K.-G.; Xiao, H.-Q.; Liang, Y.-M. Chem.;Eur.
SN or SN pathways, leading to alkynyl alkoxyalcohols
€
ꢀ
J. 2008, 14, 5282–5289. (c) Hashmi, A. S. K.; Buhrle, M.; Salathe, R.; Bats, J.
W. Adv. Synth. Catal. 2008, 350, 2059–2064. (d) Lin, G.-Y.; Li, C.-W.; Hung,
S.-H.; Liu, R.-S. Org. Lett. 2008, 10, 5059–5062. (e) Dai, L.-Z.; Shi, M.
Chem.;Eur. J. 2008, 14, 7011–7018.
(6) Cordonnier, M.-C.; Blanc, A.; Pale, P. Org. Lett. 2008, 10, 1569–1572.
(7) Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 346, 432–438.
(8) Blanc, A.; Tenbrink, K.; Weibel, J.-M.; Pale, P. J. Org. Chem. 2009,
74, 4360–4363.
(9) Yoshida, M.; Al-Amin, M.; Matsuda, K. S. Tetrahedron Lett. 2008,
49, 5021–5023.
(10) Miller, D. J. Chem. Soc. C 1969, 12–15.
(15) Compound 1a was obtained following Carlson’s procedure:
(a) Carlson, R. G.; Cox, W. W. J. Org. Chem. 1977, 42, 2382–2386. (b)
Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. Tetrahedron 1991, 47,
1677–1686.
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Blanc et al.
SCHEME 3. Possible Mechanisms of the Transition-Metal-Catalyzed Formation of Substituted Furans from Alkynyloxiranes
JOCArticle
TABLE 1. Screening of Reaction Conditions for the Silver-Catalyzed Transformation of Alkynyloxirane 1a in the Presence of Methanol
entry
catalyst (mol %)
conditionsa
time (h)
yield of 2ab (%)
3a/4ac
1
2
3
4
5
AgOTf (5)
AgOTf (5)
AgSbF6 (5)
AgNTf2 (5)
AgOTf/pTsOH (5/5)
CH2Cl2 (dry), rt
24
24
24
24
24
30
73
55
41
80
CH2Cl2/MeOH (9/1), rt
CH2Cl2/MeOH (9/1), rt
CH2Cl2/MeOH (9/1), rt
CH2Cl2/MeOH (9/1), rt,
80/20
74/26
64/36
88/12
1
a Reactions run under argon, C=0.1 mol/L. b Yields of 2a were calculated from H NMR integration relative to hexamethylbenzene as internal
standard. c Ratio of transient intermediates 3a and 4a determined by 1H NMR after 10 min (their presence could already be detected by TLC just after
catalyst addition).
SCHEME 4. Reactivity of Compound 3a and 4a in the Presence
of AgOTf
TABLE 2. Screening of Reaction Conditions for the Gold-Catalyzed
Transformation of Alkynyloxirane 1a in the Presence of Methanol
entry catalyst (mol %)
conditionsa
time (h) yieldb (%)
1
2
3
4
5
6
7
8
9
AuCl3 (5)
AuCl3 (5)
AuCl3 (5)
AuCl (5)
AuCl (5)
CH3CN (dry), rt
CH2Cl2 (dry), rt
CH2Cl2/MeOH (9/1), rt
CH2Cl2 (dry), rt
CH2Cl2/MeOH (9/1), rt
1
1
24
24
24
1
0.1
0.1
1
31c
36
10
12
11
51
90
84
70
nucleophile was a priori present. However, this reaction
proceeded in low yield and at a slow rate (Table 1, entry 1).
Control experiments revealed that adventitious water either
in the solvent or more importantly in the salt was able to
catalyze the reaction, leading to variable yields. As expected,
the same reaction performed in the presence of methanol as
nucleophile provided the furan 2a in good yield (entry 2).
Under the same conditions, silver hexafluoroantimonate as
well as silver triflimide induced the same transformation but
at a lower rate and some degradation occurred; the product
was thus only obtained in modest yields (entries 3 and 4).
Monitoring of the later reactions allowed detecting the very
fast transient formation of two intermediates, while none
of them could be seen in the control experiment without
methanol (Table 1, right column, entries 2-5 vs 1). As
expected (cf. Scheme 3), these intermediates corresponded
to 1a opening products. However, independent synthesis
and comparison with these authentic samples revealed that
these intermediates corresponded to the two possible alco-
hols 3a and 4a resulting from methanol SN2 reaction. The
major intermediate 3a corresponded to epoxide opening at
Ph3PAuOTf (5) CH2Cl2 (dry), rt
Ph3PAuOTf (5) CH2Cl2/MeOH (9/1), rt
Ph3PAuSbF6 (5) CH2Cl2/MeOH (9/1), rt
Ph3PAuNTf2 (5) CH2Cl2/MeOH (9/1), rt
a Reactions run under argon, C = 0.1 mol/L. b Yields of 2a were
calculated from 1H NMR integration relative to hexamethylbenzene as
internal standard. c Cycloisomerization conditions; see ref 7
(4 Hz) as well as its by characteristic chair coupling pattern
and especially the shift of two equatorial protons (a broad
doublet of triplet centered at 2.08 ppm and a complex broad
doublet centered at 1.85 ppm).
Interestingly, both regioisomers behave in a very different
way in the presence of silver catalyst. The alcohol resulting
from opening at the propargylic position 3a quantitatively
yielded the furan 2a, while its isomer 4a remained untouched
in separate experiments (Scheme 4). With these results in
hand and since the regioselectivity of the in situ oxirane
opening seemed to vary with the catalyst nature (entry 4 vs
3 vs 2), we tried to favor the formation of the reactive
intermediate 3a, and the best condition we found was to
3
the propargylic position, as shown by a JH-OH coupling
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JOCArticle
FIGURE 1. 1H NMR spectra of the transient intermediates 3a and 4a in gold-catalyzed formation of furan (the ppm scale was calibrated on
residual CH2Cl2 of the (h) spectrum).
add catalytic amount of p-toluenesulfonic acid together with
silver triflate. Under these conditions, a high yield of furan
was achieved (entry 5).16
With gold(I) complexes as catalysts (entries 7-9), the
reaction was much faster than with silver catalysts (5 min
vs 24 h; see Table 1 vs Table 2). No intermediate could be
detected during these fast reactions under the conditions set
up above. However, running the reaction in a NMR tube at
-60 °C in the presence of Ph3PAuNTf2 and monitoring the
evolution of the starting material 1a upon warming to room
temperature revealed again the formation of the two inter-
mediates 3a and 4a, even at low temperature (Figure 1; see
the Supporting Information for 1H NMR spectra of 3a and
4a in CD2Cl2+MeOH). Both appeared at -45 °C, but 3a
already started evolving to the furan 2a at -30 °C (lines b and
c, respectively). Upon warming, 3a gradually disappeared
and at 10 °C, only 4a was left (line g). However, and in sharp
contrast with the Ag-catalyzed version, 4a was also con-
verted to furan at 25 °C (line h).
Mechanisms. These results showed that in both Ag- and
Au(I)-catalyzed furan formation from alkynyloxiranes 1, the
same intermediates 3 and 4 resulting from oxirane opening
by methanol were produced (Scheme 5). However, in the
gold(I)-catalyzed version, both intermediates could be con-
verted to furan, although at different rates, while in the
Ag-catalyzed version, only one of the intermediates, i.e., 3,
could evolve further (see Scheme 4). Furthermore, NMR
Gold-Catalyzed Reaction. The gold species was similarly
screened in the same transformation (Table 2). Gold trichlor-
ide in acetonitrile has been mentioned as catalyst for the
cycloisomerization of some alkynyloxiranes to furans.7
However, under these conditions, the yield of 2a obtained
from 1a was low, and 1a mostly gave unidentified polymeric
materials. Replacing acetonitrile by dichloromethane did
not significantly improve the reaction yield (entry 1 vs 2).
In the presence of methanol, the reaction was surprisingly
even less effective and mostly gave degradation products
(entry 3). Similar results were obtained with gold(I) chloride
in the presence or absence of methanol (entries 4-5). In
contrast, gold(I) complexes were better catalysts (entries 6-
9), especially in the presence of methanol (entry 6 vs 7).17 The
best results were achieved with triphenylphosphinogold tri-
flate (entry 7). Less coordinating counterions proved less
effective (entries 8-9 vs 7).
(16) A control experiment showed that p-TsOH is not able to allow
cyclization of both alcohol 3a and 4a.8
(17) The reported yield (Table 2, entry 6) is dependent on the quality of
CH2Cl2 and AgOTf used.
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SCHEME 5. Mechanism of Au- or Ag-Catalyzed Furan For-
or methoxy groups adjacent to gold, and thus the Lewis acid
character of gold could facilitate the elimination of these
groups.10 With silver, only the intermediate with the alkoxy
group adjacent to the metal was formed and could also
evolve by Lewis acid promoted elimination (Scheme 5, bot-
tom part).19 Nevertheless, protonation by the catalytic
amounts of p-toluenesulfonic acid could not be excluded in
this case.
mation by Alcohol Addition-Cyclization-Elimination
It is worth noting that other hydroxy nucleophiles, such as
water or ethanol, 2-propanol, could also be used in this
cascade reaction. A slight decrease in isolated yields was
nevertheless observed with larger alcohols.
These mechanistic studies allowed us to understand the
role of water or alcohol, either added in purpose or adventi-
tiously, in the known related reactions (see Scheme 2). In the
Pt- and Hg-catalyzed reaction, water or ethanol was required
as well as high temperatures, and under these conditions, they
most probably induced oxirane opening. The formed inter-
mediates probably evolved as described above for the Ag-
and Au-catalyzed reactions. On the other hand, the AuCl3-
catalyzed reaction required substrate carrying free hydroxyl
group. This alcohol most probably acted as water, methanol,
or ethanol and induced the same cascade of events.
Scope. With these results in hands, we then explored the
scope of this silver- or gold(I)-catalyzed furan formation.
Various alkynyloxiranes were prepared by epoxidation of the
corresponding enynes with m-chloroperbenzoic acid.20 Non-
commercially available enynes were obtained by Sonogashira-
type21 coupling reaction or by Carlson’s15 procedure (see the
Supporting Information). The overall yields of this two- to
three-step sequence were routinely higher than 30%.
For comparison purposes, each alkynyloxirane was sub-
mitted both to AgOTf and p-TsOH and to Ph3PAuOTf as
catalyst in the CH2Cl2/MeOH mixture at room temperature
(Table 3).
In order to examine the role of alkyne substituents in these
rearrangements, we compared a series of epoxycyclohexanes
carrying a hexynyl, a phenylethynyl, or just an ethynyl chain
(entries 1-3). As mentioned above, 1,2-epoxy-1-hexynylcy-
clohexane 1a gave the corresponding 2-hexynyltetrahydro-
benzofuran 2a in high yields under both conditions (entry 1).
However, 1,2-epoxy-1-phenylethynylcyclohexane 1b gave
low yield of product with Ag as catalyst due to degrada-
tion but high yield with Au as catalyst (entry 2). The
simplest ethynyl derivative 1c only led to decomposition
products in the presence of AgOTf/p-TsOH, probably due
to the formation of alkynyl silver under these conditions,22
while Au catalyst gave the expected tetrahydrobenzofuran 2c
in high yield (entry 3).
monitoring (Figure 1, lines b, c) suggested that Au(I) was
able to promote oxirane opening at both positions leading to
almost equivalent amount of intermediates 3 and 4, while
Ag was mostly responsible for opening at the propargylic
position of 1 (Table 1). These observations are in full
agreement with the higher Lewis acidity of gold compared
to silver and clearly exemplified this Lewis acid character.3,4
Such oxirane-opening is also consistent with the recent view
of gold as cationic intermediates promoter.18
In sharp contrast with silver, gold(I) was also clearly able
to promote the cyclization of both intermediates, but for one
of them, i.e., the homopropargylic alcohol 3, the reaction was
fast and even proceeded at low temperature, while it was slow
and only proceeded at room temperature for the other
regioisomer 4. Such behavior differences could be rationa-
lized by the demetalation step (Scheme 5, bottom part). For
3, deauration could easily be achieved by proton loss, while
for 4, a methyl group must be removed, probably through
nucleophilic displacement by either the water released upon
elimination or excess of methanol (Scheme 5, left side). The
latter process was clearly less easy than the former, account-
ing for the different evolution observed by NMR. Similar
reasons could also contribute to the lack of reactivity of 4 in
the presence of Ag, reinforcing its lower Lewis acid character
(Scheme 5, right side).
The size of the ring joined to the epoxide was also
examined, expecting that with a strained system the cascade
reaction would be easier. Surprisingly, the five-membered
derivative 1d mostly gave degradation products with both
One of the late steps of this cascade, i.e., elimination, could
be assisted by electrophilic interaction with silver or gold.
With gold, both intermediates exhibited either the hydroxy
(19) Hayes, S. J.; Knight, D. W.; Menzies, M. D.; O’Halloran, M.; Tan,
W.-F. Tetrahedron Lett. 2007, 48, 7709–7712.
(20) For a review of alkynyloxirane preparations, see: Chemla, F.;
Ferreira, F. Curr. Org. Chem. 2002, 6, 539–570.
(21) (a) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442–1443; (b)
For a review of enyne preparations, see: Halbes-Letinois, U.; Pale, P. In
Leading Edge Organometallic Chemistry Research; Cato, M. A., Ed.; Nova
Publishers: New York, 2006; pp 93-131.
€
(18) (a) Seidel, G.; Mynott, R.; Furstner, A. Angew. Chem., Int. Ed. 2009,
48, 2510–2513. (b) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2008, 47, 6754–
€
6756. (c) Furstner, A.; Morency, L. Angew. Chem., Int. Ed. 2008, 47, 5030–
ꢀ
5033. (d) Santos, L. L.; Ruiz, V. R.; Sabater, M. J.; Corma, A. Tetrahedron
2008, 64, 7902–7909.
(22) Halbes-Letinois, U.; Pale, P.; Berger, S. J. Org. Chem. 2005, 70,
9185–9190.
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TABLE 3. Scope of Silver(I) or Gold(I)Catalyzed Furan Formations
a Method A: AgOTf/pTsOH (5 mol%); b Method B: Ph3PAuOTf (5 mol%); c Isolated yields; d Yields calculated by 1H NMR of the crude mixture;
e Degradation occurred giving unidentified polymeric materials; f Reaction run at 0 °C.
catalysts, and only the gold-catalyzed reaction allowed us to
detect some of the expected furan (entry 4). The seven
membered derivative 1e gave the same results under both
conditions, but the furan formation was slightly less effective
than with the six-membered epoxyalkyne 1a (entry 5 vs 1).
The reverse trend was observed with the eight membered
derivative 1f, which gave the corresponding furan in excel-
lent yield with both catalysts (entry 6 vs 1).
Although they could compete as nucleophiles, free alco-
hols without protecting group were tolerated in these
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JOCArticle
Ag- and Au-catalyzed reactions (entry 7). As expected from
our mechanistic studies, the Au-catalyzed version was so
efficient that the reaction was best performed at 0 °C.
Protection as ester or silyl ether proved nevertheless more
efficient, the corresponding furans being isolated with higher
yields (entries 8-9 vs 7). In these cases, the Ag catalyst was
slightly more effective than the Au catalyst. The latter results
contrasted with all other examples, for which gold catalysis
proved to be milder than silver catalysis and gave better
yields (column B vs A). This was clearly evidenced with the
reaction of 1b-d but also with the reaction of the benzyl
protected epoxyalkyne 1j, since in this case, the Ag catalyst
led to decomposition while the Au catalyst allowed to isolate
the expected furan in high yields (entry 10). The latter
example showed that benzyl ether as protecting group was
also well tolerated. The mildness and high efficiency of the
Au-catalyzed rearrangement was highlighted with the reac-
tion of a diepoxydiyne 1k which could be cyclized twice
under the Au catalysis conditions but not at all under the
Ag catalysis conditions (entry 11).
were removed in vacuo, and the crude residue was purified by
flash chromatography.
Method B (Gold Catalysis). Alkynyloxirane (1 mmol in 1 mL
of CH2Cl2) was added to a stirred solution of premixed
Ph3PAuCl (0.05 mmol) and AgOTf (0.05 mmol) in CH2Cl2/
MeOH (5 mL, 9/1 v/v) at 0 °C or room temperature. The
reaction was monitored by thin-layer chromatography until
completion. The reaction mixture was filtered throughout
a pad of silica gel with CH2Cl2. Solvents were removed in
vacuo, and the crude residue was purified by flash chromatog-
raphy.
2-Butyl-4,5,6,7-tetrahydrobenzofuran (2a). Following method
B, alkynyloxirane 1a (200 mg, 1.12 mmol) gave 2a (170 mg,
85%) as a colorless oil: Rf = 0.64 (cyclohexane/EtOAc 20%);
IR (neat) νmax 2935, 2870, 1738, 1674, 1520, 1446, 1379, 1220,
1165, 1120, 1095, 982 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.94
(t, J = 7.3 Hz, 3 H), 1.39 (sext, 7.4 Hz, 2 H), 1.58 (quint, J =
5.7 Hz, 2 H), 1.66-1.75 (m, 2 H), 1.78-1.85 (m, 2 H), 2.37-2.40
(m, 2 H), 2.54-2.60 (m, 4 H), 5.79 (s, 1 H); 13C NMR (75 MHz,
CDCl3) δ 13.8, 22.1, 22.3, 23.1, 23.2, 23.3, 27.8, 30.4, 105.4,
117.1, 148.6, 154.2; MS (ESI) m/z 357 (100, 2M•++2H), 179 (95,
M•++H); HR-MS 179.1438 (C12H18O+H calcd 179.1430).
Following method A, alkynyloxirane 1a (100 mg, 0.56 mmol)
gave 2a (80 mg, 80%).
Conclusion
2-(Benzyloxymethyl)-3-methyl-5-propylfuran (2j). Following
method B, alkynyloxirane 1j (75 mg, 0.3 mmol) gave 2j (60 mg,
80%) as a colorless oil: Rf = 0.58 (cyclohexane/EtOAc 5%); IR
(neat) νmax 2963, 2932, 3874, 1725, 1682, 1496, 1453, 1377, 1314,
In conclusion, we have found that alkynyloxiranes iso-
merized to highly substituted furans in a cascade reac-
tion promoted by alcohols and catalyzed by Ag or Au
catalysts. Mechanistic investigations revealed that such
reactions proceed through a cascade of events: epoxide
opening by the added alcohol, cyclization of the intermedi-
ates and elimination of alcohol. These observations also
highlighted the dual role of silver or gold species in organic
reactions.
1
1270, 1176, 1095, 1069, 1026, 934 cm-1; H NMR (300 MHz,
C6D6) δ 0.82 (t, J = 7.4 Hz, 3 H), 1.55 (sext, 7.5 Hz, 2 H), 1.85 (s,
3 H), 2.43 (t, J = 7.8 Hz, 2 H), 4.36 (s, 2 H), 4.41 (s, 2 H), 5.72 (s,
1 H), 7.05-7.16 (m, 3 H), 7.30 (d, J = 6.7 Hz, 2 H); 13C NMR
(75 MHz, C6D6) δ 9.9, 13.8, 21.6, 30.3, 62.2, 71.5, 108.7, 119.7,
127.5, 127.8, 128.4, 139.2, 146.3, 155.6; MS (ESI) m/z 283 (100,
M•++K), 267 (43, M•++Na); HR-MS 283.1068 (C16H20O2+
K calcd 283.1095).
Experimental Section
Acknowledgment. We gratefully acknowledge the CNRS
and the French Ministry of Research for financial support.
General Procedure for Silver(I)- or Gold(I)-Catalyzed Forma-
tion of Furans from Alkynyloxiranes. Method A (Silver Cataly-
sis). To a solution of alkynyloxirane (1 mmol) in CH2Cl2/
MeOH (5 mL, 9/1 v/v) were added successively p-toluenesul-
fonic acid (APTS, 0.05 mmol) and AgOTf (0.05 mmol) at
room temperature. The reaction was monitored by thin-layer
chromatography until completion. The reaction mixture was
filtered throughout a pad of silica gel with CH2Cl2. Solvents
€
K.T. thanks the Friedrich-Alexander-Universitat Erlagen-
Nurnberg and ULP for their exchange program and support.
€
Supporting Information Available: Experimental proce-
dures and copies of 1H and 13C spectra for all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
5348 J. Org. Chem. Vol. 74, No. 15, 2009