A novel propargylation/cycloisomerization tandem process catalyzed by a ruthenium(II)/trifluoroacetic acid system: One-pot entry to fully substituted furans from readily available secondary propargylic alcohols and 1,3-dicarbonyl compounds

Article abstract of DOI:10.1002/adsc.200600366

A simple and highly efficient method for the preparation of tetrasubstituted furans starting from readily accessible propargylic alcohols and commercially available 1,3-dicarbonyl compounds has been developed. The process, which proceeds in a one-pot mann

Full text of DOI:10.1002/adsc.200600366

FULL PAPERS
DOI: 10.1002/adsc.200600366
A Novel Propargylation/Cycloisomerization Tandem Process Cat-
alyzed by a Ruthenium(II)/Trifluoroacetic Acid System: One-Pot
Entry to Fully Substituted Furans from Readily Available Secon-
dary Propargylic Alcohols and 1,3-Dicarbonyl Compounds
Victorio Cadierno,a,* JosØ Gimeno,a,* and Noel Nebraa
a
Departamento de Química Orgµnica e Inorgµnica, Instituto Universitario de Química Organometµlica “Enrique Moles”
(Unidad Asociada al CSIC), Facultad de Química, Universidad de Oviedo, E-33071 Oviedo, Spain
Fax : +(34)-985-103-446; e-mail: vcm@uniovi.es or jgh@uniovi.es
Received: July 19, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A simple and highly efficient method for of the resulting g-ketoalkyne catalyzed by the 16-
the preparation of tetrasubstituted furans starting electron allyl-ruthenium(II) complex [Ru(h3-2-
from readily accessible propargylic alcohols and C3H4Me)(CO)
commercially available 1,3-dicarbonyl compounds
ACHRTUNEG(dppf)]ACHTRE[UGN SbF6].
has been developed. The process, which proceeds in
a one-pot manner, involves the initial propargylation Keywords: cycloisomerization; 1,3-dicarbonyl com-
of the 1,3-dicarbonyl compound promoted by tri- pounds; furans; propargylic alcohols; propargylic
fluoroacetic acid, and subsequent cycloisomerization substitution reactions; ruthenium
Introduction
ic alcohols A into enals B (Meyer–Schuster-type rear-
rangement)[4] which further undergo aldol-type con-
In the course of our current studies directed to the densations with enolizable ketones or 1,3-dicarbonyl
application of ruthenium complexes as catalysts in or- compounds (see Scheme 1).[5]
ganic synthesis,[1,2] we have recently reported the
While extending these initial studies to the coupling
preparation, in excellent yields and with total E-ste- of secondary alkynols with 1,3-dicarbonyl compounds
reoselectivity,[3] of conjugated dienones C and diene- we have now discovered that the corresponding dien-
diones D via a tandem process involving the catalytic ones D are not formed, the reactions giving instead
isomerization of diaryl-substituted terminal propargyl- keto- or ester-functionalized furans E which are gen-
Scheme 1. Catalytic transformations of diaryl-substituted propargylic alcohols promoted by complex 1.
382
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
Scheme 2. Synthesis of furans from propargylic alcohols and 1,3-dicarbonyl compounds.
ꢀ
erated through an unexpected C C coupling process ed propargylic substitution of the secondary alkynol
(Scheme 2).[6]
by the 1,3-dicarbonyl compound, and (ii) subsequent
The furan ring represents a key structural subunit ruthenium-catalyzed cyclosiomerization of the result-
in many natural and pharmaceutically important sub- ing g-ketoalkyne.
stances, being also found in the molecular skeleton of
several flavor and fragrance compounds.[7] Further-
more, substituted furans are useful and versatile inter- Results and Discussion
mediates in synthetic organic chemistry.[7] As a conse-
quence, much attention has been paid to the synthesis Access to Fully Substituted Furans from Secondary
of furan derivatives in the last decades, the most inno- Propargylic Alcohols and 1,3-Dicarbonyl
vative and efficient strategies involving transition Compounds: Optimization of the Reaction
metal-catalyzed heteroannulation reactions of suitable Conditions and Scope
acyclic precursors such as (Z)-enynols, a-epoxyal-
kynes, b-ketoalkynes or a-ketoallenes, among Following the optimal experimental conditions to pro-
others.[8] Nevertheless, by following these cycloisome- mote the catalytic C C coupling of diaryl-substituted
ꢀ
rization-based methodologies, the construction of propargylic alcohols A with 1,3-dicarbonyl com-
furan rings with the desired substitution pattern is pounds (Scheme 1) using the 16eꢀ Ru(II) complex
sometimes a problematic task due to the difficult [Ru(h3-2-C3H4Me)(CO)
A
[SbF6]
(1)
{i.e.,
access to the corresponding functionalized starting [A]:[1,3-dicarbonyl]:ACHTREUNG
materials.[8] Thereby, the development of novel syn- 758C; sealed tube; without solvent},[3] we have found
thetic routes allowing the facile assembly of polysub- that the secondary terminal propargylic alcohol 1-(1-
stituted furans from readily available and inexpensive naphthyl)-2-propyn-1-ol (2a) reacts with 2,4-pentane-
precursors still remains an important objective for dione to afford, after 8 h, a mixture containing the ex-
synthetic organic chemists. Herein, a novel and highly pected diene-dione 3a (ca. 10% yield; GC deter-
efficient catalytic method for the preparation of fully mined) and 2,5-dimethyl-3-acetyl-4-(1-naphthyl)furan
substituted furans, in which easily accessible secon- (4a; ca. 65% yield; GC determined) along with minor
dary propargylic alcohols and commercially available amounts of other uncharacterized by-products (see
1,3-dicarbonyl compounds are used as starting materi- Scheme 3).[9] The tetrasubtituted furan 4a formally re-
als, is reported. The process outlined in Scheme 2, sults from an intermolecular condensation between
which proceeds in a one-pot manner, involves two dif- the propargylic alcohol 2a and the 1,3-diketone
ferent steps based on: (i) an initial CF3CO2H-promot- through an unprecedented cycloaddition reaction.[10,11]
Scheme 3. The reaction of alkynol 2a with 2,4-pentanedione catalyzed by 1/CF3CO2H.
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
383

Victorio Cadierno et al.
FULL PAPERS
Table 1. Synthesis of furans 4–10a from alkynol 2a and 1,3-dicarbonyl compounds.[a]
Entry
1
1,3-Dicarbonyl
Product
Time
Yield[b]
81%
4a
5a
6a
7a
8a
9a
10a
4 h
3 h
3 h
3 h
4 h
2 h
22 h
2
3
4
5
6
76%
79%
92%
93%
91%
62%
7
[a]
Reactions performed under N2 atmosphere at 758C using 1 mmol of 2a and 10 mmol of the corresponding 1,3-dicarbonyl
compound. [2a]:[1,3-dicarbonyl]:CATHRE[UNG CF3CO2H]:[Ru] ratio=20:200:10:1.
Isolated yield.
[b]
By increasing the quantity of trifluoroacetic acid in chromatographic work-up (entry 1 in Table 1), was
the reaction media, both the selectivity and the rate readily assigned by its MS, IR and NMR spectroscop-
of this cyclocondensation process could be easily im- ic data (see the Experimental Section).
proved. Thus, when 50 mol% of CF3CO2H was used,
i.e., [2a]:[2,4-pentanedione]:[CF3CO2H]:[1] ratio= ied by using other 1,3-dicarbonyl compounds (see
20:200:10:1, furan 4a was formed in >92% yield (GC Table 1). Thus, under the optimized reaction condi-
determined) after 4 h, the presence of 3a being in this tions {[2a]:[1,3-dicarbonyl]:[CF3CO2H]:[1] ratio=
The generality of this transformation has been stud-
AHCTREUNG
AHCTREUNG
case not detected by GC. This result indicates that 20:200:10:1}, other 1,3-diketones, such as 3,5-heptane-
the ability of complex 1 to perform the Meyer–Schus- dione (entry 2) or 1,3-cyclohexanedione (entry 3), as
ter isomerization of alkynols is completely inhibited well as a variety of b-keto esters (entries 4–7) also re-
under these reaction conditions.[4] The identity of acted with alkynol 2a to afford the corresponding
furan 4a, isolated in pure form in 81% yield after furans 5–10a (62–93% isolated yields) regardless the
384
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
Scheme 4. Synthesis of the trisubstituted furan 13a.
presence of aliphatic (entries 1–5) or aromatic (en- tuted alkynols, independent of the substitution pat-
tries 6 and 7) substituents. Remarkably, when b-keto tern and electronic properties of the aromatic ring.
esters are used as substrates (entries 4–7) the reac- Thus, as shown in Table 2, terminal propargylic alco-
tions proceed in all cases in a regioselective manner hols 2b–g readily and cleanly react with 2,4-pentane-
since only the keto group participates in the cycliza- dione or ethyl acetoacetate to afford in good yields
tion process, the ester function behaving as a simple (66–94%), after only 2–5 h, the tetrasubstituted
spectator. It should be also noted that, although the furans 4b–g (odd entries) and 8b–g (even entries), re-
starting propargylic alcohol 2a is completely con- spectively. In contrast, starting from alkyl-monosubsti-
sumed, no furan formation was observed in the reac- tuted alkynols such as 1-octyn-3-ol or 3-butyn-2-ol,
tion 2a with dimethyl malonate [CH2ACHTREU(NG CO2Me)], the mixtures containing the expected tetrasubstituted
precipitation of a highly insoluble material being in furans, albeit in very low yields (15–28% yield; GC
this case observed. This result suggests that the pres- determined), are obtained. The major formation of
ence of at least one keto function is indispensable to several uncharacterized by-products prevented the
promote this coupling process. The characterization isolation of the furans.
of compounds 5–10a was achieved by means of stan-
Interestingly, internal aryl-monosubstituted alky-
1
dard spectroscopic techniques (MS, IR as well as H nols can also participate in this cycloaddition process.
and 13C{1H} NMR) and, in the case of solid samples, Nevertheless, the furan ring formation requires in
by elemental analyses, all data being fully consistent these cases longer reaction times. As an example,
with the proposed formulations (see the Experimental treatment of 1-phenyl-3-butyn-1-ol (2h) with ethyl
Section).
acetoacetate in the presence of CF3CO2H/1 generates
The high-yield formation of furans 4–10a demon- the tetrasubstituted furan 15h in only a moderate
strates the wide scope of this cycloaddition process. yield (43%) after 72 h at 758C (see Scheme 5). Re-
Nevertheless, it should be noted that a disappointing markably, the GC/MS monitoring of this reaction
result was encountered in the reaction of 2a with the showed after 3 h the almost quantitative formation of
b-keto ester tert-butyl acetoacetate. Thus, under the an intermediate species which could be isolated in
standard reaction conditions, the trisubstituted furan 93% yield after chromatographic work-up. Spectro-
13a, instead of the expected tetrasubstituted one 11a, scopic IR, MS and NMR (1H and 13C{1H}) data al-
is obtained (79% yield after 8 h; see Scheme 4). Ap- lowed the identification of this intermediate as the g-
parently, furan 11a is initially formed[12] but the hy- ketoalkyne 14h (details are given in the Experimental
drolysis of the tert-butyl ester (Boc) function (proba- Section), resulting from a formal propargylic substitu-
bly mediated by CF3CO2H)[13] leads to carboxylic acid tion process of the alkynol 2h by the b-keto ester.
ꢀ
12a which undergoes a ruthenium-catalyzed decarbox- Since this C C coupling process involves the forma-
ylation to give 13a.[14,15] Although in both individual tion of two stereogenic centers, compound 14h is
steps well-known reactions are involved, the overall formed as a ca. 1.2:1 mixture of two non-separable
11a!13a transformation can be considered as rather diastereoisomers. Under the standard reaction condi-
unusual.[16]
tions, both isomers slowly and cleanly evolve into the
We have also found that this cyclization reaction final furan 15h without detection of any other inter-
can be successfully applied to other aryl-monosubsti- mediate species.
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
385

Victorio Cadierno et al.
Table 2. Synthesis of furans 4b–g and 8b–g from propargylic alcohols 2b–g and 1,3-dicarbonyl compounds.[a]
FULL PAPERS
Entry
Alkynol
Product
Time
Yield[b]
1
2
R2 =Me 4b
R2 =OEt 8b
4 h
3 h
80%
87%
2b
2c
3
4
R2 =Me 4c
R2 =OEt 8c
5 h
4 h
83%
86%
5
6
R2 =Me 4d
R2 =OEt 8d
5 h
4 h
66%
80%
2d
2e
7
8
R2 =Me 4e
R2 =OEt 8e
5 h
4 h
86%
94%
9
10
R2 =Me 4f
R2 =OEt 8f
5 h
5 h
73%
85%
2f
2g
11
12
R2 =Me 4g
R2 =OEt 8g
3 h
2 h
90%
94%
[a]
Reactions performed under N2 atmosphere at 758C using 1 mmol of the corresponding propargylic alcohol 2 and
10 mmol of the appropriate 1,3-dicarbonyl compound. [2]:[1,3-dicarbonyl]:ACHTREU[GN CF3CO2H]:[Ru] ratio=20:200:10:1.
Isolated yield.
[b]
Scheme 5. Coupling of the internal propargylic alcohol 2h with ethyl acetoacetate.
386
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
Mechanistic Proposal for the Cycloaddition Reaction
of Propargylic Alcohols with 1,3-Dicarbonyl
Compounds
ably, in the absence of ruthenium, g-ketoalkynes 16a,
b are stable and do not evolve into the final furans
7a,b even when heated at 758C for 24 h in the pres-
ence of CF3CO2H (50 mol%), the formation of 7a,b
It is well-established that a series of transition-metal being only observed when complex 1 was added to
complexes are able to catalyze substitution reactions the reaction media. This fact strongly suggests that
of alkynols.[17] In particular, allenylidene-rutheni- the generation of the furan ring is the result of a
um(II) species formed from terminal alkynol sub- ruthenium-catalyzed cycloisomerization of the inter-
strates are prone to catalyze propargylic substitutions mediate g-ketoalkyne. As far as we are aware, this is
using a wide variety of carbon- and heteroatom-cen- the first ruthenium-catalyzed cycloisomerization of g-
tered nucleophiles.[17a] The results shown in Scheme 5, ketoalkynes to afford furans reported to date.[21,22]
along with a recent report showing the catalytic activi-
In accordance with these particular features, a
ty of Brønsted acids when internal propargylic alco- mechanistic proposal accounting for the catalytic cy-
hols are used,[18] raises the question whether complex cloisomerization of g-ketoalkynes A into furans E is
1 is the actual catalytic species of the initial propargy- shown in Scheme 7. We assume that the initial step in-
lation process.[19] To this regard, the reactivity of alky- volves the activation of the C C triple bond of the
ꢁ
nols 2a,b towards methyl acetoacetate using only alkyne, via coordination to the metal, to give the p-
CF3CO2H (50 mol%) in the absence of complex 1 alkyne ruthenium intermediate B. Subsequent intra-
was studied (Scheme 6). The reaction affords the cor- molecular nucleophilic attack of the enolic form of
responding g-ketoalkynes 16a and 16b which are se- the keto group at the C2 position of the coordinated
lectively formed after 1.5 or 4 h, respectively.[20] Chro- alkyne (endo addition) generates the alkenyl-rutheni-
matographic work-up allowed the isolation (81–90%) um derivative C, which after protonolysis liberates
and spectroscopic characterization of these function- the heterocycle D regenerating the catalytically active
alized alkynes (see the Experimental Section), which ruthenium species. Final acid-promoted aromatization
are generated in both cases as a non-separable mix- of the five-membered ring of D leads to the tetrasub-
ture of two diastereoisomers in ca. 1:1 ratio. Remark- stituted furan E. We note that, although it is well-
Scheme 6. Formation and cycloisomerization of g-ketoalkynes 16a,b.
Scheme 7. Reaction pathway for the Ru-catalyzed cycloisomerization reaction.
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
387

Victorio Cadierno et al.
ACRTHUEN(G dppf)]ACHTRENUG
plex [Ru(h3-2-C3H4Me)(CO) [SbF6] (1),[4a] the termi-
FULL PAPERS
known that terminal p-alkyne ruthenium complexes
nal propargylic alcohols 2a, b, d–g[25] and the internal one
2h[26] which were prepared by following the methods report-
ed in the literature. Infrared spectra were recorded on a
Perkin–Elmer 1720-XFT spectrometer. Elemental C and H
analyses were carried out with a Perkin–Elmer 2400 micro-
analyzer. NMR spectra were recorded on a Bruker DPX-
300 instrument at 300 MHz (1H), or 75.4 MHz (13C) or a
Bruker AC-400 instrument at 400.1 MHz (1H), or
100.6 MHz (13C). Chemical shifts are referred to the residual
peak of the deuterated solvent used (CDCl3). DEPT experi-
ments have been carried out for all the compounds report-
ed. Gas chromatographic (GC) measurements were made
on a Hewlett–Packard HP6890 equipment using a HP-IN-
NOWAX cross-linked polyethyleneglycol (30 m, 250 mm) or
a Supelco Beta-DexTM 120 (30 m, 250 mm) column. GC/MS
measurements were performed on a Agilent 6890N equip-
ment coupled to a 5973 mass detector (70 eV electron
impact ionization) using a HP-1MS column. High-resolution
mass spectra were recorded on a Finnigan-Mat 95 spectrom-
eter.
2
ꢁ
[LnRu
A
merize into h1-vinylidene species [LnRu
A
C(H)R}],[23] such an isomerization reaction seems to
be completely inhibited when terminal alkynols 2a–g
are used as substrates since cyclization of the corre-
sponding intermediates should give rise to the forma-
tion of six-membered pyranic rings (exo addition).[10]
Conclusions
In this work a novel and highly efficient catalytic ap-
proach of tetrasubstituted furans has been developed
using as starting materials readily accessible secon-
dary aryl-substituted propargylic alcohols and an
excess (10 equivalents) of commercially available 1,3-
dicarbonyl compounds. The process, which takes
place in a one-pot manner and under solvent-free con-
ditions (the 1,3-dicarbonyl compound itself acts as sol-
vent), is shown to proceed through two different steps
involving: (i) an initial CF3CO2H-promoted propar-
gylic substitution of the secondary alkynol by the 1,3-
dicarbonyl compound, leading to an intermediate g-
ketoalkyne, and (ii) a subsequent ruthenium-catalyzed
cycloisomerization reaction to give the final tetrasub-
General Procedure for the Synthesis of Furans 4–13
Complex [Ru(h3-2-C3H4Me)(CO)
ACHTERNGU(dppf)]ACHRTE[UGN SbF6] (1) (0.049 g,
0.05 mmol), the corresponding propargylic alcohol 2a–g
(1 mmol), the appropriate 1,3-dicarbonyl compound
(10 mmol) and CF3CO2H (37 mL, 0.5 mmol) were introduced
stituted furans.[24] This unprecedented cyclization re- into a sealed tube under nitrogen atmosphere. The reaction
mixture was then heated at 758C for the indicated time (see
Table 1, Table 2 and Scheme 4; the course of the reaction
was monitored by regular sampling and analysis by GC or
GC/MS). After removal of volatiles under vacuum, the resi-
due was purified by column chromatography (silica gel)
using a mixture EtOAc/hexane (1:50) as eluent.
action is quite general being applicable both to termi-
nal and internal monosubstituted alkynols, as well as
to a variety of b-dicarbonyl compounds.
At present, the most innovative and efficient syn-
thetic approaches of substituted furans involve transi-
tion metal-catalyzed heteroannulation reactions of
acyclic precursors such as (Z)-enynols, a-epoxyal-
kynes, b-ketoalkynes or a-ketoallenes, among
others.[8] Nevertheless, a major drawback of these
The following furans obtained in this paper are known
compounds: 2,5-dimethyl-3-acetyl-4-phenylfuran (4c),[27] 2,5-
dimethyl-3-acetyl-4-(4-methoxyphenyl)furan (4e),[28] 2,5-di-
methyl-3-acetyl-4-(2-methoxyphenyl)furan (4g)[29] and 2,5-di-
methodologies is the difficult access of suitable pre- methyl-4-phenylfuran-3-carboxylic acid ethyl ester (8c).[29]
Analytical and spectroscopic data for the new compounds
are as follows:
cursors containing preloaded functional groups at the
desired positions. The methodology herein described,
which allows the introduction of carbonyl functionali-
ties in the furanic skeleton, represents a very competi-
tive and more desirable synthetic approach since it
stems from readily available and inexpensive precur-
sors.
2,5-Dimethyl-3-acetyl-4-(1-naphthyl)furan (4a): Colourless
oil; yield: 0.214 g (81%); IR (Nujol): n=1564 (s, C=C),
1668 cmꢀ1 (s, C=O); 1H NMR (CDCl3): d=1.65 (s, 3H,
COCH3), 2.09 and 2.68 (s, 3H each, CH3), 7.41–7.58 (m, 4H,
C10H7), 7.72 (m, 1H, C10H7), 7.90–7.94 (m, 2H, C10H7);
13C{1H} NMR (CDCl3): d=11.6 and 14.5 (s, CH3), 29.8 (s,
COCH3), 118.4 and 123.5 (s, =C), 125.4, 125.5, 126.0, 126.5,
128.2, 128.3 and 128.4 (s, CH of C10H7), 131.4, 133.0 and
In summary, selectivity, time/cost saving and experi-
mental simplicity, concepts to be assembled by
modern academic and industrial synthetic chemists to 133.6 (s, C of C10H7), 147.7 and 157.0 (s, =C-O), 195.8 (s, C=
O); MS (EI 70 eV): m/z=264 (100%) [M+], 249 (92%)
reach the maximum of efficiency, are clearly repre-
[M+ꢀMe], 221 (12%) [M+ꢀCOMe], 178 (22%)
sented in this one-pot catalytic transformation making
[C10H7CCCO], 152 (10%) [C10H7CC]; HR-MS: m/z=
it appealing for a wide range of synthetic organic
264.11418, calcd. for C18H16O2: 264.11448.
chemists.
2,5-Dimethyl-3-acetyl-4-(2-naphthyl)furan (4b): Yellow
solid; yield: 0.211 g (80%); IR (Nujol): n=1564 and 1597
1
(m, C=C), 1681 cmꢀ1 (s, C=O); H NMR (CDCl3): d=1.96
Experimental Section
(s, 3H, COCH3), 2.22 and 2.60 (s, 3H each, CH3), 7.37 (d,
J=8.5 Hz, 1H, C10H7), 7.51 (m, 2H, C10H7), 7.74 (br, 1H,
All reagents were obtained from commercial suppliers and
used without further purification with the exception of com-
C10H7), 7.84–7.90 (m, 3H, C10H7); 13C{1H} NMR (CDCl3):
d=11.6 and 14.3 (s, CH3), 30.8 (s, COCH3), 120.8 and 123.1
388
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
(s, =C), 126.1, 126.3, 127.7, 127.8, 128.0, (2 C) and 128.4 (s,
CH of C10H7), 131.2, 132.5 and 133.3 (s, C of C10H7), 147.3
and 156.3 (s, =C-O), 196.1 (s, C=O); MS (EI 70 eV): m/z=
264 (100%) [M+], 249 (87%) [M+ꢀMe], 221 (17%)
[M+ꢀCOMe], 193 (7%) [M+ꢀ2MeꢀCOMe], 178 (30%)
[C10H7CCCO], 152 (10%) [C10H7CC]; anal. calcd. for
C18H16O2: C 81.79, H 6.10%; found: C 82.13, H 6.25%.
233
(7%)
[M+ꢀMeꢀ2CH2],
205
(30%)
[M+ꢀCH2CH2CH2CO], 152 (7%) [C10H7CC]; HR-MS:
m/z=276.11445, calcd. for C19H16O2: 276.11448.
2,5-Dimethyl-4-(1-naphthyl)furan-3-carboxylic
methyl ester (7a): White solid; yield: 0.258 g (92%); IR
(Nujol): n=1593 (s, C=C), 1720 cmꢀ1 (s, C=O); 1H NMR
(CDCl3): d=2.13 and 2.71 (s, 3H each, CH3), 3.42 (s, 3H,
OCH3), 7.37–7.56 (m, 4H, C10H7), 7.71 (d, J=8.2 Hz, 1H,
acid
2,5-Dimethyl-3-acetyl-4-(4-chlorophenyl)furan
(4d):
Yellow oil; yield: 0.164 g (66%); IR (Nujol): n=1568 (s, C= C10H7), 7.87–7.93 (m, 2H, C10H7); 13C{1H} NMR (CDCl3):
1
C), 1674 cmꢀ1 (s, C=O); H NMR (CDCl3): d=2.00 (s, 3H,
COCH3), 2.17 and 2.55 (s, 3H each, CH3), 7.20 and 7.40 (m,
2H each, C6H4Cl); 13C{1H} NMR (CDCl3): d=11.5 and 14.3
(s, CH3), 30.7 (s, COCH3), 119.7 and 122.8 (s, =C), 128.6 and
131.1 (s, CH of C6H4Cl), 132.2 and 133.3 (s, C of C6H4Cl),
147.1 and 156.3 (s, =C-O), 195.4 (s, C=O); MS (EI 70 eV):
m/z=248 (85%) [M+], 233 (100%) [M+ꢀMe], 213 (1%)
d=11.7 and 14.1 (s, CH3), 50.8 (s, OCH3), 114.6 and 119.1 (s,
=C), 125.1, 125.5, 125.7, 125.8, 127.7 (2C) and 128.1 (s, CH
of C10H7), 131.2, 132.9 and 133.4 (s, C of C10H7), 148.0 and
157.7 (s, =C-O), 164.6 (s, C=O); MS (EI 70 eV): m/z=280
(100%) [M+], 265 (1%) [M+ꢀMe], 248 (46%) [M+ꢀOMe],
233 (9%) [M+ꢀMeꢀOMe], 220 (25%) [M+ꢀCO2Me], 205
(29%) [M+ꢀMeꢀCO2Me], 191 (7%) [M+ꢀ2MeꢀCO2Me],
178 (22%) [C10H7CCCO], 152 (7%) [C10H7CC]; anal. calcd.
for C18H16O3: C 77.12, H 5.75%; found: C 76.99, H 5.83%.
[M+ꢀCl],
205
(20%)
[M+ꢀCOMe],
191
(2%)
[M+ꢀMeꢀCOMe], 177 (5%) [M+ꢀ2MeꢀCOMe], 162
(8%) [C6H4ClCCCO], 141 (5%) [M+ꢀ2MeꢀCOMeꢀCl];
HR-MS: m/z=248.05943, calcd. for C14H13O2Cl: 248.05985.
2,5-Dimethyl-4-(2-naphthyl)furan-3-carboxylic
acid
methyl ester (7b): Reaction time: 4 h; yellow oil; yield:
0.246 g (88%); IR (Nujol): n=1584 and 1597 (m, C=C),
2,5-Dimethyl-3-acetyl-4-(3-methoxyphenyl)furan
(4f):
1
Colourless oil; yield: 0.178 g (73%); IR (Nujol): n=1575
1717 cmꢀ1 (s, C=O); H NMR (CDCl3): d=2.29 and 2.65 (s,
1
and 1598 (m, C=C), 1674 cmꢀ1 (s, C=O); H NMR (CDCl3):
3H each, CH3), 3.67 (s, 3H, OCH3), 7.42–7.53 (m, 3H,
C10H7), 7.73 (br, 1H, C10H7), 7.86–7.91 (m, 3H, C10H7);
13C{1H} NMR (CDCl3): d=11.8 and 14.1 (s, CH3), 50.9 (s,
OCH3), 113.3 and 121.3 (s, =C), 125.7, 125.8, 126.9, 127.6,
127.8, 128.2 and 128.6 (s, CH of C10H7), 130.8, 132.3 and
133.1 (s, C of C10H7), 147.5 and 157.7 (s, =C-O), 164.7 (s, C=
O); MS (EI 70 eV): m/z=280 (100%) [M+], 265 (2%)
d=1.95 (s, 3H, COCH3), 2.16 and 2.51 (s, 3H each, CH3),
3.81 (s, 3H, OCH3), 6.77–6.89 (m, 3H, C6H4OMe), 7.31 (m,
1H, C6H4OMe); 13C{1H} NMR (CDCl3): d=11.6 and 14.2 (s,
CH3), 30.6 (s, COCH3), 55.2 (s, OCH3), 112.7, 115.6, 122.4
and 129.5 (s, CH of C6H4OMe), 120.7 and 123.0 (s, =C),
135.1 (s, C of C6H4OMe), 147.0, 156.1 and 159.5 (s, =C-O
and C of C6H4OMe), 196.2 (s, C=O); MS (EI 70 eV): m/z=
244 (95%) [M+], 229 (100%) [M+ꢀMe], 201 (20%)
[M+ꢀCOMe], 187 (7%) [M+ꢀMeꢀCOMe], 171 (10%)
[M+ꢀ2MeꢀCOMe], 159 (12%) [C6H4OMeCCCO]; HR-
MS: m/z=244.10911, calcd. for C15H16O3: 244.10939.
[M+ꢀMe],
248
(51%)
[M+ꢀOMe],
233
(5%)
[M+ꢀMeꢀOMe], 220 (22%) [M+ꢀCO2Me], 205 (20%)
[M+ꢀMeꢀCO2Me], 191 (5%) [M+ꢀ2MeꢀCO2Me], 178
(26%) [C10H7CCCO], 152 (10%) [C10H7CC]; HR-MS:
m/z=280.10956, calcd. for C18H16O3: 280.10939.
2-Ethyl-3-ethylcarbonyl-5-methyl-4-(1-naphthyl)furan
2,5-Dimethyl-4-(1-naphthyl)furan-3-carboxylic acid ethyl
ester (8a): Yellow oil; yield: 0.274 g (93%); IR (Nujol): n=
(5a): Colourless oil; yield: 0.222 g (76%); IR (Nujol): n=
1
1
1557 (s, C=C), 1673 cmꢀ1 (s, C=O); H NMR (CDCl3): d=
1595 (s, C=C), 1708 cmꢀ1 (s, C=O); H NMR (CDCl3): d=
0.72 (t, J=7.3 Hz, 3H, COCH2CH3), 1.38 (t, J=7.6 Hz, 3H,
CH2CH3), 1.79 and 2.01 (m, 1H each, CH2CH3), 2.09 (s, 3H,
CH3), 3.09 (m, 2H, COCH2CH3), 7.41–7.58 (m, 4H, C10H7),
7.72 (m, 1H, C10H7), 7.90–7.95 (m, 2H, C10H7); 13C{1H}
NMR (CDCl3): d=7.7, 11.7 and 12.3 (s, CH3), 21.8 (s, CH2),
34.8 (s, COCH2), 118.0 and 122.5 (s, =C), 125.4, 125.6, 126.0,
126.5, 128.1, 128.2 and 128.3 (s, CH of C10H7), 131.6, 132.9
and 133.6 (s, C of C10H7), 147.7 and 161.5 (s, =C-O), 199.0 (s,
C=O); MS (EI 70 eV): m/z=292 (60%) [M+], 277 (2%)
[M+ꢀMe], 263 (100%) [M+ꢀEt], 248 (22%) [M+ꢀMeꢀEt],
233 (2%) [M+ꢀ2Et], 219 (7%) [M+ꢀMeꢀCOEt], 205
(10%) [M+ꢀEtꢀCOEt], 190 (9%) [M+ꢀMeꢀEtꢀCOEt],
179 (5%) [C10H7CCCO], 152 (2%) [C10H7CC]; HR-MS:
m/z=292.14574, calcd. for C20H20O2: 292.14578.
0.57 (t, J=7.1 Hz, 3H, CH2CH3), 2.17 and 2.73 (s, 3H each,
CH3), 3.85 (m, 2H, CH2CH3), 7.37–7.56 (m, 4H, C10H7), 7.73
(m, 1H, C10H7), 7.87–7.93 (m, 2H, C10H7); 13C{1H} NMR
(CDCl3): d=11.7, 13.1 and 13.9 (s, CH3), 59.3 (s, CH2), 114.9
and 119.1 (s, =C), 125.1, 125.5, 125.6, 126.0, 127.6 (2C) and
128.0 (s, CH of C10H7), 131.6, 133.2 and 133.4 (s, C of
C10H7), 147.8 and 157.7 (s, =C-O), 164.2 (s, C=O); MS (EI
70 eV): m/z=294 (100%) [M+], 279 (1%) [M+ꢀMe], 265
(17%) [M+ꢀEt], 248 (47%) [M+ꢀOEt], 233 (7%)
[M+ꢀMeꢀOEt], 220 (20%) [M+ꢀCO2Et], 205 (20%)
[M+ꢀMeꢀCO2Et], 191 (7%) [M+ꢀ2MeꢀCO2Et], 178
(22%) [C10H7CCCO], 152 (10%) [C10H7CC]; HR-MS:
m/z=294.12509, calcd. for C19H18O3: 294.12504.
2,5-Dimethyl-4-(2-naphthyl)furan-3-carboxylic acid ethyl
ester (8b): Yellow oil; yield: 0.256 g (87%); IR (Nujol): n=
1582 and 1601 (m, C=C), 1710 cmꢀ1 (s, C=O); 1H NMR
(CDCl3): d=1.09 (t, J=7.1 Hz, 3H, CH2CH3), 2.29 and 2.66
(s, 3H each, CH3), 4.15 (q, J=7.1 Hz, 2H, CH2CH3), 7.44–
7.55 (m, 3H, C10H7), 7.74 (br, 1H, C10H7), 7.86–7.91 (m, 3H,
C10H7); 13C{1H} NMR (CDCl3): d=11.8, 13.9 and 14.1 (s,
2-Methyl-3-(1-naphthyl)-6,7-dihydro-5H-benzofuran-4-one
(6a): Colourless oil; yield: 0.218 g (79%); IR (Nujol): n=
1
1577 (s, C=C), 1681 cmꢀ1 (s, C=O); H NMR (CDCl3): d=
2.20 (s, 3H, CH3), 2.25, 2.53 and 2.99 (m, 2H each, CH2),
7.43–7.58 (m, 4H, C10H7), 7.71 (d, J=7.9 Hz, 1H, C10H7),
7.91–7.95 (m, 2H, C10H7); 13C{1H} NMR (CDCl3): d=11.8
(s, CH3), 22.5, 23.6 and 38.1 (s, CH2), 116.7 and 121.3 (s, = CH3), 59.8 (s, CH2), 113.6 and 121.3 (s, =C), 125.7, 125.8,
C), 125.2, 125.6, 125.8, 125.9, 128.0, 128.1 and 128.3 (s, CH
of C10H7), 129.6, 132.4 and 133.6 (s, C of C10H7), 150.0 and
166.4 (s, =C-O), 194.8 (s, C=O); MS (EI 70 eV): m/z=276
(100%) [M+], 261 (5%) [M+ꢀMe], 248 (36%) [M+ꢀ2CH2],
126.8, 127.6, 127.8, 128.3 and 128.8 (s, CH of C10H7), 130.9,
132.3 and 133.1 (s, C of C10H7), 147.4 and 157.6 (s, =C-O),
164.3 (s, C=O); MS (EI 70 eV): m/z=294 (100%) [M+], 279
(2%) [M+ꢀMe], 265 (25%) [M+ꢀEt], 248 (58%)
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
389

Victorio Cadierno et al.
FULL PAPERS
[M+ꢀOEt], 233 (5%) [M+ꢀMeꢀOEt], 220 (15%)
[M+ꢀCO2Et], 205 (15%) [M+ꢀMeꢀCO2Et], 191 (5%)
[M+ꢀ2MeꢀCO2Et], 178 (25%) [C10H7CCCO], 152 (10%)
[C10H7CC]; HR-MS: m/z=294.12498, calcd. for C19H18O3:
294.12504.
C6H4OMe), 147.2, 156.6 and 157.4 (s, =C-O and C of
C6H4OMe), 164.6 (s, C=O); MS (EI 70 eV): m/z=274
(80%) [M+], 259 (1%) [M+ꢀMe], 245 (5%) [M+ꢀEt], 228
(17%) [M+ꢀMeꢀOMe], 213 (100%) [M+ꢀEtꢀOMe], 201
(15%) [M+ꢀCO2Et], 185 (34%) [M+ꢀMeꢀCO2Et], 172
(10%) [M+ꢀ2MeꢀCO2Et]; HR-MS: m/z=274.11969, calcd.
for C16H18O4: 274.11996.
2,5-Dimethyl-4-(4-chlorophenyl)furan-3-carboxylic
acid
ethyl ester (8d): Yellow oil; yield: 0.223 g (80%); IR
(Nujol): n=1584 and 1599 (m, C=C), 1712 cmꢀ1 (s, C=O);
1H NMR (CDCl3): d=1.16 (t, J=7.3 Hz, 3H, CH2CH3), 2.20
and 2.60 (s, 3H each, CH3), 4.16 (q, J=7.3 Hz, 2H,
CH2CH3), 7.21 and 7.36 (m, 2H each, C6H4Cl); 13C{1H}
NMR (CDCl3): d=11.6, 13.9 and 14.0 (s, CH3), 59.8 (s,
CH2), 113.2 and 120.3 (s, =C), 127.8 and 131.3 (s, CH of
C6H4Cl), 131.7 and 132.7 (s, C of C6H4Cl), 147.2 and 157.6
(s, =C-O), 164.1 (s, C=O); MS (EI 70 eV): m/z=278
(100%) [M+], 263 (1%) [M+ꢀMe], 249 (95%) [M+ꢀEt],
233 (37%) [M+ꢀOEt], 214 (2%) [M+ꢀEtꢀCl], 204 (7%)
[M+ꢀCO2Et], 189 (5%) [M+ꢀMeꢀCO2Et], 162 (8%)
[C6H4ClCCCO], 141 (5%) [M+ꢀ2MeꢀCO2EtꢀCl]; HR-
MS: m/z=278.07052, calcd. for C15H15O3Cl: 278.07042.
2,5-Dimethyl-4-(4-methoxyphenyl)furan-3-carboxylic acid
ethyl ester (8e): Yellow solid; yield: 0.258 g (94%); IR
(Nujol): n=1584 and 1606 (m, C=C), 1709 cmꢀ1 (s, C=O);
1H NMR (CDCl3): d=1.17 (t, J=7.1 Hz, 3H, CH2CH3), 2.21
and 2.60 (s, 3H each, CH3), 3.85 (s, 3H, OCH3), 4.17 (q, J=
7.1 Hz, 2H, CH2CH3), 6.94 and 7.21 (m, 2H each,
C6H4OMe); 13C{1H} NMR (CDCl3): d=11.6, 14.0 and 14.1
(s, CH3), 55.1 (s, OCH3), 59.6 (s, CH2), 113.0 and 131.1 (s,
CH of C6H4OMe), 113.5 and 120.9 (s, =C), 125.4 (s, C of
C6H4OMe), 146.9, 157.2 and 158.5 (s, =C-O and C of
C6H4OMe), 164.3 (s, C=O); MS (EI 70 eV): m/z=274
(100%) [M+], 259 (1%) [M+ꢀMe], 245 (34%) [M+ꢀEt],
227 (41%) [M+ꢀMeꢀOMe], 213 (2%) [M+ꢀEtꢀOMe],
200 (12%) [M+ꢀCO2Et], 185 (7%) [M+ꢀMeꢀCO2Et], 172
(3%) [M+ꢀ2MeꢀCO2Et], 159 (10%) [C6H4OMeCCCO];
anal. calcd. for C16H18O4: C 70.06, H 6.61%; found: C 69.88,
H 6.69%.
2,5-Dimethyl-4-(3-methoxyphenyl)furan-3-carboxylic acid
ethyl ester (8f): Yellow oil; yield: 0.233 g (85%); IR
(Nujol): n=1589 and 1602 (m, C=C), 1711 cmꢀ1 (s, C=O);
1H NMR (CDCl3): d=1.11 (t, J=7.0 Hz, 3H, CH2CH3), 2.20
and 2.57 (s, 3H each, CH3), 3.81 (s, 3H, OCH3), 4.12 (q, J=
7.0 Hz, 2H, CH2CH3), 6.79–6.86 (m, 3H, C6H4OMe), 7.26
(m, 1H, C6H4OMe); 13C{1H} NMR (CDCl3): d=11.8, 13.9
and 14.0 (s, CH3), 55.2 (s, OCH3), 59.8 (s, CH2), 112.2, 115.8,
122.6 and 128.5 (s, CH of C6H4OMe), 113.5 and 121.2 (s, =
C), 134.6 (s, C of C6H4OMe), 147.1, 157.4 and 158.9 (s, =C-
O and C of C6H4OMe), 164.3 (s, C=O); MS (EI 70 eV): m/
z=274 (78%) [M+], 245 (25%) [M+ꢀEt], 228 (100%)
[M+ꢀMeꢀOMe], 213 (5%) [M+ꢀEtꢀOMe], 200 (32%)
[M+ꢀCO2Et], 185 (24%) [M+ꢀMeꢀCO2Et]; HR-MS:
m/z=274.11982, calcd. for C16H18O4: 274.11996.
2,5-Dimethyl-4-(1-naphthyl)furan-3-carboxylic acid benzyl
ester (9a): Yellow solid; yield: 0.324 g (91%); IR (Nujol):
1
n=1586 (s, C=C), 1713 cmꢀ1 (s, C=O); H NMR (CDCl3):
d=2.15 and 2.75 (s, 3H each, CH3), 4.90 (m, 2H, CH2), 6.59
(d, J=7.6 Hz, 2H, Ph), 7.09–7.22 (m, 3H, Ph), 7.36–7.52 (m,
4H, C10H7), 7.73 (d, J=8.2 Hz, 1H, C10H7), 7.86–7.93 (m,
2H, C10H7); 13C{1H} NMR (CDCl3): d=11.7 and 14.1 (s,
CH3), 65.5 (s, CH2), 114.7 and 118.9 (s, =C), 125.2, 125.6,
125.8 (2C), 127.3, 127.4, 127.6, 127.7, 128.0 and 128.1 (s, CH
of C10H7 and Ph), 131.4, 133.1, 133.5 and 135.5 (s, C of C10H7
and Ph), 148.0 and 158.3 (s, =C-O), 164.1 (s, C=O); MS (EI
70 eV): m/z=356 (100%) [M+], 265 (83%) [M+ꢀBn], 249
(51%) [M+ꢀOBn], 234 (8%) [M+ꢀMeꢀOBn], 219 (17%)
[M+ꢀCO2Bn], 178 (18%) [C10H7CCCO], 152 (5%)
[C10H7CC]; anal. calcd. for C24H20O3: C 80.88, H 5.66%;
found: C 80.71, H 5.45%.
5-Methyl-4-(1-naphthyl)-2-phenylfuran-3-carboxylic acid
ethyl ester (10a): Yellow solid; yield: 0.221 g (62%); IR
(Nujol): n=1582 and 1592 (m, C=C), 1716 cmꢀ1 (s, C=O);
1H NMR (CDCl3): d=0.47 (t, J=7.1 Hz, 3H, CH2CH3), 2.28
(s, 3H, CH3), 3.80 (q, J=7.1 Hz, 2H, CH2CH3), 7.44–7.59
(m, 7H, C10H7 and Ph), 7.81–8.04 (m, 5H, C10H7 and Ph);
13C{1H} NMR (CDCl3): d=12.0 and 12.8 (s, CH3), 60.0 (s,
CH2), 116.0 and 121.0 (s, =C), 125.2, 125.6, 125.8, 125.9,
127.6, 127.7, 127.9, 128.2 (2C) and 128.9 (s, CH of Ph and
C10H7), 130.0, 131.2, 133.0 and 133.4 (s, C of Ph and C10H7),
149.2 and 155.0 (s, =C-O), 164.1 (s, C=O); MS (EI 70 eV):
m/z=356 (100%) [M+], 328 (5%) [M+ꢀEt], 309 (20%)
[M+ꢀOEt], 295 (2%) [M+ꢀMeꢀOEt], 282 (10%)
[M+ꢀCO2Et], 268 (4%) [M+ꢀMeꢀCO2Et], 252 (7%)
[M+ꢀPhꢀEt], 239 (20%) [C10H7CCCPh], 205 (3%)
[M+ꢀPhꢀCO2Et], 176 (3%) [C10H7CCCC]; anal. calcd. for
C24H20O3: C 80.88, H 5.66%; found: C 80.59, H 5.72%.
2,5-Dimethyl-4-(1-naphthyl)furan (13a): Colourless oil;
yield: 0.176 g (79%); IR (Nujol): n=1592 cmꢀ1 (s, C=C);
1H NMR (CDCl3): d=2.25 and 2.40 (s, 3H each, CH3), 6.15
(s, 1H, =CH), 7.38–7.55 (m, 4H, C10H7), 7.83–8.01 (m, 3H,
C10H7); 13C{1H} NMR (CDCl3): d=12.3 and 13.5 (s, CH3),
109.3 (s, =CH), 120.0 (s, =C), 125.4, 125.6, 125.7, 126.1, 127.2
(2C) and 128.2 (s, CH of C10H7), 132.2, 132.4 and 133.7 (s, C
of C10H7), 147.0 and 149.4 (s, =C-O); MS (EI 70 eV): m/z=
222 (100%) [M+], 207 (9%) [M+ꢀMe], 192 (5%)
[M+ꢀ2Me], 179 (64%) [C10H7CCCO], 165 (12%)
[C10H7CCC], 152 (15%) [C10H7CC]; HR-MS: m/z=
222.10392, calcd. for C16H14O: 222.10391.
2,5-Dimethyl-4-(2-methoxyphenyl)furan-3-carboxylic acid
ethyl ester (8g): Yellow oil; yield: 0.258 g (94%); IR
(Nujol): n=1579 and 1602 (m, C=C), cmꢀ1 1712 (s, C=O);
1H NMR (CDCl3): d=1.04 (t, J=7.0 Hz, 3H, CH2CH3), 2.18
and 2.56 (s, 3H each, CH3), 3.76 (s, 3H, OCH3), 4.07 (q, J=
7.0 Hz, 2H, CH2CH3), 6.89–6.99 (m, 2H, C6H4OMe), 7.15
(m, 1H, C6H4OMe), 7.30 (m, 1H, C6H4OMe); 13C{1H} NMR
(CDCl3): d=11.8, 13.8 and 13.9 (s, CH3), 55.3 (s, OCH3),
59.5 (s, CH2), 110.3, 120.1, 128.5 and 131.1 (s, CH of
Synthesis of 2-Acetyl-3-phenylhex-4-ynoic Acid Ethyl
Ester (14h)
Complex [Ru(h3-2-C3H4Me)(CO)
ACHTERNGU(dppf)]ACHRTE[UGN SbF6] (1) (0.049 g,
0.05 mmol), 1-phenyl-2-butyn-1-ol (2h) (0.146 g, 1 mmol),
ethyl acetoacetate (1.32 mL, 10 mmol) and CF3CO2H
(37 mL, 0.5 mmol) were introduced into a sealed tube under
a nitrogen atmosphere. The reaction mixture was then
heated at 758C for 3 h. After removal of volatiles under
C6H4OMe), 114.5, 117.3 and 122.5 (s, =C and
C of
390
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
vacuum, the residue was purified by column chromatogra-
phy (silica gel) using a mixture EtOAc/hexane (1:10) as
eluent. The resulting g-ketoalkyne 14h was isolated as a
mixture of two diastereoisomers in ca. 1.2:1 ratio; yellow
oil; yield: 0.240 g (93%); IR (Nujol): n=1723 and 1749 (s,
1H NMR (CDCl3): d=2.00 and 2.45 (s, 3H each, CH3), 2.36
and 2.37 (d, J=2.6 Hz, 1H each, C CH), 3.42 and 3.83 (s,
ꢁ
ꢁ
3H each, OCH3), 4.40 (d, J=9.7 Hz, 2H, CHCHC CH),
5.25 (m, 2H, CHC CH), 7.43–7.65 (m, 8H, C10H7), 7.80–
ꢁ
7.91 (m, 4H, C10H7), 8.27–8.30 (m, 2H, C10H7); 13C{1H}
C=O), 2237 cmꢀ1 (w, C C); MS (EI 70 eV): m/z=258 (1%)
NMR (CDCl3): d=30.1 and 30.4 (s, CH3), 33.2 and 33.4 (s,
ꢁ
[M+], 229 (3%) [M+ꢀEt], 215 (50%) [M+ꢀCOMe], 185
(100%) [M+ꢀCO2Et], 170 (50%) [M+ꢀMeꢀCO2Et], 142
(20%) [M+ꢀCOMeꢀCO2Et], 129 (80%) [PhCHCCMe];
HR-MS: m/z=258.12555, calcd. for C16H18O3: 258.12504.
NMR data for the major diastereoisomer: 1H NMR
(CDCl3): d=1.01 (t, J=7.1 Hz, 3H, CH2CH3), 1.79 (d, J=
CHC CH), 52.5 and 52.7 (s, OCH3), 64.2 and 64.3 (s,
ꢁ
ꢁ
ꢁ
ꢁ
CHCHC CH), 72.4 and 72.8 (s, C CH), 82.8 (2C) (s, C
CH), 123.2, 123.3, 125.3 (2C), 125.8, 125.9, 126.1, 126.4,
126.6 (2C), 128.6, 128.7, 129.0 and 129.1 (s, CH of C10H7),
130.4, 130.6, 133.1, 133.2 and 134.1 (2C) (s, C of C10H7),
167.2 and 167.8 [s, C(=O)OMe], 200.1 and 200.6 [s, C(=
O)Me]; MS (EI 70 eV): m/z=280 (5%) [M+], 262 (5%)
[M+ꢀMeꢀ2H], 248 (2%) [M+ꢀOMe], 237 (9%)
[M+ꢀCOMe], 221 (41%) [M+ꢀCO2Me], 205 (30%)
[M+ꢀMeꢀCO2Me], 178 (17%) [M+ꢀCOMeꢀCO2Me], 165
(100%) [C10H7CHCCH], 152 (9%) [C10H7CHC]; HR-MS:
m/z=280.10932, calcd. for C18H16O3: 280.10939.
ꢁ
2.5 Hz, 3H, C CCH3), 2.38 (s, 3H, COCH3), 3.87 (d, J=
10.7 Hz, 1H, CHCHC CCH3), 3.94 (q, J=7.1 Hz, 2H,
ꢁ
ꢁ
CH2), 4.35 (m, 1H, CHC CCH3), 7.20–7.35 (m, 5H, Ph);
13C{1H} NMR (CDCl3): d=3.5 (s, C CCH3), 13.7 (s,
ꢁ
ꢁ
CH2CH3), 29.5 (s, COCH3), 37.4 (s, CHC CCH3), 61.4 (s,
ꢁ
ꢁ
CH2), 66.9 (s, CHCHC CCH3), 77.7 and 80.3 (s, C C),
127.4, 128.0 and 128.4 (s, CH of Ph), 138.8 (s, C of Ph),
166.9 [s, C(=O)OEt], 201.1 [s, C(=O)Me].
2-Acetyl-3-(2-naphthyl)pent-4-ynoic acid methyl ester
(16b): Yellow oil; yield: 0.227 g (81%); IR (Nujol): n=1720
NMR data for the minor diastereoisomer: 1H NMR
(CDCl3): d=1.30 (t, J=7.1 Hz, 3H, CH2CH3), 1.80 (d, J=
and 1749 (s, C=O), 2118 (w, C C), 3286 cm (m, C-H);
ꢀ1
ꢁ
ꢁ
1H NMR (CDCl3): d=1.97 and 2.42 (s, 3H each, CH3), 2.36
ꢁ
ꢁ
2.6 Hz, 3H, C CCH3), 1.95 (s, 3H, COCH3), 3.95 (d, J=
(d, J=2.7 Hz, 1H, C CH), 2.37 (d, J=2.5 Hz, 1H, CꢁCH),
ꢁ
10.0 Hz, 1H, CHCHC CCH3), 4.25 (q, J=7.1 Hz, 2H,
3.48 and 3.81 (s, 3H each, OCH3), 4.09 (d, J=10.8 Hz, 1H,
ꢁ
ꢁ
ꢁ
CH2), 4.35 (m, 1H, CHC CCH3), 7.20–7.35 (m, 5H, Ph);
CHCHC CH), 4.15 (d, J=10.4 Hz, 1H, CHCHC CH), 4.63
13C{1H} NMR (CDCl3): d=3.5 (s, CꢁCCH3), 14.0 (s,
(m, 2H, CHC CH), 7.47–7.53 (m, 6H, C10H7), 7.81–7.84 (m,
ꢁ
8H, C10H7); 13C{1H} NMR (CDCl3): d=29.7 and 30.4 (s,
ꢁ
CH2CH3), 30.5 (s, COCH3), 37.3 (s, CHC CCH3), 61.6 (s,
ꢁ
ꢁ
ꢁ
CH2), 66.5 (s, CHCHC CCH3), 78.0 and 79.6 (s, C C),
127.4, 128.1 and 128.6 (s, CH of Ph), 138.8 (s, C of Ph),
167.2 [s, C(=O)OEt], 200.6 [s, C(=O)Me].
CH3), 36.7 (2C) (s, CHC CH), 52.2 and 52.5 (s, OCH3), 65.5
ꢁ
ꢁ
and 65.9 (s, CHCHC CH), 72.0 and 72.7 (s, C CH), 82.4
ꢁ
and 82.7 (s, C CH), 125.4 (2C), 125.8, 125.9, 126.0, 126.1,
126.9, 127.1, 127.3 (2C), 127.5, 127.6, 128.2 and 128.3 (s, CH
of C10H7), 132.4, 132.5, 132.9, 133.0, 134.5 and 134.6 (s, C of
C10H7), 166.7 and 167.1 [s, C(=O)OMe], 199.7 and 200.0 [s,
C(=O)Me]; MS (EI 70 eV): m/z=280 (5%) [M+], 262
(26%) [M+ꢀMeꢀ2H], 248 (2%) [M+ꢀOMe], 237 (68%)
[M+ꢀCOMe], 221 (90%) [M+ꢀCO2Me], 205 (46%)
[M+ꢀMeꢀCO2Me], 178 (29%) [M+ꢀCOMeꢀCO2Me], 165
(100%) [C10H7CHCCH], 152 (10%) [C10H7CHC]; HR-MS:
m/z=280.10950, calcd. for C18H16O3: 280.10939.
Synthesis of 5-Ethyl-2-methyl-4-phenylfuran-3-
carboxylic Acid Ethyl Ester (15h)[30]
Complex [Ru(h3-2-C3H4Me)(CO)
ACHTERNGU(dppf)]ACHRTE[UGN SbF6] (1) (0.049 g,
0.05 mmol), 1-phenyl-2-butyn-1-ol (2h) (0.146 g, 1 mmol),
ethyl acetoacetate (1.32 mL, 10 mmol) and CF3CO2H
(37 mL, 0.5 mmol) were introduced into a sealed tube under
a nitrogen atmosphere. The reaction mixture was then
heated at 758C for 72 h (the reaction was monitored by reg-
ular sampling and analysis by GC or GC/MS). After remov-
al of volatiles under vacuum, the residue was purified by
column chromatography (silica gel) using a mixture EtOAc/
hexane (1:50) as eluent. The resulting furan 15h was isolated
as a yellow oil; yield: 0.111 g (43%).
Supporting Information Available
Copies of the 13C{1H} NMR spectra of all compounds syn-
thesized in this work.
Acknowledgements
General Procedure for the Synthesis of g-Ketoalkynes
16
We are indebted to the Ministerio de Ciencia y Tecnología
(MCyT) of Spain (Project BQU2003–00255) and the Gobier-
no del Principado de Asturias (FICYT Project IB05–035) for
financial support. V.C. thanks the MCyT and the European
Social Fund for the award of a “Ramón y Cajal” contract.
The corresponding propargylic alcohol 2a–b (0.182 g,
1 mmol), methyl acetoacetate (1.08 mL, 10 mmol) and
CF3CO2H (37 mL, 0.5 mmol) were introduced into a sealed
tube under nitrogen atmosphere. The reaction mixture was
then heated at 758C for 1.5 h (16a) or 4 h (16b) (the course
of the reaction was monitored by regular sampling and anal-
ysis by GC or GC/MS). After removal of volatiles under References
vacuum, the residue was purified by column chromatogra-
phy (silica gel) using a mixture EtOAc/hexane (1:10) as
eluent.
2-Acetyl-3-(1-naphthyl)pent-4-ynoic acid methyl ester
[1] Isomerization of allylic alcohols into carbonyl com-
pounds: a) V. Cadierno, S. E. García-Garrido, J.
Gimeno, Chem. Commun. 2004, 232–233; b) V. Cadier-
no, P. Crochet, S. E. García-Garrido, J. Gimeno, Dalton
Trans. 2004, 3635–3641; c) P. Crochet, J. Díez, M. A.
(16a): Yellow oil; yield: 0.252 g (90%); IR (Nujol): n=1719
ꢀ1
ꢁ
ꢁ
and 1750 (s, C=O), 2117 (w, C C), 3290 cm (m, C-H);
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
391

Victorio Cadierno et al.
FULL PAPERS
Fernµndez-Zfflmel, J. Gimeno, Adv. Synth. Catal. 2006,
348, 93–100; d) V. Cadierno, S. E. García-Garrido, J.
Gimeno, A. Varela-lvarez, J. A. Sordo, J. Am. Chem.
Soc. 2006, 128, 1360–1370; deprotection of N-allylic
amines: e) V. Cadierno, S. E. García-Garrido, J.
Gimeno, N. Nebra, Chem. Commun. 2005, 4086–4088;
cyclosiomerization of (Z)-enynols into furans: f) A. E.
Díaz-lvarez, P. Crochet, M. Zablocka, C. Duhayon, V.
Cadierno, J. Gimeno, J. P. Majoral, Adv. Synth. Catal.
2006, 348, 1671–1679.
try II, (Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriv-
en), Pergamon Press, Oxford, 1996, vol. 2, pp. 259–295;
c) H. Heaney, J. S. Ahn, in: Comprehensive Heterocy-
clic Chemistry II, (Eds.: A. R. Katritzky, C. W. Rees,
E. F. V. Scriven), Pergamon Press, Oxford, 1996, vol. 2,
pp. 297–350; d) W. Friedrichsen, in: Comprehensive
Heterocyclic Chemistry II, (Eds.: A. R. Katritzky, C. W.
Rees, E. F. V. Scriven), Pergamon Press, Oxford, 1996,
vol. 2, pp. 351–393; e) B. A. Keay, P. W. Dibble, in:
Comprehensive Heterocyclic Chemistry II, (Eds.: A. R.
Katritzky, C. W. Rees, E. F. V. Scriven), Pergamon
Press, Oxford, 1996, vol. 2, pp. 395–436; f) X. L. Hou,
Z. Yang, H. N. C. Wong, in: Progress in Heterocyclic
Chemistry, (Eds.: C. W. Gribble, T. L. Gilchrist), Perga-
mon Press, Oxford, 2003, vol. 15, pp. 167–205.
[2] For reviews and books covering the burgeoning role of
ruthenium catalysts in organic synthesis see: a) C. Bru-
neau, P. H. Dixneuf, Chem. Commun. 1997, 507–512;
b) T. Naota, H. Takaya, S.-I. Murahashi, Chem. Rev.
1998, 98, 2599–2660; c) B. M. Trost, F. D. Toste, A. B.
Pinkerton, Chem. Rev. 2001, 101, 2067–2096; d) T. M.
Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18–29;
e) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002,
102, 1731–1769; f) Ruthenium in Organic Synthesis
(Ed.: S.-I. Murahashi), Wiley-VCH, Weinheim, 2004;
g) Ruthenium Catalysts and Fine Chemistry, (Eds.: C.
Bruneau, P. H. Dixneuf), Springer, Berlin, 2004;
h) B. M. Trost, M. U. Fredericksen, M. T. Rudd, Angew.
Chem. Int. Ed. 2005, 44, 6630–6666; i) C. Bruneau,
P. H. Dixneuf, Angew. Chem. Int. Ed. 2006, 45, 2176–
2203; j) Ruthenium Catalyzed Processes, (Guest Ed.: J.
Gimeno), in: Curr. Org. Chem. 2006, 10, 113–225 (a
thematic issue devoted to this topic).
[8] For recent reviews on the synthesis of furans see:
a) X. L. Hou, H. Y. Cheung, T. Y. Hon, P. L. Kwan,
T. H. Lo, S. Y. Tong, H. N. C. Wong, Tetrahedron 1998,
54, 1955–2020; b) B. A. Keay, Chem. Soc., Rev. 1999,
28, 209–215; c) A. Jeevanandam, A. Ghule, Y.-C. Ling,
Curr. Org. Chem. 2002, 6, 841–864; d) R. C. D. Brown,
Angew. Chem. Int. Ed. 2005, 44, 850–852; e) S. F.
Kirsch, Org. Biomol. Chem. 2006, 4, 2076–2080.
[9] Attempts to isolate diene-dione 3a in pure form from
this crude reaction mixture failed, being characterized
only by MS (EI 70 eV): m/z=264 (100%) [M+], 249
(12%) [M+ꢀMe], 234 (10%) [M+ꢀ2Me], 221 (50%)
[M+ꢀCOMe], 205 (40%) [M+ꢀMeꢀCOMe], 178
[3] V. Cadierno, J. Díez, S. E. García-Garrido, J. Gimeno,
N. Nebra, Adv. Synth. Catal. 2006, 348, 2125–2132.
[4] The 16eꢀ (h3-allyl)-ruthenium(II)complex [Ru(h3-2-
(60%) [M+ꢀ2COMe], 165 (34%) [M+ꢀC
ACHTREUNG
152
(15%)
[M+ꢀCHC
ACHTREU(NG COMe)2],
[M+ꢀCHCHC
ACHTREUNG
C3H4Me)(CO)
G
G
ACHTRECUNG (COMe)2].
phosphino)ferrocene], associated with CF3CO2H, is a
highly efficient catalyst for the isomerization of diaryl-
substituted terminal propargylic alcohols A into enals
B (Meyer–Schuster-type rearrangement): a) V. Cadier-
no, J. Díez, S. E. García-Garrido, J. Gimeno, Chem.
Commun. 2004, 2716–2717; b) V. Cadierno, S. E.
García-Garrido, J. Gimeno, Adv. Synth. Catal. 2006,
348, 101–110.
[10] A closely related cycloaddition reaction of terminal
secondary alkynols and cyclic 1,3-dicarbonyl com-
pounds to give 4,6,7,8-tetrahydrochromen-5-ones or
4H-cyclopenta[b]pyran-5-ones, catalyzed by the thio-
late-bridged dirutheniumACHTERNGU(III)complexes [Cp*RuClACHTREUNG
(m2-
SR)2RuCp*Cl] (R=Me, n-Pr, i-Pr) (5 mol%) in the
presence of NH4BF4 (10 mol%), has been recently re-
ported: Y. Nishibayashi, M. Yoshikawa, Y. Inada, M.
Hidai, S. Uemura, J. Org. Chem. 2004, 69, 3408–3412.
[11] Formation of tri- and tetrasubstituted furans from sec-
ondary propargylic alcohols and enolizable ketones, in
[5] We note that the dinuclear Ru
XMe)2RuCp*(OH2)][OTf]2 (X=S, Se, Te) are also able
(m2-
ACHRTEUG(N III) species [Cp*RuACHTREUGN
A
ACHTREUNG
ꢀ
to catalyze related C C coupling reactions between
propargylic alcohols and acetone: G. Onodera, H. Mat-
sumoto, Y. Nishibayashi, S. Uemura, Organometallics
2005, 24, 5799–5801.
the presence of catalytic amounts of [Cp*RuClACHTREUNG
(m2-
SMe)2RuCp*Cl] (10 mol%), NH4BF4 (20 mol%) and
PtCl2 (20 mol%), has been reported. This process in-
volves also the initial formation of a g-ketoalkyne, via
Ru-catalyzed propargylic substitution of the alkynol
with the ketone, which undergoes a Pt-catalyzed Mar-
kovnikov hydration of the alkyne moiety to give a 1,4-
diketone. Subsequent cyclization of this diketone, also
catalyzed by Pt, generates the final furans. We note
that (i) no 1,3-dicarbonyl compounds were used as sub-
strates in this catalytic reaction, and (ii) the process is
ꢁ
[6] We note that, although monosubstituted alkynols HC
CC(OH)HR (R=aryl group) also undergo the Meyer–
Schuster isomerization into enals in the presence of
complex 1 (see ref.[4]), attempts to promote its one-pot
coupling with acetone resulted in the formation of the
corresponding (EE)-dienones RCH=CHCH=C(H)C(=
O)Me (C) in remarkably low yields (see ref.[3]). The
monitoring of these reactions by GC showed, in addi-
tion to the complete consumption of the starting prop-
argylic alcohol, that some uncharacterized by-products
are also formed pointing out the existence of competi-
tive processes in solution involving probably furan ring
formation.
ꢁ
only operative with terminal alkynols HC CC(OH)-
HAr (Ar=aryl group): Y. Nishibayashi, M. Yoshikawa,
Y. Inada, M. D. Milton, M. Hidai, S. Uemura, Angew.
Chem. Int. Ed. 2003, 42, 2681–2684.
[12] Formation of the intermediate tetrasubstituted furan
11a was confirmed by monitoring the catalytic reaction
by GC/MS. MS (EI 70 eV) data of 11a are as follows:
m/z=322 (48%) [M+], 266 (100%) [M+ꢀt-Bu], 249
[7] For general reviews on its occurrence and applications
see: a) B. H. Lipshutz, Chem. Rev. 1986, 86, 795–820;
b) R. Benassi, in: Comprehensive Heterocyclic Chemis-
392
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394

One-Pot Entry to Fully Substituted Furans
FULL PAPERS
1
(44%) [M+ꢀO-t-Bu], 234 (5%) [M+ꢀMeꢀO-t-Bu],
[18] a) Propargylic substitution reactions of alkynols R C
ꢁ
219
(20%)
[M+ꢀ2MeꢀO-t-Bu],
206
(25%)
CC(OH)R2R3 with a variety of carbon- and hetero-
1
[M+ꢀMeꢀCO2-t-Bu], 191 (5%) [M+ꢀ2MeꢀCO2-t-
atom-centered nucleophiles (NuH) to afford R C
ꢁ
Bu], 178 (20%) [C10H7CCCO].
CC(Nu)R2R3 catalyzed by Brønsted acids (PTS, CSA,
HCl, etc.) have been recently described. These reac-
tions are believed to proceed through the intermediate
[13] The Boc group is known to be a versatile and widely
used protecting group for carboxylic acids. Several
methods have been reported for its removal, most of
them involving the use of Brønsted (HCl, H2SO4,
HNO3 or CF3CO2H) or Lewis (I2, TiCl4, ZnBr2, CeCl3,
SiO2 or silyl triflates) acids. Representative references
are the following: a) J. S. Yadav, E. Balanarsaiah, S. Ra-
ghavendra, M. Satyanarayana, Tetrahedron Lett. 2006,
47, 4921–4924; b) P. Strazzolini, N. Misuri, P. Polese,
Tetrahedron Lett. 2005, 46, 2075–2078; c) R. Kaul, Y.
Brouillette, Z. Sajjadi, K. A. Hansford, W. D. Lubell, J.
Org. Chem. 2004, 69, 6131–6133; d) E. Marcantoni, M.
Massaccesi, E. Torregiani, G. Bartoli, M. Bosco, L.
Sambri, J. Org. Chem. 2001, 66, 4430–4432; e) R. W.
Jackson, Tetrahedron Lett. 2001, 42, 5163–5165; f) P.
Strazzolini, M. Scuccato, A. G. Giumanini, Tetrahedron
2000, 56, 3625–3633; g) Y.-Q. Wu, D. L. Limburg, D. E.
Wilkinson, M. J. Vaal, G. S. Hamilton, Tetrahedron Lett.
2000, 41, 2847–2849; h) M. Valencic, T. van der Does,
E. de Vroom, Tetrahedron Lett. 1998, 39, 1625–1628;
i) A. B. Jones, A. Villalobos, R. G. Linde II, S. J. Dani-
shefsky, J. Org. Chem. 1990, 55, 2786–2797.
1
+
2
3
ꢁ
formation of a propargylic cation R C CC R R which
undergoes the addition of the nucleophile (in our case
the enolic form of the 1,3-dicarbonyl compound acts as
a carbon-centered nucleophile): R. Sanz, A. Martínez,
J. M. lvarez-GutiØrrez, F. Rodríguez, Eur. J. Org.
Chem. 2006, 1383–1386; b) it should be also noted that
very recently two general and highly efficient proce-
dures for the propargylic substitution of alkynols cata-
lyzed by the Lewis acids BiCl3 and FeCl3 have been re-
ported: Z.-P. Zhan, W.-Z. Yang, R.-F. Yang, J.-L. Yu, J.-
P. Li, H.-J. Liu, Chem. Commun. 2006, 3352–3354; Z.-
P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang, W.-
Z. Yang, J.-P. Li, J. Org. Chem. 2006, 71, 8298–8301.
[19] Although complex 1 is known to be an active catalyst
in propargylic substitution processes of alkynols with
alcohols (see ref.[4a]), it is not active at all when carbon-
centered nucleophiles, such as enolizable ketones, are
used as substrates (see ref.[3]).
[20] In accord with previous results, the treatment of 2a
with methyl acetoacetate and complex 1 (5 mol%), at
758C and in the absence of CF3CO2H, results in the ex-
clusive formation of enal (E)-RHC=CHCHO (R=1-
naphthyl) as the result of the Meyer–Schuster isomeri-
zation of the alkynol (see ref.[4b]).
[14] The carboxylic acid 12a could not be detected by GC/
MS pointing out that its decarboxylation is a highly fav-
oured process.
[15] Transition metal-catalyzed decarboxylation of carboxyl-
ic acids is a well-documented process. Representative
examples can be found in: a) S. Matsubara, Y. Yokota,
K. Oshima, Org. Lett. 2004, 6, 2071–2073; b) D.
Tanaka, A. G. Myers, Org. Lett. 2004, 6, 433–436;
c) E. M. O’Brien, E. A. Bercot, T. Rovis, J. Am. Chem.
Soc. 2003, 125, 10498–10499; d) A. G. Myers, D.
Tanaka, M. R. Mannion, J. Am. Chem. Soc. 2002, 124,
11250–11251; e) L. J. Gooben, L. Winkel, A. Dçhring,
K. Ghosh, J. Paetzold, Synlett 2002, 1237–1240; f) D. J.
Darensbourg, E. M. Longridge, M. W. Holtcamp, K. K.
Klausmeyer, J. H. Reibenspies, J. Am. Chem. Soc. 1993,
115, 8839–8840; g) D. J. Darensbourg, E. M. Longridge,
E. V. Atnip, J. H. Reibenspies, Inorg. Chem. 1992, 31,
3951–3955.
[16] Although very rare, some metal-catalyzed reductive de-
carboxylation of esters RCO2Rꢁ to form the corre-
sponding hydrocarbons RH are known: a) N. Chatani,
H. Tatamidani, Y. Ie, F. Kakiuchi, S. Murai, J. Am.
Chem. Soc. 2001, 123, 4849–4850; b) H. Tatamidani, K.
Yokota, F. Kakiuchi, N. Chatani, J. Org. Chem. 2004,
69, 5615–5621, and references cited therein.
[17] See, for example: a) Y. Nishibayashi, S. Uemura, Curr.
Org. Chem. 2006, 10, 135–150, and references cited
therein; b) E. Bustelo, P. H. Dixneuf, Adv. Synth. Catal.
2005, 347, 393–397; c) C. Fischmeister, L. Toupet, P. H.
Dixneuf, New J. Chem. 2005, 29, 765–768; d) M.
Georgy, V. Boucard, J.-M. Campagne, J. Am. Chem.
Soc. 2005, 127, 14180–14181; e) J. J. Kennedy-Smith,
L. A. Young, F. D. Toste, Org. Lett. 2004, 6, 1325–1327;
f) M. R. Luzung, F. D. Toste, J. Am. Chem. Soc. 2003,
125, 15760–15761; g) B. D. Sherry, A. T. Radosevich,
F. D. Toste, J. Am. Chem. Soc. 2003, 125, 6076–6077.
[21] Pd(0)-, Pd(II)- and Au
tions of internal b-ketoalkynes R C CCH(R )C(=O)R
into furans are known. Similarly, a-ketoalkynes
ACHTRE(UGN III)-catalyzed cycloisomeriza-
1 2 3
ꢁ
1
2
ꢁ
R CH2C CC(=O)R can be cycloisomerized into
furans in the presence of copper(I) salts. All these reac-
tions are believed to proceed through the intermediate
formation of allenyl isomers that undergo metal-medi-
ated cyclization: a) H. Sheng, S. Lin, Y. Huang, Synthe-
sis 1987, 1022–1023; b) Y. Fukuda, H. Shiragami, K.
Utimoto, H. Nozaki, J. Org. Chem. 1991, 56, 5816–
5819; c) A. S. K. Hashmi, L. Schwarz, J.-H. Choi, T. M.
Frost, Angew. Chem. Int. Ed. 2000, 39, 2285–2288;
d) A. S. K. Hashmi, T. M. Frost, J. W. Bats, J. Am.
Chem. Soc. 2000, 122, 11553–11554; e) A. V. Kelꢁin, V.
Gevorgyan, J. Org. Chem. 2002, 67, 95–98; f) J. T. Kim,
A. V. Kelꢁin, V. Gevorgyan, Angew. Chem. Int. Ed.
2003, 42, 98–101; g) A. W. Sromek, A. V. Kelꢁin, V. Ge-
vorgyan, Angew. Chem. Int. Ed. 2004, 43, 2280–2282.
[22] Ru(II)-catalyzed cycloisomerizations of (Z)-2-en-4-yn-
1-ols and a-epoxyalkynes into furans are well-known
processes. Representative examples can be found in
ref.[1f] and: a) B. Seiller, C. Bruneau, P. H. Dixneuf, Tet-
rahedron 1995, 51, 13089–13102; b) H. Kücükbay, B.
Cetinkaya, S. Guesmi, P. H. Dixneuf, Organometallics
1996, 15, 2434–2439; c) B. C¸ etinkaya, I. Özdemir, C.
Bruneau, P. H. Dixneuf, Eur. J. Inorg. Chem. 2000, 29–
32; d) C.-Y. Lo, H. Guo, J.-J. Lian, F.-M. Shen, R. S.
Liu, J. Org. Chem. 2002, 67, 3930–3932; e) B. C¸ etin-
kaya, N. Gürbüz, T. SeÅkin, I. Özdemir, J. Mol. Catal.
A: Chem. 2002, 184, 31–38.
[23] For reviews on this topic see: a) M. I. Bruce, Chem.
Rev. 1991, 91, 197–257; b) C. Bruneau, P. H. Dixneuf,
Adv. Synth. Catal. 2007, 349, 382 – 394
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
393

Victorio Cadierno et al.
FULL PAPERS
Acc. Chem. Res. 1999, 32, 311–323; c) M. C. Puerta, P.
Valerga, Coord. Chem. Rev. 1999, 193–195, 977–1025;
d) V. Cadierno, M. P. Gamasa, J. Gimeno, Coord.
Chem. Rev. 2004, 248, 1627–1657.
which give furan 8c in 60% and 64% yield (GC deter-
mined), respectively, after 8 h (to be compared with
entry 4 in Table 2).
[25] M. M. Midland, J. Org. Chem. 1975, 40, 2250–2252.
[26] J. Suffert, D. Toussaint, J. Org. Chem. 1995, 60, 3550–
3553.
[27] T. S. Balaban, M. Hiegemann, Tetrahedron 1992, 48,
9827–9840.
[24] It should be noted that other ruthenium(II) sources,
such as [RuCl
Cl)(h6-p-cymene)}2], [RuCl
C9H7) CHTREUNG
(PPh3)2] and [Ru(h3–2-C3H4Me)
2A
G
ACHTRE(UNG m-
G
ACHTREUNG
N
also found to be operative in this furan-ring formation
reaction. Nevertheless, their efficiency is by far lower
than that shown by complex 1. Thus, using the coupling
of alkynol 2c with ethyl acetoacetate as a model reac-
[28] M. S. Akhtar, M. Seth, A. P. Bhaduri, J. Heterocycl.
Chem. 1985, 22, 1323–1324.
[29] M. H. Suhre, M. Reif, S. F. Kirsch, Org. Lett. 2005, 7,
3925–3927.
[30] F. Boberg, G. R. Schultze, Chem. Ber. 1957, 90, 1215–
1225.
tion ([2c]:[ethyl acetoacetate]:
ACHTREUNG
20:200:10:1), the best results were obtained using
[RuCl
2A
and
2ACHTRE(UNG COD)]
394
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 382 – 394