Sequential synthesis of furans from alkynes: Successive ruthenium(II)- and copper(II)-catalyzed processes

Article abstract of DOI:10.1002/anie.200805531

(Chemical Equation Presented) Step in time: 2,5-Disubstituted furans can be prepared from terminal alkynes in one pot using two successive catalytic reactions (see scheme; p-TSA=para-toluene-sulfonic acid). First, a 1,3-dienyl alkyl ether is produced by t

Full text of DOI:10.1002/anie.200805531

Angewandte
Chemie
DOI: 10.1002/anie.200805531
Furan Synthesis
Sequential Synthesis of Furans from Alkynes: Successive
Ruthenium(II)- and Copper(II)-Catalyzed Processes**
Min Zhang, Huan-Feng Jiang, Helfried Neumann, Matthias Beller,* and Pierre H. Dixneuf*
Functionalized furans are frequent subunits in a variety of
biologically active molecules[1] and have also been used as
communicating moieties in molecular materials.[2] Although
these properties have motivated the development of efficient
methods for furan synthesis,[3,4] there is still a need for new
improved routes, which should be suitable for constructing
molecular materials and avoid the use of stoichiometric
reagents. In this respect synthetic innovations making use of
atom-economical reaction cascades or one-pot multistep
catalytic reactions are of special interest.[5]
In recent years the discovery of new activation processes
and selective ruthenium-catalyzed multistep transformations
of alkynes,[6,7] in parallel to the increasing availability of a
variety of alkynes in particular by the use of catalytic
Sonogashira reaction,[8] has significantly contributed to this
field. The simple head-to-head dimerization of terminal
alkynes is of special interest as a convenient way to build
conjugated C4 units.[9] Although the intramolecular oxidative
coupling of nonconjugated diynes takes place readily with
ruthenium complexes,[10] the catalytic intermolecular dimeri-
zation of alkynes could not be applied to the formation of
dienyl ethers.[9] This apparently simple catalytic formation of
1,3-dienyl ethers remains a challenge as they are usually more
easily obtained via enolates.[11] Noteworthy, the resulting 1,3-
dienyl ethers are useful building blocks, such as for Diels–
Alder reactions.[12]
dienyl ethers and 2) the copper(II)-catalyzed cyclization of
the in situ formed unsaturated ketones into furans [Eq. (1)].
It has been demonstrated that [RuCl(cod)Cp*] (cod =
cyclooctadiene, Cp* = C5Me5) promotes the head-to-head
dimerization of alkynes, leading to a bis(carbene)–ruthenium
intermediate, and that subsequent 1,4-addition of carboxylic
acids results in the catalytic formation of 1,3-dienyl esters.[9]
Unfortunately, this catalytic system did not allow the addition
of non-acidic pronucleophiles such as alcohols. Our search for
a more electrophilic intermediate led us to evaluate the ionic
catalyst [Ru(NCMe)3Cp*][PF6]. This catalyst allowed a very
fast reaction of phenylacetylene (1a) with methanol in THFat
room temperature. After a reaction time of only 1 min the
corresponding 1,3-dienyl methyl ether 3a was isolated in 92%
yield (Scheme 1).
As shown in Scheme 1 this catalytic reaction is highly
stereoselective and appears to be quite general. It proceeded
rapidly within a few minutes for a variety of terminal alkynes
1a–1e in the presence of methanol, ethanol, and 2-methoxy-
ethanol to produce the (1E,3E) 1,4-disubstituted 1,3-dienyl
ethers 3a–3k in good to excellent yields (75–92%). We
believe that this reaction is one of the most facile routes to
1,4-disubstituted dienyl ethers.[11–12]
Here, we report a novel synthesis of 2,5-disubstituted
furans directly from terminal alkynes[13] by sequential one-pot
reactions: 1) The ruthenium(II)-catalyzed “click” dimeriza-
tion of terminal alkynes to produce stereoselectively 1,3-
The catalytic alkyne dimerization is assumed to proceed
by the head-to-head coupling of terminal alkynes to generate
bis(carbene)–Ru(Cp*)(NCMe)+ complex with mixed
[*] M. Zhang, Prof. Dr. P. H. Dixneuf
Laboratoire Catalyse et Organomꢀtalliques
Institut Sciences Chimiques de Rennes
UMR 6226 CNRS-Universitꢀ de Rennes
Campus de Beaulieu, 35042 Rennes (France)
Fax: (+33)2-2323-6939
a
Fischer- and Schrock-type behavior[9] (Scheme 2). This ionic
intermediate is more reactive towards the alcohol addition
than the intermediate arising from [RuCl(cod)Cp*].
Next, we were interested in the formation of the related
b,g-unsaturated ketones. The analogous reaction of aryl
alkynes with water led to a complex mixture of products
and not to the formation of ketones. Also attempts to
hydrolyze the dienyl ether 3a in situ under mild conditions
failed. However, when FeCl3 was used as Lewis acid in water
at 808C, hydrolysis took place, and the b,g-unsaturated
ketone 4a was formed together with a small amount of the
a,b-unsaturated ketone 4b (82% GC combined yield, 4a/
4b = 20:3). It is noteworthy that 2,5-diphenylfuran (5a) could
be also isolated from the reaction mixture in 3% yield from
the reaction mixture [Eq. (2)].
E-mail: pierre.dixneuf@univ-rennes1.fr
M. Zhang, Prof. Dr. H. F. Jiang
School of Chemistry and Chemical Engineering
South China University of Technology
Guangzhou, 510640 (China)
Dr. H. Neumann, Prof. Dr. M. Beller
Leibniz-Institut fꢁr Katalyse e.V.
an der Universitꢂt Rostock
Albert-Einstein-Strasse 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
[**] The authors are grateful to the European Network IDECAT for
support and to the China Scholarship Council for a grant to M.Z.
Inspired by the partial formation of furan 5a, we inves-
tigated the hydrolysis/cyclization sequence for the conversion
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200805531.
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ation. Selected results are reported in Table 1. The best yields
were obtained in the presence of p-toluenesulfonic acid (p-
TSA) and a stoichiometric amount of an electrophilic salt in
THF with one equivalent of water under microwave irradi-
Table 1: Optimization of the intramolecular cyclization of dienyl ether 3a
to give furan 5a.[a]
Entry
Acid
Additive
Yield [%][d]
1
2
3
4
5
6
7
8
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA[e]
none
FeCl3
FeCl3
3[b]
87[c]
5[c]
Cu(OAc)2
CuO
CuCl2
CuCl2
CuCl2
CuCl2
37[c]
[e]
–
59[c]
59[b]
99[c]
p-TSA
p-TSA
[a] A solution of 3a (0.5 mmol, 118 mg) in 2 mL of THF was treated with
p-TSA·H2O (0.1 mmol, 19 mg), H2O (1 mmol), and additive (1 mmol);
the resulting mixture was stirred. [b] The reaction was conducted at 808C
for 3 h. [c] The reaction mixture was subjected to microwave irradiation
(50 W, 1508C) for 20 min. [d] Yields determined by GC with tetradecane
as internal standard. [e] Without water in the reaction mixture.
ation. Here, furan 5a was formed in 87% yield with FeCl3 and
in 99% yield with CuCl2 (Table 1, entries 2 and 8). Since in
the absence of water (Table 1, entry 5) the formation of furan
5a was not observed, the reaction is expected to proceed by
formation of the unsaturated ketone 4a. In agreement with
this proposal the isolated ketone 4a was fully converted into
5a with CuCl2 under microwave irradiation and the reaction
conditions listed in Table 1, entry 8.
Scheme 1. Ruthenium-catalyzed synthesis of 1,3-dienyl ethers from
terminal alkynes and alcohols. Reaction time and yield of isolated
products are listed.
Having the optimized conditions in hand, we studied the
synthesis of 2,5-disubstituted furans directly from terminal
alkynes by one-pot combined successive ruthenium-catalyzed
and copper(II)-promoted reactions. The results are listed in
Scheme 3. In all cases studied—with alkynes 1a–1e already
used for the synthesis of dienyl ethers and the alkynes 1 f–1i—
the cyclization reaction proceeded smoothly to give the 2,5-
disubstituted furans 5a–5i in good to excellent yields,
including the fluorinated derivatives 5e, 5h, and 5i
(Scheme 3).[14]
Scheme 2. Proposed mechanism for the formation of dienyl ethers 3.
The reaction mechanism has not yet been elucidated, but
as Cu salts readily interact with the heteroatoms of ketones
and imines,[15] the interaction of Cu2+ with the oxygen atom of
4 may promote deprotonation and formation of dienolate
intermediate A, which is able to cyclize into B (Scheme 4).
Alternatively, the interaction of Cu2+ with the C C bond of 4
=
may also promote the formation of a p-carbon-bonded
dienolate before cyclization into B. Such a cyclization would
lead to the reduction of CuII to CuI.[15]
of 3a into furan 5a in more detail. For comparison, reactions
in acidic media in the presence of Fe or Cu salts were
performed under thermal conditions and microwave irradi-
Consequently, we attempted to transform the Cu2+-
promoted stoichiometric cyclization into a catalytic reaction
by regenerating the copper(II) species with oxygen. Thus, the
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substituents, was formed in lower yield. Noteworthy, the furan
formation tolerates aryl bromides, and 5j was obtained in
77% yield (Scheme 4). This reaction thus offers potential for
further functionalization of furans by, for example, catalytic
cross-coupling reactions.
In conclusion, we have established a facile and highly
stereoselective method to synthesize 1,3-dienyl ethers from
terminal alkynes in the presence of the [Ru(NCMe)3Cp*]-
[PF6] catalyst, in only a few minutes at room temperature as a
click reaction. Moreover, a novel method for the one-pot
synthesis of 2,5-disubstituted furans from 1,3-dienyl alkyl
ethers, and related unsaturated ketones, is described and
takes place with catalytic amounts of CuCl2 in the presence of
air. Both catalytic reactions with ruthenium (II) and copper
(II) can be performed successively in one pot directly from
terminal alkynes. As the reaction tolerates aryl halides, it
could potentially provide access to a variety of molecular
materials, as well as mixed aryl–furan polymers from aromatic
diynes.
Experimental Section
Typical procedure for the synthesis of the dienyl ether 3a: Phenyl-
acetylene (1a) (1 mmol, 102 mg) was added to a mixture of [Cp*Ru-
(MeCN)3][PF6] (20 mg, 0.04 mmol, 4 mol%) and MeOH (1 mmol,
32 mg) in distilled THF (2 mL). The mixture was stirred at RT for
1 min, the resulting mixture was concentrated
and purified by flash column chromatography on
silica, eluting with ethyl acetate/petroleum ether
(1:10) to give 3a as a white solid (109 mg, 92%).
Typical procedure for the synthesis of 2,5-
Scheme 3. One-pot synthesis of 2,5-disubstituted furans directly from
alkynes.
disubstituted furan 5a from alkyne 1a: Phenyl-
acetylene (1a) (1 mmol, 102 mg) was added to a
mixture of [Cp*Ru(MeCN)3][PF6] (20 mg,
0.04 mmol, 4 mol%) and MeOH (1 mmol,
32 mg) in distilled THF (2 mL). The mixture
was stirred at RT for 5 min. Then para-toluene-
sufonic acid monohydrate (0.1 mmol, 19 mg),
H2O (1 mmol), CuCl2 (0.1 mmol, 13.5 mg), and
toluene (1 mL) were added. The resulting mix-
ture was heated and aerated with air at 708C for
10 h. After cooling, the solution was diluted with
diethyl ether (10 mL), washed with NaHCO3,
and dried with anhydrous MgSO4. The solvent
was removed, and the crude product was purified
by flash column chromatography on silica, elut-
ing with petroleum ether/diethyl ether (50:1) to
give 2,5-diphenylfuran 5a as
a white solid
(90 mg, 82%).
Received: November 12, 2008
Published online: January 23, 2009
Keywords: alkynes · copper · dienyl ethers ·
.
Scheme 4. Copper(II)-catalyzed cyclization reaction and proposed mechanism.
furans · ruthenium
second step of the reaction sequence was modified and
performed with 10 mol% CuCl2 in the presence of air in THF/
toluene (10:1) at 708C. Indeed, formation of furans took
place: reaction of terminal alkynes 1 provided the furans 5a–
5e in 70–82% yield; 5d, which contains electron-donating
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