Cobalt(II)-catalyzed electrophilic alkynylation of 1,3-dicarbonyl compounds to form polysubstituted furans via π-π Activation

Article abstract of DOI:10.1002/adsc.201400857

Polysubstituted furans were obtained with excellent yields via the electrophilic alkynylation of 1,3-dicarbonyl compoundsws with phenyl- or ester-substituted brominated alkynes. The reaction is catalyzed by the inexpensive and readily available catalyst, cobalt(II) chloride, and has a wide substrate scope. The C(sp)-C(sp³) coupling occurs under mild conditions with short reaction times and does not require an inert atmosphere or ligands. It is proposed that the reaction proceeds through a chelation complex of cobalt(II) with the deprotonated 1,3-dicarbonyl compound.

Full text of DOI:10.1002/adsc.201400857

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DOI: 10.1002/adsc.201400857
Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-Dicarbonyl
Compounds To Form Polysubstituted Furans via p–p Activation
Irwan Iskandar Roslan,a Jiulong Sun,a Gaik-Khuan Chuah,a
and Stephan Jaenickea,*
a
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
Fax : (+65)-6779-1691; phone: (+65)-6516-2918; e-mail: chmsj@nus.edu.sg
Received: August 29, 2014; Revised: November 24, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400857.
Abstract: Polysubstituted furans were obtained with
excellent yields via the electrophilic alkynylation of
1,3-dicarbonyl compoundsws with phenyl- or ester-
substituted brominated alkynes. The reaction is cat-
alyzed by the inexpensive and readily available cat-
frequently are only accessible via multiple-step syn-
theses. However, Leiꢀs group recently showed that
polysubstituted furans can be obtained from readily
available starting materials, arylacetylenes and 1,3-di-
carbonyls, via an Ag(I)-mediated dehydrogenative
cross-coupling reaction.[7]
“Umpolung” of this reaction with electrophilic al-
kynylating reagents such as brominated acetylenes in-
creases the flexibility and versatility of the acetylene
chemistry and extends the scope of the reaction.[8,9]
The sp–sp2 alkynylation of aryl and heteroaromatic
compounds catalyzed by group 10–13 metals such as
Pd, Cu, Ni, Au or Ga has been extensively studied.[10]
In contrast, there are few studies on the sp–sp3 elec-
trophilic alkynylation of aliphatic compounds. One of
the first reports was by Ano et al. on the alkynylation
of carboxylic acid derivatives using brominated acety-
lenes.[11] Huang et al. utilized electrophilic alkynyla-
tion to form various aromatic H-pyrazolo[5,1-a]iso-
alyst, cobalt(II) chloride, and has a wide substrate
3
À
scope. The C(sp) C(sp ) coupling occurs under
mild conditions with short reaction times and does
not require an inert atmosphere or ligands. It is pro-
posed that the reaction proceeds through a chelation
complex of cobalt(II) with the deprotonated 1,3-di-
carbonyl compound.
À
Keywords: alkynes; C H activation; cobalt(II) cata-
lysts; cyclization; heterocycles
Polysubstituted furans are an important class of 5- quinolines from (bromoethynyl)benzene and N’-(2-
membered heterocycles that are ubiquitous in natural alkACTHNUTRGNEUNG
ynylbenzylidene)hydrazide.[12] Wipf and Venkatra-
products, pharmaceuticals and agrochemicals.[1] Many man constructed thiazoles from alkynyliodonium salts
naturally occurring furans have medicinal properties and thioamides.[13] More recently, Jiangꢀs group
such as antiallergic, antiasthmatic, antispasmodic, an- showed that (bromoethynyl)benzene and ethyl 2-pyri-
titumor and antidiabetic activities.[2] Furans are im- dylacetate formed 2,3,4-trisubstituted furans via
portant intermediates in the total synthesis of com- a silver-catalyzed sequential nucleophilic addition and
plex natural products,[3] and can be transformed to cyclization reaction.[14] The reaction was conducted
bio
and macrocycles with selective binding for biomole- gether with 1 equivalent of DABCO (1,4-diazabicy-
cules.[4]
clo[2.2.2]octane) as a strong base. These works moti-
ACHTUNGTRENNUNfG uels, polymers with electrochemical properties using 20 mol% AgNO3 as a Lewis acid catalyst to-
Polysubstituted furans are typically constructed vated us to explore the possibility of an sp–sp3 elec-
from 1,4-diketones via the Paal–Knorr reaction,[5] but trophilic alkynylation to form polysubstituted furans
this synthesis requires high reaction temperatures and from (bromoethynyl)benzene derivatives[15] and 1,3-
harsh acidic conditions. Thus, the quest for improved dicarbonyls. This approach has the advantage that
methods to obtain polysubstituted furans from a varie- (bromoethynyl)benzene derivatives can be easily syn-
ty of starting materials continues.[6] Most of the re- thesized with a short reaction sequence while 1,3-di-
cently developed syntheses are indeed more effective carbonyls are readily available as starting materials.
and usually require milder conditions, but they are
We first searched for a suitable catalyst to bring
hampered by a limited scope of reaction or difficulties about the reaction between methyl acetoacetate 1 and
with the acquisition of the starting reagents, which (bromoethynyl)benzene 2. In addition to the desired
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Irwan Iskandar Roslan et al.
Table 1. Optimization of the parameters for the electrophilic alkynylation.[a]
No
Catalyst
Solvent
V [mL]
Temperature [8C]
Ligand
Time [h]
3a Yield [%][b]
1
2
3
4
5
6
7
8
CuI
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Toluene
DCE
Dioxane
DMA
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
DMA/toluene
2
2
2
2
2
2
2
2
2
2
5
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
110
110
110
110
110
110
110
110
110
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
12
12
12
12
12
12
12
12
12
8
8
8
8
8
8
8
8
5
5
5
5
5
5
5
5
5
4
12
PdCl2
ZnCl2
NiCl2
CoCl2
CoBr2
CoI2
68 (61)
86 (82)
93 (90)
70 (65)
61 (53)
traces
traces
47 (42)
60 (53)
95 (92)
4
26 (10)
51(44)
86 (82)
99 (94)
81 (76)
99 (92)
91 (80)
87 (78)
60 (49)
95 (92)
95 (90)
65 (59)
67
–
9[c]
10
11
12
13
14
15
16
17
18
19
20
21
22
23[d]
24[e]
25[f]
26[g]
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
–
–
PCy3
PPh2(o-tol)
P(o-tol)3
PPh3
–
–
–
–
[a]
Reaction conditions: 1 (2.0 equiv.), 2 (0.5 mmol), catalyst (10 mol%), ligand (20 mol%), Ag2CO3 (2 equiv.).
Yield determined by GC analysis, isolated yields in parentheses.
Reaction with no Ag2CO3.
[b]
[c]
[d]
[e]
[f]
Reaction with 2.5 equiv. of 1.
Reaction with 2.5 equiv. of 1 and 1.3 equiv. of Ag2CO3.
Reaction with 2.5 equiv. of 1 and 1.0 equiv. of Ag2CO3.
Reaction with 1 equiv. of TEMPO and 1.3 equiv. of Ag2CO3.
[g]
polysubstituted furan 3a, we observed the formation larly, without Ag2CO3, only traces of 3a were formed
of side products such as the debrominated alkyne, (Table 1, entry 9). These results show that both CoCl2
phenylacetylene 4, and the homocoupling product, and Ag2CO3 are required for the reaction to proceed
1,4-diphenyldiacetylene 5. Various metals were with high yield. The finding that CoCl2 was the most
screened as catalysts in the presence of Ag2CO3 as effective catalyst is fortuitous as it is inexpensive and
mediator to scavenge the liberated bromide. Cu(I) or easy to handle, allowing the reaction to proceed read-
Pd(II) salts (Table 1, entries 1 and 2) gave mainly the ily without the need for an inert atmosphere.
homocoupling product 5. In contrast, the reaction
The reaction conditions were optimized with CoCl2
proceeded with moderate to good yields when Zn(II), as catalyst at a lower temperature of 808C. Diluting
Co(II) or Ni(II) chlorides were used (Table 1, en- the reaction mixture reduced the formation of the un-
tries 3–5). The isolated yield of 3a was 90% after 12 h wanted homodimer 5. When the volume of the dime-
at 1108C with CoCl2 as catalyst. Both CoBr2 and CoI2 thylformamide (DMF) solvent was increased from 2
gave lower yields than CoCl2 (Table 1, entries 6 and to 8 mL, the yield of the polysubstituted furan 3a
7). In the absence of any cobalt halide, the conversion after 8 h reaction time went up from 47 to 95%
was low, with only small amounts of the debrominat- (Table 1, entries 10–12). The polarity of the solvent
ed product 4 and traces of 3a (Table 1, entry 8). Simi- also affected the yield of 3a. Non-polar solvents like
2
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Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-Dicarbonyls
Table 2. Electrophilic alkynylation of various b-keto compounds and brominated alkynes.[a]
[a]
Isolated yields. Reaction conditions: 1 (2.50 equiv.), 2 (0.5 mmol), CoCl2 (10 mol%), Ag2CO3 (1.3 equiv.), DMA/toluene
(v/v=1/1) (8.0 mL), 808C, 5 h.
toluene and dichloroethene (DCE) gave low yields of ed 91–99% of 3a after a reaction time of only 5 h.
the desired product whereas polar aprotic solvents Nevertheless, the saving in reaction time to obtain
like dimethylacetamide (DMA) and DMF resulted in high yields of 3a does not justify the extra costs and
excellent yields of 86 and 95%, respectively (Table 1, increased work-up with the addition of the ligand. In
entries 12–16). This can be attributed to the higher fact, by increasing methyl acetoacetate from 2 to
solubility of CoCl2 and Ag2CO3 in polar aprotic sol- 2.5 equivalents, a similarly high yield of 95% could be
vents as compared to non-polar solvents.[16] To opti- achieved in 5 h, suggesting that methyl acetoacetate
mize the solubility of both the organic substrates and acts as a stabilizing ligand as well (Table 1, entry 23).
the metal salts, mixtures containing DMA and tolu- Reducing the amount of Ag2CO3 from 2 to 1.3 equiv-
ene in various ratios were tested. The best yield of 3a, alents did not affect the reaction but a further de-
99% after 8 h, was obtained with a DMA/toluene crease to 1 equivalent resulted in a significant drop in
(v/v=1/1) mixture.
the yield of 3a to 65% (Table 1, entries 23–25).
The effect of phosphine ligands was next investigat- Hence, the optimized conditions for high yields of 3a
ed (Table 1, entries 19–22). The addition of phos- are 10 mol% CoCl2 as catalyst, 1.3 equiv. Ag2CO3 as
phines with an electron-withdrawing phenyl substitu- bromide acceptor, and a mixed solvent system of 1:1
ent had a negative effect. The yield of 3a decreased DMA/toluene at 808C.
from 81% in the ligand-free system to only 60%. On
The scope of the reaction using the optimized con-
the other hand, electron-rich phosphines with electron ditions was next investigated (Table 2). Good to ex-
donating cyclohexyl and ortho-tolyl substituents yield- cellent yields of 74–95% were obtained for various b-
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Irwan Iskandar Roslan et al.
keto esters with 2 (Table 2, 3a–3i). However, the yield alkynes but also proceeds well with a propiolate
was significantly lower, 47%, when using the b-keto moiety. However, terminal aliphatic alkynes were un-
ester with a bulky tert-butyl substituent (Table 2, 3j). suitable for the reaction, with only traces of the de-
The reaction proceeded well with secondary b-keto sired products formed (Table 2, 3y and 3z).
amides and acetylacetones (Table 2, 3k, 3k’ and 3l).
The effect of the halogen substituent of the alkyne
However, no reaction occurred with 1,3-cyclohexane- was examined. While (chloroethynyl)benzene gave
dione as substrate (Table 2, 3m). Apparently, after de- a similar yield of 3a, 94%, as 2, the reaction with (io-
protonation on C-2 the rigid diketone cannot form doethynyl)benzene unexpectedly proceeded with only
the chelation complex with Co2+. However, benzoyl- 63% yield. When (iodoethynyl)benzene was reacted
nitromethane and pivaloylacetonitrile with electron- with the more sterically hindered tert-butyl acetoace-
withdrawing CN and NO2 groups are good substrates tate, the desired product 3j did not form at all, com-
for this reaction (Table 2, 3n, 3o).
pared to 47% with (bromoethynyl)benzene. Further-
Various brominated phenylacetylene derivatives more, the yield of 3s’ decreased from 47% to 30%
were tested with methyl acetoacetate to form poly- when 1-tert-butyl-4-(iodoethynyl)benzene was used in-
substituted furans. High yields were observed for both stead of the corresponding bromoalkyne. A similar
para-tolyl and meta-tolyl derivatives (Table 2, 3p and observation had been made by Jiang and co-workers
3p’). However, only traces of product were formed for the synthesis of 2,3,4-trisubstituted furans from
with mesityl derivatives, suggesting that steric con- haloalkynes and 2-pyridylacetic acid esters.[14] As io-
straints at the ortho position are important (Table 2, doacetylenes usually perform better than their bromo
3q). Both electron-withdrawing and electron-donating equivalents due to weaker bond strengths, their lower
substituting groups at the para position including Et, reactivity may be due to the larger size of iodine as
n-Bu, OMe and F were well tolerated under the reac- compared to bromine. Hence, the results suggest that
tion conditions (Table 2, 3r–3t). However, for the ster- the reaction is very sensitive to steric constraints.
ically hindered 1-tert-butyl-4-(bromoethynyl)benzene,
To gain some insight into the mechanism of this
the yield was only 47% (Table 2, 3s’). Furthermore, electrophilic alkynylation reaction, phenylacetylene
other aromatic and heteroaromatic moieties including was used instead of its brominated analogue. No
thiophene and naphthalene reacted to form 3v and furans were formed, ruling out the possibility that de-
3w with good yields of 90% and 76%, respectively. It halogenation at the sp carbon initiated the reaction
was pleasing to see that the non-aromatic methyl 3- (Table 3, entry 1). The introduction of silver phenyl-
bromopropiolate was also suitable for this reaction
acetylide[7] together with
ACHTUNGTERNNUNG 1 or 2 equivalents of
forming 3x with an excellent yield of 95%. This exam- Ag2CO3 produced the desired product only in low
ple shows that the reaction is not limited to aromatic yields. Instead, more of the side products 4 and 5
Table 3. Mechanistic studies for electrophilic alkynylation.[a]
Entry
Alkyne/
Mediator/Reductant
Yield [%][b]
3a
4
5
1
2
2 equiv. Ag2CO3
1 equiv. Ag2CO3
–
1
–
–
43
56
3
2 equiv. Ag2CO3
1 equiv. Zn, 2 equiv. Ag2CO3
2 equiv. Ag2CO3
2 equiv. AgOAc
12
5
55
–
33
4
4[c]
5[d]
6
–
–
18
7
87
92
46
–
7
2 equiv. Ag2O
2
5
8
2 equiv. AgOTf
43
11
[a]
Reaction conditions: 1 (2.5 equiv.), 2 (0.5 mmol), 10 mol% CoCl2 in DMA/toluene (v/v=1/1) (8.0 mL), 808C, 5 h.
Yield determined by GC analysis.
Zn and CoCl2 were mixed for 10 min in solvent prior to adding the substrates and Ag2CO3.
1.25 equiv. of methyl 2-bromoacetoacetate and 1.25 equiv. of methyl acetoacetate were used.
[b]
[c]
[d]
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Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-Dicarbonyls
were formed (Table 3, entries 2 and 3), showing that
the reaction did not proceed via the initial formation
of the silver species. Co(II) salts as mediators for cou-
pling reactions of bromoalkynes with organozinc hal-
ides and Grignard reagents have been described
before, but the mechanism involved free radicals.[17]
Similarly, a Co(II) porphyrin complex for the regiose-
lective synthesis of polysubstituted furans initiated
the metalloACHTUNGTRENNUNGradical cyclization of alkynes with a-diazo-
carbonyl compounds.[18] The possibility that the pres-
ent reaction was initiated by radicals was investigated
by introducing one equivalent of 2,2,6,6-tetramethyl-
piperidinyl 1-oxyl (TEMPO) as radical scavenger to
the reaction mixture. The yield of 3a was 67%, which
is only moderately lower than in the absence of
TEMPO (Table 1, entry 26). The observation of
a silver mirror on the inside walls of the round-bot-
tomed flask shows that some Ag(I) had been reduced
to Ag(0), lowering the Ag+ concentration to below
optimum. Indeed, the obtained yield of 3a was com-
parable to that obtained when only 1 equivalent
Ag2CO3 was used.
To elucidate if the catalyst operates via an oxidative
mechanism involving Co(I)/Co(III) or a p-activation
mechanism involving Co(II), zinc was used to reduce
Co(II) to the Co(I) species in-situ prior to the reac-
tion (Table 3, entry 4).[17b,19] An excess of zinc was
used to ensure the complete reduction of Co(II) to
Co(I). It was noted that the presence of zinc also led
to the reduction of some Ag2CO3 to metallic silver.
As only trace amounts of 3a formed under these con-
ditions, it can be inferred that the reaction does not
proceed via a Co(I)/Co(III) mechanism but rather via
p-activation.
Scheme 1. Proposed mechanism for the Co-catalyzed elec-
trophilic alkynylation reaction.
To exclude the possibility that bromination of
methyl acetoacetate occurs by reaction with 2, the re-
action was carried out using equal amounts of methyl
2-bromoacetoacetate and methyl acetoacetate with
phenylacetylene (Table 3, entry 5). No 3a was formed,
instead the phenylacetylene reacted exclusively to the
dimer 5. It is therefore unlikely that the reaction pro-
ceeds via the formation of methyl 2-bromoacetoace-
tate as an intermediate. Different Ag salts were
tested and a higher furan yield was found when
AgOAc or Ag2O were used rather than AgOTf
(Table 3, entries 6–8). This suggests that in addition to
increasing the electrophilicity of the brominated
alkyne, Ag(I) also acts as a base that assists in the
proton abstraction to form the methyl acetoacetate
anion.
Figure 1. Proposed alignment of (bromoethynyl)benzene
and the Co-methyl acetoacetate complex for p–p interac-
tion.
Based on these results, we propose that the electro-
philic alkynylation reaction proceeds via the mecha- teract with the phenyl moiety as well as with the
nism shown in Scheme 1. Deprotonation of the 1,3-di-
carbonyl at the a-position assisted by Ag2CO3 forms the p–p interaction, the molecules are brought close
the methyl acetoacetate anion which chelates to the together (B) so that a C C bond can form between
cobalt ion to give a Co(II) complex A (Figure 1). The the C-2 of the methyl acetoacetate anion and the
p electron clouds of the methyl acetoacetate anion in- electrophilic carbon of (bromoethynyl)benzene (C).
À ꢀ
C
À
C
moiety of (bromoethynyl)benzene. As a result of
À
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Irwan Iskandar Roslan et al.
À
This is followed by b-elimination to yield the Co Br
complex D and intermediate E which undergoes cy-
cloisomerization to form the desired polysubstituted
furan 3a. Reaction of D with another molecule of 1,3-
dicarbonyl under elimination of the bromide as AgBr
regenerates the Co(II) complex A, thus completing
the catalytic cycle.
The p–p interaction between the phenyl moiety
and the methyl acetoacetate anion appears to be im-
portant for the reaction. The bulky tert-butyl group in
the b-keto ester or at the para position of the bromi-
Scheme 2. Reaction Scheme for the electrophilic alkynyla-
tion to form 7.
nated phenylacetylene interferes with the alignment, lyzed electrophilic alkynylation reaction and pioneers
resulting in low yields of 3j and 3s’, respectively. Re- its application in the formation of furans via cycliza-
acting these bulky substrates with the larger and tion.
therefore more sterically hindered iodide instead of
bromide causes further reduction in the yields of 3a,
3j and 3s’. Similarly, only trace amounts of 3q were Experimental Section
formed because the ortho methyl-substituent at the
phenyl group prevents proper alignment of the General Procedure for Electrophilic Alkynylation
phenyl group and the Co(II)-methyl acetoacetate Reaction to form Polysubstituted Furans
complex. In contrast, excellent yields of 3w were ob-
A 25-mL round-bottomed flask was charged with methyl
acetoacetate 1 (134.8 mL, 1.25 mmol), (bromoethynyl)ben-
tained with methyl propiolate which may be due to
the formation of a h3 allyl p–p interaction with the
zene
2 (59.8 mL, 0.5 mmol), anhydrous CoCl2 (6.5 mg,
Co(II)-methyl acetoacetate complex. Brominated ali-
phatic alkynes are not suitable substrates as they
cannot form the p–p interaction. The formation of
a square planar complex between the metal and the
1,3-diketo compound facilitates the reaction by allow-
ing favorable p–p interaction between the methyl ace-
toacetate anion and the phenyl component of 2 possi-
ble. Whereas Co(II) and especially Ni(II) are known
to form square planar complexes,[20] and can catalyze
the reaction effectively, Zn(II) is less likely to adopt
such a configuration and has lower activity (Table 1,
entries 3–5). To prove that the reaction proceeds via
an intermediate E (Scheme 1), ethyl 2-oxocyclopent-
0.05 mmol), Ag2CO3 (179 mg, 0.65 mmol) in a solvent mix-
ture of DMA and toluene (v/v=1/1) (8.0 mL). The reaction
mixture was stirred at 808C for 5 h. The mixture was
quenched with 2M HCl (2 mL), extracted with ethyl acetate
(3ꢂ5 mL) and the solvent was removed via a rotary evapo-
rator. The crude product was subjected to column chroma-
tography using hexane and ethyl acetate (v/v=10/1) as
eluent to afford 3a in 95% yield.
Methyl
2-methyl-5-phenylfuran-3-carboxylate
(3a):
1H NMR (300 MHz, CDCl3): d=7.64 (d, J=7.2 Hz, 2H),
7.38 (t, J=7.5 Hz, 2H), 7.27 (t, J=7.4 Hz, 1H), 6.88 (s, 1H),
3.85 (s, 3H), 2.65 (s, 3H); 13C NMR (300 MHz, CDCl3): d=
164.4, 158.7, 151.7, 130.0, 128.7, 127.6, 123.6, 115.0, 105.3,
51.3, 13.8.
ACHTUNGTRENNUNGanecarboxylate 6 was used as substrate under the op-
timized conditions (Scheme 2). This substrate lacks
a hydrogen at the a-position, and once formed, an in-
termediate 7 should not be able to undergo cycliza-
tion (unlike E). Alkyne 7 was indeed formed and
could be isolated with 80% yield, lending further sup-
port to the proposed mechanism.
Acknowledgements
Financial support from the NUS research grants R-143-000-
476-112 and R-143-000-550-112 is gratefully acknowledged.
I.I.R. thanks NUS for the award of an NUS-PGF Scholar-
ship.
In summary, we have developed an efficient p–p
activated electrophilic alkynylation reaction to form
polysubstituted furans using Co(II) as the catalyst.
3
À
The reaction proceeds via a C(sp) C(sp ) coupling
References
between 1,3-dicarbonyls and bromoethynyl moieties.
Ag(I) serves as a base for abstracting the a-hydrogen
from the 1,3-dicarbonyl, increases the electrophilicity
of the alkyne moiety, and is a sacrificial acceptor for
the bromide anion. Using this novel methodology,
polysubstituted furans can be synthesized under mild
conditions and with short reaction times. Further-
more, the method has a wide scope of reaction and
does not require an inert atmosphere. To the best of
our knowledge, this is a first example of a cobalt-cata-
[1] a) B. A. Lipshutz, Chem. Rev. 1986, 86, 795–819;
b) S. F. Kirsch, Org. Biomol. Chem. 2006, 4, 2076–2080;
c) 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; d) A. Speicher, S. Hauptmann, T.
Eicher, The Chemistry of Heterocycles, Wiley-VCH,
Weinheim, 2012, pp 61–80; e) S. Natori, in: Natural
Products Chemistry, Vol. 3, (Eds.: K. Nakanishi, T.
Goto, S. Itꢃ, S. Natoir, S. Nozo), Kodansha, Tokyo,
6
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Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-Dicarbonyls
1 983, pp 427–524; f) Y. Yang, H. N. C. Wong, Tetrahe-
dron 1994, 50, 9583–9608.
[9] a) F. Diederich, P. J. Stang, R. R. Tykwinski, Acetylene
Chemistry: Chemistry, Biology and Material Science,
Wiley-VCH, Weinheim, 2005, pp 508; b) A. Fraile, S.
Dꢆaz-Tendero, M. Tortosa, C. Alvarado, L. Marzo, J.
Alemꢇn, J. L. Garcꢆa Ruano, Chem. Eur. J. 2012, 18,
8414–8422; c) A. Fraile, S. Dꢆaz-Tendero, M. Tortosa,
C. Alvarado, L. Marzo, J. Alemꢇn, J. L. Garcꢆa-Ruano,
Angew. Chem. 2012, 124, 2766–2770; Angew. Chem.
Int. Ed. 2012, 51, 2712–2716; d) A. P. Schaffner, V. Dar-
mency, P. Renaud, Angew. Chem. 2006, 118, 5979–5981;
Angew. Chem. Int. Ed. 2006, 45, 5847–5849; e) D. Fer-
nandez-Gonzalez, J. P. Brand, J. Waser, Chem. Eur. J.
2010, 16, 9457–9461; f) S. Nicolai, C. Piemontes, J.
Waser, Angew. Chem. 2011, 123, 4776–4779; Angew.
Chem. Int. Ed. 2011, 50, 4680–4683; g) G. Evano, A.
Coste, K. Jouvin, Angew. Chem. 2010, 122, 2902–2921;
Angew. Chem. Int. Ed. 2010, 49, 2840–2859.
[10] a) A. S. Dudnik, V. Gevorgyan, Angew. Chem. 2010,
122, 2140–2142; Angew. Chem. Int. Ed. 2010, 49, 2096–
2098; b) E. Hupe, P. Knochel, Angew. Chem. 2001, 113,
3109–3112; Angew. Chem. Int. Ed. 2001, 40, 3022–3025;
c) R. Amemiya, A. Fujii, M. Yamaguchi, Tetrahedron
Lett. 2004, 45, 4333–4337; d) J. P. Brand, J. Charpentier,
J. Waser, Angew. Chem. 2009, 121, 9510–9513; Angew.
Chem. Int. Ed. 2009, 48, 9346–9349; e) Y. Gu, X. M.
Wang, Tetrahedron Lett. 2009, 50, 763–766; f) N. Mat-
suyama, K. Hirano, T. Satoh, M. Miura, Org. Lett.
2009, 11, 4156–4159; g) F. Besseliꢅvre, S. Piguel,
Angew. Chem. 2009, 121, 9717–9720; Angew. Chem.
Int. Ed. 2009, 48, 9553–9556; h) S. H. Kim, S. Chang,
Org. Lett. 2010, 12, 1868–1871; i) J. P. Brand, J. Waser,
Angew. Chem. 2010, 122, 7462–7465; Angew. Chem.
Int. Ed. 2010, 49, 7304–7307; j) T. Kawano, N. Matsuya-
ma, K. Hirano, T. Satoh, M. Miura, J. Org. Chem. 2010,
75, 1764–1766; k) Y. Ano, M. Tobisu, M. Chatani, Org.
Lett. 2012, 14, 354–357; l) Y. Ano, M. Tobisu, N. Chata-
ni, Synlett 2012, 23, 2763–2767; m) Y. Li, J. P. Brand, J.
Waser, Angew. Chem. Int. Ed. 2013, 52, 6743–6747.
[11] a) Y. Ano, M. Tobisu, N. Chatani, J. Am. Chem. Soc.
2011, 133, 12984–12986; b) Y. Li, X. Liu, H. Jiang, B.
Liu, Z. Chen, P. Zhou, Angew. Chem. 2011, 123, 6465–
6469; Angew. Chem. Int. Ed. 2011, 50, 6341–6345.
[2] a) J. B. Summers, J. L. Moore, U.S. Patent 4,769,387,
1998; b) J. Kobayashi, Y. Ohizumi, H. Nakamura, Tet-
rahedron Lett. 1986, 27, 2113–2116; c) J. Clardy, S. F.
Donovan, W. Fenical, M. M. Bandurraga, J. Am. Chem.
Soc. 1982, 104, 6463–6465; d) G. Schulte, P. S. Scheuer,
Helv. Chim. Acta 1980, 63, 2159–2167; e) R. Malvey,
H. E. Largis, V. S. Wong, F. W. Sum, Bioorg. Med.
Chem. Lett. 2003, 13, 2191–2194.
[3] a) G. Bꢄchi, H. Wꢄest, J. Org. Chem. 1966, 31, 977–
978; b) L. Carles, K. Narkunan, S. Penlou, L. Rousset,
D. Bouchu, M. A. Ciufolini, J. Org. Chem. 2002, 67,
4304–4308; c) M. Stratakis, G. Vassilikogiannakis,
Angew. Chem. 2003, 115, 5623–5626; Angew. Chem.
Int. Ed. 2003, 42, 5465–5468; d) S. P. Brown, N. C.
Goodwin, D. W. C. MacMillan, J. Am. Chem. Soc. 2003,
125, 1192–1194; e) Q. Tan, S. J. Danishefsky, Angew.
Chem. 2000, 112, 4683–4685; Angew. Chem. Int. Ed.
2000, 39, 4509–4511; f) I. Efremov, L. A. Paquette, J.
Am. Chem. Soc. 2000, 122, 9324–9325.
[4] a) A. Velty, S. Iborra, A. Corma, Chem. Rev. 2007, 107,
2411–2502; b) A. Benahmed-Gasmi, P. Frꢅre, J. Ronca-
li, J. Electroanal. Chem. 1996, 406, 231–234; c) A. Gan-
dini, M. N. Belgacem, Prog. Polym. Sci. 1997, 22, 1203–
1379; d) E. Lasseuguette, A. Gandini, M. N. Belgacem,
H. J. Timpe, Polymer 2005, 46, 5476–5483; e) T. K.
Chakraborty, A. Arora, S. Roy, N. Kumar, S. Maiti, J.
Med. Chem. 2007, 50, 5537–5542.
[5] K. Amarnath, V. Amarnath, J. Org. Chem. 1995, 60,
301–307.
[6] a) W. Liu, H. Jiang, C. Qi, M. Zhang, J. Org. Chem.
2010, 75, 966–968; b) J. S. Yadav, B. V. S. Reddy, S. Shu-
bashree, K. Sadashiv, J. J. Naidu, Synthesis 2004, 2376–
2380; c) X. H. Duan, X. Y. Liu, L. N. Guo, M. C. Liao,
W. M. Liu, M. Y. Liang, J. Org. Chem. 2005, 70, 6980–
6983; d) Y. Xiao, J. Zhang, Angew. Chem. 2008, 120,
1929–1932; Angew. Chem. Int. Ed. 2008, 47, 1903–1906;
e) Z. P. Zhan, S. P. Wang, X. B. Cai, H. J. Liu, J. L. Yu,
Y. Y. Cui, Adv. Synth. Catal. 2007, 349, 2097–2102; f) R.
Liu, J. Zhang, Chem. Eur. J. 2009, 15, 9303–9306;
g) Y. M. Pan, S. Y. Zhao, W. H. Ji, W. H. Zhan, J.
Comb. Chem. 2009, 11, 103–109; h) X. Z. Shu, X. Y.
Liu, H. Q. Xiao, K. G. Ji, L. N. Guo, C. Z. Qi, Y. M.
Liang, Adv. Synth. Catal. 2007, 349, 2493–2498; i) J.
Fournier, S. Arseniyadi, J. Cossy, Angew. Chem. 2012,
124, 7680–7684; Angew. Chem. Int. Ed. 2012, 51, 7562–
7566; j) M. H. Suhre, M. Reif, S. F. Kirsch, Org. Lett.
2005, 7, 3295–3298; k) X. Du, F. Song, Y. Lu, H. Chen,
Y. Liu, Tetrahedron 2009, 65, 1839–1845; l) L. Li, M. N.
Zhao, Z. H. Ren, J. Li, Z. H. Guan, Synthesis 2012,
532–540; m) J. Zhang, H. G. Schmalz, Angew. Chem.
2006, 118, 6856–6859; Angew. Chem. Int. Ed. 2006, 45,
6704–6707; n) H. Tsuhi, K. I. Yamagata, Y. Ueda, E.
Nakamura, Synlett 2011, 1015–1017; o) J. Wang, R.
Zhou, Z. R. He, Z. He, Eur. J. Org. Chem. 2012, 6033–
6041.
[12] P. Huang, Q. Yang, Z. Chen, Q. Ding, J. Xu, Y. Peng, J.
Org. Chem. 2012, 77, 8092–8098.
[13] a) P. Wipf, S. Venkatraman, J. Org. Chem. 1996, 61,
8004–8005. For mechanism, see: b) K. Miyamoto, Y.
Nishi, M. Ochiai, Angew. Chem. 2005, 117, 7056–7059;
Angew. Chem. Int. Ed. 2005, 44, 6896–6899.
[14] W. Zeng, W. Wu, H. Jiang, Y. Sun, Z. Chen, Tetrahe-
dron Lett. 2013, 54, 4605–4609.
[15] Y. Sasson, J. L. Moore, U.S. Patent 5,138,107, 1992. See
the Supporting Information for a more detailed, slight-
ly modified synthesis of (bromoethynyl)benzene.
[16] a) Z.-X. Jiang, J. Yang, Q.-Q. Min, X. Wan, C.-Y. He, S.
Fan, X. Zhang, J. Am. Chem. Soc. 2010, 132, 4506–
4507; b) P. Lu, C. Sanchez, J. Cornella, I. Larrosa, Org.
Lett. 2009, 11, 5710–5713; c) A. Wagner, C. L. Drian, C.
Catala, J.-M. Becht, Org. Lett. 2007, 9, 1781–1783; d) J.
Wu, X. He, Q. Ding, Z. Wang, Tetrahedron 2009, 65,
4635–4638; e) F. Zhang, M. F. Greaney, Org. Lett. 2010,
12, 4745–4747; f) J. Wang, Z. Cui, Y. Zhang, H. Li, L.-
M. Wu, Z. Liu, Org. Biomol. Chem. 2011, 9, 663–666;
[7] C. He, S. Guo, J. Ke, J. Hao, H. Xu, H. Chen, A. Lei, J.
Am. Chem. Soc. 2012, 134, 5766–5769.
[8] J. P. Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165–
4179.
Adv. Synth. Catal. 0000, 000, 0 – 0
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COMMUNICATIONS
Irwan Iskandar Roslan et al.
g) K. Xie, Z. Yang, X. Zhou, X. Li, S. Wang, Z. Tan, X.
An, C.-C. Guo, Org. Lett. 2010, 12, 1564–1567; h) J.
Cornella, H. Lahlali, I. Larrosa, Chem. Commun. 2010,
46, 8276–8278; i) K. Ouchaou, D. Georgin, F. Taran,
Synlett 2010, 2083–2086.
[19] Examples where Zn was used to reduce Co(II) in-situ
to Co(I) species: a) K.-J. Chang, D. K. Rayabarapu, C.-
H. Cheng, Org. Lett. 2003, 5, 3963–3966; b) D. K. Raya-
barapu, C.-H. Yang, C.-H. Cheng, J. Org. Chem. 2003,
68, 6726–6731; c) C.-C. Wang, P.-S. Lin, C.-H. Cheng,
Tetrahedron Lett. 2004, 45, 6203–6206; d) C.-C. Wang,
P.-S. Lin, C.-H. Cheng, J. Am. Chem. Soc. 2002, 124,
9696–9697; e) G. Hilt, J. Treutwein, Angew. Chem.
2007, 119, 8653–8655; Angew. Chem. Int. Ed. 2007, 46,
8500–8502.
[17] a) M. S. Kharasch, F. L. Lambert, W. H. Urry, J. Org.
Chem. 1945, 10, 298–306; b) M. Corpet, X.-Z. Bai, C.
Gosmini, Adv. Synth. Catal. 2014, 356, 2937–2942; c) X.
Qian, Z. Yu, A. Auffrant, C. Gosmini, Chem. Eur. J.
2013, 19, 6225–6229.
[18] C. Xin, X. Xue, L. Wojtas, M. M. Kim, X. P. Zhang, J.
[20] Y. Nishida, S. Kida, Coord. Chem. Rev. 1979, 27, 275–
298.
Am. Chem. Soc. 2012, 134, 19981–19984.
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Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-
Dicarbonyl Compounds To Form Polysubstituted Furans via
p–p Activation
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Irwan Iskandar Roslan, Jiulong Sun, Gaik-Khuan Chuah,
Stephan Jaenicke*
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