Condensation of propargylic alcohols with 1,3-dicarbonyl compounds and 4-hydroxycoumarins in ionic liquids (ILs)

Article abstract of DOI:10.1016/j.tetlet.2011.10.021

Propargylic alcohols are activated toward 1,3-diketones by Lewis or Br?nsted acidic ionic liquids (ILs) without an added catalyst, but significantly better conversions are achieved with metallic triflates [in particular Sc(OTf)₃ and Ln(OTf)

Full text of DOI:10.1016/j.tetlet.2011.10.021

Tetrahedron Letters 52 (2011) 6859–6864
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Tetrahedron Letters
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Condensation of propargylic alcohols with 1,3-dicarbonyl
compounds and 4-hydroxycoumarins in ionic liquids (ILs)
⇑
Gopalakrishnan Aridoss, Kenneth K. Laali
Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Propargylic alcohols are activated toward 1,3-diketones by Lewis or Brønsted acidic ionic liquids (ILs)
without an added catalyst, but significantly better conversions are achieved with metallic triflates [in
particular Sc(OTf)3 and Ln(OTf)3] and bismuth nitrate in imidazolium ILs. The scope of this condensation
reaction was investigated with a variety of propargylic alcohols and a host of acyclic and cyclic dicarbonyl
compounds. Concomitant cycloisomerization leading to tetrasubstituted furans was observed with the
propargylic alcohols 1b and 1c in reaction with 1,3-diketone 2b and the b-ketoester 2c. With propargylic
alcohol 1c, propargylation, cycloisomerization, or dienone formation were observed, depending on the
structure of the 1,3-dicarbonyl compound. The [BMIM][PF6]/Bi(NO3)3Á5H2O system proved efficient for
propargylation, vinylation, and alkylation of 4-hydroxycoumarins. The recycling and reuse of the IL are
added advantages of this method.
Received 13 September 2011
Revised 4 October 2011
Accepted 6 October 2011
Available online 12 October 2011
Keywords:
Propargylation
1,3-Dicarbonyl compounds
Ionic liquids
Metallic triflates
Bismuth nitrate
Ó 2011 Elsevier Ltd. All rights reserved.
Tetrasubstitued furans
4-Hydroxycoumarins
Condensation of 1,3-dicarbonyl compounds with benzylic,
allylic, and propargylic moieties is an important C–C bond forming
method capable of generating a wide range of valuable synthetic
intermediates that are utilized in the synthesis of functional mate-
rials, natural products, and pharmaceuticals. There has been a flur-
ry of research activity in this area in the past few years and a
number of methods employing various catalysts have been re-
ported. Thus tris(pentafluorophenyl)borane,1 bismuth nitrate
pentahydrate,2 and phosphomolybdic acid supported on silica gel
(PMA/SiO2)3 were employed for alkylation of 1,3-dicarbonyl com-
pounds with benzylic alcohols, and PMA/SiO2,3 FeCl3,4 and
Yb(OTf)3/MeCN.11 Propargylation and cycloisomerization leading
to furans were observed in variable amounts in the reaction of 1-
phenylprop-2-yn-1-ol with 1,3-dicarbonyl compound by using
Au(III) catalysis in organic solvents.12 Tandem propargylation/
cycloisomerization leading to substituted furans was observed
with FeCl3 in refluxing toluene.13 A two-step process using TFA
to effect propargylation followed by an allyl-ruthenium complex
to effect cycloisomerization has also been reported.14
Propargylation of coumarins represents a related useful trans-
formation. Alkylation of 4-hydroxycoumarin with benzylic, allylic,
and propargylic alcohols was reported by using amberlite IR-120
(H+)15 and with Yb(OTf)3.11
5
MoO2(acac)2/NH4PF6 were used as catalysts in propargylation.
Other workers employed an Ir-Sn bimetallic complex in DCE sol-
vent to achieve propargylation or allenylation, depending on the
structure of the propargylic alcohol.6 The rhenium-catalyzed cou-
pling of 2-propynyl alcohols with 1,3-diketones via dehydration
was also studied.7 Indium tribromide was employed in annulation
of cyclic 1,3-diketones with aryl propargyl alcohols to synthesize
2,4-diaryldihydropyrans.8 Cycloaddition between propargylic alco-
hols and cyclic 1,3-dicarbonyl compounds was effected by using
thiolate-bridged diruthenium complexes via allenylidene interme-
diates.9 Depending on the structure of alkynol, propargylation or
allenylation products were obtained with PTS/MeCN10 and with
To our knowledge one study on propargylation of 1,3-dicar-
bonyl compounds in ILs has so far appeared,16 in which a Brønsted
acidic IL was used as catalyst with an imidazolium IL acting as sol-
vent to effect benzylation, allylation, and propargylation of 1,3-
dicarbonyl compounds at 100 °C.
In continuation of our work on electrophilic chemistry in room
temperature ionic liquids (RT-IL),17 and in relation to a recent study
from this laboratory focusing on propargyl group introduction into
aromatics and heteroaromatics and cross coupling of propargylic
alcohols,18 we report here on propargylation of acyclic and cyclic
1,3-dicarbonyl compounds and 4-hydroxycoumarins in ILs.19
With propargylation of 1,3-diphenylpropan-1,3-dione as
benchmark ( Fig. 1) survey study was performed using
various ILs, with and without an added catalyst (Table 1). With
a
a
⇑
Corresponding author. Tel.: +1 904 620 1503; fax: +1 904 620 3535.
E-mail address: kenneth.laali@UNF.edu (K.K. Laali).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.021

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G. Aridoss, K. K. Laali / Tetrahedron Letters 52 (2011) 6859–6864
O
O
OH
O
O
Lewis Acid
IL
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1a
Ph
2a
3
Figure 1. Screening of IL/Lewis acid systems as catalysts in condensation of 1a with 2a as model reaction.
Table 1
Screening of IL/Lewis acid systems as catalysts in condensation of 1a with 2a as model reaction
S. No.
Lewis acid
IL
Temp (°C)
Isolated yield (%)
1
2
3
4
5
6
7
8
[C2H5NH3][NO3]
Bi(NO3)3Á5H2O
Bi(NO3)3Á5H2O
Bi(OTf)3
Al(OTf)3
Ln(OTf)3
[C2H5NH3][NO3]
[C2H5NH3][NO3]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][BF4]
[BMIM][PF6]
50
50
30
50
60
50
40
40
21
48
91 (90a, 85a)
10
Trace
81
Sc(OTf)3
Sc(OTf)3
88 (86a, 80a)
85
O2N
Butyl
O2N
Butyl
N
NTf2
N
NTf2
9
50
52
N
N
Et
Et
a
Yield corresponds to second and third runs respectively without re-loading catalyst.
O
R2
O
OH
O
O
Lewis Acid
IL ; 30-60 o
R3
R
R2
R3
R1
C
R
2a-2d
R2 & R3 - various groups
1a-1d
R1
3-15
R = Ph, CH3,
1 = H, Ph, Si(CH3)3
R
Figure 2. Condensation of propargylic alcohols with 1,3-dicarbonyl compounds with IL/Lewis acid systems.
ethylammonium nitrate (EAN) the yield was modest, but conver-
sion was improved with EAN/Bi(NO3)3. Under comparable
conditions, the Lewis acidic IL nitro-substituted butyl-ethyl-
limidazolium-NTf2 gave 52% isolated yield without an added
catalyst. Among the IL/Lewis acid systems studied [BMIM][PF6]/
Bi(NO3)3Á5H2O and [BMIM][PF6]/Sc(OTf)3 proved most effective
and were therefore selected to examine the scope of this transfor-
mation (Fig. 2 and Table 2).
In selected cases (Table 1 runs 3 and 7) the reactions were re-
peated in used [BMIM][PF6] IL without addition of fresh Lewis acid.
A slight decrease in the isolated yields was observed for these
cases.
Propargylic alcohols 1a–1d reacted with acyclic 1,3-diketones
2a and 2b, the ketoester 2c, and the cyclic 2d. In many cases, the
direct propargylation products were obtained in respectable iso-
lated yields under very mild conditions. The dipropargylic ethers
6b18 and 9a20 were obtained as minor byproducts (see runs 4, 7
and 10—Table 2).
1,3-dicarbonyl compound. Furan formation became predominant
in reaction with the ketoester 2c. Condensation of 1c with the cyc-
lic 2d resulted in isolation of the corresponding allene 14. For com-
parison, allyl alcohol 1e reacted with 2b to give the condensation
product 15 in 86% isolated yield. Figure 3 gives a summary of the
reactions of 2b and 2c with 1b and 1c leading to the observed
products.
The next phase of this study focused on propargylation of
4-hydroxycoumarins ( Fig. 4). Thus 4-hydroxycoumarin 16a
and 6-chloro-4-hydroxycoumarin 16b reacted with the prop-
argylic alcohols 1a–1c, as well as allyl alcohol 1e, and
diphenylmethanol 1f to give the corresponding 3-substituted
coumarins in isolated yields ranging from 96% to 81% except
for reaction of 1a with 16b where the formation of byprod-
ucts 22b and 22c lowered the isolated yield of the desired
product.
The present method offers a number of advantages over the ear-
lier reported procedures as it avoids the use of volatile solvents and
gives respectable isolated yields under very mild conditions. The
recycling/reuse of the IL is an added advantage.
Competing cycloisomerization to form tetrasubstituted furans
were observed with 1b and 1c, depending on the structure of the

G. Aridoss, K. K. Laali / Tetrahedron Letters 52 (2011) 6859–6864
6861
Table 2
Condensation of propargylic alcohols with 1,3-dicarbonyl compounds in IL/ Bi(NO3)3Á5H2O or IL/Sc(OTf)3 systems
S. No.
Alcohol
Diketone
Products
Time (h)
2.0
Temp (°C)
Isolated yield (%)
OH
O
O
O
Ph
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2a
1
À
30
91
92
1a
Ph
3
OH
O
O
O
Ph
Ph
Ph
Si
2a
2
À
À
1.5
30
Ph
1b
Si
4
OH
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3
4
3.0
50
60
83
2a
1c
Ph
O
5
OH
O
O
O
Ph
Ph
Ph
16
47 (6a)/36 (6b)a
2a
Ph
1d
Ph
Ph
6b
6a
OH
O
O
O
O
Ph
Ph
92b
Ph
2b
5
À
2
40
Ph
O
1a
Ph
7
OH
O
O
O
O
Ph
Si
79 (8a & 8b)c
Refer to Figure 3
81d
2b
6
7
8
4
9
6
45
60
45
Ph
O
8b
1b
TMS
8a
OH
O
O
O
Ph
Ph
Mixture of products 8b, 9a–9c
2b
O
1c
OH
O
O
OEt
OEt
Ph
2c
À
Ph
1a
Ph
10
OH
O
O
O
O
O
O
EtO
OEt
Ph
Ph
OEt
OEt
O
O
2c
Si
9
5
45
60
68 (11a & 11bd)e
Ph
Ph
Si
1b
11a
11b
OH
O
O
Ph
EtO
O
10
10
51 (11a & 9a)f
2c
1c
Ph
Ph
9a
11a
(continued on next page)

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G. Aridoss, K. K. Laali / Tetrahedron Letters 52 (2011) 6859–6864
Table 2 (continued)
S. No.
Alcohol
OH
Diketone
Products
Time (h)
Temp (°C)
Isolated yield (%)
O
O
O
O
Ph
Ph
Ph
Si
11
À
3
40
88d
1a
2d
2d
Ph
12
OH
O
O
O
O
Ph
Ph
12
À
3.5
40
82d
1b
Si
13
OH
O
O
O
O
O
O
H
Ph
Ph
.
13
14
À
À
6
40
35
67d
1c
H
2d
2b
Ph
14
OH
Ph
O
O
1.5
86g
1e
Ph
Ph
15
a
b
c
d
e
f
Dipropargylic ether (6b) exists in two geometrical isomers (in 1:0.74 ratio by NMR) and the unreacted alcohol (1d) was recovered.
90% yield was achieved with [BMIM][BF4]/Sc(OTf)3.
GC yield (8a:8b = 60.7:39.3).
Exists as two diastereomers.
GC–MS yield (11a:11b = 92.2:7.8).
GC–MS yield (11a:9a = 73.5:26.5).
g
82% yield was achieved with [BMIM][BF4]/Sc(OTf)3.
OH
O
O
O
O
O
O
OH
Ph
Ph
EtO
Ph
OEt
Ph
TMS
45 o
C
1b
1b
45 oC
TMS
Ph
Ph
O
O
8b
TMS
8a
60.7% (by GC)
Cycloisomerization
TMS
11b
11a
39.3% (by GC)
92.2% (by GC-MS) 7.8% (by GC-MS)
O
O
Bi(NO3)3.5H2O
Bi(NO3)3.5H2O
-TMS
Cycloisomerization
-TMS
R
[BMIM][PF6]
if R = OEt
[BMIM][PF6]
if R = Me
2b
8a and 8b obtained as mixture (79%)
11a and 11b obtained as mixture (68%)
2c
O
O
O
Ph
O
Cycloisomerization
8b
O
O
EtO
60 o
C
60 o
OH
C
O
Ph
Ph
Ph
OH
Ph
62% (by GC)
Ph
11a
9a
Ph
Ph
73.5% (by GC-MS)
O
26.5% (by GC-MS)
1c
1c
9a
8b and 9a obtained as mixture (29%)
Ph
11a
9a
38% (by GC)
and
obtained as mixture (51%)
Meyer–Schuster
rearrangement
of alcohol
H2O
O
O
O
O
Ph
O
H
Ph
9b
55.5% (by GC)
9b and 9c obtained as mixture (61%)
9c
45.5% (by GC)
Figure 3. Product distribution as a function of propargylic alcohol.

G. Aridoss, K. K. Laali / Tetrahedron Letters 52 (2011) 6859–6864
6863
OH
OH
OH
R
O
R2
Lewis Acid
R2
R
IL ; 35-60 oC
R1
R1
O
O
O
1a-1f
16a
; 16b
(R2 =H)
(R2 = Cl)
17-23
R = Ph, CH3
R1 = H, Ph, Si(CH3)3
Figure 4. Propargylation of 4-hydroxycoumarins in IL/Lewis acid systems.
Table 3
C-3 alkylation of 4-hydroxycoumarins in IL/Bi(NO3)3Á5H2O system
Entry
Alcohol
Coumarin
OH
Product
Temp (°C)
Time (h)
Isolated yield (%)
OH
Ph
O
OH
O
Ph
Ph
Si
Ph
15
35
1
90
92
87
81
93
O
16a
O
O
O
O
O
1a
17
OH
OH
OH Ph
Ph
Ph
Ph
Ph
Ph
Ph
Si
16
17
18
19
35
40
35
35
1.5
O
O
O
16a
1b
18
OH
OH
OH Ph
4
1c
O
16a
O
19
O
OH
Ph
OH
OH Ph
Ph
1e
1.5
O
16a
O
O
20
OH
Ph
OH
OH Ph
Ph
1f
1
O
16a
O
21
O
OH
OH
O
OH Ph
Cl
Cl
Cl
Cl
43a
Ph
Ph
20
21
60
40
10
O
O
O
O
1a
22a
16b
OH
Ph
OH
O
OH Ph
Ph
5
96
1f
O
O
23
16b
a
Dipropargylic ether 22b [present as a mixture of two geometrical isomers (1:0.74)] and ketone 22c were also formed (in 1:1 ratio; 48%), unreacted alcohol (1a) was also
recovered.
Ph
O
O
Ph
Ph
Ph
Ph
Ph
22c
22b

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G. Aridoss, K. K. Laali / Tetrahedron Letters 52 (2011) 6859–6864
16. Funabiki, K.; Komeda, T.; Kubota, K.; Matsui, M. Tetrahedron 2009, 65, 7457–
Acknowledgment
7463.
17. (a) Laali, K. K.; Gettwert, V. J. J. Org. Chem. 2001, 66, 35–40; (b) Laali, K. K.;
Gettwert, V. J. J. Fluorine. Chem. 2001, 107, 31–34; (c) Laali, K. K.; Borodkin, G. I.
J. Chem. Soc. Perkin Trans. 2 2002, 953–957; (d) Sarca, V. D.; Laali, K. K. Green
Chemistry 2004, 6, 245–248; (e) Laali, K. K.; Sarca, V. D.; Okazaki, T.; Brock, A.;
Der, P. Org. Biomol. Chem. 2005, 3, 1034–1042; (f) Sarca, V. D.; Laali, K. K. Green
Chemistry 2006, 8, 615–620; (g) Laali, K. K.; Okazaki, T.; Bunge, S. J. Org. Chem.
2007, 72, 6758–6762; (h) Hubbard, A.; Okazaki, T.; Laali, K. K. Aust. J. Chem.
2007, 60, 923–927; (i) Hubbard, A.; Okazaki, T.; Laali, K. K. J. Org. Chem. 2008,
73, 316–319; (j) Pavlinac, J.; Laali, K. K.; Zupan, M.; Stavber, S. Aust. J. Chem.
2008, 61, 946–955; (k) Pavlinac, J.; Zupan, M.; Laali, K. K.; Stavber, S.
Tetrahedron 2009, 65, 5625–5662; (l) Kalkhambkar, R. G.; Waters, S. N.; Laali,
K. K. Tetrahedron Lett. 2011, 52, 867–871; (m) Kalkhambkar, R. G.; Laali, K. K.
Tetrahedron Lett. 2011, 52, 1733–1737; (n) Aridoss, G.; Laali, K. K. Eur. J. Org.
Chem. 2011, 2827–2835; (o) Aridoss, G.; Laali, K. K. Eur. J. Org. Chem. 2011, 2,
6343–6355; (p) Aridoss, G.; Laali, K. K. J. Org. Chem. 2011, 76, 8088–8094.
18. Aridoss, G.; Sarca, V. D.; Ponder, J. F., Jr.; Crowe, J.; Laali, K. K. Org. Biomol. Chem.
2011, 9, 2518–2529.
We thank University of North Florida for support and Dr. Nelson
Zhao of this department for NMR assistance.
Supplementary data
Supplementary data (NMR analysis of the products and other
characterization data for the new compounds are furnished) asso-
ciated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2011.10.021.
References and notes
1. Reddy, C. R.; Vijaykumar, J.; Grée, R. Synthesis 2010, 21, 3715–3723.
2. J. Escano, D. Bandyopadhyay, B.K. Banik, Abstracts of Papers, 238th, National
Meeting of the American Chemical Society, Washington, DC, Aug 16–20, 2009;
American Chemical Society: Washington, DC, 2009; ORGN-107.
3. Yadav, J. S.; Subba Reddy, B. V.; Pandurangam, T.; Raghavendra Rao, K. V.;
Praneeth, K.; Narayana Kumar, G. G. K. S.; Madavi, C.; Kunwar, A. C. Tetrahedron
Lett. 2008, 49, 4296–4301.
4. Maiti, S.; Biswas, S.; Jana, U. Synth. Commun. 2011, 41, 243–254.
5. Zhang, M.; Yang, H.; Cheng, Y.; Zhu, Y.; Zhu, C. Tetrahedron Lett. 2010, 51, 1176–
1179.
6. Chatterjee, P. N.; Roy, S. Tetrahedron 2011, 67, 4569–4577.
7. Kuninobu, Y.; Ueda, H.; Takai, K. Chem. Lett. 2008, 37(8), 878–879.
8. Yadav, J. S.; Subba Reddy, B. V.; Raghavendra Rao, K. V.; Narender, R.
Tetrahedron Lett. 2009, 50, 3963–3965.
9. Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Org. Chem.
2004, 69, 3408–3412.
10. Sanz, R.; Miguel, D.; Martínez, A.; Álvarez-Gutiérrez, J. M.; Rodríuez, F. Org. Lett.
2007, 9(4), 727–730.
11. Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Tetrahedron 2007, 63, 11636–11643.
12. Arcadi, A.; Alfonsi, M.; Chiarini, M.; Marinelli, F. J. Organomet. Chem. 2009, 694,
576–582.
13. Ji, W.-h.; Pan, Y.-m.; Zhao, S.-y.; Zhan, Z.-p. Synlett 2008, 3046–3052.
14. Cadierno, V.; Gimeno, J.; Nebra, N. Adv. Synth. Catal. 2007, 349, 382–394.
15. Reddy, C. R.; Srikanth, B.; Narsimha Rao, N.; Shin, D.-S. Tetrahedron 2008, 64,
11666–11672.
19. General procedure for propargylation of diketones and 4-hydroxycoumarins: The
desired ionic liquid (2 mL if the reactants were liquids and 3.00–3.5 mL for
solids) was charged into an oven-dried Schlenk tube under
a nitrogen
atmosphere. The Lewis acid (10 mol %) was then introduced and was
dissolved or immobilized in the IL upon sonication (for about 15 min). No
catalyst was used in entries 1 and 9 in Table 1. The respective 1,3-diketone or
the 4-hydroxycoumarin was then introduced into the Schlenk tube under a
nitrogen atmosphere followed by the desired propargylic alcohol. The reaction
mixture was magnetically stirred, initially at rt for about 10 min followed by
stirring in a pre-heated oil bath at 30–60 °C (as specified; refer to Tables 1–3),
until completion (monitored by TLC). Once the reaction was over, the contents
were cooled to rt and extracted with dry diethyl ether or with EtOAc–Hexane
(2:3)—(until the final extraction showed no spot corresponding to the starting
material or to the product). The combined organic extracts were washed with
DI water, dried with MgSO4 and concentrated to give the crude product, which
upon purification through column chromatography furnished the desired
products. In some cases the crude reaction mixture obtained upon evaporation
of the combined organic extracts was directly charged onto a column for
purification without a water wash.
Re-use and recycling of IL: After extraction, the ionic liquid was dried under
high-vacuum at 60–70 °C for about 6 h and re-used for successive runs.
20. Maraval, V.; Duhayon, C.; Coppel, Y.; Chauvin, R. Eur. J. Org. Chem. 2008, 5144–
5156.