Inexpensive and efficient synthesis of propargylic substituted active methylene compounds catalyzed by FeCl3

Article abstract of DOI:10.1080/00397910903534031

A highly efficient and practical method for the synthesis of propargylic substituted 1,3-dicarbonyl compounds with direct use of propargylic alcohols in the presence of inexpensive and environmentally benign FeCl₃ (5mol%) has been presented. Th

Full text of DOI:10.1080/00397910903534031

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Inexpensive and Efficient Synthesis of
Propargylic Substituted Active Methylene
Compounds Catalyzed by FeCl3
Sukhendu Maiti a , Srijit Biswas a & Umasish Jana a
a Department of Chemistry , Jadavpur University , Kolkata, West
Bengal, India
Published online: 15 Dec 2010.
To cite this article: Sukhendu Maiti , Srijit Biswas & Umasish Jana (2010) Inexpensive and Efficient
Synthesis of Propargylic Substituted Active Methylene Compounds Catalyzed by FeCl3 , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:2, 243-254, DOI: 10.1080/00397910903534031
To link to this article: http://dx.doi.org/10.1080/00397910903534031
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Synthetic Communications1, 41: 243–254, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903534031
INEXPENSIVE AND EFFICIENT SYNTHESIS OF
PROPARGYLIC SUBSTITUTED ACTIVE METHYLENE
COMPOUNDS CATALYZED BY FeCl3
Sukhendu Maiti, Srijit Biswas, and Umasish Jana
Department of Chemistry, Jadavpur University, Kolkata, West Bengal, India
A highly efficient and practical method for the synthesis of propargylic substituted
1,3-dicarbonyl compounds with direct use of propargylic alcohols in the presence of inex-
pensive and environmentally benign FeCl3 (5 mol%) has been presented. The reaction
works with varieties of substrates at room temperature without an inert atmosphere with
an excellent yield. The present method can also be employed for the large-scale synthesis
of propargylic substituted active methylene compounds.
Keywords: Atom economical; carbon–carbon bond; iron salt; propargylic alcohols; sustainable chemistry
INTRODUCTION
Because of their efficient transformation into various functional groups,[1,2] the
alkynes are important building blocks in the synthesis of natural products, drug can-
didates, and material science.[3] Consequently, a wide variety of strategies have been
developed to achieve highly substituted alkynes with the required complexity in the
structure. Among the various strategies to construct complex alkynes molecules, pro-
pargylic substitution with various nucleophiles has attracted much attention. Tra-
ditionally, propargylic substitution is carried out using the Nicholas reaction[4] via
cobalt complex–stabilized propargylic carbocation intermediate. However, it has
several drawbacks, such as use of a stoichiometric amount of Co2(CO)8 and a multi-
step reaction. Thus, to avoid these problems, many methods have been described for
the direct substitution of propargylic alcohols in the presence of various transition
metals such as ruthenium, rhenium, bismuth, gold, and Brønsted acids.[5] Although
these direct substitutions of propargylic alcohols are attractive processes in organic
synthesis because of easy availability of the substrates, the reaction is also highly
atom economical as the water is the only by-product.[6] However, compared to
heteroatom-centered nucleophiles such as alcohols, thiols, amides, and so on,
carbon-centered nucleophiles were unfortunately limited to allylsilanes and electron-
rich aromatic compounds.
Received August 23, 2009.
Address correspondence to Umasish Jana, Department of Chemistry, Jadavpur University,
Kolkata 700032, West Bengal, India. E-mail: jumasish2004@yahoo.co.in
243

244
S. MAITI, S. BISWAS, AND U. JANA
Scheme 1. Reaction of propargylic alcohols with 1,3-dicarbonyl compounds.
On the other hand, alkylation of 1,3-dicarbonyl compounds is very important
and a fundamental reaction in organic synthesis. Recently, a number of methods
have been developed for the synthesis of substituted active methylene compounds
by the direct substitution of alcohol in the presence of a catalytic amount of tran-
sition metal and Lewis and Brønsted acids. However, such a strategy has been
applied mostly to the synthesis of allylic- and benzylic-substituted 1,3-dicarbonyl
compounds,[7] and the synthesis of propargylic substituted 1,3-dicarbonyl com-
pounds has been little explored. The reagents available to effect this substitutions
are Yb(OTf)3,[8] InCl3,[9] p-toluenesulfonic acid (PTS),[10] ruthenium(II) with trifluor-
oacetic acid,[11] copper(II) triflate,[12] and phosphomolybdic acid supported on silica
gel (PMA=SiO2).[13] Most of these reagents have been used for the one-pot synthesis
of furan derivatives, and only a few have been demonstrated for the synthesis of pro-
pargylic substituted active methylene compounds. Recently, Cheng and Bao
reported synthesis of these compounds using 2,3-dichloro-5,6-dicyanobenzoquinone
(DDQ) via an oxidative cross-coupling reaction.[14] Although these methods are suit-
able for certain synthetic reaction conditions, many of these procedures are associa-
ted with one or more disadvantages such as long reaction time; use of expensive,
toxic, and moisture-sensitive reagents; poor yield; requirement of excess of reagents
or catalysts; and harsh reaction conditions.
The development of sustainable, environmentally benign C-C bond-forming
processes is one of the fundamental goals in organic chemistry. As a result,
iron-catalyzed reactions have received considerable attention because they are less
expensive, readily available, environmentally benign, and perform many useful
organic transformations under mild conditions.[15] Considering the significance of
direct substitution of alcohols, several researchers[7b,16,17] have demonstrated
efficient iron salts–catalyzed direct substitution of alcohols with various nucleo-
philes. In continuation of our previous work on the direct substitution of benzylic
and allylic alcohols with active methylene compounds,[7b] we report herein an
efficient synthesis of propargylic substituted 1,3-dicarbonyl compounds under mild
conditions by direct substitution of propargylic alcohols in the presence of catalytic
FeCl3 (Scheme 1).
RESULTS AND DISCUSSION
Although propargylic substitution reactions between various nucleophiles with
propargylic acetate[18] and alcohols[16a,16d,17a] in the presence of iron salts have been
reported recently, the synthesis of propargylic substituted 1,3-dicarbonyl compounds

FeCl3 AS AN EFFICIENT CATALYST
245
by the direct substitution of propagylic alcohols has not been reported. Thus,
encouraged by our previous work, we decided to study systematically the reaction
between various active methylene compounds and propargylic alcohols to synthesize
the propargylic substituted active methylene compounds.[19]
First, we investigated the model reaction of active methylene compound 2a
with propargylic alcohol 1a using FeCl3 under different reaction conditions to stan-
dardize the reaction condition. The reaction worked well in various solvents such as
dichloromethane, dichloroethane, nitromethane, and acetonitrile with comparable
yield at room temperature without an inert atmosphere. The reaction was sluggish
in toluene solvent at room temperature but completed within a few minutes under
reflux.[20] Dichloromethane was found to be the most effective solvent in this reac-
tion in terms of time and yield of the propargylic substituted products. Moreover,
we also observed that anhydrous FeCl3 gave slightly better yield compared to the
hydrated FeCl3. The reaction was reasonably fast and clean, and 5 mol% of FeCl3
was sufficient for complete conversion of reactants to product in dichloromethane
solvent with an excellent yield of 3a (92%).
Having optimized the reaction conditions, we then explored the generality and
efficiency of this reaction between various active methylene compounds and second-
ary propargylic alcohol 1a. In general, the reaction proceeded smoothly for all cases
in very good to excellent yields within a short period of time with complete regio-
selectivities with respect to both of the reactants. The results are summarized in
Table 1. The procedure worked efficiently for both acyclic (Table 1, entries 1–4)
and cyclic (Table 1, entry 5) b-diketones. Moreover, methyl substituted b-diketone
2b (Table 1, entry 2) also reacted smoothly with alcohol 1a and gave the greatest
yield of the product 3b (90%).
Furthermore, b-ketoesters also reacted smoothly at room temperature with
propargylic alcohol 1a to produce the corresponding desired product in 88–92%
yields (Table 1, entries 6–8). The FeCl3-catalyst propargylation reaction also worked
efficiently for the synthesis of propargylic substituted coumarin 3i in good yield
(77%) in 1:1 dichloromethane and 1,4-dioxane solvent at 50 ꢀC (Table 1, entry 9).
Synthesis of substituted coumarins is very important in organic synthesis because
of their biological significance and their unique role as a valuable synthetic inter-
mediate in pharmaceuticals.[21] However, the synthesis of substituted coumarines
mostly relied on the alkylation of 4-hydroxy coumarine using alkyl halide in the
presence of a base or in the presence of transition metals. Moreover, alkyne substi-
tuted coumarins would be valuable intermediates because of their further synthetic
manipulation.
Encouraged by these results, we subsequently tested this reaction for various
substituted propargylic alcohols, and the results are summarized in Table 2. Both
electron-rich and moderately electron-poor propargylic alcohols reacted efficiently
with various 1,3-dicarbonyl compounds, affording the corresponding propargylated
products in good yields. Functional groups, such as chloride, methoxy, and nitro, in
propargylic alcohols did not affect the formation of the products under the reaction
conditions. More interestingly, heterocylic molecules such as thiophene substituted
propargylic alcohols also reacted smoothly with b-diketones, such as 2a and 2d,
and gave the desired products 3p and 3q in good yields (Table 2, entries 7 and 8)
without formation of any side product. It is interesting to note that acid-sensitive

246
S. MAITI, S. BISWAS, AND U. JANA
Table 1. FeCl3-catalyzed propargylic substitution between propargyl alcohol 1a and various active
methylene compounds 2
Entry
1
2
Time
Product
Yields (%)a Ref.
1
2
92
90
92
8
8
2
3
1a
1a
2
2
10
4
5
6
1a
1a
1a
2
2
3
94
90
8
10
––
90b
7
8
1a
1a
3
3
88b
8
92b
––
(Continued )

FeCl3 AS AN EFFICIENT CATALYST
247
Table 1. Continued
Entry
9
1
2
Time
Product
Yields (%)a Ref.
1a
3
77c
8
aThe yields refer to pure isolated products obtained after column chromatography and characterized
by spectral data.
b1.2 eq. alcohol was used.
cThe reaction was carried out in 1:1 dichloromethane=1,4 dioxan solvent at 50 ꢀC.
secondary aliphatic alcohol 1f (Table 2, entry 11) also participated in this reaction,
but the reaction was sluggish at room temperature in CH2Cl2 solvent. However, the
desired product 3t was obtained in 63% yield in nitromethane solvent at 60 ꢀC. After
demonstrating the generality of this reaction for secondary propargylic alcohols and
active methylene compounds under iron-salt catalysis, we studied the reaction of ter-
tiary propargylic alcohol. We have observed that in contrast to the Yb(OTf)3-
catalyzed reaction, which gave allene derivatives,[8] for the same substrate the iron
salt–catalyzed reaction produced only the conjugated diene-dione 3v in 90% yield
(Table 2, entry 13). This product was possibly formed via allenylation of 1,3-
diketones followed by isomerization of the double bond, leading to the most stable
conjugated carbonyl compound. This reaction can be regarded as an alternative of
classical base-catalyzed Knoevenagel reaction between active methylene compounds
and a,b-unsaturated carbonyl compounds for the synthesis of diene-dione, and
this structural motif is a very useful intermediate for the further synthetic trans-
formations such as Diels–Alder and Michael additions.[22] However, the primary
propargylic alcohol 1i did not react under the similar reaction conditions, even
at higher temperature. This experimental observation suggested that a propargylic
carbocation intermediate is involved during the course of the reaction. However,
because of the instability of the primary carbocation, the alcohol 1i did not react.
Finally, to investigate the efficiency of this methodology on a multigram scale,
we conducted a reaction between propargylic alcohol 1a (1.65 g, 7.96 mmol) and
active methylene compound 2d (1.78 g, 7.96 mmol). Significantly, we observed that
this reaction also afforded the desire product 3d with excellent yield, 91% (3.00 g,
7.24 mmol), almost same as that of the small-scale (1 mmol) reaction.
In conclusion, we have developed an efficient method for the synthesis of pro-
pargylic substituted active methylene compounds in the presence of FeCl3 (5 mol%)
by the direct use of propargylic alcohols (highly atom economical). The present
method has many advantages over the previously reported methods, such as mild
reaction conditions, operational simplicity, good yields, inexpensive components,
and use of nontoxic iron salt as a catalyst [compared to Yb(OTf)3 and p-TsOH].
Functional groups such as chloride, methoxy, nitro, ester, triple bond, and ketones
remained unaffected under the reaction conditions. The reaction also worked with
similar efficiency on a moderate scale at room temperature. Additionally, this
method was also efficient for the synthesis of propargylic substituted 4-hydroxy

248
S. MAITI, S. BISWAS, AND U. JANA
Table 2. FeCl3-catalyzed propargylic substitution between propargyl alcohol 1 and various active
methylene compounds 2
Entry
1
2
Time (h)
Product
Yields (%)a Ref.
1
2a
2
90
8
2
3
4
5
1b
1b
1b
2d
2
92
8
2f
3
84b
82b
90
––
––
14
2g
3
2a
1.5
6
7
1c
2d
1.5
94
85
14
––
2a
2
(Continued )

FeCl3 AS AN EFFICIENT CATALYST
249
Table 2. Continued
Entry
1
2
Time (h)
Product
Yields (%)a Ref.
8
1d
2d
2
88b
8
8
9
2a
2
85b,c
10
11
1e
2d
2d
2
3
88b,c
8
8
63b,c
12
2d
2
93
––
13
14
2d
2d
2
6
90
10
—
NRe
aThe yields refer to pure isolated product obtained after column chromatography and characterized
by spectral data.
b1.2 eq. alcohol was used.
cThe reaction worked in nitromethane solvent.
dThe reaction worked at 60 ꢀC in nitromethane solvent.
eRoom temperature for 3 h, then reflux for 5 h.

250
S. MAITI, S. BISWAS, AND U. JANA
coumarin derivatives. Thus, we believe that the present method would be an attrac-
tive and environmentally friendly alternative process for the synthesis of propargylic
substituted active methylene compounds and related applications both in academic
and industrial applications.
EXPERIMENTAL
Representative Experimental Procedure for the Synthesis of
3-(1,3-Diphenyl-2-propynyl)pentane-2,4-dione (3a)[8]
Anhydrated FeCl3 (8 mg, 0.05 mmol) was added to a stirred solution of alcohol
1a (208 mg, 1 mmol) and acetyl acetone 2a (100 mg, 1 mmol) in dichloromethane
(3 mL), and the resulting mixture was stirred vigorously at room temperature for a
set period of time. After completion of the reaction [by thin-layer chromatography
(TLC)], dichloromethane was evaporated under reduced pressure, and the residue
was purified by silica gel (60–120 mess) column chromatography using 5–10% ethyl
acetate–petroleum ether solution (v=v) to afford the desired product 3a as a white
solid (267 mg, 0.92 mmol, 92%), mp 91–92 ꢀC. IR (KBr) 1722, 1701, 1359, 754,
690 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 1.94 (s, 3H), 2.40 (s, 3H), 4.23 (d,
.
J ¼ 10.9 Hz, 1H), 4.68 (d, J ¼ 10.9 Hz, 1H), 7.28–7.43 (m, 10H) ppm. 13C NMR
(CDCl3, 75 MHz) d 28.8, 31.1, 38.1, 75.6, 77.5, 88.1, 122.7, 127.8, 128.2, 128.3,
128.4, 128.9, 131.6, 138.2, 201.6, 201.6 ppm.
Methyl 2-Acetyl-3,5-diphenylpent-4-ynoate (3f)
Alcohol 1a (250 mg, 1.2 mmol) and 1,3-dicarbonyl compound 2d (116 mg,
1 mmol) in dichloromethane (3 mL) and anhydrated FeCl3 (8 mg, 0.05 mmol) yielded
a sticky yellowish liquid (90%, 1:1 mixture of two diastereoisomers). IR (neat) 1743,
1712, 1491, 758, 692 cmꢁ1. 1H NMR (CDCl3, 300 MHz) d 2.01 (s, 3H), 2.44 (s, 3H),
3.55 (s, 3H), 3.82 (s, 3H), 4.01–4.12 (m, 2H), 4.63–4.68 (m, 2H), 7.27–7.47 (m, 20H)
ppm. 13C NMR (CDCl3, 75 MHz): d ¼ 30.0, 30.7, 38.0, 52.5, 52.8, 66.5, 66.7, 84.6,
84.9, 88.0, 88.4, 122.8, 123.0, 127.8, 128.2, 128.2, 128.3, 128.3, 128.7, 128.8, 131.7,
138.2, 167.3, 167.6, 200.3, 200.7 ppm.
Ethyl 1-(1,3-Diphenylprop-2-ynyl)-2-oxocyclohexanecarboxylate (3h)
Product 3h (92%, 1:2 mixture of two diastereoisomers). Diastereomer 1 (31%):
1
obtained as a white solid, mp 109–111 ꢀC. IR (neat) 1709, 1491, 1229, 754 cmꢁ1. H
NMR (CDCl3, 300 MHz) d 1.27 (t, J ¼ 7.1 Hz, 3H), 1.45–1.55 (m, 2H), 1.76–1.84 (m,
2H), 1.90–1.97 (m, 1H), 2.34–2.51 (m, 3H), 4.21–4.28 (q, 2H), 4.93 (s, 1H), 7.24–7.35
(m, 6H), 7.41–7.44 (m, 2H), 7.55 (d, J ¼ 7.7 Hz, 2H) ppm. 13C NMR (CDCl3,
75 MHz) d 14.0, 22.4, 26.5, 32.6, 41.3, 41.5, 61.7, 65.9, 76.6, 84.3, 88.7, 123.3,
127.3, 127.8, 127.9, 128.1, 130.6, 131.6, 137.0, 169.5, 204.8 ppm. HRMS: m=z calcd.
for C24H24NaO3: 383.1624; found: 383.1628.
Diastereomer 2 (61%): obtained as a pale yellowish sticky liquid. IR (neat)
.
1717, 1491, 1229, 758 cmꢁ1
3H), 1.65–1.73 (m, 2H), 1.76–1.89 (m, 1H), 2.01–2.05 (m, 1H), 2.17–2.38 (m, 2H),
1H NMR (CDCl3, 300 MHz) d 1.15 (t, J ¼ 7.1 Hz,

FeCl3 AS AN EFFICIENT CATALYST
251
2.54–2.63 (m, 2H), 4.01–4.04 (q, 2H), 4.93 (s, 1H), 7.27–7.36 (m, 8H), 7.40–7.45 (m,
2H) ppm. 13C NMR (CDCl3, 75 MHz) d 13.8, 22.5, 26.6, 31.2, 41.4, 42.0, 61.5, 65.9,
84.9, 88.9, 123.5, 127.6, 127.9, 128.1, 128.1, 129.2, 131.7, 137.2, 168.9, 204.4 ppm.
HRMS: m=z calcd. for C24H24NaO3: 383.1624; found: 383.1623.
Methyl 2-Acetyl-3-(4-chlorophenyl)-5-phenylpent-4-ynoate (3l)
Sticky yellowish liquid (84%, 1:1 mixture of two diastereoisomers). IR (neat)
1748, 1721, 1489, 1244, 758 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.07 (s, 3H),
.
2.45 (s, 3H), 3.58 (s, 3H), 3.81 (s, 3H), 3.97–4.07 (m, 2H), 4.60–4.67 (m, 2H),
7.28–7.42 (m, 18H) ppm.13C NMR (CDCl3, 75 MHz) d 30.0, 30.7, 37.0, 37.2, 52.6,
52.9, 66.4, 66.4, 85.0, 85.1, 87.5, 87.8, 122.5, 122.8, 128.3, 128.3, 128.5, 128.9,
129.2, 129.6, 129.8, 130.0, 130.2, 131.6, 133.6, 133.6, 133.7, 136.8, 136.9, 167.1,
167.4, 200.0, 200.4 ppm. HRMS: m=z calcd. for C20H17ClNaO3: 363.0764; found:
363.0769.
Ethyl 2-Acetyl-3-(4-chlorophenyl)-5-phenylpent-4-ynoate (3m)
Sticky yellowish liquid (82%, 1:1 mixture of two diastereoisomers). IR (neat)
1744, 1721, 1489, 1242, 758 cmꢁ1. 1H NMR (CDCl3, 300 MHz) d 1.09 (t, J ¼ 7.1 Hz,
3H), 1.29 (t, J ¼ 7.1 Hz, 3H), 2.07 (s, 3H), 2.43 (s, 3H), 3.95–4.06 (m, 4H), 4.24–4.31
(m, 2H), 4.59–4.67 (m, 2H), 7.26–7.42 (m, 20H) ppm. 13C NMR (CDCl3, 75 MHz) d
13.9, 14.1, 29.9, 30.5, 37.0, 37.2, 61.8, 62.0, 66.6, 84.7, 85.0, 87.6, 87.9, 122.6, 122.8,
128.3, 128.4, 128.5, 128.7, 128.8, 128.9, 129.7, 129.8, 130.2, 131.6, 133.5, 133.6, 136.8,
137.0, 166.7, 166.9, 200.0, 200.4 ppm. HRMS: m=z calcd. for C21H19ClNaO3:
377.0920; found: 377.0920.
3-(3-Phenyl-1-(thiophen-2-yl)prop-2-ynyl)pentane-2,4-dione (3p)
1
Sticky deep brown liquid (85%). IR (neat) 1701, 1489, 1356, 758 cmꢁ1. H
NMR (CDCl3, 300 MHz) d ¼ 2.07 (s, 3H), 2.37 (s, 3H), 4.27 (d, J ¼ 10.6 Hz, 1H),
5.03 (d, J ¼ 10.6 Hz, 1H), 6.93 (dd, J ¼ 3.9, 1.1 Hz, 1H), 7.21–7.23 (m, 1H),
7.28–7.37 (m, 4H), 7.38–7.40 (m, 2H) ppm. 13C NMR (CDCl3, 75 MHz) d 28.9,
31.8, 32.9, 75.7, 84.9, 88.4, 122.3, 124.8, 125.1, 126.2, 126.8, 128.2, 128.4, 128.5,
131.6, 141.1, 200.9, 201.2 ppm. HRMS: m=z calcd. for C18H16NaO2S: 319.0769;
found: 319.0763.
2-(1-(3’-Nitrobiphenyl-2-yl)-3-phenylprop-2-ynyl)-1,3-
diphenylpropane-1,3-dione (3u)
Reaction was performed in nitromethane solvent at room temperature. Pale
1
yellow solid (93%) mp 151–153 ꢀC. IR (neat) 1691, 1662, 1525, 1350, 759 cmꢁ1. H
NMR (CDCl3, 300 MHz) d ¼ 5.08 (d, J ¼ 10.6 Hz, 1H), 6.06 (d, J ¼ 10.5 Hz, 1H),
7.03 (d, J ¼ 6.7 Hz, 2H), 7.14–7.22 (m, 4H), 7.26–7.31 (m, 3H), 7.37–7.49 (m, 4H),
7.56–7.61 (m, 1H), 7.64–7.76 (m, 4H), 7.89 (d, J ¼ 7.5 Hz, 1H), 8.08 (d, J ¼ 7.5 Hz,
2H), 8.30 (s, 2H) ppm.13C NMR (CDCl3, 75 MHz) d 35.3, 62.1, 85.7, 89.2, 122.3,
122.6, 124.7, 127.5, 127.9, 128.0, 128.1, 128.3, 128.7, 128.8, 128.9, 129.1, 129.2,

252
S. MAITI, S. BISWAS, AND U. JANA
130.5, 131.4, 133.4, 133.6, 135.7, 136.0, 136.8, 139.7, 142.5, 148.2, 191.7, 193.5 ppm.
HRMS: m=z calcd. for C36H25NNaO4: 558.1681; found; 558.1687.
Moderate-Scale Synthesis of 2-(1,3-Diphenylprop-2-ynyl)-1,3-
diphenylpropane-1,3-dione (3b)[8]
Alcohol 1a (1.65 g, 7.96mmol), 1,3-dicarbonyl compound 2d (1.78 g, 7.96 mmol),
and anhydrated FeCl3 (64 mg, 0.40mmol) were treated as described for 3a to obtain
the product 3d as a pale yellow solid (3.00 g, 7.24mmol, 91%), mp 156–157 ꢀC.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial and infrastructural support from the
University Grants Commission–Center of Advanced Study (UGC-CAS) program
of the Department of Chemistry, Jadavpur University. S. M. and S. B. are also
thankful to the UGC, Jadavpur University and New Delhi, India, respectively, for
their fellowships.
REFERENCES
1. (a) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Catalytic Markovnikov and anti-
Markovnikov functionalization of alkenes and alkynes: Recent developments and trends.
Angew. Chem. Int. Ed. 2004, 43, 3368–3398; (b) Bytschkov, I.; Doye, S. Group-IV metal
complexes as hydroamination catalysts. Eur. J. Org. Chem. 2003, 935–946; (c) Kondo, T.;
Mitsudo, T. Metal-catalyzed carbon-sulfur bond formation. Chem. Rev. 2000, 100, 3205–
3220; (d) Smith, N. D.; Mancuso, J.; Lautens, M. Metal-catalyzed hydrostannations.
Chem. Rev. 2000, 100, 3257–3284.
2. (a) Trost, B. M. Comprehensive Organic Synthesis; I. Fleming (Ed.); Pergamon Press:
Oxford, 1991; vol. 4; (b) Hudrlik, P. F.; Hudrlik, A. M. The Chemistry of the Carbon–
Carbon Triple Bond; S. Patai (Ed.); John Wiley & Sons: Chichester, 1978; chap. 7, p. 199.
3. (a) Viehe, H. G. (Ed.). Chemistry of Acetylenes; Marcel Dekker: New York, 1969; (b)
Diederich, F.; Stang, P.; Tykwinski, R. R. (Eds.). Acetylene Chemistry: Chemistry,
Biology, and Materials Science; Wiley-VCH: Weinheim, 2005.
4. (a) Teobald, B. J. The Nicholas reaction: The use of dicobalt hexacarbonyl–stabilised pro-
pargylic cations in synthesis. Tetrahedron 2002, 58, 4133–4170; (b) Green, J. R. Chemistry
of propargyldicobalt cations recent developments in the Nicholas and related reactions.
Curr. Org. Chem. 2001, 5, 809–826.
5. (a) Georgy, M.; Boucard, V.; Debleds, O.; Zotto, C. D.; Campagne, J.-M. Gold(III)-
catalyzed direct nucleophilic substitution of propargylic alcohols. Tetrahedron 2009, 65,
1758–1766, and references cited therein; (b) Kabalka, G. W.; Yao, M.-L. Direct pro-
pargylic substitution of hydroxyl group in propargylic alcohols. Curr. Org. Synth. 2008,
5, 28–32, and references cited therein; (c) Sanz, R.; Martınez, A.; Alvarez-Gutierrez,
J. M.; Rodrıguez, F. Metal-free catalytic nucleophilic substitution of propargylic alcohols.
Eur. J. Org. Chem. 2006, 1383–1386.
6. (a) Trost, B. M. Atom economy—A challenge for organic synthesis: Homogeneous cataly-
sis leads the way. Angew. Chem. Int. Ed. 1995, 34, 259–281; (b) Trost, B. M. The atom
economy: A search for synthetic efficiency. Science 1991, 254, 1471–1477.

FeCl3 AS AN EFFICIENT CATALYST
253
7. (a) Kothandaraman, P.; Rao, W.; Zhang, X.; Chan, P. W. H. Gold- and silver-catalyzed
allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols. Tetrahedron 2009, 65,
1833–1838, and references cited therein; (b) Jana, U.; Biswas, S.; Maiti, S. A simple and
efficient FeCl3-catalyzed direct alkylation of active methylene compounds with benzylic
and allylic alcohols under mild conditions. Tetrahedron Lett. 2007, 48, 4065–4069; (c)
Sanz, R.; Miguel, D.; Martınez, A.; Alvarez-Gutierrez, F. Rodrıguez, J. M. Brønsted
acid–catalyzed benzylation of 1,3-dicarbonyl derivatives. Org. Lett. 2007, 9, 2027–2030;
(d) Motokura, K.; Nakagiri, N.; Muzugaki, T.; Ebitani, K.; Kaneda, K. Nucleophilic sub-
stitution reactions of alcohols with use of montmorillonite catalysts as solid Brønsted
acids. J. Org. Chem. 2007, 72, 6006–6015; (e) Reping, M.; Nachtsheim, B. J.; Kuenkel,
A. Efficient metal-catalyzed direct benzylation and allylic alkylation of 2,4-pentanediones.
Org. Lett. 2007, 9, 825–828; (f) Yasuda, M.; Somyo, T.; Baba, A. A mild and direct
indium-catalyzed process for the CꢁC bond formation from alcohols and active methy-
lenes, alkoxyketones or indoles was developed. Angew. Chem. Int. Ed. 2006, 45, 793–794.
8. Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Yb(OTf)3-catalyzed propargylation and alleny-
lation of 1,3-dicarbonyl derivatives with propargylic alcohols: One-pot synthesis of
multi-substituted furocoumarin. Tetrahedron 2007, 63, 11636–11643.
9. Feng, X.; Tan, Z.; Chen, D.; Shen, Y.; Guo, C.-C.; Xiang, J.; Zhu, C. Synthesis of
tetrasubstituted furans via in-catalyzed propargylation of 1,3-dicarbonyl compounds–
Cyclization tandem process. Tetrahedron Lett. 2008, 49, 4110–4112.
´
´
´
´
10. Sanz, R.; Miguel, D.; Martınez, A.; Alvarez-Gutierrez, J. M.; Rodrıguez, F. Brønsted
acid–catalyzed propargylation of 1,3-dicarbonyl derivatives: Synthesis of tetrasubstituted
furans. Org. Lett. 2007, 9, 727–730.
11. Cadierno, V.; Gimeno, J.; Noel, N. 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. Adv. Synth. Catal. 2007, 349, 382–394.
12. Zhan, Z.-P.; Wang, S.-P.; Cai, X.-B.; Liu, H.-J.; Jing-liang, Y.; Yu, J.-L.; Cuia, Y.-Y.
Copper(II) triflate–catalyzed nucleophilic substitution of propargylic acetates with enox-
ysilanes: A straightforward synthetic route to polysubstituted furans. Adv. Synth. Catal.
2007, 349, 2097–2102.
13. Yadav, J. S.; Reddy, B. V. S.; Pandurangam, T.; Rao, K. V. R.; Praneeth, K.; Kumar, G.
G. K. S. N.; Madavi, C.; Kunwar, A. C. Heteropoly acid–catalyzed highly efficient alky-
lation of 1,3-dicarbonyl compounds with benzylic and propargylic alcohols. Tetrahedron
Lett. 2008, 49, 4296–4301.
14. Cheng, D.; Bao, W. Propargylation of 1,3-dicarbonyl compounds with 1,3-diarylpropynes
via oxidative cross-coupling between sp3 CꢁH and sp3 CꢁH. J. Org. Chem. 2008, 73,
6881–6883.
15. For general reviews, see (a) Correa, A.; Mencheno, O. G.; Bolm, C. Iron-catalyzed
carbon–heteroatom and heteroatom–heteroatom bond-forming processes. Chem. Soc.
Rev. 2008, 37, 1108–1117; (b) Sherry, B. D.; Frustner, A. The promise and challenge of
iron-catalyzed cross coupling. Acc. Chem. Res. 2008, 41, 1500–1511; (c) Bolm, C.; Legros,
J.; Paih, J. L.; Zani, L. Iron-catalyzed reactions in organic synthesis. Chem. Rev. 2004,
104, 6217–6254.
16. (a) Biswas, S.; Maiti, S.; Jana, U. New and efficient iron halide–mediated synthesis of
alkenyl halides through coupling of alkynes and alcohols. Eur. J. Org. Chem. 2009,
2354–2359; (b) Jana, U.; Biswas, S.; Maiti, S. Iron(III)-catalyzed addition of benzylic alco-
hols to aryl alkynes––A new synthesis of substituted aryl ketones. Eur. J. Org. Chem.
2008, 5798–5804; (c) Jana, U.; Maiti, S.; Biswas, S. An efficient FeCl3-catalyzed amidation
reaction of secondary benzylic and allylic alcohols with carboxamides or p-toluenesulfo-
namide. Tetrahedron Lett. 2008, 49, 858–862; (d) Jana, U.; Maiti, S.; Biswas, S. An

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S. MAITI, S. BISWAS, AND U. JANA
FeCl3-catalyzed highly C3-selective Friedel–Crafts alkylation of indoles with alcohols.
Tetrahedron Lett. 2007, 48, 7160–7163.
17. (a) Zhan, Z.-P.; Yu, J.-L.; Cui, Y.- Y.; Yang, R.-F.; Yang, W.-Z.; Li, J.-P. A general and
efficient FeCl3-catalyzed nucleophilic substitution of propargylic alcohols: FeCl3-catalyzed
direct substitution of alcohols. J. Org. Chem. 2006, 71, 8298–8301; (b) Iovel, I.; Kristin, M.;
Kischel, J.; Zapf, A.; Mathias, B. An efficient and general iron-catalyzed arylation of benzyl
alcohols and benzyl carboxylates. Angew. Chem. Int. Ed. 2005, 44, 3913–3917.
18. Zhan, Z.-P.; Cai, X.-B.; Wang, S.-P.; Yu, J.-L.; Liu, H.-J.; Cui, Y.-Y. FeCl3-catalyzed
nucleophilic substitution of propargylic acetates with enoxysilanes. J. Org. Chem. 2007,
72, 9838–9841.
19. During our study, the FeCl3-catalyzed synthesis of propargylic substituted active methyl-
ene compounds by the direct substitution of substituted propargylic alcohols, a tandem
FeCl3-catalyzed propargylation–cycloisomerization reaction of tetramethyl silane substi-
tuted propargylic alcohols or acetates with 1,3-dicarbonyl compounds for the synthesis
of furan derivative was reported. See Ji, W.-H.; Pan, Y.-M.; Zhao, S.-Y.; Zhan, Z.-P.
FeCl3-catalyzed propargylation–cycloisomerization tandem reaction: A facile one-pot
synthesis of substituted furans. Synlett. 2008, 3046–3052.
20. We anticipated the formation of furan derivative under the refluxing condition during our
study of propargylation reaction; however no such furan product was observed for the
propargylated product 3a, even after prolonged heating. The same observation was also
reported by Ji et al. (see ref. 19). They concluded that for the cycloisomerization step,
alkyne should bear TMS group, or instead of propargylic alcohols propargylic acetate
should be used.
21. Staunton, J. Comprehensive Organic Chemistry; P. G. Sammes (Ed.); Pergamon: Oxford,
1979, vol. 4, pp. 651–653.
22. Tietze, L. F. Domino reactions in organic synthesis. Chem. Rev. 1996, 96, 115–136.