Iron(III)-catalyzed addition of benzylic alcohols to aryl alkynes - A new synthesis of substituted aryl ketones

Article abstract of DOI:10.1002/ejoc.200800713

A new, efficient and direct addition of benzylic alcohols with terminal aryl alkynes was developed with the inexpensive, non-toxic, FeCl₃ catalyst in nitromethane. The reaction provides a simple method for the synthesis of substituted aryl ketones under mild conditions, and the reaction is highly atom-economical. Several substituted terminal alkynes underwent smooth reaction with various substituted benzylic alcohols. The electron-rich alkynes reacted more efficiently and gave higher yields than did the neutral or electron-deficient alkynes. A wide range of functional groups were tolerated in the developed protocol. The intermediate of this reaction was isolated, and a possible mechanism has been proposed. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800713

FULL PAPER
DOI: 10.1002/ejoc.200800713
Iron(III)-Catalyzed Addition of Benzylic Alcohols to Aryl Alkynes –
A New Synthesis of Substituted Aryl Ketones
Umasish Jana,*[a] Srijit Biswas,[a] and Sukhendu Maiti[a]
Keywords: Alkynes / Alcohols / Ferric chloride / Addition reaction / Atom economy
A new, efficient and direct addition of benzylic alcohols with
terminal aryl alkynes was developed with the inexpensive,
and gave higher yields than did the neutral or electron-de-
ficient alkynes. A wide range of functional groups were toler-
non-toxic, FeCl3 catalyst in nitromethane. The reaction pro- ated in the developed protocol. The intermediate of this reac-
vides a simple method for the synthesis of substituted aryl
ketones under mild conditions, and the reaction is highly
atom-economical. Several substituted terminal alkynes
underwent smooth reaction with various substituted benzylic
alcohols. The electron-rich alkynes reacted more efficiently
tion was isolated, and a possible mechanism has been pro-
posed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
zylic, allylic and propargylic electrophiles.[10] The prepara-
tion of internal alkynes still relies on traditional methods
that involve either the substitution of alcohol derivatives
such as halides and carboxylates with alkynylide anions or
the elimination of 1,2-dihalides. These processes require the
conversion of alkynes to the corresponding alkynylide
anions with stoichiometric amounts of a strong base (e.g.
organolithium or organomagnesium reagents). However,
the problem associated with all these methods is the pro-
duction of a large amount waste salts both in the derivati-
zation of alcohols and during the substitution or coupling
reaction (Scheme 1), which makes the reaction less atom-
efficient. Therefore, an alternative route that avoids all these
limitations is highly desirable.
Introduction
The regioselective functionalization of asymmetrically
substituted alkynes is of fundamental importance in or-
ganic synthesis.[1] Those proceeding in an atom-economical
manner, in which all the atoms of the reactants end up in
the final product, are the most useful in organic synthesis.[2]
In particular, the hydration of alkynes to carbonyl com-
pounds is the most typical example of atom-economical
transformations since no byproducts are generated. Conse-
quently, a large number of methods have been developed
for the hydration of alkynes to synthesize the corresponding
carbonyl compounds.[3] Although a wide range of methods
and reagents are available to achieve selectively either Mar-
kovnikov or anti-Markovnikov products from terminal al-
kynes.[1,3,4] The hydration of internal alkynes is always
problematic, usually giving a mixture of two ketones.[3,5] To
avoid this, a few indirect methods for the hydrolysis of in-
ternal alkynes with anti-Markovnikov selectivities have been
described, which involve a regioselective hydroamination
and a subsequent hydrolysis of the generated imine.[6] Very
recently, the microwave-assisted, p-toluenesulfonic-acid cat-
alyzed, regioselective hydration of an internal alkyne,[7] and
a one-pot synthesis of internal alkynes and their hydration
have also been described.[8] However, in all these methods,
the preparation of internal alkynes is required. Among the
methods to synthesize internal alkynes, the palladium-cata-
lyzed, Sonogashira coupling reaction between terminal al-
kynes and aryl/alkenyl halides is widely used.[9] However,
little work has been done on the cross-coupling with ben-
Scheme 1. Hydration of internal alkynes.
The direct utilization of benzylic alcohols as electrophiles
for carbon–carbon bond formation would be very useful
since it would be both atom-economical and environmen-
tally friendly, as water is the only by-product. However car-
bon–carbon bond formation with the direct use of alcohols
is very difficult because of their poor leaving-group ability,
and generally a large excess or stoichiometric amount of
reagents are required for the direct substitution of alcohols.
Therefore, the development of a catalytic version of this re-
action remains a major challenge in modern organic synthe-
[a] Department of Chemistry, Jadavpur University,
Kolkata 700032, West Bengal, India
Fax: +91-33-2414-6584
E-mail: jumasish2004@yahoo.co.in
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Iron(III)-Catalyzed Addition of Benzylic Alcohols to Aryl Alkynes
sis. To date, a few catalytic methods have been developed with hydrated FeCl3 with alcohol 2a (1.2 equiv.). The other
for variety of carbon–carbon and carbon–heteroatom bond catalysts employed [Yb(OTf)3, p-toluenesulfonic acid and
formations by direct substitution of alcohols, such as palla- InCl3] can also activate benzylic alcohols, but in those cases,
dium(0), NaAuCl4, Bi(OTf)3, InCl3, Yb(OTf)3, trifluoro- the desired product was obtained in low yield. No reaction
methanesulfonic acid, H-montmorillonite and p-toluenesul- occurred with transition-metal salts such as those of nickel
fonic acid.[11] More recently, a direct substitution of ben- and copper. However, the reaction with PdCl2 did occur but
zylic alcohols by alkynyl boron dihalides in the presence of led to a mixture of products.
nBuLi has also been demonstrated to afford internal al-
kynes.[12] However, the disadvantages associated with these
Table 1. Reaction of phenylacetylene and benzhydrol with different
catalysts.[a]
reagents are moisture sensitivity, high toxicity, low selectiv-
ity and relative expense. In order to circumvent these prob-
lems, the iron salts have attracted much attention in syn-
thetic organic chemistry, since iron is highly abundant in
nature, and consequently, iron and its salts are inexpensive,
commercially available and environmentally friendly.[13]
Very recently, we[14] and others[15] have demonstrated the
use of FeCl3 for the catalytic activation of alcohols towards
various nucleophiles. During our study, we anticipated that
a new domino reaction between the alkyne and alcohol
might be possible with a suitable Lewis- or Brønsted-acid
catalyst. The carbon–carbon bond formation in this reac-
tion would be initiated by a carbocation, which would then
generate an alkenyl cation. A subsequent nucleophilic at-
tack by hydroxide ion, which represent a novel atom-eco-
nomical synthesis of substituted ketones (Scheme 2).
[a] Reaction condition: Phenylacetylene (1 mmol), benzhydrol
(1.2 mmol), nitromethane (3 mL), catalyst (10 mol-%), 80 °C, 2 h,
and then catalyst (5 mol-%) was again added, and the reaction was
heated for 3 h. [b] Pure, isolated yield after column chromatog-
raphy.
Scheme 2.
The effect of solvent was also investigated. We found the
yield to be highly depended on solvent polarity. Among the
Although, the intermolecular electrophilic addition of a
various solvents, nitromethane was the most effective. The
carbonium ion to an alkyne is well-known, this transforma-
reaction did not proceed at all in coordinating solvents such
tion has not been much explored in organic synthesis.[16] In
as tetrahydrofuran and dimethyl formamide. However, 20%
this paper, we describe the discovery of the FeCl3-catalyzed,
of product was obtained in acetonitrile. Hydrocarbon sol-
novel, sequential, C–C and C–O bond-forming reactions of
vents such as toluene gave a mixture of products, and the
benzylic alcohols with aryl acetylenes for the regioselective
desired product was obtained only in trace amount. Dichlo-
synthesis of aryl ketones.
romethane and dichloroethane gave only 2–4% of the de-
sired product.[18]
The experimental procedure for this reaction was very
simple. The mixture of aryl acetylene and benzylic alcohol
Results and Discussion
Although the functionalization of alkynes with FeCl3 has in nitromethane was heated at 80 °C with catalytic
been reported recently,[17] to the best of our knowledge, FeCl3·6H2O (15 mol-%) for a set period of time (monitored
there is no report of the sequential C–C and C–O bond- by TLC) without the removal of air and moisture. The
forming reactions of benzylic alcohols with aryl acetylenes product was then isolated by extraction with ethyl acetate.
either with FeCl3 or with any other catalyst.[16a] In our ini-
Having optimized the reaction conditions, the scope of
tial studies, phenylacetylene 1a was treated with benzhydrol this new reaction was investigated with various benzylic
2a in presence of different catalysts to test the hypothesis. alcohols with phenylacetylene. The results are summarized
After screening a large number of catalysts under similar in Table 2. In general, the reaction proceeded smoothly and
conditions (Table 1), we observed that the target ketone was was complete within 2 h to produce various substituted aryl
formed in a moderate yield (39%) with anhydrous FeCl3 ketones with high Markovnikov selectivity in moderate
(15 mol-%) in nitromethane at 80 °C. Further studies indi- yield. The regioselectivity may be explained by the forma-
cated that the addition of H2O (2 equiv.) could improve the tion of the more stable alkenyl carbocation intermediate
yield up to 42%, and the yield was improved up to 45% during the course of the reaction. Both the electron-rich
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U. Jana, S. Biswas, S. Maiti
FULL PAPER
Table 2. FeCl3-catalysed reaction of phenylacetylene 1 with various benzylic alcohols 2.[a]
[a] Reaction conditions: Phenylacetylene 1 (1.0 mmol), benzylic alcohols 2 (1.2 mmol), FeCl3·6H2O (0.1 mmol), nitromethane (3 mL),
80 °C, 2 h, and then FeCl3·6H2O (0.05 mmol), 3 h. [b] The yields refer to pure isolated product.
and electron-deficient benzylic alcohols reacted smoothly FeCl3 as the catalyst in MeNO2), we obtained the desired
with phenylacetylene, affording the desired ketones in mod- product and a reasonable amount of p-methoxy aceto-
erate to good yields. But the reaction did not proceed at all, phenone.
with the phenyl ring of the benzylic alcohol bearing a
Surprisingly, high yields of the desired product was ob-
strongly electron-withdrawing group such as -NO2 (Table 2, tained for electron-rich alkynes (Table 3, Entries 1–4 and
Entry 7). Alcohols that are sensitive to acid-catalyzed dehy- 6–7) with anhydrous FeCl3 (10 mol-%) at r.t. However, a
dration were also tolerated under the present conditions sterically hindered alkyne (1c) gave moderate yield at 60 °C
(Table 2, Entries 3–6). It should be noted that besides the (Table 3, Entry 5). On the other hand, phenylacetylene
formation of the desired ketone, the concomitant formation bearing the strong electron-withdrawing -NO2 group
of a small amount of acetophenone (≈ 6%) by the simple (Table 3, Entry 12) did not react under the standard condi-
hydration of phenylacetylene[17c] was also observed in the tions. Moreover, internal alkyne such as diphenylacetylene
1
crude H NMR. Although this reaction worked well for a and alkyl alkyne did not give any of the desired ketone.
wide range of secondary benzylic alcohols, benzyl alcohol
was unchanged even after prolonged reaction times.
The mechanism of this reaction can only be speculated
(Scheme 3) at present based on experimental observations.
Encouraged by these results, we next examined the scope We[14] and others[20] have previously observed that with a
of this domino reaction in various substituted alkynes, catalytic amount of FeCl3, benzylic alcohols were rapidly
which were prepared according to the literature method,[19] converted to dimeric ether 2b by eliminating water
and the results are shown in Table 3. The reaction appeared (Scheme 3). Presumably, in the presence of a nucleophile,
to be quite general with respect to the alkynes. We found the ether is polarized by FeCl3 and generates an incipient
that electron-donating groups (such as -OMe, -Me or -OTs, benzylic carbocation. The stability of benzylic carbocation
Table 3, Entries 1–8) in phenylacetylene were more benefi- is well-documented and has been the subject of theoretical
cial than the presence of weakly electron-withdrawing sub- and experimental studies.[21] The nucleophilic attack of the
stituents such as -Cl or -Br (Table 3, Entries 9–11) Interest- alkyne moiety onto the resulting benzyl carbocation gener-
ingly, when we performed the reaction on an electron-rich ates more stable alkenyl cation 2c. And nucleophilic attack
alkyne such as 1b under standard conditions (hydrated of water (which is being generated during ether formation
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Iron(III)-Catalyzed Addition of Benzylic Alcohols to Aryl Alkynes
Table 3. FeCl3-catalyzed reaction of substituted phenylacetylene 1 with various benzylic alcohols 2.[a]
[a] Conditions: Alkyne 1 (1.0 mmol), benzylic alcohol 2 (1.2 mmol), anhydrous FeCl3 (0.1 mmol) nitromethane (3 mL), 5 h, r.t. [b] The
yields refer to pure isolated product based on alkyne. [c] 4 h at r.t., then 60 °C for 2 h. [d] FeCl3·6H2O (0.1 mmol), 80 °C for 2 h, catalyst
(0.05 mmol), 80 °C for 3 h.
and/or from the hydrated FeCl3 whenever used) onto the
alkenyl cation, followed by deprotonation and subsequent
tautomerization, leads to the final product 3a. The genera-
tion of the alkenyl cation can be supported by the fact that
for the case of electron-rich alkynes, the reaction worked
efficiently event at room temperature. Similarly, the genera-
tion of the benzylic carbocation from the corresponding
alcohols can also be explained from the observations that
benzyl alcohol and a benzylic alcohol bearing a -NO2 group
did not react. To confirm the formation of the ether inter-
mediate, a separate experiment was performed between
ether 2b and phenylacetylene; we observed that the ether
reacted smoothly with phenylacetylene in the presence of
FeCl3·6H2O to produce the desired ketone in a similar yield
(≈ 42%) to that obtained when starting from 2a. The ether
was prepared from the alcohol with a catalytic amount of Scheme 3. Probable mechanism.
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U. Jana, S. Biswas, S. Maiti
FULL PAPER
General Procedure for the Addition of Benzylic Alcohols to Alkynes:
Representative experimental procedure for the synthesis of 1,3,3-
triphenylpropan-1-one (3a): A 5 mL screw-cap vial was charged
with phenylacetylene (102 mg, 1 mmol), benzhydrol (221 mg,
1.2 mmol) and nitromethane (3 mL). To this stirred solution,
FeCl3·6H2O (27 mg, 0.1 mmol) was added, and the reaction mix-
ture was heated at 80 °C for 2 h. FeCl3·6H2O (13.5 mg, 0.05 mmol)
was added, and heating was continued for another 3 h. The pro-
gress of the reaction was followed by TLC. The reaction mixture
was allowed to attain r.t. and was then taken up in water (10 mL).
FeCl3 (10 mol-%) in nitromethane in the absence of the al-
kyne at r.t. in quantitative yield. A similar reaction with
InCl3 only gave 26% of the desired product. This concluded
that FeCl3 is more efficient for this reaction.
Despite the draw back of low yields under the current
conditions, the reactions of aryl alkynes with benzylic
alcohols are quite remarkable as a synthetic method. In ge-
neral, the reactions are quite efficient, simple and can be
performed in the presence of air and moisture and only a
catalytic amount of FeCl3 is necessary. The conditions are The reaction mixture was extracted with ethyl acetate (2ϫ25 mL),
and the organic phase was dried with anhydrous Na2SO4. The sol-
vent was removed under reduced pressure, and the product was
purified by silica gel column chromatography (5% ethyl acetate in
petroleum spirit) to afford 3a (129 mg, 0.45 mmol, 45%) as a white
solid; m.p. 88 °C. 1H NMR (300 MHz, CDCl3): δ = 3.75 (d, J =
7.5 Hz, 2 H), 4.84 (t, J = 7.4 Hz, 1 H), 7.15–7.58 (m, 13 H), 7.95
(d, J = 3 Hz, 2 H) ppm.[22]
very mild, as even the electron-rich alkynes worked at r.t.
The reaction did not proceed at all without any catalyst,
and a wide range of functional groups such as, -OMe, -Cl,
-Br and -OTs can tolerate this method.
Conclusions
This procedure was followed for all reactions in Tables 2 and 3
except where otherwise mentioned. The melting points (m.p.) and
In summary, we have developed a novel tandem reaction
between terminal aryl acetylenes and benzylic alcohols to
synthesize aryl ketones with catalytic FeCl3 with high atom
economy. The notable advantages of this method are the
operational simplicity (one-pot reaction), mild reaction
conditions, direct use of alcohols and the use of inexpensive
and non-toxic FeCl3. This method is energy saving, environ-
mentally friendly and provides a straightforward alternative
to the classical stepwise method. In addition, due to the
easy availability of the starting materials and catalyst, this
reaction may prove very useful in organic synthesis. Further
studies in this area to explore the mechanism and synthetic
applications of this reaction are being carried out in our
laboratory.
1
spectroscopic data (IR, H and 13C NMR, HRMS and elemental
analysis) for all unknown compounds and only the m.p. and 1H
NMR spectroscopic data for known compounds are provided be-
low.
3-(4-Chlorophenyl)-1,3-diphenylpropan-1-one (3b):[23] Alkyne 1a
(102 mg, 1 mmol), alcohol 2b (263 mg, 1.2 mmol) and hexahy-
drated FeCl3 (41 mg, 0.15 mmol) in nitromethane (3 mL) were
treated as described for 3a to obtain the product 3b as a pale yellow
oil (170 mg, 0.53 mmol, 53%). 1H NMR (300 MHz, CDCl3): δ =
3.72 (d, J = 7.2 Hz, 2 H), 4.81 (t, J = 7.2 Hz, 1 H), 7.12–7.32 (m,
9 H), 7.43–7.59 (m, 3 H), 7.94 (d, J = 7.7 Hz, 2 H) ppm.
1,3-Diphenylbutan-1-one (3c):[22] Alkyne 1a (102 mg, 1 mmol)
alcohol 2c (147 mg, 1.2 mmol) and hexahydrated FeCl3 (41 mg,
0.15 mmol) in nitromethane (3 mL) were treated as described for
3a to obtain the product 3c as a white solid (105 mg, 0.47 mmol,
1
47%); m.p. 58–59 °C. H NMR (300 MHz, CDCl3): δ = 1.35 (d, J
= 6.7 Hz, 3 H), 3.19 (dd, J = 8.0, 16.4 Hz, 1 H), 3.31 (dd, J = 5.6,
16.4 Hz, 1 H), 3.46–3.57 (m, 1 H), 7.18–7.58 (m, 8 H), 7.93 (d, J
= 7.6 Hz, 2 H) ppm.
Experimental Section
General: 1H NMR spectra were recorded with a Bruker 300
(300 MHz) spectrometer as solutions in CDCl3. Chemical shifts are
expressed in parts per million (ppm, δ) and are referenced to CHCl3
(δ = 7.26 ppm) as an internal standard. All coupling constants are
absolute values and are expressed in Hz. The description of the
signals include: s = singlet, d = doublet, t = triplet, m = multiplet
and dd = doublet of doublets. 13C NMR spectra were recorded
with a Bruker 300 (75 MHz) spectrometer as solutions in CDCl3
with complete proton decoupling. Chemical shifts are expressed in
parts per million (ppm, δ) and are referenced to CHCl3 (δ =
77.0 ppm) as an internal standard. High-Resolution Mass Spectra
(HRMS) were performed with a Qtof Micro YA263 spectrometer.
The molecular fragments are quoted as the relation between mass
and charge (m/z). IR (infrared spectroscopy) was recorded with an
FT-IR spectrometer, the IR spectra of solids were recorded in KBr
and those of oils and liquids were recorded as thin films with KBr.
The routine monitoring of reactions was performed with silica gel-
coated glass slides (Merck, silica gel G for TLC), which were ana-
lyzed with iodine. Solvents, reagents and chemicals were purchased
from Aldrich, Fluka, Merck, SRL, Spectrochem and Process
Chemicals. Nitromethane was distilled from calcium hydride prior
to use. All reactions involving moisture-sensitive reactants were ex-
ecuted with oven-dried glassware. All the benzylic alcohols were
prepared either by the reduction of ketones or by a Grignard reac-
tion.
3-(4-Chlorophenyl)-1-phenylbutan-1-one (3d):[22] Alkyne 1a (102 mg,
1 mmol), alcohol 2d (188 mg, 1.2 mmol) and hexahydrated FeCl3
(41 mg, 0.15 mmol) in nitromethane (3 mL) were treated as de-
scribed for 3a to obtain the product 3d as a pale yellow oil (129 mg,
1
0.51 mmol, 51%). H NMR (300 MHz, CDCl3): δ = 1.32 (d, J =
6.8 Hz, 3 H), 3.17 (dd, J = 7.7, 16.7 Hz, 1 H), 3.28 (dd, J = 6.4,
16.6 Hz, 1 H), 3.47–3.56 (m, 1 H), 7.19–7.37 (m, 4 H), 7.42–7.58
(m, 3 H), 7.92 (d, J = 7.3 Hz, 2 H) ppm.
1,3-Diphenylpentan-1-one (3e):[24] Alkyne 1a (102 mg, 1 mmol),
alcohol 2e (163 mg, 1.2 mmol) and hexahydrated FeCl3 (41 mg,
0.15 mmol) in nitromethane (3 mL) were treated as described for
3a to obtain the product 3e as a colorless oil (102 mg, 0.43 mmol,
1
43%). H NMR (300 MHz, CDCl3): δ = 0.81 (t, J = 7.5 Hz, 3 H),
1.62–1.67 (m, 1 H), 1.75–1.82 (m, 1 H), 3.2–3.32 (m, 3 H), 7.16–
7.32 (m, 5 H), 7.39–7.56 (m, 3 H), 7.91 (d, J = 7.5 Hz, 2 H) ppm.
1-Phenyl-3-p-tolylbutan-1-one (3f):[22] Alkyne 1a (102 mg, 1 mmol),
alcohol 2f (163 mg, 1.2 mmol) and hexahydrated FeCl3 (41 mg,
0.15 mmol) in nitromethane (3 mL) were treated as described for
3a to obtain the product 3f as a pale yellow oil (110 mg, 0.46 mmol,
46%). 1H NMR (300 MHz, CDCl3): δ = 1.33 (d, J = 7.0 Hz, 3 H),
2.32 (s, 3 H), 3.17 (dd, J = 8.3, 16.5 Hz, 1 H), 3.29 (dd, J = 5.7,
16.4 Hz, 1 H), 3.42–3.51 (m, 1 H), 7.10–7.19 (m, 4 H), 7.42–7.58
(m, 3 H), 7.94 (d, J = 7.9 Hz, 2 H) ppm.
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Iron(III)-Catalyzed Addition of Benzylic Alcohols to Aryl Alkynes
1-(4-Methoxyphenyl)-3,3-diphenylpropan-1-one (3g):[25] A mixture
of alkyne 1b (132 mg, 1 mmol), alcohol 2a (221 mg, 1.2 mmol), an-
hydrous FeCl3 (16 mg, 0.1 mmol) and nitromethane (3 mL) were
stirred at r.t. for 5 h, and the product was isolated as described for
3a. The product 3g was obtained as a white solid (253 mg,
0.8 mmol, 80%); m.p. 92 °C. 1H NMR (300 MHz, CDCl3): δ = 3.69
(d, J = 7.2 Hz, 2 H), 3.86 (s, 3 H), 4.83 (t, J = 7.2 Hz, 1 H), 6.91
(d, J = 8.8 Hz, 2 H), 7.17–7.27 (m, 10 H), 7.93 (d, J = 8.8 Hz, 2
H) ppm.
found 303.1360. C19H20O2 (280.37): calcd. C 81.40, H 7.19; found
C 81.32, H 7.15.
3,3-Diphenyl-1-p-tolylpropan-1-one (3l):[26] A mixture of alkyne 1d
(116 mg, 1 mmol), alcohol 2a (221 mg, 1.2 mmol), anhydrous FeCl3
(16 mg, 0.1 mmol) and nitromethane (3 mL) were stirred at r.t. for
4 h and then heated at 60 °C for 2 h, and the product was isolated
as described for 3a. The product 3l was obtained as a white solid
(165 mg, 0.55 mmol, 55%); m.p. 86 °C. 1H NMR (300 MHz,
CDCl3): δ = 2.40 (s, 3 H), 3.72 (d, J = 7.3 Hz, 2 H), 4.83 (t, J =
7.3 Hz, 1 H), 7.15–7.28 (m, 12 H), 7.84 (d, J = 8.2 Hz, 2 H) ppm.
3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-phenylpropan-1-one (3h):
Alkyne 1b (132 mg, 1 mmol), alcohol 2b (262 mg, 1.2 mmol), anhy-
drous FeCl3 (16 mg, 0.1 mmol) and nitromethane (3 mL) were
treated as described for 3g to obtain the product 3h as a white solid
2-(1,2,3,4-Tetrahydronaphthalen-1-yl)-1-p-tolylethanone (3m): Al-
kyne 1d (116 mg, 1 mmol), alcohol 2h (178 mg, 1.2 mmol), anhy-
drous FeCl3 (16 mg, 0.1 mmol) and nitromethane (3 mL) were
treated as described for 3g to obtain the product 3m as a pale yel-
(218 mg, 0.62 mmol, 62%); m.p. 99 °C. IR (KBr): ν = 3023, 2838,
˜
1679, 1600, 1510, 1490, 1264, 1246, 1212, 1168, 1027, 986, 838,
822, 701 cm–1. 1H NMR (300 MHz, CDCl3): δ = 3.66 (dd, J = 2.0,
7.1 Hz, 2 H), 3.87 (s, 3 H), 4.80 (t, J = 7.1 Hz, 1 H), 6.92 (dd, J =
1.6, 6.9 Hz, 2 H), 7.19–7.31 (m, 9 H), 7.92 (dd, J = 1.8, 7.0 Hz, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 44.2, 45.4, 55.5, 113.8,
126.5, 127.7, 128.6, 129.2, 130.0, 130.3, 132.1, 142.8, 143.9, 163.6,
196.2 ppm. HRMS: calcd. for C22H19ClNaO2 373.0971; found
373.0978. C22H19ClO2 (350.11): calcd. C 75.32, H 5.46; found C
74.96, H 5.46.
low oil (135 mg, 0.51 mmol, 51%). IR (neat): ν = 2929, 2862, 1682,
˜
1607, 1450, 1286, 1180, 806, 751 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 1.60–1.95 (m, 4 H), 2.42 (s, 3 H), 2.76–2.82 (m, 2 H),
3.26–3.29 (m, 2 H), 3.60–3.65 (m, 1 H), 7.07–7.28 (m, 6 H), 7.89
(d, J = 8.1 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.8,
21.7, 28.3, 29.7, 33.7, 46.2, 125.9, 128.3, 128.5, 129.3, 129.4, 134.9,
137.3, 140.3, 143.9, 199.1 ppm. HRMS: calcd. for C19H20NaO
287.1412; found 287.1410. C19H20O (264.37): calcd. C 86.32, H
7.63; found C 86.30, H 7.42.
1-(4-Methoxyphenyl)-3-p-tolylbutan-1-one (3i): Alkyne 1b (132 mg,
1 mmol), alcohol 2c (163 mg, 1.2 mmol), anhydrous FeCl3 (16 mg,
0.1 mmol) and nitromethane (3 mL) were added as described for
3g to obtain the product 3i as a pale yellow oil (169 mg, 0.63 mmol,
4-(3,3-Diphenylpropanoyl)phenyl 4-Methylbenzenesulfonate (3n): Al-
kyne 1e (272 mg, 1 mmol), alcohol 2a (221 mg, 1.2 mmol), hexahy-
drated FeCl3 (41 mg, 0.15 mmol) and nitromethane (3 mL) were
treated as described for 3a to obtain the product 3n as a light brown
63%). IR (neat): ν = 2974, 2933, 1670, 1599, 1508, 1263, 1165, 816,
˜
solid (265 mg, 0.58 mmol, 58%); m.p. 171 °C. IR (KBr): ν = 3048,
˜
1
542 cm–1. H NMR (300 MHz, CDCl3): δ = 1.31 (d, J = 7.0 Hz, 3
2919, 1682, 1598, 1373, 1151, 870, 706, 551 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 2.45 (s, 3 H), 3.69 (d, J = 7.3 Hz, 2 H),
4.78 (t, J = 7.2 Hz, 1 H), 7.05 (d, J = 8.6 Hz, 2 H), 7.16–7.33 (m,
12 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.86 (d, J = 8.6 Hz, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.6, 44.7, 45.8, 122.4, 126.4,
127.7, 128.4, 128.5, 129.7, 129.8, 132.1, 135.5, 143.8, 145.6, 152.9,
196.5 ppm. HRMS: calcd. for C28H24NaO4S 479.1293; found
479.1232. C28H24O4S (456.56): calcd. C 73.66, H 5.30; found C
73.64, H 5.42.
H), 2.32 (s, 3 H), 3.11 (dd, J = 8.5, 16.2 Hz, 1 H), 3.23 (dd, J =
5.6, 16.0 Hz, 1 H), 3.87 (s, 3 H), 6.92 (dd, J = 1.9, 7.0 Hz, 2 H),
7.10–7.19 (m, 4 H), 7.92 (dd, J = 1.9, 6.9 Hz, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.0, 22.0, 35.4, 46.8, 55.4, 113.7, 126.7,
129.2, 130.4, 130.4, 135.7, 143.8, 163.4, 197.7 ppm. C18H20O2
(268.35): calcd. C 80.56, H 7.51; found C 80.67, H 7.45.
1-(4-Methoxyphenyl)-2-(1,2,3,4-tetrahydronaphthalen-1-yl)ethanone
(3j): Alkyne 1b (132 mg, 1 mmol), alcohol 2h (178 mg, 1.2 mmol),
anhydrous FeCl3 (16 mg, 0.1 mmol) and nitromethane (3 mL) as
described for 3g to the obtain product 3j as a pale yellow solid
1-(4-Chlorophenyl)-3,3-diphenylpropan-1-one (3o):[26] Alkyne 1f
(137 mg, 1 mmol), alcohol 2a (221 mg, 1.2 mmol), hexahydrated
FeCl3 (41 mg, 0.15 mmol) and nitromethane (3 mL) were treated
as described for 3a to obtain the product 3o as a pale yellow oil
(135 mg, 0.42 mmol, 42%). 1H NMR (300 MHz, CDCl3): δ = 3.71
(d, J = 7.3 Hz, 2 H), 4.81 (t, J = 7.2 Hz, 1 H), 7.18–7.36 (m, 10
H), 7.41 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.6 Hz, 2 H) ppm.
(221 mg, 0.79 mmol, 79%); m.p. 70 °C. IR (KBr): ν = 2933, 2870,
˜
1669, 1603, 1578, 1509, 1420, 1291, 1256, 1210, 1171, 1030, 810,
751 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.64–1.93 (m, 4 H),
2.77–2.82 (m, 2 H) 3.23–3.27 (m, 2 H), 3.60–3.65 (m, 1 H), 3.88 (s,
3 H), 6.95 (d, J = 8.7 Hz, 2 H), 7.11–7.20 (m, 4 H), 7.98 (d, J =
8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.7, 28.3,
29.7, 33.7, 45.9, 55.5, 113.8, 125.9, 128.5, 129.3, 130.4, 137.3, 140.3,
163.5, 198.0 ppm. HRMS: calcd. for C19H20NaO2 303.1361; found
303.1360. C19H20O2 (280.37): calcd. C 81.40, H 7.19; found C
81.32, H 7.15.
1,3-Bis(4-chlorophenyl)-3-phenylpropan-1-one (3p):[26] Alkyne 1f
(137 mg, 1 mmol), alcohol 2b (263 mg, 1.2 mmol), hexahydrated
FeCl3 (41 mg, 0.15 mmol) and nitromethane (3 mL) were treated
as described for 3a to obtain the product 3p as a pale yellow oil
(142 mg, 0.40 mmol, 40%). 1H NMR (300 MHz, CDCl3): δ = 3.67
(d, J = 7.4 Hz, 2 H), 4.78 (t, J = 7.2 Hz, 1 H), 7.17–7.34 (m, 9 H),
7.42 (d, J = 8.3 Hz, 2 H), 7.86 (d, J = 8.6 Hz, 2 H) ppm.
1-(2-Methoxyphenyl)-2-(1,2,3,4-tetrahydronaphthalen-1-yl)ethanone
(3k): Alkyne 1c (132 mg, 1 mmol), alcohol 2h (178 mg, 1.2 mmol),
anhydrous FeCl3 (16 mg, 0.1 mmol) and nitromethane (3 mL) were
treated as described for 3g to obtain the product 3k as a pale yellow
1-(2-Bromophenyl)-3,3-diphenylpropan-1-one (3q): Alkyne 1g
(181 mg, 1 mmol), alcohol 2a (221 mg, 1.2 mmol), hexahydrated
FeCl3 (41 mg, 0.15 mmol) and nitromethane were treated as de-
solid (135 mg, 0.48 mmol, 48%); m.p. 67 °C. IR (KBr): ν = 2936,
˜
2861, 1671, 1660, 1595, 1484, 1436, 1298, 1250, 1026, 766, 753
1
cm–1. H NMR (300 MHz, CDCl3): δ = 1.65–1.92 (m, 4 H), 2.75– scribed for 3a to obtain the product 3q as a pale yellow oil (142 mg,
2.81 (m, 2 H), 3.28 (dd, J = 9.5, 16.7 Hz, 1 H), 3.38 (dd, J = 4.3,
0.39 mmol, 39%). IR (neat): ν = 3061, 3028, 1660, 1598, 1493,
˜
16.8 Hz, 1 H), 3.53–3.61 (m, 1 H), 3.90 (s, 3 H), 6.96–7.23 (m, 6 1448, 1318, 1278, 1211, 1176, 1028, 942, 920, 762, 701, 693 cm–1.
H), 7.44–7.50 (m, 1 H), 7.7 (dd, J = 1.7, 7.7 Hz, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 19.8, 28.4, 29.7, 33.7, 51.4, 55.5,
111.5, 120.7, 125.6, 125.7, 128.4, 128.9, 129.1, 130.3, 133.2, 137.3,
140.4, 158.2, 202.2 ppm. HRMS: calcd. for C19H20NaO2 303.1361;
1H NMR (300 MHz, CDCl3): δ = 3.74 (d, J = 7.6 Hz, 2 H), 4.74
(t, J = 7.6 Hz, 1 H), 7.02–7.05 (m, 1 H), 7.20–7.32 (m, 10 H), 7.54–
8.00 (m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 46.5, 48.8,
118.4, 126.4, 127.2, 127.8, 128.2, 128.5, 128.9, 129.8, 130.0, 131.4,
Eur. J. Org. Chem. 2008, 5798–5804
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5803

U. Jana, S. Biswas, S. Maiti
FULL PAPER
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C21H17BrNaO 387.0360; found 387.0363. C21H17BrO2 (381.27):
calcd. C 69.05, H 4.69; found C 69.08, H 4.66.
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Received: July 18, 2008
Published Online: October 20, 2008
5804
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5798–5804