Gallium(III) chloride-catalyzed three-component coupling of naphthol, alkyne and aldehyde: a novel synthesis of 1,3-disubstituted-3H-benzo[f] chromenes

Article abstract of DOI:10.1016/j.tetlet.2009.07.134

Three-component coupling of naphthol, alkyne and aldehyde has been achieved in the presence of 10 mol % gallium(III) chloride in toluene under reflux conditions to afford the corresponding 1,3-disubstituted-3H-benzo[f]chromenes in good yields. This is the

Full text of DOI:10.1016/j.tetlet.2009.07.134

Tetrahedron Letters 50 (2009) 5798–5801
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Gallium(III) chloride-catalyzed three-component coupling of naphthol,
alkyne and aldehyde: a novel synthesis of 1,3-disubstituted-3H-benzo[f]
chromenes
*
J. S. Yadav , B. V. Subba Reddy, Swapan Kumar Biswas, Sandip Sengupta
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 December 2008
Revised 18 July 2009
Accepted 28 July 2009
Available online 6 August 2009
Three-component coupling of naphthol, alkyne and aldehyde has been achieved in the presence of
10 mol % gallium(III) chloride in toluene under reflux conditions to afford the corresponding 1,3-disubsti-
tuted-3H-benzo[f]chromenes in good yields. This is the first example on the preparation of chromenes
from naphthol, alkyne and aldehyde.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Gallium(III) chloride
Three-component reaction
Chromene
Heterocycles
There has been considerable interest in chromenes and their
benzo-derivatives, not least because of their value for a variety of
industrial, biological and chemical synthetic uses.1 In particular,
benzo[f]chromenes (naphthopyrans) are of special interest as pho-
tochromic compounds, which have a wide variety of applications
such as ophthalmic glasses, electronic display systems, optical
switches and temporary or permanent memories.2 Consequently,
there have been some reports on the preparation of
benzo[f]chromenes.3 Recently; there has been considerable inter-
est in gallium-mediated transformations.4 Owing to their unique
catalytic properties, gallium halides have been widely used for a
variety of organic transformations. In particular, gallium(III) com-
pounds are considered as effective Lewis acids to activate alkynes
under extremely mild conditions.5 However, there have been no
reports on the use of gallium(III) chloride for the synthesis of
1,3-disubstituted-3H-benzo[f]chromenes.
In this Letter, we report a novel protocol for the one-pot synthe-
sis of 1,3-diaryl-3H-benzo[f]chromenes by means of coupling of
naphthol, alkyne and aldehyde using a catalytic amount of GaCl3.6
Accordingly, we first attempted a three-component coupling (3CC)
of 2-naphthol (1) with phenyl acetylene (2) and benzaldehyde (3)
using 10 mol % GaCl3 in toluene. The reaction proceeded at 110 °C
in toluene and the desired product, 1,3-phenyl-3H-benzo[f]chro-
mene 4a, was obtained in 75% yield (Scheme 1).
This result provided incentive to extend this process for various
substrates. Interestingly, a wide variety of aldehydes such as cyclo-
hexanecarboxaldehyde, 1-octanal, 4-methoxy-benzaldehyde, 2-
bromobenzaldehyde, cinnamaldehyde and citral underwent
smooth coupling with 2-naphthol and phenyl acetylene under
identical conditions (Table 1, entries c–h). Other alkynes such as
1-ethynyl-4-methylbenzene and 1-octyne also underwent cou-
pling with naphthol and benzaldehyde to give the corresponding
chromene derivatives in good yields (Table 1, entries b, l and i). Be-
sides b-naphthol, a-naphthol and p-cresol also participated in the
3CC reaction (Table 1, entries j–m). The products were fully char-
acterized by NMR, IR and mass spectroscopy. Both aromatic and
aliphatic aldehydes were found to be equally effective for this con-
version (Table 1).
In the absence of catalyst, no reaction was observed even after
long reaction time (12 h) under reflux conditions. The effects of
various metal halides such as FeCl3, BiCl3, InCl3, ZnCl2 and
CeCl3Á7H2O and metal triflates such as In(OTf)3, Bi(OTf)3, Sc(OTf)3
and Yb(OTf)3 were screened for this conversion. Surprisingly, none
O
GaCl3
OH
CHO
+
+
Toluene, reflux
4a
2
3
1
* Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512.
E-mail addresses: yadav@iict.res.in, yadavpub@iict.res.in (J.S. Yadav).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.134

J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5798–5801
5799
Table 1
Gallium(III) chloride-catalyzed three-component coupling of naphthol, alkyne and aldehyde
Entry
Naphthol/phenol
Alkyne
Aldehyde
Producta
Time (h)
2.0
Yieldb (%)
Ph
Ph
OH
CHO
a
75
72
75
70
O
Ph
OH
OH
OH
CHO
CHO
b
2.0
2.5
2.5
O
c
O
O
d
CHO
OMe
CHO
OH
OH
OH
OH
e
2.5
3.0
2.0
2.0
69
76
68
70
O
O
MeO
Br
CHO
f
Br
Ph
CHO
g
O
O
CHO
h
Ph
CHO
OH
i
j
3.0
2.0
68
72
O
Ph
OH
CHO
O
(continued on next page)

5800
J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5798–5801
Table 1 (continued)
Entry
Naphthol/phenol
Alkyne
Aldehyde
Producta
Time (h)
2.0
Yieldb (%)
Ph
OH
Br
Br
O
CHO
k
72
Ph
OH
CHO
CHO
O
l
2.0
4.0
70
65
Ph
OH
O
m
CH3
a
Products were characterized by NMR, IR and mass spectroscopy.
Yield refers to pure products after column chromatography.
b
Ga
urated ketone was obtained from the reaction of alkyne with alde-
hyde under similar reaction conditions.8 The reaction probably
proceeds via arylation of alkyne to afford vinyl naphthalen-2-ol.
This intermediate may subsequently undergo cyclization with
aldehyde to give the desired chromene (Scheme 2).
Ga(III)
Ph
H
O
..
OH
Protodemetallation
+
-H+
Alternatively, in situ formed propargyl alcohol, from aldehyde
and alkyne in presence of gallium(III) chloride may react with 2-
naphthol to give the propargyl ether which may undergo Claisen
rearrangement and a subsequent cyclization of the resulting qui-
nonemethide would give the desired naphthopyran.3a Further
studies addressing these issues are currently underway in our lab-
oratory. The scope of this method is illustrated with respect to var-
ious aldehydes and alkynes and the results are presented in Table
1.9 The effects of various solvents were examined in the three-
component coupling of 2-naphthol, phenylacetylene and benzalde-
hyde and the results are presented in Table 2. As seen from Table 2,
the reaction did not proceed in dichloromethane even at reflux
temperature. Although, the reaction was successful in acetonitrile
and 1,2-dichloroethane under reflux conditions, the desired prod-
uct was obtained in low yields. Among these solvents, toluene gave
the best conversions (Table 2).
+
O Ga(III)
H
H
OGa(III)
Ph
Ph
H
H
Ph
Ph
Ph
OH
..
O
O
-H+
Scheme 2.
of these catalysts gave the desired product under the reaction con-
ditions. The reaction was successful only with GaCl3. Furthermore,
Brønsted acids such as montmorillonite K10, heteropoly acid and
ion-exchange resins also failed to produce the desired product. In
the absence of aldehyde, only 1-(1-phenylvinyl)naphthalen-2-ol
was obtained exclusively.7 In the absence of 2-naphthol,
a,b-unsat-
In conclusion, we have developed a novel one-pot procedure
for the preparation of 1,3-disubstituted-3H-benzo[f]chromenes
from naphthol, alkyne and aldehyde using a catalytic amount of
GaCl3. It is entirely a new approach for the preparation of
benzo[f]chromenes in a single-step operation. The products are
potentially very useful precursors for the preparation of photo-
chromic materials.
Table 2
Effects of various solvents in the coupling of naphthol, phenylacetylene and
benzaldehyde
Entry
Solvent
Time (h)
Catalyst
(mol %)
Yielda (%)
Conversionb (%)
i
Toluene
9
5
10
20
75
90
90
80
98
98
ii
Benzene
CH3CN
9
19
11
24
5
10
20
72
80
80
80
85
85
Acknowledgement
S.K.B. and S.S. thank the CSIR, New Delhi for the award of
fellowships.
iii
iv
v
5
10
20
40
50
55
50
60
60
References and notes
CH2ClCH2Cl
CH2Cl2
5
10
20
35
45
45
45
50
50
1. Geen, G. R.; Evans, J. M.; Vong, A. K., 1st ed.. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: New
York, 1996; Vol. 5, pp 469–500.
2. (a) Pozzo, J.-L.; Samat, A.; Guglielmetti, R.; Lokshin, V.; Minkin, V. Can. J. Chem.
1996, 74, 1649–1659; (b) Ercole, F.; Davis, T. P.; Evans, R. A. Macromolecule 2009,
42, 1500–1511; (c) Takakazu, N.; Nobuyuki, N.; Hirochika, S. Sci. Prog. 2001, 84,
137–156; (d) Gemert, B. V. In Organic Photochromic and Thermochromic
Compounds; Crano, J. C., Guglielmetti, R. J., Eds.; Plenum Press: New York, 1999.
5
10
20
0
0
a
Yield refers to pure product after column chromatography.
Conversion refers to crude product determined by GC analysis.
b

J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5798–5801
5801
3. (a) Tanaka, K.; Aoki, H.; Hosomi, H.; Ohba, S. Org. Lett. 2000, 2, 2133; (b) Dong, Y.
W.; Wang, G. W.; Wang, L. Tetrahedron 2008, 64, 10148; (c) Bigi, F.; Carloni, S.;
Maggi, R.; Muchetti, C.; Sartori, G. J. Org. Chem. 1997, 62, 7024–7027.
4. (a) Chatani, N.; Inoue, H.; Kotsuma, T.; Murai, S. J. Am. Chem. Soc. 2002, 124,
10294; (b) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. J. Am. Chem. Soc. 1999,
121, 4074; (c) Asao, N.; Asano, T.; Ohishi, T.; Yamamoto, Y. J. Am. Chem. Soc. 2000,
122, 4817.
5. (a) Kobayashi, K.; Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc. 2002, 124, 8528;
(b) Yadav, J. S.; Reddy, B. V.; Eeshwaraiah, B.; Gupta, M. K.; Biswas, S. K.
Tetrahedron Lett. 2005, 46, 1161; (c) Viswanathan, G. S.; Wang, M.; Li, C.-J.
Angew. Chem., Int. Ed. 2002, 41, 2138; (d) Viswanathan, G. S.; Li, C.-J. Synlett 2002,
1553; (e) Viswanathan, G. S.; Li, C.-J. Tetrahedron Lett. 2002, 43, 1613.
6. (a) Yadav, J. S.; Reddy, B. V. S.; Padmavani, B.; Gupta, M. K. Tetrahedron Lett. 2004,
45, 7577; (b) Yadav, J. S.; Reddy, B. V. S.; Vijaya Bhasker, E.; Raghavendra, S.;
Narsaiah, A. V. Tetrahedron Lett. 2007, 48, 677.
2853, 1953, 1736, 1686, 1600, 1492, 1449, 1336, 1265, 1246, 1211, 1177, 1083,
1064, 1023, 805, 752, 698, 566, 487 cmÀ1 1H NMR (300 MHz, CDCl3): d 7.99 (d,
;
1H, J = 8.3 Hz), 7.90 (d, 1H, J = 8.3 Hz), 7.63–7.35 (m, 8H), 7.31 (d, 2H, J = 9.8 Hz)
7.26–7.17 (m, 3H), 7.08 (d, 1H, J = 8.3 Hz) 6.04 (d, 1H, J = 1.5 Hz), 5.34 (d, 1H,
J = 1.5 Hz) ppm; 13C NMR (100 MHz, Proton decoupled CDCl3): d 154.1, 140.7,
138.9, 138.1, 135.1, 133.8, 132.9, 130.7, 129.8, 129.3, 128.5, 128.3, 127.8, 127.5,
127.0, 126.6, 125.3, 124.1, 123.4, 117.8, 75.6 ppm; ESIMS: m/z 335 [M+H]+, 323,
391; HRMS calcd for C25H18O: 334.4173, found: 334.4171. 3-Cyclohexyl-1-
phenyl-3H-benzo[f]-chromene (4c): Liquid, IR (KBr):
m
max 2926, 2855, 1734, 1622,
1461, 1380, 1234, 1163, 1110, 813, 758, 698 cmÀ1
;
1H NMR (300 MHz, CDCl3): d
7.82 (d, 1H, J = 8.0 Hz), 7.70 (dd, 1H, J = 8.0, 1.4 Hz), 7.51–7.20 (m, 8H), 7.00 (d,
1H, J = 3.6 Hz), 5.62 (d, 1H, J = 5.8 Hz), 4.12 (dd, 1H, J = 2.9, 5.8 Hz), 1.81 (m, 1H),
1.58–1.18 (m, 10H) ppm; 13CNMR (100 MHz, Proton decoupled CDCl3): d 152.5,
136.8, 134.4, 134.0, 132.7, 132.4, 131.7, 129.9, 127.8, 127.5, 127.0, 126.7, 126.7,
126.4, 126.2, 125.2, 122.2, 67.5, 38.9, 30.5, 30.2, 27.7 ppm; ESIMS: m/z 341
[M+H]+, 342, 376; HRMS calcd for C25H24O: 340.4649; found: 340.4651. 3-(2-
Bromophenyl)-1-phenyl-3H-benzo[f]chromene (4f): Liquid, IR (KBr): mmax 3056,
2854, 1696, 1623, 1589, 1511, 1463, 1438, 1334, 1225, 1090, 1025, 998, 861,
7. Yadav, J. S.; Reddy, B. V.; Sengupta, S.; Biswas, S. K. Synthesis 2009, 1301.
8. Viswanathan, G. S.; Li, C.-J. Tetrahedron Lett. 2002, 43, 1613.
9. General procedure:
A mixture of b-napthol (1 mmol), phenyl acetylene
(1.2 mmol), aldehyde (1 mmol) and GaCl3 (0.1 mmol) was refluxed in toluene
for the appropriate time (Table 1). After complete conversion as indicated by
TLC, the reaction mixture was quenched with water (10 mL) and extracted with
ethyl acetate (3 Â 10 mL). The combined organic extracts were dried over
anhydrous Na2SO4, and concentrated in vacuo. The resulting product was
purified by column chromatography on silica gel (Merck, 100–200 mesh, ethyl
acetate–hexane) to afford the pure product. Spectral data for selected products.
1,3-Diphenyl-3H-benzo[f]chromene (4a): Liquid, IR (KBr): mmax 3059, 3028, 2922,
817, 751, 699, 629 cmÀ1 1H NMR (300 MHz, CDCl3): d 7.90 (d, 1H, J = 3.6 Hz),
;
7.87 (d, 1H, J = 3.6 Hz), 7.75–7.53 (m, 5H), 7.47–7.31 (m, 4H), 7.29–7.20 (m, 2H),
7.11 (d, 1H, J = 10.2 Hz), 7.04 (t, 1H, J = 8.0 Hz), 5.96 (d, 1H, J = 3.6 Hz), 5.80 (d,
1H, J = 3.6 Hz) ppm; 13C NMR (100 MHz, Proton decoupled CDCl3): d 154.2,
140.8, 139.0, 138.1, 135.2, 133.7, 132.9, 130.8, 130.4, 129.9, 129.4, 128.3, 127.8,
127.5, 127.4, 127.0, 126.6, 125.3, 124.1, 123.4, 122.1, 117.3, 75.4 ppm; ESIMS:
m/z 435[M+Na]+, 437, 452, 238; HRMS calcd for C25H17BrNaO: 435.3031; found:
436.3036.