An environmentally benign synthesis of octahydro-2 H-chromen-4-ols via modified montmorillonite K10 catalyzed Prins cyclization reaction

Article abstract of DOI:10.1055/s-0032-1316915

(-)-Isopulegol undergoes Prins cyclization reaction in the presence of 20 wt% of acid-treated montmorillonite K10 to produce octahydro-2H-chromen-4-ols in good yields and with high cis selectivities under solvent-free conditions. The solid-acid catalyst c

Full text of DOI:10.1055/s-0032-1316915

LETTER
▌1137
lAettner Environmentally Benign Synthesis of Octahydro-2H-chromen-4-ols via
Modified Montmorillonite K10 Catalyzed Prins Cyclization Reaction
Synthesis of Octahydro-2H-chromen-4-ols
Gakul Baishya,* Barnali Sarmah, Nabajyoti Hazarika
Natural Products Chemistry Division, CSIR-North East Institute of Science & Technology, Jorhat-785006, Assam, India
Fax +91(376)2370011; E-mail: b.gakul@gmail.com
Received: 22.01.2013; Accepted after revision: 20.03.2013
ported in the literature on this important reaction, most of
Abstract: (–)-Isopulegol undergoes Prins cyclization reaction in
them possess at least one drawback; among these are the
the presence of 20 wt% of acid-treated montmorillonite K10 to pro-
need for stoichiometric excess of the promoting acid cat-
duce octahydro-2H-chromen-4-ols in good yields and with high cis
alysts, use of an additive such as TMSCl, requirement for
the homoallylic alcohol or the aldehyde to be used in ex-
cess, need for anhydrous reaction conditions and/or inert
atmosphere, and limitation to aldehydes as the carbonyl
component. The synthesis of octahydro-2H-chromen-4-
ols from isopulegol via Prins cyclization reaction is limit-
ed to one example reported by Silva Jr. et al. where they
used molecular iodine as a homogeneous catalyst to cata-
lyze the Prins cyclization of (–)-isopulegol with p-
anisaldehyde6 (Scheme 1). Recently, Yadav et al. also de-
scribed an efficient method for the synthesis of octahydro-
2H-chromen-4-ol from (R)-citronellal and aldehydes via
direct ene-Prins reaction using a catalytic amount of
Sc(OTf)3 under mild conditions (Scheme 2).7 In the for-
mer case the authors only reported one example; whereas
in the latter they used Sc(OTf)3 as catalyst at low temper-
ature. The increasing demand for environmentally friend-
ly and sustainable chemical processes prompted us to
develop a novel catalytic system for the Prins cyclization
to synthesize a variety of octahydro-2H-chromen-4-ols.
selectivities under solvent-free conditions. The solid-acid catalyst
can be reused without loss of its activity.
Key words: (–)-isopulegol, Prins cyclization, H-K10 mont, octa-
hydro-2H-chromen-4-ols, reusability
Saturated six-membered heterocycles bearing oxygen are
a common structural motif of many biologically active
natural products such as avermectins, aplysiatoxin, oscil-
latoxins, latrunculins, talaromycins, acutiphycins, apicu-
larens, phorboxazoles, and bryostatins.1 The construction
of six-membered oxygen heterocycles in a single-step
chemical reaction is of particular interest to synthetic or-
ganic chemists, and among all existing methods the Prins
cyclization2 has emerged as a powerful single-step reac-
tion for the synthesis of this type of heterocycle. There
have been many reports in the literature where the Prins
cyclization reaction was employed in the key step of sev-
eral total syntheses of natural products.3 Generally, Lewis
acids and Brønsted acids promote this important consecu-
tive C–O and C–C bond-forming coupling reaction of ho-
moallylic alcohols with aldehydes and ketones to produce
a wide range of tetrahydropyran derivatives under mild
conditions.4,5 Although there have been many methods re-
Recently, modified montmorillonite K10 solid-acid cata-
lysts have received much attention in organic synthesis
due to their unique properties including their ability to ex-
change cations in the interlayers, expandable interlayer
CHO
I2 (10 mol%)
+
H
O
H
O
+
CH2Cl2, r.t.
OH
H
H
H
H
HO
OMe
HO
OMe
OMe
6
Scheme 1 Prins cyclization of (–)-isopulegol with p-anisaldehyde using I2
Sc(OTf)3
(5 mol%)
H
H
O
+
+ RCHO
CHO
O
–78 °C
CH2Cl2
H
H
H
H
HO
R
R
HO
7
Scheme 2 Ene-Prins cyclization of (R)-citronellal with aldehydes using Sc(OTf)3
SYNLETT 2013, 24, 1137–1141
Advanced online publication: 16.04.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1316915; Art ID: ST-2013-D0071-L
© Georg Thieme Verlag Stuttgart · New York

1138
G. Baishya et al.
LETTER
space, and tunable acidity.8 Ease of catalyst separation a 42% yield of a diastereomeric mixture of octahydro-2H-
and reutilization properties of modified montmorillonite chromen-4-ols 3c and 4c (Table 1, entry 1). Repeating the
K10 solid-acid catalysts make the chemical process very reaction at 80 °C for three hours failed to enhance the
simple and also environmentally benign. Recent reports yield of the product (Table 1, entry 2). However, when the
by Wang et al.9 and Wallis et al.10 have established the ef- same mixture was irradiated with microwaves for three
ficacy of acid-treated montmorillonite K10 (H-K10 minutes (Table 1, entry 3), a significant acceleration of the
mont).
reaction rate was observed leading to a 70% yield of the
corresponding cyclized product with excellent diastere-
oselectivity (20:1). In search of further improvement, we
found that 20 wt% of H-K10 mont smoothly catalyzed the
reaction to give 86% yield under microwave irradiation.
Finally, the reaction was also performed at different pow-
ers. Thus, we performed the Prins cyclization reaction of
(–)-isopulegol (1, 1.0 mmol) and p-anisaldehyde (2c, 1.2
mmol) at 180 W, 360 W, and 500 W power for three min-
utes using 20 wt% of H-K10 mont (Table 1, entries 4–6).
However, the products were obtained with almost similar
diastereomeric ratios, although the reaction performed at
180 W afforded the product in comparatively lower yield.
Thus, the optimal reaction conditions involved the use of
20 wt% of H-K10 mont catalyst, isopulegol (1, 1.0 mmol)
and aldehyde 2 (1.2 mmol) under microwave irradiation
(360 W) and solvent-free conditions.
As an alternative to classical heating conditions, research-
ers have used microwave irradiation under solvent-free
conditions to carry out a range of chemical processes.11,12
To the best our knowledge, there have been no reports in
the literature on the use of H-K10 mont as catalyst under
solvent-free and microwave-irradiation conditions for this
important cylization reaction. We report herein the first
example of H-K10 mont catalyzed Prins cylization of (–)-
isopulegol to produce octahydro-2H-chromen-4-ol deriv-
atives (Scheme 3).
20 wt%
H-K10 mont
H
O
H
O
+ RCHO
+
OH
microwave (360 W)
solvent-free
H
H
H
R
H
HO
R
HO
After optimization of the reaction conditions, the general
applicability of this protocol was explored with various
aromatic, heteroaromatic, and aliphatic aldehydes and
also with ketone to produce a variety of substituted octa-
hydro-2H-chromen-4-ol. The results of this protocol are
summarized in Table 2. Initially, we explored the Prins
cyclization reaction of (–)-isopulegol with various aro-
matic aldehydes. It was observed that yields and diastereo-
selectivities of products were strongly variable according
to the nature of the substituent present in the arene ring.
Scheme 3 Prins cyclization of (–)-isopulgol with aldehydes using H-
K10 mont under microwave irradiation and solvent-free conditions
Our initial studies began with the search for optimal reac-
tion conditions for the synthesis of octahydro-2H-chro-
men-4-ol derivatives. Initially, we performed the reaction
of isopulegol (1) and p-anisaldehyde (2c) in the presence
of 10 wt% of H-K10 mont under solvent-free conditions
at room temperature for six hours. These conditions led to
Table 1 Reaction Conditions Optimization Studies Using (–)-Isopulegol (1) and p-Anisaldehydea
CHO
H
O
H
O
+
+
OH
H
H
H
H
HO
OMe
HO
1
2c
OMe
OMe
3c
4c
Entry
Catalyst (wt%)b
Conditions
Time
Yield (%)c
1
2
3
4
5
6
7
10
10
10
20
20
20
0
25 °C
6 h
42
46
70
86
60
65
0
80 °C
3 h
MW (360 W)
MW (360 W)
MW (180 W)
MW (500 W)
MW (360 W)
3 min
3 min
3 min
3 min
3 min
a Reaction performed with 2c (1.2 mmol) and 1 (1 mmol).
b Solid-acid catalyst H-K10 mont prepared by reported method.9,13
c Isolated yield.
Synlett 2013, 24, 1137–1141
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Octahydro-2H-chromen-4-ols
1139
Aldehydes with electron-donating substituents at the para
position gave very good yields and excellent diastereose-
lectivites of the corresponding Prins products (Table 2,
entries 3 and 5); whereas o-anisaldehyde afforded an in-
separable mixture of products 3d and 4d in a 6.5:1 diaste-
Table 2 Synthesis of Octahydro-2H-chromen-4-ols via Prins Cycli-
zation of (–)-Isopulegol with Different Aldehydesa
20 wt%
H-K10 mont
H
O
H
O
+
RCHO
2
+
1
microwave (360 W)
solvent-free
reomeric ratio as determined by HNMR spectroscopic
OH
H
H
H
R
H
R
HO
analysis (Table 2, entry 4). Aldehydes with electron-with-
drawing groups also underwent cyclization, but their cor-
responding octahydro-2H-chromen-4-ol derivatives were
obtained in lower yields and diastereoselectivities (Table
2, entries 6–13). Unsubstituted aromatic aldehydes such
as benzaldehyde and 2-napthaldehyde also underwent
smooth cyclization with the yield of the chromenol deriv-
ative for the latter being higher than the former (Table 2,
entries 1 and 2). Diastereoselectivities in both cases were
found to be very good.
HO
1
3
4
Entry
R
Product
Ratio of 3/4a Yield (%)b
1
2
Ph
3a + 4a
3b + 4b
3c + 4c
3d + 4d
3e + 4e
3f + 4f
3g + 4g
3h + 4h
3i + 4i
9:1
10:1
20:1
76
80
86
76
82
78
72
78
65
70
64
50
64
56
50
2-naphthyl
4-MeOC6H4
2-MeOC6H4
4-MeC6H4
4-ClC6H4
3
4
6.5:1c
Next, we extended our studies to heteroaromatic alde-
hydes. When 2-furfuraldehyde and 2-thiophene carbalde-
hyde were reacted with (–)-isopulegol under the same
reaction conditions, the corresponding chromen deriva-
tives were obtained in good yields but with poor diastere-
oselectivities (Table 2, entries 14 and 15). Pyridine-2-
carbaldehyde and pyridine-3-carbaldehyde did not under-
go reaction (Table 2, entries 16 and 17).
5
25:1
5:1
4:1
9:1
3:1
2:1
3:1
1:1
3:1
3:1
2:1
–
6
7
2,4-Cl2C6H3
4-BrC6H4
3-BrC6H4
2-BrC6H4
4-FC6H4
8
9
10
11
12
13
14
15
16
17
18
19
3j + 4j
3k + 4k
To extend the utility of this protocol further, various ali-
phatic aldehydes were investigated. Propanal and 3-phen-
ylpropanal underwent smooth cyclization to give their
corresponding chromen derivatives in good yields and
good diastereoselectivities (Table 2 entries 18 and 19).
2,4,5-F3C6H3
3-O2NC6H4
2-furfuryl
3l + 4l
3m + 4m
3n + 4n
3o + 4o
n.r.
Finally, the efficacy of the catalyst has also been tested
with cyclohexanone 5 under the same reaction conditions
to afford a 4:1 diasteromeric mixture of products 6 and 7
in 68% yield (Scheme 4).
2-thiophenyl
2-pyridinyl
3-pyridinyl
Pr
n.r.
–
O
20 wt%
H-K10 mont
3r + 4r
3s + 4s
5:1
4:1
70
76
H
O
H
O
+
+
OH
microwave
(360 W)
solvent-free
3-phenylpropyl
H
H
HO
5
a Diastereomeric ratios obtained from the isolated yield of the prod-
HO
1
68%
ucts.
6
7
b Isolated yield.
c Determined by 1HNMR analysis; n.r.: no reaction.
Scheme 4 Prins cylization of (–)-isopulegol with cyclohexanone
In summary, a variety of aldehydes with both electron-
donating and electron-withdrawing substituents undergo
H-K10 mont promoted Prins cyclization reaction with
(–)-isopulegol to generate a library of octahydro-2H-chro-
men-4-ols under microwave irradiation and solvent-free
conditions. (–)-Isopulegol also underwent Prins cycliza-
tion with cyclohexanone to afford a spiro chromenol de-
rivative under the same reaction conditions. This protocol
offers an environmentally benign synthesis of chromen
derivatives using reusable and eco-friendly clay catalyst
and it can also be utilized as an effective alternative meth-
od over the two existing classical methods.
Concerning the recovery and reuse of the catalyst we ob-
served that the catalyst can be reused up to five times
without loss of any significant catalytic activity. After
completion of the reaction of (–)-isopulegol with p-tolual-
dehyde the catalyst was recovered from the reaction mix-
ture by a simple filtration process. The solid residue was
washed with ethyl acetate, dried under vacuum, and kept
in oven at 100 °C before its use for another cycle. The
same method was applied for subsequent other three cy-
cles. The results are summarized in Table 3.
The efficiency of other solid-acid catalysts such as mont-
morillonite K10, amberlyst-15, PPA-silica, and silica sul-
furic acid was also examined, and the results are presented
in Table 4.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1137–1141

1140
G. Baishya et al.
LETTER
Table 3 Reusability of H-K10 Mont in the Synthesis of 3e and 4ea,b
CHO
H
O
H
O
H-K10
+
+
H
H
H
H
microwave (360 W)
HO
OH
HO
1
2e
3e
4e
Run
Yield (%)c
1
2
3
4
5
82
80
80
78
75
a Reaction performed with 2e (1.2 mmol) and 1 (1.0 mmol).
b Solid-acid catalyst: 20 wt% H-K10 mont.
c Isolated yield.
Nishimura, N. B.; Travers, W.; Waas, J. R. Synlett 1996,
1162. (c) Pansare, S. V.; Jain, R. P. Org. Lett. 2000, 2, 175.
(d) Marumoto, S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky, S.
D. Org. Lett. 2002, 4, 3919. (e) Cossey, K. N.; Funk, R. L. J.
Am. Chem. Soc. 2004, 126, 12216. (f) Dalgard, J. E.;
Rychnovsky, S. D. Org. Lett. 2005, 7, 1589. (g) Vitale, J. P.;
Wolckenhauer, S. A.; Do, N. A.; Rychnovsky, S. D. Org.
Lett. 2005, 7, 3255. (h) Meilert, K.; Brimble, M. A. Org.
Lett. 2005, 7, 3497. (i) Miranda, L. S. M.; Meireles, B. A.;
Costa, J. S.; Pereira, V. L. P. Synlett 2005, 869. (j) Barry, C.
S.; Busby, N.; Harding, J. R.; Willis, C. L. Org. Lett. 2005,
7, 2683. (k) Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew.
Chem. Int. Ed. 2005, 44, 3485; Angew. Chem. 2005, 117,
3551 . (l) Yang, X.-F.; Wang, M. W.; Zhang, Y.; Li, C.-J.
Synlett 2005, 1912. (m) Tian, X.; Jaber, J. J.; Rychnovsky, S.
D. J. Org. Chem. 2006, 71, 3176. (n) Chan, K.-P.; Ling, Y.
H.; Loh, T.-P. Chem. Commun. 2007, 939. (o) Ko, H. Y.;
Lee, D. G.; Kim, M. A.; Kim, H. J.; Park, J. M.; Lah, S.; Lee,
E. Org. Lett. 2007, 9, 141. (p) Yadav, J. S.; Kumar, N. N.;
Reddy, M. S.; Prasad, A. R. Tetrahedron 2007, 63, 2689.
(q) Yadav, J. S.; Rao, P. P.; Reddy, M. S.; Rao, N. V.;
Prasad, A. R. Tetrahedron Lett. 2007, 48, 1469.
Table 4 A Comparative Studya of Different Solid-Acid Catalysts for
the Synthesis of 3c and 4c
Entry
Catalyst (20 wt%)
Yield (%)b
1
2
3
4
5
H-K10 mont
K-10 mont
86
15
c
Amberlyst-15
PPA-silica
–
c
–
c
silica sulfuric acid
–
a Reaction conditions: Aldehyde 2c (1.2 mmol) and (–)-isopulegol
(1 mmol) and catalyst. Microwave irradiation at 360 W for 3 min un-
der solvent-free conditions.
b Isolated yield.
c Complex mixture of products.
Acknowledgment
(4) (a) Yadav, J. S.; Reddy, B. V. S.; Kumar, G. M.; Murthy, C.
V. S. R. Tetrahedron Lett. 2001, 42, 89. (b) Crosby, S. R.;
Harding, J. R.; King, C. D.; Parker, G. D.; Willis, C. L. Org.
Lett. 2002, 4, 3407. (c) Dobbs, A. P.; Martinovic, S.
Tetrahedron Lett. 2002, 43, 7055. (d) Aubele, D. L.; Lee, C.
A.; Floreancig, P. E. Org. Lett. 2003, 5, 4521. (e) Liu, F.;
Loh, T.-P. Org. Lett. 2007, 9, 2063. (f) Tadpetch, K.;
Rychnovsky, S. D. Org. Lett. 2008, 10, 4839. (g) Miranda,
P. O.; Carballo, R. M.; Martin, V. S.; Padron, J. I. Org. Lett.
2009, 11, 357.
(5) (a) Yadav, J. S.; Subba Reddy, B. V.; Narayana Kumar, G.
G. K. S.; Swamy, T. Tetrahedron Lett. 2007, 48, 2205.
(b) Yadav, J. S.; Subba Reddy, B. V.; Narayana Kumar, G.
G. K. S.; Reddy, M. G. Tetrahedron Lett. 2007, 48, 4903.
(c) Yadav, J. S.; Subba Reddy, B. V.; Maity, T.; Narayana
Kumar, G. G. K. S. Tetrahedron Lett. 2007, 48, 7155.
(d) Yadav, J. S.; Subba Reddy, B. V.; Maity, T.; Narayana
Kumar, G. G. K. S. Tetrahedron Lett. 2007, 48, 8874.
(e) Yadav, J. S.; Subba Reddy, B. V.; Aravind, S.; Narayana
We are grateful to the Department of Science & Technology New
Delhi for financial support of this work and for a fellowship to B.S.
We thank the Director, CSIR-NEIST, Jorhat for his keen interest
and encouragement.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
References
(1) Nicolaou, K. C.; Sorensen, E. J. In Classics in Total
Synthesis; VCH: Weinheim, 1996.
(2) (a) Arundale, E.; Mikeska, L. A. Chem. Rev. 1952, 51, 505.
(b) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977, 661.
(c) Snider, B. B. In Comprehensive Organic Synthesis; Vol.
2; Trost, B. M., Ed.; Pergamon Press: New York, 1991, 527.
(3) (a) Bratz, M.; Bullock, W. H.; Overman, L. E.; Takemoto, T.
J. J. Am. Chem. Soc. 1995, 117, 5958. (b) Charonat, J. A.;
Synlett 2013, 24, 1137–1141
© Georg Thieme Verlag Stuttgart · New York

LETTER
Kumar, G. G. K. S.; Madhavi, C.; Kunwar, A. C.
Synthesis of Octahydro-2H-chromen-4-ols
1141
catalyst was dried under vacuum and kept in oven at 100 °C
before its use for another cycle. The sturctures of the
compounds 3a, 4a, 3c, 4c, 3e, 4e, 3f, 4f, 3h, 4h, 3r, 4r, 3s,
and 4s were confirmed by comparison of their analytical data
with those reported in the literature.7 The analytical data of
all new compounds are given in the Supporting Information.
Selected Analytical Data
Compound 3g: viscous liquid. IR (CHCl3): 3376, 2949,
2924, 2869, 1590, 1562, 1473, 1455, 1377, 1092, 942, 824,
759 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.52 (d, 1 H, J =
8.4 Hz), 7.32 (d 1 H, J = 1.9 Hz), 7.24 (m, 1 H), 4.76 (dd, 1
H, J = 1.4, 11.4 Hz), 3.27 (dt, 1 H, J = 4.2, 10.4 Hz), 2.08–
1.93 (m, 2 H), 1.75 (m, 1 H), 1.60 (br s, 1 H, OH), 1.45–1.30
(m, 3 H), 1.32 (s, 3 H), 1.27–0.98 (m, 4 H), 0.94 (d, 3 H, J =
6.4 Hz). 13C NMR (75 MHz, CDCl3): δ = 138.7, 133.3,
131.8, 128.8, 128.2, 127.4, 77.6, 73.0, 70.8, 52.1, 48.6, 41.4,
34.3, 31.4, 23.0, 22.2, 21.0. ESI-MS: m/z = 330 [M + 1]+.
Anal. Calcd for C17H22Cl2O2: C, 62.01; H, 6.73. Found: C,
61.96; H, 6.80.
Compound 4g: viscous liquid. IR (CHCl3): 3481, 2926,
2854, 1589, 1563, 1472, 1455, 1375, 1251, 1095, 777 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.50 (d, 1 H, J = 8.4 Hz),
7.31 (d 1 H, J = 2.0 Hz), 7.23 (d, 1 H, J = 1.9 Hz), 5.12 (dd,
1 H, J = 1.7, 11.4 Hz), 3.59 (dt, 1 H, J = 4.0, 11.0 Hz), 1.99–
1.94 (m, 2 H), 1.85–1.65 (m, 2 H), 1.55 (br s, 1 H, OH),
1.50–1.40 (m, 2 H), 1.25 (s, 3 H), 1.23–0.96 (m, 4 H), 0.94
(d, 3 H, J = 6.5 Hz). 13C NMR (75 MHz, CDCl3): δ = 139.3,
133.1, 132.0, 128.8, 128.3, 127.3, 75.8, 71.2, 69.4, 49.5,
46.6, 41.3, 34.4, 31.2, 28.1, 22.5, 22.2. ESI-MS: m/z = 330
[M + 1]+.
Tetrahedron 2008, 64, 3025. (f) Yadav, J. S.; Subba Reddy,
B. V.; Narayana Kumar, G. G. K. S.; Aravind, S. Synthesis
2008, 395.
(6) Silva, L. F. Jr.; Quintiliano, S. A. Tetrahedron Lett. 2009,
50, 2256.
(7) Yadav, J. S.; Subba Reddy, B. V.; Ganesh, A. V.; Narayan
Kumar, G. G. K. S. Tetrahedron Lett. 2010, 51, 2963.
(8) (a) Nowrouzi, F. A.; Thadani, N.; Batey, R. A. Org. Lett.
2009, 11, 2631. (b) Dintzner, M. R.; Mondjinou, Y. A.;
Unger, B. Tetrahedron Lett. 2009, 50, 6639. (c) Lu, J.-M.;
Shi, M. Tetrahedron 2007, 63, 7545. (d) Azizian, J.; Karimi,
A. R.; Kazemizadeh, Z.; Mohammadi, A. A.;
Mohammadizadeh, M. R. J. Org. Chem. 2005, 70, 1471.
(e) Bandgar, B. P.; Pandit, S. S.; Sadavarte, V. S. Green
Chem. 2001, 3, 247.
(9) Wang, T.; Ma, R.; Liu, L.; Zhan, Z. Green Chem. 2010, 12,
1576.
(10) (a) Wallis, P. J.; Gates, W. P.; Patti, A. F.; Scott, J. L.; Teoh,
E. Green Chem. 2006, 8, 333. (b) Wallis, P. J.; Gates, W. P.;
Patti, A. F.; Scott, J. L.; Teoh, E. Green Chem. 2007, 9, 980.
(11) (a) Hamelin, J.; Bazureau, J-P.; Boullet, F. T. In Microwaves
in Organic Chemisry, 2nd ed.; Loupy A., Wiley-VCH:
Weinheim, 2003, Chap. 8,: 253. (b) de la Hoz, A.; Diaz-
Ortiz, A.; Moreno, A. Chem. Soc. Rev. 2005, 34, 164.
(c) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127.
(12) (a) Loupy, A. C. R. Chim. 2004, 7, 103. (b) Microwaves in
Organic Synthesis; Loupy, A., Ed.; 2nd ed.; Wiley-VCH:
Weinheim, 2006. (c) Strauss, C. R.; Varma, R. S. Top. Curr.
Chem. 2006, 266, 199. (d) Varma, R. S. Green Chem. 1999,
1, 43. (e) Varma, R. S. Pure Appl. Chem. 2001, 73, 193.
(f) Varma, R. S. Green Chem. Lett. Rev. 2007, 1, 37.
(g) Jeselnik, M.; Varma, R. S.; Polanca, S.; Kocevar, M.
Chem. Commun. 2008, 3048.
Compound 3i: white solid; mp 97 °C. IR (CHCl3): 3387,
2923, 2867, 1597, 1569, 1454, 1376, 1354, 1321, 1206,
1102, 1034, 781, 689 cm–1. 1H NMR (300 MHz, CDCl3): δ
= 7.45 (s, 1 H), 7.32 (dd, 1 H, J = 1.4, 3.1 Hz), 7.18 (d, 1 H,
J = 1.5 Hz), 7.10 (d, 1 H, J = 7.7 Hz), 4.33 (dd, 1 H, J = 2.0,
11.7 Hz), 3.53 (dt, 1 H, J = 4.2, 10.5 Hz), 1.84–1.96 (m, 1
H), 1.82 (dd, 1 H, J = 2.3, 12.8 Hz), 1.20–1.76 (m, 5 H), 1.23
(13) Experimental Procedure and Analytical Data
Preparation of the Catalyst H-K10 Mont
A slurry of commercially available montmorrilonite K10 (5
gm) in 1 M HCl (100 mL) was stirred vigorously at 80 °C for
6 h. The solid was filtered out and washed several times with
deionized H2O to remove Cl– completely. The solid residue
was then dried at 120 °C for 12 h to afford the catalyst.
General Procedure for the Synthesis of Octahydro-2H-
chromen-4-ol Derivatives
A mixture of (–)-isopulegol (1, 1 mmol), an aldehyde 2 (1.2
mmol), and H-K10 mont [20% (wt/wt of 1] were irradiated
in a closed vessel in the absence of any solvent in a Synthos
3000 microwave reactor at 360 W for 3 min. After 3 min of
reaction time EtOAc was added to the crude reaction
mixture, and the mixture was filtered. The residue was
further washed with EtOAc to completely remove any
product. The EtOAc layer was concentrated under reduced
pressure, and the residue was purified by chromatography on
silica gel using EtOAc–hexane (3:7) as the eluent to furnish
pure the chromenol derivatives 3 and 4. The solid acid
(s, 3 H), 0.95–1.19 (m, 3 H), 0.87 (d, 3 H, J = 6.5 Hz). 13
NMR (75 MHz, CDCl3): δ = 145.3, 130.2, 129.8, 129.0,
C
124.6, 122.5, 75.6, 74.0, 69.4, 49.3, 48.1, 41.2, 34.4, 31.3,
28.2, 22.5, 22.2. ESI-MS: m/z = 362 [M + Na]+. Anal. Calcd
for C17H23BrO2: C, 60.18; H, 6.83. Found: C, 60.14; H, 6.81.
Compound 4i: semi-solid. IR (CHCl3): 3455, 2927, 2869,
1597, 1570, 1476, 1455, 1424, 1375, 1327, 1253, 1162,
1097, 1063, 1036, 901, 782, 757 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 7.53 (s, 1 H), 7.38 (dd, 1 H, J = 1.2, 2.9 Hz), 7.32
(d, 1 H, J = 1.5 Hz), 7.15 (d, 1 H, J = 7.7 Hz), 4.75 (dd, 1 H,
J = 2.1, 11.6 Hz), 3.53 (dt, 1 H, J = 4.1, 11.0 Hz), 1.98 (m, 1
H), 1.70–1.80 (m, 1 H), 1.35–1.76 (m, 3 H), 1.24 (s, 3 H),
1.05–1.19 (m, 3 H), 0.96 (d, 3 H, J = 6.5 Hz). 13C NMR (75
MHz, CDCl3): δ = 145.3, 130.2, 129.8, 129.0, 124.6, 122.5,
75.6, 74.0, 69.4, 49.3, 48.1, 41.2, 34.4, 31.3, 28.2, 22.5, 22.2.
ESI-MS: m/z = 362 [M + Na].
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1137–1141

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.