Amberlyst-15-catalyzed efficient cyclization of γ-and δ-unsaturated alcohols: Green synthesis of oxygen heterocycles

Article abstract of DOI:10.1080/00397910902945345

Amberlyst-15 (H+) resin catalyzes efficient cationic endo-cyclization of-and-unsaturated alcohols to yield tetrahydro-(2H)-pyrans and oxepanes. The merits of the present protocol are good yield of the products under mild conditions, simple workup, and reusability of the resin.

Full text of DOI:10.1080/00397910902945345

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Amberlyst-15–Catalyzed Efficient
Cyclization of γ- and δ-Unsaturated
Alcohols: Green Synthesis of Oxygen
Heterocycles
Soni A. Singh a , Shilpi Kabiraj a , Reena P. Khandare a , Shrikant P.
Nalawade a , Kiran B. Upar a & Sujata V. Bhat a
a Laboratory for Advanced Research in Natural and Synthetic
Chemistry, V. G. Vaze College, University of Mumbai, Mumbai, India
Version of record first published: 09 Dec 2009.
To cite this article: Soni A. Singh , Shilpi Kabiraj , Reena P. Khandare , Shrikant P. Nalawade , Kiran B.
Upar & Sujata V. Bhat (2009): Amberlyst-15–Catalyzed Efficient Cyclization of γ- and δ-Unsaturated
Alcohols: Green Synthesis of Oxygen Heterocycles, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:1, 74-80
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Synthetic Communications1, 40: 74–80, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902945345
AMBERLYST-15–CATALYZED EFFICIENT CYCLIZATION
OF c- AND d-UNSATURATED ALCOHOLS: GREEN
SYNTHESIS OF OXYGEN HETEROCYCLES
Soni A. Singh, Shilpi Kabiraj, Reena P. Khandare,
Shrikant P. Nalawade, Kiran B. Upar, and Sujata V. Bhat
Laboratory for Advanced Research in Natural and Synthetic Chemistry,
V. G. Vaze College, University of Mumbai, Mumbai, India
Amberlyst-15 (Hþ) resin catalyzes efficient cationic endo-cyclization of c- and
d-unsaturated alcohols to yield tetrahydro-(2H)-pyrans and oxepanes. The merits of the
present protocol are good yield of the products under mild conditions, simple workup,
and reusability of the resin.
Keywords: Cation exchange resin; cyclization; oxepane; tetrahydropyran; unsaturated alcohols
Cationic cyclization is a powerful synthetic tool for the preparation of carbocyclic
and heterocyclic compounds. Its attractiveness lies in the readiness with which highly
substituted carbon–carbon and carbon–hetero atom bonds are formed. Various
efforts have been directed toward acid-catalyzed transformations of unsaturated
terpene alcohols such as dehydrolinalool 1a and linalool 1f for the applications in
fragrance industry. For example, the synthesis of tetrahydropyran 2a from dehydro-
linalool 1a was achieved using catalysts such as polyphosphoric acid, phosphoric
acid,[1] tin tetrachloride,[2] and oxymercuration=reduction.[3] The cyclization of
linalool 1f using aqueous citric acid (2–4 h, 100ꢀC) was evaluated to give the product
mixture, which was found to have application in the perfumery industry.[4] Recently,
oxepane synthesis through 7-endo cyclization of alkenylsulfides in the presence of
N-iodo-succinimide has been reported.[5] Other recent reports on the synthesis of
tetrahydropyrans from unsaturated alcohols include 6-exoselenoetherification,[6]
bismuth-mediated exoconjugate addition,[7] and palladium- and platinum-
catalyzed[8,9] cyclizations. Synthesis of naturally occurring (ꢁ)-curcumene ether with
a tetrahydropyran ring has recently been achieved through cyclization with 1%
hydrochloric acid at 100ꢀC.[10]
In recent years, heterogeneous catalysts such as ion exchange resins, clay, solid
acids, and zeolites have been widely used in different areas of organic syntheses
Received November 25, 2008.
Address correspondence to Sujata V. Bhat, Laboratory for Advanced Research in Natural and
Synthetic Chemistry, V. G. Vaze College, University of Mumbai, Mithagar Road, Mulund (E),
Mumbai 400 081, India. E-mail: sujata8b@gmail.com
74

AMBERLYST-15-CATALYZED CYCLIZATION
75
because of their simplicity in operation, environmental compatibility, reusability,
greater selectivity, non corrosiveness, and low cost.[11–13]
We report herein Amberlyst-15 catalyzed efficient endo-cyclizations of c- and
d-unsaturated alcohols to give tetrahydro-(2H)-pyrans and oxepanes respectively.
RESULTS AND DISCUSSION
We have evaluated the cyclization of dehydrolinalool, linalool, melanol
and other unsaturated alcohols in the presence of Amberlyst-15 (Hþ) resin
(Scheme 1). The reactions were carried out at room temperature or at 60–70ꢀC in
the absence or presence of solvent such as toluene or dichloromethane (DCM;
Table 1).
Interestingly, dehydrolinalool 1a in the presence of Amberlyst-15 resin at
60–70ꢀC in toluene underwent exclusive cyclization to give 2-ethynyl-2,6,6-
trimethyl-tetrahydro-(2H)-pyran (2a) (94%; Table 1, entry 1). The tetrahydropyran
2a was obtained in 98% yield when this reaction was repeated in the absence of sol-
vent (Table 1, entry 2). Similarly, when this reaction was repeated at room tempera-
ture for 40 h, tetrahydro-(2H)-pyran 2a was formed in 85% yield (Table 1, entry 3).
Other unsaturated alcohols 1b–e gave the corresponding tetrahydropyrans 2b–e
respectively in good yields (Table 1, entries 4–7). The reaction of linolool (1f), how-
ever, gave ocimene (40%) and allo-ocimene (30%) along with minor amounts of tet-
rahydropyran 2f (Table 1, entry 8). Melanol (1 g) and derivatives 1 h and 1i gave
oxepane derivatives 2 g, 2 h, and 2i respectively (Table 1, entries 9–11). The con-
trolled hydrogenation of tetrahydro-(2H)-pyran 2a over Pd=CaCO3 afforded 2,6,6-
trimethyl-2-vinyl-tetrahydro-(2H)-pyran 2f (limetol)[14] in 90% overall yield, the
highest among reported procedures.
Scheme 1. Amberlyst-catalyzed cyclizations of unsaturated alcohols.

76
S. A. SINGH ET AL.
Table 1. Amberlyst-catalyzed cyclizations of terpene alcohols
Tem
(ꢀC)
Time
(h)
Yield
(%)
Entry
Substrate
Solventa
Productb,c
1
A
60–70
5
94
2
B
60–70
6
98
3
A
Rtd
40
85
4
C
35–40
6
70
5
A
60–70
6
62
6
A
60–70
6
83
(Continued )

AMBERLYST-15-CATALYZED CYCLIZATION
77
Table 1. Continued
Tem
(ꢀC)
Time
(h)
Yield
(%)
Entry
Substrate
Solventa
Productb,c
7
A
60–70
7
82
8
A
60–70
5
9e
9
A
60–70
6
65
10
A
60–70
6
62
11
A
60–70
6
65
aSolvent A ¼ toluene, B ¼ no solvent, and C ¼ dichloromethane.
bResin–substrate ratio 1:10.
cYield of the products were obtained by GC-MS.
dRoom temperature.
eMajor products are ocimene and allo-ocimene formed by dehydration.

78
S. A. SINGH ET AL.
EXPERIMENTAL
Gas chromatographic (GC) analysis of the products was performed on
a HP-5890 Series 2 instrument equipped with a flame ionization detector, using capil-
lary column HP-1 (cross-linked methyl siloxane), 30 m 0.25 mm  0.32 mm. Nitrogen
was used as the carrier gas at 10-psi inlet pressure. Temperature programming was
from 50 to 250ꢀC at 5ꢀC=min. The injector and detector temperatures were 250ꢀC
and 300ꢀC respectively. Neat samples (0.1–0.2 ml) were injected. Gas chromato-
graphy (GC)–MS analysis was carried on an Agilent instrument, where GC-6890
was coupled with mass spectrometer MS-5973 N with quadrupole mass detector,
using an HP-5 (5% phenyl methyl siloxane) column (30 m  250 mm  0.25 mm).
Helium is used as carrier gas at 9.35-psi inlet pressure, adjusted to linear velocity
30=s, split ratio 1:20, and ionization scan range of 40–450 m=z. Temperature pro-
gramming was from 80 to 250ꢀC at 3ꢀC=min. NMR spectra were recorded on a
Varian 400-MHz instrument, and infrared (IR) spectra were recorded on a
Perkin-Elmer Spectrum One instrument.
General Procedure for Cation-Exchange Resin–Catalyzed Reaction
A mixture of unsaturated alcohol (60 mmol) in solvent (50.0 ml) and ion
exchange resin (Amberlyst-15, 1.0 g) was subjected to the appropriate reaction
conditions, mentioned in Table 1. The progress of the reaction was monitored
by GC. After the completion of the reaction, the resin catalyst was recovered by fil-
tration, and the filtrate was evaporated under reduced pressure. The resulting residue
was subjected to vacuum distillation or column chromatography over silica gel to
yield the desired products. The recovered resin catalyst could be reused at least
four times.
Controlled Hydrogenation of
2-Ethynyl-2,6,6-trimethyl-tetrahydropyran 2a
2-Ethynyl-2,6,6-trimethyl-tetrahydropyran 2a (1.54 g) was subjected
to controlled hydrogenation over Pd=CaCO3(100 mg) for 4 h. The reaction mixture
was filtered, and the filtrate was concentrated. The residue was distilled in vacuum
(15 mmHg) to give 2-vinyl-2,6,6-trimethyl-tetrahydropyran (limetol, 2f), 1.41 g
(overall yield 90%).
Representative Spectral Data for Products
2-Ethynyl-2,6,6-trimethyl-3,4,5,6-tetrahydro-(2H)-pyran (2a). IR: nmax
1
cmÀ1 3290, 2104, 1381, 1367, 1347 and 1220. H NMR (400 MHz, CDCl3, Me4Si):
dH 1.18 (3H, s), 1.46 (6H, s), 1.3–2.0 (6H, m), 2.35 (1H, s). HRMS: found m=z
152.2352 (calc. for C10H16O: 152.2358), 137, 109, 95, 91, 84, 79, 66 (100%), 56, 51, 43.
2,2,6,6-Tetramethyl-3,4,5,6-tetrahydro-(2H)-pyran (2c). IR 2929, 1376,
1226, 1124, 1005, 825, 772; NMR: 1.2 (s, 12H), 1.4–2.0 (m, 6H); HRMS: found
142.2427 (calc. for C9H18O 142.2413), 127, 112, 97, 82, 70, 56, 42.

AMBERLYST-15-CATALYZED CYCLIZATION
79
2-Vinyl-2,6,6-trimethyl-3,4,5,6-tetrahydro-2H-pyran (2f). IR: nmax cmꢁ1
1
2929, 1381, 1367, 1347 and 1220. H NMR (400 MHz, CDCl3, Me4Si): dH 1.18
(6H, s), 1.19 (3H, s), 1.3–2.2 (6H, m), 4.95 (2H, m), 5.95 (1H, dd, J ¼ 18, 10.8).
HRMS: found 154.2509 (calc. for C10H18O: 154.2516), 137, 121, 109, 93 (100%),
95, 84, 79, 71, 66, 43.
2,2,6-Trimethyl-oxepane (2g). IR: nmax cmꢁ1 2920, 1470, 1384, 1164, 1089,
879, 772. NMR (400 MHz, CDCl3, and Me4Si): dH 0.85 (3 H, d, J ¼ 7.0 Hz), 1.2 (6 H,
s), 1.5–1.8 (6 H, m), 3.4 (2H, m). HRMS: found 142.2420 (calc. for C9H18O
142.2413), 127, 112, 97, 84, 70, 56, 42.
ACKNOWLEDGMENTS
We thank the Kelkar Education Trust and S. H. Kelkar Company for research
support and encouragement.
REFERENCES
1. Prevedello, A.; Salvatori, T.; Platone, E. Zwei monoterpenoxide aus dem sog destillierten
Limetten oil. BE Patent 590810, 1977.
2. Lombardi, V. P.; Cookson, R. C. Synthesen der diastereoisomeren caparrapioxide. Helv.
Chim. Acta 1976, 59, 1158–1168.
3. Brieger, G.; Burrows, E. P. Oxymercuration of terpenoid alcohols. J. Agric. Food Chem.
1972, 20, 1010–1013.
4. Zampino, M. J.; Mookherjee, B. D. Flavouring with reaction product of linalool with
citric acid. US Pat. 5137–741, 1992; Chem. Abst. 117, 211297.
5. Kover, A.; Matheu, M. I.; Diaz, Y.; Castillion, S. A study of the oxepane synthesis by a
7-endo elecrophile–induced cyclization reaction of alkenyl sulfides. Arkivoc 2007, 4, 364.
6. Gruttadauria, M.; Aprile, C.; Riela, S. Synthesis of 2,4,6-trisubstituted tetrahydropyrans
via 6-exo selenoetherification of unsaturated alcohols. Tetrahedron Lett. 2001, 42,
2213–2215.
7. Evans, P. A.; Andrew, W. J. Stereoselective construction of cis-2,6-disubstituted tetrahy-
dropyrans via an intramolecular bismuth-medicated oxa-conjugated addition reaction.
Tetrahedron Lett. 2005, 46, 5625–5627.
8. Kawai, N.; Lagrange, J. M.; Ohmi, M.; Uenishi, J. Palladium-catalyzed stereospecific
synthesis of 2,6-disubstituted tetrahydropyrans. J. Org. Chem. 2006, 71, 4530–4537.
9. Qian, H.; Han, X.; Widenhoefer, R. A. Platium-catalyzed intramolecular hydroalkoxyla-
tion of olefins to form cyclic ethers. J. Am. Chem. Soc. 2004, 126, 9536–9537.
10. Vickers, T. D.; Keay, B. A. Synthesis of (ꢂ)-curcumene ether. Synlett. 2003, 1349–1351.
11. Sen, S. E.; Smith, S. M.; Sullivan, K. A. Organic transformations using zeolite and zeo-
type materials. Tetrahedron 1999, 55, 12652–12698.
12. Dintzner, M. R.; Little, A. J.; Pileggi, P. D.; Osner, Z. R.; Lyone, T. W. Montmorillonite
clay-catalyzed hetero-Diels-Alder reaction of 2,3-dimethyl-1,3-butadiene with benzalde-
hydes. Tetrahedron Lett. 2007, 48, 1577–1579.
13. (a) Goel, A.; Dixit, M. Amberlyst-15 catalyzed efficient synthesis of 5-acetyl-4-hydroxy-
coumarone and 5-acetyl-6-hydroxy-coumarone: Crucial precursors of several naturally
occurring furanoflavones. Synlett 2004, 1990–1994; (b) Tajbakhsh, M.; Heydari, A.;
Alinezhad, H.; Ghanei, M.; Khaksar, S. Coupling of aldehyde, amine, and phophite pro-
moted by Amberlyst-15: Efficient synthesis of a-amino-phosphonates. Synthesis 2008,

80
S. A. SINGH ET AL.
352–354; (c) Gao, F.; Burnell, D. J. Reactions of 1,2-bis(trimethylsilyloxy)-cycloalkenes
with the diethyl acetals of aldehydes. J. Org. Chem. 2006, 71, 356–359; (d) Yadav, J. S.;
Reddy, B. V. S.; Eshwaraiah, B.; Anuradha, K. Amberlyst-15, a novel and recyclable
reagent for the synthesis of 1,5-benzodiazepines in ionic liquids. Green Chem. 2002, 4,
592–594; (e) Sabou, R.; Hoelderich, W. F.; Ramprasad, D.; Weinand, R. Synthesis of
7-hydroxy-4-methyl-coumarin via the Pechmann reaction with Amberlyst-ion-exchange
resins as catalysts. J. Catal. 2005, 232, 34–37; (f) Tian, Q.; Zhu, X. M.; Yang, J. S.
Amberlyst-15 catalyzes efficient synthesis of 2,3-unsaturated glycosides via Ferrier
rearrangement of glycal. Synth. Commun. 2007, 37, 691–701.
14. Strickler, H.; Kovats, E. Zwie monoterpenoxide aus dem sog destillierten limetten-oil.
Helv. Chem. Acta 1966, 49, 2055–2067.