Amberlyst-15: A reusable heterogeneous catalyst for the dehydration of tertiary alcohols

Article abstract of DOI:10.1016/j.tet.2012.06.083

Tertiary alcohols react under mild conditions in the presence of Amberlyst-15 (dry) (solid-supported sulfonic acid) to give predominantly the most stable alkene in very good yield. The dehydration of tertiary alcohol functionality occurs without observation of rearrangement and polymerization products, and with outstanding substrate tolerance, which include the NHCBz, NHBoc, OSEM, OTBDMS, OBOM and ethylene ketal functional groups. Amberlyst-15 (dry) can be easily recovered from the reaction medium and reused for five cycles, maintaining the catalytic efficiency. In addition, the dehydration can occur under continuous operation.

Full text of DOI:10.1016/j.tet.2012.06.083

Tetrahedron 68 (2012) 7414e7421
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AmberlystÒ-15: a reusable heterogeneous catalyst for the dehydration of tertiary
alcohols
,
b
,
b,
Luís M.T. Frija a , Carlos A.M. Afonso
*
*
a
ꢀ
ꢀ
CQFM and Institute of Nanoscience and Nanotechnology (IN), Dep. Eng. Química e Biologica, Instituto Superior Tecnico, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal
iMed.UL, Faculdade de Farmacia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
b
ꢀ
a r t i c l e i n f o
a b s t r a c t
Tertiary alcohols react under mild conditions in the presence of AmberlystÒ-15 (dry) (solid-supported
sulfonic acid) to give predominantly the most stable alkene in very good yield. The dehydration of ter-
tiary alcohol functionality occurs without observation of rearrangement and polymerization products,
and with outstanding substrate tolerance, which include the NHCBz, NHBoc, OSEM, OTBDMS, OBOM and
ethylene ketal functional groups. AmberlystÒ-15 (dry) can be easily recovered from the reaction medium
and reused for five cycles, maintaining the catalytic efficiency. In addition, the dehydration can occur
under continuous operation.
Article history:
Received 13 April 2012
Received in revised form 18 June 2012
Accepted 19 June 2012
Available online 28 June 2012
Keywords:
Dehydration
Tertiary alcohols
Olefins
Ó 2012 Elsevier Ltd. All rights reserved.
Amberlyst-15
Heterogeneous catalysis
Catalyst recycling
1. Introduction
conditions, increased yields and greater selectivity. Moreover, the
regioselective dehydration of tertiary alcohols by treatment with
The hydroxyl functionality in alcohols is often instrumental in
functional group interconversions. Conversion of hydroxyl into new
functional groups, such as carbonyl, carboxyl, ether, epoxide, amine
or alkene, has been the subject of a large number of studies for
decades, leading to a plethora of synthetic methods. Particularly,
selective dehydration of tertiary alcohols emerges as a significant
synthetic tool. Several studies have been performed towards
optimization of the dehydration procedures available or the de-
velopment of new methodologies.1 However, the generality of
methods described so far for tertiary alcohol dehydration involve
heterogeneous (for instance, Al2O3, FeCl3eSiO2, CuSO4eSiO2,
Fe2(SO4)3eSiO2, NaHSO4eSiO2, NH4SO4eSiO2) or homogeneous
(such as, TsOHePhH, BF3eOEt2, Ph3BiBr2eI2, I2 or CF3COCCl3) acid
catalysts in a stoichiometric amount, or the use of strong mineral
acids, high temperatures or transformation to their ester de-
rivatives, which, in some cases, preclude their use with substrates
bearing other sensitive functional groups.2 Such heterogeneous
reactions compared with their homogeneous counterparts, often
have the advantage of ease of set-up and work-up, mild reaction
triphenylphosphineeiodine has been described recently.3 Besides,
particularly relevant work in dehydration of alcohols has been done
using Martin’s sulfurane reagent (Ph2S[OC(CF3)2Ph]2),4 DCC/CuCl,5
Grieco reaction6 or Burgess reagent (methyl N-(triethylammo-
niumsulfonyl)carbamate).7 However the standing need of a milder
and more efficient method prompted us to further investigate this
transformation.
In the course of our investigation, substrate 1a (trans-terpin),
containing two tertiary alcohols, was used as a model molecule in
dehydration reactions. Among the 11 dehydrating agents tested
with 1a, AmberlystÒ-15 resin (dry)8a was identified as the more
efficient promoter. To our delight the dehydration of trans-terpin
occurs in a substrate/AmberlystÒ-15 (dry) ratio of 1:1 (w/w) (cor-
responding to a substrate/AmberlystÒ-15 (dry) ratio of 1.2:1 (mol/
mol)) at room temperature, exclusively at the cyclic tertiary alcohol
leaving the acyclic tertiary alcohol unreacted to form the endo-al-
kene 2a (alfa-terpineol).
AmberlystÒ-15 (dry) is a strong cation exchange resin in the Hþ
form, developed particularly for heterogeneous acid catalysis of
a wide variety of organic reactions (such as alkylation, esterifica-
tion, etherification or condensation hydrolysis), was used as a cat-
alyst. This is a sulfonated styrene divinyl benzene copolymer with
a macroreticular structure. The macroreticular pore structure of
AmberlystÒ-15 permits ready access of liquid or gaseous reactants
ꢀ
* Corresponding authors. iMed. UL, Faculdade de Farmacia da Universidade de
Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Fax: þ351 21 7946476;
e-mail addresses: lfrija@ff.ul.pt (L.M.T. Frija), carlosafonso@ist.utl.pt, carlosafonso@
ff.ul.pt (C.A.M. Afonso).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.083

L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
7415
Table 2
to the hydrogen ion sites located throughout the bead, thus en-
Dehydration of trans-terpin in different solventsa
suring successful performance even in non-swelling organic media.
In fact, this resin was used before in the dehydration of tert-
butyl-alcohol in a semi-batch reactor and in a continuous stirred
tank reactor with wet or dry resins.8b,c Very recently, AmberlystÒ-
15 was successfully applied in the dehydration of phenyl ethanol to
produce styrene.8d So far, to the best of our knowledge and
excluding tert-butyl-alcohol, there has been no reports to use
a resin catalyst like AmberlystÒ-15 in the dehydration of tertiary
alcohols even though diverse resins have been used widely in acid
catalysis.8eei
l
Entry
Solvent
Time (h)
Yield (%)
1
2
3
4
5
CH2Cl2
EtOAc
Diethyl ether
n-Hexane
EtOH
3.5
8
18
18
18
85
74
68
46
0
Based on the preliminary results achieved with compound 1a,
we decided to extend the dehydration study using AmberlystÒ-15
(dry) as catalyst, to a series of tertiary alcohols. In this paper, we
present and discuss the results of our research in this topic.
a
All reactions were carried out in 15 mL of solvent, by using a substrate/
AmberlystÒ-15 ratio of 1.2:1 (0.435 mmol/0.355 mmol); corresponding to a sub-
strate/AmberlystÒ-15 ratio of 1:1 (w/w). Mass of substrate used in every
reaction¼75 mg.
2. Results and discussion
After selection of the best solvent an additional study was
conducted using alcohol 1a with the aim of optimizing the sub-
strate/AmberlystÒ-15 (w/w) ratio to be used. From this study we
observed that the best yield for the selective dehydration of 1a
occurs when a 1:1.2 ratio of substrate/AmberlystÒ-15 (w/w) is used
(Fig.1). In fact, the change of yield when going from an AmberlystÒ-
Alcohol 1a (trans-terpin) was used, in a first approach, as
a model molecule for the study of dehydration reactions of tertiary
alcohols. A series of 11 acid promoters (heterogeneous and homo-
geneous) were tested in the dehydration of 1a using equivalent
reaction conditions (see Table 1). Among the different promoters
Table 1
Dehydration of trans-terpin using different acid promotersa
OH
Promoter
+
+
HO
HO
rt, 3.5h, CH2Cl2
1a
2a
2a'
2a''
Entry
Promoter
2a Yieldb (%)
2a0 Yieldb (%)
2a00 Yieldb (%)
1
2
3
4
5
6
7
8
AmberlystÒ-15 (dry)
85
39
n.r.
25
26
24
21
33
10
0
0
0
0
0
AmberlystÒ-15 (wet)
ꢁ
Molecular sieve 4 A
n.r.
30
0
21
23
0
32
0
27
n.r.
23
23
31
0
FeCl3eSiO2
CF3COOH
CF3SO3H
Phosphomolybdic acid
I2
p-Toluenesulfonic acid
H2SO4
0
9
10
11
25
21
32
BF3eOEt2
13
a
All reactions were carried out in 15 mL of solvent, by using a substrate/promoter ratio of 1.2:1 (0.435 mmol/0.355 mmol).
Isolated yield. n.r.¼no reaction. Mass of substrate used in every reaction¼75 mg.
b
used, AmberlystÒ-15 (dry) is the one that clearly leads to better
15/alcohol mass ratio of 0.7:4 is not significant. Besides, we decided
to use a mass ratio of 1.2 (catalyst/substrate) to prevent a possible
faster deactivation of AmberlystÒ-15.
results. This is true both in terms of yield and selectivity. Thus, if we
consider the 11 examined promoters presented in Table 1, only 4 of
these lead to the formation of an exclusive product of reaction
(entries 1, 2, 8 and 10). In most cases, we observed the formation of
two (entries 5 and 7) or three (entries 4, 6, 9 and 11) products of
dehydration (i.e., monoterpenes 2a (alfa-terpineol), 2a0 (limonene)
Accordingly, all further dehydration reactions of tertiary alco-
hols tested were carried out in CH2Cl2, using 1:1.2 substrate/
AmberlystÒ-15 (w/w). Next, we examined the possibility of recy-
cling the AmberlystÒ-15 resin. As can be seen from Fig. 2 the resin
can be efficiently reused during five cycles. The recovery of
AmberlystÒ-15 from the reaction medium is made simply by fil-
tration and washing with CH2Cl2. The easy recovery of the de-
hydration agent and the possibility of reuse in six cycles are the
major advantages of this new dehydration methodology.
Table 3 summarizes the results of dehydration for the range of
alcohols 1aen, tested under optimized conditions. Testosterone
derivative 1b was effectively dehydrated at room temperature to
give adduct 2b, possessing a new endocyclic double bond, in 86%
yield (entry 2). As previously noted for 1a, also for 1c a sole
hydroxyl group suffered elimination. However, while in 1a selec-
tivity between the two tertiary alcohol functions favours the
elimination that leads to formation of the endocyclic double bond,
or 2a00 (terpinolene)). The use of molecular sieve 4 A (entry 3) was
ꢁ
not effective in dehydration of alcohol 1a. Based on the results
obtained with compound 1a, shown in Table 1, it was decided to
extend the study of dehydration at different tertiary alcohols using
AmberlystÒ-15 (dry) as catalyst. From this point on whenever we
refer Amberlyst, will always mean AmberlystÒ-15 (dry).
Table 2 summarizes results obtained for the dehydration of 1a in
different solvents at room temperature. We observed selective
dehydration in all tested solvents, except ethanol. The best yield for
dehydration was achieved in dichloromethane (CH2Cl2) for
a
shorter reaction time (entry 1). In view of these results
dichloromethane was used as solvent in the dehydration of a range
of tertiary alcohols (1aen; Table 3).

7416
L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
Table 3
100
90
Dehydration of tertiary alcohols with AmberlystÒ-15a
Entry
Substrate
Temp.
Time
(h)
Olefin
Yieldb (%)
80
70
60
50
40
30
20
10
0
1
rt
3.5
6
90
1a
2a
OH
H
H
H
2
rt
86
H
H
H
O
O
2b
1b
0.1 0.2 0.5 0.7
1
1.1 1.2 1.5
2
3
4
OH
OH
H C
H C
OH
3
4
rt
8
73
85
Amberlyst/Alcohol ratio (w/w)
CH
CH
1c
2c
Fig. 1. Dehydration yield optimization by variation of AmberlystÒ-15/alcohol 1a
(75 mg) ratio (w/w). All reactions were carried out in 15 mL of CH2Cl2.
HO
reflux
1.5
1d
2d
R
1e: R ¼ Me
1f: R ¼ Et
1g: R ¼ Bu
2e: R ¼ Me
2f: R ¼ Et
2g: R ¼ Bu
5
6
7
4
3.5
3.5
85
88
78
rt
rt
HO
H C
R
R
(CH ) CH
H C
CH(CH ) CH
2h: R ¼ Me
2i: R ¼ Et
2j: R ¼ Bu
1h: R ¼ Me
1i: R ¼ Et
1j: R ¼ Bu
8
9
10
3
3.5
2.5
87
85
88
R
HO
R
MeO
MeO
1k: R ¼ Me
1l: R ¼ Bu
2k: R ¼ Me
2l: R ¼ Bu
11
12
1
1.5
89
79
reflux
reflux
HO Et
MeO
MeO
Fig. 2. AmberlystÒ-15 recycle study; (formation of olefin 2a from alcohol 1a; reactions
in CH2Cl2 (15 mL) and substrate/AmberlystÒ-15 ratio of 1:1.2 (75 mg/90 mg) and 1:0.7
(75 mg/52.5 mg)).
13
1.5
90c
2m
2n
1m
1n
2
2.5
91d
14
reflux
,e
85d
formation of a mixture of two styrene isomers was confirmed by
NMR spectroscopy (entry 13).
HO
a
All reactions were carried out in CH2Cl2 (15 mL) using a substrate/AmberlystÒ-15
Afterwards, we decided to scale up our dehydration system in
order to produce higher amounts of olefins from tertiary alcohols,
attesting the practicability of the method. In the first instance, we
applied the methodology in aliphatic alcohol 1n using a 5 g scale
(entry 14). The reason for choosing 1n for studies in larger scale and
not any of the other tertiary alcohols presented in this study is due
to the fact that this molecule is relatively cheap and easily acces-
sible. Alcohol 1n is very similar to the acyclic aliphatic alcohols
1hej tested previously. However, and surprisingly, dehydration of
1n does not occur at room temperature as noticed for 1hej. Re-
action of 1n with Amberlyst in refluxing dichloromethane pro-
duced a mixture of alkene isomers (entry 14).
This last result prompted us to perform new tests in order to
understand if our system would be able to isomerize olefins
(Table 4). The submission of an exo-olefin to the same conditions
used in the dehydration of tertiary alcohols with AmberlystÒ-15
could give us the answer. Accordingly, the next step consisted in the
dehydration of alcohol 1n using a synthetic approach, which might
lead predominantly to the formation of the corresponding exo-
olefin. In this method, dehydration of 1n occurred in presence of
a mixture of SOCl2 and pyridine in dichloromethane at ꢀ78 ꢁC.
Table 4 (entries 1 and 2) shows the percentage of olefin isomers
(2n0, 2n00 and 2n000) obtained by dehydration of 1n for the two
ratio of 1:1.2 (75 mg/90 mg).
b
Isolated yield.
Mixture of two isomers.
c
d
Mixture of three isomers.
Reaction performed in a 5 g scale (5 g of 1n; 6 g of AmberlystÒ-15).
e
for diol 1c the dehydration occurs at room temperature with re-
markable selectivity only on the tertiary alcohol, keeping un-
changed the secondary alcohol function leading to the endocyclic
allylic alcohol carveol 2c in 73% yield (entry 3).
As expected, in agreement with the result obtained for alcohol
1a, the dehydration of alcohol 1d at room temperature was not
effective. In contrast, when the reaction was conducted in refluxing
dichloromethane, olefin 2d was produced in 85% yield (entry 4).
Alcohols 1eem were synthesized in high yields from the respective
ketones following the Ishihara methodology.9
Dehydration of cyclic tertiary alcohols 1eeg occurred at room
temperature, furnishing endo-olefins 2eeg in very good yields
(entries 5e7). Under similar conditions, acyclic aliphatic alcohols
1hej were rapidly dehydrated to give 2hej in similar yields
85e88% (entries 8e10). In contrast, dehydration of tertiary benzylic
alcohols 1kem to form adducts 2kem only occurred under
refluxing dichloromethane (entries 11e13). For alcohol 1m,

L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
7417
Table 4
Table 5
Influence of AmberlystÒ-15 on the possible occurrence of isomerization of olefins
Dehydration of 1n under continuous operation in different conditionsa
l
l
l
Entry Reagent
Reaction conditions Productsa (%)
2n0 2n00 2n000
Entry Concn Flow
Volume of
Amount of
Mass of product
of 1n
(mL/min) 1n solution
1n passed in 2nf,g (g) [yield, %]
1
2
3
4
5
1n
1n
AmberlystÒ-15
CH2Cl2, reflux
2.5 h
10 49 41
(M)
passed in the the column
column (mL)
(g) [mmol]
1
2
0.1
0.1
0.1b
25
0.40 [2.5]
0.40 [2.5]
0.294 [84]
0.130 [38]
{61}h
0.158 [45]
0.151 [43]
0.301 [87]
0.147 [42]
{65}h
0.112 [16]
0.154 [22]
0.315 [45]
0.049 [7]
{26}h
SOCl2, Py
82 10
8
25 (50)e
CH2Cl2, ꢀ78 ꢁ
C
30 min
3
4
5
6
0.5b
0.3c
0.1d
25
25
0.40 [2.5]
0.40 [2.5]
0.40 [2.5]
0.40 [2.5]
2n0þ2n00þ2n000 (mixture, entry 1) AmberlystÒ-15
9
78
80
47 44
CH2Cl2, reflux
overnight, 17 h
25
25 (50)e
2n0þ2n00þ2n000 (mixture, entry 2) AmberlystÒ-15
9
8
9
CH2Cl2, reflux
7
8
9
10
0.2
0.5b
0.3c
0.1d
25
25
0.80 [5.0]
0.80 [5.0]
0.80 [5.0]
0.80 [5.0]
2.5 h
2n0þ2n00þ2n000 (mixture, entry 2) AmberlystÒ-15
CH2Cl2, reflux
12
25
25 (50)e
overnight, 17 h
a
Percentage calculated by integration of olefinic proton signals from 1H NMR.
a
All tests were conducted at 50 ꢁC except those listed in entries 1 and 2, which
were carried out at 45 ꢁC.
Test done with fresh AmberlystÒ-15 resin (1.986 g).
Test done with resin reused.
Test done with resin reused a second time.
Total volume of 1n solution passed in the column at fixed flow.
b
systems. Afterwards, the two olefin mixtures (from dehydration of
1n with Amberlyst and SOCl2) were submitted to identical reaction
conditions used for tertiary alcohol dehydration with Amberlyst,
with an increase in reaction times (Table 4, entries 3e5). None of
these reactions revealed the isomerization of the olefins remaining
unchanged the initial ratio of 2n isomers.
c
d
e
f
Isolated yield.
g
Mixture of three isomers (see structure 2n).
Overall yield based on total volume of 1n solution passed in the column at fixed
h
flow.
Besides, dehydration of 1n was performed in a continuous
process using a CH2Cl2 solution of alcohol of known concentration.
The solution was passed through an HPLC column packed with
AmberlystÒ-15 resin, using a fixed flow that allows full conversion
of 1n at the end of the column (see page S4, Supplementary data).
In order to further investigate the reaction, diverse tests were
conducted for dehydration of 1n under continuous operation using
different concentrations of alcohol (see Table 1S, Supplementary
data). The solutions were passed in the column packed with
AmberlystÒ-15 varying the flow and temperature of operation.
Table 5 shows the results obtained for dehydration of 1n using
0.1 and 0.2 M solutions at 45 ꢁC (entries 1 and 2) and 50 ꢁC (entries
3e10). In fact, good yields were achieved for dehydration of 1n by
using a 0.1 M solution and a fixed flow of 0.1 mL/min, either at
45 ꢁC (entries 1 and 2) or at 50 ꢁC (entries 5 and 6). However, the
use of a 0.2 M solution of 1n at 50 ꢁC and an equivalent flow
(0.1 mL/min), led to a considerable decrease in the yield of con-
version of tertiary alcohol in product 2n (entries 9 and 10). In-
creasing the flow values for transportation of alcohol through the
column, clearly affects the efficiency of dehydration process
(entries 3, 4, 7 and 8). Even, taking into account that the developed
system for dehydration has used a small column, packed with ap-
proximately 2 g of resin, we are certain that this system can be
improved by using larger columns, permitting to obtain higher
amounts of olefins in continuous flow. Additionally, given that this
system is characterized as a method in which the catalyst remains
static inside the column, contrary to what happens when the re-
action occurs in a flask under stirring, the yields for dehydration of
alcohol 1n appear to be attractive.
of 1k with AmberlystÒ-15 in the presence of compounds 3aef
proceeded in refluxed dichloromethane affecting the protecting
groups in small extend. These results further demonstrate the
selectivity of the dehydration process developed.
3. Conclusion
In summary, we have developed a highly efficient and in-
expensive system for transformation of tertiary alcohols into the
most stable alkene under very mild conditions, using AmberlystÒ-
15 as a heterogeneous catalyst. Rearranged products and poly-
merization have not been observed. Some functional groups, gen-
erally affected under acidic conditions, such as acetal, Boc and
TBDMS, remain practically unaltered under conditions of alcohol
dehydration. The catalyst may be reused for five cycles. Further
studies on selective dehydration of the tertiary alcohol function-
ality in several natural products are in progress.
4. Experimental
4.1. General methods
All solvents were freshly distilled from commercial grade. Com-
mercially available reagents were used as received without further
purification, such as MeMgCl (3.0 M in THF), EtMgCl (2.0 M in THF)
and BuMgCl (2.0 M in THF). AmberlystÒ-15 was purchased to Sig-
maeAldrich (AmberlystÒ-15 hydrogen form, dry, moisture <2%).
Column chromatography was performed using Silica gel 60 MN and
aluminium-backed silica gel Merck 60 F254 plates were used for
analytical thin layer chromatography (TLC). Mass spectra (MS) and
accurate masses (HRMS) were obtained from the Mass Spectrometry
Services of University of Santiago de Compostela (Spain). Infrared
spectra (IR) were recorded on a Jasco FT/IR-430 spectrophotometer.
1H and 13C NMR spectra were recorded on a Bruker ARX 400 spec-
Encouraged by the results obtained for the series of tertiary al-
cohols, we also tested the new methodology of dehydration in the
presence of molecules bearing other sensitive functionalities. Six
compounds (3aef) possessing different protecting groups (NHCBz,
OBOM, OSEM, OTBDMS, NHBoc and ethylene ketal) were tested in
a competitive process with tertiary alcohol 1k (see entries 1e6,
Table 6). Based on the results of isolated yields for 3aef after pre-
parative column chromatography, it was verified that dehydration
trometer. Chemical shifts are reported as
d values relative to

7418
L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
Table 6
4.3. Procedure for the catalyst reuse
Dehydration of 1k by using AmberlystÒ-15 in the presence of substrates with dif-
ferent functional groupsa
,b
AmberlystÒ-15 (dry) (90 mg) was added to a dichloromethane
solution (15 mL) of 4-(2-hydroxypropan-2-yl)-1-methylcyclohexanol
(1a, trans-terpin) (75 mg; 0.43 mmol). The reaction was stirred at rt
and monitored by TLC [Et2O/hexane (3:1) as eluent] until verification
of the disappearance of the reagent (3.5 h). The AmberlystÒ-15 was
filtered from the solvent, which was evaporated under reduced
pressure at rt to give a residue (crude of 2-(4-methylcyclohex-3-enyl)
propan-2-ol (2a)). The AmberlystÒ-15 was washed with dichloro-
methane (50 mL) and dried at rt. The same catalyst was used in the
dehydration of 1a in 10 cycles.
l
l
l
l
l
l
l
Entry
1
Protected
molecule
Yield of 2kc (%) Yield of recovered 3d
(%)
H
N
O
Ph
This procedure was repeated for a trans-terpin/AmberlystÒ-15
ratio of 1:0.7 (75 mg/52.5 mg) (see Fig. 2).
86
76
81
73
O
OH
3a
4.4. General procedure for the preparation of alcohols 1eem
(ZnCl2-catalysed alkylation of ketones with Grignard
reagents)9
2
3
OBOM
3b
To a solution of MeMgCl (3.0 M in THF, 4 mL, 12 mmol) was
added ZnCl2 (95.2 mg; 0.70 mmol) at rt under nitrogen atmo-
sphere. This solution was stirred at that temperature for 1 h. Then,
the solution was cooled to 0 ꢁC, and 4-tert-butylcyclohexanone
(1.08 g, 7.00 mmol) was added at 0 ꢁC. The mixture was stirred for
2 h at 0 ꢁC, and the reaction was monitored by TLC. The resulting
mixture was quenched by saturated aqueous NH4Cl (15 mL),
extracted with EtOAc (3ꢂ50 mL) and washed with brine (30 mL).
The combined extracts were dried over Na2SO4. The organic phase
was concentrated under reduced pressure and the resultant residue
was purified by neutral silica gel column chromatography (eluent:
hexane/EtOAc (1:1)), to give alcohol 1e (0.95 g, 80% yield). Alcohols
1fem were prepared from the correspondent ketones and RMgBr
(R¼Me, Et or Bu) following this procedure.
68
70
SEMO
H
3c
OTBDMS
4
5
81
80
86
78
3d
3e
6
73
64
O
4.5. General procedure for the dehydration of tertiary
alcohols 1aen
O
H
3f
a
Protected molecule/2k ratio (1:1) equiv mol.
b
All reactions were carried out in 25 mL of CH2Cl2, in the presence of a protected
AmberlystÒ-15 (dry) (90 mg) was added to a CH2Cl2 solution
(15 mL) of tertiary alcohol 1aen (75 mg) [corresponding to a sub-
strate/AmberlystÒ-15 ratio of 1:1.2 (w/w)]. The reaction was stirred
at rt and monitoredbyTLC until the verification of the disappearance
of the reagent. The AmberlystÒ-15 was filtered and the solvent was
removed under reduced pressure at rt to give a residue. To this
residue was added additional 30 mL of CH2Cl2. The organic phase
was dried (Na2SO4), filtered and evaporated to dryness at rt to give
olefin 2aen. Olefins 2c, 2eeg and 2kem were submitted to
additional purification by conventional column chromatography
(eluent: from hexane to hexane/EtOAc (3:6)). Dehydration of alco-
hols 1d and 1ken occurred under CH2Cl2 reflux. See 1H and 13C NMR
spectra of olefins 2aen in Supplementary data. 1H and 13C NMR
spectra of compounds 2a and 2c are identical to the ones reported.
molecule (0.3 mmol)þ1k (0.3 mmol)/AmberlystÒ-15 ratio of (1:1.2) (w/w).
c
Isolated yield.
d
Isolated yield, relative to the recovered protected molecule by preparative
chromatography.
tetramethylsilane (dH¼0 ppm), CDCl3
yses were performed on Gas Chromatograph Mass Spec-
trometerdQP2010S, Shimadzu by using the column TRB-
(dC¼77.0 ppm). GCeMS anal-
a
5MSdTeknokroma (30 mꢂ0.25 mmꢂ0.25
mm) (conditions: solvent:
CH2Cl2; Tinitial¼50 ꢁC, Tfinal¼250 ꢁC, slope¼5 ꢁC/min, hold
time¼5 min).
4.2. General procedure for the dehydration of trans-terpin (1a)
AmberlystÒ-15 (dry) (75 mg) was added to a dichloromethane
solution (15 mL) of 4-(2-hydroxypropan-2-yl)-1-methylcyclohexanol
(1a, trans-terpin) (75 mg; 0.43 mmol). The reaction was stirred at
room temperature (rt) and monitored by TLC [diethyl ether/hexane
(3:1) as eluent] until the verification of the disappearance of the re-
agent (3.5 h). The AmberlystÒ-15 was removed by filtration and the
solvent was evaporated under reduced pressure at rt to give a residue.
Dichloromethane (30 mL) was added to re-dissolve this residue. The
organic phase was dried (Na2SO4), filtered and evaporated to dryness
at rt to give 2-(4-methylcyclohex-3-enyl)propan-2-ol (2a) as a pale
yellow oil (56.5 g; 85% yield). MS (EI), m/z 153 [M]þ. 1H and 13C NMR
spectra of 2a are identical to the described.10 This procedure was re-
peated for the five solvents tested (Table 2) and during dehydration
yield optimization by variation of AmberlystÒ-15/alcohol 1a ratio
(Fig. 1).
4.6. Procedure for the dehydration of alcohol 1n in
a 0.032 mol scale (5g)
AmberlystÒ-15(dry)(6 g)wasaddedtoaCH2Cl2 solution(200 mL)
of tertiaryalcohol 1n (5 g) [corresponding to a substrate/AmberlystÒ-
15 ratio of 1:1.2 (w/w)]. The reaction was stirred under CH2Cl2 reflux
and monitored by TLC (eluent: diethyl ether/hexane (4:1)) until the
verification of the disappearance of the reagent (2.5 h). The
AmberlystÒ-15 was filtered and the solvent was removed under re-
duced pressure at rt to give a residue. CH2Cl2 (100 mL) was added to
re-dissolve this residue. The organic phase was dried (Na2SO4), fil-
tered and evaporated to dryness at rt to give olefin 2n (85% yield) as
a pale yellow oil (mixture of three isomers 2n0 (15%), 2n00 (33%) and
2n000 (52%); see NMR data in Supplementary data).

L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
7419
4.7. General procedure for the dehydration of 1k in the
4.10. Characterization data for compounds 1e3
presence of additional substrate (3aef)
4.10.1. 4-tert-Butyl-1-methylcyclohexanol (1e).12 Compound 1e was
7-Methoxy-1-methyl-1,2,3,4-tetrahydronaphthalen-1-ol
(1k,
obtained as pale yellow thick syrup. 1H NMR (400 MHz, CDCl3):
57.5 mg; 0.30 mmol) and (((octan-2-yloxy)methoxy)methyl)ben-
zene (3b, 76.5 mg; 0.30 mmol) were dissolved in 25 mL of CH2Cl2.
AmberlystÒ-15 (dry) (160 mg) was added and the mixture was
stirred under reflux until the verification of total transformation of
alcohol 1k (TLC; eluent CH2Cl2/hexane (3:1)). The AmberlystÒ-15
was filtered and the solvent was removed under reduced pressure at
rt to give a residue. To this residue was added additional 50 mL of
CH2Cl2. The organic phase was dried (Na2SO4), filtered and evapo-
rated to dryness at rt to give a mixture of olefin 2k and substrate 3b
(yellow oil). This mixture suffered additional purification by con-
ventional column chromatography (eluent: from H to H/EtOAc
(3:6)). Isolated yields after chromatography: 2k: 76%; 3b: 73%. This
procedure was repeated with the six different substrates possessing
various protecting groups (3aef; Table 3). 13C NMR spectra of de-
rivatives 3aef recovered after dehydration process and 1H NMR
spectra of 2kþ3c and 2kþ3d reaction mixtures before chromato-
graphic separation (Supplementary data).
d 5.21 (s, 1H, eOH), 1.50e1.67 (m, 4H), 1.18–1.34 (m, 5H), 1.13 (s, 3H),
0.80 (s, 9H); 13C NMR (125 MHz, CDCl3):
d 68.9, 47.7, 40.9, 39.3, 31.4,
27.7, 25.0, 22.7. MS (EI): m/z 170 [M]þ.
4.10.2. 4-tert-Butyl-1-ethylcyclohexanol (1f).13 Compound 1f was
obtained as colourless oil. 1H NMR (400 MHz, CDCl3):
5.29 (s, 1H,
d
eOH), 1.81e1.78 (m, 2H), 1.66e1.52 (m, 4H), 1.46e1.40 (m, 1H),
1.34e1.27 (m, 4H), 0.91e0.88 (t, 3H), 0.86 (s, 9H); 13C NMR
(125 MHz, CDCl3):
d 70.7, 48.1, 38.4, 36.9, 36.6, 27.6, 24.4, 22.5, 7.5.
MS (EI): m/z 184 [M]þ.
4.10.3. 4-tert-Butyl-1-butylcyclohexanol (1g).14 Compound 1g was
obtainedascolourlessoil.1HNMR(400 MHz,CDCl3):
d
5.24(s,1H, OH),
1.61e1.58(m, 2H),1.54e1.41 (m, 3H),1.34e1.23 (m, 9H), 0.87e0.84 (m,
4H), 0.80 (s, 9H); 13C NMR (125 MHz, CDCl3):
d 70.7, 48.0, 44.1, 38.9,
37.4, 27.6, 25.4, 24.5, 23.4, 22.5, 14.2. MS (EI): m/z 212 [M]þ.
4.10.4. 2-Methyldodecan-2-ol (1h).15 Compound 1h was obtained
as colourless thick syrup. 13C NMR (125 MHz, CDCl3):
d 70.9, 44.0,
31.9, 30.2, 29.6, 29.4, 29.2, 24.4, 22.7, 14.1. MS (EI): m/z 200 [M]þ.
4.8. Preparationofmajorolefin2n0 bydehydrationofalcohol1n
This experiment was performed under modified condition in
4.10.5. 3-Methyltridecan-3-ol (1i).16 Compound 1i was obtained as
colourless oil. 13C NMR (125 MHz, CDCl3):
d 72.9, 41.3, 34.2, 31.9,
the literature;11 to
a stirred solution of alcohol 1n (1.0 g;
30.3, 29.7, 29.6, 29.4, 26.4, 23.9, 22.7,14.1, 8.2. MS (EI): m/z 214 [M]þ.
6.30 mmol; 1.0 equiv) in dry dichloromethane (20 mL) at rt was
added dry pyridine (1.02 mL; 12.60 mmol; 2.0 equiv). After cooling
to ꢀ78 ꢁC a solution of thionyl chloride (2.2 mL; 31.50 mmol;
5.0 equiv) in dry dichloromethane (10 mL) and dry pyridine (4 mL;
50.40 mmol; 8.0 equiv) was added dropwise. The reaction mixture
was stirred for 30 min at the same temperature before quenching
with saturated aqueous NaHCO3 (30 mL). The reaction mixture was
allowed to warm to rt and the organic layer was separated. The
aqueous phase was extracted with dichloromethane (5ꢂ50 mL).
The combined organic layers were dried over MgSO4 by filtration to
give a crude (pale yellow) oil. This residue was further purified by
conventional column chromatography (eluent: from hexane to
hexane/EtOAc (3:6)) to give (0.70 g; 79% overall yield) of a mixture
of olefins 2n0 (82%), 2n00 (7%) and 2n000 (11%), ratio determined by
NMR; see NMR data of mixture in Supplementary data.
4.10.6. 5-Methylpentadecan-5-ol (1j).17 Compound 1j was obtained
as colourless oil. 13C NMR (125 MHz, CDCl3):
d 72.7, 41.9, 41.6, 31.9,
30.3, 29.7, 29.4, 26.9, 26.1, 23.9, 23.3, 22.7,14.1. MS (EI): m/z 242 [M]þ.
4.10.7. 7-Methoxy-1-methyl-1,2,3,4-tetrahydronaphthalen-1-ol
(1k).18 Compound 1k was obtained as pale yellow thick syrup. 1H
NMR (400 MHz, CDCl3):
6.75e6.78 (q, 1H), 5.53 (s, 1H), 3.81 (s, 3H), 2.68e2.79 (m, 2H),
1.88e1.97 (m, 4H), 1.56 (s, 3H); 13C NMR (125 MHz, CDCl3):
158.1,
d 7.13e7.14 (d, 1H), 6.99e7.01 (d, 1H),
d
144.0, 129.8, 128.4, 113.8, 110.8, 70.9, 55.4, 39.8, 30.8, 29.1, 20.1. MS
(EI): m/z 192 [M]þ.
4.10.8. 1-Butyl-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol (1l).
Compound 1l was obtained as pale yellow thick syrup. 13C NMR
(125 MHz, CDCl3):
d 158.1, 144.1, 129.7, 128.4, 113.7, 110.8, 70.8, 55.3,
53.5, 39.8, 30.8, 29.1, 20.7. MS (EI): m/z 234 [M]þ. HRMS (EI (DE))
4.9. Procedure for the dehydration of alcohol 1n under
continuous operation
calcd for C15H22O2, 234.16198; found, 234.16213.
4.10.9. 1-Ethyl-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol (1m).
Compound 1m was obtained as pale yellow thick syrup. 1H NMR
Initially, an empty HPLC column was packed with 1.986 g of
AmberlystÒ-15 (dry) resin (Fig. 2S, Supplementary data). The col-
umnwas connected to a simple pistonpump (Fig. 3S, Supplementary
data) and immersed in water at 45 ꢁC (see column in a thermostatic
water bath in Fig. 3S). A CH2Cl2 solution of alcohol 1n of known
concentrationwas passed through the column using a constant flow.
The mixture passed through the columnwas collected in a container
and analysed by TLC (eluent: Et2O/hexane (4:1); TLC analysis
allowed determination of when total dehydration of alcohol oc-
curred). Different flows and volumes of the reaction mixture col-
lected (dichloromethane alcoholic solution) were tested (at 45 ꢁC
and 50 ꢁC) in order to reach the optimal conditions, that is, the total
conversion of alcohol 1n into olefin 2n (Table 1S, Supplementary
data). The CH2Cl2 solution was dried (Na2SO4), filtered and evapo-
rated to dryness at rt to give a crude (pale yellow) oil. This residue
was further purified by conventional column chromatography (el-
uent: from hexane to hexane/EtOAc (3:6) to give olefin 2n (as
a mixture of three isomers, 2n0, 2n00 and 2n000)).
(400 MHz, CDCl3):
5.48 (s, 1H), 3.76 (s, 3H), 2.73e2.60 (m, 2H), 2.01e1.69 (m, 6H),
0.89e0.85 (t, 3H); 13C NMR (125 MHz, CDCl3):
158.0, 143.5, 129.8,
d 7.03e7.02, (d,1H), 6.96 (s,1H), 6.72e6.71 (d, 1H),
d
129.0,113.5,110.8, 72.8, 55.3, 53.5, 35.3, 29.1,19.9, 8.6. MS (EI): m/z 206
[M]þ. HRMS (EI (DE)) calcd for C13H18O2, 206.13068; found, 206.13051.
4.10.10. 2-(4-Methylcyclohex-3-enyl)propan-2-ol (2a).19 Compound
2a was obtained as colourless oil. 13C NMR (125 MHz, CDCl3):
d
133.9, 120.6, 72.7, 45.0, 31.0, 27.4, 26.9, 26.2, 24.0, 23.3. MS (EI): m/
z 154 [M]þ.
4.10.11. (þ)-Limonene (2a0).20 Compound 2a0 was obtained as col-
ourless oil. 13C NMR (125 MHz, CDCl3):
d 149.5, 133.1, 120.9, 108.4,
41.1, 30.8, 30.6, 28.0, 23.6, 20.5. MS (EI): m/z 136 [M]þ.
4.10.12. Terpinolene (2a00). Compound 2a0 was obtained as pale
yellow oil. 13C NMR (125 MHz, CDCl3):
d 133.1, 126.2, 125.1, 120.1,

7420
L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
31.6, 30.1, 28.1, 23.5, 19.1. MS (EI): m/z 136 [M]þ. Spectral data
CDCl3):
d 7.06e7.03 (d, 1H), 6.83e6.82 (d, 1H), 6.76e6.73 (dd, 1H),
identical to an authentic sample.
5.62e5.60 (t, 1H), 3.84 (s, 3H), 2.96e2.93 (t, 2H), 2.78e2.74 (q, 2H),
1.37 (s, 3H); 13C NMR (125 MHz, CDCl3):
d 157.6, 143.4, 130.1, 127.1,
4.10.13. (8S,9S,10R,13S,14S)-10,13,17-Trimethyl-7,8,9,11,12,13,14,15-
octa-hydro6H-cyclopenta[a]phenanthren-3(10H)-one(2b). Compound
2b was obtained as pale yellow thick syrup. 1H NMR (400 MHz,
123.3, 118.0, 111.4, 102.8, 55.3, 31.5, 22.9, 20.7. MS (EI): m/z 174 [M]þ.
4.10.23. 4-Butyl-6-methoxy-1,2-dihydronaphthalene (2l). Compound
2l was obtained as a pale yellow oil. 1H NMR (400 MHz, CDCl3):
CDCl3):
d 7.13e7.16 (d, 1H), 6.21e6.25 (dd, 1H), 6.06e6.07 (t, 1H),
2.47e2.53 (dd, 1H), 2.33e2.40 (m, 2H), 2.14e2.19 (m, 3H), 2.01e2.07
(m, 2H), 1.83e1.92 (m, 2H), 1.61 (s, 3H), 1.23e1.24 (d, 1H), 1.20 (s, 3H),
1.18 (s, 1H), 1.02 (s, 1H), 0.95 (s, 3H), 0.91 (s, 3H); 13C NMR (125 MHz,
d 7.10e7.08 (d, 1H), 6.89 (s, 1H), 6.73e6.72 (d, 1H), 5.92e5.90 (t, 1H),
3.85 (s, 3H), 2.73e2.69 (t, 2H), 2.47e2.44 (t, 2H), 2.29e2.24 (q, 2H),
1.60e1.40 (m, 4H), 1.00e0.98 (t, 3H); 13C NMR (125 MHz, CDCl3):
CDCl3):
d
186.4, 169.0, 155.7, 141.9, 134.2, 127.6, 124.3, 60.8, 49.5, 45.4,
d 158.3, 136.5, 129.1, 128.1, 125.4, 121.8, 110.6, 109.7, 55.4, 32.5, 30.7,
43.4, 39.4, 36.6, 33.3, 32.6, 30.0, 26.7, 26.5, 24.1, 22.1, 18.6. HRMS
27.6, 23.5, 22.7, 14.1. MS (EI): m/z 216 [M]þ. HRMS (EI (DE)) calcd for
(ESIþ) calcd for C20H26O, 282.19837; found, 282.19821.
C15H20O, 216.15141; found, 216.15125.
4.10.14. (1S)-2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-enol (2c).21
Compound 2c was obtained as colourless oil. 13C NMR (125 MHz,
4.10.24. 4-Ethyl-6-methoxy-1,2-dihydronaphthalene (2m). Comp-
ound 2m was obtained as pale yellow oil (mixture of two styrene
isomers). NMR data for 2m containing endo and exo isomers: 13C
CDCl3):
d 148.6, 135.0, 124.8, 111.4, 68.3, 36.5, 35.4, 30.3, 20.9, 20.3.
MS (EI): m/z 152 [M]þ.
NMR (125 MHz, CDCl3): d 157.6, 157.5, 138.8, 130.3, 129.8, 128.1,
126.2, 125.3, 124.3, 123.4, 117.8, 113.6, 111.5, 110.7, 109.5, 102.5, 55.3,
39.5, 29.4, 29.1, 27.0, 23.5, 20.2, 14.6, 12.0. MS (EI): m/z 188 [M]þ.
HRMS (EI(DE)) calcd for C13H16O, 188.12011; found, 188.12004.
4.10.15. 1-Methyl-4-(prop-1-en-2-yl)cyclohexane (2d).22 Compound
2d was obtained as colourless oil. 1H NMR (400 MHz, CDCl3):
d
5.23
(s, 2H), 2.17e1.97 (m, 3H), 1.20e1.17 (m, 5H), 1.09 (s, 1H), 0.93e0.92
(d, 3H), 0.81e0.69 (m, 4H); 13C NMR (125 MHz, CDCl3):
148.1,
111.7, 44.0, 36.0, 35.6, 33.1, 22.8, 20.0. MS (EI): m/z 138 [M]þ.
d
4.10.25. cis-Benzyl N-(1-hydroxyindan-2-yl)carbamate (ꢃ) (3a).27
White solid. Mp 139e141 ꢁC. 1H NMR (400 MHz, CDCl3):
d 2.06 (br s,
1H, OH), 2.90 (d, 1H, CH2), 3.12 (dd, 1H, CH2), 4.58 (br s, 1H, CH),
4.10.16. 4-tert-Butyl-1-methylcyclohex-1-ene (2e).23 Compound 2e
5.08e5.20 (m, 3H, OCH2Ph, CH), 5.48(d,1H, NH), 7.24e7.39 (m, 9H, Ar);
was obtained as colourless thick syrup. 1H NMR (400 MHz, CDCl3):
13C NMR (125 MHz, CDCl3):
d 156.8, 140.9, 139.8, 136.5, 128.4, 128.1,
d
5.33e5.30 (t, 1H), 1.36e1.29 (m, 1H), 1.25e1.18 (m, 3H), 1.16e1.11
(m, 3H), 0.79 (s, 3H), 0.78 (s, 9H); 13C NMR (125 MHz, CDCl3):
137.9,122.0, 45.0, 30.8, 30.2, 27.6, 25.6, 24.5. MS (EI): m/z 152 [M]þ.
128.0, 126.9, 125.2, 124.4, 73.0,66.9, 59.1, 39.6. MS (EI): m/z 297 [M]þ.
d
4.10.26. (((Octan-2-yloxy)methoxy)methyl)benzene (3b). Compound
1m was obtained as pale yellow thick syrup. 13C NMR (125 MHz,
4.10.17. 4-tert-Butyl-1-ethylcyclohex-1-ene (2f).24 Compound 2f
CDCl3): d 137.9,128.5,128.4,128.0,127.9, 127.8, 127.7, 93.9, 92.9, 73.3,
was obtained as colourless oil. 1H NMR (400 MHz, CDCl3):
69.6, 69.4, 37.1, 32.0, 29.5, 25.7, 22.7, 20.3,14.2. MS (EI): m/z 250 [M]þ.
d
5.32e5.30 (t,1H),1.29e1.19 (m, 5H), 0.93e0.89 (m, 4H), 0.85 (s, 3H),
HRMS (ESIþ) calcd for C16H26O2Na, 273.18249; found, 273.18234.
0.78 (s, 3H), 0.79 (br s, 9H); 13C NMR (125 MHz, CDCl3):
d 139.4,119.5,
44.3, 32.2, 30.2, 29.8, 27.3, 26.8, 24.3, 12.4. MS (EI): m/z 166 [M]þ.
4.10.27. 5
a
-Cholestan-3-one ((methoxy)ethyl)trimethylsilane (3c).
13C NMR (125 MHz, CDCl3):
d
92.9, 76.2, 64.9, 56.6, 56.4, 54.5, 45.0,
4.10.18. 4-tert-Butyl-1-butylcyclohex-1-ene (2g).25 Compound 2g
42.7, 40.2, 39.7, 37.2, 36.3, 35.9, 35.8, 35.6, 35.4, 32.3, 29.0, 28.8,
28.4, 28.2, 24.4, 24.0, 23.0, 22.7, 21.4, 18.8, 18.2, 12.4, 12.2. MS (EI):
m/z 518 [M]þ. HRMS (ESI) calcd for C33H62O2NaSi, 541.44113; found,
541.44157.
was obtained as pale yellow oil. 1H NMR (400 MHz, CDCl3):
d
5.30e5.32 (br s, 1H), 1.91e1.40 (m, 7H), 1.26e1.19 (m, 5H),
0.85e0.82 (m, 4H), 0.79 (s, 9H); 13C NMR (125 MHz, CDCl3):
d 138.1,
121.1, 53.7, 48.3, 44.4, 39.6, 37.7, 27.9, 22.8,14.4. MS (EI): m/z 194 [M]þ.
4.10.28. tert-Butyldimethyl(1-phenylethoxy)silane (3d).28 13C NMR
4.10.19. 2-Methyldodec-2-ene (2h).26 Compound 2h was obtained
(125 MHz, CDCl3):
d 147.0, 128.2, 126.7, 125.2, 70.9, 27.4, 26.0, 18.3.
as colourless oil. 1H NMR (400 MHz, CDCl3):
d
5.06e5.02 (t, 1H),
MS (EI): m/z 236 [M]þ.
1.94e1.86 (m, 2H),1.61 (s, 3H),1.52 (s, 3H),1.19 (br s,14H), 0.82e0.79
(t, 3H); 13C NMR (125 MHz, CDCl3):
d
131.4, 125.4, 32.4, 30.4, 30.1,
4.10.29. tert-Butyl 1-phenylethylcarbamate (3e).29 White solid. Mp
30.0, 29.8, 28.5, 26.1, 23.1, 18.0, 14.5. MS (EI): m/z 182 [M]þ.
78e79 ꢁC. 13C NMR (125 MHz, CDCl3):
d
155.2, 145.1, 128.7, 127.2,
126.0, 79.6, 50.3, 28.6, 22.8. MS (EI): m/z 221 [M]þ.
4.10.20. 3-Methyltridec-3-ene (2i). Compound 2i was obtained as
a pale yellow oil. 1H NMR (100 MHz, CDCl3):
d
5.10e5.07 (t, 1H),
1.99e1.90 (m, 4H), 1.64e1.55 (m, 3H) 1.23 (br s, 14H), 0.97e0.93 (t,
3H), 0.87e0.83 (t, 3H); 13C NMR (125 MHz, CDCl3):
136.5, 123.7,
4.10.30. 5
a
-Cholestan-3-one ethylene ketal (3f).30 13C NMR
(125 MHz, CDCl3): 109.5, 64.2, 56.2, 54.1, 43.7, 42.6, 40.1, 39.6,
d
d
38.0, 35.8, 35.5, 35.4, 31.9, 31.2, 28.6, 28.3, 28.0, 24.2, 23.8, 22.9,
32.3, 30.1, 30.04, 30.03, 30.0, 29.8, 28.4, 28.3, 23.7, 23.1,14.5,13.2. MS
(EI): m/z196[M]þ. HRMS(EI (DE))calcd forC14H28,196.21910; found,
196.21921.
22.6, 21.2, 18.7, 12.1, 11.4. MS (EI): m/z 430 [M]þ.
Acknowledgements
ˇ
~
4.10.21. 5-Methylpentadec-5-ene (2j). Compound 2j was obtained
The authors acknowledge Fundac¸ ao para a Ciencia e Tecnologia
as a pale yellow oil. 1H NMR (400 MHz, CDCl3):
d
5.03 (t, 1H),
(FCT-Portugal) and FEDER (PTDC/QUI/73061/2006, PTDC/QUI-QUI/
2.35e2.28 (m, 2H), 1.94e1.87 (m, 6H), 1.50 (s, 3H), 1.18 (br s, 14H),
102460/2008 and SFRH/BPD/43853/2008) for financial support.
0.83e0.78 (m, 6H); 13C NMR (125 MHz, CDCl3):
d 135.7, 124.9, 32.3,
30.3, 30.0, 29.7, 28.4, 24.2, 23.0, 14.4. MS (EI): m/z 224 [M]þ. HRMS
Supplementary data
(EI (DE)) calcd for C16H32, 224.25040; found, 224.25057.
Copies of1Hand13C NMRspectraofcompounds 1eem, 2aen and
3aef and 1H NMR spectra of reaction mixtures resulting from de-
hydration of 1k in the presence of substrates 3c and 3d.
4.10.22. 6-Methoxy-4-methyl-1,2-dihydronaphthalene (2k).18 Com-
pound 2k was obtained as colourless thick syrup.1H NMR (400 MHz,

L.M.T. Frija, C.A.M. Afonso / Tetrahedron 68 (2012) 7414e7421
7421
854; (d) Khan, N. A.; Hwang, J.-S.; Jhung, S. H. Bull. Korean Chem. Soc. 2011, 32,
1327; (e) Sharma, M. M. React. Funct. Polym. 1995, 26, 3; (f) Yoon, J. W.; Chang,
J.-S.; Lee, H.-D.; Kim, T.-J.; Jhung, S. H. J. Mol. Catal. A 2006, 260, 181; (g) Yoon, J.
W.; Jhung, S. H.; Chang, J.-S. Bull. Korean Chem. Soc. 2008, 29, 339; (h) Yoon, J.
W.; Jhung, S. H.; Lee, J. S.; Kim, T.-J.; Lee, H.-D.; Chang, J.-S. Bull. Korean Chem.
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Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.06.083.
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