Aluminium triflate catalysed cyclisation of unsaturated alcohols: novel synthesis of rose oxide and analogues

Article abstract of DOI:10.1002/ejoc.200900841

Aluminium trifluoromethanesulfonate was used as an efficient catalyst for the cycloisomerisation of several unsaturated alcohols into cyclic ethers such as rose oxide and some of its ether analogues.

Full text of DOI:10.1002/ejoc.200900841

FULL PAPER
DOI: 10.1002/ejoc.200900841
Aluminium Triflate Catalysed Cyclisation of Unsaturated Alcohols:
Novel Synthesis of Rose Oxide and Analogues
Lydie Coulombel,[a] Michel Weïwer,[a] and Elisabet Duñach*[a]
Keywords: Aluminum / Alkenes / Alcohols / Cyclization / Superacidic systems
Aluminium trifluoromethanesulfonate was used as an ef-
ficient catalyst for the cycloisomerisation of several unsatu-
rated alcohols into cyclic ethers such as rose oxide and some
of its ether analogues.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Cyclic ethers are important structures frequently found
in polyether antibiotics and other biologically active natural
products, and great interest is focused on the development
of new and efficient methods for the synthesis of cyclic
ethers.[1] One of the most appealing approaches for the syn-
thesis of these heterocycles is the direct intramolecular hy-
droalkoxylation, in which the cyclic ether is formed by ad-
dition of an alcohol to a nonactivated C=C bond.[2] These
atom-economic processes, known to be catalysed by
Brønsted acids in super-stoichiometric amounts, have been
recently reported by the use of strong Lewis acids in cata-
lytic amounts.[3] Thus, SnIV[4] and AlIII[5] triflates as well as Scheme 1.
PtII/PR3,[6] FeIII[7] and Au derivatives[8] have shown interest-
ing catalytic activities in the formation of cyclic ethers from
Several synthetic procedures for the preparation of 1
nonactivated olefins. The high activity of the metallic tri-
flate catalysts is due to the strongly electron-withdrawing
trifluoromethanesulfonate group.[9]
have been described, and in almost all cases, citronellol is
used as the starting material.[11b,13] The synthetic pathways
generally involve the oxidation (including bromination) of
the double bond of citronellol followed by elimination to a
diene structure and further acid-catalysed cyclisation. How-
ever, this procedure lacks selectivity, because several iso-
meric byproducts are produced at the different steps.
In order to improve the olfactory properties of rose ox-
ide, Firmenich reported in 1993 the synthesis of 4-methyl-
2-phenyltetrahydropyran 2 (Doremox®), in which the iso-
butenyl moiety of 1 was substituted by a phenyl group.[14]
This substitution increased the substantivity of rose
scent,[15] that is, the persistence of the perfume material on
blotters or skins.
Pursuing the development of the cycloisomerisation of
unsaturated alcohols involving the use of metallic trifluoro-
methanesulfonates as Lewis “superacid” catalysts,[10] we de-
scribe here some novel examples of this catalytic methodol-
ogy applied to the synthesis of racemic cyclic ethers of the
rose oxide family, such as compounds 1–5 (Scheme 1).
Rose oxide (1), first isolated from Bulgarian rose oil in
1959, is known to be the responsible component for the
floral and green top notes of rose odorants.[11] This cyclic
ether is present in its different isomeric forms and has been
further identified in many plants, flowers and fruits such as
Eucalyptus citriodora, geranium and tropical fruits.[12] It is
used as a fragrance ingredient for the preparation of many
perfuming compositions as well as perfumed goods.
Results and Discussion
[a] Laboratoire de Chimie des Molécules Biactives et des Arômes,
Université de Nice-Sophia Antipolis, CNRS UMR 6001, Insti-
tut de Chimie de Nice,
Preparation of Unsaturated Alcohols
The Lewis acid cyclisation for the preparation of pyranyl
ethers 1–5 requires the preparation of alcohols 6, as shown
Parc Valrose, 06108 Nice cedex 2, France
E-mail: dunach@unice.fr
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Aluminium Triflate Catalysed Cyclisation of Unsaturated Alcohols
in Scheme 2. The unsaturated alcohols were prepared in Al(OTf)3-Catalysed Cycloisomerisation of Alcohols 6a–e
three steps via intermediate γ-aldehyde–esters 7.
Al(OTf)3 was shown to be an efficient catalyst for the
cycloisomerisation of nonactivated unsaturated alcohols,
Table 2. Al(OTf)3-catalysed cycloisomerisation of alcohols 6a–e.
Scheme 2.
Compounds 7a and 7b were obtained from butyl 2- and
butyl 3-methyl-4-pentenoate by its olefin oxidative cleavage
in the presence of NaIO4 and a catalytic amount of rutheni-
um(III) chloride in 79 and 70% yield, respectively
(Scheme 3).[16,17]
The reaction of 7a,b with phosphonium salts 8a–c af-
forded unsaturated esters 9a–e in 66–79% isolated yield
(Scheme 3, Table 1). Esters 9 were obtained in Z/E ratios
ranging from 14:86 to 45:55. Further reduction of the ester
functionality of 9 in the presence of lithium aluminium hy-
dride afforded desired alcohols 6 in almost quantitative iso-
lated yields and the same Z/E ratios.
Table 1. Yields and Z/E ratios for esters 9a–e and unsaturated
alcohols 6a–e.
Entry R1
R2 R3 Ester 9a–e Z/E Alcohols 6a–e
Z/E
Yield [%]
Yield [%]
1
2
3
4
5
(CH3)2C=CH Me
H
H
H
Me
Me
9a, 70
9b, 79
9c, 66
9d, 71
9e, 71
28:72
15:85
14:86
45:55
30:70
6a, 87
6b, 92
6c, 94
6d, 83
6e, 78
28:72
15:85
14:86
45:55
30:70
Ph
Me
Me
H
ortho-tolyl
(CH3)2C=CH
Ph
H
Scheme 3.
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L. Coulombel, M. Weïwer, E. Duñach
FULL PAPER
leading quantitatively and regioselectively to the corre- six-membered ring ether 5 was obtained from 6e in 84%
sponding cyclic ethers.[5] This catalytic Lewis “superacid” yield and with a cis/trans ratio of 86:14 (Table 2, Entry 7).
system was used for the cyclisation of unsaturated alcohols
6a–e. The cycloisomerisation was run in the presence of Al-
(OTf)3 (5 mol-%) and led to the synthesis of rose oxide (1)
and its analogues 2–5, as illustrated in Table 2.
Mechanistic Considerations
The cyclisation of alcohol 6a (Z/E = 28:72) in refluxing
Concerning the regiochemical outcome of the cycli-
CH2Cl2 afforded rose oxide (1) in 70% yield with a cis/trans sation, for example, the formation of five- vs. six-membered
ratio of 82:18 after 1 h (Table 2, Entry 1). The diastereoiso- ring ethers with dienic alcohols 6a and 6d, the experimental
meric cis/trans ratio was determined by NOESY-NMR ex- results revealed that the cyclisation led exclusively to the
periments. The major cis isomer is known to present the corresponding oxanes 1 and 4, respectively. The mechanism
most powerful odorant properties.[13e] The cyclisation was of the reaction can be explained by a first coordination of
regioselective and no formation of five- or seven-membered Al3+ to the hydroxy group of the alcohols leading to an
ring ethers was observed. Only the six-membered ring ether increased acidity of the proton of the OH group, according
was formed; the intramolecular hydroalkoxylation of 6a oc- to the results of theoretical calculations.[5] Proton addition
curred exclusively at the internal position of the diene, on to the diene unit may afford the formation of cationic allyl
the less-substituted double bond. This regioselectivity can intermediates of type A or B (Scheme 4). Alkoxide addition
be explained by a carbocationic-type mechanism as dis- can then either occur onto intermediate A to afford the for-
cussed hereafter.
mation of six- vs. eight-membered ring ethers. Alkoxide ad-
In order to prepare aryl substitutes oxane rings 2 and 3, dition onto intermediate B should lead to five- and/or
the cyclisation of alcohols 6b and 6c was carried out in re- seven-membered ring ethers. The cyclisation towards tetra-
fluxing dichloroethane. The cyclisation was also completely hydrofuran and tetrahydropyran derivatives should be more
regioselective, leading exclusively to the corresponding six- favourable than seven- and eight-membered ring ethers.
membered ring ethers 2 and 3 in isolated yields of 60–86% This experimental regiospecificity can be explained by the
(Table 2, Entries 2–5). The observed regioselectivities can be selective formation of the π-allyl carbocation type interme-
explained by the stabilisation of a benzylic-type cation in- diate A, which is more stable than B as a result of the higher
termediate formed in the presence of the metal triflate. Con- substitution by the presence of the gem-dimethyl groups.
cerning the stereoselectivity of the cyclisation leading to 2
Cyclisation of alcohols 6b, 6c and 6e was regiospecific
and 3, the cis isomers were formed as the major products and afforded exclusively the corresponding oxanes 2, 3 and
with 90–95% selectivities. The cyclisation of regioisomer- 5, respectively. Here as well, the regioselectivity can be ex-
ically pure (E)-6b afforded 2 as a mixture of cis and trans plained by the formation of a carbocation-type intermedi-
isomers in a 95:5 ratio and 60% yield (Table 2, Entry 3). ate after the coordination of Al3+ to the hydroxy oxygen
This cis/trans ratio was very similar to that of 90:10 ob- atom and the specific proton transfer from the OH group.
tained for 6b with Z/E of 15:85 or 28:72 (Table 2, Entries 2 The proton transfer occurs only on the carbon atom at the
and 4), suggesting that the cyclisation could take place β-position of the phenyl group to form a stabilised carbo-
through a common carbocationic intermediate. The dia- cationic intermediate.
stereoisomeric cis/trans ratio of the cyclic ethers was mainly
dependent on stereochemical requirements of the interme- lysed cycloisomerisation of differently 2- or 3-substituted
diates and not on the Z/E ratios of starting alcohols 6. alcohols 6a–e formed the cis isomers of cyclic ethers 1–5 as
From a stereochemical point of view, the Al(OTf)3-cata-
The Al(OTf)3-catalysed cyclisation of 6d (Z/E mixture of the main products. For 3-methyl-substituted alcohols 6a–c,
45:55) afforded regiospecifically oxane 4 in 77% yield, with the cyclisation led to the thermodynamically more stable
a cis/trans ratio of 90:10 (Table 2, Entry 6). The expected cis-1,3-diequatorial stereoisomer.
Scheme 4.
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Aluminium Triflate Catalysed Cyclisation of Unsaturated Alcohols
Scheme 5.
For the 2-methyl-substituted alcohols 6d and 6e, the Table 3. Olfactory properties of cyclic ethers 1–5 of cis/trans mix-
tures as obtained in Table 2.
mechanism of the cyclisation is proposed in Scheme 5. A
first coordination of Al(OTf)3 to the hydroxy group, which
activates the proton transfer to the double bond, may afford
the formation of two carbocation-type intermediates C and
D in equilibrium as a result of the free rotation across the
CH2–CH+ bond. In the more-stable chair-like conforma-
tion, carbocation C is sterically less hindered than D
towards alkoxide addition. According to simple calcula-
tions,[18] carbocation C is slightly more stable than D,
mainly affording the cis-1-axial-4-equatorial isomers 4 [R =
CH=C(CH3)2] and 5 (R = Ph) by kinetic control with
cis/trans ratios of 90:10 and 86:14, respectively.
Cyclic ethers
Olfactory properties
1
2
3
4
5
floral, green, herbal
rose oxide, green
liquorice, weak
anise, spearmint, rose oxide
creamy, vanilla, exotic fruits, citral
Conclusion
In conclusion, we present a novel and modulable selec-
tive synthesis of cyclic ethers of the rose oxide family in
four steps and in high yields. The key step is based on the
intramolecular hydroalkoxylation of unsaturated alcohols
in a Lewis “superacid” catalysed process, which was found
to be regiospecific and stereoselective. The Al(OTf)3-cata-
lysed cycloisomerisation afforded 1,3- and 1,4-disubstituted
six-membered ring ethers with high selectivities in favour of
the cis isomer.
Olfactory Evaluation of Cyclic Ethers 1–5
The olfactory properties for cyclic ethers 1–5 were evalu-
ated to examine the influence of the different methyl sub-
stituents (Table 3).[19] Whereas 1 and 2 presented the ex-
pected characteristics of strong floral and green notes al-
ready as reported for rose oxide[11] and Doremox®,[14,20]
ether 3 was analysed as weak and with a liquorice note.
Ethers 4 and 5, analogues of 1 and 2 by changing the posi-
tion of the methyl group in the tetrahydropyran cycle, pre-
sented interesting notes: 4 was evaluated with anise, spear-
mint and rose oxide notes, whereas 5 presented creamy, va-
nilla, exotic fruits and citral notes.
Experimental Section
General: All reactions were performed under a nitrogen atmosphere
by using standard Schlenk techniques. Solvents were dried accord-
ing to standard procedures prior to use. Chemicals were obtained
from commercial sources and were used without further purifica-
tion. Gas chromatography analyses were performed with a Varian
CP 3380 instrument equipped with a Chrompack fused silica capil-
lary column (WCOT fused silica, 25 mϫ0.5 mm i.d.). H and 13C
1
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L. Coulombel, M. Weïwer, E. Duñach
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NMR spectra were recorded with a Bruker AC-200 (200 MHz)
spectrometer. Chemical shifts are reported in ppm relative to tet-
ramethylsilane. GC–MS were realised with a Thermo Quest
J = 14.5 Hz, 2 H, -CH2Ph) ppm. 13C NMR (50 MHz, CDCl3): δ =
135.3 (3 C), 134.9 (6 C), 133.1, 131.9 (2 C), 130.6 (6 C), 129.2 (2
C), 128.8, 119.2 (3 C), 31.5 ppm. 31P NMR (200 MHz, CDCl3): δ
TRACE GC 2000 chromatograph (column DBTMS, = 24.6 (s) ppm.
15 mϫ0.20 mm i.d.) equipped with a mass selective detector Auto-
mass III multi.
ortho-Methylbenzyltriphenylphosphonium Chloride (8c): 1H NMR
(200 MHz, CDCl3): δ = 7.9–7.6 (m, 15HAr), 7.3–6.9 (m, 4HAr), 5.2
(d, J = 14.0 Hz, 2 H, -CH2-Ar), 1.7 (s, 3 H, CH3) ppm. 13C NMR
(50 MHz, CDCl3): δ = 139.0, 135.6 (3 C), 134.7 (6 C), 131.8, 131.4,
130.8 (6 C), 129.3, 127.2, 126.0, 118.9 (3 C), 29.3, 20.0 ppm. 31P
NMR: δ = 23.3 (s) ppm.
General Procedure for Synthesis of Aldehydes 7a and 7b: To a stirred
solution of butyl 2- or butyl 3-methyl-4-pentenoate (6.80 g,
40 mmol) and RuCl3·xH2O (1.4 mmol, 3.5 mol-%) in CH3CN
(240 mL) and distilled water (60 mL) was added NaIO4 (17.11 g,
80 mmol) in portions over a period of 15 min at room temperature.
The reaction was complete after 2 h, and the reaction mixture was
quenched with saturated aqueous solution of Na2S2O3. The layers
were separated, and the aqueous layer was extracted three times
with Et2O. The combined organic layer was washed with water and
brine, dried with MgSO4, filtered and concentrated under reduced
pressure. The crude product was analysed by 1H NMR spec-
troscopy to determine the portion of α-diols formed. A glycol
cleavage oxidation was then performed to transform the resulting
diols (20%) into the corresponding aldehydes. To a vigorously
stirred solution of silica gel supported NaIO4 reagent (16.0 g) in
CH2Cl2 (45 mL) was added the obtained crude product containing
the vicinal diol (8 mmol) in CH2Cl2 (45 mL). The reaction was
monitored by GC analysis and was complete after 30 min. The
mixture was filtered, and the silica gel was thoroughly washed three
times with CH2Cl2. The filtrate was concentrated to afford the alde-
hyde that was pure enough (Ͼ95%) to be used in the next step
without further purification.
Butyl 3-Methyl-4-oxobutanoate (7a): 1H NMR (200 MHz, CDCl3):
δ = 9.7 (d, J = 0.4 Hz, 1 H, Hald), 4.1 (t, J = 6.7 Hz, 2 H,
-OCH2CH2), 2.9–2.6 (m, 2 H, -CH2CO), 2.5–2.3 (m, 1 H,
-CHCH3), 1.7–1.5 (m, 2 H, -CH2CH2CH2-), 1.5–1.3 (m, 2 H,
-CH2CH2CH3), 1.2 (d, J = 7.3 Hz, 3 H, -CHCH3), 0.9 (t, J =
7.3 Hz, 3 H, -CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
203.2, 172.3, 65.0, 43.0, 35.4, 31.0, 19.5, 14.1, 13.8 ppm. MS (70 eV,
EI): m/z (%) = 144 (9) [M – 8]+·, 116 (2), 99 (100), 88 (70), 73 (86),
71 (44), 57 (69).
General Procedure for the Synthesis of Esters Derivatives 9: To a
stirred suspension of NaH (0.432 g, 18 mmol) in THF (30 mL) was
added phosphonium salt derivatives 8 (15 mmol) in portions over
a period of 15 min at room temperature. Compounds 8a–c were
quantitatively prepared as white powders from a suspension of tri-
phenylphosphane (10.48 g, 40 mmol) and substituted allyl halides
(40 mmol) in toluene (70 mL) after stirring overnight at 110 °C.
The colour turned from white to orange-red, indicating the forma-
tion of the corresponding ylide. After stirring for 1 h, aldehyde 7
(2.58 g, 15 mmol) was added in THF (5 mL) to the orange-red
solution and stirring was continued at room temperature for 2 h.
The reaction mixture was diluted with Et2O and quenched with
HCl (1 ). The layers were separated, and the aqueous layer was
extracted three times with Et2O. The combined organic layer was
washed with water and brine, dried with MgSO4, filtered and con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography (pentane/Et2O, 95:5) to afford esters 9a–e as
a colourless oils. The Z/E ratios were determined by GC analysis
1
and H NMR spectroscopy.
1
Butyl 3,7-Dimethylocta-4,6-dienoate [(E)-9a; Z/E, 28:72]: H NMR
(200 MHz, CDCl3): δ = 6.2 [dd, J = 15.2, 10.7 Hz, 1 H, -CH=CH-
CH=C(CH3)2], 5.8 [d, J = 10.7 Hz, 1 H, -CH=CH-CH=C(CH3)2],
5.4 [dd, J = 15.2, 7.6 Hz, 1 H, -CH=CH-CH=C(CH3)2], 4.1 (t, J =
6.6 Hz, 2 H, -OCH2CH2), 2.7–2.5 (m, 1 H, -CHCH3), 2.3–2.1 (m,
2 H, -CH2CO), 1.8 [s, 6 H, -CH=C(CH3)2], 1.7–1.5 (m, 2 H,
-OCH2CH2), 1.5–1.3 (m, 2 H, -CH2CH2CH3), 1.0 (d, J = 6.6 Hz,
3 H, -CHCH3), 0.9 (t, J = 7.3 Hz, 3 H, -CH2CH3) ppm. 13C NMR
(50 MHz, CDCl3): δ = 173.1, 135.6, 134.4, 126.0, 125.2, 64.5, 42.4,
34.4, 31.1, 26.3, 20.8, 19.6, 18.6, 14.1 ppm. MS (70 eV, EI): m/z (%)
= 224 (62) [M]+·, 167 (38), 151 (16), 135 (7), 125 (20), 122 (73), 109
(100), 107 (95), 93 (71), 91 (62), 81 (64), 79 (63), 69 (49), 67 (73),
55 (59). Data for (Z)-9a: 1H NMR (200 MHz, CDCl3): δ = 6.1–
6.0 [m, 2 H, -CH=CH-CH=C(CH3)2], 5.2–5.0 [m, 1 H, -CH=CH-
CH=C(CH3)2], 4.1 (t, J = 6.7 Hz, 2 H, -OCH2CH2), 3.1–2.9 (m, 1
H, -CHCH3), 2.3–2.1 (m, 2H2, -CH2CO), 1.8 [s, 6 H, -CH=C-
Butyl 2-Methyl-4-oxobutanoate (7b): 1H NMR (200 MHz, CDCl3):
δ = 9.8 (br. s, 1 H, Hald), 4.1 (t, J = 6.6 Hz, 2 H, -OCH2CH2), 3.1–
2.7 (m, 2 H, -CH2CO), 2.6–2.4 (m, 1 H, -CHCH3), 1.7–1.5 (m, 2
H, -CH2CH2CH2-), 1.5–1.3 (m, 2 H, -CH2CH2CH3), 1.2 (d, J =
7.1 Hz, 3 H, -CHCH3), 0.9 (t, J = 7.2 Hz, 3 H, -CH2CH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 200.6, 175.6, 65.1, 47.3, 34.1,
31.0, 19.5, 17.5, 14.1 ppm. MS (70 eV, EI): m/z (%) = 144 (4) [M –
28]+·, 116 (2), 99 (100), 88 (39), 73 (60), 71 (53), 57 (67).
General Procedure for Synthesis of Phosphonium Salt Derivatives 8:
A suspension of triphenylphosphane (10.48 g, 40 mmol) and sub-
stituted allyl or benzyl halides (40 mmol) in toluene (70 mL) was
stirred overnight at 110 °C. After the reaction was complete, the
reaction mixture was cooled in an ice bath and the phosphonium
salt was precipitated. The reaction crude was then filtered and
washed with cold toluene. After drying it overnight under vacuum,
the phosphonium salt was obtained as a white powder.
Prenyltriphenylphosphonium Bromide (8a): 1H NMR (200 MHz,
CDCl3): δ = 7.9–7.6 (m, 15HAr), 5.2–5.0 [m, 1 H, -CH=C(CH3)2],
4.5 (dd, J = 14.6, 7.8 Hz, 2 H, -CH2CH=), 1.7 (d, J = 5.7 Hz, 3 H,
CH3), 1.3 (d, J = 3.7 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz,
CDCl3): δ = 143.8, 135.2 (3 C), 133.9 (6 C), 130.6 (6 C), 118.9 (3
C), 108.3, 26.1, 24.9, 18.6 ppm. 31P NMR (200 MHz, CDCl3): δ =
21.5 (s) ppm.
(CH3)2], 1.7–1.5 (m,
2 H, -OCH2CH2), 1.5–1.3 (m, 2 H,
-CH2CH2CH3), 1.0 (d, J = 6.6 Hz, 3 H, -CHCH3), 0.9 (t, J =
7.3 Hz, 3 H, -CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
173.1, 136.3, 133.3, 124.6, 120.5, 64.5, 42.6, 31.1, 29.7, 26.7, 21.4,
19.6, 18.5, 14.1 ppm. MS (70 eV, EI): m/z (%) = 224 (38) [M]+·, 167
(20), 151 (8), 135 (4), 125 (9), 122 (68), 109 (100), 107 (95), 93 (65),
91 (42), 81 (53), 79 (52), 69 (28), 67 (65), 55 (41).
Butyl 3-Methyl-5-phenyl-4-pentenoate [(E)-9b; Z/E, 15:85]: 1H
NMR (200 MHz, CDCl3): δ = 7.3–7.0 (m, 5HAr), 6.3 (d, J =
16.0 Hz, 1 H, -CH=CHPh), 6.1 (dd, J = 16.0, 7.4 Hz, 1 H,
-CH=CHPh), 4.0 (t, J = 6.4 Hz, 2 H, -OCH2CH2), 2.9–2.7 (m, 1
H, -CHCH3), 2.4–2.2 (m, 2 H, -CH2CO), 1.6–1.4 (m, 2 H,
-CH2CH2CH2), 1.4–1.1 (m, 2 H, -CH2CH2CH3), 1.1 (d, J = 6.7 Hz,
3 H, -CHCH3), 0.8 (t, J = 7.2 Hz, 3 H, -CH2CH3) ppm. 13C NMR
(50 MHz, CDCl3): δ = 172.9, 137.8, 134.6, 129.3, 129.2 (2 C), 127.5,
126.5 (2 C), 64.6, 42.2, 34.5, 31.1, 20.7, 19.5, 14.1 ppm. MS (70 eV,
EI): m/z (%) = 246 (7) [M]+·, 190 (2), 171 (3), 144 (48), 131 (100),
Benzyltriphenylphosphonium Chloride (8b): 1H NMR (200 MHz,
CDCl3): δ = 7.8–7.5 (m, 15HAr), 7.2–6.9 (m, 5 H, -CH2Ph), 5.5 (d,
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Aluminium Triflate Catalysed Cyclisation of Unsaturated Alcohols
129 (97), 115 (24), 103 (8), 91 (59), 77 (15), 65 (8), 57 (8), 51 (9). H, -OCH2CH2), 1.5–1.3 (m, 2 H, -CH2CH2CH3), 1.2 (d, J =
Data for (Z)-9b: 1H NMR (200 MHz, CDCl3): δ = 7.3–7.0 (m,
5HAr), 6.4 (d, J = 11.6 Hz, 1 H, -CH=CHPh), 5.4 (dd, J = 11.6,
6.7 Hz, 3 H, -CHCH3), 0.9 (t, J = 7.2 Hz, 3 H, -CH2CH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 176.5, 137.8, 132.4, 129.2, 128.9
10.4 Hz, 1 H, -CH=CHPh), 4.0 (t, J = 6.4 Hz, 2 H, -OCH2CH2), (2 C), 127.5, 126.5 (2 C), 64.6, 40.2, 37.5, 31.2, 19.6, 17.2, 14.1 ppm.
3.3–3.1 (m, 1 H, -CHCH3), 2.4–2.2 (m, 2 H, -CH2CO), 1.6–1.4 (m, MS (70 eV, EI): m/z (%) = 246 (22) [M]+·, 190 (6), 173 (13), 144
2 H, -CH2CH2CH2), 1.4–1.1 (m, 2 H, -CH2CH2CH3), 1.0 (d, J = (70), 129 (24), 115 (42), 103 (6), 91 (46), 77 (14), 65 (11), 57 (18),
1
6.7 Hz, 3 H, -CHCH3), 0.8 (t, J = 7.2 Hz, 3 H, -CH2CH3) ppm. 51 (10). Data for (Z)-9e: H NMR (200 MHz, CDCl3): δ = 7.4–7.1
13C NMR (50 MHz, CDCl3): δ = 172.9, 136.9, 134.4, 129.0, 129.2 (m, 5HAr), 6.5 (d, J = 11.6 Hz, 1 H, -CH=CHPh), 5.6 (dt, J = 11.6,
(2 C), 127.1, 126.5 (2 C), 66.3, 42.6, 31.0, 30.1, 21.3, 19.5, 15.7 ppm.
MS (70 eV, EI): m/z (%) = 246 (7) [M]+·, 190 (2), 171 (3), 144 (48),
131 (100), 129 (97), 115 (24), 103 (8), 91 (59), 77 (15), 65 (8), 57
(8), 51 (9).
7.2 Hz, 1 H, -CH=CHPh), 4.0 (t, J = 6.6 Hz, 2 H, -OCH2CH2),
2.7–2.5 (m, 2 H, -CHCH3CH2), 2.5–2.3 (m, 1 H, -CHCH3CH2),
1.7–1.5 (m, 2 H, -OCH2CH2), 1.5–1.3 (m, 2 H, -CH2CH2CH3), 1.2
(d, J = 6.7 Hz, 3 H, -CHCH3), 0.9 (t, J = 7.2 Hz, 3 H,
-CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 176.5, 137.78,
131.0, 129.7, 128.6 (2 C), 127.7 (2 C), 126.1, 64.6, 40.4, 32.8, 31.1,
19.6, 17.2, 14.1 ppm. MS (70 eV, EI): m/z (%) = 246 (8) [M]+·, 190
(3), 173 (8), 144 (38), 129 (14), 115 (21), 103 (3), 91 (24), 77 (9), 65
(7), 57 (11), 51 (6).
Butyl 3-Methyl-5-ortho-tolyl-4-pentenoate [(E)-9c; Z/E, 14:86]: 1H
NMR (200 MHz, CDCl3): δ = 7.3–7.0 (m, 4HAr), 6.6 (d, J =
15.7 Hz, 1 H, -CH=CHPh), 6.0 (dd, J = 15.7, 7.6 Hz, 1 H,
-CH=CHPh), 4.1 (t, J = 6.7 Hz, 2 H, -OCH2CH2), 2.9–2.7 (m, 1
H, -CHCH3), 2.4 (dd, J = 7.2, 4.2 Hz, 2 H, -CH2CO), 2.3 [s, 3 H,
CH3(tolyl)], 1.7–1.5 (m, 2 H, -CH2CH2CH2), 1.5–1.2 (m, 2 H, General Procedure for Synthesis of Unsaturated Alcohols 6: To a
-CH2CH2CH3), 1.2 (d, J = 6.8 Hz, 3 H, -CHCH3), 0.9 (t, J =
7.2 Hz, 3 H, -CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
172.9, 137.0, 136.1, 135.5, 130.6, 127.5, 127.4, 126.2, 125.9, 64.7,
42.4, 34.9, 31.1, 20.8, 20.2, 19.6, 14.1 ppm. MS (70 eV, EI): m/z (%)
= 260 (15) [M]+·, 204 (3), 187 (4), 158 (38), 145 (93), 143 (100), 129
(32), 115 (27), 105 (47), 91 (22), 77 (12), 65 (8), 57 (10). Data for
(Z)-9c: 1H NMR (200 MHz, CDCl3): δ = 7.3–7.0 (m, 4HAr), 6.4
stirred suspension of LiAlH4 (0.378 g, 10 mmol) in THF (20 mL)
was added ester 9 (10 mmol) in THF (5 mL) at room temperature.
After being stirred for 1 h, the reaction mixture was cooled with
an ice bath and carefully quenched with water. The mixture was
then diluted with Et2O and with HCl (0.1 ). The layers were sepa-
rated, and the aqueous layer was extracted three times with Et2O.
The combined organic layer was washed with water and brine and
(d, J = 11.4 Hz, 1 H, -CH=CHPh), 5.5 (dd, J = 11.4, 10.3 Hz, 1 dried with MgSO4. After filtration and removal of the solvent un-
H, -CH=CHPh), 4.1 (t, J = 6.7 Hz, 2 H, -OCH2CH2), 2.9–2.7 (m, der reduced pressure, alcohol 6 was obtained as a colourless oil.
1 H, -CHCH3), 2.4 (dd, J = 7.2, 4.2 Hz, 2 H, -CH2CO), 2.3 [s, 3 The Z/E ratios were determined by GC analysis and were similar
1
H, CH3(tolyl)], 1.7–1.5 (m, 2H2, -CH2CH2CH2), 1.5–1.2 (m, 2 H, to the H NMR integration of characteristic ethylenic protons.
-CH2CH2CH3), 1.1 (d, J = 6.8 Hz, 3 H, -CHCH3), 0.9 (t, J =
3,7-Dimethylocta-4,6-dienol [(E)-6a; Z/E, 28:72]:[21] 1H NMR
7.2 Hz, 3 H, -CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
(200 MHz, CDCl3): δ = 6.5 [dd, J = 15.0, 10.9 Hz, 1 H, -CH=CH-
172.7, 136.7, 136.1, 135.5, 130.6, 130.1, 130.0, 129.1, 128.2, 64.6,
CH=C(CH3)2], 5.8 [d, J = 10.9 Hz, 1 H, -CH=CH-CH=C(CH3)2],
42.5, 34.9, 31.0, 20.8, 21.4, 19.5, 14.1 ppm. MS (70 eV, EI): m/z (%)
5.4 [dd, J = 15.0, 8.2 Hz, 1 H, -CH=CH-CH=C(CH3)2], 3.6 (t, J =
= 260 (12) [M]+·, 204 (2), 187 (4), 158 (38), 145 (90), 143 (100), 129
(32), 115 (28), 105 (47), 91 (24), 77 (15), 65 (8), 57 (13).
6.6 Hz, 2 H, -CH2OH), 2.4 (m, 1 H, -CHCH3), 1.7 [s, 6 H,
-CH=C(CH3)2], 1.6–1.3 (m, 2 H, -CH2CH2OH), 1.0 (d, J = 6.7 Hz,
1
Butyl 2,7-Dimethylocta-4,6-dienoate [(E)-9d; Z/E, 45:55]: H NMR
3 H, -CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 137.4, 133.9,
(200 MHz, CDCl3): δ = 6.2 [dd, J = 14.9, 10.9 Hz, 1 H, -CH=CH- 125.9, 125.3, 61.7, 40.3, 34.5, 26.3, 21.5, 18.6 ppm. MS (70 eV, EI):
CH=C(CH3)2], 5.7 [d, J = 10.9 Hz, 1 H, -CH=CH-CH=C(CH3)2],
5.4 [dt, J = 14.9, 7.2 Hz, 1 H, -CH=CH-CH=C(CH3)2], 4.0 (t, J =
6.6 Hz, 2 H, -OCH2CH2), 2.6–2.1 [m, 3 H, -CH(CH3)CH2-], 1.7 [s,
m/z (%) = 154 (24) [M]+·, 139 (13), 121 (48), 109 (80), 95 (51), 93
(59), 91 (44), 81 (73), 79 (58), 77 (40), 69 (57), 67 (100), 55 (62).
Data for (Z)-6a: 1H NMR (200 MHz, CDCl3): δ = 6.2–6.0 [m, 2
6 H, -CH=C(CH3)2], 1.6–1.4 (m, 2 H, -OCH2CH2), 1.4–1.2 (m, 2 H, -CH=CH-CH=C(CH3)2], 5.1 [dd, J = 9.7, 9.7 Hz, 1 H,
H, -CH2CH2CH3), 1.1 (d, J = 6.8 Hz, 3 H, -CHCH3), 0.9 (t, J = -CH=CH-CH=C(CH3)2], 3.6 (t, J = 6.6 Hz, 2 H, -CH2OH), 2.8–
7.3 Hz, 3 H, -CH2CH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
176.6, 134.1, 129.3, 128.3, 125.2, 64.5, 40.3, 37.4, 31.1, 26.3, 19.6,
18.6, 17.0, 14.1 ppm. MS (70 eV, EI): m/z (%) = 224 (32) [M]+·, 168
2.6 (m, 1 H, -CHCH3), 1.7 [s, 6 H, -CH=C(CH3)2], 1.6–1.3 (m, 2
H, -CH2CH2OH), 1.0 (d, J = 6.7 Hz, 3 H, -CHCH3) ppm. 13C
NMR (50 MHz, CDCl3): δ = 136.3, 135.3, 124.4, 120.5, 61.8, 40.6,
(2), 151 (7), 122 (39), 109 (100), 107 (22), 95 (100), 81 (16), 79 (20), 29.3, 26.7, 21.8, 18.5 ppm. MS (70 eV, EI): m/z (%) = 154 (24)
69 (6), 67 (30), 55 (28). Data for (Z)-9d: 1H NMR (200 MHz, [M]+·, 139 (13), 121 (48), 109 (80), 95 (51), 93 (59), 91 (44), 81 (73),
CDCl3): δ = 6.3–6.1 [m, 1 H, -CH=CH-CH=C(CH3)2], 6.0 [d, J =
11.4 Hz, 1 H, -CH=CH-CH=C(CH3)2], 5.2 [dt, J = 10.6, 7.2 Hz, 1
H, -CH=CH-CH=C(CH3)2], 4.0 (t, J = 6.6 Hz, 2 H, -OCH2CH2),
2.6–2.1 [m, 3 H, -CH(CH3)CH2-], 1.7 [s, 6 H, -CH=C(CH3)2], 1.6–
1.4 (m, 2 H, -OCH2CH2), 1.4–1.2 (m, 2 H, -CH2CH2CH3), 1.1 (d,
J = 6.7 Hz, 3 H, -CHCH3), 0.9 (t, J = 7.3 Hz, 3 H, -CH2CH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 176.7, 136.3, 127.0, 125.8, 120.5,
64.6, 40.2, 31.9, 31.1, 26.3, 19.6, 18.5, 17.0, 14.1 ppm. MS (70 eV,
EI): m/z (%) = 224 (32) [M]+·, 168 (2), 151 (7), 122 (39), 109 (100),
107 (22), 95 (100), 81 (16), 79 (20), 69 (6), 67 (30), 55 (28).
79 (58), 77 (40), 69 (54), 67 (100), 55 (60).
3-Methyl-5-phenyl-4-pentenol [(E)-6b; Z/E, 15:85]:[22] 1H NMR
(200 MHz, CDCl3): δ = 7.3–7.0 (m, 5HAr), 6.3 (d, J = 15.9 Hz, 1
H, -CH=CHPh), 6.0 (dd, J = 15.9, 8.1 Hz, 1 H, -CH=CHPh), 3.6
(t, J = 6.6 Hz, 2 H, -CH2OH), 2.5–2.3 (m, 1 H, -CHCH3), 1.7 (br.
s, 1 H, -CH2OH), 1.6–1.4 (m, 2 H, -CH2CH2OH), 1.0 (d, J =
6.7 Hz, 3 H, -CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
138.0, 136.4, 129.0, 128.9 (2 C), 127.4, 126.4 (2 C), 61.6, 40.1, 34.6,
21.3 ppm. MS (70 eV, EI): m/z (%) = 176 (15) [M]+·, 157 (5), 143
(68), 131 (86), 128 (50), 116 (28), 115 (45), 103 (15), 91 (100), 77
(26), 71 (13), 65 (13), 63 (8), 51 (14). Data for (Z)-6b: 1H NMR
Butyl 2-Methyl-5-phenyl-4-pentenoate [(E)-9e; Z/E, 30:70]: 1H
NMR (200 MHz, CDCl3): δ = 7.4–7.1 (m, 5HAr), 6.4 (d, J = (200 MHz, CDCl3): δ = 7.3–7.0 (m, 5HAr), 6.35 (d, J = 11.6 Hz, 1
15.8 Hz, 1 H, -CH=CHPh), 6.1 (dt, J = 15.8, 7.1 Hz, 1 H, H, -CH=CHPh), 5.4 (dd, J = 11.6, 10.5 Hz, 1 H, -CH=CHPh), 3.6
-CH=CHPh), 4.0 (t, J = 6.6 Hz, 2 H, -OCH2CH2), 2.7–2.5 (m, 2 (t, J = 6.6 Hz, 2 H, -CH2OH), 3.0–2.7 (m, 1 H, -CHCH3), 1.7 (br.
H, -CHCH3CH2), 2.5–2.3 (m, 1 H, -CHCH3CH2), 1.7–1.5 (m, 2
s, 1 H, -CH2OH), 1.6–1.4 (m, 2 H, -CH2CH2OH), 0.95 (d, J =
Eur. J. Org. Chem. 2009, 5788–5795
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5793

L. Coulombel, M. Weïwer, E. Duñach
6.7 Hz, 3 H, -CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = and Al(OTf)3 (71 mg, 0.15 mmol) in distilled CH2Cl2 or
FULL PAPER
138.9, 134.5, 129.1, 128.9 (2 C), 127.1, 126.4 (2 C), 61.6, 40.7, 29.5,
21.6 ppm. MS (70 eV, EI): m/z (%) = 176 (15) [M]+·, 157 (5), 143
(68), 131 (86), 128 (50), 116 (28), 115 (45), 103 (15), 91 (100), 77
(26), 71 (13), 65 (13), 63 (8), 51 (14).
ClCH2CH2Cl (15 mL) was stirred at reflux for 1 to 3 h. The pro-
gress of the reaction was monitored by GC analysis. After comple-
tion of the reaction, the mixture was cooled and quenched with
HCl (1 ). The layers were separated, and the aqueous layer was
extracted three times with Et2O. The combined organic layer was
washed with water and brine and dried with MgSO4. After fil-
tration and removal of the solvent under reduced pressure, the resi-
due was purified by column chromatography (pentane/Et2O, 95:5)
to afford cyclic ethers 1–5.
3-Methyl-5-ortho-tolyl-4-pentenol [(E)-6c; Z/E, 14:86]: 1H NMR
(200 MHz, CDCl3): δ = 7.2–7.0 (m, 4HAr), 6.6 (d, J = 15.8 Hz, 1
H, -CH=CHPh), 6.0 (dd, J = 15.8, 8.3 Hz, 1 H, -CH=CHPh), 3.7
(t, J = 6.6 Hz, 2 H, -CH2OH), 2.7–2.4 (m, 1 H, -CHCH3), 2.3 [s,
3 H, CH3(tolyl)], 1.7–1.5 (m, 2 H, -CH2CH2OH), 1.5 (br. s, 1 H,
-CH2OH), 1.1 (d, J = 6.8 Hz, 3 H, -CHCH3) ppm. 13C NMR
(50 MHz, CDCl3): δ = 137.9, 137.1, 135.4, 130.6, 127.4, 126.9,
126.4, 125.9, 61.7, 40.2, 35.0, 21.4, 20.3 ppm. MS (70 eV, EI): m/z
(%) = 190 (25) [M]+·, 172 (10), 157 (68), 145 (90), 129 (48), 115
(48), 105 (100), 91 (62), 77 (32), 65 (18), 51 (13). Data for (Z)-6c:
1H NMR (200 MHz, CDCl3): δ = 7.4–7.3 (m, 4HAr), 6.4 (d, J =
11.4 Hz, 1 H, -CH=CHPh), 5.5 (dd, J = 11.4, 10.5 Hz, 1 H,
-CH=CHPh), 3.7 (t, J = 6.6 Hz, 2 H, -CH2OH), 2.7–2.4 (m, 1 H,
-CHCH3), 2.2 [s, 3 H, CH3(tolyl)], 1.7–1.5 (m, 2 H, -CH2CH2OH),
1.5 (br. s, 1 H, -CH2OH), 1.0 (d, J = 6.7 Hz, 3 H, -CHCH3) ppm.
13C NMR (50 MHz, CDCl3): δ = 138.5, 135.4, 130.6, 130.2, 129.2,
128.1, 127.4, 126.4, 63.2, 40.5, 35.3, 21.7, 19.3 ppm. MS (70 eV,
EI): m/z (%) = 190 (16) [M]+·, 172 (8), 157 (68), 145 (84), 129 (48),
115 (53), 105 (100), 91 (64), 77 (35), 65 (18), 51 (13).
1
Rose Oxide (cis-1; cis/trans, 94:6): H NMR (200 MHz, CDCl3): δ
= 5.2 [dsept., J = 8.1, 1.3 Hz, 1 H, -CH=C(CH3)2], 4.0–3.9 (m, 2
H, -CH-O-CHH-), 3.5 (ddd, J = 12.4, 12.1, 2.3 Hz, 1 H, -CH-O-
CHH-), 1.73 [d, J = 1.3 Hz, 3 H, -CH=C(CH3)2], 1.68 [d, J =
1.3 Hz, 3 H, -CH=C(CH3)2], 1.7–1.5 [m, 3 H, -CH(CH3)-CH2-CH-
O], 1.3–1.0 (m, 2 H, -CH2-CH2-O), 0.9 (d, J = 6.3 Hz, 3 H,
-CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 135.5, 126.8,
75.0, 68.3, 41.2, 34.8, 30.7, 26.1, 22.7, 18.8 ppm. MS (70 eV, EI):
m/z (%) = 154 (63) [M]+·, 139 (93), 121 (16), 112 (34), 109 (26), 97
(53), 95 (32), 93 (44), 91 (34), 83 (89), 69 (100), 55 (89). Data for
trans-1: 1H NMR (200 MHz, CDCl3):
δ = 5.3 [m, 1 H,
-CH=C(CH3)2], 4.4–4.3 (m, 1 H, -CH-O-CH2-), 3.8–3.7 (m, 2 H,
-CH-O-CH2-), 1.73 [d, J = 1.3 Hz, 3 H, -CH=C(CH3)2], 1.68 [d, J
= 1.3 Hz, 3 H, -CH=C(CH3)2], 1.7–1.5 [m, 3 H, -CH(CH3)-CH2-
CH-O], 1.3–1.0 (m, 2 H, -CH2-CH2-O), 0.9 (d, J = 6.3 Hz, 3 H,
-CHCH3) ppm. MS (70 eV, EI): m/z (%) = 154 (12) [M]+·, 139 (83),
121 (4), 112 (4), 109 (5), 97 (6), 95 (4), 93 (7), 91 (4), 83 (55), 69
(100), 55 (50).
2,7-Dimethylocta-4,6-dienol [(E)-6d; Z/E, 45:55]:[23] 1H NMR
(200 MHz, CDCl3): δ = 6.2 [dd, J = 14.9, 10.9 Hz, 1 H, -CH=CH-
CH=C(CH3)2], 5.7 [d, J = 10.9 Hz, 1 H, -CH=CH-CH=C(CH3)2],
5.5 [dt, J = 14.9, 7.2 Hz, 1 H, -CH=CH-CH=C(CH3)2], 3.6–3.3 (m,
2 H, -CH2OH), 2.3–1.7 [m, 3 H, -CH2CH(CH3)OH], 1.7 [s, 6 H,
-CH=C(CH3)2], 1.4 [br. s, 1 H, -CH(CH3)OH], 0.9 (d, J = 6.7 Hz,
3 H, -CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 133.7, 129.8,
128.8, 125.3, 68.4, 37.2, 36.6, 26.3, 16.9 (2 C) ppm. MS (70 eV, EI):
m/z (%) = 154 (27) [M]+·, 139 (2), 121 (12), 107 (8), 95 (100), 93
(32), 81 (34), 79 (28), 77 (19), 69 (15), 67 (62), 55 (42). Data for (Z)-
Doremox® (cis-2; cis/trans, 95:5): 1H NMR (200 MHz, CDCl3): δ
= 7.3–7.1 (m, 5HAr), 4.2 (dd, J = 11.5, 1.9 Hz, 1 H, -CH-O), 4.1
(ddd, J = 11.5, 4.6, 1.5 Hz, 1 H, -CHH-O), 3.5 (ddd, J = 12.3, 12.2,
2.3 Hz, 1 H, -CHH-O), 1.8–1.5 [m, 3 H, -CH(CH3)-CH2-CH-O],
1.4–1.1 (m, 2 H, -CH2-CH2-O), 0.9 (d, J = 6.7 Hz, 3 H,
-CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 143.6, 128.7 (2
C), 127.7, 126.3 (2 C), 80.3, 69.0, 43.1, 34.9, 31.2, 22.7 ppm. MS
(70 eV, EI): m/z (%) = 176 (48) [M]+·, 175 (45), 143 (2), 128 (4),
115 (6), 105 (100), 99 (4), 91 (32), 77 (48), 70 (17), 69 (26), 65 (6),
55 (42). Data for trans-2: 1H NMR (200 MHz, CDCl3): δ = 7.3–
7.1 (m, 5HAr), 4.6 (dd, J = 9.7, 3.2 Hz, 1 H, -CH-O), 3.8–3.7 (m,
2 H, -CH2-O), 1.8–1.5 [m, 3 H, -CH(CH3)-CH2-CH-O], 1.4–1.1 (m,
2 H, -CH2-CH2-O), 1.1 (d, J = 7.0 Hz, 3 H, -CHCH3) ppm. MS
(70 eV, EI): m/z (%) = 176 (48) [M]+·, 175 (45), 143 (2), 128 (4),
115 (6), 105 (100), 99 (4), 91 (32), 77 (48), 70 (17), 69 (26), 65 (6),
55 (42).
1
6d: H NMR (200 MHz, CDCl3): δ = 6.3–6.1 [m, 1 H, -CH=CH-
CH=C(CH3)2], 6.0 [d, J = 11.5 Hz, 1 H, -CH=CH-CH=C(CH3)2],
5.3 [m, 1 H, -CH=CH-CH=C(CH3)2], 3.6–3.3 (m, 2 H, -CH2OH),
2.3–1.7 [m, 3 H, -CH2CH(CH3)OH], 1.7 [s, 6 H, -CH=C(CH3)2],
1.4 [br. s, 1 H, -CH(CH3)OH], 0.9 (d, J = 6.7 Hz, 3 H,
-CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 133.0, 127.5,
126.4, 120.6, 68.4, 36.8, 31.6, 26.7, 17.0 (2 C) ppm. MS (70 eV, EI):
m/z (%) = 154 (25) [M]+·, 139 (2), 121 (14), 107 (9), 95 (100), 93
(35), 81 (41), 79 (32), 77 (22), 69 (19), 67 (72), 55 (48).
2-Methyl-5-phenyl-4-pentenol [(E)-6e; Z/E, 30:70]:[24] 1H NMR
(200 MHz, CDCl3): δ = 7.4–7.1 (m, 5HAr), 6.4 (d, J = 15.8 Hz, 1
H, -CH=CHPh), 6.1 (dt, J = 15.8, 7.1 Hz, 1 H, -CH=CHPh), 3.6–
3.4 (m, 2 H, -CH2OH), 2.5–2.2 (m, 1 H, -CHHCH=), 2.2–2.0 (m,
1 H, -CHHCH=), 1.9–1.7 (m, 1 H, -CHCH3), 1.6 [br. s, 1 H,
-CH(CH3)OH], 1.0 (d, J = 6.7 Hz, 3 H, -CHCH3) ppm. 13C NMR
(50 MHz, CDCl3): δ = 137.8, 131.6, 128.9, 128.6 (2 C), 127.1, 126.1
(2 C), 68.0, 37.0, 36.2, 16.2 ppm. MS (70 eV, EI): m/z (%) = 176
(39) [M]+·, 143 (33), 129 (79), 117 (100), 91 (99.7), 77 (54), 65 (56),
55 (10). Data for (Z)-6e: 1H NMR (200 MHz, CDCl3): δ = 7.4–7.1
(m, 5HAr), 6.5 (d, J = 11.6 Hz, 1 H, -CH=CHPh), 5.6 (dt, J = 11.6,
7.2 Hz, 1 H, -CH=CHPh), 3.6–3.4 (m, 2 H, -CH2OH), 2.5–2.2 (m,
1 H, -CHHCH=), 2.2–2.0 (m, 1 H, -CHHCH=), 1.9–1.7 (m, 1 H,
-CHCH3), 1.6 [br. s, 1 H, -CH(CH3)OH], 0.9 (d, J = 6.6 Hz, 3 H,
-CHCH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 137.7, 131.0,
130.2, 128.3 (2 C), 126.7, 126.1 (2 C), 68.0, 36.7, 32.2, 16.2 ppm.
MS (70 eV, EI): m/z (%) = 176 (25) [M]+·, 143 (31), 129 (53), 115
(99.9), 104 (44), 91 (100), 77 (61), 65 (59), 55 (12).
4-Methyl-2-ortho-tolyltetrahydropyran (cis-3; cis/trans, 94:6): 1H
NMR (200 MHz, CDCl3): δ = 7.4–7.0 (m, 4HAr), 4.4 (dd, J = 11.3,
1.5 Hz, 1 H, -CH-O), 4.1 (ddd, J = 11.9, 4.6, 1.2 Hz, 1 H, -CHH-
O), 3.6 (ddd, J = 11.9, 11.8, 2.1 Hz, 1 H, -CHH-O), 2.3 [s, 3 H,
CH3(tolyl)], 1.8–1.4 [m, 3 H, -CH(CH3)-CH2-CH-O], 1.4–1.1 (m, 2
H, -CH2-CH2-O), 0.9 (d, J = 6.2 Hz, 3 H, -CHCH3) ppm. 13C
NMR (50 MHz, CDCl3): δ = 141.6, 134.8, 130.6, 127.5, 126.6,
125.8, 77.1, 69.1, 41.7, 35.0, 31.3, 22.7, 19.4 ppm. MS (70 eV, EI):
m/z (%) = 190 (36) [M]+·, 175 (26), 172 (14), 157 (25), 145 (14), 129
(6), 119 (100), 105 (80), 91 (94), 77 (22), 69 (20), 65 (19), 51 (38).
C13H18O (190.28): calcd. C 82.06, H 9.53; found C 82.35, H 9.58.
Data for trans-3: MS (70 eV, EI): m/z (%) = 190 (36) [M]+·, 175
(26), 172 (14), 157 (25), 145 (14), 129 (6), 119 (100), 105 (80), 91
(94), 77 (22), 69 (20), 65 (19), 51 (38).
2-Isobutenyl-5-methyltetrahydropyran (cis-4; cis/trans, 90:10): 1H
NMR (200 MHz, CDCl3): δ = 5.1 [dsept., J = 8.1, 1.3 Hz, 1 H,
General Procedure for the Al(OTf)3-Catalysed Cycloisomerisation of -CH=C(CH3)2], 3.9–3.7 (m, 2 H, -CH-O-CHH-), 3.0 (dd, J = 11.1,
Unsaturated Alcohols 6: A mixture of unsaturated alcohol (3 mmol) 11.0 Hz, 1 H, -CH-O-CHH-), 1.8–1.7 (m, 1 H, -CHCH3), 1.63 [d,
5794
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Eur. J. Org. Chem. 2009, 5788–5795

Aluminium Triflate Catalysed Cyclisation of Unsaturated Alcohols
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J = 1.3 Hz, 3 H, -CH=C(CH3)2], 1.60 [d, J = 1.3 Hz, 3 H,
-CH=C(CH3)2], 1.5–1.2 (m, 3 H, -CH2-CHHCH-O), 1.2–1.0 (m, 1
H, -CH2CHHCH-O), 0.7 (d, J = 6.6 Hz, 3 H, -CHCH3) ppm. 13C
NMR (50 MHz, CDCl3): δ = 135.7, 126.6, 75.0, 74.9, 32.8, 32.5,
31.0, 26.1, 18.8, 17.7 ppm. MS (70 eV, EI): m/z (%) = 154 (16)
[M]+·, 139 (63), 112 (6), 87 (47), 85 (47), 69 (100), 55 (45). Data for
trans-4: 1H NMR (200 MHz, CDCl3): δ = 5.2 [dsept., J = 8.0,
1.4 Hz, 1 H, -CH=C(CH3)2], 4.0–3.9 (m, 1 H, -CH-O-CH2-), 3.6–
3.5 (m, 2 H, -CH-O-CH2-), 1.8–1.7 (m, 1 H, -CHCH3), 1.63 [d, J
= 1.3 Hz, 3 H, -CH=C(CH3)2], 1.60 [d, J = 1.3 Hz, 3 H,
-CH=C(CH3)2], 1.5–1.2 (m, 3 H, -CH2-CHHCH-O), 1.2–1.0 (m, 1
H, -CH2CHHCH-O), 1.0 (d, J = 7.2 Hz, 3 H, -CHCH3) ppm. MS
(70 eV, EI): m/z (%) = 154 (5) [M]+·, 139 (53), 112 (3), 85 (42), 69
(100), 55 (63).
5-Methyl-2-phenyltetrahydropyran (cis-5; cis/trans, 86:14): 1H NMR
(200 MHz, CDCl3): δ = 7.4–7.1 (m, 5HAr), 4.2 (dd, J = 11.0,
2.2 Hz, 1 H, -CH-O-CH2-), 4.0 (ddd, J = 11.1, 4.3, 2.2 Hz, 1 H,
-CH-O-CHH-), 3.2 (dd, J = 11.1, 11.0 Hz, 1 H, -CH-O-CHH-),
2.0–1.3 [m, 5 H, -CH2CH2CH(CH3)-], 0.9 [d, J = 6.6 Hz, 3 H,
-CH(CH3)] ppm. 13C NMR (50 MHz, CDCl3): δ = 143.5, 128.7 (2
C), 127.7, 126.3 (2 C), 80.2, 75.6, 34.4, 32.3, 31.1, 17.7 ppm. MS
(70 eV, EI): m/z (%) = 176 (94) [M]+·, 129 (3), 117 (9), 105 (100),
91 (50), 77 (88), 55 (76). Data for trans-5: 1H NMR (200 MHz,
CDCl3): δ = 7.4–7.1 (m, 5HAr), 4.4–4.3 (m, 1 H, -CH-O-CH2-), 3.8–
3.7 (m, 2 H, -CH-O-CH2-), 2.0–1.5 [m, 5 H, -CH2CH2CH(CH3)-],
1.1 [d, J = 6.9 Hz, 3 H, -CH(CH3)] ppm. 13C NMR (50 MHz,
CDCl3): δ = 143.5, 128.7 (2 C), 127.7, 126.3 (2 C), 80.2, 73.5, 29.9,
29.1, 28.5, 17.1 ppm. MS (70 eV, EI): m/z (%) = 176 (94) [M]+·, 129
(3), 117 (9), 105 (100), 91 (50), 77 (88), 55 (76).
Acknowledgments
The authors would like to thank “V. Mane & Fils S. A.” (Bar sur
Loup, France) and “Rhodia Organique” (Lyon, France) for olfac-
tory evaluations and the French Ministry of Education and Re-
search for scholarships to L.C. and M.W.
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Received: July 24, 2009
Published Online: October 8, 2009
Eur. J. Org. Chem. 2009, 5788–5795
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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