Lithium-potassium superbases as key reagents for the base-catalysed isomerisation of some terpenoids

Article abstract of DOI:10.1039/b106906c

Some representative monoterpenes have been isomerised under the influence of Schlosser's lithium-potassium mixed superbases, promoting β-elimination reactions. The results are compared with those obtained with butyllithium and LDA. Different selectivities and different reaction yields are achieved as a function of the base employed. These results confirm the particular reactivity of bimetallic reagents. In this paper it is proposed that the observed selectivities might depend on the conformational features of the substrate, on the strength of the organometallic reagent, as well as on steric requirements of the elimination reaction.

Full text of DOI:10.1039/b106906c

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Lithium–potassium superbases as key reagents for the
base-catalysed isomerisation of some terpenoids
Annamaria Deagostino, Paolo Balma Tivola, Cristina Prandi† and Paolo Venturello*
1
Dipartimento di Chimica Generale ed Organica Applicata, Corso Massimo D’Azeglio,
48-I 10125 Torino, Italy
Received (in Cambridge, UK) 1st August 2001, Accepted 17th September 2001
First published as an Advance Article on the web 17th October 2001
Some representative monoterpenes have been isomerised under the influence of Schlosser’s lithium–potassium mixed
superbases, promoting β-elimination reactions. The results are compared with those obtained with butyllithium and
LDA. Different selectivities and different reaction yields are achieved as a function of the base employed. These
results confirm the particular reactivity of bimetallic reagents. In this paper it is proposed that the observed
selectivities might depend on the conformational features of the substrate, on the strength of the organometallic
reagent, as well as on steric requirements of the elimination reaction.
produced carbenoid undergoes various reactions such as isom-
Introduction
erisation to carbonyl compounds, backbone rearrangement,
Monoterpenes can be considered relatively inexpensive building
and C–H insertion reaction. In particular, the insertion reaction
blocks, simple and efficacious structural elaboration of which
should be possible by base-induced isomerisation. Oxiranes are
may involve the carbon–lithium bond of a lithium reagent
molecule (path c), affording alkene 5.
The first base-promoted isomerisation of an oxirane was
versatile compounds that can be easily isomerised both under
acidic1 and basic2 conditions to give useful derivatives such as
reported by Heilbron, Jones, Haynes and Sondheimer when
aldehydes, ketones and allylic alcohols. From the literature data
they treated 2-benzyloxirane with sodium amide in liquid
it can be seen that aliphatic oxiranes react in strong basic milieu
ammonia and isolated cinnamyl alcohol (in 80% yield).3 The
according to several pathways, depending on their structure and
metalation and the ring opening of oxiranes promoted by alkyl-
the reaction conditions (Scheme 1).
lithium reagents4 and by mixed bases5 have been reported
and used in various syntheses. Crandall and co-workers have
extensively studied various base-promoted isomerisations of
oxiranes,2 and in particular have described from the synthetic
point of view, among other reactions, the isomerisation of
α-pinene oxide to trans-pinocarveol.6 The isomerisation
described by these authors was carried out in the presence of
lithium diethylamide in anhydrous diethyl ether at reflux tem-
perature. We were interested in investigating the feasibility of
base-induced isomerisation of terpenic structures containing
an oxirane ring, resorting to the use of Schlosser’s lithium–
potassium mixed bases.7 Moreover, simple and efficacious
structural elaboration should be also possible in terpenes
containing five- and six-membered heterocyclic rings, resorting
to the particular reactivity of lithium–potassium mixed super-
bases that are more effective than a metal amide alone. Previous
examples of ring opening of functionalised tetrahydrofuran
structures have been reported.8
Results and discussion
The isomerisations have been studied and the obtained
1
structures have been assigned by 200 and 400 MHz H NMR
spectra either on the crude mixture or on purified samples. We
have examined the influence of different basic reagents on
Scheme 1 Base-promoted reactions of epoxides.
the isomerisation reaction of α-pinene oxide, β-pinene oxide,
3-carene oxide, 1,4-cineole and 1,8-cineole (Chart 1), and the
obtained results are presented below according to the starting
First of all the oxirane 1 undergoes isomerisation to the
allylic alcohol 2 (path a). Moreover, metalation may occur at a
position adjacent to the heterocyclic oxygen atom (path b). By
material. In particular, we started our study by considering
this route an oxiran-2-yl anion intermediate 3 results, which
the isomerisation of α-pinene oxide and β-pinene oxide in
rearranges to α-oxido carbenoid 4 by α-elimination. The
the presence of Schlosser bases, since the behaviour of these
terpenes with LDA (also termed LIDA in this paper: see below)
has been deeply investigated in previous works of other authors
† Permanent address: Dipartimento di Scienze e Tecnologie Avanzate
dell’Università, Corso Borsalino, 54, I 15100 Alessandria, Italy.
and the results clearly reported in the literature.3
2856
J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b106906c

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Table 1 Effect of the base on the isomerisation of α-pinene oxidea (see Scheme 2)
Entry
Base (equiv.)
6 : 7 Ratiob
Reaction time (reaction temp. T /ЊC)
Yield (%)c
1
2
3
4
5
6
7
BuLi (2.5)
LDA (2.5)
LIC–KOR (1.0)
LIC–KOR (2.5)
LIDA–KOR (2.0)
LIDA–KOR (2.5)
LITMP–KOR (2.5)d
50 : 50
100 : 0
66 : 33
66 : 33
90 : 10
93 : 7
24 h (25)
24 h (25)
30 min (Ϫ95)
30 min (Ϫ95)
30 min (Ϫ95)
30 min (Ϫ95)
30 min (Ϫ95)
80
90
25
90
90
90
90
95 : 5
a Substrate: 2.0 mmol; solvent: THF. b On the basis of separated products by column chromatography. c Isolated and purified products. d 2,2,6,6-
Tetramethylpyperidine was used.
Fig. 1 α-Pinene oxide.
Fig. 2 β-Pinene oxide.
steric encumbrance (actually, alcohol 6 has been selectively
produced, or predominates in most cases reported in Table 1),
while the Hb site suffers due to its ‘wrong’ geometry with respect
to the correct syn-periplanar arrangement. Despite this,
product 7 was obtained, even if as the minor isomer (a 50 : 50
Chart 1
mixture was obtained only when using BuLi: see Table 1). From
a mechanistic point of view it cannot be excluded that
α-metalation and α-elimination of the oxirane ring could take
place, and that the subsequent isomerisation of the resulting
carbenoid species might contribute to the formation of
compound 7. This hypothesis has been previously formulated
in the case of the base-promoted isomerisation of cis-1,2-
epoxycyclodecane.3
ꢀ-Pinene oxide
The influence of the base has been examined by considering
the isomerisation shown in Scheme 2, and the results are
ꢁ-Pinene oxide
Scheme 2 Base-promoted isomerisation of α-pinene oxide.
The influence of the base has been examined by considering the
isomerisation shown in Scheme 3, and the results are reported
reported in Table 1. As can be seen from the data in Table 1
lithium–potassium mixed bases LIDA–KOR (LIDA = lithium
diisopropylamide, KOR
= potassium tert-butoxide) and
LITMP–KOR (LITMP = lithium 2,2,6,6-tetramethylpiper-
idide, KOR = potassium tert-butoxide) react with a selectivity
comparable to that shown by LDA and reported by Crandall
and Crawley.6 In addition, the mixed bases are greatly more
reactive than the amide alone and high reaction yields are
indeed achieved in a very much shorter reaction time working at
Ϫ95 ЊC (compare entry 2 with entries 5, 6 and 7 in Table 1).
Butyllithium alone and LIC–KOR (LIC = butyllithium, KOR =
potassium tert-butoxide) that afford a mixture of exocyclic (6)
and endocyclic (7) alkenes appear to be less selective. Therefore,
a clear control of the deprotonation site of α-pinene oxide takes
place upon a simple change of the base. The structures of alkyl-
lithium reagents and bimetallic superbase in solution are of
course quite different, and this parameter is probably highly
relevant in understanding this problem. However, these results
could be tentatively explained by considering the conformation
of α-pinene oxide proposed in Fig. 1.
It has been recognised that β-elimination in oxiranes prefers a
syn-periplanar arrangement between the deprotonation site and
the leaving oxirane oxygen.9 α-Pinene oxide can be metalated
at two sites of comparable acidity (Ha and Hb in Fig. 1), thus
undergoing β-elimination. On the other hand, the two sites
differ from a stereochemical point of view. The Ha site is
expected to be the preferred deprotonation target, being free of
Scheme 3 Base-promoted reaction of β-pinene oxide.
in Table 2. In the case of β-pinene oxide three compounds were
obtained and the ratio among the products strongly depends on
the nature of the basic reagent. Working with butyllithium only
the two isomeric structure 8 and 9 were obtained, and the allylic
alcohol 10 was not produced. On the other hand, in the pres-
ence of LIDA–KOR mixed base the allylic alcohol 10 was
selectively obtained in quantitative yield (compare entries 1
and 2 in Table 2). This compound clearly derives from the
β-elimination mechanism reported in path a of Scheme 1, while
the formation of the isomeric products 8 and 9 can be readily
rationalised by considering path c of Scheme 1. Other com-
ments can be made from consideration of the conformation of
β-pinene shown in Fig. 2. The stronger bimetallic superbase is
able to react with the Ha site (Fig. 2), promoting β-elimination
according to the syn-periplanar fashion, while in the case of the
weaker butyllithium, α-metalation successfully competes, and
therefore only path c can take place.
J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860
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Table 2 Effect of the base on the isomerisation of β-pinene oxidea (see Scheme 3)
Entry
Base (equiv.)
8 : 9 : 10 Proportionsb
Reaction time (reaction temp. T /ЊC)
Yield (%)c
1
2
3
BuLi (2.5)
LDA (2.5)
LIDA–KOR (2.5)
40 : 60 : 0
0 : 0 : 100
0 : 0: 100
1 h (Ϫ95)
2 h (25)
30 min (Ϫ95)
1 h (25)
30
70
99
a Substrate: 2.0 mmol; solvent: THF. b On the basis of separated products by column chromatography. c Isolated and purified products.
Table 3 Effect of the base on the isomerisation of 3-carene oxidea (see Scheme 4)
Entry
Base (equiv.)
11 : 12 Ratiob
Reaction time (reaction temp. T /ЊC)
Yield (%)c
1
2
3
4
BuLi (2.5)
LDA
LIC–KOR
LIDA–KOR (2.5)
50 : 50
70 : 30
94 : 6
1 h (Ϫ95)
1 h (Ϫ95)
30 min (Ϫ95)
30 min (Ϫ95)
1 h (25)
1 h (25)
70
75
75
80
>99 : <1
a Substrate: 2.0 mmol; solvent: THF. b On the basis of separated products by column chromatography. c Isolated and purified products.
Fig. 4 1,4-Cineole.
Fig. 3 3-Carene oxide.
reactions. In these compounds the basic reagent induces an
eliminative ring opening in five- and six-membered rings that
3-Carene oxide‡
does not benefit from relief of ring strain. Notwithstanding
this, we have considered that it is well known that alkyl-
amides are endowed with an exceptionally high ‘kinetic
basicity’ (velocity of proton abstraction).10 What is more,
working with a lithium–potassium mixed base, the potassium
metal would confer high basicity to its anionic counterpart,
thereby facilitating deprotonation, while the lithium metal,
through its electrophilic properties, could efficaciously promote
ring opening by interaction with the oxygen atom. We have
indeed found a noticeable difference between the reactivity of
butyllithium and that of bimetallic reagents, and the results
obtained are gathered in the Schemes and Tables.
The influence of the base has been examined by considering the
isomerisation shown in Scheme 4, and the results are reported
Scheme 4 Base-promoted isomerisation of 3-carene oxide.
in Table 3. Three metalation sites of comparable acidity are
present in 3-carene oxide, i.e. Ha, Hb and Hc (Fig. 3). In spite of
this, upon treatment with LIDA–KOR reagent 3-carene oxide
selectively (and partly also with LIC-KOR) affords compound
11,§ while butyllithium alone gives a mixture of the isomeric
allylic alcohols 11 and 12¶ (compare entry 1 with entry 2 in
Table 3). The rationalisation of this result can be tentatively
understood after considering that the Ha, Hb, and Hc sites enjoy
the correct arrangement that allows syn-periplanar elimination.
However, what is more, only Ha and Hc sites are constrained
with the right syn-periplanar arrangement (Fig. 3). This fact
could favour metalation at these positions, which furthermore
leads to endocyclic alkenes by β-elimination reaction. The
encumbering bimetallic reagent selects the Ha target that does
not suffer the hindrance of the methyl substituent at the α
position of the oxirane ring. By contrast, the less encumbering
butyllithium, and partly also LDA, afford, in addition, the
isomer 12.
1,4-Cineole
Four metalation targets of comparable acidity are present in
1,4-cineole, i.e. Ha, Hb, Hc, and Hd (Fig. 4). The deprotonation
reaction of these sites should lead to compounds 14, 13, 15, and
16, respectively. In spite of this, the elimination product 14 has
been selectively recovered in fairly good yield. This result can
be tentatively explained by considering the conformation of
1,4-cineole shown in Fig. 4, which points out the constrained
right anti-periplanar geometry of the Ha and Hc protons.
Moreover, the Ha proton is more free with respect to Hc, which
suffers the hindrance of the more encumbering isopropyl
substituent. Possible products obtainable from 1,4-cineole are
presented in Scheme 5. Results of the elimination are given in
Table 4.
We then extended the study to 1,4-cineole and 1,8-cineole in
order to control the feasibility of base-promoted isomerisation
without resorting to the assistance of ring strain that provides
sufficient driving force to overcome the reluctance of the ether
oxygen to act as a nucleofugal leaving group in β-elimination
Scheme 5 Base-promoted isomerisation of 1,4-cineole.
‡ Irradiation of C(4)H (δ 2.70) does not cause an NOE effect at C(1)H
or at C(6)H (δ 0.38 and 0.42).
§ Irradiation of the C(3)Me group (δ 1.19) does not cause an NOE
effect at C(1)H or at C(6)H (δ 0.95–1.08).
¶ Irradiation of the C(4)H (δ 3.67) does not cause an NOE effect on
C(1)H or on C(6)H (δ 0.92–1.10).
1,8-Cineole
Scheme 6 shows the three products 17, 18 and 19 (60% overall
yield) obtained starting from 1,8-cineole by reaction with 4.0
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J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860

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Table 4 Effect of the base on the isomerisation of 1,4-cineolea (see Scheme 5)
Entry
Base (equiv.)
13 : 14 : 15 : 16 Proportionsb
Reaction time (reaction temp. T /ЊC)
Yield (%)
1
2
3
4
BuLi (2.0)
BuLi (2.0)
LIC–KOR (2.0)
LIDA–KOR (2.5)
40 h (25)
7 d (60)
40 h (60)
15 h (60)
0
0 : 100 : 0 : 0
0 : 100 : 0 : 0
0 : 100 : 0 : 0
20c
50c
50c
a Substrate: 2.0 mmol; solvent: hexane. b By GC analysis. c Isolated and purified products.
BuLi (Aldrich) was used as 1.6 M solution in hexanes, t-BuOK
was sublimed in vacuo (0.1 mmHg), and diisopropylamine was
distilled from calcium hydride. β-Pinene oxide, 1,4-cineole, 1,8-
cineole, and all other commercially available reagents were used
as received. α-Pinene oxide and 3-carene oxide were synthesized
according to standard procedure.12 Purification by column
chromatography was performed on Merck silica gel 60 as
stationary phase and diethyl ether–light petroleum (distillation
range 40–60 ЊC) as eluent. 1H and 13C NMR spectra were
recorded at 400 and 100.4 MHz, respectively and were recorded
out at the Dipartimento IFM (Università di Torino). Coupling
constants (J) are given in Hz. Mass spectra were obtained on a
mass-selective detector HP 5970 B instrument operating at
an ionising voltage of 70 eV connected to an HP 5890 GC,
cross-linked methyl silicone capillary column (25 m × 0.2 mm ×
0.33 µm film thickness).
Fig. 5 1,8-cineole.
Scheme 6 Base-promoted isomerisation of 1,8-cineole.
mole equivalents of LIC–KOR superbase. All the other con-
ditions we experimented with [BuLi (4.0 equiv.), 3 days at 60 ЊC
in hexane; KNSiMe3 (4.0 equiv.), 3 days at 60 ЊC in hexane;
LIC–KOR/HMPA (2.5 equiv.), 4 days at 60 ЊC in hexane;
LIC–KOR 60 h at 25 ЊC in hexane] are ineffective. These results
strongly stress the important role of ring strain in oxirane ring
opening: only a large excess of the bimetallic superbase
LIC–KOR in hexane, at the reflux temperature, effectively
metalates the substrate, promoting ring fission by β-elimination
reaction. Four sites of deprotonation, that is Ha, Hb, Hc, and
Hd, endowed with comparable acidity, are present in 1,8-cineole
(Fig. 5). Notwithstanding this isomer 19 is the major one. On
the basis of the conformation shown in Fig. 5 we can consider
that the Ha proton adopts an axial orientation, giving to the
dihedral angle between Ha and the leaving oxygen a value of
about 180Њ. Isomer 19 could also predominate owing to its
superior thermodynamic stability.
Reactions of ꢀ-pinene oxide, ꢁ-pinene oxide, and 3-carene oxide
with organometallic basic reagents. General procedures
Method A. BuLi (2.5 ml, 4.0 mmol) was added dropwise with
stirring to a solution of the selected substrate (0.30 g, 2.0 mmol)
in anhydrous THF (5.0 ml). The solution was stirred at Ϫ95 ЊC
for 1.5 h, and whenever no reaction was observed at this tem-
perature the cooling bath was removed and the reaction mixture
allowed to reach 25 ЊC. After the time indicated in Tables 1–3,
the reaction was quenched with an aqueous solution of THF
(5.0 ml). The two phases were separated, the aqueous one was
extracted with diethyl ether (3 × 10 ml), and the collected
organic phases were washed with brine (2 × 10 ml) and dried
(Na2SO4). After evaporation of the solvent the crude residue
was purified by column chromatography.
Method B (LDA). Diisopropylamine (0.40 g, 4.0 mmol) and
BuLi (2.5 ml, 4.0 mmol) were added at 0 ЊC to anhydrous THF
(5.0 ml). After 10 min the mixture was cooled to Ϫ95 ЊC, and
then the reaction proceeds in accordance with the procedure
above described.
Conclusions
In summary these base-mediated isomerisations of some ter-
penoids indicate that interesting structures can be obtained
using easily accessible starting materials. Moreover, a few
features can be clearly recognised. In particular, butyllithium
is unselective and gives poor yields, while, depending on sub-
strate, LIC–KOR, LIDA–KOR or LDA give best results.
Moreover, two major conclusions can be drawn. First, even if
methylene groups are sterically and electronically more shielded
than methyl groups, both compete as centres of deprotonation
in β-elimination. The regioselectivity outcome depends on
the H–C–C–O dihedral angles (the elimination mode being
syn-periplanar5,9). Second, ring strain, as present in oxiranes,
facilitates the elimination reaction but is not a prerequisite.
Also, five- and six-membered oxygen-containing rings are
opened by strong bases, although under more severe conditions.
Method C (LIC–KOR). Sublimed t-BuOK (0.45 g, 4.0
mmol), substrate (0.30 g, 2.0 mmol), and BuLi (2.5 ml, 4.0
mmol) were consecutively added to cooled (Ϫ95 ЊC) anhydrous
THF (5.0 ml). Afterwards the reaction and the work-up condi-
tions were the same as described in Method A.
Method D (LIDA–KOR; LITMP–KOR). At 0 ЊC, diisopro-
pylamine (0.40 g, 4.0 mmol) (or 2,2,6,6-tetramethylpiperidine,
0.56 g, 4.0 mmol) and sublimed t-BuOK (0.45 g, 4.0 mmol)
were consecutively added to a solution of BuLi (2.5 ml, 4.0
mmol) in dry THF (5.0 ml). After 15 min of vigorous stirring
the temperature was decreased to Ϫ95 ЊC, and the substrate
(0.30 g, 2.0 mmol) was added; the method proceeds then
according to that specified in Method A.
Experimental
trans-Pinocarveol 6.13 Purification by column chrom-
atography (90 : 10, light petroleum–diethyl ether). Colourless
oil, δH (CDCl3) 0.65 (s, 3 H), 1.24 (s, 3 H), 1.69 (br s, 1 H), 1.71
(d, J 9.8, 1 H), 1.81 (dd, J 14.6, 4.3, 1 H), 2.00 (ddd, J 12.6, 5.8,
2.3, 1 H), 2.25 (ddt, J 14.7, 7.6, 2.3, 1 H), 2.38 (dtd, J 12.6, 5.5,
2.3, 1 H), 2.50 (t, J 5.5, 1 H), 4.40 (d, J 7.6, 1 H), 4.81 (s, 1 H),
General
Reactions were performed in flame-dried glassware under an
argon atmosphere. The temperature of slush liquid nitrogen–
acetone is indicated as Ϫ95 ЊC, and ‘room temperature’ as
25 ЊC. THF was distilled from sodium benzophenone ketyl.11
J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860
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5.00 (s, 1 H); δC (CDCl3) 22.0, 25.8, 27.5, 34.5, 39.9, 40.5, 50.6,
66.9, 111.5, 156.0; m/z (EI, 70 eV, rel. int.) 134 (Mϩ Ϫ H2O, 2%),
55 (83), 43 (46), 41 (100), 39 (70).
4-Terpineol 14.18 Purification by column chromatography
(60 : 40, light petroleum–diethyl ether). Colourless oil, νmax
(film)/cmϪ1 3421, 1377, 1070; δH (CDCl3) 0.86 (d, J 6.9, 3 H),
0.92 (d, J 6.9, 3 H), 1.52–1.60 (m, 2 H), 1.61–1.68 (m, 5 H),
1.85–1.94 (m, 2 H), 2.10–2.16 (m, 2 H), 5.28 (br d, J 2.7, 1 H);
δC (CDCl3) 16.8, 16.9, 23.3, 27.1, 30.9, 34.5, 36.8, 71.8, 118.5,
133.7; m/z (EI, 70 eV, rel. int.) 154 (Mϩ, 1%), 71 (99), 55 (37),
43 (100), 41 (75).
trans-Pin-3-en-2-ol 7.14 Purification by column chrom-
atography (90 : 10, light petroleum–diethyl ether). Colourless
oil, δH (CDCl3) 0.85 (s, 3 H), 1.27 (s, 3 H), 1.32 (s, 3 H), 1.45 (d,
J 9.9, 1 H), 2.00 (m, 1 H), 2.17 (m, 1 H), 2.35 (m, 1 H), 2.40 (br
s, 1 H), 5.46 (dd, J 8.8, 1.2, 1 H), 6.22 (dd, J 8.8, 6.4, 1 H);
δC (CDCl3) 24.2, 25.9, 27.5, 33.4, 42.7, 47.0, 54.0, 74.3, 129.9,
138.1; m/z (EI, 70 eV, rel. int.) 137 (Mϩ Ϫ Me, 5%), 67 (86), 43
(98), 41 (100), 39 (73).
ꢀ-Terpineol 19.19 Purification by column chromatography
(50 : 50, light petroleum–diethyl ether). Colourless oil, δH
(CDCl3) 1.08 (d, J 6.5, 6 H), 1.30–1.50 (m, 2 H), 1.60 (br s, 3 H),
1.65–1.95 (m, 2 H), 1.90–2.10 (m, 3 H), 2.27 (s, 1 H), 5.36 (br s,
1 H); δC (CDCl3) 22.7, 24.0, 25.9, 26.8, 27.0, 31.6, 45.1, 71.0,
121.0, 133.3; m/z (EI, 70 eV, rel. int.) 136 (Mϩ Ϫ H2O, 30%), 121
(38), 93 (52), 59 (100), 43 (48).
6,6-Dimethyl-2-pentylidenebicyclo[3.1.1]heptane 8. Purifi-
cation by column chromatography (light petroleum). Colour-
less oil, νmax (film)/cmϪ1 2990, 1663; δH (CDCl3) 0.71 (s, 3 H),
0.89 (t, J 8.2, 3 H), 1.28 (s, 3 H), 1.25–1.38 (m, 6 H), 1.47 (d,
J 9.7, 1 H), 1.75–2.10 (m, 4 H), 2.25–2.38 (m, 2 H), 2.79 (t, J 5.5,
1 H), 5.13 (td, J 5.5, 1.8, 1 H); δC (CDCl3) 14.1, 21.8, 22.4, 24.0,
24.1, 25.0, 26.1, 26.3, 32.7, 41.0, 45.1, 52.6, 121.7, 140.8; m/z
(EI, 70 eV, rel. int.) 192 (Mϩ, 1%), 93 (41), 79 (27), 69 (50), 41
(100).
Acknowledgements
This work was supported by grants from Italian MURST and
CNR. We thank Professor Manfred Schlosser for useful
suggestions.
6,6-Dimethyl-2-pentylbicyclo[3.1.1]hept-2-ene 9. Purification
by column chromatography (light petroleum). Colourless oil,
νmax (film)/cmϪ1 2995, 1660: δH (CDCl3) 0.71 (s, 3 H), 0.89 (t,
J 8.2, 3 H), 1.21 (s, 3 H), 1.20–1.35 (m, 6 H), 1.65–2.05 (m, 4 H),
2.10 (dd, J 16.5, 8.4, 2 H), 2.32 (m, 1 H), 2.56 (dtt, J 16.5, 8.2,
2.2, 1 H), 4.94 (tt, J 5.8, 2.2, 1 H); δC (CDCl3) 14.3, 19.8, 21.8,
24.1, 25.9, 26.1, 26.1, 26.2, 28.0, 32.5, 40.9, 45.1, 121.8, 141.7;
m/z (EI, 70 eV, rel. int.) 192 (Mϩ, 1%), 93 (43), 69 (50), 41 (100),
39 (37).
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4 M. Lautens, E. Fillion and M. Sampat, J. Org. Chem., 1997, 62,
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D. M. Hodgson and S. L. M. Norsikian, Org. Lett., 2001, 3, 461.
5 A. Mordini, E. Ben Rayana, C. Margot and M. Schlosser,
Tetrahedron, 1990, 46, 2401; P. Saravanan, A. DattaGupta,
D. Bhuniya and V. K. Singh, Tetrahedron, 1997, 53, 1855; P. O’Brien
and J. J. Tournayre, Tetrahedron, 1997, 53, 17527; A. Mordini,
S. Bindi, A. Capperucci, D. Nistri, G. Reginato and M. Valacchi,
J. Org. Chem., 2001, 66, 3201 and references therein.
6 J. K. Crandall and L. H. Chang, J. Org. Chem., 1967, 32, 435; J. K.
Crandall and L. C. Crawley, Org. Synth., 1988, Coll Vol. 6, p. 948.
7 M. Schlosser, J. Organomet. Chem., 1967, 8, 9; M. Schlosser,
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8 F. Cominetti, A. Deagostino, C. Prandi and P. Venturello,
Tetrahedron, 1998, 54, 14603.
9 R. P. Thummel and B. Rickborn, J. Am. Chem. Soc., 1970, 92, 2064;
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10 Huisgen and Sauer were the first to report that phenyllithium
converts piperidine instantaneously and quantitatively into lithium
piperidide. Despite its weaker thermodynamic basicity, the latter
reagent brings about the dehydrohalogenation of bromobenzene
almost 100 times faster than its organometallic precursor, see
R. Huisgen and J. Sauer, Angew. Chem., 1960, 72, 91; R. Huisgen
and J. Sauer, Chem. Ber., 1959, 92, 192.
11 W. Schlenk and E. Bergann, Justus Liebigs Ann. Chem., 1928, 464, 22.
12 H. Hubbert and P. Burt, Org. Synth., 1921, Coll. Vol. 1, 494.
13 J. K. Crandall and L. C. Crawley, Org. Synth., 1973, 53, 17; J. M.
Coxon and E. Dansted, Org. Synth., 1976, 56, 25.
Myrtenol 10.15 Purification by column chromatography (90 :
10, light petroleum–diethyl ether). Colourless oil, νmax (film)/
cmϪ1 3345, 2960; δH (CDCl3) 0.81 (s, 3 H), 1.15 (d, J 9.2, 1 H),
1.19–1.25 (m, 1 H), 1.26 (s, 3 H), 2.10 (qm, J 5.3, 2 H), 2.21 (dm,
J 15.2 1 H), 2.29 (br d, J 15.2, 1 H), 2.38 (dt, J 9.2, 5.2, 1 H),
3.95 (s, 2 H), 5.45 (br s, 1 H); δC (CDCl3) 21.2, 26.2, 31.2, 31.7,
38.0, 41.0, 43.4, 65.9, 117.8, 147.9; m/z (EI, 70 eV, rel. int.) 152
(Mϩ, 5%), 108 (26), 91 (47), 79 (100), 67 (18).
(؉)-Car-4-en-3-ol 11.16 Purification by column chrom-
atography (70 : 30, light petroleum–diethyl ether). Colourless
oil, νmax (film)/cmϪ1 3384, 1639; δH (CDCl3) 0.85 (s, 3 H), 0.95–
1.08 (m, 2 H), 1.10 (s, 3 H), 1.19 (s, 3 H), 1.40 (dd, J 15.2, 5.1, 1
H), 1.88 (br s, 1 H), 2.06 (ddd, J 15.2, 9.2, 0.7, 1 H), 5.76 (ddd,
J 9.7, 2.4, 0.7 1 H), 5.80 (br d, J 9.7, 1 H); δC (CDCl3) 14.8, 18.3,
22.5, 23.5, 27.7, 28.9, 34.5, 65.7, 128.9, 136.5; m/z (EI, 70 eV, rel.
int.) 137 (Mϩ Ϫ Me, 10%), 119 (73), 109 (61), 91 (64), 43 (100).
(؉)-cis-2-Caren-4-ol 12.17 Purification by chromatography
(70 : 30, light petroleum–diethyl ether). δH (CDCl3) 0.80 (s, 3 H),
0.92–1.10 (m, 2 H), 1.01 (s, 3 H), 1.06 (s, 3 H), 1.77–1.94
(m, 2 H), 3.33 (br s, 1 H), 3.67 (br s, 1 H), 5.53 (br s, 1 H);
δC (CDCl3) 15.0, 18.5, 20.2, 22.6, 22.8, 27.1, 27.6, 64.2, 121.7,
136.8; m/z (EI, 70 eV, rel. int.) 152 (Mϩ, 2%), 109 (100), 43 (58),
41 (45), 39 (39).
14 M. K. Lajunen, T. Maunula and A. M. P. Koskinen, Tetrahedron,
2000, 56, 8167.
15 H. Heikman, P. Baeckström and K. Torssell, Acta Chem. Scand.,
1968, 22, 2034; C. Filliatre, J.-J. Villenav and J. Prévot, Bull. Soc.
Chim. Fr., 1979, II, 473.
Reaction of 1,4-cineole and 1,8-cineole with organometallic basic
reagents. General procedure
16 M. H. Shastri, D. G. Patil, V. D. Patil and Sukh Dev, Tetrahedron,
1985, 41, 3083; G. Rücker and K. Frey, Liebigs Ann. Chem., 1987,
389.
17 T. Satoh, T. Okuda, Y. Kaneko and K. Yamakawa, Chem. Pharm.
Bull., 1984, 32, 1401.
18 K. N. Gurudutt, M. A. Pasha, B. Ravindranath and P. Srinivass,
Tetrahedron, 1984, 40, 1629; F. Delay and G. Ohloff, Helv. Chim.
Acta, 1979, 62, 2168.
19 N. Bluthe, J. Ecoto, M. Fetizon and S. Lazare, J. Chem. Soc., Perkin
Trans. 1, 1980, 1747; M. Bertrand, B. Waegell and J. P. Zahra, Bull.
Soc. Chim. Fr., 1991, 128, 904.
BuLi (2.5 ml, 4.0 mmol) was added dropwise to a cooled (Ϫ95
ЊC) and stirred solution of sublimed t-BuOK (0.45 g, 4.0 mmol)
and of substrate (0.31 g, 2.0 mmol) in dry hexane (5.0 ml). The
solution was heated to 60 ЊC, and after the time reported in
Table 4 and in the text and the reaction was quenched with
water (1.5 ml). The two phases were separated and the aqueous
one was extracted with Et2O (3 × 10 ml). The collected organic
phases were washed with brine (2 × 10 ml), dried (Na2SO4), and
concentrated to give the crude reaction product.
2860
J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860