Unusual α-hydroxyaldehyde with a cyclopentane framework from verbenol epoxide

Article abstract of DOI:10.1016/j.mencom.2007.09.020

The isomerization of (-)-cis-verbenol epoxide in the presence of K10 clay forms optically active 2-(2,2-dimethylcyclopent- 3-enyl)-2-hydroxypropanal as one of the products.

Full text of DOI:10.1016/j.mencom.2007.09.020

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 303–305
Unusual α-hydroxyaldehyde with a cyclopentane
framework from verbenol epoxide
Oleg V. Ardashov,a Irina V. Il’ina,b Dina V. Korchagina,b
Konstantin P. Volcho*b and Nariman F. Salakhutdinovb
a Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russian Federation
b N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of
Sciences, 630090 Novosibirsk, Russian Federation. Fax: +7 383 330 9752; e-mail: volcho@nioch.nsc.ru
DOI: 10.1016/j.mencom.2007.09.020
The isomerization of (–)-cis-verbenol epoxide in the presence of K10 clay forms optically active 2-(2,2-dimethylcyclopent-
3-enyl)-2-hydroxypropanal as one of the products.
Interest in the chemistry of pinane terpenoids is due to the
useful properties of these substances such as accessibility,1
chemical lability, and generally high optical purity, which are of
importance to asymmetric synthesis.2–4 Recently,5 we found
that the storage of (–)-cis-verbenol epoxide 1 on natural
montmorillonite askanite-bentonite clay unexpectedly formed
trans-diol 2 with a p-menthane framework as the major pro-
duct (47%). Hydroxyketone 3, which had been obtained before
as the major product of this reaction in the presence of ZnBr2,6
was isolated in minor quantities (5%) (Scheme 1). The possible
mechanism leading to diol 2 involves the stage of an opening
transformation of the cation with a pinane framework into a
cation with a p-menthane framework; for compound 3, the
reaction probably follows the traditional route to compounds
of the campholene aldehyde type. Diol 2 may be regarded as
a unique, easily accessible and optically active precursor in
asymmetric synthesis.
A larger scale synthesis of compound 2 was performed in the
presence of synthetic montmorillonite K10 clay. In addition to
products 2 and 3, the reaction mixture contained one more
compound with a cyclopentane framework, 2-(2,2-dimethyl-
cyclopent-3-enyl)-2-hydroxypropanal 4.†
In compound 4, we can also observe a rather unusual
arrangement of methyl groups. Formation of this compound
cannot be explained by a traditional set of rearrangements
of pinene epoxide and its derivatives into compounds with
campholene or isocampholene frameworks.1,5 Synthesis of a
compound structurally related to α-hydroxyaldehyde 4 has been
reported previously.7 The behaviour of cis- and trans-δ-pinene
epoxides 5a,b in the presence of ZnBr2 has been studied, and it
was shown that the reaction afforded compounds 6a,b related
to compound 4 (Scheme 2). The mechanism suggested led to
the formation of cation 7 at the key stage of the process.
3
8
2
4
9
O
1
10
5
clay
6
CHO
7
†
A mixture of CH2Cl2 (150 ml) and (–)-cis-verbenol epoxide 1 {11.50 g,
HO
OH
20
[a] –44 (c 12, CHCl3)}, obtained from (–)-verbenone by oxidation
580
1
4
with aqueous H2O2 and further reduction with LiAlH4 according to
published procedures,5,9 was added with stirring to a suspension of K10
clay (30.0 g, Fluka), preliminarily calcinated for 3 h at 120 °C, in CH2Cl2
(200 ml). The reaction mixture was stirred for 1 h at room temperature.
The catalyst was filtered off and washed with ethyl acetate, and the
solvent was distilled off. The residue was separated by SiO2 column
chromatography (63–200 µ; Merck) using a 50–100% hexane solution of
diethyl ether as an eluent. This gave 5.10 g (44%) of (1R,2R,6S)-3-methyl-
6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 2 {[a]D31 –49.1 (c 2.6, CHCl3)},
1.86 g (16%) of (S)-2-hydroxy-1-(2,2,3-trimethylcyclopent-3-enyl)-
ethanone 3 {[a]D31 –21.6 (c 2.1, CHCl3)} and 1.13 g (10%) of com-
clay
OH
OH
OH
OH
~C–C
~C–C
~C–C
OH
OH
1
pound 4. The H NMR spectra of compounds 2 and 3 coincided with
the published spectra.5
For 4: [a]D31 –2.4 (c 2.3, CHCl3). 1H NMR (400 MHz, CDCl3) d: 0.85
(s, 3H, C9H3), 1.01 (s, 3H, C8H3), 1.25 (s, 3H, C10H3), 2.20 (dd, 1H, H1,
J1,5' 10 Hz, J1,5 8 Hz), 2.41 (dddd, 1H, H5, J5,5' 16 Hz, J5,1 8 Hz, J5,4 3 Hz,
J5,3 1.5 Hz), 2.62 (dddd, 1H, H5', J5',5 16 Hz, J5',1 10 Hz, J5',3 2.5 Hz,
J5',4 2 Hz), 3.14 (br. s, 1H, OH), 5.30 (ddd, 1H, H3, J3,4 6 Hz, J3,5' 2.5 Hz,
J3,5 1.5 Hz), 5.54 (ddd, 1H, H4, J4,3 6 Hz, J4,5 3 Hz, J4,5' 2 Hz), 9.64 (s,
1H, H7). 13C NMR, d: 53.70 (d, C1), 46.15 (s, C2), 142.35 (d, C3), 125.78
(d, C4), 32.39 (t, C5), 79.28 (s, C6), 203.66 (d, C7), 29.61 (q, C8), 23.26
(q, C9), 23.62 (q, C10). The presence of a hydroxyl group at the C6 atom
is confirmed by the 13C NMR spectrum recorded for a CDCl3 solution
of the substance with a D2O addition, in which the high-field singlet at
79.28 ppm is shifted by 0.12 ppm due to the isotope effect. MS, m/z:
168.11479 [M+]. Calc. for C10H16O2: 168.11502.
HO
OH
–H+
~H –H+
OH
OH
O
OH
2
3
Scheme 1
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Mendeleev Commun., 2007, 17, 303–305
R1 R2
R1 R2
R1 R2
OH
O
OH
~C–C
O
ZnBr2
OH
1
5a,b
7
clay
A
clay
C
R1 R2
R1
clay
B
H+
R2
OH
~C–C
–H+
OH
O
O
CHO
OH2
OH
O
6a,b
a R1 = H, R2 = Me
b R1 = Me, R2 = H
OH2
8
– H2O
O
Scheme 2
We can suggest three routes leading to cation 7 from verbenol
epoxide 1 (Scheme 3). Route A includes the formation of
neutral intermediate 8, which undergoes epoxide ring cleavage
after protonation to give cation 9 structurally similar to cation 7.
Processes of this kind, however, have been described only for
highly basic media,8 and they hardly take place in the presence
of an acid catalyst such as K10 clay.
OH
OH
OH
2
OH2
OH
10
4
~C–C
9
Route B suggests initial protonation of the hydroxyl group
and elimination of the water molecule, leading to cation 10.
Further rearrangements of cation 10 can yield compound 4.
For route B to be feasible we have to assume that the reaction
does not start with cleavage of the protonated epoxide ring
as it normally does when epoxides are kept in acid media.
Furthermore, we assume that, before epoxide ring cleavage,
the intermediate cation has enough time to undergo a number
of skeletal rearrangements. We have not found any examples of
O
~H+
OH
~C–C
OH
+ H2O
~C–C
OH
OH
H
H
O
OH2
O
O
such a very unusual behaviour in the literature.
20
The optical purity of verbenone {[a]
–179.5 (c 21.5,
580
CHCl3)}9 employed for the synthesis of (–)-cis-verbenol epoxide
1 is ~60% {lit.,10 [a]D22 –264 (c 3, CHCl3) for verbenone with
90% optical purity}. We determined the optical purity of com-
pound 4 by recording its 1H NMR spectrum with the chiral
shift reagent Eu(hfc)3. The optical purity of hydroxyaldehyde 4
was 60%; that is, the reaction is stereospecific. This also agrees
– H2O
~C–C
OH
OH
OH2
OH
O
OH
O
1
with the H and 13C NMR spectra, which contain no signals of
the diastereomers of 4.
11
+ H2O – H+
9
In view of the high stereoselectivity of the reaction that
leads to compound 4, one can assume that carbocation 11 is not
produced in a pure form if the reaction follows mechanism B.
Otherwise, the addition of the water molecule to the α-position
relative to the aldehyde group would be accompanied by the
formation of two diastereomers. Therefore, it seems most likely
that the water molecule interacts with the cation containing an
epoxy group.
CHO
HO
According to mechanism C, the reaction starts with cleavage
of the epoxy group involving a water molecule. This stage is
possibly followed by protonation of the hydroxyl group at the
4-position and elimination of the water molecule, leading to
the formation of cation 9. Further transformations of this carbo-
cation can follow route A. The most serious disadvantages of
this version are the following: (1) this kind of epoxide cleavage
into trans-diols in the presence of clay has never been observed
previously;5,9,11,12 (2) the reasons for protonation of the hydroxyl
group in the intermediate triol are vague; it is not clear why the
water molecule should be further eliminated in the 4-position,
and why it should lead to the formation of a secondary rather
than tertiary carbocation, as would be expected in protonation
of the hydroxyl group at the 2-position.
4
Scheme 3
pentane framework. To explain the formation of this compound,
we have to invoke mechanisms not typical of these compounds.
The reaction routes as unusual as these may be explained by
specific adsorption of compound 1 on montmorillonite clay.
This work was supported by the Presidium of the Russian
Academy of Sciences (programme no. 18.2).
References
1 W. F. Erman, Chemistry of the Monoterpenes, Part A, Marcel Dekker
Inc., New York, 1985, p. 213.
2 K. P. Volcho, L. N. Rogoza, N. F. Salakhutdinov, A. G. Tolstikov and
G. A. Tolstikov, Preparativnaya khimiya terpenoidov, Chast’ 1. Bitsikli-
cheskie monoterpenoidy (The Preparative Chemistry of Terpenes. Part 1.
Bicyclic Monoterpenes), Izdatel’stvo SO RAN, 2006 (in Russian).
Despite of its singularity, route B seems to be more probable.
Thus, when investigating the isomerization of (–)-cis-verbenol
epoxide 1 in the presence of K10 clay, we found that this
reaction gives new unusual α-hydroxyaldehyde 4 with a cyclo-
– 304 –

Mendeleev Commun., 2007, 17, 303–305
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Received: 7th May 2007; Com. 07/2931
– 305 –