Oxidative bromination of tricyclic sesquiterpenoids (1S,3S,5R,6S,9S)-5-hydroxy-6,10,10-trimethyl-tricyclo[7.2.0.0 1,6]udecan-2-one and clovane-2β,9α-diol with the HBr-DMSO system

Article abstract of DOI:10.1023/A:1012737123973

Oxidation of tricyclic sesquiterpenoids of the caryophyllene type with the HBr-DMSO system afforded α,β-unsaturated a-bromoketones. Since tricyclic derivatives, unlike simple alicyclic ketones, cannot undergo aromatization, all intermediate oxidation prod

Full text of DOI:10.1023/A:1012737123973

Russian Chemical Bulletin, International Edition, Vol. 50, No. 8, pp. 1419—1422, August, 2001
1419
Oxidative bromination of tricyclic sesquiterpenoids
(1S,3S,5R,6S,9S)-5-hydroxy-6,10,10-trimethyl-
tricyclo[7.2.0.01,6]udecan-2-one and clovane-2β,9α-diol
with the HBr—DMSO system
M. S. Yusubov,a L. A. Drygunova,a and A. V. Tkachevb«
aDepartment of Chemistry, Siberian Medical University,
634050 Tomsk, Russian Federation.
E-mail: yusubov@mail.ru
bNovosibirsk Institute of Organic Chemistry,
9, prosp. Acad. Lavrentjeva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 344 855. E-mail: atkachev@nioch.nsc.ru
Oxidation of tricyclic sesquiterpenoids of the caryophyllene type with the HBr—DMSO
system afforded α,β-unsaturated α-bromoketones. Since tricyclic derivatives, unlike simple
alicyclic ketones, cannot undergo aromatization, all intermediate oxidation products can be
isolated, which provide evidence that oxidation proceeds according to the following scheme:
ketone→α-bromoketone→α,α-dibromoketone→α,β-unsaturated α-bromoketone.
Key words: hydrobromic acid, dimethyl sulfoxide, tricyclic sesquiterpenoids, caryophyllene,
ketones, oxidation, bromination.
The HBr—DMSO system is known as a selective
reagent used for oxidation of simplest alkenes, vicinal
dibromides and diols, epoxides and ketones to form
1,2-diketones.1—3 Oxidation of more structurally com-
plex compounds with the HBr—DMSO system is some-
times accompanied by formation of products of bromi-
nation and deeper oxidation. For example, oxidation of
dimedone under the action of the HBr—DMSO system
afforded a mixture of 3,5-dibromo-2,6-dihydroxy-4,4-di-
methylcyclohexa-2,5-dien-1-one (46%) and 3,5,5-tri-
bromo-2-hydroxy-4,4-dimethylcyclopent-2-en-1-one
(17%).4 In the present study, we demonstrate the capa-
bilities of this reagent in oxidation of a series of terpenic
compounds whose oxidation products can subsequently
be used in the synthesis of various bromo derivatives.
Oxidation of the simplest cyclic terpenic ketone,
viz., menthone 1, with the HBr—DMSO system gave
rise to 2,4-dibromo-6-isopropyl-3-methylphenol (2,4-di-
bromothymol) (2) in 62% yield (Scheme 1). This reac-
tion pathway is, apparently, typical of all cyclohexanone
derivatives capable of undergoing aromatization.
Under the action of the HBr—DMSO system,
hydroxyketone 3 was initially converted into α-bromo-
ketone 4. Subsequent oxidation of compound 4 at higher
temperature afforded successively α,α-dibromoketone 5,
α,β-unsaturated α-bromoketone 6, and, finally, unsat-
urated bromodiketone 7. Analysis of the spectral data
(MS, IR, and 2D NMR) for compounds 4—7 demon-
strated that their formation was not accompanied by the
rearrangement of the carbon skeleton and only the
substituted cyclohexanone fragment of the starting com-
pound 3 underwent a change (Scheme 2). Monobromo
derivative 4 was formed as the only stereoisomer with
the S configuration of the C(3) atom, which corre-
sponds to the attack of the Br+ ion on intermediate enol
of ketone 3 from the less hindered α-side. The configu-
ration of the C(3) atom in compound 4 follows from
3
analysis of the spin-spin coupling constants JH—H
.
Judging from these constants, the twist conformation
with the pseudoequatorial bromine atom and the
pseudoequatorial hydroxyl group is the most favorable
conformation of the six-membered ring in molecule 4.
It is known that bromoketones are oxidized in DMSO
to form bromo derivatives of 1,2-diketones,5 whereas
oxidation of substituted cyclic bromoketones in DMSO
can afford either 1,2-diketones or unsaturated mono-
bromoketones.6 In our case, bromoketone 4 was not
oxidized to 1,2-diketone under the action of the
HBr—DMSO system; instead, it underwent the suc-
cessive conversions α-bromoketone→α,α-dibromo-
ketone→α,β-unsaturated α-bromoketone, which ended
with oxidation of the OH group at the C(5) atom. When
isolated in pure form, compounds 5 and 6 were readily
Scheme 1
Br
Br
HBr—DMSO, 75 °C
62%
O
OH
ꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1350—1353, August, 2001.
1066-5285/01/5008-1419 $25.00 ©ꢀ2001 Plenum Publishing Corporation

1420
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Ysubov et al.
Scheme 2
than the subsequent conversions of the resulting keto
derivatives. Thus, oxidation of tricyclic derivative 8,
while afforded the final product 9 in good yield, re-
quired substantially more drastic conditions (110 °C).
In the latter case, attempts to isolate intermediate prod-
ucts failed; however, the oxidation mechanism is, most
likely, analogous to the mechanism of oxidation 3→6
(Scheme 3). The surprising thing is that only one of two
hydroxyl groups of the starting diol 8 was involved in
the reaction. Thus, the hydroxyl group in the six-
membered ring was oxidized, whereas the hydroxyl group
in the five-membered ring remained intact. It is note-
worthy that in the latter case, no skeletal rearrange-
ments were also observed in spite of the high tempera-
ture and the presence of the strong acid. The retention
of the carbocyclic core of the molecule was confirmed
by analysis of the 2D NMR spectra and the spin-spin
coupling constants for compound 9.
OH
OH
12
5
3
HBr—DMSO
45 °C
8
6
1
9
H
H
Br
13
11
O
O
14
!
"
OH
HBr—DMSO
85 °C
Br
Br
H
O
#
OH
O
To summarize, oxidation of the tricyclic sesquiterpe-
noid derivatives under study afford products, which do
not undergo aromatization because of the presence of
quaternary carbon atoms in the six-membered ring of
compound 3. Because of this, the oxidation process can
be followed step by step and all intermediates can be
isolated, which provides proof of the scheme of the
multistage oxidation process involving ketones. Analogous
oxidative conversions involving the corresponding sec-
ondary alcohols can also be performed; however, attempts
to isolate intermediates failed because alcohols are oxi-
dized to ketones under more severe conditions, and only
the final product in the oxidative chain can be obtained.
H
H
Br
Br
O
O
$
%
converted into diketone 7 under the same conditions,
which confirmed that these compounds are intermedi-
ates in the path 4→7. In this case, the ratio of the
oxidation rates of the products is such that either com-
pound 4 or compound 7 can be obtained under particu-
lar conditions as the only product. Thus, oxidation of
hydroxyketone 3 at 45 °C for 8 h afforded compound 4
in 95% yield, whereas oxidation of hydroxyketone 3 first
at 45 °C for 8 h and then at 85 °C for 24 h gave rise to
compound 7 in 85% yield.
The ratio of the rates characterizing the individual
stages of the oxidative conversions in the HBr—DMSO
system depends substantially on the structure of the
remaining portion of the molecule and is, apparently,
associated primarily with the steric hindrances caused
by molecular fragments, which are not involved in the
reaction. It should be noted that not only ketones but
also alcohols can undergo oxidative bromination. The
latter are initially oxidized to the corresponding ke-
tones; however, the reaction conditions should be more
severe because oxidation of alcohols to ketones under
the action of this system proceeds much more difficultly
Experimental
Thin-layer chromatography was carried out on Silufol
plates with a SILPEARL silica gel layer fixed on an aluminum
foil (Czech Republic). The components were visualized by
spraying the plates with concentrated H2SO4 followed by heat-
ing to 100—150 °C. Column chromatography was performed on
KSK silica gel (Russia; the particle size was 0.10—0.20 mm),
which was dried in air and activated by heating at 140 °C for
5 h. The IR spectra were recorded on a Specord M-80 spectro-
photometer for solutions in CHCl3 (c 1%). The UV spectra
were measured on a Specord UV VIS spectrophotometer for
solutions in 95% EtOH. The optical rotation was measured on a
Polamat A polarimeter at the wavelength of 578 nm for solu-
tions in CHCl3. The melting points were determined on a
Kofler stage. Microanalyses were carried out on Hewlett
Packard 185 and Carlo Erba 1106 analyzers. The mass spectra
Scheme 3
15
OH
O
O
O
O
9
Br
Br
6
12
HBr—DMSO
110 °C
Br
Br
H
H
H
H
H
5
1
11
76%
14
OH
OH
OH
OH
OH
13
3
&
'

Oxidation of sesquiterpenoids with HBr—DMSO
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
1421
were obtained on a Finnigan MAT-8200 mass spectrometer
(EI, 70 eV). The NMR spectra were recorded on a Bruker
AM-400 spectrometer (400.13 MHz for 1H and 100.61 MHz for
13C) at room temperature (23—25 °C), unless otherwise stated,
using the signals of the solvent as the internal standard
(δC = 76.900 and δH = 7.240 for CDCl3, δC = 128.000 and
3 : 1 v/v). 2,4-Dibromo-6-isopropyl-3-methylphenol (2)9 was
obtained as a yellow oil in a yield of 0.413 g (62%). IR (CHCl3),
ν/cm–1: 3501 (O—H). 13C NMR (CDCl3), δ: 22.27 (Ar—CH3);
26.86 (2 C, CH3); 28.01 (Ar—CH); 114.00 and 115.03 (C(2)
and C(4)); 129.2 (C(5)); 134.9 (C(6)); 148.8 (C(1)). MS,
m/z (Irel (%)): 306/308/310 [M]+ (31), 293 [M – 15]+ (100),
212/214 [M – Br – Me]+ (38), 133 [C9H9O]+ (8), 115 [C9H7]+
(10). Found (%): C, 39.0; H, 3.8. C10H12Br2O. Calculated (%):
C, 38.99; H, 3.93.
(1S,3S,5R,6S,9S)-3-Bromo-5-hydroxy-6,10,10-trimethyl-
tricyclo[7.2.0.01,6]undecan-2-one (4). Keto alcohol 3 (0.220 g,
1.00 mmol) was added to a solution of 40% aqueous HBr
(0.5 mL) in DMSO (5 mL). The resulting mixture was heated at
45 °C for 8 h, cooled to ∼20 °C, diluted with water (100 mL),
and extracted with Et2O (2½50 mL). The combined organic
extracts were washed successively with water (3½50 mL) and a
saturated aqueous solution of NaCl (50 mL) and then dried
with MgSO4. The solvent was distilled off in vacuo and the solid
residue was crystallized from C6H6. Bromoketone 4 was isolated
δ
H = 7.150 for C6D6, δC = 123.500 and δH = 7.190 for C5D5N).
The assignment of the signals was made using the 13C NMR
spectra, which were recorded with J modulation (proton-noise-
decoupled spectra, the opposite phases for the signals of the
atoms with the odd and even numbers of the attached protons,
tuning to the constant J = 135 Hz), and based on the 2D
1
spectra, viz., 1) homonuclear H—1H correlation, 2) hetero-
nuclear 13C—1H correlation at the direct spin-spin coupling
constants (J = 135 Hz), and 3) heteronuclear 13C—1H correla-
tion at the long-range spin-spin coupling constants (J = 10 Hz).
(–)-Caryophyllene ([α]20 –9 in pure form; > 97% accord-
ing to GLC; prepared by rectification of the hydrocarbon
fraction of a clove oil) was converted into 4β,5α-epoxide
(caryophyllene epoxide), which was oxidized with KMnO4 to
the 4,5-epoxy-8-oxo-13-nor derivative (kobusone). Cyclization
of the latter in an alkaline medium afforded keto alcohol 3.7
Clovane-2β,9α-diol 8 was prepared by acid isomerization of
caryophyllene epoxide as described previously.8
as white crystals in a yield of 0.285 g (95%), m.p. 167—169 °C
–1
(from benzene), [α]22 ±0 (c 6.00, CHCl3). IR (CHCl3), ν/cm
:
3616 (O—H), 1712 (C=O). 1H NMR (CDCl3), δ: 0.85 (s, 3 H,
H(12)); 0.87 (s, 3 H, H(13)); 0.97 (s, 3 H, H(14)); 1.48 (d, 1 H,
Ha(11), J = 12.4 Hz); 1.66 (ddd, 1 H, Ha(7), J = 13.0, 12.7,
and 7.5 Hz); 1.82 (dd, 1 H, Ha(8), J = 14.8 and 7.5 Hz); 1.75
(br.s, OH); 1.98 (dddd, 1 H, Hb(8), J = 14.8, 13.0, 8.6, and
7.5 Hz); 2.05 (dd, 1 H, Hb(7), J = 12.7 and 7.5 Hz); 2.26 (ddd,
1 H, Ha(4), J = 13.9, 12.5, and 12.0 Hz); 2.31 (dd, 1 H, H(9),
J = 8.6 and 3.1 Hz); 2.58 (dd, 1 H, Hb(11), J = 12.4 and
3.1 Hz); 2.59 (ddd, 1 H, Hb(4), J = 12.5, 5.5, and 4.0 Hz); 3.92
(dd, 1 H, H(5), J = 12.0 and 4.0 Hz); 4.78 (dd, 1 H, H(3),
J = 13.9 and 5.5 Hz). 13C NMR, δ: 11.52 (C(12)); 24.29
(C(13)); 25.08 (C(9)); 29.78 (C(14)); 31.50 (C(10)); 34.53
(C(11)); 37.28 (C(7)); 42.43 (C(4)); 50.36 (C(3)); 53.78 (C(6));
55.13 (C(9)); 57.41 (C(1)); 69.74 (C(5)); 202.25 (C(2)). High-
resolution MS. Found: m/z = 300.07174 [M]+. C14H21BrO2.
Calculated: M = 300.07253. MS, m/z (Irel (%)): 302/300 [M]+
(3/3), 247/245 (43/43), 221 (100), 203 (30), 175 (9), 166 (10),
165 (59), 163 (38), 161 (14), 147 (30), 137 (25), 135 (12), 123
(18), 121 (30), 119 (24), 109 (30), 107 (20), 105 (18), 95 (16),
93 (22), 85 (43), 81 (20), 79 (26), 77 (19), 69 (20), 67 (18), 57
(13), 56 (33), 55 (32), 53 (14), 43 (19), 41 (50), 39 (13).
Oxidation of keto alcohol 3. Keto alcohol 3 (0.103 g,
0.46 mmol) was added to a solution of 40% aqueous HBr
(0.25 mL) in DMSO (2.5 mL). The resulting mixture was
heated successively at 45 °C for 8 h (according to TLC, com-
pound 4 was formed in quantitative yield) and at 85 °C for 12 h.
Then the reaction mixture was treated as in the case of forma-
tion of bromoketone 4 (see above) and the resulting product
(0.150 g) was chromatographed with a EtOAc—hexane mixture.
Unsaturated bromodiketone 7 (0.050 g, 36% yield), dibromo-
ketone 5 (0.044 g, 25% yield), and unsaturated bromoketo
alcohol 6 (0.032 g, 23% yield) were successively eluted.
(1S,5R,6S,9S)-5-Hydroxy-6,10,10-trimethyltricyc-
lo[7.2.0.01,6]undecan-2-one (3). 1H NMR (C6D6—CCl4,
1 : 4 v/v), δ: 0.73 (s, 3 H, H(12)); 0.83 (s, 3 H, H(13)); 0.97 (s,
3 H, H(14)); 1.27 (d, 1 H, Ha(11), J = 12.1 Hz); 1.31 (br.s, 1 H,
OH); 1.51 (ddd, 1 H, Hb(7), J = 12.6, 12.6, and 7.5 Hz); 1.67
(dddd, 1 H, Hb(4), J = 14.0, 12.7, 11.4, and 4.2 Hz); 1.69 (dd,
1 H, Hb(8), J = 14.0 and 7.5 Hz); 1.76 (dddd, 1 H, Ha(4),
J = 12.7, 5.6, 4.3, and 3.0 Hz); 1.87 (dddd, Ha(8), J = 14.0, 12.4,
8.6, and 7.5 Hz); 1.99 (dd, 1 H, Ha(7), J = 12.6 and 5.8 Hz);
2.15 (dd, 1 H, H(9), J = 7.5 and 3.1 Hz); 2.18 (ddd, 1 H, Ha(3),
J = 14.1, 4.2, and 3.0 Hz); 2.29 (ddd, 1 H, Hb(3), J = 14.1, 14.0,
and 5.6 Hz); 2.49 (dd, 1 H, Hb(11), J = 12.1 and 3.0 Hz); 3.60
(dd, 1 H, H(5), J = 11.7 and 4.3 Hz). 13C NMR, δ: 12.18
(C(12)); 24.95 (C(13)); 25.50 (C(9)); 30.18 (C(14)); 30.80 (C(4));
31.45 (C(10)); 33.60 (C(11)); 36.31 (C(3)); 37.74 (C(7)); 53.26
(C(6)); 54.94 (C(9)); 58.25 (C(1)); 70.27 (C(5)); 209.42 (C(2)).
(1S,2S,5S,8R,9R)-4,4,8-Trimethyltricyclo[6.3.1.01,5]do-
decane-2,9-diol (clovane-2β,9α-diol) (8). 1H NMR (Py-d5,
+30 °C), δ: 0.91 (s, 3 H, H(14)); 1.03 (d, 3 H, Ha(12),
J = 11.9 Hz, W1/2 = 6 Hz); 1.11 (s, 3 H, H(13)); 1.195 (s, 3 H,
H(15)); 1.200 (m, H(7a)); 1.35 (m, 1 H, Ha(7)); 1.38—1.45
(m, 2 H, H(6) and Ha(11)); 1.57 (dd, 1 H, H(5), J = 11.4 and
5.2 Hz); 1.87 (d, 2 H, H(3), J = 7.6 Hz); 1.92 (ddd, 1 H,
Ha(10), J = 14.3, 4.8, and 2.4 Hz); 2.12 (dddd, 1 H, Hb(10),
J = 14.3, 13.4, 4.8, and 3.2 Hz); 2.17 (d, 1 H, Hb(12),
J = 11.9 Hz); 2.47 (ddd, 1 H, Hb(11), J = 13.3, 13.3, and 4.8
Hz); 3.56 (dd, 1 H, H(9), J = 3.2 and 2.4 Hz); 4.12 (t, 1 H,
H(2), J = 7.6 Hz); 5.56 (br.s, 2 H, OH). 13C NMR, δ:
21.33 (C(6)); 25.76 (C(14)); 27.26 (C(10)); 27.84 (C(11));
29.45 (C(15)); 31.78 (C(13)); 33.77 (C(7)); 35.38 (C(8));
36.52 (C(12)); 37.32 (C(4)); 45.24 (C(1)); 48.43 (C(3));
51.15 (C(5)); 74.60 (C(9)); 80.41 (C(2)).
(1S,6S,9S)-3-Bromo-6,10,10-trimethyltricyclo[7.2.0.01,6]un-
dec-3-ene-2,5-dione (7). Yellowish crystals, m.p. 106—107 °C
(from benzene), [α]22 –329 (c 1.00, CHCl3). IR (CHCl3),
ν/cm–1: 1723 and 1699 (C=O), 1597 (C=C). UV (EtOH),
2,4-Dibromo-6-isopropyl-3-methylphenol (2). Menthone (1)
(332 mg, 2.16 mmol, Aldrich) was added to a solution of 47%
aqueous HBr (1 mL) in DMSO (10 mL) and the resulting
mixture was heated at 75 °C for 22 h. After cooling to ∼20 °C,
the mixture was diluted with water (200 mL) and the reaction
products were extracted with Et2O (2½50 mL). The combined
organic extracts were washed successively with water (3½50 mL)
and a saturated aqueous solution of NaCl (50 mL) and then
dried with MgSO4. The solvent was distilled off in vacuo and
the resulting product was chromatographed (hexane—benzene,
λ
max/nm (lg ε): 277 (3.7). 1H NMR (CDCl3), δ: 0.90 (s, 3 H,
H(13)); 0.98 (s, 3 H, H(14)); 1.15 (s, 3 H, H(12)); 1.52 (d, 1 H,
Ha(11), J = 13.0 Hz); 1.66 (dddd, 1 H, Ha(8), J = 14.5, 13.5,
8.5, and 7.0 Hz); 1.80 (dd, 1 H, Hb(8), J = 14.5 and 7.0 Hz);
1.91 (dd, 1 H, Ha(7), J = 13.0 and 7.0 Hz); 2.00 (ddd, 1 H,
Hb(7), J = 13.5, 13.0, and 7.0 Hz); 2.45 (dd, 1 H, H(9), J = 8.5
and 2.5 Hz); 2.58 (dd, 1 H, Hb(11), J = 13.0 and 2.5 Hz); 7.30
(s, 1 H, H(4)). 13C NMR, δ: 19.24 (C(12)); 23.94 (C(13)); 26.07
(C(9)); 30.31 (C(14)); 30.54 (C(10)); 32.01 (C(11)); 41.03 (C(7));

1422
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Ysubov et al.
53.54 (C(9)); 53.97 (C(6)); 59.64 (C(1)); 122.78 (C(3)); 160.97
(C(4)); 178.98 (C(5)); 193.72 (C(2)). High-resolution MS. Found:
m/z 296.03940 [M]+. C14H17BrO2. Calculated: M = 296.04124.
MS, m/z (Irel (%)): 298/296 [M]+ (13/13), 243/245 (9/9),
242/240 (60/60), 217 (92), 215 (11), 189 (20), 175 (18), 161
(22), 149 (100), 147 (13), 134 (15), 133 (65), 121 (17), 119 (9),
107 (32), 105 (32), 93 (38), 91 (22), 79 (24), 77 (29), 69 (20), 67
(13), 65 (17), 55 (35), 53 (19), 43 (10), 41 (55).
7 were detected by TLC. After 12 h, only a spot of compound 7
was observed.
Oxidation of bromoketo alcohol 6. Unsaturated bromoketo
alcohol 6 (0.01 g) was added to a solution of 40% aqueous HBr
(0.1 mL) in DMSO (1 mL) and the resulting mixture was
heated at 85 °C for 12 h after which only a spot of compound 7
was detected by TLC.
(1S,2S,5S,8R)-10-Bromo-2-hydroxy-4,4,8-trimethyl-9-oxo-
tricyclo[6.3.1.01,5]dodec-10-ene or (1R,2S,5S,8R)-10-bromo-
2β-hydroxy-10-cloven-9-one (9). Clovane-2β,9α-diol (8)
(0.970 g, 4.10 mmol) was added to a solution of 40% aqueous
HBr (2.5 mL) in DMSO (40 mL) and the resulting mixture was
heated at 110 °C for 16 h. The reaction product (1.10 g)
was purified by column chromatography (EtOAc—hexane,
15 : 85 v/v) and hydroxybromoketone 9 was obtained as colorless
needle-like crystals in a yield of 0.972 g (76%), m.p. 160—162 °C
(from a mixture of hexane and benzene, 1 : 1 v/v), [α]22 –27.9
(c 4.30, CHCl3). IR (CHCl3), ν/cm–1: 3627 and 3588 (O—H),
1685 (C=O), 1591 (C=C). UV (EtOH), λmax/nm (lg ε): 264
(3.76). 1H NMR (Py-d5, +30 °C), δ: 1.05 (s, 3 H, H(14)); 1.14
(s, 3 H, H(15)); 1.17 (s, 3 H, H(13)); 1.38 (m, 1 H, Ha(7));
1.46—1.62 (m, 3 H, Hb(7) and 2 H(6)); 1.53 (dd, 1 Ha(12),
J = 12.9 and 2.0 Hz); 1.79 (ddd, 1 H, Hb(12), J = 12.9, 1.3, and
1.3 Hz); 1.89 (dd, 1 H, Ha(3), J = 13.9 and 2.2 Hz); 1.91 (m,
1 H, H(5)); 2.04 (dd, 1 H, Hb(3), J = 13.9 and 5.0 Hz); 4.06
(dd, 1 H, H(2), J = 5.0 and 2.2 Hz); 8.18 (d, 1 H, H(11),
J = 2.0 Hz). 13C NMR, δ: 18.66 (C(6)); 26.02 (C(15)); 28.44
(C(14)); 33.87 (C(13)); 34.15 (C(7)); 39.62 (C(4)); 40.29 (C(12));
43.98 (C(8)); 45.12 (C(5)); 49.59 (C(3)); 53.82 (C(1)); 76.85
(C(2)); 122.87 (C(10)); 156.78 (C(11)); 197.00 (C(9)). High-
resolution MS. Found: m/z 312.07253 [M]+. C15H21BrO2. Cal-
culated: M = 312.07253. MS, m/z (Irel (%): 314/312 [M]+ (1/1),
296/294 (10/10), 281/279 (15/15), 233 (100), 235 (5), 215 (51),
187(18), 161(42), 159(24), 145(12), 137(55), 131(12), 121 (44),
119 (13), 107 (15), 105 (24), 95 (14), 91 (23), 79 (14), 77 (16),
69 (16), 55 (24), 53 (11), 43 (12), 41 (33), 39 (11), 29 (12).
(1S,5R,6S,9S)-3,3-Dibromo-5-hydroxy-6,10,10-trimethyl-
tricyclo[7.2.0.01,6]undecan-2-one (5). White crystals, m.p.
54—56 °C (from hexane), [α]22 –137 (c 2.10, CHCl3).
1
IR (CHCl3), ν/cm–1: 3616 (O—H), 1707 (C=O). H NMR
(CDCl3), δ: 0.85 (s, 3 H, H(12)); 0.88 (s, 3 H, H(13)); 1.11 (s,
3 H, H(14)); 1.56 (d, 1 H, Ha(11), J = 12.5 Hz); 1.63 (ddd,
1 H, Hb(7), J = 13.5, 13.0, and 7.0 Hz); 1.75 (dd, 1 H, Hb(8),
J = 14.5 and 7.5 Hz); 2.03 (dddd, 1 H, Ha(8), J = 14.5, 13.0,
8.5, and 7.0 Hz); 2.05 (br.s, OH); 2.11 (dd, 1 H, Ha(7),
J = 13.0 and 7.0 Hz); 2.56 (dd, 1 H, Hb(11), J = 12.5 and
3.0 Hz); 2.89 (dd, 1 H, H(9), J = 8.5 and 3.0 Hz); 2.90 (dd,
1 H, Ha(4), J = 14.5 and 11.5 Hz); 3.03 (dd, 1 H, Hb(4),
J = 14.5 and 4.0 Hz); 4.20 (dd, 1 H, H(5), J = 11.5 and
4.0 Hz). 13C NMR, δ: 12.28 (C(12)); 24.28 (C(13)); 24.71
(C(9)); 29.63 (C(14)); 31.20 (C(10)); 35.45 (C(11)); 37.15
(C(7)); 51.40 (C(4)); 52.00 (C(6)); 55.60 (C(1)); 60.70 (C(9));
64.48 (C(3)); 67.37 (C(5)); 197.63 (C(2)). High-resolution MS.
Found: m/z 377.98237 [M]+. C14H20Br2O2. Calculated:
M = 377.98310. MS, m/z (Irel (%)): 382/380/378 [M]+
(2.5/5/2.5), 327/325/323 (10/21/10), 301/299 (64/64), 283/281
(26/26), 259/257 (11/11), 245/243 (20/20), 220 (11), 219 (29),
217/215 (16/16), 201 (21), 191 (16), 177 (11), 173 (14), 165
(38), 164 (23), 163 (39), 159 (17), 149 (12), 147 (13), 146 (11),
145 (12), 138 (18), 137 (15), 136 (10), 135 (12), 131 (13), 125
(28), 123 (20), 121 (26), 119 (16), 117 (14), 109 (30), 107 (44),
105 (20), 95 (22), 93 (38), 91 (34), 83 (22), 81 (12), 79 (47), 69
(43), 67 (28), 65 (16), 57 (19), 56 (52), 55 (67), 53 (26), 43
(53), 41 (100), 39 (23), 29 (20), 27 (25).
(1S,5R,6S,9S)-3-Bromo-5-hydroxy-6,10,10-trimethyl-
tricyclo[7.2.0.01,6]undec-3-en-2-one (6). White crystals, m.p.
117—119 °C (from a mixture of hexane and benzene, 1 : 1 v/v),
[α]22 –174 (c 0.90, CHCl3). IR (CHCl3), ν/cm–1: 3615 (O—H),
1676 (C=O), 1613 (C=C). UV (EtOH), λmax/nm (lg ε): 259
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos. 96-15-
97017 and 00-03-32812a).
1
(3.7), 337 (2.0). H NMR (CDCl3), δ: 0.89 (s, 3 H, H(13));
References
0.93 (s, 3 H, H(12)); 1.20 (s, 3 H, H(14)); 1.55 (d, 1 H,
Ha(11), J = 13.0 Hz); 1.63 (ddd, 1 H, Hb(7), J = 13.0, 13.0,
and 7.5 Hz); 1.73—1.86 (m, 1 H, Ha(8)); 1.73—1.86 (m, 1 H,
Hb(8)); 2.02 (dd, 1 H, Ha(7), J = 13.0 and 6.5 Hz); 2.35 (dd,
1 H, Hb(11), J = 13.0 and 3.0 Hz); 2.36 (m, 1 H, H(9)); 2.9
(br.s, OH); 4.47 (d, 1 H, H(5), J = 2.0 Hz); 7.22 (d, 1 H, H(4),
J = 2.0 Hz). 13C NMR, δ: 12.28 (C(12)); 24.53 (C(13)); 25.97
(C(9)); 28.66 (C(14)); 30.42 (C(10)); 36.10 (C(7)); 36.69
(C(11)); 53.49 (C(9)); 53.74 (C(6)); 55.72 (C(1)); 70.31
(C(5)); 121.54 (C(3)); 152.48 (C(4)); 193.60 (C(2)). Found:
m/z 298.05629 [M]+. C14H19BrO2. Calculated: M = 298.05689.
MS, m/z (Irel (%)): 300/298 [M]+ (36/36), 245/243 (43/43),
244/242 (30/30), 220/218 (12/12), 219 (78), 217 (13), 216
(18), 214 (11), 213 (45), 204 (19), 203 (12), 202 (10), 201 (30),
191 (13), 175 (9), 173 (11), 165 (10), 162 (38), 161 (14), 159
(13), 147 (15), 146 (27), 137 (12), 136 (24), 134 (49), 133 (38),
131 (12), 119 (16), 117 (14), 115 (11), 109 (22), 107 (37), 105
(20), 95 (12), 93 (34), 91 (42), 83 (26), 81 (24), 79 (47), 77
(40), 69 (29), 67 (22), 65 (19), 56 (33), 55 (71), 53 (34), 43
(39), 41 (100), 29 (21), 27 (29).
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Oxidation of dibromoketone 5. Dibromoketone 5 (0.01 g)
was added to a solution of 40% aqueous HBr (0.1 mL) in
DMSO (1 mL) and the resulting mixture was heated at 85 °C.
After 4 h, spots of the starting compound and compounds 6 and
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Received July 6, 2000;
in revised form April 13, 2001