Several monoterpenoid bromination products

Article abstract of DOI:10.1007/s10600-014-0984-y

2α-Bromo,10β-pinanone-3 and 3α-bromo,10β-pinanone-4 were formed with 92-98% selectivity by bromination of isopinocamphone and cis-verbanone with Meldrum's acid dibromide. 3α-Bromo, 10β-pinanone-4 was prepared for the first time. Its structure was confirmed by an XSA. Bromination of menthone by Meldrum's acid dibromide formed mainly a mixture of diastereomeric 2-bromomenthones in a 2:1 ratio. Oxidative bromination of isopinocampheol by Ce(III)-LiBr-H₂O₂ caused rearrangement of the pinane structure into bornane and formed a mixture of 6-endo- and 6-exo-bromocamphor in a 5:1 ratio.

Full text of DOI:10.1007/s10600-014-0984-y

Chemistry of Natural Compounds, Vol. 50, No. 3, July, 2014 [Russian original No. 3, May–June, 2014]
SEVERAL MONOTERPENOID BROMINATION PRODUCTS
1*
1
1
L. L. Frolova, L. V. Bezuglaya, I. N. Alekseev,
2,3
1
P. A. Slepukhin, and A. V. Kuchin
2ꢀ-Bromo,10ꢁ-pinanone-3 and 3ꢀ-bromo,10ꢁ-pinanone-4 were formed with 92–98% selectivity by
bromination of isopinocamphone and cis-verbanone with Meldrumꢂ s acid dibromide. 3ꢀ-Bromo,
10ꢁ-pinanone-4 was prepared for the first time. Its structure was confirmed by an XSA. Bromination of
menthone by Meldrum’s acid dibromide formed mainly a mixture of diastereomeric 2-bromomenthones in a
2:1 ratio. Oxidative bromination of isopinocampheol by Ce(III)–LiBr–H O caused rearrangement of the
2
2
pinane structure into bornane and formed a mixture of 6-endo- and 6-exo-bromocamphor in a 5:1 ratio.
Keywords: terpenoids, bromination, mono- and dibromo-derivatives, Meldrum’s acid dibromide, oxidative brominating
system.
ꢀ-Dicarbonyl compounds have recently become interesting for broader application in organic synthesis because of
their high reactivity. They are used to prepare aliphatic, aromatic, and heterocyclic low- and high-molecular-weight products
with an array of valuable properties. Thus, several heterocyclic compounds such as imidazoles, quinoxalines, and pyrazines,
i.e., a unique class of chiral N,N-coordinated ligands that are widely used in asymmetric synthesis [1, 2], in addition to
quinoline derivatives that usually exhibit various biological and pharmacological activities [3, 4] were synthesized from
terpene ꢀ-diketones.
Oxidation of the corresponding ꢀ-bromoketones is one method for synthesizing ꢀ-diketones. The oxidation of
3-endo-bromocamphors by O or air in aprotic polar solvents in the presence of NaI or KI to form camphoroquinone in high
2
yield is well known [5, 6]. In a similar manner, the cyclic ꢀ-diketones 1,2-cyclooctanedione and 1,2-cyclododecanedione
were synthesized in 65–71% yield from ꢀ-bromoketones [7]. It was recently shown that biotransformation of ꢀ-bromo- and
ꢀ,ꢀꢂ-dibromoketones formed highly selectively ꢀ-hydroxyketones and diketones, respectively [8].
The goal of the present work was to synthesize secondary ꢀ-bromoketones from isopinocamphone (1), cis-verbanone
(2), and menthone (3) for possible further transformation into the corresponding ꢀ-diketones. The brominating reagents were
Br , CuBr , Meldrum’s acid dibromide, and the oxidative-brominating system Ce(III)–LiBr–H O .
2
2
2 2
Br
Br
O
O
O
OH
O
Br
O
Br
O
d
a
+
+
+
1
+
Br
Br
7
1
c
4
5
8
6
9
b
Mixture of compounds
a. Br ; b. CuBr ; c. Meldrum’s acid dibromide; d. Ce(NO ) –LiBr–H O
2 2
+
5
4
3 3
2
2
Attempted monobromination of isopinocamphone by Br inAcOH (ketone–Br mole ratio 1:1) formed mainly dibromo-
2
2
derivative 4 and monobromo-derivative 5 in yields of 48 and 12%, respectively, according to GC. Furthermore, the reaction
products included pinocamphone (15%) and an insignificant (~2%) amount of 6. 2ꢀ,4ꢀ-Dibromopinanone-3 (4) was isolated
by column chromatography over silica gel as a crystalline product.
1) Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Russian Federation,
167982, Syktyvkar, Ul. Pervomaiskaya, 48, fax: (8212) 21 84 77, e-mail: frolova-ll@chemi.komisc.ru; 2) I. Ya. Postovskii
Institute of Organic Synthesis, Ural Branch Scientific Center, Russian Academy of Sciences, Russian Federation, 620990,
Ekaterinburg, Ul. S. Kovalevskoi, 22, e-mail: slepukhin@ios.uran.ru; 3) Ural Federal University, 62002, Ekaterinburg, Ul.
Mira, 19. Translated from Khimiya Prirodnykh Soedinenii, No. 3, May–June, 2014, pp. 389–393. Original article submitted
March 3, 2014.
©
0009-3130/14/5003-0449 2014 Springer Science+Business Media New York
449

TABLE 1. Bromination of Isopinocamphone (1)
Selectivity, %
Substrate:reagent
Conversion,
%
Reagent
Time, h
Solvent
T, ꢃC
mole ratio
4
5
6
Br2
CuBr2
CuBr2
1:1
1:2
1:2
2:1
5–7
80
20
3
5
9
2
AcOH
CHCl3–EtOAc
CHCl3–EtOAc
Et2O
97
94
95
95
49
7
4
12
14
16
92
2
13
4
20
4
–
Meldrum s acid dibromide
ꢂ
10
H
H
8
O
O
H
H
H
H
O
H
H
H
Br
Br
3
Br
7
7
H
H
H
7
H
H
H
H
5
5
5
4
5
4
H
H
7H
4
O
H
H
Br
H
H
Br
4
5
6
10
Fig. 1. Characteristic NOE-interactions of bromo derivatives 4–6 and 10.
The stereochemistry of 4 was found using NOE-interactions and the splitting of the H-4 resonance in the proton
spectrum [J = 3.4 Hz (w-interaction) and J = 2.4 Hz] (Fig. 1). Monobromo derivatives 5 and 6 could not be
H4–H7
H4–H5
isolated. Bromination of isopinocamphone by Meldrum’s acid dibromide did produce 5. However, 6 was identified as a minor
product in a mixture with the dibromide (4). The change of configuration of C2 in 6 was noteworthy. We supposed that this
compound was not a product of direct bromination but resulted from isomerization of 2-bromopinanone-3, which could occur
by forming a carbonium ion at C2 or with simultaneous transfer of Br from C2 to C4 and of a proton from C4 to C2. Figure 1
shows the stereochemistry of pinane bromo-derivatives that was found using NOE-interactions in NMR spectra.
The structure of 4 was confirmed by an x-ray crystal structure analysis (XSA), according to which the molecule
crystallized in a chiral space group. The absolute configuration was confirmed by estimating the anomalous scattering effect
and corresponded to the published data [9].
The ketones were brominated using CuBr at 75–80°C in CHCl –EtOAc (1:1, v/v) for 3–5 h to produce cyclic
2
3
ꢀ-bromoketones in yields up to 90% [7]. Refluxing isopinocamphone (1) with a deficiency of brominating reagent (1–CuBr
2
mole ratio 1:0.75) for 3 h produced only isomerization product pinocamphone (1:4 equilibrium mixture) and practically no
bromination products. A complicated product mixture resulted with a substrate–CuBr ratio of 1:2 upon refluxing (5 h) and at
2
room temperature (9 h). GC identified pinocamphone (25–26%), monobromination products 5 and 6, and dibromo derivative
4 (Table 1). Two compounds amounting to 8–9% were not identified.
Next, 1 was brominated by Meldrum’s acid dibromide, which is a mild brominating reagent that was used to synthesize
aliphatic ꢀ-bromoaldehydes in the only example of its type [10]. Compound 1 was brominated in anhydrous Et O at room
2
temperature for 2 h with a ketone–dibromide mole ratio of 2:1. The reaction turned out to be rather selective with 95%
conversion. The products contained the monobromo derivative (5, 87%) and the dibromide (4, ~4%). Compound 5 was
isolated by chromatography over silica gel as a colorless oil that crystallized upon cooling. This compound was prepared
earlier via bromination of 1 enol-acetate by Br in CCl in 57% yield [11]. Table 1 presents the results for bromination of 1.
2
4
The oxidative-brominating system Ce(III)–LiBr–H O was used to synthesize ketones (with a catalytic amount of
2
2
LiBr) and ꢀ-bromoketones (with a stoichiometric amount of LiBr) from aliphatic alcohols [12]. We used this method for
oxidative bromination of isopinocampheol (7).
The reaction was carried out in aqueous MeCN (80%) at 70–72°C with a 7–Ce(NO ) –LiBr–H O mole ratio of
3 3
2 2
2:1:2:20 and formed a mixture of 1 and two monobromo bornane derivatives 6-endo- (8) and 6-exo-bromocamphor (9). GC
showed that starting 7 was 84% converted after 3 h with the main product being 1 (62%). The amount of ketone decreased to
56% and that of the bromo derivatives increased to 35% after 7 h with complete conversion of the alcohol. The reaction
mixture contained only ~16% of 1 and a total of 63% of 8 and 9 after 13 h. The amount of side products increased. The content
of the 6-exo-isomer (9) increased during the oxidation. Chromatography over SiO isolated pure 1 whereas 8 and 9 could not
2
be separated. Therefore, their spectral characteristics were taken as the mixture. Spectral data for the 6-endo-isomer are
known because it was obtained earlier via isomerization of 3-endo-bromocamphor and oxidation of 6-endo-Br-isoborneol,
which was prepared via the reaction of cis-pinocarveol and HBr [13, 14].
450

O1
C4
C1
C9
C6
C5
C2
C8
C3
C7
Br1
C10
Fig. 2. Structure of 3ꢀ-bromopinanone-4 (10) from an x-ray crystal
structure analysis with 50% probability thermal ellipsoids.
Bromination of 2, which was prepared beforehand via 1,4-conjugate reduction of verbenone, using CuBr produced
2
an even more complicated product mixture than that of 1. However, monobromo derivative 3ꢀ-bromo-10ꢁ-pinanone-4 (10)
was formed with 98% selectivity if Meldrum’s acid dibromide was used. Compound 10 was prepared for the first time. Its
structure was confirmed by NMR methods. Spectra showed the CH–CH linkage and methine CH–Br. The configurations of
3
C2 and C3 were found from NOE-interactions H-10–H-8 and H-3–H-8 (Fig. 1).
Br
a
O
O
2
10
a. Meldrum’s acid dibromide
The structure of 10 was confirmed by an XSA (Fig. 2). The compound crystallized in a centrosymmetric monoclinic
space group. The grown crystal contained a racemate because the starting cis-verbanone was not a pure enantiomer. The bond
lengths and angles were in general analogous to the previously examined 2ꢀ,4ꢀ-dibromopinanone-3 (4). The packing of 10
included no specific intermolecular contacts.
Bromination of 3 by Meldrum’s acid dibromide at room temperature occurred rather rapidly (100% conversion after
1 h). However, it formed a complicated product mixture. Lowering the temperature to 0°C reduced the conversion to 90%
(4 h). However, the reaction was more selective. The main products were epimers 11 and 12, which were formed in a 2:1 ratio
and totaled 71–74% according to GC. The amount of C6 monobromination product (13) was insignificant (7–8%). Compounds
11 and 12 were isolated relatively pure (86 and 90%, respectively) by column chromatography over SiO . The structure of 13
2
was determined in a mixture with 11.
Br
a
+
+
O
O
O
O
Br
Br
11
a. Meldrum’s acid dibromide
3
12
13
Isomers 11–13 had very different NMR spectra. The trans- and cis-isomers 11 and 12 had a single set of resonances
and differed like menthone and isomenthone in the splitting constants and NOE-interactions. On the other hand, 13 displayed
a different set of resonances from two methylenes and four methines. This indicated unambiguously that the reaction occurred
at the C6 methylene.
Camphor was practically not brominated by mild Meldrum’s acid dibromide at room temperature. The obtained
3ꢀ-bromopinanone-4 (10) will be used in the future to synthesize the corresponding diketone.
EXPERIMENTAL
GC analysis was performed on a Shimadzu GC-2010AF chromatograph with an HP1 column, flame-ionization detector,
and He carrier gas. IR spectra were taken from a thin layer or KBr pellets on a Shimadzu IR Prestige 21 instrument. NMR
451

spectra were recorded in CDCl and DMSO-d using standard Bruker pulse sequences on a Bruker Avance-II-300 instrument
3
6
1
13
at operating frequency 300 MHz for H and 75 MHz for C. Melting points were determined using a TP apparatus. Optical
rotation was determined on a P3002RS automated polarimeter (Kruss, Germany).
XSA was performed on an Xcalibur S automated four-circle x-ray diffractometer with a CCD-detector using the
standard procedure [295(2) K, Mo Kꢀ-radiation, graphite monochromator, ꢄ-scanning, scan step 1°]. An empirical absorption
correction [15] was used for 4. The absorption correction for 10 was applied analytically using a multi-faceted crystal model
[16]. The structures were solved and refined using the SHELXTL 5.1 program set by full-matrix least-squares methods over
2
F [17]. All non-hydrogen atoms were refined anisotropically. H atoms were placed in geometrically calculated positions and
were included in the refinement as a rider model with dependent thermal parameters.
The XSA results were deposited in the Cambridge Crystallographic Data Centre under Nos. 996304-996305. The
data can be accessed free by a request to www.ccdc.cam.ac.uk.
°
Compound 10 crystallized as white prisms in monoclinic space group P2 /c, a = 7.4211(5) A , b = 18.998(3),
1
° 3
3
–1
c = 8.0046(11), ꢁ = 116.470(11)°, V = 1010.2(2) A , for C H BrO Z = 4, d
= 1.768 g/cm , ꢅ = 4.022 mm ,
10 14
calcd
F(000) = 472. A data set of 5659 reflections at scattering angles 3.04° < ꢆ < 28.28° was collected. Of these, 2411 were
independent [R(int) = 0.0256] including 1116 with I > 2 (I). The experiment was 98.1% complete for ꢆ = 26°. The final
refinement parameters were R = 0.0325 and wR = 0.0563 [for reflections with I > 2 (I)] and R = 0.0926 and wR = 0.0591
1
2
1
2
(for all reflections) with quality factor S = 0.997. Peaks of maximum and minimum electron density were 0.357 and
° 3
–0.409 e/A .
Column chromatography used silica gel 60 (70–230 mesh, Alfa-Aesar). TLC was performed on Sorbfil plates using
hexane and petroleum ether–Et O eluents and phosphomolybdic acid (10%) in EtOH and vanillin (3%) in EtOH as detectors.
2
Freshly distilled solvents were used. Compounds 7 and 1 were prepared by hydroboration of ꢀ-pinene followed by oxidation
of the organoboron compounds by H O in basic solution or chromic acid as before [18]. Meldrum’s acid dibromide was
2
2
prepared by the literature method [19].
1,4-Conjugate Reduction of Verbenone. A solution of verbenone (3 g, 0.02 mol) and NiCl 46H O (1.19 g,
2
2
0.005 mol) in MeOH (50 mL) was cooled to 0°C and treated in portions over 1 h with NaBH (1.52 g, 0.04 mol) keeping the
4
temperature at 0–7°C. The reaction was monitored by TLC. After the verbenone spot disappeared, the mixture was filtered
through a Schott filter. The bulk of the MeOH was removed. The residue was diluted in a small amount of H O and Et O
2
2
[conc. HCl (2 drops) was added to destroy the emulsion]. The Et O extracts were washed with saturated NaCl solution and
2
dried over MgSO . The solvent was removed to afford the products (2.88 g, 94%) with 87% of the main compound. The
4
ketone was isolated by column chromatography over SiO .
2
cis-Verbanone (2). Yield 2.07 g, 69%, [ꢀ] +17.1° (c 0.9, EtOH) from verbenone with [ꢀ] +106° (c 0.8, EtOH,
D
D
–1
ee 37%). IR spectrum (ꢇ, cm ): 2951, 2914, 2877, 1712 (C=O), 1469, 1413, 1379, 1303, 1251, 1199, 1101, 1039, 981.
Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 0.96 (s, CH -8), 1.13 (d, J = 7.4, CH -10), 1.32 (s, CH -9), 1.40 (1H, d, J = 10.3,
1
3
3
3
3
H-7
), 2.07 (1H, dd, J = 4.6, 19.7, H-3 ), 2.09 (1H, m, H-1), 2.34 (m, H-2), 2.40 (1H, dd, J = 5.2, 5.4, H-5), 2.57 (1H, m,
endo
exo
13
J = 5.4, 10.3, H-7 ), 2.85 (1H, dd, J = 10.2, 19.7, H-3
). C NMR spectrum (CDCl , ꢈ, ppm): 213.07 (C-4), 57.74 (C-5),
exo
endo
3
47.35 (C-1), 41.41 (C-3), 40.24 (C-6), 30.80 (C-2), 28.02 (C-7), 27.18 (C-9), 24.77 (C-8), 21.33 (C-10).
Bromination of 1 by Br in AcOH. A solution of 1 (0.9 g, 0.0059 mol) {[ꢀ] +6° (c 1.0, EtOH)} in glacial AcOH
2
D
(20 mL) was stirred, cooled to 5–7°C, treated dropwise with a solution of Br (1 g) in AcOH (5 mL), and stirred for 3 h. The
2
products were extracted by Et O, washed with H O and saturated NaHCO solution, dried over MgSO , analyzed by GC, and
2
2
3
4
isolated by chromatography over SiO .
2ꢀ,4ꢀ-Dibromopinanone-3 (4). Yield 30%, mp 70–75ꢃC, [ꢀ] +27.7ꢃ (c 0.5, EtOH). IR spectrum (ꢇ, cm ): 2937,
1726 (C=O), 1469, 1446, 1373, 1315, 1249, 1170, 1112, 1074, 1041, 991, 931, 840, 779, 717 (C-Br), 636, 513. Í NMR
2
–1
D
1
spectrum (CDCl , ꢈ, ppm, J/Hz): 0.96 (s, CH -8), 1.48 (s, CH -9), 2.02 (s, CH -10), 2.45 (1H, d, J = 12.0, H-7
dd, J = 3.4, 6.0, H-5), 2.54 (1H, dd, J = 6.0, 6.0, H-1), 2.72 (1H, m, J = 12, H-7), 4.66 (1H, dd, J = 2.4, 3.4, H-4). C NMR
), 2.47 (1H,
3
3
3
3
endo
13
spectrum (CDCl , ꢈ, ppm): 201.3 (C-3), 67.9 (C-2), 53.3 (C-1), 50.6 (C-4), 46.6 (C-5), 40.8 (C-6), 32.0 (C-7), 29.3 (C-10),
3
28.1 (C-9), 22.2 (C-8).
1
4ꢀ-Bromo,10ꢀ-pinanone-3 (6). Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 0.94 (3H, s, CH -8), 1.23 (3H, d, J = 7,
3
3
CH -10), 1.42 (3H, s, CH -9), 1.60 (1H, d, J = 11, H-7ꢂ), 2.00 (1H, m, H-1), 2.50 (2H, m, H-5, 7ꢂꢂ), 2.80 (1H, m, H-2), 4.74
3
3
13
(1H, m, H-4). C NMR spectrum (CDCl , ꢈ, ppm): 208.7 (C-3), 54.8 (C-4), 47.7 (C-5), 46.6 (C-2), 44.1 (C-1), 41.3 (C-6),
3
27.0 (C-7), 26.7 (C-9), 19.4 (C-8), 15.9 (C-10).
452

General Method for Bromination of 1 and 2 by CuBr . A solution of 1 or 2 (1 g, 0.0066 mol) in CHCl –EtOAc
2
3
(1:1, v/v, 20 mL) was stirred at 75–80°C in a stream of inert gas and treated in portions with powdered CuBr (2.95 g,
2
0.0132 mol). Each CuBr portion was added after the green color disappeared. Then, the reaction mixture was cooled. The
2
CuBr was filtered off. The solvents were removed. The residue was dissolved in Et O, washed with Na CO solution (5%)
2
2
3
and saturated NaCl solution, dried over MgSO , and analyzed by GC.
4
General Method for Bromination of 1–3 by Meldrum’s Acid Dibromide. A solution of 1, 2, or 3 (1 g,
0.0066 mol), Meldrum’s acid dibromide (1 g, 0.0033 mol), and Br (1 drop) in anhydrous Et O (30 mL) was stirred under an
2
2
inert atmosphere at room temperature (for menthone, at 0°C) for 2, 9, or 4 h, respectively. When the reaction was finished
(TLC monitoring), the mixture was washed with saturated NaHCO and NaCl solutions and dried over MgSO . The solvent
3
4
was removed. The products were analyzed by GC and isolated by column chromatography over SiO .
2
2ꢀ-Bromo,10ꢁ-pinanone-3 (5). Yield 61%, R 0.76 (hexane–Et O, 2:1), colorless oil that crystallized upon cooling,
f
2
–1
mp 31–32ꢃÑ, [ꢀ] +167.8ꢃ (c 0.4, EtOH) from 1 with [ꢀ] +11.2ꢃ. IR spectrum (ꢇ, cm ): 2978, 2933, 2875, 1722 (C=O),
1469, 1446, 1409, 1373, 1319, 1263, 1240, 1207, 1143, 1097, 1047, 943, 914, 829, 709 (C-Br), 626, 534. Í NMR spectrum
D
D
1
(CDCl , ꢈ, ppm, J/Hz): 0.94 (s, CH -8), 1.41 (s, CH -9), 1.98 (d, J = 11.0, H-7 ), 2.01 (s, CH -10), 2.16 (1H, m, H-5), 2.53
3
3
3
endo
3
(1H, dd, J = 6.1, 6.2, H-1), 2.68 (1H, m, J = 11, H-7 ), 2.70 (1H, dd, J = 18.7, H-4), 2.85 (1H, dd, J = 2.2, 18.7, H-4).
exo
13
C NMR spectrum (CDCl , ꢈ, ppm): 205.7 (C-3), 71.2 (C-2), 53.8 (C-1), 43.0 (C-4), 40.2 (C-6), 38.4 (C-5), 34.3 (C-7), 28.8
3
(C-10), 27.6 (C-8), 22.8 (C-9).
3ꢀ-Bromo,10ꢁ-pinanone-4 (10). Yield 62%, R 0.64 (hexane–Et O, 1:1), [ꢀ] +14.5ꢃ (ñ 0.9 EtOH). IR spectrum (ꢇ,
f
2
D
–1
1
cm ): 2957, 2878, 1722 (C=O), 1468, 1381, 1248, 1196, 1171, 756 (C-Br), 623, 501. Í NMR spectrum (CDCl , ꢈ, ppm,
3
J/Hz): 1.05 (3H, s, CH -8), 1.33 (3H, d, J=7.4, CH -10), 1.40 (3H, s, CH -9), 1.79 (1H, d, J = 10.9, H-7 ), 2.22 (1H, ddd,
3
3
3
endo
J = 2.5, 5.8, 8.3, H-1), 2.76 (1H, m, J = 10.9, 8.3, H-7 ), 2.80 (1H, m, J = 7.4, 5.2, H-2), 2.87 (1H, dd, J = 5.8, 5.5, H-5), 4.29
exo
13
(1H, d, J = 5.2, H-3). C NMR spectrum (CDCl , ꢈ, ppm): 206.35 (C-4), 58.62 (C-5), 51.48 (C-3), 48.29 (C-1), 45.50 (C-2),
3
40.38 (C-6), 28.81 (C-7), 26.76 (CH -9), 25.05 (CH -8), 19.29 (CH -10).
3
3
3
–1
2-Bromomenthone (11). Yield 35%. IR spectrum (ꢇ, cm ): 2958, 2929, 2873, 1712 (C=O), 1456, 1381, 1369,
1342, 1259, 1207, 1126, 1087, 991, 948, 875, 812 (C-Br), 719, 651, 557, 509. Í NMR spectrum (DMSO-d , ꢈ, ppm, J/Hz):
1
6
0.90 (3H, d, J = 6.7, CH -10), 0.98 (3H, d, J = 6.3, CH -7), 1.08 (3H, d, J = 6.7, CH -9), 1.61 (1H, m, H-6ꢂ), 1.78 (1H, m,
3
3
3
H-6), 1.81 (1H, m, H-1), 1.96 (1H, ddd, J = 4.0, 7.0, 15.5, H-5ꢂ), 2.20 (1H, ddd, J = 3.3, 6.7, 15.5, H-5), 2.28 (1H, ddd, J = 2,
13
4, 14, H-2ꢂ), 2.41 (1H, sept, J = 6.7, H-8), 2.77 (1H, ddd, J = 12, 14, H-2). C NMR spectrum (DMSO-d , ꢈ, ppm): 203.4 (C-3),
6
78.5 (C-4), 45.4 (C-2), 34.3 (C-8), 34.2 (C-5), 32.9 (C-1), 30.0 (C-6), 22.1 (C-7), 19.3 (C-9), 18.6 (C-10).
–1
2-Bromoisomenthone (12). Yield 16%. IR spectrum (ꢇ, cm ): 2958, 2933, 2873, 1716 (C=O), 1458, 1384, 1330,
1
1251, 1199, 1111, 1031, 887, 812 (C-Br), 567. Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 1.00 (3H, d, J = 6.5, CH -7), 1.03
3
3
(3H, d, J = 6.6, CH -8), 1.07 (3H, d, J = 6.6 CH -10), 1.61 (1H, m, H-6ꢂ), 2.02 (1H, m, H-6ꢂꢂ), 2.18–2.30 (3H, m, H-1, 2ꢂ, 5ꢂ),
3
3
13
2.37–2.50 (2H, m, H-5ꢂ, 8), 3.00 (1H, m H-2ꢂꢂ). C NMR spectrum (CDCl , ꢈ, ppm): 204.2 (C-3), 80.9 (C-4), 45.6 (C-2), 35.7
(C-5), 33.4 (C-1), 32.6 (C-8), 29.3 (C-6), 20.3 (C-7), 18.8 (C-9), 17.9 (C-10). Í NMR spectrum (DMSO-d , ꢈ, ppm, J/Hz):
3
1
6
0.82 (3H, d, J = 6.5, CH -9), 0.93 (3H, d, J = 6.7, CH -7), 0.98 (3H, d, J = 6.5, CH -10), 1.57 (1H, m, H-6ꢂ), 1.76 (1H, m,
3
3
3
H-6ꢂꢂ), 2.05 (1H, m, H-1), 2.12 (1H, m, H-5ꢂ), 2.32 (1H, dd, J = 7.5, 14, H-2ꢂ), 2.40 (1H, m, H-8), 2.48 (1H, m, H-5ꢂꢂ), 2.69
13
(1H, dd, J = 5, 14, H-2ꢂꢂ). C NMR spectrum (DMSO-d , ꢈ, ppm): 204.4 (C-3), 84.3 (C-4), 46.0 (C-2), 37.4 (C-5), 33.2
6
(C-1), 32.8 (C-8), 29.6 (C-6), 20.7 (C-7), 19.0 (C-9), 18.1 (C-10).
1
6-Bromomenthone (13). Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 0.89 (3H, d, J = 6.8, CH -9), 0.96 (3H, d,
3
3
J = 6.8, CH -10), 1.12 (3H, d, J = 6.2, CH -7), 1.37 (1H, m, H-5ꢂ), 1.68 (1H, m, H-6ꢂ), 1.76 (1H, m, H-6ꢂꢂ), 1.89 (1H, m, J = 6.2,
3
3
13
H-1), 2.05 (1H, m, H-5ꢂꢂ), 2.14 (1H, m, J = 6.8, H-8), 3.04 (1H, m, H-4), 4.26 (1H, dd, J = 1.3, 3.2, H-2). C NMR spectrum
(CDCl , ꢈ, ppm): 206.10 (C-3), 62.15 (C-2), 48.98 (C-4), 38.59 (C-1), 27.97 (C-6), 27.70 (C-5), 25.84 (C-8), 20.93 (C-10),
3
19.50 (C-7), 18.64 (C-9).
Oxidative Bromination of 7 by Ce(NO ) –LiBr–H O . A solution of 7 (1 g, 0.0033 mol), Ce(NO ) 46H O (1.41 g,
3 3
2
2
3 3
2
0.043 mol), and LiBr (0.56 g, 0.0066 mol) in aqueous MeCN (80%, 30 mL) was stirred at 70°C and treated dropwise with a
solution of H O (50%) in H O (20 mL). Each H O portion was added after the brown color disappeared. The course of the
2
2
2
2 2
reaction was monitored by TLC and GC. Then, the reaction mixture was cooled and extracted with Et O. The extract was
2
washed with H O, and dried over MgSO . The products were isolated by column chromatography.
2
4
Isopinocamphone (1). Yield 10%, identified by GC and IR spectrum. The mixture of 8 and 9 (5:1 ratio), yield 25%,
–1
light-yellow crystalline compound. IR spectrum (ꢇ, cm ) (total): 2964, 2873, 1749 (C=O), 1718 (C=O), 1448, 1415, 1375,
1323, 1296, 1271, 1238, 1116, 1095, 1051, 1006, 914, 856, 785 (C-Br), 719, 628, 547, 511.
453

1
6-endo-Bromocamphor (8). Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 0.94 (3H, s, CH -8), 1.00 (3H, s, CH -10),
3
3
3
1.02 (3H, s, CH -9), 1.90 (1H, dd, J=3.3, 14.3, H-5), 2.05 (1H, d, J = 18.5, H-3), 2.22 (1H, dd, J = 4.5, 4.6, H-4), 2.47 (1H,
3
13
dddd, J = 1.5, 3.4, 7.9, 18.5, H-3), 2.85 (1H, m, J = 10.1, 14.3, H-5), 4.22 (1H, dd, J = 3.4, 10.1, H-6). C NMR spectrum
(CDCl , ꢈ, ppm): 213.7 (C-2), 63.6 (C-6), 51.0 (C-1), 47.9 (C-7), 42.9 (C-3), 42.4 (C-4), 40.1 (C-5), 21.0 (C-8), 19.3 (C-9),
3
7.7 (C-10).
1
6-exo-Bromocamphor (9). Í NMR spectrum (CDCl , ꢈ, ppm, J/Hz): 1.22 (3H, s, CH -9), 1.25 (3H, s, CH -8),
3
3
3
1.88 (3H, s, CH -10), 2.30 (1H, m, H-4), 2.55 (1H, m, H-5), 2.66 (1H, ddd, H-3), 2.85 (1H, m, H-5), 2.92 (1H, m, H-3), 4.34
3
13
(1H, d, J = 6, H-6). C NMR spectrum (CDCl , ꢈ, ppm): 204.9 (C-2), 84.3 (C-1), 82.7 (C-6), 62.7 (C-7), 42.4 (C-4), 41.1
3
(C-3), 34.1 (C-5), 29.0 (C-8), 25.1 (C-9), 24.0 (C-10).
ACKNOWLEDGMENTS
The work was financed in part by the Ural Branch, Russian Academy of Sciences, Grant No. 12-U-3-1015.
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