Direct Oxidation of Cyclopropanated Cyclooctanes as a Synthetic Approach to Polycyclic Cyclopropyl Ketones

Article abstract of DOI:10.1002/ejoc.201701671

A series of polycyclic hydrocarbons containing cyclopropane moieties 1,2-annelated or spiro-condensed with a cyclooctane ring were investigated under oxidative conditions. Four oxidizing systems (O₃ on SiO₂, a dioxirane derived from trifluoroacetone, CrO₃, and RuO₄, generated in situ), were tested to evaluate and compare their reactivity and usefulness. RuO₄ was found to be the best of them, considering its oxidative power together with the simple operating procedure. Conditions for the specific oxidation of polycyclic hydrocarbons were found. New cyclooctane derivatives containing cyclopropyl carbonyl moieties were obtained.

Full text of DOI:10.1002/ejoc.201701671

A Journal of
Accepted Article
Title: Direct oxidation of cyclopropanated cyclooctanes as a synthetic
approach to polycyclic cyclopropylketones
Authors: Kseniya N. Sedenkova, Kristian S. Andriasov, Svetlana
A. Stepanova, Igor P. Gloriozov, Yuri Grishin, Tamara S.
Kuznetsova, and Elena B. Averina
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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to this Accepted Article as a result of editing. Readers should obtain
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content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701671
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701671
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
FULL PAPER
Direct oxidation of cyclopropanated cyclooctanes as a synthetic
approach to polycyclic cyclopropylketones
Kseniya N. Sedenkova,[a,b] Kristian S. Andriasov,[a] Svetlana A. Stepanova,[a] Igor P. Gloriozov,[a] Yuri K.
Grishin,[a] Tamara S. Kuznetsova,[a] Elena B. Averina*[a,b]
Abstract:
A
series of polycyclic hydrocarbons containing
O
O
cyclopropane moieties 1,2-annelated or spiro-condensed with
cyclooctane ring were investigated under oxidative conditions. Four
oxidizing systems (O3 on SiO2, dioxirane derived from
trifluoroacetone, CrO3 and RuO4, generated in situ), were employed
to evaluate and compare their reactivity and usefulness. RuO4 was
found to be the best one, considering its oxidative power together
with a simple preparative procedure. The conditions for specific
oxidation of polycyclic hydrocarbons were found. Novel cyclooctane
derivatives containing cyclopropyl carbonyl moieties were obtained.
O
HN
N
O
NH
Tasimelteon
Ciproxifan
(melatonin receptor agonist)
(brain H3-receptor antagonist)
H3CO
H2N
N
O
O
O
O
O
O
N
S
F
N
N
H
H
Introduction
Cl
Lenvatinib
(tyrosine kinase inhibitor)
Prasugrel
(platelet inhibitor)
Cyclopropane ring is an outstanding moiety which combines a
unique structure and bonding characteristics. Due to its high
strain cyclopropane may be involved in a variety of chemical
transformations that makes functionalized cyclopropanes
extremely valuable starting compounds with a diverse reactivity,
widely employed in organic and especially heterocyclic
synthesis.[1] Polycyclic cyclopropylketones can be used as
starting material for the preparation of unique strained molecules,
such as rotanes and triangulanes.[2]
Figure 1. Examples of cyclopropane-containing clinical drugs.
Taking these facts into account, the need for the efficient
practical methods of cyclopropanes functionalization is evident.
Selective oxidation of C(sp3)H2 groups activated by adjacent
cyclopropane moiety represents
a
direct approach to
The application of cyclopropane derivatives in a rational drug-
cyclopropylketones, in accordance with a principle of atom-
economy allowing to reduce synthetic steps.[7] Most of
preparative methods of cyclopropane-containing compounds
oxidation into cyclopropylketones employ such powerful oxidants
as ozone[2a,8], dioxiranes,[9] chromium (VI)[10] and ruthenium (VIII)
oxides[11] as the sources of oxygen; catalytic methods of
oxidation[12] also are used. Nevertheless, though the oxidation of
cyclopropane-containing compounds was described in a number
of works, a systematic study of these processes has been never
made previously. In this connection, the aim of the present work
design can hardly be overestimated.
A large number of
examples exist showing the improvement of pharmaceutical
properties of the molecules after incorporation of a three-
membered ring (Figure 1).[3] The most usual grounds for
introducing cyclopropane moiety is reducing the conformational
flexibility in order to improve binding properties and ligands
selectivity,[4] to increase chemical and metabolic stability,[5] for
fine tuning of hydro/lipophilicity.[6]
was to investigate
a
series of cyclopropane-containing
cyclooctanes under the treatment of various oxidizing systems in
order to compare their reactivity and practical use.
Results and Discussion
[a]
[b]
K. N. Sedenkova, K. S. Andriasov, S. A. Stepanova, I. P. Gloriozov,
Y. K. Grishin, E. B. Averina, T. S. Kuznetsova
Department of Chemistry
Lomonosov Moscow State University
119991, Leninskie Gory 1-3, Moscow, Russian Federation
E-mail: elaver@med.chem.msu.ru
Four available and widely used oxidative systems were chosen
for this work: O3 adsorbed on SiO2 (method of “dry”
ozonation),[2a,8,13] TFDO (methyl(trifluoromethyl)dioxirane),[9,14]
[10]
and RuO4, generated in situ from RuCl3 and NaIO4.[11]
K. N. Sedenkova, E. B. Averina
CrO3
Institute of Physiologically Active Compounds RAS
142432, Severnyi Proezd 1, Chernogolovka, Moscow Region,
Russian Federation
Under selected oxidative conditions hydrocarbons containing
three-membered rings annelated with cyclooctane were studied
in order to compare the oxidative power and selectivity of the
systems under investigation and the reactivity of CH2-groups
adjacent to 1,2-annelated or spiro-annelated cyclopropanes. The
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
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possibility to obtain the products of multiple oxidation was also
studied.
Oxidation of tricyclododecane 4[16] under the conditions of “dry”
ozonation afforded selectively ketone 5, which could not be
oxidized further on exposure to ozone (Table 2). The same
result was obtained after the treatment with TFDO. The cis-
orientation of cyclopropane rings was proven by DFT
calculations of energy and 1H NMR parameters for ketone 5 (see
SI). In the case of CrO3 and RuO4 the formation of diketone 6
was observed. The optimal conditions affording the double
oxidation product demand the treatment of 4 with RuO4 at 60 oC
for 7 h.
Bicyclononane 1[15] was the first hydrocarbon to be
systematically studied under various oxidative conditions (Table
1). Though discrete literature data[8a,9c,11a] exist for the oxidation
of hydrocarbon 1, it seemed reasonable to check up their
reproducibility. The best results were obtained with ozone or
RuO4, generated in situ from RuCl3: the reactions selectively
afforded the product of activated α-CH2 group oxidation –
cyclopropylketone 2.[8a] Oxidation of hydrocarbon 1 by CrO3 also
led to ketone 2, but the yield was lower due to decomposition of
the organic material in the reaction media. At last, the treatment
of compound 1 with TFDO provided the mixture of oxidation
products 2 and 3 with alcohol 3[9c] being the major component.
The oxidation of spirocyclodecane 7[17] was also studied (Table
3). It was shown that in all cases the main product was ketone
8[18], which resulted from the oxidation of α-CH2 group adjacent
to spiro-linked cyclopropane. The product of the oxidation of β-
site, compound 9[19], was also detected in small amounts. Yet,
no traces of the product of the double oxidation were to be found
in the reaction mixtures. The most efficient and selective
methods include the oxidation by ozone and RuO4, while TFDO
showed rather poor selectivity (8:9 3:0.8), and the application of
CrO3 led to low yield of the product due to decomposition of
organic material.
Table 1. Oxidation of bicyclo[6.1.0]nonane (1)
O
OH
[O]
+
1
2
3
Table 3. Oxidation of spirocyclodecane 7
Conditions
Conversion, %
Yield 2,[a]
%
Yield 3, [a]
%
O
O
O3/SiO2, -50 oC, 2 h
TFDO, -20 °C, 2 h
29
58
19
10
-
[O]
+
84
30
-
7
8
9
CrO3, CH2Cl2/CH3CN,
0 oC, 2 h
100
Conditions
Conversion, %
Yield 8, %[a]
Yield 9, %[a]
RuCl3, NaIO4, r.t., 24
h[b]
91
46
-
O3/SiO2, -50 oC, 1 h
TFDO, -20 °C, 2 h
51
80
89
67
54
30
4
14
4
[a] Isolated yield calculated from consumed 1. [b] RuO4 is generated in situ.
CrO3, CH2Cl2/CH3CN,
0 °C, 6 h
RuCl3, NaIO4, r.t., 24 h
93
60
3
Table 2. Oxidation of tricyclodecane 4.
[a] Isolated yield calculated from consumed 7.
O
O
[O]
+
It is interesting to compare the oxygenation processes in the
case of compounds 7 and 10, the analogue with a cyclohexane
core. According to the literature data, oxidation of 10 under
treatment with TFDO affords monoketone 11[9c] together with
small amounts of the isomeric spiro[2.5]octan-5-one and -6-one
(3% and 4%, respectively) (Scheme 1). “Dry” ozonation of this
hydrocarbon gives also the product of the double oxidation 12 in
notable amount,[8a] while no traces of diketone were found in the
case of spiro compound 7. Thus, the activation of α-position is
more efficient when a six-membered ring is spiro-annelated with
cyclopropane.
5
4
6
O
Conditions
Conversion, %
Yield 7, %[a]
Yield 8, %[a]
O3/SiO2, -50 oC, 1 h
TFDO, -20 °C, 2 h
51
60
62
53
0
90
0
CrO3,
0 °C, 6 h
CH2Cl2/CH3CN,
100
12
RuCl3, NaIO4, r.t., 24 h
RuCl3, NaIO4, 60 oC, 7 h
100
100
20
0
21
35
[a] Isolated yield calculated from consumed 4.
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
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(A) O3/SiO2, -50 oC
or
(B) TFDO, 0 oC, 35 min
Table 4. Oxidation of dispirocyclododecane 17
O
O
O
O
+
[O]
10
11, 64% (A); 12, 27% (A);
90% (B) 0% (B)
17
18
Scheme 1. Oxidation of spirocyclooctane 10 (for the method
A – the
composition of the reaction mixture is given;[8a] for the method B the yield
Yield 18, %[a]
calculated from reacted 10 is given (conversion 42%)[9c]).
Conditions
Conversion, %
O3/SiO2, -50 oC, 1 h
TFDO, -20 °C, 2 h
93
71
-
26
53
-
An alternative route to diketone 14 was elaborated using the
cyclic dialkylation of cyclooctane-1,3-dione (13) under the
treatment with dibromoethane in the presence of K2CO3 in
DMSO (Scheme 2). The side O-alkylation of ketone gave the
vinyl ether 15 as a by-product in 14:15 ratio 1:0.6. It should be
noted that this reaction, though widely used for open-chain
compounds, is not trivial for cyclic diketones. To the best of our
knowledge, the only dicarbonyl compound that could be involved
into this process was 1H-indene-1,3(2H)-dione,[20] while alicyclic
compounds such as cyclohexane-1,3-dione[21] and dimedone[20]
could not be dialkylated under the treatment with dibromoethane
and formed exclusively O-alkylation products.
CrO3, CH2Cl2/CH3CN,
0 °C, 6 h
RuCl3, NaIO4, r.t., 24 h
100
74
[a] Isolated yield calculated from consumed 17.
The subsequent oxidation of ketone 18 with RuO4 (but not
with O3 or TFDO) led slowly to the mixture of diketones 19 and
20 (Scheme 4). This again makes the difference from a more
reactive analogous tricycle based on cyclohexane, ozonation of
which afforded the mixture of monoketone and isomeric
diketones in a similar ratio.[8a]
O
O
O
BrCH2CH2Br
O
O
O
Br
+
K2CO3, DMSO
13
14, 24%
15, 14%
O
O
O
RuCl3, NaIO4
60 oC, 36 h
18
+
Scheme 2. Alkylation of cyclooctane-1,3-dione (13).
conversion 23%
20, 17%
19, 19%
O
Previously unknown tricyclic hydrocarbon 17 was obtained from
the diketone 16 via the sequence of Wittig methylenation and
Scheme 4. Oxidation of ketone 18.
Simmons-Smith
(Scheme 3).
cyclopropanation
employing
diethylzinc
OH
[23]
TFDO[23]
O
23, 3%
+
24, 25%
CrO3
1. [Ph3PCH3]+Br-,
NaH, DMSO, 68%
O
O
2. CH2I2, Et2Zn,
21
O
O
benzene, 60 oC, 6 h, 43%
22, 16%
and polyketones
17
RuCl3/NaIO4
CH3CN/CCl4
phosphate buffer
16
24 h
60 oC
Scheme 3. Synthesis of dispirocyclododecane 17.
O
O
The oxidation of compound 17 demonstrated the tendencies
similar to those characteristic for the compound 4, but
dispirocyclic hydrocarbon appeared to be less reactive in the
oxidation processes (Table 4). Product of monooxidation 18 was
obtained by most of the methods and oxidation with RuO4
provided the best result, but in the case of CrO3 complete
destruction of starting cyclopropane took place. Under all the
conditions no products of polyoxidation were formed.
+
O
O
24, 54%
23, 36%
Scheme 5. Oxidation of tetraspirocyclic hydrocarbon 21.
The synthesis and oxygenation of tetraspirocyclic hydrocarbon
21 via various methods was previously reported by our
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
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group.[22,23] The most complete oxidation was achieved when
using TFDO and triketoalcohol 22 was obtained among other
products (Scheme 5).
were measured on Jeol GCMate II mass spectrometer (70 eV). Infrared
spectra were recorded with a Thermo Nicolet FTIR-200 spectrometer.
Analytical thin layer chromatography was carried out with silica gel plates
(supported on aluminum); the detection was done by UV lamp (254 nm).
Column chromatography was performed on silica gel (0.015-0.04 mm).
Hydrocarbons 1[15], 6[16], cyclooctane-1,3-dione (15)[24] and cyclooctane-
Encouraged by the abovementioned results of oxidation of 4 and
18, we investigated the compound 23 in the reaction with RuO4
generated in situ (Scheme 5). The oxidation under the standard
conditions (r.t., 24 h) afforded the mixture of monoketone, 1,3-
diketone 23 and 1,5-diketone 24 in 1:3:4 ratio. The increase of
the reaction time up to 72 h or the reaction temperature up to 60
oC gave the mixture of diketones 23, 24 in 1:1.5 ratio, and
though monoketone was not present, further oxidation did not
proceed. This oxidant did not surpass the oxidizing ability of
CrO3, though it should be noted that the preparative yields
increased significantly. The fact that the reaction terminated
after the insertion of two carbonyl groups may be explained by
steric hindrances of the oxidized CН bonds, which prevent
deeper oxidation in the case of CrO3 and RuO4.
1,5-dione (18)[25]
were
obtained
via literature
procedures.
Spiro[2.7]decane (7) was obtained from methylidenecyclooctane via
Simmons-Smith cyclopropanation.[26] All the other starting materials were
commercially available. All reagents except commercial products of
satisfactory quality were purified by literature procedures prior to use.
Oxidation of hydrocarbons. General methods. Molar ratios are given
for one α-CH2-group. If several sites were supposed to be oxidized, the
corresponding excess of the reagents was used.
Oxidation via “dry” ozonation. Hydrocarbon (1 mmol), silica gel (1:100
mass ratio) and pentane or CH2Cl2 (70 mL) were stirred for 1 h. The
solvent was evaporated in vacuo. Silica gel containing adsorbed
hydrocarbon was placed into “U”-tube, cooled down to -50-(-60) оC and
ozonated at this temperature for 1-2 h. Then the system was allowed to
warm up to r.t., silica gel washed with CH2Cl2 (200 mL), the solvent was
evaporated in vacuo. The product was isolated via preparative column
chromatography (SiO2).
Conclusions
Direct oxidation of the series of cyclopropane-containing
cyclooctanes was studied. Three-membered rings spiro- and
1,2-annelated with cyclooctane core were shown to efficiently
activate adjacent site toward oxidation. 1,2-Annelated
cyclopropane demonstrated stronger activating effect that was
shown comparing the oxidation of hydrocarbons 17 and 4. It
should be mentioned that cyclooctane-based hydrocarbons 7
and 17 were found to be less reactive than analogues containing
six-membered ring.
The comparison of four oxidative methods revealed the following
general tendencies. The most practical approach to
cyclopropylketones is the use of RuO4 generated in situ. This
method is easy to be employed and, when necessary, allows the
variation of the reaction time and temperature in broad limits that
is impossible for O3 and TFDO. It should be noted that RuO4
promotes double oxidation, when more than one cyclopropane
moiety is present in the structure, that makes it the reagent of
choice for the synthesis of diketones. “Dry” ozonation is a
reasonable alternative for monooxidation of cyclopropanes, as a
selective and metal-free method. CrO3 is hardly to be chosen in
any case, due to difficult work-up and low yields. At last, TFDO,
though lacking selectivity and employing the most complicated
synthetic procedure, may be recommended in selected cases,
such as polyoxidation of 21. The moderate yields of oxidation
products are offset by one-step procedure to introduce the
carbonyl group into cyclopropane-containing molecule that is
useful for the synthesis of structurally complex compounds.
Oxidation with TFDO. To the solution of NaHCO3 (1 mol, 75.4 g) and
1,1,1-trifluoroacetone (1.32 mol, 100 mL) in water (140 mL) Oxone (0.26
mol, 159 g) was added carefully in portions at 0-3 оС, 200 torr, under
vigorous stirring. The reaction mixture was stirred until the end of foam
generation. The solution of TFDO in trifluoroacetone (0.33 М, 32 mmol,
98 mL) was collected at -70 оС into the flack containing hydrocarbon (1
mmol), allowed to warm up to -20 оC and stirred at this temperature for 2
h. The solvent was condensed at 25 оC into the flack cooled down to -78
оC. The product was isolated via preparative column chromatography
(SiO2).
Oxidation with chromium trioxide. To the suspension of CrO3 (2g, 20
mmol) in CH2Cl2 (4 mL) and acetonitrile (4 mL) the hydrocarbon (1 mmol)
was added. The reaction mixture was stirred at 0 оC for 2-6 h and filtered
through silica gel. The solvent was evaporated in vacuo, the product was
isolated via preparative column chromatography (SiO2).
Oxidation with ruthenium tetroxide. To the solution of hydrocarbon (1
mmol) in CCl4 (1 mL), CH3CN (1 mL) and phosphate buffer (1.5 mL, pH =
7) NaIO4 (3 mmol, 0.64 g) and RuCl3·xH2O (ca. 0.2 mmol, 58 mg, ω(Ru)
35-40%) were added in the atmosphere of argon. The reaction mixture
was stirred, diluted with H2O (3 mL), and extracted with CH2Cl2 (3x5 mL).
The combined organic layers were washed with a mixture (6 mL) of
saturated Na2S2O3, NaHCO3, and NaCl (1:1:1) and dried over anhydrous
MgSO4. The solvent was evaporated in vacuo, the product was isolated
via preparative column chromatography (SiO2).
Tricyclo[7.1.0.04,6]decan-2-one (5). Yield 46 mg (60% with O3), 84 mg
(62% with TFDO), 80 mg (53% with CrO3), 30 mg (20% with RuO4); white
crystals, m.p. 49 oC (from CH2Cl2), Rf 0.12 (CH2Cl2:petroleum ether 1:1).
3
1Н NMR (400 MHz, CDCl3, 25 °C):  = -0.15 (m, 3J = 5.3, J = 5.2, 2J = -
Experimental Section
4.9, 1 H, СН2, cy-Pr), 0.77 (m, 3J = 8.5, 3J = 8.4, 2J = -4.9, 1 H, СН2, cy-
Pr), 0.79 (m, 3J = 8.9, 3J = 7.6, 3J = 11.7, 2J = -15.5, 1 Н, СН2), 0.88 (m,
3J = -8.1, 3J = 7.5, 2J = -5.2, 1 H, СН2, cy-Pr), 0.94 (m, 3J = 11.7, 3J = 3.7,
3J = 5.3, 3J = 8.8, 3J = 8.5, 1 H, CH), 1.05 (m, 3J = 6.3, 3J = -6.4, 3J = -5.2,
1 H, СН2, cy-Pr), 1.25 (m, 3J = 8.4, 3J = 8.8, 3J = 5.2, 3J = 9.8, 3J = 7.4, 1
H, СН), 1.28 (m, 3J = 9.2, 3J = 4.2, 3J = 7.6, 2J = -15.1, 1 H, СН2), 1.47 (m,
3J = 6.0, 3J = 9.2, 3J = -6.4, 3J = -8.1, 3J = 10.3, 1 H, CH), 1.94 (m, 3J =
General experimental details. 1H and 13C NMR spectra were recorded
on a spectrometer Agilent 400MR (400.0 MHz for 1H and 100.6 MHz and
for 13C) at room temperature; chemical shifts δ were measured with
reference to the solvent for 1Н (CDCl3, δ = 7.24 ppm) and 13C (CDCl3, δ =
77.0ppm). When necessary, assignments of signals in NMR spectra
were made using 2D techniques. Accurate mass measurements (HRMS)
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
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7.5, 3J = 4.2, 3J = 3.7, 2J = -15.5, 1 H, СН2), 1.98 (dd, 3J = 9.8, 2J = -16.4,
Spiro[2.7]decane-4,10-dione (14). Yield 40 mg (24%); yellow liquid, Rf
0.61 (CH2Cl2). 1Н NMR (400 MHz, CDCl3, 25 °C):  = 1.34 (s, 4 H, 2 CH2,
cy-Pr), 1.66-1.75 (m, 2 H, CH2), 1.83-1.92 (m, 4 H, 2 CH2), 2.54-2.60 (m,
3
1 H, СН2), 2.01 (m, 3J = 6.3, J = 7.5, 3J = 10.3, 1 H, СН), 2.08 (m, 3J =
6.0, 3J = 7.5, 3J = 8.9, 2J = -15.1, 1 H, СН2), 2.85 (dd, 3J = 7.4, 2J = -16.4,
1 H, СН2) ppm; 13С NMR (100 MHz, CDCl3, 25 °C):  = 11.6 (СН2, cy-Pr),
12.1 (CH), 12.5 (СН2, cy-Pr), 14.4 (CH), 19.0 (CH), 24.2 (СН2), 25.4
(СН2), 27.7 (СН), 43.1 (СН2), 212.8 (C=O) ppm; IR (film): ν = 3072, 2956,
2918, 2879, 2850, 1695, 1468, 1277, 1178, 1161, 1060 cm–1; HRMS
4 H, 2 CH2CO) ppm; 13С NMR (100 MHz, CDCl3, 25 °C):  = 17.7 (JCH
=
168, 2 CH2, cy-Pr), 21.9 (JCH = 126, 2 CH2), 28.3 (JCH = 126, CH2), 41.4
(Cspiro), 43.2 (JCH = 127, 2 CH2), 207.2 (2 C=O) ppm; IR (film): ν = 3091,
3008, 2945, 2879, 2864, 1680, 1464, 1446, 1414, 1333, 1300, 1171,
1110, 1055, 997 cm–1; HRMS (ESI+, 70 eV, m/z): calcd. for C10H14O2
[M+H]: 167.1067, found: 167.1089.
(ESI+, 70 eV, m/z): calcd. for C10H14
O [M+Na]: 173.0937, found:
173.0935.
Tricyclo[7.1.0.04,6]decane-2,7-dione (6). Yield 20 mg (12% with CrO3), 34
mg (21%, with RuO4, r.t.), 57 mg (35%, with RuO4, 60oC); white crystals,
m.p. 88 oC (from CH2Cl2), Rf 0.18 (CH2Cl2). 1Н NMR (400 MHz, CDCl3,
25 °C):  = 1.04-1.15 (m, 4 H, 2 СН2, cy-Pr), 1.66-1.79 (m, 2 H, 2 СН),
1.97-2.04 (m, 2 H, 2 СН), 2.08 (dd, 2J = 15.5, 3J = 10.2, 2 H, 2 СН2), 2.82
(dd, 2J = 15.5, 3J 6.6, 2 H, 2 СН2) ppm; 13С NMR (100 MHz, CDCl3,
25 °C):  = 13.2 (JCH = 162, 2 CH2, cy-Pr), 17.6 (JCH = 164, 2 СН), 28.0
(JCH = 167, 2 CH), 40.1 (JCH = 129, 2 CH2), 208.5 (2 C=O) ppm; IR (film):
ν = 3020, 2999, 2925, 2854, 1739, 1693, 1464, 1452, 1383, 1363, 1167,
1097, 1045 cm–1; HRMS (ESI+, 70 eV, m/z): calcd. for C10H12O2 [M+H]:
165.0910, found: 165.0912.
3-(2-Bromoethoxy)cyclooct-2-en-1-one (15). Yield 35 mg (14%); yellow
liquid, Rf 0.23 (CH2Cl2). 1Н NMR (400 MHz, CDCl3, 25 °C) : 1.51-1.61
(m, 2 H, CH2), 1.63-1.76 (m, 4 H, 2 CH2), 2.75 (t, 3J 7.1, 2 H, CH2), 2.80
(t, 3J 7.1, 2 H, CH2), 3.55 (t, 3J 5.9, 2 H, CH2Br), 4.05 (t, 3J 5.9, 2 H,
CH2O) ppm; 13С NMR (100 MHz, CDCl3, 25 °C) : 23.1 (CH2), 23.2 (CH2),
23.6 (CH2), 28.2 (CH2Br), 32.7 (CH2), 41.5 (CH2CO), 67.7 (CH2O), 108.9
(CH=), 171.2 (C=), 201.1 (C=O) ppm; IR (film) v: 2935, 2860, 1712, 1689,
1635, 1603, 1458, 1446, 1410, 1329, 1257, 1226, 1176, 1128, 1076 cm-
1; HRMS (ESI+, 70 eV, m/z): calcd. for C10H15BrO2 [M+H]: 247.0328,
249.0308, found: 247.0330, 249.0312.
Dispiro[2.3.2.3]dodecane (17) was obtained from cyclooctane-1,5-dione
(16) via the sequence of Wittig reaction[27] and Simmons-Smith
cyclopropanation.[26] Yield 0.47 g (29% from 16); colorless liquid, Rf 0.64
(petroleum ether). 1Н NMR (400 MHz, CDCl3, 25° C):  = 0.25 (s, 8 H, 4
CH2, cy-Pr), 1.44-1.50 (m, 8 H, 4 CH2), 1.53-1.61 (m, 4 H, 2 CH2) ppm;
13С NMR (100 MHz, CDCl3, 25 °C):  = 14.3 (JCH = 160, 4 CH2, cy-Pr),
19.3 (2 Cspiro), 24.7 (JCH = 126, 2 CH2), 37.0 (JCH = 125, 4 CH2) ppm; IR
(film): ν = 3066, 2995, 2920, 2854, 1460, 1446, 1427, 1375, 1011, 843
cm–1; GC-MS (EI) m/z (I, %): 149 (3) [M-15]+, 136 (9) [M-28]+, 121 (16)
[M-43]+, 108 (89) [M-56]+.
Dispiro[2.3.2.3]dodecan-4-one (18). Yield 43 mg (26% with O3), 67 mg
(67% with TFDO), 131 mg (74%, with RuO4); yellowish liquid, Rf 0.33
(CH2Cl2:petroleum ether 1:1). 1Н NMR (400 MHz, CDCl3, 25 °C):  =
0.27-0.34 (m, 2 H, 2 CH2, cy-Pr), 0.35-0.42 (m, 2 H, 2 CH2, cy-Pr), 0.60-
0.70 (m, 2 H, 2 CH2, cy-Pr), 1.17-1.27 (m, 2 H, 2 CH2, cy-Pr), 1.40-1.47
(m, 2 H, CH2), 1.48-1.53 (m, 2 H, CH2), 1.53-1.68 (m, 2 H, CH2), 1.87-
1.92 (m, 2 H, CH2), 2.65-2.70 (m, 2 H, CH2) ppm; 13С NMR (100 MHz,
CDCl3, 25 °C):  = 13.9 (JCH = 160, 2 CH2, cy-Pr), 17.9 (Cspiro), 18.5 (JCH
=
164, 2 CH2, cy-Pr), 25.8 (JCH = 126, CH2), 31.4 (Cspiro), 32.8 (JCH = 125,
CH2), 33.0 (JCH = 126, CH2), 38.6 (JCH = 128, CH2), 40.2 (JCH = 127, CH2),
216.3 (C=O) ppm; IR (film): ν = 3070, 2999, 2922, 2852, 1684, 1462,
1444, 1365, 1329, 1176, 1095, 1016, 901, 889, 837 cm–1; HRMS (ESI+,
70 eV, m/z): calcd. for C12H18O [M+H]: 179.1430, found: 179.1434.
Acknowledgements
We thank the Russian Foundation for Basic Research (Project
16-03-00467-a) and the Grant of the President of the Russian
Federation (NSh-10268.2016.3) for financial support. The
research work was carried out using NMR spectrometer Agilent
400-MR purchased under the program of MSU development.
Dispiro[2.3.2.3]dodecane-4,6-dione (19) and dispiro[2.3.2.3]dodecane-
4,11-dione (20). Yield 4.2 mg (36%, 19:20 1.1:1); white crystals, Rf 0.29
(CH2Cl2). 1Н NMR (400 MHz, CDCl3, 25 °C): for 19  = 0.67-0.77 (m, 4 H,
2 CH2, cy-Pr), 1.24-1.34 (m, 4 H, 2 CH2, cy-Pr), 1.64-1.70 (m, 2 H, CH2),
1.78-1.83 (m, 4 H, 2 CH2), 3.72 (s, 2 H, CH2); for 20  = 0.46-0.53 (m, 4
H, 2 CH2, cy-Pr), 0.78-0.88 (m, 2 H, 2 CH2, cy-Pr), 1.35-1.45 (m, 2 H, 2
CH2, cy-Pr), 1.70-1.75 (m, 2 H, CH2), 2.48 (s, 2H, CH2), 2.81-2.87 (m, 2
H, CH2), 2.87 (s, 2 H, CH2) ppm; 13С NMR (100 MHz, CDCl3, 25 °C): for
19  = 18.7 (4 CH2, cy-Pr), 26.4 (CH2), 31.6 (2 CH2), 31.9 (2 Cspiro), 56.7
(CH2), 205.3 (C=O) ppm; for 20  = 14.5 (2 CH2, cy-Pr), 17.0 (Cspiro), 19.7
(2 CH2, cy-Pr), 28.9 (Cspiro), 39.3 (CH2), 39.5 (CH2), 48.2 (CH2), 49.7
(CH2), 209.9 (C=O), 213.3 (C=O) ppm. IR (film): ν = 3078, 3003, 2929,
2856, 1691, 1674, 1460, 1446, 1419, 1360, 1350, 1325, 1153, 1107,
1095, 1024, 935 cm–1; HRMS (ESI+, 70 eV, m/z): calcd. for C12H16O2
[M+H]: 193.1223, found: 193.1224.
Keywords: oxidation • small ring systems • ketones • polycycles
• ruthenium
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10.1002/ejoc.201701671
European Journal of Organic Chemistry
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