Unusual selectivity in the oxidative functionalization of gem-dibromocyclopropanes

Article abstract of DOI:10.1016/j.tet.2004.02.024

Oxidation of gem-dibromocyclopropanes with chromium trioxide in acetic acid or a number of other reagents is generally slower than that of the corresponding cyclopropane; in a number of cases moderate yields of products are obtained but these show unexpected oxidation patterns.

Full text of DOI:10.1016/j.tet.2004.02.024

Tetrahedron 60 (2004) 3717–3729
Unusual selectivity in the oxidative functionalization
of gem-dibromocyclopropanes
a
Alexey V. Nizovtsev,a Mark S. Bairdb and Ivan G. Bolesov
,
*
aDepartment of Chemistry, State University of Moscow, Leninskie gory, 1, Bld.3, Moscow, 119992, GSP-2, Russian Federation
bDepartment of Chemistry, University of Wales, Bangor, Gwynedd LL57 2UW, UK
Received 17 October 2003; revised 19 January 2004; accepted 12 February 2004
Abstract—Oxidation of gem-dibromocyclopropanes with chromium trioxide in acetic acid or a number of other reagents is generally slower
than that of the corresponding cyclopropane; in a number of cases moderate yields of products are obtained but these show unexpected
oxidation patterns.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
alkyldibromocyclopropane by oxidation of one or more
C–H bonds. There is ample precedent for this reaction in
the case of alkylcyclopropanes themselves. Such an
oxidation has been used for many years in determining the
structure of long chain cyclopropane containing fatty acids,
oxidation with chromium trioxide occurring adjacent to
the ring and allowing structure assignment by mass
spectrometry.2,3 Oxidation has also been applied to
bicyclo[n.1.0]alkanes, as in the conversion of 1 into 2,4 3
into 45 and 5 into 64 (Scheme 1).
Functionalized dihalocyclopropanes are of considerable
interest in view of their importance in the synthesis of a
range of natural cyclopropane containing compounds or
synthetic analogues.1 Although there are many approaches
to such compounds, one of the most effective starting points
is the dihalocyclopropanation of an alkene using haloform
and base, a reaction which generally, but not always
proceeds through the formation and trapping of a dihalo-
carbene. Although simple alkenes are efficiently trapped in
this way, more complex alkenes are either less readily
available or undergo alternative reactions. In some cases
this problem may be overcome by an appropriate use of
protecting groups. However, an alternative approach would
be to introduce carbonyl or hydroxy groups into a simple
The oxidation of such bicyclic systems with ozone is also
reported. Compound 3 leads almost exclusively to the 2-one
4, although a minor amount of the corresponding 4-one is
also observed; none of the 3-one was isolated.6 Highly
selective oxidations of cyclopropanes leading to a-cyclo-
propyl ketones have been performed with the use of other
oxidants, ruthenium tetroxide,5,7 dimethyldioxirane,8 and
ozone in the presence of silica.6,9 Oxidation of bicyclo-
[4.1.0]heptane with cytochrome P45010 or with oxometal-
loporphinates and iodosylbenzene11 leads predominantly to
endo- and exo-bicyclo[4.1.0]heptan-2-ol.
In contrast, oxidation of dihalocyclopropanes is reported
generally to be less effective. Thus chromium trioxide
oxidation of 7,7-dibromobicyclo[4.1.0]heptane 7 leads to
compounds 8 and 9 in low yields (Scheme 2).12
Scheme 1.
Keywords: Dibromocyclopropane; Oxidation.
*
Corresponding author. Tel.: þ44-1248-382-374; fax: þ44-1248-370-528;
Scheme 2.
e-mail address: chs028@bangor.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.02.024

3718
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
Other gem-dihalocyclopropanes have also been converted
into the corresponding a-cyclopropylketones using chro-
mium trioxide in glacial acetic acid12,13 or dry ozonolysis,14
but also in yields from low to modest. We now report the
oxidation of a number of gem-dibromocyclopropanes,
primarily using chromium trioxide in glacial acetic acid.
of 10 with phenylmagnesium bromide followed by water,
7,7-dibromobicyclo[4.1.0]heptan-2-one was formed.
For proof of structure, the tribromoketone 10 was reduced
with sodium borohydride to the trans-alcohol 11 which on
treatment with base gave the syn-3-oxatricyclo[5.1.0.02,4]-
octane 12 (Scheme 4), suggesting that the tribromide 11 has
the configuration shown. Epoxide 12, which could be
1
distinguished clearly from the anti-isomer by H NMR,15
2. Results and discussion
represents the first example of such a gem-dihalogeno syn-
ring system.
We could not reproduce the results of oxidation of
7,7-dibromobicyclo[4.1.0]heptane 7 described above.12 On
reaction of 7 with chromium trioxide in glacial acetic
acid, an unexpected tribromoketone 10 was obtained with
a yield of 34% instead of 8 and 9 (Scheme 3).
Scheme 4.
Attempts to ring-open the epoxide 12 using either phenyl
magnesium bromide and copper (I) iodide in THF or
benzylamine in the presence of Yb(CF3SO3)2 were not
successful. The alcohol 11 was readily converted into the
corresponding acetate; attempts to dehydrobrominate this
were largely unsuccessful, reaction with dimethylamino-
pyridine in DMSO for 3 h at 100 8C leading to the recovery
of starting material; however, reaction with 1,5-diazabi-
cyclo-undec-5-ene in DMSO for 3 h at 125 8C did lead to
2-acetoxy-7,7-dibrombicyclo[4.1.0]hept-3-ene, albeit only
in 19% yield. Attempts to prepare an enamine by reaction of
10 with morpholine or a silyl enol ether by reaction with
trimethylchlorosilane in the presence of triethylamine were
not successful and starting material was recovered. Reaction
with pyridine in DMSO, led unexpectedly to the formation
of two enones 13 and 14 (Scheme 5).
Scheme 3.
The yield of 10 depended on the amounts of chromium
trioxide and acetic acid (Table 1). It was necessary to use not
less than 15 mol. equiv. of oxidant for complete conversion of
starting material. Acid products were not obtained under these
conditions. The reaction did not proceed when ether was used
as a solvent instead of acetic acid.
Table 1. Oxidation of 7 with chromium trioxide in glacial acetic acid
Amount of 7
(mmol)
CrO3
(mol. equiv.)
AcOH
(mL)
Unreacted 7a
(%)
Yield of 10b
(%)
3
3
3
3
10
10
5
8
15
15
60
100
50
78
32
0.5
0
8
0.5
—
—
—
36
—
34
10
15
20
15
15
a
By GLC.
Isolated yield.
Scheme 5.
b
The mechanism of formation of enone 14 is probably similar
to that involved in the oxidation of a-bromoketones with
DMSO to a-dicarbonyl compounds,16,17 and includes SN2
attack of the sulfoxide oxygen at the brominated carbon
(CHBr fragment) with subsequent elimination of dimethyl
sulfide and then enolization. The mechanism of formation of
13 is not clear. When tribromoketone 10 was treated with
potassium iodide and potassium carbonate in DMSO
(reported conditions for a similar oxidation17), the product
did not contain any 13 or 14, but probably the a-iodoketone,
3-iodo-7,7-dibromobicyclo[4.1.0]heptan-2-one, related to
10 was formed. This was concluded based on the
appearance of a new double doublet at lower field in the
1H NMR spectrum compared to starting material (4.48
compared to 4.39 ppm for 10) and a new carbonyl signal in
the 13C NMR (192.5 compared to 192.8 ppm for 10). By
TLC the product showed just one spot with the same Rf as
starting material. An attempt to prepare this a-iodoketone
by reaction of 10 with sodium iodide in acetone was not
successful and the product of reduction—dibromoketone
Formation of 10 possibly occurs through replacement
of hydrogen at C(3) in the proposed intermediate 7,7-dibro-
mobicyclo[4.1.0]heptan-2-one by a bromine atom; the
source of the bromine is not clear, but may be explained
by the low yield of this product—presumably decompo-
sition of the remainder leads to a species that is a
brominating agent. Alternatively 8 may actually be an
intermediate and again be brominated under the reaction
conditions. The yield of 10 was not increased by addition to
the reaction mixture of sodium bromide or dibromo-
methane, but when the reaction was carried out in the
presence of carbon tetrabromide (10 mol. equiv.), product
10 was obtained in 38% yield.
Attempts to dehydrobrominate the ketone 10 with potas-
sium tert-butoxide in dichloromethane or ether, with sodium
hydroxide under phase transfer conditions or with 1,5-di-
azabicyclonon-5-ene led to the consumption of starting
material, but no products were isolated, while on reaction

A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
3719
16—was formed instead (Scheme 6), similar to reduction of
a-bromoketones with NaI/Me3SiCl18 or HI.19 As by-
products enones 14 and 15 were formed. Unfortunately
compounds 15 and 16 could not be separated and were
analyzed as a mixture. The assignment of structure 15 was
based on 1H and 13C NMR spectra, which had signals
similar to those for 13 except one for the carbon next to the
iodine, which was at higher field compared with 13
(93.1 ppm for 15 and 116.6 ppm for 13). The mechanism
of formation of 14 and 15 is again not understood.
Scheme 9.
the major product (Table 2). The best yield of 25 was
obtained when 8 mol. equiv. of oxidant were used (Table 2),
but even in this case a small amount of the starting material
(4%) remained unreacted. Among the other products
isolated were the 2-one 26 (13%), the 3-one 27
(,0.5%),21 and a mixture of (dibromomethano)suberic
acids 28 (7%).
Table 2. Oxidation of 24 with chromium trioxide in glacial acetic acida
Scheme 6.
Treatment of 10 with thiourea in refluxing methanol, a
standard procedure for thiazole formation from a-bromo-
ketones,20 led after 4 h to a mixture of 16 and thiazole 17 in
modest yields (Scheme 7).
CrO3 (equiv.)
Product, isolated yield (%)
24
25
26
27
28b
c
5
7
8
9
15
20
5
4
1
—
39
41
48
48
33d
14
12
13
11
1
1
—
,0.5
,0.5
,0.5
,0.5
7
7
9
c
—
Scheme 7.
a
All experiments were performed with 3 mmol of starting material in
20 mL of glacial acetic acid at 30–31 8C for 1 h.
Isolated as dimethyl diester after treatment with diazomethane.
Acid products were not worked-up.
Also isolated as a 2,4-dinitrophenyl-hydrazone (21%).
In a similar manner to 7,7-dibromobicyclo[4.1.0]heptane 7,
6,6-dibromobicyclo[3.1.0]hexane 18 reacted with chro-
mium trioxide in glacial acetic acid to give 19 as the
major product albeit in poor yield, together with a mixture
of tri- and tetrabromoketones 20, 21 (Scheme 8).
b
c
d
It is interesting to note that oxidation of exo-9-bromobi-
cyclo[6.1.0]nonane with dimethyldioxirane is reported to
lead to the corresponding 4-one, although only in 4% yield
and that the dibromide 24 does not react with this reagent.8
A number of other dihalocyclopropanes are also reported to
be inert to this reagent.8
Similar results to those with chromium trioxide were
obtained on oxidation of 24 with ruthenium tetroxide or
ozone (Table 3) suggesting that the regioselectivity of the
oxidation depends mostly on the electron withdrawing
properties of the gem-dibromocyclopropane fragments.
Scheme 8.
The exo-ketone 19 was characterized on the basis of the
larger coupling of H-3 to endo-H-4 than to exo-H-4. Isomer
20 showed an ABX pattern for the H-4, H-40 and H-5, only
the endo-H-4 coupling to H-5; in the same way H-1 was not
split by H-2, suggesting an exo-configuration for the
bromine at C-2. Compound 21 showed just two singlets in
Table 3. Yields of products in oxidation of 24 with different oxidants
Oxidant
Product (%)
1
the H NMR, (dH: 2.87 and 4.17) and four carbon signals;
24
25
26
27
28a
on the basis of the lack of coupling between H-1 and H-2
and the symmetry, it was assigned as the exo,exo-isomer.
Once again, the tribromide 19 could be reduced to a single
alcohol 22, and this was dehydrobrominated to give the
syn-epoxide 23 (Scheme 9).
CrO3 (8 mol. equiv.), AcOH
H5IO6 (8 mol. equiv.), RuCl3
(5 mol.%), 70–75 8C, 52 h
Ozone/SiO2
4
9
48
37
13
7
,0.5
2
7
17
31b
48b
6b
5b
—
c
a
Isolated as dimethyl diester after treatment with diazomethane.
Yield by GLC data.
Acid products were not worked-up.
b
c
Chromium trioxide in acetic acid reacts with 9,9-dibromo-
bicyclo[6.1.0]nonane 24 to give g-cyclopropylketone 25 as

3720
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
It is necessary to note that oxidation of 24 with periodic acid
required vigorous conditions, refluxing the reaction mixture
for 52 h (at room temperature conversion of starting
material was less 5%). By comparison oxidation of
bicyclo[6.1.0]nonane 3 with 3 equiv. sodium metaperiodate
in the presence of ruthenium trichloride proceeds at room
temperature giving after 18 h bicyclo[6.1.0]nonan-2-one
with an yield of 50%.5 Dry ozonolysis of dibromocyclo-
propane 24 on silica also proceeds more slowly than the
oxidation of the non-halogenated compound. Thus even
when the ozonolysis was repeated three times, conversion of
starting material was only 69%. Full conversion of the non-
brominated analogue of 24, bicyclo[6.1.0]nonane was
observed even after one ozonolysis cycle,6,22 and led
primarily to a different regioselectivity, the a-cyclopropyl
ketone 4 being obtained in a yield of 88% together with a
small amount only of 30 (7%) (Scheme 10).6
materials was followed by GLC (Table 4). At the start of
the reaction the relative peaks areas for 3, 29 and 24 were
37:32:31. The peak for 3 had disappeared after 10 min.
Those for the two monobromides 29 had essentially
disappeared after 45 min (it is interesting to note that ratio
of remaining monobromides 29 did not significantly change
during the experiment. This suggests that the position of
bromine in the substrate does not influence the rate of
oxidation). After 60 min, ca. 45% (by GC/MS data) of the
dibromide 24 remained.
The selective oxidation of C–H bonds adjacent to
cyclopropanes is usually considered to be due to activation
by the ring of the neighboring methylene group. The two
bromine atoms instead of hydrogen at C(9) of compound 3
seem to lead to a redistribution of the electron density in the
bicyclo[6.1.0]nonane skeleton. Because of this, the propen-
sity of an a-methylene group to be oxidized appears to be
decreased. From an MO point of view, the oxidant removes
an electron from the HOMO of the substrate. Optimization
of geometries of both compounds 24 and 3 by ab initio
methods using the STO-3G basis set followed by calculation
of the HOMO location has shown, that in 24 this is located
on the bromines and the quaternary carbon (energy
27.86 eV, Fig. 1), but in 3 it is located on positions 1, 2,
7 and 8 of the eight membered ring (energy 29.33 eV,
Fig. 2). This suggests that oxidation of the dibromide begins
Scheme 10.
The bicycloalkane 3 is also oxidized with dimethyldioxir-
ane, and in this case both the above ketones are isolated
again in a ratio of 88:7.8 9,9-Dibromobicylo[6.1.0]nonane
24 does not react with dimethyldioxirane.8 It is interesting to
note that, unlike 24, dibromide 7 was essentially unreactive
to periodic acid (10 mol. equiv.) in the presence of
ruthenium tetroxide (5 mol%) at 70 8C over 92 h. gem-
Dibromocyclopropane 24 did not react with chromium
trioxide in acetone or in dichloromethane in the presence of
3,5-dimethylpyrazole even when the reaction mixture was
refluxed for 18 h. By comparison non-halogenated cyclo-
propanes react with chromium trioxide–3,5-dimethylpyr-
azole complex in dichloromethane even at 220 8C to give,
after 3 h, a-ketones with modest yields.4
In order to examine the relative rates of oxidation of
brominated and nonbrominated cyclopropanes, a mixture
of 3, 24 and 9-bromobicyclo[6.1.0]nonane (29, exo–
endo¼1:2.5) was treated with 8 equiv. of chromium trioxide
in glacial acetic acid and the consumption of starting
Figure 1. HOMO of 9,9dibromobicyclo-[6.1.0]-nonane 24.
Table 4. Oxidation of mixture of 3, 29 and 24 with chromium trioxide
Time of
reaction
Contents of starting bicyclo[6.1.0]nonanes in the neutral
fraction of the reaction mixture by GLC or GC/MS (%)
3
29
24
0
5
10
15
60
37a
4a
32a
,19a
,7a
,3b
0b
31a
33a
31a
24b
14b
a
—
—
—
b
b
a
By GLC.
by GC/MS.
b
Figure 2. HOMO of bicyclo[6.1.0]nonane 3.

A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
3721
by coordination of the oxidant to the bromine atoms
followed by removal of an electron from the HOMO of
substrate. Interaction of the derived cyclopropyl cation-
radical 31 with a nearby g-methylene group possibly
produces the cation-radical 32 (Scheme 11). This loses a
proton giving radical 33. Reaction of this with solvent
(AcOH) or chromium trioxide would give the ester 34, this
reacting with another molecule of oxidant forming g-ketone
25. The isolation of the corresponding alcohols from the
ozonolysis of cyclopropane and gem-dichlorocyclopropane
derivatives9,14,23 can serve as evidence for participation in
the reaction of intermediates of type 34. The formation of
9,9-dibromobicyclo[6.1.0]nonan-2-one 26 can proceed by
a similar process but the difference is in the redistribution
of electrons in the intermediate 31 from the a-methylene
groups (not from g-links). A similar oxidation involving
cation-radicals and radicals was suggested for reaction of
3,6-dehydrohomoadamantane with chromyl derivatives.24
Scheme 13.
20 mol. equiv. did not change the yield of compound 37,
just the degree of conversion of starting material and the
yield of acid products (Table 5). Increasing the amount of
chromium trioxide to 30 mol. equiv. and the reaction time to
a week led to the disappearance of neutral compounds in the
reaction mixture. The acid 38 was isolated with a yield of
about 36% as a single product under these conditions.
Table 5. Oxidation of 36 with chromium trioxide in glacial acetic acid
CrO3
(mol. equiv.)
Time of
stirring (h)
36
37
38þ39a
Ratio
38:39b
8
1
1
1
1
72
34
23
12
0
20
24
25
26
0
.12
.18
.24
.32
.36
1:2.6
1:2.2
1:2.1
1:1.5
100:0
10
14
20
30
0
a
Isolated as mixture of methyl esters after treatment with diazomethane.
By GLC.
b
The formation of acid 39 is possible just from ketones 40 or
41 (Scheme 14), but not from 37. The presence of 39 in the
reaction mixture is an indirect proof of oxidation not only of
an a-methylene group, but also of b- and (or) g-groups in
the chain. By comparison dry ozonolysis of butylcyclo-
propane led to oxidation of only the a-methylene group
giving the butanoylcyclopropane with a yield of 87%.6
Scheme 11.
Oxidation of 8,8-dibromobicyclo[5.1.0]octane 35 with
chromium trioxide in glacial acetic acid proceeds more
slowly than for the other bicyclic gem-dibromocyclo-
propanes (full conversion of starting material with 15 of
CrO3 under the conditions of oxidation of 7,7-dibromo-
bicyclo[4.1.0]heptane required 2 h at 30–31 8C instead of
1 h) and afforded a complex mixture of at least four
dibromo- and tribromoketones which were not identified,
together with a mixture provisionally characterized as
(dibromomethano)pimelic acids (Scheme 12). The for-
Scheme 14.
1
mation of tribromoketones was assumed based on the H
NMR spectrum which contained signals in the region 4.2–
4.5 ppm, corresponding to the a-bromoketone CHBr
fragment. The major gem-dibromo-ketone was not 8,8-
dibromobicyclo[5.1.0]octan-4-one.25 The reason for the
lower rate of oxidation of this gem-dibromocyclopropane
compared with reactions described above remains unclear.
The oxidation of the tricycle 42 derived from (1S)-b-pinene
can be used as an example of a reaction of a 1,1-dibromo-
2,2-dialkylcyclopropane (Scheme 15).
Scheme 12.
Monocyclic gem-dibromocyclopropanes react with chro-
mium trioxide less selectively than the bicyclic compounds
above. The gem-dibromocyclopropylketones formed easily
oxidize to carboxylic acids. Thus, e.g. 1,1-dibromo-2-butyl
cyclopropane 36 reacted with chromium trioxide in acetic
acid giving the ketone 37 together with acids 38 and 39
(Scheme 13). Changing the amount of oxidant from 10 to
Scheme 15.
Just as in the case of 1,1-dibromo-2-butylcyclopropane 36,
oxidation occurs relatively equally at both the a- and

3722
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
b-carbons to give a mixture of ketones 43–45. Products of
oxidation of the bridgehead carbons were not found. This
can be contrasted to the non-halogenated system where
oxidation occurs just at the CH2-group next to the
cyclopropane and a similar oxidation of the cyclopropane
derived from b-pinene (Scheme 16).
opening of the cyclopropane ring was observed and a
mixture of acetophenone and p-bromoacetophenone deriva-
tives 52–57 was isolated (Scheme 20). It is necessary to
note that oxidation of 1-bromo-2-methyl-2-phenylcyclo-
propane or of a homologue of 51—1,1-dibromo-2-propyl-2-
phenylcyclopropane—with ruthenium tetroxide led to the
corresponding cyclopropanecarboxylic acids in good
yields.26,27
Scheme 16.
The oxidation of a methyl group is also possible under the
conditions used in the present work. Thus, for example,
reaction of 1,1-dibromo-2,2-dimethylcyclopropane 47 with
20 mol. equiv. chromium trioxide in glacial acetic acid led
after 24 h to acid 48 in low yield (Scheme 17). The neutral
fraction contained only starting material. Reaction of
cyclopropane 47 with 30 mol. equiv. of oxidant for one
week led to complete conversion of substrate but did not
lead to an increased yield of acid 48.
Scheme 20.
3. Conclusion
Oxidation of gem-dibromocyclopropanes with chromium
trioxide in acetic acid or a number of other reagents is found
to be generally slower than that of the corresponding
cyclopropane; in a number of cases moderate yields of
products are obtained but these show unexpected oxidation
patterns. Despite the yields, the products of these simple
reactions may have synthetic potential.
Scheme 17.
Introduction of a methoxycarbonyl group instead of one of
methyl group leads to an increased stability to oxidation by
chromium trioxide. Thus, in the reaction of ester 49 with
30 mol. equiv. of oxidant, 70% of the starting material was
isolated from the reaction mixture even after one week
(Scheme 18). The products of oxidation of the methyl group
were not observed in this reaction.
This work was carried out as a part of a project supported by
the INTAS programme.
4. Experimental
4.1. General
Commercial reagents were used without further purification
unless stated. The dibromides (7),28 (18),29 (24),28 (35),30
(36),31 the dibromocarbene adduct of (1S)-b-pinene (42),32
and dibromides (49),33 and (51)34 were prepared from
alkenes and bromoform in two phase reactions with
cetrimide as a phase transfer catalyst using standard
procedures. Bicyclo[6.1.0]nonane (3)35 was prepared from
(24) by reduction with lithium in a mixture of THF and
t-butanol.36 9-Bromobicyclo[6.1.0]nonane (29)37 was pre-
pared from (23) by reduction with ethylmagnesium bromide
in the presence of titanium isopropoxide.26 1,1-Dibromo-
2,2-dimethylcyclopropane (47)34 was prepared from iso-
butene and bromoform in pentane at 225 8C using
potassium tert-butoxide as a base. The acetate of
(2,2-dibromo-1-methylcyclopropyl)methanol (50) was pre-
pared from 49 as described.38 Diethyl ether and tetra-
hydrofuran were distilled over sodium wire. Petroleum was
of boiling point 40–60 8C. Reactions requiring anhydrous
conditions were performed using oven dried glassware
(250 8C) that was cooled under either dry nitrogen or argon;
experiments were conducted under a positive atmosphere
Scheme 18.
Oxidation of the methyl group was also not observed in the
reaction of acetate 50. Acid 48 was isolated in ca. 75% yield
and almost 13% starting material was recovered
(Scheme 19).
Scheme 19.
An unexpected result was found in the reaction of 1,1-di-
bromo-2-methyl-2-phenylcyclopropane 51 with chromium
trioxide. Instead of oxidation of methyl or phenyl groups,

A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
3723
of argon. Unless stated, organic solutions were dried over
anhydrous magnesium sulfate and evaporated at 14 mm Hg;
yields quoted are for purified compounds and any ratios
given are calculated by comparing integrals in the 1H NMR
spectrum or by GLC data.
solidified to give white crystals (mp 92–93 8C (hexane))
which showed dH: 2.13 (2H, m), 2.46 (3H, m), 2.77 (1H, d,
J¼9.3 Hz, H-1), 4.39 (1H, dd, J¼6.5, 3.4 Hz, H-3); dC:
18.32, 27.7, 30.22, 32.5þ, 36.9þ, 49.5þ, 192.8 (CvO);
IR (cm21, film): 1711s (CvO), 1444m, 1312m, 1206m,
1181s, 1098m, 1020m, 993m, 944m, 808m, 785m, 736m,
695m, 677m; MS: 350 (0.1), 348 (0.6), 346 (0.6), 344 (0.1),
269 (10), 267 (19), 265 (10), 71 (100); calcd C 24.24, H
2.03%, found C 24.3, H 2.4%.
New compounds were homogenous by GLC or TLC. GLC
was conducted using a Carlo Erba HRGC 5300 F.I.D. on a
capillary column (30 m£0.32 mm id Phase, DB5 split ratio
of 50:1) with nitrogen carrier gas. TLC was performed using
Aldrich silica plates coated with silica gel 60 (F254).
Compounds were visualized by examination under an
ultraviolet source, by exposure to iodine vapor or by contact
with phosphomolybdic acid hydrate (2% in ethanol)
followed by heating to 180 8C. Column chromatography
was conducted with Matrex Silica 60 (Fisher Scientific
Int.Co.) under medium pressure. Melting points are
uncorrected. Unless stated, infrared spectra were obtained
as solutions in CHCl3 or as liquid films on a Perkin–Elmer
1600 FTIR spectrometer. Low-resolution mass spectra were
measured using a Finnigan 8430 spectrometer using EI
70 eV unless stated. Accurate mass measurements refer
to 79Br isotopes unless stated and were carried out on a
Micromasse GCT spectrometer. Microanalyses were
performed on a Carlo Erba Model 1106 CHN analyzer.
NMR spectra were recorded in CDCl3, using Bruker AC250
or A500 spectrometers at 250 or 500 MHz (1H) and 62.9 or
125 MHz (13C). 13C spectra were broad-band decoupled and
in most cases corresponding DEPT spectra were also
recorded. The results of DEPT spectra are quoted in the
form of signs þ (corresponding to CH and CH3 groups) and
2 (corresponding to CH2 groups), signals which appear
with no sign correspond to quaternary carbons. All
previously described compounds were characterized by
IR, 1H and 13C NMR and gave data identical to those in the
literature.
The combined sodium bicarbonate layers were washed with
dichloromethane (2£10 mL), then acidified with hydro-
chloric acid to pH 1 and extracted with dichloromethane
(3£15 mL). The combined organic layers were washed with
water (10 mL), dried, filtered and concentrated in vacuo to
give a yellow viscous oil (40 mg), which was not identified.
The product above could be also isolated by slow crystal-
lization of the reaction mixture from hot hexane (7 mL per
1 g of mixture), compound (10) precipitating as slightly
yellow sticks with mp 92–93 8C. If the melting point of
product was below 90 8C purification could be achieved by
slow crystallization from 10:1 hexane–ethanol (10 mL per
1 g of reaction mixture), giving shiny plates with mp
93–95 8C. The yield obtained by this method was 17–22%.
(b) With chromium trioxide in ether. Dibromide (7)
(762 mg, 3 mmol) was added to a suspension of chromium
trioxide (3.00 g, 30 mmol) in dry ether (20 mL) at 0 8C. A
strong exothermic effect was observed. The mixture was
stirred at 25–30 8C for 1 h, then poured into a mixture of
water (100 mL) and ether (50 mL). The aqueous layer was
extracted with ether (3£30 mL). The combined organic
layers were extracted with sat. aq. sodium bicarbonate
(3£10 mL), brine (3£10 mL), dried and concentrated in
vacuo to give starting material (676 mg, 89%).
All calculations were performed using Hyperchem Pro 6.0.
Optimization of geometries was achieved by ab initio
methods using an STO-3G basis set. The starting MO
was the core Hamiltonian. Calculations were continued
until the RMS (root-mean-square) gradient became less
than 0.1 kcal/A mol. Conformations of all compounds were
calculated in vacuo. At the beginning the conformations
were calculated using the molecular-mechanics method
MMþand then using ab initio methods. The displayed
surfaces were generated for orbital contour value 0.06.
(c) With periodic acid. A mixture of dibromide (7) (762 mg,
3 mmol), carbon tetrachloride (10 mL), acetonitrile
(10 mL), water (15 mL), periodic acid (6.84 g, 30 mmol)
and ruthenium trichloride (42 mg, 0.15 mmol, 5 mol%) was
stirred at 70–75 8C. After 92 h, the black mixture was
cooled, poured in water (20 mL) and extracted with
dichloromethane (3£ L). The combined organic layers
were washed with water (10 mL), sat. aq. sodium bicarbo-
nate (2£10 mL) and water (10 mL), dried and concentrated
in vacuo to give an oil (574 mg) which contained by GLC
1
and H NMR data starting material (76%), exo-3,7,7-tri-
bromobicyclo[4.1.0]heptan-2-one (10) (7%) and two
unidentified compounds.
4.1.1. Oxidation of 7,7-dibromobicyclo[4.1.0]heptane (7).
(a) With chromium trioxide in acetic acid. 7,7-Dibromo-
bicyclo[4.1.0]heptane (7) (2.540 g, 10 mmol) was added to
a suspension of chromium trioxide (15.00 g, 150 mmol) in
glacial acetic acid (50 mL). The mixture was stirred at 30–
31 8C for 1 h, then poured into a mixture of water (200 mL)
and dichloromethane (100 mL). The organic layer was
separated and the aqueous layer was extracted with
dichloromethane (3£50 mL). The combined organic layers
were washed with water (2£50 mL), extracted with sat. aq.
sodium bicarbonate (2£30 mL), water (30 mL), dried and
concentrated in vacuo to give an oil (1.716 g). Chroma-
tography on Silica (100 g) eluting with petrol–ether 10:1
gave exo-3,7,7-tribromobicyclo[4.1.0]heptan-2-one (10)
(1.164 g, 34%, Rf 0.42) as a viscous oil which slowly
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), then acidified with hydrochloric
acid to pH 1 and extracted with dichloromethane (3£5 mL).
The combined organic layers were washed with water
(10 mL), dried, filtered and concentrated in vacuo to give a
yellow viscous oil (1 g), which was not identified.
4.1.2. exo-3,7,7-Tribromobicyclo[4.1.0]heptan-endo-2-ol
(11). Sodium borohydride (73 mg, 1.93 mmol) was added to
exo-3,7,7-tribromobicyclo[4.1.0]heptan-2-one (10) (67 g,
1.93 mmol) in dry ethanol (6 mL) and benzene (3 mL),
stirred at 15–20 8C for 1 h, then poured in water (30 mL)

3724
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
and extracted with dichloromethane (4£10 mL). The
combined organic layers were washed with water
(15 mL), dried and concentrated in vacuo to give an oil
(712 mg). Chromatography on Silica (20 g) eluting with 3:2
petrol–ether gave exo-3,7,7-tribromobicyclo[4.1.0]heptan-
endo-2-ol (11) (608 mg, 90%, Rf 0.40) as white crystals (mp
76.5–79 8C) which showed dH: 1.63 (1H, dddd, J¼14.7,
13.7, 5.5, 3.2 Hz, H-5endo), 1.73–1.86 (1H, m), 2.09–2.15
(1H, m), 2.15 (1H, ddd, J¼10.6, 10.2, 3.2 Hz, H-6), 2.24
(1H, dddd, J¼14.7, 10.2, 5.0, 2.2 Hz, H-5exo), 2.31 (1H, dd,
J¼10.6, 7.5 Hz, H-1), 2.59 (1H, d, J¼4.9 Hz, OH), 4.19–
4.34 (2H, m); dC: 23.02, 31.5þ, 33.5, 33.72, 34.4þ,
54.5þ, 74.3þ; IR (cm21, CHCl3): 3441br.s (OH), 2949s,
2926s, 2864s, 1443s, 1387m, 1344s, 1289m, 1262s, 1225s,
1191m, 1174s, 1129m, 1112s, 1058s, 1023s, 973m, 959m,
911s, 858m, 820s, 804s, 754s, 718s; calcd C 24.10, H
2.60%, found C 24.4, H 2.4%.
115.4þ, 145.9, 185.5 (CvO). In the reaction mixture, the
ratio (13): (14) was 1:1.4.
4.1.5. Reaction of exo-3,7,7-tribromobicyclo[4.1.0]hep-
tan-2-one (10) with sodium iodide in acetone. A solution
of exo-3,7,7-tribromide (10) (100 mg, 0.29 mmol) and
sodium iodide (96 mg, 0.64 mmol, 2.2 mol. equiv.) in
acetone (HPLC grade, 3 mL) was stirred at ambient
temperature in the dark. After 11 h, the mixture was poured
into water (15 mL), extracted with dichloromethane
(4£5 mL), decolorized with aq. sodium thiosulfate, dried
and concentrated in vacuo to give an oil (86 mg), which
1
contained by H NMR starting material (57%), (14) (8%),
(15) (13%) and (16) (22%). Chromatography of this oil
(60 mg) on Silica (20 g) eluting with petrol–ether 3:1 gave
starting material (26 mg, Rf 0.68) as a colorless viscous oil
with spectral data identical to those above, a mixture of 7,7-
dibromobicyclo-[4.1.0]heptan-2-one (16) (for data see
reaction of (10) with thiourea) and 4-iodo-7,7-dibromobi-
cyclo[4.1.0]hept-3-en-2-on-3-ol (15) (16 mg, Rf 0.46, as a
colorless oil with yellow crystals) which showed dH: 2.42–
2.48 (1H, m), 2.91 (1H, d, J¼9.5 Hz), 3.28 (1H, d,
J¼20.2 Hz), 3.44 (1H, dd, J¼20.2, 8.5 Hz), 6.57 (1H,
br.s); dC: 25.0, 34.1þ, 36.12, 37.1þ, 93.1, 148.7, 179.8;
MS (CI, 70 eV, methane): 410 (14), 409 (11), 408 (32), 407
(21), 406 (15), 405 (9), 329 (96), 327 (100), 301 (5), 299 (5);
found [M2H]þ 408.7596; calcd for C7H4O281Br2I 408.7582;
and 7,7-dibromobicyclo[4.1.0]hept-3-en-2-on-3-ol (14)39
(3 mg, Rf 0.31) as a colorless viscous oil with spectral
4.1.3. endo-8,8-Dibromo-3-oxatricyclo[5.1.0.02,4]octane
(12). Ethanolic sodium hydroxide (1.0 mL, C 0.44 M,
0.44 mmol) was added to exo-3,7,7-tribromobicyclo[4.1.0]-
heptan-endo-2-ol (11) (106 mg, 0.3 mmol), stirred for 4 h
at ambient temperature, then poured in water (5 mL),
extracted with dichloromethane (4£2 mL), dried and
concentrated in vacuo to give an oil (99 mg). This was
purified on Silica (5 g) eluting with petrol–ether 10:1 to
give endo-8,8-dibromo-3-oxatricyclo[5.1.0.02,4]octane (12)
(81 mg, 100%, Rf 0.31) as white crystals (mp 75.5–76 8C)
which showed dH: 1.25–1.41 (1H, m), 1.59–1.75 (2H, m),
1.90–2.05 (3H, m), 3.00 (1H, dd, J¼3.7, 3.5 Hz), 3.46 (1H,
ddd, J¼4.0, 3.7, 0.8 Hz); dC: 16.32, 21.22, 24.4þ, 26.6þ,
31.2, 46.8þ, 47.7þ; IR (cm21, in CHCl3): 3013m, 2940m,
1416m, 1349m, 1081s, 1053s, 984m, 893m, 834m, 818s,
622m; calcd C 31.38, H 3.01%, found C 31.6, H 2.7%.
1
data identical to those above (this contained by H NMR
about 50% unidentified impurities).
4.1.6. Reaction of exo-3,7,7-tribromobicyclo[4.1.0]hep-
tan-2-one (10) with thiourea. exo-3,7,7-Tribromobicyclo-
[4.1.0]heptan-2-one (10) (173 mg, 0.5 mmol) and thiourea
(114 mg, 1.5 mmol) were refluxed in methanol (1.5 mL) for
4 h. The mixture was cooled to room temperature, then
poured into a mixture of dichloromethane (9 mL), water
(4 mL) and sat. aq. sodium bicarbonate (1.5 mL). The water
layer was extracted with dichloromethane (4£3 mL). The
combined organic layers were washed with water (34 mL),
dried, filtered and concentrated in vacuo to give mixture of a
yellow oil with a yellow solid (149 mg). This was separated
on Silica (20 g) eluting with 1:2 petrol–ether to give (17)
(51 mg, 32%, Rf 0.36) as white solid with mp 138.5–139 8C
(dec.) which showed dH: 2.13–2.27 (3H, m), 2.61 (1H, ddd,
J¼16.4, 8.7, 7.6 Hz), 2.70 (1H, dddd, J¼16.4, 7.6, 5.4,
1.3 Hz), 2.77 (1H, d, J¼10.4 Hz), 4.70–5.10 (2H, br.s); dC:
20.02, 20.32, 29.3þ, 30.7þ, 37.1, 120.0, 141.6, 164.7; IR
(cm21, CHCl3): 1621s, 1583m, 1540s, 1524s, 1431m,
1400m, 1364m, 1308s, 1113m, 1090m, 1070m; calcd C
29.65, H 2.49, N 8.65%, found C 30.0, H 2.7, N 8.8%. A
mixture of other products (96 mg) was also isolated as white
solid together with a colorless oil. This was again separated
on Silica (15 g) eluting with 4:1 petrol–ether to give
7,7-dibromobicyclo-[4.1.0]heptan-2-one (16) (55 mg, 41%,
Rf 0.38) as a colorless oil which showed dH: 1.72–1.82 (2H,
m), 1.94–2.00 (1H, m), 2.20–2.28 (2H, m), 2.31–2.38 (1H,
m), 2.40–2.47 (1H, m), 2.50 (1H, d, J¼9.5 Hz); dC: 21.12,
23.92, 31.2, 35.0þ, 38.1þ, 38.42, 202.2; IR (cm21, film):
2947m, 2867m, 1702s, 1445m, 1412m, 1354m, 1323s,
1306m, 1232m, 1179m, 1148s, 951m, 737s; calcd C 31.38,
H 3.01%, found C 31.7, H 3.0%.
4.1.4. Reaction of exo-3,7,7-tribromobicyclo[4.1.0]hep-
tan-2-one (10) with pyridine. A solution of pyridine
(87 mg, 1.098 mmol, 3 mol. equiv.) and exo-3,7,7-tribro-
mide (10) (127 mg, 0.366 mmol) in dry DMSO (3 mL) was
stirred at 90–95 8C. After 4 h the mixture was cooled to
room temperature, diluted with dichloromethane (10 mL)
and extracted with 1 M hydrochloric acid (15 mL). The
water layer was extracted with dichloromethane (3£5 mL).
The combined organic layers were washed with water
(2£10 mL), dried and concentrated in vacuo to give a
yellow solid (108 mg). Chromatography on Silica (25 g)
eluting with 3:1 petrol–ether gave 4,7,7-tribromobicyclo-
[4.1.0]hept-3-en-2-on-3-ol (13) (24.6 mg, Rf 0.31) as white
crystals which showed dH: 2.49 (1H, dd, J¼9.5, 8.5 Hz,
H-6), 2.91 (1H, d, J¼9.5 Hz, H-1), 3.19 (1H, d, J¼20.2 Hz,
H-5endo), 3.36 (1H, dd, J¼20.2, 8.5 Hz, H-5exo), 6.37 (1H,
br.s, OH); dC: 25.0, 31.7þ, 32.42, 36.7þ, 116.6, 145.1,
182.2 (CvO); IR (cm21, in CHCl3): 3382s, 3040m, 1667s,
1633s, 1375s, 1321s, 1284m, 1189s, 1077m, 944m; MS:
364 (1.3), 362 (4.5), 360 (4.5), 358 (1.3), 283 (29), 281
(100), 279 (36), 255 (1.3), 253 (3.2), 251 (1.3), 202 (7), 200
(7), 174 (11), 172 (11); found Mþ 359.7825; calcd for
C7H5O729Br81Br2 359.7819; and 7,7-dibromobicyclo[4.1.0]-
hept-3-en-2-on-3-ol (14)39 (Rf 0.22) in a mixture with enone
(13) (40.1 mg) as a white solid which showed dH: 2.47–2.52
(1H, m), 2.76–2.85 (2H, m), 2.92 (1H, ddd, J¼21.1, 8.5,
4.1 Hz, H-5exo), 5.85 (1H, ddd, J¼4.7, 4.1, 0.9 Hz, H-4),
5.95 (1H, br.s, OH); dC: 22.62, 25.9, 32.2þ, 37.3þ,

A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
3725
4.1.7. Oxidation of 6,6-dibromobicyclo[3.1.0]hexane (18)
with chromium trioxide in acetic acid. 6,6-Dibromo-
bicyclo[3.1.0]hexane (18) (2.399 g, 10 mmol) was added to
a suspension of chromium trioxide (15.00 g, 150 mmol) in
glacial acetic acid (50 mL). The mixture was stirred at 30–
31 8C for 1 h, then poured into mixture of water (200 mL)
and dichloromethane (100 mL). The organic layer was
separated and the aqueous layer was extracted with
dichloromethane (3£50 mL). The combined organic layers
were washed with water (2£50 mL), extracted with sat. aq.
sodium bicarbonate (2£30 mL), water (30 mL), dried,
filtered and concentrated in vacuo to give an oil (1.74 g).
This was separated on Silica (100 g) eluting with 20:1
petrol–ether to give starting material (84 mg, 4%, Rf 0.91),
exo-3,6,6-tribromobicyclo[3.1.0]hexan-2-one (19) (984 mg,
30%, Rf 0.30) as white crystals (mp 44.5–46.5 8C) which
showed dH: 2.65 (1H, ddd, J¼15.5, 6.7, 5.3 Hz, H-4exo),
2.80 (1H, dd, J¼6.7, 6.7 Hz, H-5), 2.88 (1H, dd, J¼15.5,
8.2 Hz, H-4endo), 2.90 (1H, d, J¼6.7 Hz, H-1), 4.27 (1H, dd,
J¼8.2, 5.3 Hz, H-3); dC: 27.2, 25.52, 37.9þ, 42.7þ, 44.8þ,
200.42 (CvO); IR (cm21, CHCl3): 1748s (CvO), 974m;
MS: 255 (28), 253 (56), 251 (28), 55 (100); calcd C 21.65, H
1.51%, found C 21.8, H 1.7%; exo-2,6,6-tribromobicyclo-
[3.1.0]hexan-3-one (20) (100 mg, 3%, Rf 0.39) as white
crystals (mp 101–105 8C (dec.)) which showed dH: 2.48
(1H, d, J¼19.5 Hz, H-4endo), 2.54 (1H, dd, J¼8.3, 6.4 Hz,
H-5), 2.65 (1H, d, J¼8.3 Hz, H-1), 2.87 (1H, dd, J¼19.5,
6.4 Hz, H-4exo), 4.08 (1H, s, H-2); dC: 31.2þ, 33.9, 37.72,
37.8þ, 44.3þ, 206.4 (CvO); IR (cm21, CHCl3): 1753s
(CvO), 1137m, 1034m; MS: 255 (31), 253 (62), 251 (31);
calcd C 21.65, H 1.51%, found C 22.0, H 1.3%; exo,exo-
2,4,6,6-tetrabromo-bicyclo[3.1.0]hexan-3-one (21) (64 mg,
2%, Rf 0.48) as white crystals (mp 110.0–115.0 8C (dec.))
which showed dH: 2.87 (2H, s, H-1, H-5), 4.17 (2H, s, H-2,
dd, J¼15.1, 8.5 Hz, H-4endo), 4.28 (1H, ddd, J¼8.5, 6.9,
6.9 Hz, H-3), 4.86 (1H, ddd, J¼8.1, 7.9, 6.9 Hz, H-2); dC:
31.0, 37.0þ, 38.12, 40.2þ, 50.2þ, 85.4þ; IR (cm21
,
CHCl3): 3300br.s (OH), 3050m, 1438m, 1329m, 1266m,
1083s, 1070s, 1028m, 932m, 904m, 856m, 806m, 790s,
720m; calcd C 21.52, H 2.11%, found C 21.4, H 2.2%.
4.1.9. endo-7,7-Dibromo-3-oxatricyclo[4.1.0.02,4]heptane
(23). Ethanolic sodium hydroxide (1.78 mL, C 0.21 M,
0.366 mmol) was added to (22) (30.6 mg, 0.091 mmol) and
stirred for 96 h at ambient temperature, then poured into
water (25 mL), extracted with dichloromethane (4£5 mL),
dried and concentrated in vacuo to give endo-7,7-dibromo-
3-oxatricyclo[4.1.0.02,4]heptane (23) (21.4 mg, 92%) as a
yellow oil which showed dH: 1.94 (1H, ddd, J¼16.1, 7.6,
2.5 Hz), 2.04 (1H, dd, J¼16.1, 2.5 Hz), 2.25 (1H, dd, J¼8.3,
2.9 Hz), 2.73–2.76 (1H, m), 3.78–3.80 (2H, m); dC:
29.42, 33.6þ, 34.8, 47.4þ, 58.2þ, 68.3þ; IR (cm21
,
film): 3031m, 2922m, 1424m, 1306m, 1232m, 1193m,
1053m, 1019s, 957m, 873m, 841s, 788m, 724m, 705m,
681m; MS (CI, 70 eV, methane): 257 (9), 255 (18), 253
(6), 176 (22), 175 (63), 174 (27), 173 (53), 147 (97), 145
(100); found [MþH]þ 252.8858; calcd for C6H7OBr2
252.8864.
4.1.10. Oxidation of 9,9-dibromobicyclo[6.1.0]nonane
(24) with chromium trioxide. (a) In acetic acid. 9,9-Di-
bromobicyclo[6.1.0]nonane (24) (846 mg, 3 mmol) was
added to a suspension of chromium trioxide (2.40 g,
24 mmol) in glacial acetic acid (20 mL). The mixture was
stirred at 30–31 8C for 1 h, then poured into a mixture of
water (100 mL) and dichloromethane (50 mL). The organic
layer was separated and the aqueous layer was extracted
with dichloromethane (3£30 mL). The combined organic
layers were washed with water (2£30 mL), extracted with
sat. aq. sodium bicarbonate (2£15 mL), brine (2£20 mL),
dried, filtered and concentrated in vacuo to give an oil
(680 mg). This was separated on Silica (70 g) eluting with
petrol–ether 5:1 to give starting material (31 mg, 4%),
9,9-dibromobicyclo[6.1.0]nonan-4-one (25)21 (424 mg, 48%,
Rf 0.20) as white crystals (mp 55–56 8C), 9,9-dibromo-
bicyclo[6.1.0]nonan-2-one (26) (116 mg, 13%, Rf 0.36) as
white crystals (mp 66–69 8C from hexane) which showed
dH: 1.05–1.27 (1H, m), 1.32–2.0 (6H, m), 2.05–2.43 (3H,
m), 2.5–2.65 (1H, m), 2.58 (1H, d, J¼11.7 Hz); dC: 24.42,
27.02, 27.32, 28.1, 37.2þ, 39.3þ, 45.92, 205.6; IR
(cm21, in CHCl3): 2930s, 2858m, 1708s, 1452m, 1355m;
calcd C 36.52, H 4.09%, found C 36.9, H 4.0%; and
9,9-dibromobicyclo[6.1.0]nonan-3-one (27)21 (7 mg, 1%, Rf
0.27) as a yellow viscous oil.
H-4); dC: 30.2, 37.9þ, 39.0þ, 203.3 (CvO); IR (cm21
,
CHCl3): 1761s (CvO); MS: 293 (4), 291 (12), 289 (12),
287 (4), 255 (36), 253 (72), 251 (36), 227 (25), 225 (50), 223
(25), 65 (100); calcd C 17.51, H 0.98%, found C 18.0, H
0.7%.
The combined sodium bicarbonate layers were washed
with dichloromethane (2£10 mL), then acidified with
hydrochloric acid to pH 1 and extracted with dichloro-
methane (3£15 mL). The combined organic layers were
washed with water (10 mL), dried and concentrated in
vacuo to give a yellow viscous oil (103 mg), which was not
identified.
4.1.8. exo-3,6,6-Tribromobicyclo[3.1.0]hexan-endo-2-ol
(22). Sodium borohydride (19.0 mg, 0.50 mmol) was
added to a solution of (19) (167.5 mg, 0.50 mmol) in dry
ethanol (4 mL) and benzene (0.8 mL) and stirred at ambient
temperature. After 10 min, TLC showed no starting
material. The mixture was poured in water (20 mL) and
extracted with dichloromethane (4£5 mL). The combined
organic layers were washed with water (10 mL), dried and
concentrated in vacuo to give white solid (170 mg). This
was purified on Silica (40 g) eluting with 3:1 petrol–ether to
give exo-3,6,6-tribromobicyclo[4.1.0]heptan-endo-2-ol (22)
(146 mg, 87%, Rf 0.33) as white crystals (mp 111.5–
112 8C) which showed dH: 2.30 (1H, d, J¼8.1 Hz, OH), 2.33
(1H, dd, J¼7.9, 6.3 Hz, H-1), 2.49 (1H, dd, J¼8.4, 6.3 Hz,
H-5), 2.52 (1H, ddd, J¼15.1, 8.4, 6.3 Hz, H-4exo), 2.74 (1H,
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), then acidified with hydrochloric
acid to pH 1 and extracted with dichloromethane (3£5 mL).
The combined organic layers were washed with water
(10 mL), dried, filtered and concentrated in vacuo to give
colorless oil (79 mg), which was dissolved in ether
(1.5 mL), treated with diazomethane and evaporated in
vacuo to give a mixture (77 mg, 7%) of dimethyl 2,3-(di-
bromomethano)suberate, dimethyl 3,4-(dibromomethano)-
suberate and dimethyl 4,5-(dibromomethano)-suberate
(analyzed as mixture of isomers) as a slightly yellow oil
which showed dH: 1.15–2.15 (6H, m), 2.25–2.65

3726
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
(4H, m), region 3.6–3.75 contained 5 singlets at 3.65, 3.66,
3.69, 3.71, 3.72 with ratio 9:7:4:7:9 respectively by
1H NMR.
material using ether. The resulting solution was concen-
trated in vacuo and analyzed by GLC (see Table 3).
4.1.13. Oxidation of bicyclo[6.1.0]nonane (3), 9-bromo-
bicyclo[6.1.0]nonane (29) and 9,9-dibromobicyclo-
[6.1.0]nonane (24) with chromium trioxide. A solution
of a mixture of (3) (124 mg, 1 mmol), (29) (203 mg,
1 mmol, exo–endo¼1:2.5) and (24) (282 mg, 1 mmol) in
glacial acetic acid (2 mL) was added to a suspension of
chromium trioxide (2.40 g, 24 mmol) in glacial acetic acid
(18 mL). The mixture was stirred at 30–31 8C for 1 h.
Aliquots (about 0.5 mL) were taken after each 5 min,
quenched with sat. aq. sodium bicarbonate (20 mL) which
was added until the formation of CO2 was complete. This
was extracted with ether (2 mL) and the organic layer was
analyzed by GLC and GC/MS. The results of this are
presented in Table 4.
(b) In dichloromethane in the presence of 3,5-dimethyl-
pyrazole. Chromium trioxide (6.00 g, 60 mmol) and
dichloromethane were mixed and the resulting suspension
was cooled to 220 8C when 3,5-dimethylpyrazole (5.768 g,
60 mmol) was added. The mixture was stirred at 215 to
220 8C for 15 min to give a dark solution, then (24)
(846 mg, 3 mmol) was added. The mixture was stirred at
215 to 225 8C for 1 h, at 20 8C for 1 h, then refluxed for
18 h, cooled to room temperature and washed with 15%
hydrochloric acid (3£20 mL), water (2£15 mL), dried
and concentrated in vacuo to give starting material
(810 mg, 96%).
(c) In acetone. Chromium trioxide (6.00 g, 60 mmol) was
added in portions to acetone (20 mL) at 1 8C over 15 min at
below 15 8C. Then (24) (846 mg, 3 mmol) was added in one
batch. No exothermic effect was observed. The mixture was
stirred at 19–20 8C for 1 h and analyzed by GLC. No
products of oxidation were formed.
4.1.14. Oxidation of 8,8-dibromobicyclo[5.1.0]octane
(35) with chromium trioxide in acetic acid. 8,8-Di-
bromobicyclo[5.1.0]octane (35) (804 mg, 3 mmol) was
added to a suspension of chromium trioxide (4.50 g,
45 mmol) in glacial acetic acid (15 mL). The mixture was
stirred at 30–31 8C for 2 h and poured into a mixture of
water (100 mL) and dichloromethane (50 mL). The organic
layer was separated and the aqueous layer was extracted
with dichloromethane (3£30 mL). The combined organic
layers were washed with water (2£30 mL), extracted with
sat. aq. sodium bicarbonate (2£20 mL), brine (2£20 mL),
dried and concentrated in vacuo to give an oil (409 mg),
which contained at least four main products with retention
time 7.55 (6%), 8.50 (30%), 10.65 (33%) and 11.65 min
(25%). Starting material had retention time 4.55 min and it
was fully converted after 2 h, but after 1 h the reaction
mixture contained approximately 50% of dibromide (35).
Chromatography on Silica (200 g) eluting with 5:1 petrol–
ether gave 7 fractions (the reaction mixture showed on TLC
at least 5 spots with Rf 0.46, 0.40, 0.35, 0.20, 0.15). One of
the major products (with Rt 8.50 min) was isolated nearly
4.1.11. Oxidation of 9,9-dibromobicyclo[6.1.0]nonane
(24) with periodic acid. A mixture of dibromide (24)
(846 mg, 3 mmol), carbon tetrachloride (10 mL), aceto-
nitrile (10 mL), water (15 mL), periodic acid (5.47 g,
24 mmol) and ruthenium trichloride (42 mg, 0.15 mmol,
5 mol%) was stirred at 70–75 8C. After 52 h the black
mixture was cooled, poured into water (20 mL) and
extracted with dichloromethane (3£10 mL). The combined
organic layers were washed with water (10 mL), extracted
with sat. aq. sodium bicarbonate (2£10 mL), washed with
water (10 mL), dried, filtered and concentrated in vacuo to
give an oil (574 mg). This was separated on Silica (70 g)
eluting with 5:1 petrol–ether to give starting material
(75 mg, 9%) as a colorless oil, 2521 (325 mg, 37%) as white
crystals, 26 (61 mg, 7%) as white crystals and 2721 (18 mg,
2%) as a yellow oil with spectral and analytical data
identical to those above.
1
pure; according to H and 13C NMR spectra, it was not
8,8-dibromobicyclo[5.1.0]octan-4-one25 and showed dH:
1.03–1.26 (1H, m), 1.37–1.71 (3H, m), 1.82–2.06 (3H,
m), 2.43–2.55 (3H, m); dC: 24.02, 25.02, 29.42, 30.1,
32.0þ, 41.2þ, 44.42, 202.2. The structure of this
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), then acidified with hydrochloric
acid to pH 1. The mixture was extracted with dichloro-
methane (5£5 mL). The combined organic layers were
washed with water (10 mL), dried and concentrated in
vacuo to give a colorless oil (386 mg), which was dissolved
in ether (1.5 mL), treated with diazomethane and evapor-
ated in vacuo to give a mixture (192 mg, 17%) of dimethyl
2,3-(dibromomethano)suberate, dimethyl 3,4-(dibromo-
methano)suberate and dimethyl 4,5-(dibromomethano)-
suberate as a slightly yellow oil with spectral data
identical to those above.
1
compound is unknown. According to H NMR data some
products contained the CHBr fragment (signals at 4.2–
4.5 ppm), some of them not. According to 13C NMR data all
products contained a CvO fragment (dC: 200–202 ppm).
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), then acidified with hydrochloric
acid to pH 1 and extracted with dichloromethane
(5£10 mL). The combined organic layers were washed
with water (10 mL), dried and concentrated in vacuo to give
a yellow oil (109 mg), which was dissolved in ether (2 mL),
treated with diazomethane, dried and evaporated in vacuo to
give a mixture (95 mg, 9%) of, presumably, dimethyl 2,3-
(dibromomethano)pimelate and dimethyl 3,4-(dibromo-
methano)pimelate in 54:36 ratio by GLC (attribution of
peaks unknown) as a slightly yellow oil which showed dH:
1.62–2.12 (5H, m), 2.30–2.65 (3H, m), region 3.6–3.73
contained 4 singlets at 3.66, 3.68, 3.716, 3.723 with ratio
4:3:3:4 respectively by 1H NMR; dC: 22.82, 23.52, 26.02,
4.1.12. Dry ozonolysis of 9,9-dibromobicyclo[6.1.0]-non-
ane (24). Silica gel (34 g) was added to a solution of (24)
(846 mg, 3 mmol) in pentane (100 mL) and the solvent was
evaporated in vacuo. The resulting powder was placed in a
U-tube, cooled to 280 8C and a stream of ozone (2.5 g/h)
was then passed through it for 20 min. It was then allowed to
warm slowly, over 3 h, to room temperature and this cycle
was repeated three times followed by elution of the organic

A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
3727
28.5, 29.2þ, 32.02, 32.22, 32.3þ, 33.42, 33.8, 34.5þ,
37.2þ, 51.6þ, 51.7þ, 52.1þ, 53.2þ, 167.0, 171.5, 172.9,
173.5.
d, J¼7.3 Hz), 2.61 (1H, dd, J¼18.8, 2.5 Hz), 2.77–2.80
(2H, m) (for confirmation of structure of (43), a comparison
of the 1H NMR of this compound with spectra for the non-
brominated ketone (46) and pinocarvone were made
(supplementary information available)); dC: 21.5þ, 25.4þ,
30.6, 32.82, 34.62, 38.4þ, 40.0, 44.52, 44.8, 49.0þ,
204.5; IR (cm21, film): 2950m, 1714s, 1463m, 1410m,
1388m, 1371m, 1336m, 1256m, 1123m, 1064m, 1020m,
911m, 705m; MS (CI, 70 eV, methane): 325 (55), 324 (26),
323 (100), 322 (14), 290 (7), 289 (10), 287 (10), 281 (7), 279
(18), 277 (9); found [MþH]þ 324.9448; calcd for
C11H15O81Br2 324.9449; a mixture of a-ketone (43) with
at least four unidentified compounds (170 mg, Rf 0.56, 0.49,
0.46, 0.39 and 0.34), one of them containing a COCHBr
fragment based on the 1H NMR data (dd at 4.85 ppm) and,
as a colorless oil, a mixture of b-ketone (44) which showed
in CDCl3 dH: 1.07 (3H, s), 1.25 (3H, s), 1.66 (1H, d, J¼
7.4 Hz), 1.90–1.93 (1H, m), 2.02 (1H, d, J¼7.4 Hz), 2.13–
2.16 (2H, m), 2.36–2.39 (1H, m), 2.53 (2H, d, J¼2.4 Hz);
dC: 21.6þ, 21.8þ, 33.0, 35.72, 37.82, 39.3, 40.52, 48.7,
54.0þ, 61.0þ, 215.6 and in C6D6 dH: 0.64 (3H, s), 0.66 (3H,
s), 1.00 (1H, d, J¼7.3 Hz), 1.31 (1H, dd, J¼4.4, 1.6 Hz),
1.40 (1H, d, J¼7.3 Hz), 1.50 (1H, dd, J¼14.5, 4.7 Hz), 1.96
(1H, d, J¼14.5 Hz), 2.03 (1H, dd, J¼4.7, 1.6 Hz), 2.20 (1H,
dd, J¼18.3, 4.4 Hz), 2.48 (1H, d, J¼18.3 Hz) (signals for
this ketone were distinguished from crude NMR data by
2D spectra {COSY and HNQC} and selective decoupling
experiments); GC/MS (Rt 15.75 min, EI, 70 eV): 324 (0.6),
322 (1.8), 320 (1), 243 (9), 242 (3), 241 (9), 240 (3), 214 (6),
212 (12), 210 (6); found Mþ 319.9411; calcd for
C11H14O79Br2 319.9425; with cyclobutanone derivative
(45) which showed dH: two methyl groups at 0.97 and
1.40 ppm and two doublets for one proton each at 1.63 and
1.71 ppm with J¼7.8 Hz; dC: for CvO bond 209.9 ppm
(other signals were not distinguished from crude NMR);
GC/MS (Rt 15.88 min, EI, 70 eV): 243 (5), 242 (2), 241 (5),
240 (2); found [M2HBr]þ 240.0150; calcd for
C11H13O79Br 240.0152. Assignment of structure for cyclo-
butanone derivative (45) is based on the MS spectrum,
which was similar to that of b-ketone (44), and the IR
spectrum for the mixture which showed signals for CvO
4.1.15. Oxidation of 1,1-dibromo-2-butylcyclopropane
(36) with chromium trioxide in acetic acid. 1,1-Dibromo-
2-butylcyclopropane (36) (768 mg, 3 mmol) was added to
a suspension of chromium trioxide (3.00 g, 30 mmol) in
glacial acetic acid (20 mL). The mixture was stirred at
30–31 8C for 1 h, then poured into water (100 mL) and
dichloromethane (50 mL). The organic layer was separated
and the aq. layer was extracted with dichloromethane
(3£30 mL). The combined organic layers were washed with
water (2£50 mL), extracted with sat. aq. sodium bicarbo-
nate (3£20 mL), brine (2£20 mL), dried and concentrated
in vacuo to give oil (606 mg). This was separated on Silica
(70 g) eluting with petrol–ether 20:1 to give (36) (176 mg,
23%) and 1-(2,2-dibromocyclopropyl)-butan-1-one (37)
(196 mg, 24%, Rf 0.35) as a colorless oil which showed
dH: 1.00 (3H, t, J¼7.4 Hz), 1.73 (2H, m), 1.93 (1H, dd,
J¼9.1, 7.4 Hz), 2.23 (1H, dd, J¼7.8, 7.4 Hz), 2.68 (2H, m),
2.83 (1H, dd, J¼9.1, 7.8 Hz); dC: 13.4þ, 16.62, 21.0,
27.02, 38.5þ, 46.42, 201.5; IR (cm21, film): 2962m,
2874m, 1716s, 1370s, 1105m, 1069m; found Mþ 271.9047;
81
10
calcd for C7H Br2 271.9057.
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), acidified with hydrochloric acid
to pH 1, then extracted with dichloromethane (4£10 mL).
The combined organic layers were washed with water
(20 mL), dried and concentrated in vacuo to give a colorless
oil (151 mg) which was dissolved in ether (2 mL), treated
with diazomethane and evaporated in vacuo to give a
mixture (143 mg, ca. 18%) of methyl 2,2-dibromocyclo-
propanecarboxylate and methyl (2,2-dibromocyclo-propyl)-
acetate40 (ratio 1:2, respectively by 1H NMR and GLC) as a
colorless oil. Methyl (2,2-dibromocyclopropyl)acetate
showed dH: 1.36 (1H, dd, J¼7.1, 7.1 Hz), 1.85–2.02 (2H,
m), 2.50 (1H, dd, J¼17.0, 7.0 Hz), 2.73 (1H, dd, J¼17.0,
6.8 Hz), 3.75 (3H, s); GC/MS: 274 (0.5), 272 (1), 270 (0.5),
243 (1), 241 (2), 239 (1), 53 (100); found Mþ 273.8846;
calcd for C6H8O821Br2 273.8850.
bonds at 1750 cm21, attributed to (45) and 1717 cm21
,
attributed to (44). Treatment of this mixture (170 mg) in dry
ethanol (2 mL) at 5 8C with 2,4-dinitrophenylhydrazine
(123 mg, 0.62 mmol) in dry ethanol (2 mL) and sulfuric
acid (0.26 mL) afforded after 5 min an orange precipitate,
which was filtered after 2 h, washed with cold ethanol
(2£5 mL), dried in vacuo over calcium chloride and
recrystallized from 2:1 hexane–benzene (6 mL) to give
the 2,4-dinitrophenylhydrazone of (44) (16 mg) as orange
crystals (mp 168–169 8C (dec.)) which showed dH: 0.95
(3H, s), 1.43 (3H, s), 1.70 (1H, d, J¼11.0 Hz), 1.73 (1H, d,
J¼7.9 Hz), 1.78 (1H, d, J¼7.9 Hz), 2.17 (1H, dd, J¼5.7,
5.4 Hz), 2.51 (1H, d, J¼18.6 Hz), 2.73 (1H, ddd, J¼11.0,
5.7, 5.4 Hz), 2.92 (1H, dd, J¼5.4, 5.4 Hz), 3.37 (1H, d,
J¼18.6 Hz), 7.97 (1H, d, J¼9.5 Hz), 8.31 (1H, dd, J¼9.5,
2.5 Hz), 9.13 (1H, d, J¼2.5 Hz), 11.04 (1H, s); dC: 23.3þ,
25.5þ, 27.42, 30.7, 32.72, 36.1, 36.52, 42.3, 50.5þ,
50.8þ, 116.3þ, 123.5þ, 129.2, 130.0þ, 137.9, 145.0,
160.7; IR (cm21, in CHCl3): 3302m, 2964m, 1618s,
1584s, 1538m, 1517m, 1497s, 1426s, 1368m, 1338s,
1309s, 1273s, 1256s, 1129m, 1066m, 695m, 669m; calcd
C 40.66, H 3.61, N 11.16%, found C 40.8, H 3.7, N 11.5%.
4.1.16. Oxidation of dibromocarbene adduct of (1S)-b-
pinene (42) with chromium trioxide in acetic acid. gem-
Dibromocyclopropane (42) (924 mg, 3 mmol) was added to
a suspension of chromium trioxide (3.00 g, 30 mmol) in
glacial acetic acid (20 mL). The mixture was stirred at 30–
31 8C for 1 h, then poured into a mixture of water (100 mL)
and dichloromethane (50 mL). The organic layer was sepa-
rated and the aqueous layer was extracted with dichloro-
methane (3£30 mL). The combined organic layers were
washed with water (2£30 mL), extracted with sat. aq.
sodium bicarbonate (2£15 mL), brine (2£20 mL), dried and
concentrated in vacuo to give an oil (680 mg), which
contained by 1H NMR starting material (42) (25%),
a-ketone (43) (38%), b-ketone (44) (27%) and cyclobuta-
none derivative (45) (10%). This oil was separated on Silica
(70 g) eluting with 5:1 petrol–ether to give (42) (72 mg,
8%, Rf 0.95), a-ketone (43) (31 mg, Rf 0.56) as a colorless
oil which showed dH: 0.92 (3H, s), 1.37 (3H, s), 1.63 (1H, d,
J¼7.3 Hz), 1.65 (1H, d, J¼10.7 Hz), 2.17 (1H, dd, J¼6.0,
6.0 Hz), 2.28 (1H, dddd, J¼6.0, 5.0, 3.9, 2.5 Hz), 2.51 (1H,

3728
A. V. Nizovtsev et al. / Tetrahedron 60 (2004) 3717–3729
The combined sodium bicarbonate layers were washed with
dichloromethane (2£10 mL), then acidified with hydro-
chloric acid to pH 1 and extracted with dichloromethane
(3£10 mL). The combined organic layers were washed with
water (10 mL), dried and concentrated in vacuo to give a
colorless oil, which was dissolved in ether (3 mL), treated
with diazomethane and evaporated in vacuo to give a
mixture (191 mg) of unidentified methyl esters.
layers were washed with water (2£20 mL), extracted with
sat. aq. sodium bicarbonate (3£10 mL), brine (2£20 mL),
dried and concentrated in vacuo to give starting material
(49) (570 mg, 70%) as slightly yellow oil.
The combined sodium bicarbonate layers were washed with
dichloromethane (20 mL), then acidified with hydrochloric
acid to pH 1 and extracted with dichloromethane
(4£10 mL). The combined organic layers were washed
with water (20 mL), dried and concentrated in vacuo to give
2,2-dibromo-1-methylcyclopropanecarboxylic acid (48)
(87 mg, 11%) as a white solid.41
Oxidation of gem-dibromocyclopropane (42) (3.081 g,
10 mmol) as above with subsequent addition of 2,4-dinitro-
phenylhydrazine (1.183 g, 5.97 mmol) in dry ethanol
(15 mL) and sulfuric acid (2.5 mL) to a solution of the
neutral fraction of the reaction mixture (1.988 g) in dry
ethanol (5 mL) and stirring over 24 h, afforded an orange
precipitate. This was washed with cold water–methanol
(1:1) and recrystallized from isopropanol (precipitation was
very slow) to give 2,4-dinitrophenylhydrazone of a-ketone
(43) (65 mg) as orange crystals (mp 180–183 8C (dec.))
which showed dH: 0.98 (3H, s), 1.23 (3H, s), 1.58 (1H, d,
J¼7.6 Hz), 1.87 (1H, m), 1.96 (1H, d, J¼7.6 Hz), 2.09 (1H,
d, J¼13.9 Hz), 2.18 (1H, dd, J¼13.9, 4.4 Hz), 2.68 (1H, dd,
J¼4.4, 1.6 Hz), 2.70 (2H, m), 7.88 (1H, d, J¼9.6 Hz), 8.24
(1H, dd, J¼9.6, 2.6 Hz), 9.08 (1H, d, J¼2.6 Hz), 10.79 (1H,
s); dC: 21.4þ, 21.8þ, 31.02, 33.0, 38.02, 38.42, 39.2,
50.4, 54.5þ, 55.2þ, 116.4þ, 123.6þ, 129.1, 130.0þ, 137.7,
145.1, 166.9; IR (cm21, in CHCl3): 3308m, 3110m, 2991m,
2958m, 2940m, 1650m, 1613s, 1589s, 1638s, 1513s,
1470m, 1455m, 1420s, 1393m, 1364s, 1336s, 1312s,
1288s, 1268s, 1180m, 1137s, 1070s, 1042m, 1027m,
1015m, 922m, 842m, 833m, 691m; MS: 504 (39), 502
(91), 500 (37), 461 (8), 459 (16), 457 (8), 423 (20), 421 (20),
242 (16), 240 (20); found Mþ 499.9690; calcd for
C17H18N4O4Br2 499.9695.
4.1.19. Oxidation of acetate of (2,2-dibromo-1-methyl-
cyclopropyl)methanol (50) with chromium trioxide. The
acetate (50) (572 mg, 2 mmol) was added to a suspension of
chromium trioxide (4.00 g, 40 mmol) in glacial acetic acid
(12 mL). The mixture was stirred at ambient temperature for
24 h, then poured into water (100 mL) and dichloromethane
(50 mL). The organic layer was separated and the aq. layer
was extracted with dichloro-methane (3£30 mL). The com-
bined organic layers were washed with water (2£50 mL),
extracted with sat. aq. sodium bicarbonate (2£20 mL),
water (30 mL), dried and concentrated in vacuo to give
starting material (50) (74 mg, 13%) as slightly yellow oil.
The combined sodium bicarbonate layers were washed with
dichloromethane (10 mL), acidified with hydrochloric acid
to pH 1 and extracted with dichloromethane (4£10 mL).
The combined organic layers were washed with water
(10 mL), dried and concentrated in vacuo to give 2,2-di-
bromo-1-methylcyclopropancarboxylic acid (48) (385 mg,
75%) as a white solid.41
4.1.20. Oxidation of 1,1-dibromo-2-methyl-2-phenyl-
cyclopropane (51) with chromium trioxide in glacial
acetic acid. Dibromide (51) (870 mg, 3 mmol) was added
to a suspension of chromium trioxide (6.00 g, 60 mmol)
in glacial acetic acid (20 mL). The mixture was stirred at
30–31 8C for 1 h, then poured into water (100 mL) and
dichloro-methane (50 mL). The organic layer was separated
and the aq. layer was extracted with dichloromethane
(3£30 mL). The combined organic layers were washed with
water (2£50 mL), extracted with sat. aq. sodium bicarbo-
nate (2£20 mL), water (30 mL), dried and concentrated in
vacuo to give a mixture (672 mg) of acetophenone (52),
a-bromoacetophenone (53),42 a,a-dibromoacetophenone
(54),42 p-bromoacetophenone (55),43 a,p-dibromoaceto-
phenone (56)42 and a,a,p-tribromoacetophenone (57),44 in
4.1.17. Oxidation of 1,1-dibromo-2,2-dimethylcyclopro-
pane (47) with chromium trioxide. The dibromide (47)
(684 mg, 3 mmol) was added to a suspension of chromium
trioxide (6.00 g, 60 mmol) in glacial acetic acid (20 mL),
stirred at room temperature for 24 h, then poured into water
(100 mL) and dichloromethane (50 mL). The organic layer
was separated and the aqueous layer was extracted with
dichloromethane (3£30 mL). The combined organic layers
were washed with water (2£50 mL), extracted with sat. aq.
sodium bicarbonate (2£20 mL), brine (2£20 mL), dried and
concentrated at normal pressure to give starting material.
The combined sodium bicarbonate layers were washed with
dichloromethane (20 mL), acidified with hydrochloric acid
to pH 1 and extracted with dichloromethane (5£10 mL).
The combined organic layers were washed with water
(20 mL), dried and concentrated in vacuo to give 2,2-di-
bromo-1-methylcyclopropanecarboxylic acid (48) (67 mg,
9%) as a white solid.41
1
ratio 13:56:5:8:17:1 respectively by H NMR. The identity
of acetophenone derivatives was confirmed by direct
1
comparison of H NMR and GC/MS spectral data with
those of authentic samples or by comparison with literature
data.
4.1.18. Oxidation of methyl 2,2-dibromo-1-methylcyclo-
propanecarboxylate (49) with chromium trioxide.
Methyl
2,2-dibromo-1-methylcyclopropanecarboxylate
(49) (816 mg, 3 mmol) was added to a suspension of
chromium trioxide (9.00 g, 90 mmol) in glacial acetic acid
(20 mL), stirred at room temperature for 168 h, then poured
into water (100 mL) and dichloromethane (50 mL). The
organic layer was separated and the aq. layer was extracted
with dichloromethane (3£30 mL). The combined organic
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