Functional derivatives of α-bromocyclopropylmagnesium bromides

Full text of DOI:10.1007/s11178-005-0354-0

Russian Journal of Organic Chemistry, Vol. 41, No. 9, 2005, pp. 1394–1396. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 9, 2005,
pp. 1422–1424.
Original Russian Text Copyright © 2005 by Solov’eva, Baird, Bolesov.
SHORT
COMMUNICATIONS
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on His 70th Anniversary
Functional Derivatives
of α-Bromocyclopropylmagnesium Bromides
1
2
1
V. A. Solov’eva , M. S. Baird , and I. G. Bolesov
1
Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: ivbolesov@mail.ru
2
Department of Chemistry, University of Wales Bangor, LL 57 2UW Gwynedd, UK
Received June 2, 2005
The present communication reports on the results
of partial hydrodehalogenation of a series of func-
tionalized geminal dibromocyclopropanes. These sub-
strates attract interest as readily accessible precursors
neither products resulting from opening of cyclo-
propane ring nor other cyclopropane derivatives.
Therefore, we concluded that under the given condi-
tions the major or the only intermediates are α-bromo-
cyclopropylmagnesium bromides A and B.
(
or analogs) of practically important compounds [1, 2].
As shown in [3, 4], 1,1-dibromo-2-methyl-2-phenyl-
cyclopropane (I) reacts with 3–4 equiv of Grignard
compounds in THF at –60°C with subsequent decom-
position of the reaction mixture with methanol to
afford an approximately equimolar mixture of stereo-
isomeric monobromo derivatives (Scheme 1, see
table). Analogous reaction with allyl ether II and
acetate III also led to formation of ~1:1 mixtures of
the corresponding stereoisomeric partial hydrodebro-
mination products. The reaction mixtures contained
The depth of partial hydrodebromination of cyclo-
propanecarboxylic acid IV strongly depended on the
amount of the Grignard compound. The complete con-
version of acid IV was attained only with the use of
6 equiv of isopropylmagnesium bromide. It is known
that hydrodebromination of acid IV with methyl-
lithium is diastereoselective and enantioselective: it
leads to formation of the corresponding trans-bromo-
substituted carboxylic acid [5–7]. By contrast, the re-
action of IV with isopropylmagnesium bromide gave
Scheme 1.
(
1) MeOH
Br
Me
Ph
BrMg
Br
Me
H
Me
Ph
Br
Me
Ph
i-PrMgBr
(2) H O, HCl
2
+
Br
Ph
Br
H
I
A
Va
Vb
Br
Me
Br
BrMg
(1) MeOH
H
Br
i-PrMgBr
(2) H O, HCl
2
+
Br
CH OR
Br
Me
CH OR
Br
Me
VIa, VIIa
CH OR
H
CH OR
2
2
2
2
Me
II, III
Me
Me
Me
Me
B
VIb, VIIb
(1) MeOH
Me
COOH
BrMg
Br
Me
COOMgBr
H
Me
Br
Me
COOH
i-PrMgBr
(2) H O, HCl
2
+
Br
Br
COOH
H
IV
C
VIIIa
VIIIb
2 2
II, VI, R = CH =CHCH ; III, VII, R = MeCO.
1
070-4280/05/4109-1394 © 2005 Pleiades Publishing, Inc.

FUNCTIONAL DERIVATIVES OF α-BROMOCYCLOPROPYLMAGNESIUM BROMIDES
Hydrodebromination of dibromocyclopropanes I–IV
1395
Initial
compound no.
i-PrMgBr, equiv
(–60°C, 30 min)
Decomposition, min
(MeOH, –60°C)
a
cis/trans-Isomer ratio, %
Yield, %
I
0.2.5
05
10
10
10
34:66
37:63
45:55
75:25
87
79
95
83
II
3
3
6
III
IV
a
The isomer ratio was determined from the intensity ratio of signals from the CHBr protons, δ 3.0–3.7 ppm.
a mixture of stereoisomeric acids VIIIa and VIIIb, the
fraction of cis isomer VIIIa being about 75%.
organic phase was separated, the aqueous phase was
extracted with chloroform, the organic extract was
shaken with a saturated solution of potassium car-
bonate, and the aqueous solution was washed with
chloroform and acidified to pH 1 with concentrated
hydrochloric acid. Acids VIIIa and VIIIb were ex-
tracted into chloroform, the extract was dried over
magnesium sulfate, and the solvent was distilled off to
obtain a mixture of cis- and trans-bromocyclopropane-
carboxylic acids VIIIa and VIIIb.
Thus partial hydrodebromination of some func-
tional derivatives of geminal dibromocyclopropanes by
the action of isopropylmagnesium bromide in THF at
–
60°C, followed by treatment with methanol, gives
the corresponding monobromo derivatives V–VIII in
preparative yields without involving the other func-
tional groups. Analogous reaction with dibromocyclo-
propanecarboxylic acid IV leads to predominant
formation of cis-monobromide VIIIa.
cis-1-Bromo-2-methyl-2-phenylcyclopropane
1
(
Va) [3]. Colorless oily substance. H NMR spectrum,
Preparation of functionalized α-bromocyclo-
propylmagnesium bromides and their subsequent
decomposition (general procedure). A dry flask was
filled with argon and charged with a solution of
δ, ppm: 1.34–1.40 m (2H, J = 4.6, 7.3 Hz), 1.45 s (3H),
3.08 d.d (1H, J = 4.6, 7.3 Hz), 7.18–7.37 m (5H).
trans-1-Bromo-2-methyl-2-phenylcyclopropane
1
1
–3 mmol of dibromocyclopropane in 9 ml of anhy-
drous tetrahydrofuran. The solution was cooled to
65°C, and a solution of 2.5–6 equiv of isopropyl-
(Vb) [3]. Colorless oily substance. H NMR spectrum,
δ, ppm: 1.06 d.d (1H, J = 4.8, 6.3 Hz), 1.61 s (3H),
1.64 d.d (1H, J = 6.3, 8.0 Hz), 3.21 d.d (1H, J = 4.8,
8.0 Hz), 7.18–7.37 m (5H).
–
magnesium bromide in THF was added dropwise,
maintaning the temperature within the range from
cis-1-Allyloxymethyl-2-bromo-3,3-dimethyl-
cyclopropane (VIa) [4]. Colorless oily substance. IR
–
60 to –75°C. The mixture was stirred for 30 min and
cooled to –70°C, 1 ml of methanol was added main-
taining the temperature below –60°C, the mixture
was allowed to warm up to 0°C, and 1 ml of water
was added.
–1
spectrum, ν, cm : 3090, 3000–2865, 1730, 1650,
1
1
1
470–1460, 1420, 1380, 1350 w, 1275, 1210, 1160–
140, 1000, 930, 680. H NMR spectrum, δ, ppm:
.07 d.d (1H, J = 6.8, 7.1 Hz), 1.14 s (3H), 1.16 s (3H),
1
Compounds V and VI were isolated as follows.
Petroleum ether, 20 ml, was added to the mixture, the
organic layer was separated by decanting, the remain-
ing suspension of magnesium salts was dissolved in
2.99 d (1H, J = 7.5 Hz), 3.5 d.d (1H, J = 6.8, 10.6 Hz),
3.54 d.d (1H, J = 10.6, 7.1 Hz), 4.0 m (2H, J = 1.5,
5.8, 17.2, 10.4 Hz), 5.18 d.q (1H, J = 1.5, 10.4 Hz),
5.29 d.q (1H, J = 1.5, 17.2 Hz), 5.93 m (1H, J = 10.4,
1
3
4
M hydrochloric acid and extracted with petroleum
5.8, 17.2 Hz). C NMR spectrum, δ , ppm: 17.14,
C
ether, and the organic extracts were combined, washed
26.19, 26.86, 29.67, 34.99, 68.31, 71.79, 117.05,
with water, dried over MgSO , and evaporated. The
134.89. Mass spectrum (EI, 70 eV; retention time
4
+
residue was subjected to chromatographic separation
to isolate the corresponding cis- and trans-isomeric
monobromocyclopropanes.
6.16 min), m/z (I , %): 218, 220 (0.016) [M] , 175,
rel
+
+
177 (0.11) [M – C H ] , 161, 163 (1.7) [M – C H O] ,
3
7
3
5
+
+
147, 149 (5) [M – C H O] , 139 (9.6) [M – Br] .
4
7
The reaction mixture obtained by addition of the
Grignard compound to a solution of acid IV was
diluted with 20 ml of chloroform at room temperature,
and excess 15% hydrochloric acid was then added. The
trans-1-Allyloxymethyl-2-bromo-3,3-dimethyl-
cyclopropane (VIb) [4]. Colorless oily substance. IR
spectrum, ν, cm : 3085, 3000–2870, 1740, 1650, 1460,
–
1
1420, 1380, 1300, 1270–1250, 1205, 1145, 1100–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

1
1
396
SOLOV’EVA et al.
1
090, 1000, 935, 820 w, 680. H NMR spectrum, δ,
trum, δ, ppm: 1.32 d.d (1H, J = 7.6, 6.7 Hz), 1.41 s
(3H), 1.81 d.d (1H, J = 6.7, 5.8 Hz), 3.02 d.d (1H, J =
7.6, 5.8 Hz), 10.6 s (1H).
ppm: 1.14 s (3H), 1.28 s (3H), 1.25 m (1H, J =
4
1
.3 Hz), 2.71 d (1H, J = 4.3 Hz), 3.36 d.d, (1H, J = 8.1,
0.9 Hz), 3.58 d.d (1H, J = 5.9, 10.9 Hz), 3.98 m (2H,
trans-2-Bromo-1-methylcyclopropanecarboxylic
J = 1.5, 5.8, 5.5 Hz), 5.19 d.d (1H, J = 1.5, 10.5 Hz),
1
acid (VIIIb) [6, 7]. Colorless crystals. H NMR spec-
5
1
1
.28 d.d (1H, J = 1.5, 17.2 Hz) 5.91 m (1H, J = 10.5,
trum, δ, ppm: 1.09 d.d (1H, J = 5.5, 5.8 Hz), 1.48 s
1
3
7.2, 5.8, 5.5 Hz). C NMR spectrum, δ , ppm:
C
(
3H), 1.92 d.d (1H, J = 8.2, 5.8 Hz), 3.57 d.d (1H, J =
9.43, 21.81, 24.45, 33.15, 33.71, 68.52, 71.46,
5
.5, 8.2 Hz), 10.6 s (1H).
117.08, 134.73.
1
13
The H and C NMR spectra were recorded from
solutions in CDCl on a Varian VXR-400 spectrometer
cis-2-Bromo-3,3-dimethylcyclopropylmethyl
acetate (VIIa). Colorless oily substance. IR spectrum,
3
(
400 and 100 MHz, respectively); the chemical shifts
–1
ν, cm : 3000–2880, 1740, 1460, 1380, 1240, 1150 w,
were measured relative to tetramethylsilane as internal
reference. The IR spectra were obtained on a UR-20
instrument from samples prepared as films (liquids) or
mulls in mineral oil (crystalline substances). The mass
spectra were run on a Finnigan MAT SSQ-7000
GC–MS system using a 25-m OV-1 quartz capillary
column.
1
125 w, 1050, 1000, 990, 930–920 w, 905 w, 850 w,
10 w, 710 w, 695 w. H NMR spectrum, δ, ppm:
1
8
1
2
.12 m (1H, J = 7.6 Hz), 1.16 s (3H), 1.17 s (3H),
.07 s (3H), 3.0 d (1H, J = 7.6 Hz), 4.12–4.21 m (2H).
1
3
C NMR spectrum, δ , ppm: 19.95, 22.19, 22.62,
C
2
7
4.88, 29.63, 34.35, 63.36, 170.99. Mass spectrum (EI,
0 eV; retention time 8.56 min), m/z (I , %): 222, 220
rel
+
+
This study was performed under financial support
by the Kopernikus and INTAS programs.
(
(
0.02) [M] , 163, 161 (0.11) [M – C H O ] , 147, 149
2.7) [M – C H O ] , 141 (10) [M – Br] .
2 3 2
+
+
3
5
2
trans-2-Bromo-3,3-dimethylcyclopropylmethyl
acetate (VIIb). Colorless oily substance. IR spectrum,
ν cm : 3000–2880, 1740, 1460, 1380, 1240, 1150 w,
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–1
1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005