Preparation of cis-1,2-Dialkylcyclopropanols
FULL PAPER
(
(
=
0
2
Z)-1-tert-Butyl-2-methylcyclopropanol (trans-1b): 1H NMR
400 MHz, CDCl ): δ = 0.10 (m, 1 H, cycloprop. 3-H), 0.74 (dd, J
9.7, 5.4 Hz, 1 H, cycloprop. 3-H), 0.90 [s, 9 H, C(CH ], 0.84–
.93 (m, 1 H, cycloprop. 2-H), 1.14 (d, J = 6.0 Hz, 3 H, cycloprop.
-CH ):
), 2.20 (brs, 1 H, OH) ppm. 13C NMR (100.6 MHz, CDCl
), 14.2 (CH), 16.6 (CH ), 26.1
], 64.5 (COH) ppm.
(100.6 MHz, CDCl
64.5, 64.5, 110.1 ppm. IR (CCl ): ν˜ = 3600, 3475, 3072 cm .
4
3
): δ = 14.2, 19.5, 20.5, 23.6, 28.2, 35.6, 58.5,
–
1
3
3 3
)
Reaction between Benzaldehyde and a Mixture Obtained after Treat-
ment of Methyl Hexanoate (2d) with n-Propylmagnesium Bromide,
3
3
Ti(OiPr)
Et O, 7.5 mmol) was added over 1–2 min at room temperature to
a solution of Ti(OiPr) (1.42 g, 5 mmol in 5 mL of Et O) and the
mixture was cooled to 0 °C. Methyl hexanoate (2d, 0.65 g, 5 mmol)
): in Et O (3 mL) and, over 10 min, n-propylmagnesium bromide
δ = 0.04 (dd, J = 6.4, 5.1 Hz, 1 H, cycloprop. 3-H), 0.81 (ddq, J =
(6.3 mL, 1.2 in Et O, 7.5 mmol) were then added. The red-brown
0.8, 5.1, 0.6 Hz, 1 H, cycloprop. 3-H), 0.89 (t, J = 6.9 Hz, 3 H,
mixture was stirred for 40 min at room temperature, and benzalde-
CH in nBu), 0.90–1.02 (m, 1 H, cycloprop. 2-H), 1.05–1.20 (m, 1
hyde (2.12 g, 20 mmol) in Et O (5 mL) was added in one portion
H, 1H in nBu), 1.22–1.45 (m, 5 H, 5H in nBu), 1.39 (d, J = 0.6 Hz, at 0 °C. The reaction mixture was kept overnight and hydrolyzed
H, cycloprop. 1-CH
), 1.97 (br s, 1 H, OH) ppm. 13C NMR
with sulfuric acid (10%, 18 mL) at 0 °C. The aqueous phase was
100.6 MHz, CDCl
): δ = 14.1, 20.2, 20.5, 22.5, 25.6, 29.5, 31.9, extracted with Et O (3ϫ5 mL), and the combined organic phases
were washed with satd. NaHCO and brine and dried with MgSO
The H NMR spectrum of the residue obtained after evaporation
of Et O showed the absence of the starting compound and the
4
, and MeMgI: Methylmagnesium iodide (5.4 mL, 1.4 in
δ = 12.5 (cycloprop. 2-CH
3
2
2
[C(CH
3
)
3
], 34.2 [C(CH
3 3
)
4
2
(
8
E)-2-Butyl-1-methylcyclopropanol (cis-1c): Yield 2.05–2.10 g (80–
1
2%) in Et
2
O and THF, colorless oil. H NMR (400 MHz, CDCl
3
2
2
1
3
2
3
(
5
3
3
2
–1
5.6 ppm. IR (CCl
4
): ν˜ = 3602, 3325, 3071 cm . Spectral data are
3
4
.
1
consistent with those previously reported for this compound in
[
14]
Ref.
E)-2-Methyl-1-pentylcyclopropanol (cis-1d): Yield 2.13 g (75%) in
Et ): δ =
O and THF, colorless oil. 1H NMR (400 MHz, CDCl
0.01 to 0.05 (m, 1 H, cycloprop. 3-H), 0.78–0.85 (m, 1 H, cy-
cloprop. 3-H), 0.90 (t, J = 6.9 Hz, 3 H, CH in n-C 11), 1.01 (d,
J = 1.8 Hz, 3 H, cycloprop. 2-CH ), 0.98–1.10 (m, 1 H, cycloprop.
in n-C 11), 1.47–1.60 (m, 4 H,
11), 1.82 (br s, 1 H, OH) ppm. C NMR
2
formation of 2-methyl-1-pentylcyclopropanol [1d, (E)/(Z) 85:15], 1-
phenylethanol, hydrobenzoin (9, dl/meso 65:35), and benzyl alcohol
in a molar ratio of 1:0.15:0.30:2.6.
(
2
3
–
H
Reaction between Benzaldehyde and a Mixture Obtained after Treat-
ment of Methyl Hexanoate (2d) with n-Propylmagnesium Bromide
3
5
3
2
2
-H), 1.23–1.40 (m, 4 H, 2ϫCH
ϫ CH in n-C
2
5
H
and Ti(OiPr)
Et O, 15 mmol) was added at 0 °C over 15 min to a solution of
): δ = 14.0, 14.2, 19.6, 20.6, 22.7, 25.5, 32.0, Ti(OiPr) (1.42 g, 5 mmol) and methyl hexanoate (2d, 0.65 g,
5 mmol) in Et O (8 mL). The red-brown mixture was stirred for
40 min at room temperature. Benzaldehyde (2.12 g, 20 mmol) in
Et O (5 mL) was then added in one portion at 0 °C, and the reac-
tion mixture was kept overnight and hydrolyzed with sulfuric acid
4
: n-Propylmagnesium bromide (12.5 mL, 1.2 in
1
3
2
5
H
2
(
3
(
100.6 MHz, CDCl
3.9, 58.8 ppm. IR (CCl
142.24): C 76.00, H 12.76; found: C 75.65, H 12.43.
3
4
–1
4
): ν˜ = 3600, 3350, 3070 cm . C
9
H
18
O
2
2
(
2
(
0
CH
1
E)-1-(3-Chloropropyl)-2-methylcyclopropanol (cis-1e): Yield 2.17–
.20 g (73–74 %) in Et
O and THF, colorless oil. 1H NMR
400 MHz, CDCl ): δ = 0.04–0.12 (m, 1 H, cycloprop. 3-H), 0.82–
.90 (m, 1 H, cycloprop. 3-H), 1.00–1.10 (m, 4 H, cycloprop. 2-H,
), 1.67–1.74 (m, 2 H, CH CH CH Cl), 1.82 (brs, 1 H, OH),
.95–2.15 (m, 2 H, CH CH CH Cl), 3.64 (t, J = 6.5 Hz, 2 H,
CH CH CH ): δ = 14.1,
Cl) ppm. 13C NMR (100.6 MHz, CDCl
9.7, 20.7, 29.1, 31.3, 45.3, 58.2 ppm. IR (CCl ): ν˜ = 3599, 3350,
13ClO (148.63): C 56.57, H 8.82; found: C 56.31, H
2
(10%, 18 mL) at 0 °C. The aqueous phase was extracted with Et
2
O
3
(
3ϫ5 mL), and the combined organic phases were washed with
1
satd. NaHCO
spectrum of the residue after evaporation of Et
sence of the starting compound. 2-Methyl-1-pentylcyclopropanol
1d, (E)/(Z) 85:15], hydrobenzoin (9, dl/meso 65:35), and benzyl
3
and brine and dried with MgSO
4
. The H NMR
3
2
2
2
2
O showed the ab-
2
2
2
2
2
2
3
[
1
3
8
4
alcohol were found in a molar ratio of 1:0.46:2.7.
–
1
076 cm . C
7
H
.47.
Acknowledgments
(
(
E)-2-Methyl-1-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]cyclopropanol
cis-1f): This compound was prepared by a slight modification of
This work was carried out with the support of the Ministry of
Education of the Republic of Belarus.
Procedure D. Methylmagnesium bromide (10 mL, 1.5 in THF,
5 mmol) was added over 5 min at room temperature to a solution
of Ti(OiPr) (2.84 g, 10 mmol) in THF (20 mL), and the resulting
yellow solution was cooled to 0 °C. Ester 2f (10 mmol) in THF
10 mL) and, over 30 min, n-propylmagnesium bromide (27 mL,
.9 solution in THF, 24 mmol) were then added. The slurry mix-
1
4
[1] D. H. Gibson, C. H. De Puy, Chem. Rev. 1974, 74, 605–623.
[2] O. G. Kulinkovich, Chem. Rev. 2003, 103, 2597–2632.
(
0
[
[
3] Yu. Yu. Kozyrkov, O. G. Kulinkovich, Synlett 2002, 443–446.
4] O. G. Kulinkovich, Yu. Yu. Kozyrkov, A. V. Bekish, E. A. Mat-
iushenkov, I. L. Lysenko, Synthesis 2005, 1713–1717.
5] G. Kulinkovich, S. V. Sviridov, D. A. Vasilevski, A. I. Savch-
enko, T. S. Pritytskaya, Zh. Org. Khim. 1991, 27, 294–298; G.
Kulinkovich, S. V. Sviridov, D. A. Vasilevski, A. I. Savchenko,
T. S. Pritytskaya, J. Org. Chem. USSR (Engl. Transl.) 1991,
27, 250–253.
ture was warmed to room temperature and stirred for 2 h and the
reaction was quenched by addition of water (5 mL). The obtained
heterogeneous mixture was vigorously stirred for 40 min, and the
white precipitate was filtered off and washed with THF
[
(
3ϫ20 mL). Solvent was evaporated under reduced pressure, the
residue was diluted with Et O (50 mL), and the aqueous phase was
separated. The organic phase was washed with brine and dried with
Na SO . After removal of the solvent, cyclopropanol cis-1f was
2
[6] O. G. Kulinkovich, D. A. Vasilevskii, A. I. Savchenko, S. V. Svi-
ridov, Zh. Org. Khim. 1991, 27, 1428–1430; O. G. Kulinkovich,
D. A. Vasilevskii, A. I. Savchenko, S. V. Sviridov, J. Org. Chem.
USSR (Engl. Transl.) 1991, 27, 1249–1251.
2
4
purified by column chromatography over silica gel (hexane/ethyl
acetate), to afford (E)-2-methyl-1-[2-(2-methyl-1,3-dioxolan-2-yl)-
ethyl]cyclopropanol 1f (1.48 g, 80%) as a colorless oil. H NMR
1
[7] E. J. Corey, S. A. Rao, M. S. Noe, J. Am. Chem. Soc. 1994, 116,
9
345–9346.
(
0
2
CH
(
400 MHz, CDCl
3
): δ = –0.02 to 0.03 (m, 1 H, cycloprop. 3-H),
.77–0.83 (m, 1 H, cycloprop. 3-H), 0.98–1.08 (m, 1 H, cycloprop.
-H), 1.02 (d, J = 1.5 Hz, 3 H, cycloprop. 2-CH ), 1.36 (s, 3 H,
), 1.65–1.71 (m, 2 H, CH ), 1.90–1.96 (m, 2 H, CH
brs, 1 H, OH), 3.95–4.00 (m, 4 H, OCH
[
8] For recent review see: O. G. Kulinkovich, Izv. Akad. Nauk. Ser.
Khim. 2004, 1022–1043; O. G. Kulinkovich, Russ. Chem. Bull.,
Int. Ed. 2004, 53, 1065–1086.
3
3
2
2
), 3.06 [9] O. G. Kulinkovich, S. V. Sviridov, D. A. Vasilevski, Synthesis
1
3
2
CH
2
O) ppm. C NMR
1991, 234.
Eur. J. Org. Chem. 2007, 2121–2132
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2131