Catalytic Cyclopropanation of Fluorine-Containing Alkenes and Dienes
FULL PAPER
5.4, Jcis ϭ 8.3 Hz, 1 H, 1-H), 1.87 (ddd, Jcis ϭ 8.3, Jtrans ϭ 5.4, Methyl 3,4-Difluorobicyclo[4.1.0]hept-3-ene-7-carboxylate (17): The
Jgem ϭ 4.4 Hz, 1 H, 3-Hb), 2.21 (m, 1 H, 2-H), 2.4 (m, 2 H, 4Ј-H), cyclopropanation of 1,2-difluoro-1,3-cyclohexadiene (5) was car-
3.71 (s, 3 H, COOMe), 3.84 (s, 3 H, OMe) ppm. 19F NMR
(188.3 MHz, CDCl3, CCl3F): δ ϭ Ϫ108.7 (br. s, CF2) ppm.
ried out by the same way as used for treatment of 2-fluoro-3-
methyl-1,3-butadiene (2) with methyl diazoacetate. In the presence
of [Rh2(OAc)4] methyl 3,4-difluorobicyclo[4.1.0]hept-3-ene-7-car-
boxylate (17) was obtained in 72% total yield as a mixture of anti
and syn isomers in a ratio of approx. 2:1. In the presence of Cu
catalyst the compound 17 was obtained in 68% total yield (ratio of
anti and syn 2.1:1). The isomers obtained were separated by TLC
on silica gel (eluent: hexane/diethyl ether, 3:1; Rf ϭ 0.5 and 0.4
for anti-17 and syn-17, respectively) and characterized as enriched
fractions up to 90Ϫ93% (colourless oily liquid, b.p. 75Ϫ76 °C,
1 Torr). The interaction between the alkene 5 and methyl diazoacet-
ate in the presence of [(PhCN)2PdCl2] occurred only in very low
yield (Ͻ 5%).
Isomer cis-8: 1H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 1.25 (dt,
Jcis ϭ 8.2, Jgem ϭ 4.9 Hz, 1 H, 3-Ha), 1.40 (dt, Jcis ϭ 8.3, Jtrans
ϭ
6.4 Hz, 1 H, 1-H), 1.45 (dt, Jtrans ϭ 6.4, Jgem ϭ 4.9 Hz, 1 H, 3-Hb),
1.96 (m, 1 H, 2-H), 2.26 (br. dt, Jgem ϭ 10, J ϭ 3 Hz, 1 H, 4Ј-Ha),
2.5 (ddd, Jgem ϭ 10, J ϭ 4.0, J ϭ 2.0 Hz, 1 H, 4Ј-Hb), 3.62 (s, 3
H, COOMe), 3.68 (s, 3 H, OMe) ppm. 19F NMR (188.3 MHz,
CDCl3, CCl3F, 25 °C): δ ϭ Ϫ107.8 and Ϫ110.4 (both br. d, 2JFF
ഠ
200 Hz, CF2) ppm.
Mixture of Isomers: EIMS (probe, 70 eV): m/z (%): 218 (60) [M]ϩ,
203 (10) [M Ϫ Me]ϩ, 183 (30) [M Ϫ Me Ϫ HF]ϩ, 171 (20), 159
(100), 139 (30), 127 (50), 115 (35), 109 (40), 97 (30), 81 (40), 59
(40), 52 (40), 45 (30), 39 (60). C10H12F2O3 (218.2): calcd. C 55.05,
H 5.54; found C 55.18, H 5.67.
1
Isomer anti-17: H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 1.67 (br.
t, Jtrans ϭ 3.0 Hz, 1 H, 7-H), 1.75 (m, 2 H, 1-H, 6-H), 2.58Ϫ2.78
(m, 4 H, 2-H, 5-H), 3.70 (s, 3 H, Me) ppm. 13C NMR (50.3 MHz,
CDCl3, 25 °C): δ ϭ 20.9 (m, C-1 and C-6), 23.0 (br. s, C-7), 24.5
Methyl 3-Chloro-3,4,4-trifluorobicyclo[4.1.0]heptane-7-carboxylate
(14): The cyclopropanation of 4-chloro-4,5,5-trifluoro-1-cyclohex-
ene (4) was carried out in the same way as used for treatment of 2-
fluoro-3-methyl-1,3-butadiene (2) with methyl diazoacetate. In the
presence of [Rh2(OAc)4] as the catalyst, methyl 3-chloro-3,4,4-tri-
fluorobicyclo[4.1.0]heptane-7-carboxylate (14) was obtained in 50%
total yield as a difficult to separate mixture of two diastereomers
in an approximately equal ratio (colourless oily liquid, b.p. 89Ϫ90
°C, 1 Torr). The olefin 4 was hardly cyclopropanated with methyl
diazoacetate in the presence of [Cu(acac)2] or [(PhCN)2PdCl2].
1
2
(m, C-2 and C-5), 52.0 (s, Me), 139.2 (dd, JC,F ϭ 249, JC,F
ϭ
11.5 Hz, C-3 and C-4), 173.94 (s, CO) ppm. 19F NMR (188.3 MHz,
CDCl3, CCl3F, 25 °C): δ ϭ Ϫ141.2 (br. s, ϭCF) ppm. EIMS (probe,
70 eV): m/z (%) ϭ 188 (11) [M]ϩ, 168 (22) [M Ϫ HF]ϩ, 157 (13),
127 (32), 109 (38), 98 (100), 83 (30), 77 (18), 59 (29), 51 (20), 43
(11), 39 (27).
1
Isomer syn-17: H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 1.55 (m,
2 H 1-H, 6-H), 1.75 (m, 1 H, 7-H), 2.58Ϫ2.78 (m, 4 H, 2-H, 5-H),
3.68 (s, 3 H, Me) ppm. 13C NMR (50.3 MHz, CDCl3, 25 °C): δ ϭ
14.9 (m, C-1 and C-6), 22.0 (br. s, C-7), 23.0 (m, C-2 and C-5),
1
Mixture of Isomers (14): H NMR (200 MHz, CDCl3, 25 °C): δ ϭ
1
2
51.6 (s, Me), 140.1 (dd, JC,F ϭ 247, JC,F ϭ 11.8 Hz, C-3 and C-
4), 169.9 (s, CO) ppm. 19F NMR (188.3 MHz, CDCl3, CCl3F): δ ϭ
Ϫ141.3 (br. s, ϭCF) ppm. EIMS (probe, 70 eV): m/z (%) ϭ 188
(10) [M]ϩ, 168 (21) [M Ϫ HF]ϩ, 157 (21), 136 (23), 127 (83), 114
(16), 109 (100), 97 (20), 77 (31), 63 (13), 59 (40), 51 (38), 43 (17),
39 (45). C9H10F2O2 (for mixture of isomers) (188.2): calcd. C 57.45,
H 5.36; found C 57.31, H 5.18.
1.77 (m, 3 H, 1-H, 6-H, 7-H), 2.32Ϫ3.08 (m, 4 H, 2-H, 5-H), 3.69
(s, 3 H, OMe) ppm. EIMS (probe; 70 eV): m/z (%) ϭ 244 (2) and
242 (6) [M]ϩ, 207 (22) [M Ϫ Cl]ϩ, 175 (4), 127 (20), 111 (15), 84
(100). C9H10ClF3O2 (242.6): calcd. C 44.55, H 4.15; found C 44.42,
H 4.26.
Isomer 14a: 19F NMR (188.3 MHz, CDCl3, CCl3F): δ ϭ Ϫ111.1
(br. s, CF2), Ϫ120.9 (br. s, CFCl) ppm.
Methyl 1-Fluoro-5-methylbicyclo[3.1.0]hexane-6-carboxylate (18):
The cyclopropanation of 1-fluoro-2-methyl-1-cyclopentene (6) was
carried out by the same way as used for treatment of 2-fluoro-3-
methyl-1,3-butadiene (2) with methyl diazoacetate. In the presence
of [Rh2(OAc)4] or [Cu(acac)2], methyl 1-fluoro-5-methylbicyclo-
[3.1.0]hexane-6-carboxylate (18) was obtained in 33 or 44% total
yields as mixtures of two isomers (ratio of anti and syn 1.4 : 1 and
2.1 : 1). The isomers obtained were separated by TLC on silica gel
(eluent: heptane/diethyl ether, 3:1; Rf ϭ 0.64 and 0.53 for anti-18
and syn-18, respectively) and characterized as enriched fractions up
to 92Ϫ95% (colourless oily liquid, b.p. 95Ϫ100 °C, 45 Torr). The
interaction of the alkene 6 with methyl diazoacetate in the presence
of [(PhCN)2PdCl2] occurred with a very low yield (Ͻ 5%).
Isomer 14b: 19F NMR (188.3 MHz, CDCl3, CCl3F, 25 °C): δ ϭ
Ϫ104.6 and Ϫ109.3 (both br. d, 2JFF ϭ 255 Hz, CF2), Ϫ122.31 (br.
s, CFCl) ppm.
Methyl 3,4,4-Trifluorobicyclo[4.1.0]hept-2-ene-7-carboxylate (15):
Potassium tert-butoxide (0.93 g, 0.0083 mol) was added under ar-
gon at Ϫ20°C to a solution of methyl 3-chloro-3,4,4-trifluorobicy-
clo[4.1.0]heptane-7-carboxylate (14, 0.67 g, 0.0028 mol) in THF
(15 mL). The mixture was stirred under argon at this temperature
for 8 h, and was then neutralized with a solution of HCl in THF.
The suspension obtained was passed through a silica gel layer
(1 cm) and distilled in vacuo (b.p. 85Ϫ86° °C, 1 Torr). Methyl 3,4,4-
trifluorobicyclo[4.1.0]hept-2-ene-7-carboxylate (15) was obtained
as a colourless, oily liquid; yield 300 mg, 52%. 1H NMR (200 MHz,
CDCl3, 25 °C): δ ϭ 1.65 (ddd, Jtrans ϭ 5.0, 3.5, 2.0 Hz, 1 H, 7-H),
2.00 (m, 1 H, 6-H), 2.08 (m, 1 H, 1-H), 2.52 (dddd, J ϭ 26.5, J ϭ
15.5, J ϭ 12.8, J ϭ 5.0 Hz, 1 H, 5-Hb), 2.78 (m, 1 H, 5-Ha), 6.0
(dddd, J ϭ 12.5, J ϭ 5.5, J ϭ 3.5, J ϭ 0.8 Hz, 1 H, 2-H), ppm.
19F NMR (188.3 MHz, CDCl3, CCl3F): δ ϭ Ϫ136.4 (m, CF),
1
Isomer anti-18: H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 1.12 (br.
d, JH,F ϭ 18.7 Hz, 1 H, H-6), 1.43 (s, 3 H, Me), 1.73 (m, 4 H, 3-
H and 4-H), 2.22 (m, 2 H, 2-H), 3.70 (s, 3 H, OMe) ppm. 19F
NMR (188.3 MHz, CDCl3, CCl3F, 25 °C): δ ϭ Ϫ188.29 (br. t,
JH,F ϭ 14.7 Hz) ppm. EIMS (probe, 70 eV): m/z (%) ϭ 173 (75)
[M ϩ H]ϩ, 141 (25) [M Ϫ OMe]ϩ, 113 (100), 93 (43), 77 (20),
40 (30).
1
Ϫ104.05 (br. t, JFF 274, JFH ϭ 12.8 Hz, CF2), Ϫ83.10 (br. dd,
2
1
1JFF 274, JFF ϭ 47.0, JFH ϭ 22.0 Hz, CF2,), ppm. EIMS (probe, Isomer syn-18: H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 1.23 (d,
70 eV): m/z (%) ϭ 206 (5) [M]ϩ, 186 (3) [M Ϫ HF]ϩ, 175 (22), 172
(18), 163 (50), 154 (11), 153 (31), 148 (30), 145 (15), 142 (13), 128 4-H), 2.32 (m, 2 H, 2-H), 3.69 (s, 3 H, OMe) ppm. 19F NMR
JH,F ϭ 4.0 Hz, 1 H, 6-H), 1.31 (s, 3 H, Me), 1.80 (m, 4 H, 3-H and
(20), 127 (100). C9H9F3O2 (206.2): calcd. C 52.43, H 4.40; found
C 52.59, H 4.49.
(188.3 MHz, CDCl3, CCl3F): δ ϭ Ϫ206.2 (br. s) ppm. EIMS
(probe, 70 eV): m/z (%) ϭ 173 (25) [M ϩ H]ϩ, 141 (22) [M Ϫ
Eur. J. Org. Chem. 2004, 3136Ϫ3144
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3143