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3461
C]C), 3.47 (2H, t, J 6.8 Hz, –CH2–N), 2.12 (1H, d, J 9.0 Hz, H–C7), 2.08
(1H, d, J 9.0 Hz, H–C7), 2.03–1.88 (4H, m, –CH2CH2– in pyrrolidine);
dC (100.6 MHz, CDCl3) 181.2, 167.4 (q, J 37 Hz), 148.1, 136.0, 119.0 (q, J
290 Hz), 106.4, 62.1, 55.2, 53.5, 52.6, 48.1, 25.7, 25.0.
J 16.0 Hz, AB-system, CH2–C]O), 1.41 (3H, s, CH3), 1.03 (3H, s, CH3);
dC (100.6 MHz, CDCl3) 203.2, 134.3, 129.6, 128.9, 126.8, 124.8 (q, J
290 Hz), 77.4 (q, J 30 Hz), 68.4, 59.7, 32.5, 31.7, 21.1.
4.3.3. 1-[2,2,2-Trifluoro-1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]spiro[3.3]-
heptan-2-one (6b). From 3b and 2-thiazolyllithium. White crystals
(from hexane); mp 139–140 ꢁC; yield 1.12 g (64%). Found: C, 49.54;
H, 4.19; F, 19.43; N, 4.59; S, 11.20. C12H12F3NO2S requires: C, 49.48;
H, 4.15; F, 19.57; N, 4.81; S, 11.01%. IR (mineral oil) 3559, 3010, 2994,
4.2.6. 2,2,2-Trifluoro-1-(3-pyrrolidin-1-ylbicyclo[2.2.2]octa-2,5-
dien-2-yl)ethanone (4h). From 1h and pyrrolidine. Yellowish crys-
tals (from hexane); mp 65–66 ꢁC; yield 1.29 g (95%). Found: C,
62.15; H, 5.97; F, 20.96; N, 5.06. C14H16F3NO requires: C, 61.98; H,
5.94; F, 21.01; N, 5.16%. IR (mineral oil) 3008, 2994,1663,1638,1590,
1790, 1204, 1153 cmꢀ1
; dH (400 MHz, CDCl3) 7.89 (1H, d, J 1.4 Hz,
1304, 1210, 1156 cmꢀ1
;
dH (400 MHz, CDCl3) 6.30 (1H, dd, J 5.3,
H–Ar), 7.56 (1H, d, J 1.4 Hz, H–Ar), 4.60 (1H, br s, H–O), 4.11 (1H, s,
HC–C]O), 2.97 (1H, d, J 15.4 Hz), 2.68 (1H, d, J 15.4 Hz, AB-system,
CH2–C]O), 2.19 (m), 1.82 (m), 1.15 (m, totally 6H, –(CH2)3–); dC
(100.6 MHz, CDCl3) 207.0, 166.8, 142.8, 124.7 (q, J 290 Hz), 123.3,
80.2 (q, J 30 Hz), 67.9, 59.9, 39.4, 35.8, 32.6, 17.6.
2.6 Hz, HC]C), 6.16 (1H, dd, J 5.3, 2.6 Hz, HC]C), 4.28 (1H, m, H–
C1), 4.03 (1H, m, H–C4), 4.06 (2H, t, J 6.6 Hz, –CH2–N), 3.49 (2H, t, J
6.6 Hz, –CH2–N), 1.96 (4H, m, –CH2CH2– in pyrrolidine), 1.45 (m),
1.19 (m, totally 4H, H2C7–H2C8); dC (100.6 MHz, CDCl3) 176.4, 164.9
(q, J 38 Hz), 134.9, 131.5, 117.8 (q, J 290 Hz), 111.6, 48.0, 46.3, 45.0,
43.2, 25.2, 24.7, 24.1, 22.7.
4.3.4. 1-[2,2,2-Trifluoro-1-(4-fluorophenyl)-1-hydroxyethyl]spiro[3.3]-
heptan-2-one (6e). From 2b and 4-fluorophenyllithium. White
crystals (from hexane); mp 155–156 ꢁC; yield 0.77 g (44%). Found: C,
59.83; H, 4.79; F, 25.30. C15H14F4O2 requires: C, 59.60; H, 4.67; F,
4.3. General procedure for preparation 1,2-addition products
(5–8) and 1,4-addition products (9–16)
25.14%. IR (mineral oil) 3496, 3006, 2993, 1790, 1201, 1155 cmꢀ1
; dH
(a) From organolithiums. To the stirred solution or suspension of
organolithium (0.007 mol) in THF (7 mL) at ꢀ70 ꢁC the solution of
one of enaminoketones 2, 3 (0.006 mol) in THF (2 mL) was added
dropwise. The resulting mixture was allowed to warm to 0 ꢁC (30–
40 min) and then was quickly poured into vigorously stirred satu-
rated solution of NaH2PO4 (15 mL). After the additional 5 min (no
more!) of stirring or shaking the organic layer was separated, the
aqueous phase was extracted with ether (2ꢂ10 mL), dried with
Na2SO4, and the solvent was removed in vacuum. The residue was
diluted with cold hexane (15 mL) and exposed at 10 ꢁC for 1 h. The
crystalline 1,2-adducts 5–8 were filtered off and crystallized from
hexane. Filtrate was concentrated and the residue was chromato-
graphed on a column (silica gel, hexane/AcOEt¼20:1) to afford 1,4-
adducts 9–16. In the case of thiazolyl derivatives 9, 10, 12–16 of
series (b) the eluent was hexane/AcOEt¼2:1.
(400 MHz, CDCl3) 7.57 (2H, dd, J 8.4, 6.5 Hz, H–Ar), 7.16 (2H, dd, J 7.5,
6.5 Hz, H–Ar), 4.40 (1H, br s, H–O), 3.99 (1H, s, HC–C]O), 2.93 (1H, d,
J 16.0 Hz), 2.70 (1H, d, J 16.0 Hz, AB-system, CH2–C]O), 2.11 (m),1.72
(m),1.19 (m, totally 6H, –(CH2)3–); dC (100.6 MHz, CDCl3) 204.7,159.7
(d, J 245 Hz), 133.3(d, J 8.2 Hz), 124.4, 123.6 (q, J 290 Hz), 121.8 (d, J
22.6 Hz), 75.8 (q, J 30 Hz), 68.1, 59.1, 36.4, 33.9, 30.5, 17.5.
4.3.5. 1-[2,2,2-Trifluoro-1-(2-furyl)-1-hydroxyethyl]spiro[3.5]nonan-
2-one (8c). From 3d and 2-furyllithium. White crystals (from hex-
ane); mp 84–85 ꢁC; yield 1.00 g (55%). Found: C, 59.80; H, 5.75; F,
18.69. C15H17F3O3 requires: C, 59.60; H, 5.67; F, 18.86%. IR (mineral
oil) 3495, 3014, 3000, 1793, 1210, 1155 cmꢀ1
; dH (400 MHz, CDCl3)
7.53 (1H, d, J 2.2 Hz, H–C5 in furyl), 6.62 (1H, d, J 3.4 Hz, H–C3 in furyl),
6.47 (1H, dd, J 3.4, 2.2 Hz, H–C4 in furyl), 4.09 (1H, br s, H–O), 3.70 (1H,
s, HC–C]O), 2.91 (1H, d, J 15.5 Hz), 2.62 (1H, d, J 15.5 Hz, AB-system,
CH2–C]O),1.88 (m),1.65 (m),1.48 (m),1.24 (m, totally 10H, –(CH2)5–
); dC (100.6 MHz, CDCl3) 201.8, 147.4, 142.2, 124.0 (q, J 289 Hz), 109.3,
75.3 (q, J 30 Hz), 66.8, 59.9, 35.1, 32.0, 30.4, 24.5, 23.9, 14.5.
(b) From Grignard reagents (only for 1,4-addition products 9–
16). To the stirred solution of Grignard reagent (0.007 mol) in ether
or THF (7 mL) at 20 ꢁC the solution of one of enaminoketones 4
(0.006 mol) in the same solvent was added dropwise (in the case of
2-thiazolylmagnesiumbromide the equimolar amount of enami-
noketone was used and the starting temperature was 0 ꢁC and then
was gradually increased to 20 ꢁC). After the stirring for 0.5 h at
20 ꢁC the resulting mixture was treated with saturated solution of
NaH2PO4 (15 mL) and isolation of the target compounds 9–16 was
performed similarly to the procedure for organolithiums.
4.3.6. 1-[4,4-Dimethyl-2-(2-thienyl)cyclobut-1-en-1-yl]-2,2,2-tri-
fluoroethanone (9a). From 4a and 2-thienylmagnesiumbromide.
Yellowish crystals; mp 38–39 ꢁC; bp 84–85 ꢁC (1 Torr); yield 1.35 g
(87%). Found: C, 55.51; H, 4.23; F, 21.80. C12H11F3OS requires: C,
55.38; H, 4.26; F, 21.90%. IR (mineral oil) 3010, 2995, 1714, 1608,
1432, 1226, 1169 cmꢀ1
; dH (400 MHz, CDCl3) 7.82 (1H, d, J 5.0 Hz, H–
C5 in thienyl), 7.72 (1H, d, J 3.9 Hz, H–C3 in thienyl), 7.23 (1H, dd, J
5.0, 3,9 Hz, H–C4 in thienyl), 2.83 (2H, s, CH2–C]C), 1.52 (6H, s,
(CH3)2C); dC (100.6 MHz, CDCl3) 175.4 (q, J 38 Hz),156.0, 137.0,134.1,
133.4, 133.2, 128.0, 116.2 (q, J 289 Hz), 45.1, 42.1, 26.2.
4.3.1. 3,3-Dimethyl-2-[2,2,2-trifluoro-1-hydroxy-1-(2-thienyl)-
ethyl]cyclobutanone (5a). From 3a and 2-thienyllithium. White
crystals (from hexane); mp 108–109 ꢁC; yield 1.22 g (73%). Found:
C, 51.84; H, 4.74; F, 20.33; S, 11.39. C12H13F3O2S requires: C, 51.79; H,
4.71; F, 20.48; S, 11.52%. IR (mineral oil) 3425, 3001, 2990, 1798,
4.3.7. 2,2,2-Trifluoro-1-[2-(1,3-thiazol-2-yl)spiro[3.3]hept-1-en-1-
yl]ethanone (10b). From 4b and 2-thiazolylmagnesiumbromide
prepared from thiazole (0.68 g, 0.008 mol) and EtMgBr (0.006 mol)
in THF (10 mL) at 50 ꢁC. Yellowish crystals; mp 45–46 ꢁC; yield
0.98 g (60%). Found: C, 52.80; H, 3.83; F, 20.65; N, 5.01; S, 11.60.
C12H10F3NOS requires: C, 52.74; H, 3.69; F, 20.86; N, 5.13; S, 11.73%.
IR (mineral oil) 3014, 3000, 2988, 1708, 1602, 1422, 1225,
1206, 1157 cmꢀ1 dH (400 MHz, CDCl3) 7.39 (1H, d, J 5.0 Hz, H–C5 in
;
thienyl); 7.09 (2H, m, H–C3 and H–C4 in thienyl), 4.10 (1H, br s, H–
O), 3.92 (1H, s, HC–C]O), 3.03 (1H, d, J 16.0 Hz), 2.63 (1H, d, J
16.0 Hz, AB-system, CH2–C]O), 1.40 (3H, s, CH3), 0.98 (3H, s, CH3);
dC (100.6 MHz, CDCl3) 202.6, 137.2, 126.7, 126.2, 125.4, 124.0 (q, J
286 Hz), 76.1 (q, J 30 Hz), 68.2, 59.0, 31.4, 31.0, 21.9.
1141 cmꢀ1
; dH (400 MHz, CDCl3) 8.30 (1H, d, J 1.7 Hz, H–Ar), 7.88
4.3.2. 3,3-Dimethyl-2-(2,2,2-trifluoro-1-hydroxy-1-phenyl-
ethyl)cyclobutanone (5d). From 2a and phenyllithium. White crys-
tals (from hexane); mp 133–134 ꢁC; yield 0.69 g (42%). Found: C,
61.92; H, 5.60; F, 21.09. C14H15F3O2 requires: C, 61.76; H, 5.55; F,
(1H, d, J 1.7 Hz, H–Ar), 3.17 (2H, s, CH2–C]C), 2.76 (2H, dd, J 12.6,
8.6 Hz, 2C–H in cyclobutane), 2.20 (4H, m, 4C–H in cyclobutane); dC
(100.6 MHz, CDCl3) 172.9 (q, J 38 Hz), 169.0, 159.6, 143.8, 135.8,
132.5, 119.1 (q, J 290 Hz), 48.9, 47.9, 33.3, 17.0.
20.93%. IR (mineral oil) 3475, 3019, 2990, 1790, 1206, 1155 cmꢀ1
; dH
(400 MHz, CDCl3) 7.66 (2H, m, H–Ar), 7.45 (3H, m, H–Ar), 4.03 (1H,
4.3.8. 2,2,2-Trifluoro-1-[2-(2-furyl)spiro[3.5]non-1-en-1-yl]ethanone
s, HC–C]O), 3.90 (1H, br s, H–O), 2.97 (1H, d, J 16.0 Hz), 2.70 (1H, d,
(12c). From 4d and 2-furylmagnesiumbromide. Yellowish oil; yield