1704
R. Ortiz, M. Yus / Tetrahedron 61 (2005) 1699–1707
after the substrate addition, the reaction mixture was stirred
until the green colour was recovered (ca. 40 min) and then,
the lithium excess was filtered off using inert conditions.
The resulting solution was added to a solution of
CuCN$2LiCl [prepared by dissolving copper(I) cyanide
(100 mg, 1.1 mmol) and lithium chloride (93 mg, 2.2 mmol)
in THF (5 mL)] and the mixture changed to black colour.
The solution was stirred 10 min at 0 8C and the correspond-
ing acid chloride (1.1 mmol) was added. After 3 h stirring,
the reaction was hydrolysed with water (10 mL), acidified
(10 mL of HCl 2 M) and extracted with ethyl acetate (3!
20 mL). The organic layer was washed with NaCl saturated
solution (2!15 mL) and dried over MgSO4, and the
solvents were evaporated (15 Torr) to yield a residue
which was purified by column chromatography (silica gel,
hexane/ethyl acetate) to give compounds 9. Structures and
yields are given in Chart 2 and Table 2; physical,
spectroscopic and analytical data follow.
4.3.5. 30-Methyl-a-cyclopentylacetophenone (9e). Rf 0.5
(hexane/ethyl acetate, 9/1); n (film) 3060, 3046, 3027, 1604
(C]C), 1684 cmK1 (C]O); dH 1.18 (m, 2H, CH2), 1.59
(m, 4H, 2!CH2), 1.87 (m, 2H, CH2), 2.38 (m with a s at
2.40, 4H, CH and CH3), 2.96 (d, JZ7.0 Hz, 2H, COCH2),
7.33 (m, 2H, 2!ArH), 7.75 (m, 2H, 2!ArH); dC 21.2
(CH3), 24.9, 32.6 (4!CH2), 36.0 (CH), 44.7 (COCH2),
125.2, 128.3, 128.5, 133.5, 137.2, 138.2 (6!ArC), 200.5
(C]O); m/z 202 (MC, 11.58%), 135 (12), 134 (82), 119
(100), 92 (12), 91 (50), 65 (15). HRMS: found MC,
202.1354. C14H18O requires 202.1358.
4.3.6. 40-Methyl-a-cyclopentylacetophenone (9f). Rf 0.5
(hexane/ethyl acetate, 9/1); n (film) 3086, 3054, 3030, 1607
(C]C), 1683 cmK1 (C]O); dH 1.18 (m, 2H, CH2), 1.59 (m,
4H, 2!CH2), 1.87 (m, 2H, CH2), 2.37 (m with a s at 2.39, 4H,
CH and CH3), 2.94 (d, JZ7.0 Hz, 2H, COCH2), 7.23 (d, JZ
8.0 Hz, 2H, 2!ArH), 7.85 (d, JZ8.1 Hz, 2H, 2!ArH); dC
21.4 (CH3), 24.8, 32.6 (4!CH2), 36.0 (CH), 44.5 (COCH2),
128.1, 129.1, 134.5, 143.4 (6!ArC), 199.9 (C]O); m/z 202
(MC, 4.90%), 134 (78), 119 (100), 91 (39), 65 (13). HRMS:
found MC, 202.1362. C14H18O requires 202.1358.
4.3.1. 1-Cyclopentyl-2-pentanone (9a). Rf 0.6 (hexane/
ethyl acetate, 9/1); n (film) 1713 cmK1 (C]O); dH 0.90 (t,
JZ7.3 Hz, 3H, CH3), 1.07 (m, 2H, CH2), 1.30 (sext, JZ
7.4 Hz, 2H, CH3CH2), 1.57 (m, 4H, 2!CH2), 1.81 (m, 2H,
CH2), 2.22 (sept, JZ7.7 Hz, 1H, CH), 2.40 (m, 4H,
CH2COCH2); dC 13.8 (CH3), 22.3, 24.9, 25.9, 25.8, 32.6
(5!CH2), 35.6 (CH), 42.7, 49.1 (CH2COCH2), 211.5
(C]O); m/z 169 (MCC1, 2.3%), 168 (MC, 17.4%), 111
(45), 101 (47), 100 (11), 85 (51), 83 (100), 67 (11), 59 (39),
58 (86), 57 (63), 55 (70). HRMS: found MC, 168.1499.
C11H20O requires 168.1514.
4.3.7. 40-tert-Butyl-a-cyclopentylacetophenone (9g). Rf
0.6 (hexane/etil acetate, 9/1); n (film) 3088, 3056, 3034
(C]CH), 1717, 1681 (C]O), 1606 cmK1 (C]C); dH 1.19
(m, 2H, CH2), 1.33 (s, 9H, 3!CH3), 1.59 (m, 4H, 2!CH2),
1.85 (m, 2H, CH2), 2.37 (def sept, JZ7.7 Hz, 1H, CH), 2.96
(d, JZ7.0 Hz, 2H, ArCOCH2), 7.46 (m, 2H, 2!ArH), 7.90
(m, 2H, 2!ArH); dC 24.9 (2!CH2), 31.0 (3!CH3), 32.6
(2!CH2), 36.0 (CH2CH), 44.6 (ArCOCH2), 125.1, 128.0,
134.6, 166.6 (6!ArC), 199.8 (C]O); m/z 245 (MCC1,
0.2%), 244 (MC, 0.1%), 187 (18), 176 (44), 162 (12), 161
(100), 118 (11). HRMS: found MCKCH3, 229.1558.
C16H21O requires 229.1592.
4.3.2. 1-Cyclopentyl-3,3-dimethyl-2-butanone (9b).21 Rf
0.7 (hexane/ethyl acetate, 9/1); n (film) 1076 cmK1 (C]O);
dH 1.03 (m, 2H, CH2), 1.12 (s, 9H, 3!CH3), 1.58 (m, 4H,
2!CH2), 1.82 (m, 2H, CH2), 2.26 (def sept, JZ7.7 Hz, 1H,
CH), 2.51 (d, JZ6.9 Hz, 2H, CH2CO); dC 25.0 (2!CH2),
26.3 (3!CH3), 32.6 (2!CH2), 35.2 (CH), 42.7
(CH2C]O), 43.9 [C(CH3)3], 215.9 (C]O); m/z 168
(MC, 6.6%), 111 (59), 83 (100), 57 (57), 55 (39). HRMS:
found MC, 168.1507. C11H20O requires 168.1514.
4.3.8. a-Cyclopentyl-40-methoxyacetophenone (9h).23 Rf
0.3 (hexane/ethyl acetate, 9/1); n (film) 3074, 3053
(C]CH), 1711, 1676 (C]O), 1258, 1031 cmK1 (ArC–O–
C); dH 1.17 (m, 2H, CH2), 1.58 (m, 4H, 2!CH2), 1.86 (m,
2H, CH2), 2.37 (def sept, JZ7.7 Hz, 1H, CH), 2.93 (d, JZ
7.2 Hz, 2H, CH2CO), 3.85 (s, 3H, OCH3), 6.92 (d, JZ
8.9 Hz, 2H, 2!ArH), 7.94 (d, JZ8.9 Hz, 2H, 2!ArH); dC
24.8, 32.6 (4!CH2), 36.2 (CH), 44.3 (CH2), 55.3 (OCH3),
113.5, 130.2, 131.4, 163.1 (6C!ArC), 198.9 (C]O); m/z
218 (MC, 1.0%), 150 (78), 135 (100), 92 (14), 77 (18).
HRMS: found MC, 218.1325. C14H18O2 requires 218.1307.
4.3.3. a-Cyclopentylacetophenone (9c).22 Rf 0.7 (hexane/
ethyl acetate, 9/1); n (film) 3063, 3027 (C]CH), 1599,
(C]C), 1688 cmK1 (C]O); dH 1.18 (m, 2H, CH2), 1.60
(m, 4H, 2!CH2), 1.88 (m, 2H, CH2), 2.39 (def sept, JZ
7.6 Hz, 1H, CH), 2.99 (d, JZ7.0 Hz, 2H, CH2CO), 7.45,
7.55, 7.96 (3m, 2H, 1H and 2H respectively, 5!ArH); dC
24.9, 32.7 (4!CH2), 36.0 (CH), 44.8 (CH2C]O), 128.1,
128.5, 132.8, 137.2 (6!ArC), 200.4 (C]O); m/z 189
(MCC1, 1.0%), 188 (MC, 6.2%), 121 (17), 120 (87), 105
(100), 77 (45), 51 (11).
4.4. Conjugate addition of intermediate 5 to a,b-
unsaturated ketones and aldehydes. Isolation of
compounds 10. General procedure
4.3.4. 20-Methyl-a-cyclopentylacetophenone (9d). Rf 0.4
(hexane/ethyl acetate, 9/1); n (film) 3062, 3021, 1600
(C]C), 1686 cmK1 (C]O); dH 1.15 (m, 2H, CH2), 1.59
(m, 4H, 2!CH2), 1.85 (m, 2H, CH2), 2.33 (sept, JZ7.7 Hz,
1H, CH), 2.48 (s, 3H, CH3), 2.90 (d, JZ7.2 Hz, 2H,
COCH2), 7.23 (def t, JZ6.8 Hz, 2H, 2!ArH), 7.75 (m, 2H,
2!ArH); dC 21.2 (CH3), 24.9, 32.6 (4!CH2), 36.0 (CH),
44.7 (COCH2), 125.2, 128.3, 128.5, 133.5, 137.2, 138.2
(6!ArC), 200.5 (C]O); m/z 202 (MC, 1.98%), 134 (14),
119 (100), 91 (33). HRMS: found MC, 202.1368. C14H18O
requires 202.1358.
To a stirred green suspension of lithium powder (40 mg,
5.8 mmol) and DTBB (13.3 mg, 0.05 mmol) in THF (4 mL)
at K30 8C was added 6-chlorohex-1-ene (0.138 mL,
1.0 mmol) under argon atmosphere. The colour disappeared
after the substrate addition, the reaction mixture was stirred
until the green colour was recovered (ca. 40 min) and the
lithium excess was filtered off using inert conditions. The
resulting solution was added to a solution of CuCN$2LiCl
[prepared by dissolving copper(I) cyanide (100 mg,
1.1 mmol) and lithium chloride (93 mg, 2.2 mmol) in THF
(5 mL)] and the resulting mixture changed to black colour.