650
A. G. Csꢀak€y et al. / Tetrahedron: Asymmetry 15 (2004) 647–652
AcOEt (3 · 25 mL). The combined extracts were dried
on MgSO4 and the solvent was evaporated under
reduced pressure. The resulting oil was purified by
chromatography (hexane/EtOAc, 2:1) to give (+)-6 as a
4.2.3. (4R,5S)- and (4R,5R)-5-Ethyl-4-methyl-5-phenyl-
cyclopentenone, 1c. (+)-6 (100 mg, 0.53 mmol), NaH
(64 mg, 60% mineral oil, 1.59 mmol) and EtBr (48 lL,
0.64 mmol) were reacted as described above. Compound
1c was obtained as a 95:05 mixture of diastereomers
(4R,5S)-1b and (4R,5R)-1b. Yield 75 mg (70%);
colourless oil. Yield 570 mg (60%); ½aꢀ ¼ +42.0 (c 1.57,
D
1
CHCl3); H NMR (CDCl3) d 7.30–7.13 (3H, m), 7.02–
6.98 (2H, m), 3.20 (1H, d, 3J ¼ 12:6 Hz), 2.48–2.46 (2H,
½aꢀ ¼ )232.5 (c 0.65, CHCl3); IR (CHCl3) m 1701 cmꢁ1
;
7.64 (1HI, dd,
D
3
m), 2.37–2.13 (1H, m), 1.04 (3H, d, J ¼ 6:7 Hz). Anal.
1H NMR (200 MHz, CDCl3)
d
3
3
Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.55;
H, 7.61.
3J ¼ 5:9 Hz, J ¼ 2:7 Hz), 7.52 (1HII, dd, J ¼ 5:9 Hz,
3J ¼ 2:4 Hz), 7.38–7.06 (5HI+5HII, m), 6.28 (1HI, dd,
4
3
3J ¼ 5:9 Hz, J ¼ 1:9 Hz), 6.19 (1HII, dd, J ¼ 5:9 Hz,
4J ¼ 2:4 Hz), 3.24–3.15 (1HII, m), 3.04–2.87 (1HI, m),
2.18 (1HI, B part of ABX system, 2J ¼ 13:7 Hz,
3J ¼ 7:3 Hz), 1.97 (1HI, A part of ABX system,
2J ¼ 13:7 Hz, 3J ¼ 7:3 Hz), 0.84 (3HI+3HII, t,
3J ¼ 7:3 Hz), 0.66 (3HI+3HII, d, 3J ¼ 7:6 Hz); 13C NMR
(50.5 MHz, CDCl3) d 213.1, 168.6, 141.1, 132.9, 128.1,
128.0, 126.9, 58.9, 47.6, 30.3, 17.2, 8.6; MS (m=z, %) 200
(M, 22), 185 (31), 172 (92), 171 (100), 143 (64), 129 (31),
128 (62), 115 (31), 91 (24), 77 (16).
4.2. General procedure for the synthesis of (4R,5S)-5-
alkyl-4-methyl-5-phenylcyclopentenones
To a solution of (+)-6 (100 mg, 0.53 mmol) in THF
(5 mL) at 0 ꢁC were sequentially added NaH (64 mg,
60% mineral oil, 1.59 mmol), and RX (0.64 mmol). The
mixture was allowed to reach rt, was stirred for 5 h, and
hydrolysed with saturated NH4Cl solution (5 mL). The
organic layer was decanted and the aqueous one was
extracted with Et2O (3 · 5 mL). The combined organic
layers were dried over MgSO4 and concentrated under
reduced pressure to afford an oil that was purified by
chromatography (hexane/Et2O, 10:1).
4.2.4. (4R,5S)-5-Allyl-4-methyl-5-phenylcyclopentenone,
(+)-6 (100 mg, 0.53 mmol), NaH (64 mg, 60%
())-1d.
mineral oil, 1.59 mmol) and allyl bromide (56 lL,
0.64 mmol) were reacted as described above to afford
())-1d as a single diastereomer. Yield 90 mg (80%); white
4.2.1. (4R,5S)- and (4R,5R)-4,5-Dimethyl-5-phenyl-cy-
clopentenone, 1a.
solid, mp 59–60 ꢁC; ½aꢀ ¼ )314.8 (c 1.06, CHCl3); IR
D
1
(+)-6 (100 mg, 0.53 mmol), NaH
(CHCl3) m 1701 cmꢁ1; H NMR (300 MHz, CDCl3) d
3
4
(64 mg, 60% mineral oil, 1.59 mmol) and MeI (40 lL,
0.64 mmol) were reacted as described above. Compound
1a was obtained as a 90:10 mixture of diastereomers
(4R,5S)-1a and (4R,5R)-1a. Yield 65 mg (65%);
7.61 (1H, dd, J ¼ 5:8 Hz, J ¼ 2:4 Hz), 7.33–7.12 (5H,
3
4
m), 6.31 (1H, dd, J ¼ 5:8 Hz, J ¼ 1:8 Hz), 5.68–5.62
(1H, m), 5.12–5.01 (2H, m), 3.05–3.01, (1H, m), 2.93–
2.86 (1H, m), 2.78–2.70 (1H, m), 0.70 (3H, d,
3J ¼ 7:5 Hz); 13C NMR (50.5 MHz, CDCl3) d 212.6,
168.8, 141.0, 133.3, 133.0, 128.1, 128.0, 126.6, 118.8,
58.2, 46.3, 41.4, 16.5; MS (m=z, %) 212 (M, 62), 197 (22),
171 (97), 167 (22), 149 (28), 143 (33), 141 (25), 129 (57),
128 (100), 115 (35), 105 (61), 97 (22), 85 (23), 83 (27), 81
(25), 77 (23), 71 (44), 57 (52), 55 (36), 41 (21). Anal.
Calcd for C15H16O: C, 84.87; H, 7.60. Found: C, 85.08;
H, 7.88.
½aꢀ ¼ )295.7 (c 1.50, CHCl3); 1H NMR (300 MHz,
D
CDCl3)
d
7.65–7.61 (1HI+1HII, m), 7.32–7.11
(5HI+5HII, m), 6.32 (1HI, dd, 3J ¼ 5:7 Hz, 4J ¼ 1:6 Hz),
3
6.26 (1HII, d, J ¼ 5:7 Hz), 3.21–3.18 (1HII, m), 2.95–
2.88 (1HI, m), 1.57 (3HI, s), 1.39 (1HII, s), 0.70 (3HI, d,
3J ¼ 7:5 Hz), 0.64 (3HII, d, 3J ¼ 6:5 Hz); 13C NMR
(50.5 MHz, CDCl3, majoritary diastereomer) d 213.6,
168.2, 141.5, 131.8, 128.0, 127.7, 126.5, 54.8, 50.1, 24.2,
16.8; MS (m=z, %) 186 (M, 85), 171 (100), 143 (86), 142
(19), 141 (16), 129 (25), 128 (70), 127 (15), 115 (30), 91
(17), 77 (30), 70 (17), 51 (21).
4.2.5. (4R,5S)-5-Ethoxycarbonylmethyl-4-methyl-5-phe-
(+)-6 (100 mg, 0.53 mmol),
nylcyclopentenone, ())-1e.
NaH (64 mg, 60% mineral oil, 1.59 mmol) and ethyl
bromoacetate (71 lL, 0.64 mmol) were reacted as
described above to afford ())-1e as a single diastereo-
4.2.2.
(4R,5S)-5-Benzyl-4-methyl-5-phenylcyclopent-
enone, ())-1b. (+)-6 (100 mg, 0.53 mmol), NaH (64 mg,
60% mineral oil, 1.59 mmol) and benzyl bromide (76 lL,
0.64 mmol) were reacted as described above to afford
())-1d as a single diastereomer. Yield 125 mg (90%);
mer. Yield 110 mg (80%); colourless oil; ½aꢀ ¼ )232.5 (c
D
1
0.30, CHCl3); H NMR (300 MHz, CDCl3) d 7.61 (1H,
3
3
dd, J ¼ 5:8 Hz, J ¼ 2:2 Hz), 7.28–7.23 (3H, m), 7.09–
3
3
white solid, mp 107–108 ꢁC; ½aꢀ ¼ )203.5 (c 1.10,
7.06 (2H, m), 6.48 (1H, dd, J ¼ 5:8 Hz, J ¼ 2:3 Hz),
4.12 (2H, c, 3J ¼ 7:2 Hz), 3.38–3.10 (1H, m), 3.23 (1H, B
D
CHCl3); IR (CHCl3) m 1697 cmꢁ1; H NMR (300 MHz,
1
2
CDCl3) d 7.40–7.00 (11H, m), 6.09 (1H, dd, 3J ¼ 5:8 Hz,
part of AB system, J ¼ 16:4 Hz), 3.15 (1H, A part of
4J ¼ 2:0 Hz), 3.50 (1H, B part of AB system, 2J ¼
AB system, 2J ¼ 16:4 Hz), 1.25 (3H, t, 3J ¼ 7:2 Hz), 0.74
2
3
12:9 Hz), 3.30 (1H, A part of AB system, J ¼ 12:9 Hz),
(3H, d, J ¼ 7:6 Hz); 13C NMR (75.5 MHz, CDCl3) d
3.22–3.13 (1H, m), 0.72 (3H, d, J ¼ 7:5 Hz); 13C NMR
211.6, 171.0, 168.1, 140.5, 133.5, 128.2, 127.3, 127.0,
60.7, 55.9, 46.5, 39.7, 15.5, 14.1; MS (m=z, %) 258 (M,
23), 213 (49), 212 (100), 197 (20), 184 (41), 171 (28), 156
(27), 143 (35), 142 (52), 141 (41), 129 (26), 128 (38), 115
(18), 77 (18). Anal. Calcd for C16H18O3: C, 74.39; H,
7.02. Found: C, 74.51; H, 6.89.
2
(50.5 MHz, CDCl3) d 212.9, 169.2, 141.4, 136.5, 133.3,
130.7, 128.1, 128.0, 128.0, 126.7, 126.6, 59.6, 44.8, 42.4,
16.6; MS (m=z, %) 262 (M, 34), 171 (38), 143 (22), 128
(32), 115 (10), 92 (13), 91 (100). Anal. Calcd for
C19H18O: C, 86.99; H, 6.92. Found: C, 87.11; H, 7.17.