(1ꢀ,3ꢀ,5ꢀ)-3-Butyl-6-oxabicyclo[3.1.0]hexane-3-methanol 31b
1037s; δ (400 MHz) 5.96 (1H, dd, J 5 and 2, CH᎐), 5.62 (1H, d,
᎐
H
J 5, CH᎐), 4.68 (1H, ddd, J 5, 2 and 2, CHO), 3.47 (1H, d, J 8,
᎐
Following the procedure for the preparation of epoxy alcohol
31a, but using alcohol 30b (1.00 g, 6.5 mmol) and tert-butyl
hydroperoxide (6.9 mol dmϪ3 in CH2Cl2; 1.88 cm3, 13.0 mmol)
gave, after purification by column chromatography (50% Et2O
in light petroleum) a colourless oil, epoxy alcohol 31b (0.87 g,
79%); Rf 0.35 (50% Et2O in light petroleum); νmax/cmϪ1 3420m,
2954s, 1051s and 868m; δH(400 MHz) 3.55 (1H, d, J 5, CHHO),
3.51 (1H, d, J 5, CHHO), 3.47–3.38 (2H, m, 2 × CHO), 2.15
(2H, d, J 10, 2 × CHH), 1.72 (2H, d, J 10, 2 × CHH), 1.45–1.10
(6H, m, 3 × CH2) and 0.92 (3H, t, J 7, Me); δC(100 MHz) 69.2
(CH2O), 58.8 (2 × CHO), 45.1 (C, quat.), 39.3 (2 × CH2), 37.1
(CH2), 26.8 (CH2), 23.1 (CH2) and 13.8 (Me); m/z (EI) 170 (Mϩ,
24%), 111 (44), 97 (43) and 81 (100) (Found: Mϩ, 170.1307.
C10H18O2 requires M, 170.1307).
CHHO), 3.43 (1H, d, J 8, CHHO), 3.30–2.92 (1H, br s, OH),
2.89–2.15 (1H, br s, OH), 1.95 (1H, dd, J 12 and 2, CHH), 1.64
(1H, dd, J 12 and 5, CHH), 1.40–1.10 (6H, m, 3 × CH2) and
0.87 (3H, t, J 7, Me); δ (100 MHz) 139.6 (CH᎐), 133.9 (CH᎐),
᎐
᎐
C
75.7 (CHO), 66.7 (CH2O), 53.9 (C, quat.), 42.1 (CH2), 36.1
(CH2), 26.5 (CH2), 23.3 (CH2) and 13.9 (Me); m/z (CI, NH3)
188 (M ϩ NH4ϩ, 12%), 170 (32), 139 (47), 122 (86), 83 (49), 80
(100) and 79 (98) [Found: (M ϩ NH4ϩ), 188.1651. C10H22NO2
requires M, 188.1651].
(1S,4S)-4-Benzyloxymethyl-4-hydroxymethylcyclopent-2-en-1-
ol 32c
Following the procedure for the preparation of diol 32a, but
using epoxy alcohol 31c (0.10 g, 0.43 mmol), BuLi (2.2
mol dmϪ3 in hexanes; 1.18 cm3, 2.60 mmol) and (1R,2S)-
norephedrine (0.196 g, 1.29 mmol) gave, after purification by
column chromatography (30% EtOAc in Et2O) a pale yellow
oil, cis-diol 32c (76 mg, 76%); Rf 0.21 (Et2O); [α]D20 Ϫ77.0 (c 6.1 in
CHCl3); νmax/cmϪ1 3353s, 3061s, 3032s, 2928s, 2859s, 1665m,
1455s, 1364s and 1096s; δH(400 MHz) 7.37–7.28 (5H, m, Ar),
(1ꢀ,3ꢀ,5ꢀ)-3-Benzyloxymethyl-6-oxabicyclo[3.1.0]hexane-3-
methanol 31c
Following the procedure for the preparation of epoxy alcohol
31a, but using alcohol 30c (0.30 g, 1.38 mmol) and tert-butyl
hydroperoxide (6.9 mol dmϪ3 in CH2Cl2; 0.40 cm3, 2.76 mmol)
gave, after purification by column chromatography (35% Et2O
in light petroleum) a colourless oil, epoxy alcohol 31c (143 mg,
45%); Rf 0.63 (Et2O); νmax/cmϪ1 3430s, 3082s, 2849s, 2659m,
1715m and 1619w; δH(400 MHz) 7.37–7.28 (5H, m, Ar), 4.52
(1H, d, J 7, CHHPh), 4.48 (1H, d, J 7, CHHPh), 3.51 (1H, d,
J 6.5, CHHOH), 3.49 (1H, d, J 6.5, CHHOH), 3.41 (2H, s,
2 × CHO), 3.29 (2H, s, CH2OBn), 2.06 (2H, d, J 15, 2 × CHH)
and 1.76 (2H, d, J 15, 2 × CHH); δC(100 MHz) 137.9 (Ar,
quat.), 128.4 (2 × Ar), 127.7 (Ar), 127.6 (2 × Ar), 76.6 (CH2Ph
or CH2OBn), 73.4 (CH2Ph or CH2OBn), 69.5 (CH2OH), 58.9
(2 × CHO), 46.5 (C, quat.) and 34.4 (2 × CH2); m/z (CI, NH3)
249 (M ϩ NH4ϩ, 70%), 235 (M ϩ Hϩ, 44), 217 (15), 160 (15),
144 (48) and 127 (100) (Found: M ϩ Hϩ, 235.1334. C14H19O3
requires M, 235.1334).
5.99 (1H, dd, J 5 and 2, CH᎐), 5.81 (1H, d, J 5, CH᎐), 4.66 (1H,
᎐
᎐
dd, J 5 and 2, CHO), 4.51 (1H, d, J 7, CHHPh), 4.49 (1H, d,
J 7, CHHPh), 3.64 (1H, d, J 11, CHHOH), 3.58 (1H, d, J 11,
CHHOH), 3.36 (1H, d, J 11, CHHOCH2), 3.32 (1H, d, J 11,
CHHOCH2), 2.03 (1H, dd, J 14 and 5, CHH) and 1.67 (1H,
d, J 14, CHH); δ (100 MHz) 138.5 (Ar, quat.), 136.7 (CH᎐),
᎐
C
135.7 (CH᎐), 128.4 (2 × Ar), 128.0 (Ar), 127.7 (2 × Ar), 75.6
᎐
(CH2Ph), 73.4 (CH2OBn), 66.2 (CH2OH), 57.5 (CHOH), 55.3
ϩ
(C, quat.) and 40.9 (CH2); m/z (CI, NH3) 252 (M ϩ NH4
,
12%), 234 (Mϩ, 35), 217 (15), 108 (12) and 96 (15) (Found:
M ϩ NH4ϩ, 252.1600. C14H22NO3 requires M, 252.1600).
(4R)-4-Hydroxymethyl-4-methylcyclopent-2-en-1-one 33a
PDC (293 mg, 0.78 mmol) was added in one portion to a stirred
solution of cis-diol 32a (100 mg, 0.78 mmol) in EtOAc (10 cm3)
and AcOH (0.2 cm3) at room temperature. After 1.5 h Et2O (10
cm3) was added, the reaction filtered and the residue washed
with Et2O (2 × 10 cm3). The volatile solvents were evaporated
under reduced pressure and the remaining AcOH removed by
azeotropic distillation with toluene (5 cm3). Purification of the
residue by column chromatography (75% EtOAc in hexane)
gave a colourless oil, hydroxy enone 33a (69 mg, 70%). Rf 0.32
(30% EtOAc in Et2O); [α]D20 ϩ97.0 (c 1.0 in CHCl3); νmax/cmϪ1
3423s, 2933s, 2861s, 1712s, 1678s and 1583m; δH(400 MHz) 7.40
(1S,4R)-4-Hydroxymethyl-4-methylcyclopent-2-en-1-ol 32a
BuLi (2.5 mol dmϪ3 in hexanes; 1.84 cm3, 4.60 mmol) was
added dropwise to a stirred solution of (1R,2S)-norephedrine
(0.36 g, 2.34 mmol) in benzene (12 cm3) and THF (8 cm3) at
0 ЊC. After 30 min a solution of epoxy alcohol 31a (0.10 g, 0.78
mmol) in THF (2 cm3) was added dropwise to the reaction
mixture over a period of 15 min. The solution was then allowed
to warm to room temperature overnight. MeOH (10 cm3) was
added and the solution filtered through Celite and evaporated
under reduced pressure. The residue was adsorbed onto silica
(1.0 g) and purified by column chromatography (30% EtOAc in
Et2O) to give a pale yellow oil, cis-diol 32a (63 mg, 63%); Rf 0.32
(30% EtOAc in Et2O); [α]D20 Ϫ24.7 (c 6.03 in CHCl3); νmax/cmϪ1
3310s, 2952s, 1669w, 1358m and 1042s; δH(400 MHz) 5.97 (1H,
(1H, d, J 5.5, CH᎐), 6.08 (1H, d, J 5.5, CH᎐), 3.55 (1H, d, J 10,
᎐
᎐
CHHO), 3.50 (1H, d, J 10, CHHO), 2.38 (1H, d, J 18.5, CHH),
2.03 (1H, d, J 18.5, CHH) and 1.02 (3H, s, Me); δC(100 MHz)
208.4 (C᎐O), 169.4 (CH᎐), 133.9 (CH᎐), 69.0 (CH O), 45.1
᎐
᎐
᎐
2
(CH2) and 22.5 (Me); m/z (EI) 126 (Mϩ, 28%), 111 (22), 95 (100),
81 (31), 67 (100) and 41 (75) (Found: Mϩ, 126.0681. C7H10O2
requires M, 126.0681). The ee of the 2,4-dinitrobenzoate
derivative was determined to be 99% by HPLC (75:25 EtOH–
hexane, 1 cm3 minϪ1), tRmj, 19.2; tRmn, 36.4.
dd, J 7 and 2, CH᎐), 5.66 (1H, d, J 7, CH᎐), 4.72 (1H, ddd, J 7,
᎐
᎐
2 and 2, CHO), 3.49 (1H, d, J 7, CHHO), 3.45 (1H, d, J 7,
CHHO), 2.93–2.45 (1H, br s, OH), 2.40–2.09 (1H, br s, OH),
1.92 (1H, dd, J 14 and 2, CHH), 1.75 (1H, dd, J 14 and 7,
CHH) and 1.04 (3H, s, Me); δ (100 MHz) 140.7 (CH᎐), 133.9
᎐
C
(CH᎐), 75.9 (CHO), 67.7 (CH O), 50.1 (C, quat.), 45.0 (CH )
᎐
2
2
and 23.1 (Me); m/z (EI) 129 (M ϩ Hϩ, 12%), 111 (33), 97 (26),
80 (100) and 79 (43) [Found: M ϩ Hϩ (Self protonated),
129.0916. C7H13O2 requires M, 129.0916].
(4R)-4-Butyl-4-hydroxymethylcyclopent-2-en-1-one 33b
Following the procedure for the preparation of hydroxy enone
33a, but using cis-diol 32b (180 mg, 1.06 mmol) and PDC (398
mg, 1.06 mmol) gave, after purification by column chromato-
graphy (75% EtOAc in hexane) a colourless oil, hydroxy enone
33b (103 mg, 58%); Rf 0.36 (25% EtOAc in Et2O); [α]D20 ϩ109 (c
1.0 in CHCl3); νmax/cmϪ1 3423s, 2930s, 2860s, 1710s, 1678s and
1586m; δ (400 MHz) 7.46 (1H, d, J 6, CH᎐), 6.17 (1H, d, J 6,
(1S,4R)-4-Butyl-4-hydroxymethylcyclopent-2-en-1-ol 32b
Following the procedure for the preparation of diol 32a, but
using epoxy alcohol 31b (0.30 g, 1.76 mmol), BuLi (2.5 mol
dmϪ3 in hexanes; 4.2 cm3, 10.5 mmol) and (1R,2S)-norephed-
rine (0.80 g, 5.28 mmol) gave, after purification by column
chromatography (30% EtOAc in Et2O) a pale yellow oil, cis-diol
᎐
H
CH᎐), 3.68 (1H, d, J 10, CHHO), 3.60 (1H, d, J 10, CHHO),
᎐
2.28 (1H, d, J 18, CHH), 2.22 (1H, d, J 18, CHH), 1.60–1.10
(6H, m, 3 × CH2) and 0.89 (3H, t, J 7, Me); δC(100 MHz) 209.8
(C᎐O), 169.3 (CH᎐), 134.3 (CH᎐), 67.8 (CH O), 51.0 (C, quat.),
32b (203 mg, 67%); Rf 0.38 (30% EtOAc in Et2O); [α]D20 ᎐ Ϫ28.9
᎐
(c 6.08 in CHCl3); νmax/cmϪ1 3331s, 2927s, 1620w, 1380m and
᎐
᎐
᎐
2
J. Chem. Soc., Perkin Trans. 1, 1999, 3579–3590
3585