7844 J . Org. Chem., Vol. 65, No. 23, 2000
Hamon and Tuck
30.3 (CH2, C6), 31.6 (CH2, C3), 37.7 (CH2, C4), 44.3 (q), 45.1
A suspension of the tosylhydrazone 9 (1.04 g, 3.59 mmol)
and TMEDA (15 mL) was cooled to -78 °C, under a nitrogen
atmosphere. A solution of nBuLi (2.3 M, 4.6 mL, 10.58 mmol)
was added dropwise to the frozen suspension, and the solution
generated was kept at -78 °C for 15 min and then allowed to
warm to ambient temperature, whereupon it turned a dark
red color. This solution was stirred for a further 5 h, it was
cooled to 0 °C, DMF (0.4 mL, 5.18 mmol) was added, and the
solution was stirred at ambient temperature overnight. It was
then poured into 7.5% HCl(aq) (60 mL) and extracted with CH2-
Cl2 (4 × 40 mL). The combined organic phases were washed
with sat. NaCl(aq) (40 mL) and dried, and solvent was removed
in vacuo. The crude material was used directly in the next
reaction. A small portion was purified by flash chromatography
(CH2Cl2) to give a pure sample for spectroscopic analysis. δH
(300 MHz): 1.30 (s, 3H), 1.6-2.1 (m, 3H), 2.2-2.6 (m, 3H),
3.02 (br d, 1H, J ) 8.2 Hz), 6.87 (br s, 1H), 9.78 (s, 1H). δC (75
MHz): 23.4, 24.6, 33.0, 44.4, 46.9, 47.9, 150.8, 152.6, 190.1.
(CH, C1), 57.0 (CH2, C1′), 67.2 (q). m/z: 138(M+•, 30%), 55(100).
(1S R ,5S R )-5-Me t h yl-2-m e t h yle n e b icyclo[3.2.0]h e p -
ta n e 7. Compound 7 has been previously prepared by Rosini,
by an alternative procedure.7 To a solution of methyltri-
phenylphosphonium iodide (4.23 g, 10.5 mmol) in Et2O (25
mL), under a nitrogen atmosphere, was added, over 5 min,
t-BuOK (1.62 g, 14.5 mmol). The mixture was stirred at
ambient temperature for 20 min, the yellow reaction mixture
was cooled to 0 °C, and (1SR,5SR)-5-methylbicyclo[3.2.0]-
heptan-2-one 4 (1.10 g, 8.94 mmol) was added dropwise. After
being stirred for 15 h at ambient temperature, the still-yellow
solution was filtered through Celite, and solvent was removed
at atmospheric pressure. An evaporative distillation (kugel-
rohr) 760 mm/60 °C gave the title compound as a colorless
liquid (436 mg, 40%). δH (200 MHz): 1.20 (s, 3H), 1.2-2.0
(complex, 5H), 2.30 (complex, 2H), 2.42 (dm, 1H, 16.6 Hz), 2.75
(m, 1H), 4.66 (br s, 1H), 4.76 (br s, 1H). δC (50 MHz): 22.0,
26.4, 30.2, 33.2, 40.2, 45.8, 48.7, 104.3, 158.5. Analysis and
HR MS were not obtained.
υ
max(neat): 1680(s) cm-1. m/z: 136(M+•, 11%), 79(100).
Red u ction of th e Ald eh yd e 10. To the crude aldehyde
10 (∼2 g, max. 3.5 mmol) dissolved in MeOH (15 mL) was
added ceric chloride (0.1 mL), and the reaction vessel placed
under a nitrogen atmosphere. Solid NaBH4 (201 mg, 5.32
mmol) was added with stirring over 10 min, and after 4 h the
solution was diluted with CH2Cl2 and washed with 7.5%
HCl(aq). The aqueous phase was further extracted with CH2-
Cl2. The combined organic extracts were washed with sat.
NaCl(aq) and dried, and solvent was removed in vacuo. Flash
chromatography (CH2Cl2) gave the title compound (477 mg,
83% over two steps). δH (600 MHz):40 1.27 (s, 3H, CH3), 1.69
(m, 1H, H7a), 1.79 (m, 1H, H6a), 1.94 (m, 1H, H6b), 2.1-2.3
(complex, 3H, H4, H7b), 2.74 (d, J ) 7.8 Hz, 1H, H1), 4.12 (AB
quartet, J ) 15.5 Hz, 1H, H1a′), 4.20 (AB quartet, J ) 15.5
Hz, 1H, H1b′), 5.62 (s, 1H, H3). δC and DEPT (75 MHz): 23.2
(CH2), 25.0 (CH), 33.2 (CH2), 44.4 (q), 47.2 (CH2), 50.1 (CH3),
60.5 (CH2), 125.0 (CH), 146.9 (q).M/z: 138(M+•, 15%), 95(100).
Anal. Calcd for C9H14O: C, 78.21; H, 10.20 Found: C, 78.19;
H, 9.96.
(1SR,2RS,5SR)-5-Meth yl-2-m eth ylen e oxid e bicyclo-
[3.2.0]h ep ta n e 5 a n d (1SR,2SR,5SR)-5-Meth yl-2-m eth yl-
en e oxid e bicyclo[3.2.0]h ep ta n e 6. The alkene 7 (30 mg,
0.25 mmol) was added to the two-phase solution of Et2O (3
mL) and 0.68 M NaHCO3(aq) (3 mL). After the mixture was
cooled to -5 °C, mCPBA (90% mCPBA, 71 mg, ∼0.37 mmol)
was added portionwise over 15 min. The mixture was then
allowed to stir at ambient temperature for 15 h. CH2Cl2 (20
mL) and water (10 mL) were added, the organic phase was
separated, this was washed successively with 1 M NaOH(aq)
and water and dried, and the solvent was removed in vacuo
to give the title compounds (21 mg, 60%). 1H NMR showed
the presence of the two epoxides in a 20:80 ratio (endo-5:exo-
6). The major signals were for the isomer 6. δH (600 MHz):
1.20 (s, 3H, CH3), 1.5-2.2 (complex, 8H, H1, H3a, H4, H6, H7),
2.56 (td, J ) 7.8, 13.8 Hz, 1H, H3b), 2.70 (d, J ) 4.5 Hz, 1H,
H1′), 2.79 (d, J ) 4.5 Hz, 1H, H1′). δC (50 MHz): 17.5, 26.4,
29.6, 32.7, 38.9, 45.3, 47.9, 48.5, 69.4.
1-Oxa sp ir o[2.5]oct-2-ylm eth a n ol 12 fr om Sh a r p less
Asym m etr ic Ep oxid a tion Rea ction . F or m a tion of 2-(1-
Cycloh exen yl)oxir a n e 13. Following the procedure of Sharp-
less,28 an anhydrous flask was flushed with nitrogen and
charged with n-decane (40 µL), (L)-(+)-DIPT (27 mg, 0.12
mmol), activated powdered 4 Å sieves (38 mg), and a solution
of the alcohol 11 (100 mg, 0.80 mmol) in anhydrous CH2Cl2 (2
mL), previously dried over 3 Å sieves for 1 h. The flask was
cooled to -20 °C, titanium(IV) isopropoxide (0.35 mL, 0.08
mmol) was added, and the solution was stirred at -20 °C for
1 h. The flask was then cooled to -40 °C, and tert-butyl
hydroperoxide solution (0.15 mL of a 4.2 M CH2Cl2 solution,
0.63 mmol), previously dried19 and then freshly dried over
freshly activated 3 Å sieves for 15 min, was added. At timed
intervals, aliquots (0.1 mL) of the reaction mixture were taken
(with an oven dried syringe) and quenched with 0.1 mL of a
solution of FeSO4 (1.6 g/5 mL) and citric acid (0.5 g/5 mL),
CH2Cl2 (0.1 mL) was added, and the organic layer was
separated. The organic layer was then analyzed by GLC (150
°C) for the remaining allylic alcohol relative to the internal
standard n-decane. After the reaction was complete, it was
quenched with a solution of FeSO4 (1.6 g/5 mL) and citric acid
(0.5 g/5 mL) and then left for 15 h. The reaction mixture was
diluted with CH2Cl2, the organic layer was separated, and the
aqueous layer was re-extracted with CH2Cl2. The combined
organic phases were washed with sat. NaCl(aq) and dried, and
solvent was removed in vacuo. Flash chromatography (hex-
anes/EtOAc, 70/30 v/v) did not give the expected product but
a colorless liquid identified as 2-(1-cyclohexenyl)oxirane32 13
(47%). δΗ (200 MHz): 1.5 (complex, 4H), 1.8 (complex, 4H),
3.4-3.7 (AB of ABX, 2H), 3.9-4.1 (X of ABX, 1H), 5.66 (br s,
1H). δC (150 MHz): 22.4, 22.5, 24.8, 24.9, 65.4, 76.2, 123.9,
136.7. GC/MS: 124 (M+, 65%), 95 (100).
Attem p ted F or m a tion of [(1RS,5SR)-5-Meth ylbicyclo-
[3.2.0]h ep t-2-en -2-yl]m eth a n ol 3. To a solution of CH2Cl2
(1.5 mL), DBU (0.2 mL), and endo-epoxide 5 (99 mg, 0.72
mmol) was added TMSOTf (0.2 mL). The solution was stirred
for 15 h under a nitrogen atmosphere and at ambient tem-
perature, 15% HCl(aq) (5 mL) and CH2Cl2 (10 mL) were added,
and the aqueous layer was separated. The aqueous phase was
re-extracted with CH2Cl2 (2 × 10 mL). The combined organic
phases were washed with sat. NaCl(aq) (10 mL) and dried, and
solvent was removed in vacuo. Flash chromatography (CH2-
Cl2/hexanes 15/85 v/v) gave the title compound as a colorless
liquid (27 mg, 27%). 1H NMR data was identical with that
obtained later for the alcohol 3.
A Mixtu r e of E a n d Z Isom er s of N′-1-[(1SR,5SR)-5-
Met h ylb icyclo[3.2.0]h ep -2-ylid en ]-4-m et h yl-1-t olu en e-
su lfon oylh yd r a zon e 9. Tosylhydrazine (3.53 g, 18.9 mmol)
was added to 60% MeOH(aq) (46 mL) heated to 60 °C.
(1SR,5SR)-Methylbicyclo[3.2.0]heptan-2-one 4 (2.33 g, 18.8
mmol) was then added dropwise to the clear solution. The
reaction mixture was immediately stored at 5 °C for 15 h. The
resultant white crystals were filtered, washed with 60%
MeOH(aq), and air-dried for 10 min. The title compound was
1
obtained as white crystals (4.91 g, 89%), mp 174-176 °C. H
NMR revealed a 1:1 mixture of isomers. δH (200 MHz): 1.21
(s, 3H, CH3), 1.23 (s, 3H, CH3), 2.42 (br s, 6H, Ar-CH3), 1.35-
2.9 (m, 18H, ring protons), 4.06 (br s, 2H, NH), 7.30 (dm, J )
8.0 Hz, 4H, Ar), 7.82 (d, J ) 8.0 Hz, 4H, Ar). δC (50 MHz):
18.6, 21.4, 21.5, 25.3, 25.5, 27.9, 29.8, 30.0, 33.2, 36.7, 37.3,
42.1, 44.1, 45.9, 48.0, 127.9, 129.5, 135.6, 143.58, 171.4, 172.3.
υ
max: 3297, 3220 (2 peaks, NH) cm-1. m/z: 293 (M+•,100%),
137 (94). Anal. Calcd for C15H20O2SN: C, 61.61; H, 6.89.
Found: C, 61.48; H, 7.03.
[(1RS,5SR)-5-Meth ylbicyclo[3.2.0]h ep t-2-en -2-yl]m eth -
a n ol 3. F or m a tion of th e Ald eh yd e 10. [CAUTION: Ni-
trogen is produced in this reaction and allowance must be
made for its escape. Do not use a sealed system.]
F or m a tion of 1-Oxa sp ir o[2.5]oct-2-ylm eth a n ol 12. The
above procedure was repeated with the following quantities:
n-decane (40 µL), (L)-(+)-DIPT (24 mg, 0.10 mmol), activated
powdered 4 Å sieves (33 mg), a solution of the alcohol 11 (102