Davis et al.
Rf 0.64 (15:85 Et2O-hexane); 1H NMR (500 MHz, CDCl3) δ
0.90 (d, 3H, J ) 6.6 Hz, 1′R), 0.94 (d, 3H, J ) 6.2 Hz, 1′â),
1.08 (s, 6H, 1′R + 1′â), 1.101 (s, 3H, 1′â), 1.104 (s, 3H, 1′R), δ
1.21 (s, 3H, 1′â), 1.22 (s, 3H, 1′R), 1.43-1.79 (m, 12H), 1.74
and 1.81 (ABq, 2H, J AB ) 13.6 Hz, 1′R), 1.74 and 1.82 (ABq,
2H, J AB ) 13.6 Hz, 1′â), 1.93 (qd, 1H, J ) 8.0, 5.3 Hz, 1′R),
2.00 (m, 2H), 2.07 (dddd, 1H, J ) 14.0, 8.9, 8.0, 3.2 Hz, 1′R),
2.19 (d, 1H, J ) 5.3 Hz, 1′â), 2.21 (d, 1H, J ) 5.3 Hz, 1′R),
3.40 (m, 2H), 3.56 (m, 2H); 13C NMR (126 MHz, CDCl3) (1′R-
isomer) δ 16.3, 26.7, 28.08, 29.1, 29.8, 32.3, 36.5, 38.7, 41.7,
44.5, 47.1, 49.4, 50.1, 62.5, 226.1 (C2); (1′â-isomer) δ 17.0, 26.8,
28.12, 28.9, 30.4, 32.4, 36.0, 38.0, 41.6, 44.6, 47.0, 48.9, 50.0,
61.4, 226.3; IR (CCl4) 1731 (CdO); MS (EI, 70 eV) m/z 302.
Kugelrohr distillation at 130-135 °C (0.09 Torr) gave a sample
for elemental analysis. Anal. Calcd for C15H24O (301.27): C,
60.00; H, 8.36. Found: C, 59.52; H, 8.25. HRMS (EI, 70 eV)
calcd for C15H25OBr 300.1089, found 300.1097 (∆ ) -2.7 ppm).
A subsequent reaction carried out as described above with a
1:1.8 (1′R-Me:1′â-Me) mixture of keto olefins (150 mg, 0.68
mmol) gave 148 mg (72%) of a 1:1.8 mixture of bromo ketones.
were allowed to stir at 0 °C for 30 min and room temperature
for 15 min. The ethereal supernatant was pipetted from the
white salts, and the salts were washed with ether (2 × 4 mL).
The ethereal solution and washes were combined, dried
(MgSO4), and evaporated to give a white solid residue (79 mg)
that was a 1.4:1 mixture of R:â-ÃΗ isomers by GC. Purification
by column chromatography (8:92 Et2O-pentane) gave 74 mg
(86%) (isomer ratio of 1.4:1 by GC). Further column chroma-
tography (2:98 Et2O-pentane) followed by HPLC purification
(Method B) of fractions containing a mixture of R:â alcohols
afforded 34 mg (GC purity: 100%) of 6-OH and 24 mg (GC
purity: 99%) of 18-OH as crystalline solids with mp 48-49
and 62-63 °C, respectively. The spectral data were identical
with those previously reported5a except for coupling observed
in the present case between the hydroxyl and the carbinol
protons. Physical data for 6-OH and 18-OH are given in the
Supporting Information.
(()-Ca m er oon a n -7r a n d 7â-yl Meth a n esu lfon a tes:
(1S*,2R*,5S*,8S*,9R*)- a n d (1S*,2S*,5S*,8S*,9R*)-3,3,5,9-
Tet r a m et h ylt r icyclo[6.3.0.01,5]u n d eca n -2-yl Met h a n e-
su lfon a tes (6-OMs, 18-OMs). A solution of MsCl (262 µL,
3.38 mmol) and a 1.5:1 mixture of R:â-cameroonanols (376 mg,
1.69 mmol) in pyridine (2.7 mL) was stirred at room temper-
ature for 3 h. The reaction was stopped upon dilution with
pentane (20 mL) and 5% HCl (5 mL). The organic layer was
washed with 5% HCl (5 mL), satd. NaHCO3 (5 mL), and satd.
NaCl (5 mL), dried (MgSO4), and evaporated to give 404 mg
of crude oil. Column purification (20:79:1 Et2O-pentane-
Et3N) afforded 357 mg (70%) of colorless oil that was a 1.5:1
mixture of R- and â-mesylates: TLC Rf 0.41 (15:85 EtOAc-
hexane); 1H NMR (500 MHz, CDCl3) (6-OMs) δ 1.00 (d, 3H, J
) 6.4 Hz), 1.018 (s, 3H), 1.021 (s, 3H), 1.17 (s, 3H), 1.21 (m,
1H), 1.34 (ddm, 1H, J ) 13.0, 6.1 Hz), 1.37-1.90 (m, 9H), 2.09
(t, 1H, J ) 8.4 Hz), 3.05 (s, 3H), 4.78 (s, 1H); (18-OMs) δ 0.94
(d, 3H, J ) 6.4 Hz), 0.97 (s, 3H), 1.07 (s, 3H), 1.09 (s, 3H),
1.37-1.90 (m, 11H), 1.97 (ddd, 1H, J ) 13.8, 8.4, 3.0 Hz), 3.05
(s, 3H), 4.56 (s, 1H); 13C NMR (126 MHz, CDCl3) (C7-RMs) δ
19.4, 25.1, 28.9, 31.8, 35.2, 35.2, 38.6, 38.8, 39.6, 43.8, 48.3,
52.4, 52.6, 66.9, 98.3; (C7-âMs) δ 19.0, 23.4, 26.3, 27.5, 27.9,
28.5, 36.3, 39.1, 41.8, 42.6, 49.5, 51.8, 61.2, 65.5, 96.9.
(()-Ca m er oon a n on e a n d (()-9-Ep ica m er oon a n on e:
(1S*,5S*,8S*,9R*)- a n d (1S*,5S*,8S*,9S*)-3,3,5,9-Tetr a -
m eth yltr icyclo[6.3.0.01,5]u n d eca n -2-on es (17a ,b). The cy-
clization was based on a procedure by Piers.25 An aliquot of
1.0 M KOtBu (2.79 mL, 2.79 mmol) in THF was added
dropwise over 4 min to a stirred solution of 613 mg (560 mg of
pure ketone, 1.86 mmol, 1:1 1′-R:â isomer ratio) of 16a ,b in
THF (42 mL). After 10 min, the excess base was neutralized
by adding 10% HCl (6 mL). The solution was diluted with
hexane (35 mL). The organic layer was washed with satd.
NaHCO3 (17 mL) and satd. NaCl (17 mL), dried (MgSO4), and
evaporated to give 387 mg of crude ketone that was a 1.2:1
mixture of 17a and 17b by GC. Purification by column
chromatography (57 g SiO2; 0.75:99.25 Et2O-hexane) afforded
152 mg (37%) of colorless oil 17a , 162 mg (40%) of colorless
oil that was a 5:1 mixture of 17b:17a , and 67 mg (15%
corrected for purity) of colorless oil that was a 2:1 mixture of
17b:17a that was 89% pure by GC. Two additional column
chromatographies (25 g of SiO2 and 32 g of SiO2, respectively;
0.75:99.25 Et2O-hexane) of the fractions containing a mixture
of epimeric ketones afforded 15 mg (GC purity: 100%) of 17a
in addition to 16 mg (GC purity: 100%) and 82 mg (GC
purity: 98%) of 17b. HPLC purification (Method A) gave an
analytical sample of 17b (68 mg, GC purity: 100%). The NMR
spectral data were identical with those previously reported for
17a .5a (()-17b : tR ) 12.67 min (Method B); TLC Rf 0.74
(()-Silp h ip er fol-6-en e (5), (()-P r en op sa n ol (7), a n d
(()-Silp h ip er fola n -7â-ol (9). This preparative solvolysis
procedure is based on that described by Coates.2b A solution
of 6-OMs and 18-OMs (316 mg, 1.05 mmol, R:â ) 1.5:1) and
pyridine (340 µL, 4.2 mmol) in 3:1 acetone-d6:D2O (6 mL) was
stirred at 25 °C for 24 h while the reaction progress was
monitored by 1H NMR analysis of reaction aliquots. The
solution was neutralized upon dilution with 5% HCl (10 mL)
and Et2O (40 mL). The organic layer was washed with satd.
NaHCO3 (10 mL) and satd. NaCl (10 mL), dried (MgSO4), and
evaporated to give 231 mg of crude oil that was an 11:7:1
mixture (1H NMR) of 6-OMs, prenopsanol, and silphiperfol-
6-ene. Column purification (5:95 EtOAc:pentane) afforded 13
mg of colorless oil that was a 3.2:2.5:1 mixture (GC) of
(()-silphiperfol-6-ene (5, 6%) and unknown olefins A (2%) and
B (2%), 3 mg of colorless oil that was a 4:1 (GC) mixture of
silphiperfolan-7â-ol (9, 2%) and unknown alcohol C (<1%), 59
mg of (()-prenopsanol (7, 41%), and 123 mg (66%) of 6-OMs.
Unknown olefin A: tR ) 9.64 min (Method B); TLC Rf 0.80
1
(15:85 Et2O-hexane); H NMR (500 MHz, CDCl3) δ 0.93 (d,
3H, J ) 6.8 Hz), 1.06 (s, 3H), 1.09 (s, 3H), 1.14 (m, 1H), 1.15
(s, 3H), 1.46 (m, 1H), 1.56-1.82 (m, 6H), 1.65 and 1.76 (ABq,
2H, J AB ) 13.6 Hz), 2.05 (m, 1H), 2.40 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 15.2, 24.5, 24.6, 27.4, 28.6, 29.9, 34.8, 37.9,
43.1, 45.2, 48.5, 49.2, 57.1, 71.5, 228.1; IR (CCl4) 1728 (CdO);
MS (EI, 70 eV) m/z 220. Kugelrohr distillation at 45-50 °C
(0.65 Torr) gave an analytical sample. Anal. Calcd for C15H24
O
(220.34): C, 81.76; H, 10.98. Found: C, 81.41; H, 11.06. A
subsequent reaction carried out as described above with a 1:1.8
(1′R-Me:1′â-Me) mixture of bromo ketones (65 mg, 0.22 mmol)
gave 37 mg (77%) of a 1:1.6 mixture of ketones 17a and 17b.
Physical data for 17a and additional NMR spectral data for
17b are listed in the Supporting Information.
1
(pentane); H NMR (500 MHz, CDCl3) δ 0.93 (d, 3H, J ) 7.3
(()-Ca m er oon a n -7r a n d 7â-ols: (1S*,2R*,5S*,8S*,9S*)-
a n d (1S*,2S*,5S*,8S*,9S*)-3,3,5,9-Tet r a m et h ylt r icyclo-
[6.3.0.01,5]u n d eca n -2-ols (6-OH, 18-OH). The reduction was
performed according to the procedure described by Weyerstahl.5a
A suspension of LiAlH4 (22 mg, 0.579 mmol) in ether (3 mL)
was stirred and cooled at 0 °C as (()-cameroonanone (85 mg,
0.386 mmol) in ether (2 mL) was added dropwise over 1 min.
After 30 min at 0 °C, the excess hydride was consumed by the
sequential addition of water (22 µL), 15% NaOH (22 µL), and
water (66 µL)26 at 1-min intervals, and the suspended salts
Hz), 0.96 (s, 3H), 4.69 (dt, ∼1H, J ) 6.5, 1.7 Hz), 4.94 (m, 1H);
GCMS (EI, 70 eV) m/z (rel intensity %) 204 (52), 189 (100),
175 (55), 161 (29), 147 (37), 133 (43), 119 (62), 105 (47), 91
(41), 77 (22). GC-HRMS (EI, 70 eV) calcd for C15H24 204.1878,
found 204.1886 (∆ ) -3.9). Unknown olefin B: tR ) 9.38 min
(Method B); TLC Rf 0.80 (pentane); 1H NMR (500 MHz, CDCl3)
δ 0.94 (s, 3H), 1.03 (s, 3H), 4.96 (app q, 1H, J ) 1.5 Hz); GCMS
(EI, 70 eV) m/z (rel intensity %) 204 (29), 189 (11), 175 (100),
162 (9), 147 (14), 133 (24), 121 (31), 105 (22), 91 (22), 77 (15).
GC-HRMS (EI, 70 eV) calcd for
C15H24 204.1878, found
(25) Piers, E.; Hall, T. W. Can. J . Chem. 1980, 58, 2613.
6942 J . Org. Chem., Vol. 68, No. 18, 2003
(26) Kraus, G. A.; Taschner, M. J . J . Org. Chem. 1980, 45, 1175.