SYNTHESIS
August 1998
1127
(5 mL of 1 M in Et2O, 5 mmol), stirred at this temperature for 45 min,
and quenched with satd NH4Cl solution. The product was extracted
into Et2O, dried, concentrated, and subjected to chromatography on
silica gel (elution with 1:8 EtOAc/hexanes). There were isolated two
isomers of 16 [combined weight of 126 mg (77%)] and 13 mg (8%)
of 17.
lution, the product was extracted into 1:3 EtOAc/hexanes, and the
combined organic layers were dried and evaporated. Chromatography
of the residue on silica gel (elution with 1:5 EtOAc/hexanes) gave
33 mg (95%) of 18 as a colorless oil.
IR (film): ν = 1698 cm–1.
1H NMR (C6D6): δ = 2.58–2.43 (m, 1 H), 2.27 (dt, J = 11.5, 3.5 Hz, 1
H), 2.14 (ddd, J = 13.3, 3.5, 0.8 Hz, 1 H), 2.04–1.92 (m, 2 H), 1.89 (t,
J = 7.0 Hz, 2 H), 1.77 (dd, J = 16.8, 6.1 Hz, 1 H), 1.63–1.40 (m, 2 H),
1.35–1.10 (series of m, 6 H); 0.90 (t, J = 7.3 Hz, 3 H), 0.94–0.84 (m,
1 H).
16a: colorless solid; mp 63–64°C.
IR (film): ν = 3383 cm–1.
1H NMR (C6D6): δ = 5.45 (t, J = 1.2 Hz, 1 H), 2.24 (m, 1 H), 2.12–
1.98 (m, 2 H), 1.84 (q, J = 7.5 Hz, 2 H), 1.79–1.30 (series of m, 9 H),
1.25–1.10 (m, 3 H), 1.04 (s, 1 H), 0.95 (t, J = 7.5 Hz, 3 H).
13C NMR (C6D6): δ = 136.7, 129.7, 70.5, 43.4, 35.5, 35.0, 32.4, 31.3,
30.7, 30.5, 25.5, 22.4, 12.4.
13C NMR (C6D6): δ = 213.5, 208.3, 48.6, 46.8, 42.4, 36.2, 33.7, 32.2,
27.5, 25.6, 23.8, 7.8.
HRMS (EI): m/z (M+) calcd 196.1463, obsd 196.1463.
Anal. Calcd for C12H20O2 (196.3): C, 73.42; H, 10.27. Found: C,
73.15; H, 10.22.
HRMS (EI): m/z (M+) calcd 194.1671, obsd 194.1670.
Anal. Calcd for C13H22O (194.3): C, 80.35; H, 11.41. Found: C,
80.19; H, 11.40.
10-Methylbicyclo[5.3.1]undec-1(10)-en-9-one (11):
A solution of 18 (38 mg, 0.19 mmol) in MeOH (5 mL) was treated
with NaOMe (40 mg, excess) and refluxed for 30 min prior to being
quenched with satd NH4Cl solution and extracted with 1:3 EtOAc/
hexanes. The combined organic phases were dried and evaporated to
leave a residue whose purification by silica gel chromatography (elu-
tion with 1:6 EtOAc/hexanes) furnished 33 mg (95%) of 11, identical
in all respects to the material synthesized earlier.
16b: colorless oil.
IR (film): ν = 3387 cm–1.
1H NMR (C6D6): δ = 5.34 (t, J = 1.2 Hz, 1 H), 2.17 (m,1 H), 1.98 (ddd,
J = 14.4, 3.1, 2.5 Hz, 1 H), 1.92–1.35 (series of m, 14 H), 1.13 (s, 1
H), 1.13–0.80 (m, 1 H), 0.89 (t, J = 7.4 Hz, 3 H).
13C NMR (C6D6): δ = 136.7, 130.6, 71.3, 43.4, 37.6, 36.1, 33.3, 31.2,
29.7, 29.3, 27.9, 27.5, 8.4.
HRMS (EI): m/z (M+) calcd 194.1671, obsd 194.1676.
Financial support was provided by the National Cancer Institute
(Grant No. CA-63344).
17: colorless oil.
IR (film): ν = 1707 cm–1.
1H NMR (C6D6): δ = 2.13 (dddd, J = 13.1, 6.5, 0.8, 0.6 Hz, 1 H), 2.03
(dq, J = 13.0, 2.0 Hz, 1 H), 1.96 (dt, J = 13.0, 2.2 Hz, 1 H), 1.85 (d, J
= 13.0 Hz, 2 H), 1.65–1.47 (series of m, 4 H), 1.36 (dd, J = 23.3,
10.2 Hz, 2 H), 1.20–1.17 (m, 2 H), 1.02 (q, J = 7.5 Hz, 2 H), 1.06–
0.92 (m, 4 H), 0.59 (t, J = 7.5 Hz, 3 H).
(1) For reviews on this subject, see:
Taxane Anticancer Agents: Basic Science and Current Status;
Georg, G. I.; Chen, T. T.; Ojima, I.; Vyas, D. M., Eds.; ACS
Symposium Series 583; American Chemical Society: Washing-
ton, DC, 1995.
13C NMR (C6D6): δ = 209.2, 52.3, 47.8, 40.8, 35.3, 34.9, 34.5, 32.6,
32.5, 31.3, 25.4, 23.0, 7.8.
Taxol Science and Applications; Suffness, M., Ed.; CRC, Boca
Raton, FL, 1995.
HRMS (EI): m/z (M+) calcd 194.1671, obsd 194.1667.
Wender, P. A.; Natchus, M. G.; Shuker, A. J. In Taxol® Science
and Applications, Suffness, M., Ed.; CRC Press: New York,
1995, pp 123–187.
3-(2-Oxobutyl)cyclooctanone (18):
To a solution of 16 (50 mg, 0.26 mmol) in THF (3 mL) and pyridine
(0.5 mL) at 0°C was added OsO4 (65 mg, 0.26 mmol). The mixture
was stirred in the cold for 2 h, quenched with NaHSO3 solution, and
stirred for an additional hour. The products were extracted into 1:3
hexanes/EtOAc, and the combined organic layers were dried and
evaporated. The residue was chromatographed on silica gel (elution
with 1:2 hexanes/EtOAc) to give a combined 50 mg (85%) of two tri-
ol isomers A and B.
Boa, A. N.; Jenkins, P. R.; Lawrence, N. J. Contemp. Org.
Synth. 1994, 1, 47.
Nicolaou, K. C.; Dai, W. M.; Guy, R. K. Angew. Chem. 1994,
106, 38; Angew. Chem. Int. Ed. Engl. 1994, 33, 15.
Kingston, D. G. I.; Molinero, A. A.; Rimoldi, J. M. Progress in
the Chemistry of Organic Natural Products; Springer-Verlag:
New York, 1993; Vol. 61.
Paquette, L. A. Studies in Natural Products Chemistry; Else-
vier: Amsterdam, 1992, Vol. 11, pp 3–69.
Isomer A: white crystals; mp 93–94°C.
IR (film): ν = 3406 cm–1.
Swindell, C. S. Org. Prep. Proced. Int. 1991, 23, 465.
(2) (a) Miyazaki, M.; Shimizu, K.; Mishima, H.; Kurabayashi, M.
Chem. Pharm. Bull. Japan 1968, 16, 546.
(b) Erdtman, H.; Tsuno, K. Phytochem. 1969, 8, 931.
(3) Wani, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.; McPhail,
A. T. J. Am. Chem. Soc. 1971, 93, 2325.
1H NMR (CDCl3): δ = 3.35 (s, 1 H), 2.87 (br s, 3 H), 2.10–1.30 (series
of m, 17 H), 0.94 (t, J = 7.4 Hz, 3 H).
13C NMR (CDCl3): δ = 74.8, 74.1, 74.0, 38.7, 36.8, 34.6, 33.4, 33.3,
28.3, 27.9, 22.7, 20.6, 7.8.
HRMS (EI): m/z (M+) calcd 228.1725, obsd 228.1724.
Anal. Calcd for C13H24O3 (228.3): C, 68.38; H, 10.59. Found: C,
68.41; H, 10.59.
(4) Marchesini, A.; Pagnoni, U. M.; Pinetti, A. Tetrahedron Lett.
1973, 4299.
(5) Hirano, S.; Hiyama, T.; Fujita, S.; Kawaguti, T.; Hayashi, Y.;
Nozaki, H. Tetrahedron 1974, 30, 2633.
(6) (a) Paquette, L. A.; Wang, T.-Z.; Luo, J.; Cottrell, C. E.; Clough,
A. E.; Anderson, L. B. J. Am. Chem. Soc. 1990, 112, 239.
(b) Paquette, L. A.; Underiner, T. L.; Gallucci, J. C. J. Org.
Chem. 1992, 57, 86.
(7) (a) Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C.
B. W.; Wovkulich, P. M.; Uskokovic, M. R. Tetrahedron Lett.
1992, 33, 917.
Isomer B: white foam.
IR (film): ν = 3430 cm–1.
1H NMR (CDCl3): δ = 3.17 (s, 1 H), 3.12 (br, 1 H), 2.60 (dd, J = 15.3,
9.5 Hz, 1 H), 2.00–1.15 (series of m, 18 H), 0.92 (t, J = 7.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 77.0, 76.2, 74.9, 37.5, 37.2, 34.5,
31.8 (2 C), 30.5, 29.2, 25.2, 21.8, 6.1.
HRMS (EI): m/z (M+) calcd 228.1725, obsd 228.1737.
A 40 mg (0.175 mmol) sample of this triol mixture was dissolved in
MeOH (4 mL) at 0°C, treated with Pb(OAc)4 (177 mg, 0.40 mmol) in
one portion, and stirred for 4 h. After dilution with satd NaHCO3 so-
(b) Johnson, C. R.; Adams, J. P.; Collins, M. A. J. Chem. Soc.,
Perkin Trans 1 1993, 1.