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A. V. Gaidai et al.
PAPER
1H NMR (CDCl3): d = 1.04, 1.61 (AB, 3J = 10.5 Hz, 2 H), 2.30 (s,
2 H), 2.35 (s, 2 H), 2.55 (s, 2 H), 2.63 (s, 2 H), 3.79 (s, 2 H), 6.25–
6.32 (m, 2 H).
13C NMR (CDCl3): d = 34.53, 38.37, 39.91, 43.02, 45.55, 71.63.
13C NMR (CDCl3): d = 32.99, 33.69, 40.71, 41.22, 43.16, 44.27,
47.18, 47.45, 52.24, 53.48, 77.18.
GC/MS: tR = 6.50 min; m/z (%) = 162 (M+, 12), 144 (98), 95 (100),
79 (96), 66 (76), 39 (91).
GC/MS: tR = 8.83 min; m/z (%) = 178 (M+, 14), 160 (100), 95 (76),
94 (56), 91 (70), 66 (88).
Pentacyclo[6.3.0.02,6.03,10.05,9]undecan-4-one (rac-13)
Undecan-4-ol rac-12 (32.5 g, 0.2 mol) was dissolved in acetone
(500 mL). Under constant stirring and cooling with ice, Jones re-
agent [CrO3 (72.8 g, 0.728 mol), H2SO4 (60 mL), and H2O (140
mL)] was added dropwise. The temperature of the mixture re-
mained below 10 °C. After addition of the reagents stirring was con-
tinued for 4 h at 25 °C. The mixture was poured into H2O and
extracted with CH2Cl2 (3 × 50 mL); the combined organic layers
were dried (Na2SO4) and the solvent was removed at reduced pres-
sure to give rac-13 (30.8 g, 96%).
7-Iodopentacyclo[6.3.0.02,6.03,10.05,9]undecan-4-ol (10)12
Diol 9 (20 g, 0.112 mol) was heated at 100 °C in freshly distilled HI
(160 mL) with stirring for 3 h. The cooled mixture was poured out
into H2O (350 mL), and then extracted with CH2Cl2 (4 × 50 mL).
The combined organic layers were washed sequentially with H2O,
10% NaOH soln, and H2O. The organic layer was dried (Na2SO4)
and evaporated under vacuum to obtain a mixture of iodo alcohols
10 with ~5% (GC MS data) impurity of the corresponding diiodo
derivatives (27.5 g, 79%). The mixture was used in next step with-
out additional purification.
1H NMR (CDCl3): d = 1.43, 1.69 (AB, 3J = 10 Hz, 4 H), 1.78 (s, 2
H), 2.40 (s, 4 H), 2.46 (s, 2 H).
1H NMR (CDCl3): d = 1.40–1.42 (m, 2 H), 2.03–2.94 (m, 9 H),
13C NMR (CDCl3): d = 35.53, 40.95, 41.12, 47.62, 50.21, 217.31.
GC/MS: tR = 6.59 min; m/z (%) = 160 (M+, 47), 132 (37), 78 (17),
3.96–4.06 (m, 1 H), 4.22–4.25 (m, 1 H).
13C NMR (CDCl3): d = 77.08, 75.50, 57.11, 55.30, 54.79, 54.23,
53.61, 53.48, 51.81, 50.73, 48.77, 45.95, 45.12, 43.20, 41.10, 40.65,
40.25, 40.07, 34.02, 32.56, 32.14, 31.68.
66 (100), 39 (17).
Spiro[oxirane-2,4¢-pentacyclo[6.3.0.02,6.03,10.05,9]undecane]
(rac-14)
Iodo Alcohol 10a
Yield: 17.7%.
GC/MS: tR = 9.24 min; m/z (%) = 288 (M+, 14), 161 (100), 143 (58),
128 (58), 91 (59), 67 (66).
To flask containing a bubble counter, 40% NaH (12.2 g, 0.305 mol)
was added and washed with hexane (3 × 50 mL). THF (200 mL) and
Me3SI (103 g, 0.505 mol) were added, and the mixture was stirred
at 0 °C until no further release of gas was observed. A soln of unde-
can-4-one rac-13 (27 g, 0.168 mol) in DMSO (400 mL) and THF
(170 mL) was added dropwise over 30 min, the mixture was stirred
at 0 °C for 1 h and then stirring was continued for 15 h at 25°C. The
mixture was poured into H2O and extracted with CH2Cl2 (3 × 100
mL). The combined organic layers were washed with H2O (3 × 100
mL) and dried (Na2SO4). The solvent was removed under vacuum
yielding rac-14 (25.3 g, 86%) as an oily liquid; bp 121–122 °C/24
mbar.
Iodo Alcohol 10b
Yield: 76.2%.
GC/MS: tR = 9.28 min; m/z (%) = 288 (M+, 14), 161 (100), 143 (71),
128 (57), 91 (41), 77 (37).
Pentacyclo[6.3.0.02,6.03,10.05,9]undecan-4-yl Acetate (rac-11)12
Zn dust (200 g, 3.05 mol) was added portionwise to a mixture of the
crude mixture of iodo alcohols 10 (60 g, 0.208 mol) in AcOH (600
mL) preheated to 60 °C while stirred by a mechanical stirrer. The
mixture was heated under reflux with stirring for 3 h. It was then
cooled to r.t. and the mixture was filtered into a flask with H2O (1
L); the unreacted zinc was washed by H2O (200 mL) and CH2Cl2
(300 mL). The filtrate was extracted with CH2Cl2 (2 × 100 mL) and
the combined organic layers were washed by H2O and then
NaHCO3 soln (2 ×), dried (Na2SO4), and evaporated in vacuo to
yield rac-11 (37.6 g, 95%) as white viscous liquid with characteris-
tic smell; bp 130–131 °C/16 mbar.
1H NMR (CDCl3): d = 1.27–1.36 (m, 3 H), 1.43 (d, 3J = 10 Hz, 1 H),
1.91–2.12 (m, 10 H), 2.45 (s, 1 H), 4.87 (s, 1 H).
13C NMR (CDCl3): d = 21.24, 32.92, 33.57, 40.77, 41.16, 42.58,
44.68, 47.14, 47.34, 49.56, 50.65, 79.65, 171.24.
GC/MS: tR = 7.42 min; m/z (%) = 204 (M+, 2), 162 (100), 144 (58),
79 (37), 66 (27), 43 (43).
1H NMR (CDCl3): d = 1.27–1.29 (m, 2 H), 1.37–1.39 (m, 1 H),
4
1.43–1.45 (m, 2 H), 1.48 (d, J = 5 Hz, 1 H), 2.06–2.13 (m, 3 H),
2.20 (q, 4J = 5 Hz, 1 H), 2.25 (s, 1 H), 2.53 (br s, 1 H), 2.83, 2.87
(AB, 3J = 4.5 Hz, 2 H).
13C NMR (CDCl3): d = 33.73, 31.12, 41.46, 42.28, 43.90, 45.97,
47.41, 47.47, 49.06, 49.63, 49.93, 70.84;
GC/MS: tR = 6.78 min; m/z (%) = 174 (M+, 60), 108 (44), 80 (42),
79 (100), 77 (62).
Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.53; H,
8.16.
Pentacyclo[6.3.0.02,6.03,10.05,9]undecane-4-carbaldehyde (rac-15)
Epoxide rac-14 (31 g, 0.178 mol) in benzene (200 mL) was added
dropwise to the stirred soln of BF3·Et2O (49 mL) in benzene (600
mL) under cooling. After the addition of the reagents stirring was
continued for 1 h at 25 °C. The mixture was poured into H2O; the
organic layer was separated and dried (Na2SO4). The solvent was
removed at reduced pressure and the residue was distilled in vacuo
yielding aldehyde rac-15 with ~20% (NMR data) admixture of car-
boxylic acid rac-4 (20.5 g, 65%); bp 122–123 °C/26.6 mbar; mp
(dinitrophenylhydrazone) 164–165 °C.
13C NMR (CDCl3): d (without peaks of acid 4) = 32.79, 33.21,
40.59, 43.08, 44.58, 46.38, 47.33, 47.37, 49.06, 49.31, 58.87,
205.21.
GC/MS: tR = 6.83 min; m/z (%) = 174 (M+, 41), 117 (40), 91 (40),
79 (100), 77 (67), 39 (41%).
Pentacyclo[6.3.0.0.2,6.03,10.05,9]undecan-4-ol (rac-12)12
Acetate rac-11 (40 g, 0.195 mol) was dissolved in 50% aq EtOH
(800 mL) and then KOH (65 g, 1.158 mol) was added; the mixture
was refluxed for 3 h. After cooling, the mixture was poured into a
beaker and acidified with 10% H2SO4 to give a slightly acidic soln.
The reaction mass was extracted with CHCl3 (4 × 100 mL) and the
combined organic layers were dried (Na2SO4) and evaporated to ob-
tain rac-12 (28.9 g, 91%) as small white crystals.
1H NMR (CDCl3): d = 1.30–1.35 (m, 3 H), 1.47 (d, 3J = 10 Hz, 1 H),
1.92 (s, 3 H), 2.07–2.13 (m, 5 H), 2.58 (s, 1 H), 4.14 (s, 1 H).
Synthesis 2012, 44, 810–816
© Thieme Stuttgart · New York