Effect of Bulk in Dimers of 3-Methylenechloest-4-ene
A R T I C L E S
signals are observed, that at 28.61 ppm is twice as broad as the others.
The spin-relaxation time for the signal at 5.80 ppm is 0.68 s.
Experimental
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General. H NMR spectra (600 MHz) and 13C spectra (125 MHz)
The mother liquors from the ether/methanol crystallizations above
were concentrated to dryness, dissolved in ether (50 mL), and cooled
at -78 °C for 48 h to yield 215 mg of a second isomer as a colorless
solid. Recrystallization from m-xylene at 4 °C afforded a crystal suitable
for X-ray analysis. This isomer, 7 (anti-x,x), shows a single signal at
were measured in benzene-d6 with a Varian INOVA 600 instrument
and are reported in ppm (δ). The designations p, s, t, q stand for primary,
secondary, tertiary, and quaternary carbon atoms, respectively, as
determined by distortionless enhancement by polarization transfer
(DEPT). Spin relaxation times (T1) were determined by the inversion-
recovery method in benzene-d6.
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5.43 ppm. H NMR: 0.73 (s, 6H), 0.97-1.00 (m, 2H), 0.98 (dd, J )
4.25, 6.59 Hz, 12H), 1.01 (s, 6H), 1.09 (d, J ) 6.37 Hz, 6H), 1.10-
1.17 (m, 4H), 1.19-1.33 (m, 12H), 1.33-1.50 (m, 12H), 1.51-1.64
(m, 12 H), 1.67-1.84 (m, 6H), 2.01-2.13 (m, 8H), 2.20-2.28 (m,
4H), 5.43 (s, 2H). 13C NMR 12.36 (p), 19.19 (p) (this signal is double
the intensity of the other signals), 21.84 (s), 22.84, (p), 23.08 (p), 24.57
(s), 25.97 (s), 28.66 (t), 28.97 (s), 29.40 (s), 31.90 (s), 33.40 (s), 33.64
(s), 35.67 (s), 36.62 (t), 36.96 (t), 37.15 (s), 37.36 (q), 39.95 (s), 40.61
(s), 43.21 (q),45.34 (q), 55.64 (t), 56.89 (t), 57.60 (t), 127.35 (t), 145.03
(q). Relaxation time of the signal at 5.43 ppm is 0.71 ( 0.01 s.
3-Methylenecholest-4-ene (5). A solution of (+)-cholest-4-en-3-
one (3.3 g, 8.4 mmol, Aldrich Chemical) in 15 mL of THF was added
to an ice-cooled suspension of methylenetriphenylphosphorane (from
9.3 g of methyltriphenylphosphonium bromide and 16 mL of a 1.6 M
ethereal solution of methyllithium) in 90 mL of anhydrous THF. The
mixture was stirred for 24 h at room temperature. The resulting yellow
solution was treated with 5 mL of water and 60 mL of ether, washed
with water (2 × 100 mL), dried over MgSO4, filtered, and concentrated
to a solid (4.57 g), which was crystallized from ether/methanol (12
mL/4 mL) at 4 °C to give 1.83 g of colorless needles. A second crop
The remaining material in the ethereal mother liquors was chro-
matographed (neutral alumina, 2 cm i.d. × 24 cm, 10:1 hexanes/ethyl
acetate) to yield 324 mg of a mixture, which was dissolved in benzene
(0.4 mL), cooled at 4 °C for 24 h to afford 166 mg of solid. Analysis
by 1H NMR revealed the three isomers (5.80, 5.77, 5.73, and 5.43 ppm)
and a small amount of 5 (5.96, 4.87, and 4.78 ppm): 8 (syn-n,x), 64%;
6 (anti-n,n), 21%; 7 (anti-x,x), 13%; 5, 2%. The two unique features
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(0.59 g) brought the yield to 78% of theory. H NMR: 0.67 (s, 3H),
0.74 (dt, J ) 2.93, 12.01 Hz, 1H), 0.85-0.93 (m, 2H), 0.95 (dd, J )
1.47, 6.59 Hz, 6H), 0.96 (s, 3H), 1.00 (d, J ) 6.44 Hz, 3H), 1.06 (m,
4H), 1.18-1.47 (m, 11 H), 1.55 (m, 2H), 1.68 (m, 2H), 1.83 (m, 1H),
1.96 (dt, J ) 3.22, 12.89 Hz, 1H), 2.07 (m, 1H), 2.21 (dt, J ) 4.98,
13.18 Hz, 1H), 2.28 (dt, J ) 3.22, 14.64 Hz, 1H), 2.38 (t, J ) 16.69
Hz, 1H), 4.79 (s, 1H), 4.88 (s, 1H), 5.96 (s, 1H). 13C NMR: 12.22 (p),
18.47 (p), 18.96 (p), 21.77 (s), 22.77 (p), 23.03 (p), 24.38 (s), 24.56
(s), 27.69 (s), 28.40 (t), 28.64 (s), 32.77 (s), 33.13 (s), 36.15 (t), 36.22
(t), 36.64 (s), 37.59 (s), 37.64 (q), 39.92 (s), 40.24 (s), 42.71 (q), 54.44
(t), 56.37 (t), 56.56 (t), 108.39 (s), 123.54 (t), 144.07 (q), 148.60 (q).
For the vinyl H signals at 4.79, 4.88, and 5.96 ppm, values of T1 are
1.25, 1.24, and 2.12 s-1, respectively.
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of the H NMR spectrum associated with this enriched sample of 8
(syn-n,x) were signals for olefinic protons at 5.73 (s, 1H) and 5.77 (s,
1H) ppm.
Heating the Three Dimers of 3-Methylenecholest-4-ene 5: 6 (anti-
n,n), 7 (anti-x,x), and 8 (anti-n,x). Pyrex NMR tubes were prepared
by treating with 30% NaOH for 8 days, washing 20 times with water,
washing 10 times with acetone, and drying in vacuo. The sampless
9-12 mg of 6 (anti-n,n) and 7 (anti-x,x); 24-27 mg of enriched 8
(anti-n,x)sand 5 µL of a 0.4 M solution of 18-crown ether as internal
standard in benzene-d6 were placed in the NMR tubes, made up to 0.7
mL of benzene-d6, degassed through three freeze-pump-thaw cycles,
and sealed in vacuo. Heating was in the vapors of heptane (bp 98.4 (
0.2 °C), toluene (bp 110.7 ( 0.2 °C), and n-butyl alcohol (bp 117.8 (
0.1 °C) boiling under reflux. Quantitative analysis was effected by 1H
NMR using the signals for the olefinic hydrogen atoms given above.
The results are given in Tables 1, S-1, and S-2.
The stability of 3-methylenecholest-4-ene 5 is demonstrated by
heating a sample (10.5 mg) and 18-crown ether as internal standard (5
µL of a 0.4 M solution in benzene-d6) in a NaOH-washed Pyrex NMR
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tube for 72 h at 98 °C. Analysis by H NMR showed no change.
Photodimerizaton of 3-Methylenecholest-4-ene 5. 3-Methylene-
cholest-4-ene (3.2 g, 8.4 mmol) in a Pyrex flask containing freshly
distilled benzene (110 mL) was stirred and deoxygenated with a stream
of argon for 20 min. After the addition of acetophenone (0.56 g),
irradiation was conducted for 72 h at room temperature with a Hanovia
450-watt medium-pressure mercury arc lamp. Evaporation of the
benzene left a residue, which was crystallized from diethyl ether (58
mL)/methanol (10 mL) at room temperature to give 436 mg of colorless
needles 6 (anti-n,n). Recrystallization from toluene at room temperature
Acknowledgment. We express our gratitude to the Norman
Fund in Organic Chemistry in memory of Ruth Alice Norman
Weil Halsband and Edward A. Norman for its generous support
of this work. We thank Dr. Richard S. Staples for his
determination of the structures by X-ray diffraction analysis and
Dr. R. Fink for a copy of the program KINETIK. This paper is
dedicated to Professor Yoshito Kishi on the occasion of his 70th
birthday.
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afforded a crystal suitable for X-ray analysis. H NMR: 0.69 (s, 6H),
0.82 (dt, J ) 4.10, 12.37 Hz, 2H), 0.89-1.04 (m, 4H), 0.93 (dd, J )
1.68, 6.59 Hz, 12H), 0.98 (s, 6H), 1.02 (d, J ) 6.52 Hz, 6H), 1.04-
1.14 (m, 8H), 1.15-1.39 (m, 12 H), 1.40-1.48 (m. 8H), 1.49-1.61
(m, 6H), 1.62-1.67 (m, 2H), 1.70-1.75 (m, 2H), 1.76-1.90 (m, 8H),
1.95-2.04 (m, 4H), 2.16 (dt, J ) 3.22, 12.89 Hz, 2H), 2.29 (dt, J )
3.51, 13.84 Hz, 2H), 5.80 (s, 2H). 13C NMR: 12.27 (p), 18.98 (p),
19.35 (p), 21.88 (s), 22.76, (p), 23.00 (p), 24.39 (s), 24.56 (s), 28.38
(t), 28.64 (s), 30.96 (s), 33.35 (s), 33.83 (s), 34.77 (s), 36.23 (t), 36.29
(t), 36.63 (s), 37.60 (s), 39.90 (s), 40.37 (s), 42.84 (q), 45.19 (q), 54.47
(t), 56.50 (t), 56.66 (t), 125.22 (t), 144.60 (q). Although 27 13C NMR
Supporting Information Available: Two tables of kinetic
data. This material is available free of charge via the Internet
JA068971N
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J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13839