Cycloheptyne from Reaction of Cyclohexylidenemethyl Iodonium
in 1 mL of chloroform containing tetrabutylammonium sul-
fonates (0.2-0.01 M) and kept in a sealed tube at 60 °C for a
specified reaction time. To the mixture was added water and
5 µmol of tetradecane as an ether solution. The products were
extracted with ether and washed with water. The yields of the
products from the racemic 1 were determined by gas chroma-
tography with tetradecane as an internal standard, while the
ee of the products from (R)-1 was determined using a chiral
GC column (DEX-CB, i.d. 0.25 mm × 25 m). The retention
times of (R)-2Tf, (S)-2Tf, (R)-3Tf, and (S)-3Tf were 17.2, 18.1,
22.9, and 23.3 min at the column temperature of 90 °C at a
linear velocity of 32 cm s-1 of the He carrier gas, while those
of (R)-2Ms, (S)-2Ms, (R)-3Ms, and (S)-3Ms were 89.3, 90.7,
99.5 and 101.3 min at 110 °C. A normal column (DB-1, i.d.
0.25 mm × 30 m) was used for the determination of product
yields: the retention times of 2Tf, 3Tf, 2Ms, and 3Ms were
6.4, 7.4, 16.6, and 16.7 min, respectively, when the column
temperature was maintained at 100 °C during the initial 10
benzene (26 mg, 86% yield), 2Ms (18 mg, 58% yield), and 3Ms
(7 mg, 23% yield). Proton NMR of 2Ms showed only a doublet
signal at 6.29 ppm with a large coupling constant (J ) 197.4
Hz). The ratio of 1-13C-3Ms and 2-13C-3Ms was determined
by 1H and 13C NMR. The 1H NMR spectrum of the product
3Ms has two kinds of signals for 2-H at 5.74 ppm, one with a
large coupling constant (J ) 157 Hz) of 2-13C-3Ms coupled to
2-13C and the other with a small coupling constant to 1-13C of
1-13C-3Ms. The ratio of 1-13C-3Ms and 2-13C-3Ms was deter-
mined to be 35:65 by comparing the peak areas of the separate
signals of 2-H. The isolated 3Ms was also employed for 13C
NMR using decoupling without NOE. The ratio of 1-13C-3Ms
and 2-13C-3Ms was determined to be 33:67 from the peak areas
due to 1-C (152 ppm) and 2-C (121 ppm). Selected data for
13C-2Ms: 1H NMR (400 MHz, CDCl3) 6.29 (d, J H-C ) 197.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 126.6; MS (EI) m/z
(relative intensity, %) 205 (33, M+), 126 (28), 108 (85), 79 (79),
55 (100); HRMS (EI) calcd for 12C813CH16SO3 (M) 205.0854,
found 205.0867. Selected data for 2-13C-3Ms: 1H NMR (400
MHz, CDCl3) δ 5.74 (dddd, J ) 156.8, 7.8, 4.9, 1.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 121.3. Selected data for 1-13C-
3Ms: 1H NMR (400 MHz, CDCl3) δ 5.74 (qd J ) 6.8, 1.0 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 152.1. A mixture of 2-13C-
3Ms and 1-13C-3Ms: MS (EI) m/z (relative intensity, %) 205
(16, M+), 177 (20), 126 (24), 109 (49), 94 (65), 55 (100); HRMS
(EI) calcd for 12C813CH16SO3 (M) 205.0854, found 205.0882.
min and then raised to 250 °C at the rate of 10 °C min-1
.
4-Met h ylcycloh exylid en em et h yl Tr ifla t e (2Tf) a n d
5-Meth ylcycloh ep t-1-en yl Tr ifla te (3Tf). A solution con-
-
taining racemic 1a ‚BF4 (0.11 g, 0.27 mmol) and tetrabuty-
lammonium triflate (425 mg, 1.1 mmol) in chloroform (110 mL)
was stirred at 60 °C for 6 h. Then the mixture was quenched
by water and extracted with ether three times. The combined
extracts were concentrated in vacuo and the mixture was
separated by chromatography (SiO2; eluent, 15% EtOAc in
hexane) into four fractions, iodobenzene (406 mg, 72% yield),
2Tf (5 mg, 7% yield), a 1:3 mixture of 2Tf and 3Tf (37 mg,
53% yield), and 3Tf (14 mg, 20% yield). 2Tf: 1H NMR (400
MHz, CDCl3) δ 6.34 (s, 1H), 2.77-2.70 (m, 1H), 2.20-2.12 (m,
1H), 2.00-1.93 (m, 1H), 1.83-1.78 (m, 3H), 1.59-1.50 (m, 1H),
1.05-0.93 (m, 2H), 0.90 (d, J ) 6.4 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 133.3, 127.6, 118.6 (q, J ) 318.5 Hz), 35.6, 34.6,
32.2, 29.3, 25.5, 21.8; MS (EI) m/z (relative intensity, %) 258
(6, M+), 107 (78), 79 (76), 69 (83), 55 (100); HRMS (EI) calcd
The mesylate reaction of 13C-1a at various concentrations
of mesylate was carried out using a smaller amount of 13C-
1a ‚BF4- (10 mg) in chloroform (10 mL). The reaction mixture
1
extracted with ether was analyzed by H NMR to determine
the product distribution (2Ms/3Ms and 2-13C-3Ms/1-13C-3Ms).
Tr ifla te Rea ction of 13C-1a . A solution containing 13C-1a ‚
BF4- (17.3 mg, 0.043 mmol) and tetrabutylammonium triflate
(677 mg, 1.73 mmol) in chloroform (17.3 mL) was stirred at
60 °C for 6 h. The products extracted were separated by
chromatography (SiO2, eluent: hexane) to give iodobenzene
(6 mg, 68% yield), 2Tf (2 mg, 18% yield), and 3Tf (5 mg, 45%
yield). The ratio of 2Tf/3Tf was determined to be 27/73 by GC
of the crude product, while the ratio of 2-13C-3Tf/1-13C-3Tf was
found to be 95/5 from both 1H and 13C NMR spectra. Selected
1
for C9H13SO3F3 (M) 258.0538, found 258.0557. 3Tf: H NMR
(400 MHz, CDCl3) δ 5.78 (ddd, J ) 7.1, 4.9, 1.5 Hz, 1H), 2.56-
2.49 (m, 1H), 2.45-2.39 (m, 1H), 2.25-2.17 (m, 1H), 2.09-
2.02 (m, 1H), 1.80-1.65 (m, 3H), 1.36-1.30 (m, 1H), 1.28-
1.15 (m, 1H), 0.89 (d, J ) 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 152.6, 122.8, 118.5 (q, J ) 317.6 Hz), 35.3, 34.0, 32.4,
31.2, 23.2, 23.1; MS (EI) m/z (relative intensity, %) 258 (1, M+),
230 (3), 125 (17), 108 (92), 93 (96), 69 (98), 55 (100); HRMS
(EI) calcd for C9H13SO3F3 (M) 258.0538, found 258.0521.
data for 13C-2Tf: 1H NMR (400 MHz, CDCl3) 6.34 (d, J H-C
)
205.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 127.6. Selected
data for 2-13C-3Tf: 1H NMR (400 MHz, CDCl3) δ 5.78 (dddd,
J ) 158.2, 7.1, 4.9, 1.5 Hz, 1H), 13C NMR (100 MHz, CDCl3) δ
122.8. Selected data for 1-13C-3Tf: 1H NMR (400 MHz, CDCl3)
δ 5.84-5.72 (m, 1H),13C NMR (100 MHz, CDCl3) δ 152.6. A
mixture of 1-13C-3Tf and 1-13C-3Tf: MS (EI) m/z (relative
intensity, %) 259 (8, M+), 109 (48), 94 (37), 56 (100); HRMS
(EI) calcd for 12C813CH13SO3F3 (M) 259.0571, found 259.0590.
4-Meth ylcycloh exylid en em eth yl Mesyla te (2Ms) a n d
5-Meth ylcycloh ep t-1-en yl Mesyla te (3Ms). Reaction of
-
racemic 1a ‚BF4 with tetrabutylammonium mesylate in the
same way as above for triflate gave iodobenzene (70% yield),
2Ms (51% yield), and 3Ms (30% yield). 2Ms: 1H NMR (400
MHz, CDCl3) δ 6.29 (s, 1H), 3.03 (s, 3H), 2.75-2.69 (m, 1H),
2.18-2.10 (m, 1H), 1.98-1.90 (m, 1H), 1.80-1.70 (m, 3H),
1.57-1.46 (m, 1H), 1.03-0.90 (m, 2H), 0.87 (d, J ) 6.3 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 131.8, 126.6, 36.7, 35.7,
34.8, 32.3, 29.6, 25.4, 21.8; MS (EI) m/z (relative intensity, %)
204 (41, M+), 125 (28), 107 (65), 93 (79), 79 (65), 55 (100);
HRMS (EI) calcd for C9H16SO3 (M) 204.0820, found 204.0824.
3Ms: 1H NMR (400 MHz, CDCl3) δ 5.74 (ddd, J ) 7.8, 4.9, 1.0
Hz, 1H), 3.04 (s, 3H), 2.48-2.39 (m, 2H), 2.20-2.14 (m, 1H),
2.07-2.00 (m, 1H), 1.76-1.64 (m, 3H), 1.33-1.24 (m, 1H),
1.21-1.12 (m, 1H), 0.93 (d, J ) 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 152.1, 121.3, 37.5, 35.8, 34.3, 32.7, 31.5, 23.6,
23.3; MS (EI) m/z (relative intensity, %) 204 (3, M+), 176 (21),
Mesyla te Rea ction in th e P r esen ce of Cyclop en ta d i-
en on e. A solution containing racemic 1a ‚BF4 (50 mg, 0.125
-
mmol), tetrabutylammonium mesylate (168.5 mg, 0.50 mmol),
and 4 (94 mg, 0.24 mmol) in chloroform (50 mL) was stirred
at 60 °C for 5 h. Then the mixture was quenched by water
and extracted with ether three times. The combined extracts
were dried (MgSO4) and concentrated in vacuo. The mixture
was separated by chromatography (SiO2, eluent: 60% CHCl3
in hexane) to give the adduct 5 (14.1 mg, 24% yield) and a
mixture of 2Ms and 3Ms (16.3 mg, 64% yield). The ratio of
1
2Ms/3Ms was determined to be 98/2 by H NMR and GC. 5:
1
mp ) 249-253 °C; H NMR (400 MHz, CDCl3) δ 7.15-6.93
(m, 10H), 6.78-6.69 (m, 10H), 2.79-2.74 (m, 2H), 2.64-2.58
(m, 2H), 1.78-1.74 (m, 3H), 1.24-1.12 (m, 2H), 0.90 (d, J )
6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 141.4, 141.0, 140.6,
139.7, 138.5, 131.4, 131.0, 130.6, 130.3, 127.2, 127.1, 126.3,
126.2, 125.7, 124.8, 37.8, 35.9, 30.0, 23.5; MS (EI) m/z (relative
intensity, %) 464 (75, M+), 149 (100); HRMS (EI) calcd for
125 (12), 108 (20), 93 (82), 56 (100); HRMS (EI) calcd for C9H16
SO3 (M) 204.0820, found 204.0832.
-
Mesyla te Rea ction of 13C-1a . A solution containing 13C-
-
C
36H32 (M) 464.2504, found 464.2520.
The salt (S)-1a ‚BF4- (79% ee, 1 mg), tetrabutylammonium
mesylate (3.4 mg), and 4 (1.9 mg) were dissolved in chloroform,
and the mixture stirred at 60 °C for 5 h. A mixture of 2Ms
1a ‚BF4 (60 mg, 0.015 mmol) and tetrabutylammonium me-
sylate (2.04 g, 6.0 mmol) in chloroform (60 mL) was stirred at
60 °C for 5 h. The product mixture was separated by chroma-
tography (SiO2, eluent: 15% EtOAc in hexane) to give iodo-
J . Org. Chem, Vol. 67, No. 23, 2002 8145