Kinetics of Radical Cyclizations of Acylsilanes
J . Org. Chem., Vol. 64, No. 2, 1999 627
temperature for 3 h. To the resulting liquid was added one
drop of triethylamine, and the resulting mixture was chro-
matographed over silica gel (eluted with hexane/ethyl acetate,
9/1) to give 2.2 g (76%) of 39 as a colorless liquid. This material
case of acylgermanes. The radical cyclization rates of
acylgermanes are also dependent on the nature of the
initial radical. Although the radical cyclizations of acylger-
manes and acylsilanes are similar in many ways, the two
systems yield different types of end products. The acylger-
manes lead to the formation of cyclic ketones, while the
acylsilanes afford silyl-protected cyclic alcohols. The two
systems are complementary.
is a mixture of two diastereomers: IR (neat) 1632 cm-1 1H
;
NMR (200 MHz) δ 1.20-1.93 (m, 15 H), 2.00-2.18 (m, 2 H),
2.70-2.94 (m, 4 H), 3.21 (ddd, J ) 10.6, 5.8, 4.9 Hz, 1 H), 3.47
(dt, J ) 11.3, 4.5 Hz, 1 H), 3.63 (ddd, J ) 10.6, 5.3, 3.7 Hz, 1
H), 3.81 (ddd, J ) 11.3, 6.9, 3.2 Hz, 1 H), 4.00 (t, J ) 6.5 Hz,
1H), 4.53 (t, J ) 3.2 Hz, 1 H), 4.91 (br d, J ) 10.3 Hz, 1 H),
4.98 (br d, J ) 16.9 Hz, 1 H), 5.77 (ddt, J ) 16.9, 10.3, 6.6 Hz,
1 H); 13C NMR (50 MHz) δ 19.4 (t), 25.5 (t), 26.0 (t), 28.5 (t),
30.4 (t), 30.6 (t), 31.0 (t), 32.9 (t), 37.4 (d), 47.9 (d), 62.0 (t),
70.0 (t), 70.2 (t), 98.9 (d), 114.3 (t), 138.9 (d); HRMS calcd for
Exp er im en ta l Section
Melting points are uncorrected. 1H NMR spectra were
recorded at 200 or 300 MHz; 13C NMR spectra were recorded
at 50 or 75 MHz. Tetramethysilane (δ ) 0 ppm) or CHCl3 (δ
) 7.24 ppm) were used as internal standards, and CDCl3 was
used as the solvent. Benzene and THF were distilled from
sodium benzophenone ketyl under N2. Dimethylformamide
(DMF) was dried over calcium hydride. Acetone was distilled
over sodium carbonate. The benzene used for cyclization
reactions was deoxygenated by passing a gentle stream of
argon through for 0.5 h before use. All reactions were per-
formed under a blanket of N2 or Ar.
C
17H30O2S2 m/z 330.1687, found 330.1681.
2-(2-(1-(Tr im eth ylsilyl)-2,6-d ith ia cycloh exyl)eth yl)-5-
h exen -1-ol. To a solution of 640 mg (1.94 mmol) of 39 in 2
mL of THF cooled at 0 °C was added dropwise over 10 min a
solution of 1.50 N n-butyllithium in hexane (1.95 mL, 2.94
mmol). The resulting solution was stirred at the same tem-
perature for 20 min followed by the addition of a solution of
0.325 mL (2.55 mmol) of chlorotrimethylsilane in 1 mL of THF.
The reaction mixture was stirred at 0 °C for 2 h and then
partitioned between 100 mL of ether and 100 mL of water.
The ether layer was washed with brine (100 mL), dried
(MgSO4), and concentrated. The brown liquid obtained was
dissolved in 5 mL of methanol with the addition of a few
crystals of p-toluenesulfonic acid monohydrate and stirred at
room temperature for 2 h. Two drops of triethylamine was
added to the reaction mixture, and the resulting solution was
concentrated. The resulting liquid was chromatographed over
silica gel (eluted with hexane/ethyl acetate, 8/2) to give 507
mg (82%) of the alcohol as a pale yellow liquid: IR (neat) 3414,
1633 cm-1; 1H NMR (200 MHz) δ 0.17 (s, 9 H), 1.35-1.60 (m,
5 H), 1.75-2.28 (m, 7 H), 2.43 (dt, J ) 14, 4 Hz, 2 H), 3.00
(ddd, J ) 14, 12, 4 Hz, 2 H), 3.58 (d, J ) 4 Hz, 2 H), 4.94 (br
d, J ) 10 Hz, 1 H), 5.00 (br d, J ) 17 Hz, 1 H), 5.80 (ddt, J )
17, 10, 7 Hz, 1 H); 13C NMR (50 MHz) δ -2.4 (q), 23.4 (t), 25.1
(t), 28.5 (t), 30.2 (t), 31.2 (t), 34.3 (t), 38.9 (s), 40.5 (d), 65.3 (t),
114.6 (t), 138.7 (d); HRMS calcd for C15H30OS2Si m/z 318.1507,
found 318.1512.
Dim eth yl 2-(3-Bu ten yl)-2-(2-(2,6-d ith ia cycloh exyl)eth -
yl)m a lon a te (38). To a mixture of 204 mg (6.8 mmol) of
sodium hydride (80% dispersion in mineral oil) in 6 mL of DMF
cooled at 0 °C was added dropwise over 10 min a solution of
0.71 mL (6.2 mmol) of dimethyl malonate in 3 mL of DMF.
The resulting mixture was stirred at the same temperature
for 10 min followed by the addition of a solution of 1.41 g (6.2
mmol) of bromide 37 in 3 mL of DMF in one portion. The
reaction mixture was stirred at 80 °C for 3 h and then
partitioned between 100 mL of ether and 100 mL of water.
The ether phase was washed with brine (100 mL), dried
(MgSO4), and concentrated in vacuo. The resulting residual
oil was dissolved in 3 mL of DMF and then added dropwise
over 10 min to another mixture of 204 mg (6.8 mmol) of sodium
hydride (80% dispersion in mineral oil) in 6 mL of DMF at 0
°C. The resulting mixture was stirred at room temperature
for 10 min following which was added a solution of 0.66 mL
(6.5 mmol) of 4-bromo-1-butene in 3 mL of DMF in one portion.
The reaction mixture was stirred at 60 °C for 2 h and then
partitioned between 100 mL of ether and 100 mL of water.
The ether phase was washed with brine (100 mL), dried
(MgSO4), and concentrated in vacuo. The residual oil was
chromatographed over silica gel (eluted with hexane/ethyl
acetate, 89/11) to give 1.14 g (56%) of 38 as a pale yellow
liquid: IR (neat) 1727, 1633 cm-1; 1H NMR (200 MHz) δ 1.55-
1.70 (m, 2 H), 1.70-2.00 (m, 5 H), 2.00-2.18 (m, 3 H), 2.71-
2.95 (m, 4 H), 3.68 (s, 6 H), 3.94 (t, J ) 6.9 Hz, 1 H), 4.92 (br
d, J ) 10.7 Hz, 1 H), 4.99 (br d, J ) 16.6 Hz,1 H), 5.60-5.85
(m, 1 H); 13C NMR (50 MHz) δ 25.7 (t), 28.2 (t), 29.6 (t), 30.0
(t), 31.6 (t), 47.0 (d), 52.2 (q), 56.7 (s), 115.0 (t), 137.0 (d), 171.3
(s); HRMS calcd for C15H24O4S2 m/z 332.1116, found 332.1115.
2-(3-(Tet r a h yd r op yr a n yloxym et h yl)h ep t -6-en yl)-1,3-
d ith ia n e (39). To a mixture of 731 mg (14.9 mmol) of sodium
cyanide in 4 mL of DMF was added in one portion a solution
of 2.92 g (8.8 mmol) of malonate 38 in 5 mL of DMF. The
resulting mixture was heated at 164 °C for 3 h and then
partitioned between 100 mL of ether and 100 mL of water.
The aqueous phase was extracted with ether (100 mL). The
combined ether layers were washed with brine (50 mL), dried
(MgSO4), and concentrated in vacuo. The resulting brown
liquid was dissolved in 8 mL of THF and then added dropwise
over 10 min to a mixture of 500 mg (13.2 mmol) of LAH in 8
mL of THF at 0 °C. The reaction mixture was stirred at room
temperature for 1.5 h and then diluted with 10 mL of ether.
To the resulting mixture cooled at 0 °C was added in sequence
0.5 mL of water, 0.5 mL of 15% sodium hydroxide solution,
and 1.5 mL of water. The reaction mixture was then stirred
at room temperature for 30 min, filtered, and concentrated in
vacuo. To the residual oil was added a few crystals of
p-toluenesulfonic acid monohydrate and 0.963 mL (10.6 mmol)
of dihydropyran, and the resulting mixture was stirred at room
4-Br om om et h yl-1-t r im et h ylsilyl-7-oct en -1-on e (40a ).
To a solution of 259 mg (0.814 mmol) of 2-(2-(2-(trimethylsilyl)-
2,6-dithiacyclohexyl)ethyl)-5-hexen-1-ol and 0.17 mL (1.22
mmol) of triethylamine in 1 mL of dichloromethane at 0 °C
was added 94 µL (1.22 mmol) of methanesulfonyl chloride. The
resulting mixture was stirred at 0 °C for 30 min and then
partitioned between 50 mL of ether and 50 mL of water. The
ether phase was washed with brine (50 mL), dried (MgSO4),
and concentrated. The resulting yellow liquid was dissolved
in 2 mL of dry acetone and stirred with 139 mg (1.60 mmol)
of lithium bromide at 80 °C for 2 h. The resulting mixture was
partitioned between 50 mL of dichloromethane and 50 mL of
water. The organic layer was dried (MgSO4) and concentrated
to give a brown liquid. To the liquid and 121 mg (1.44 mmol)
of sodium bicarbonate in a mixture of 2 mL of acetonitrile, 2
mL of THF, and 1 mL of water was added over 5 min a solution
of 585 mg (1.36 mmol) of bis(trifluoroacetoxy)iodobenzene in
2 mL of acetonitrile. The resulting mixture was stirred at room
temperature for 5 min and then partitioned between 50 mL
of dichloromethane and 50 mL of water. The organic layer was
dried (MgSO4) and concentrated. The residual oil was chro-
matographed over silica gel (eluted with hexane/ethyl acetate,
96/4) to give 126 mg (54%) of 40a as a pale yellow liquid: IR
1
(neat) 1633 cm-1; H NMR (200 MHz) δ 0.19 (s, 9 H), 1.38-
1.68 (m, 5 H), 1.98-2.12 (m, 2 H), 2.44-2.73 (m, 2 H), 3.40 (d,
J ) 4 Hz, 2 H), 4.90-5.06 (m, 2 H), 5.76 (ddt, J ) 17, 10, 7
Hz, 1H); 13C NMR (50 MHz) δ -3.2 (q), 24.9 (t), 30.7 (t), 31.7
(t), 38.2 (d), 38.5 (t), 45.1 (t), 115.0 (t), 138.1 (d), 247.4 (s);
HRMS calcd for C15H2379BrOSi m/z 290.0701, found 290.0707.
5-Br om om eth yl-1-tr im eth ylsilyl-8-n on en -1-on e (43a ).
To a solution of 608 mg (3.16 mmol) of 41a in 6 mL of THF
cooled at 0 °C was added dropwise over 5 min a solution of
1.56 N n-butyllithium in hexane (2.40 mL, 3.74 mmol). The
resulting mixture was stirred at 0 °C for 30 min and then