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G. H. Posner et al. / Bioorg. Med. Chem. 8 (2000) 1361±1370
J=7.6, 1.6 Hz, 1H), 5.18 (s, 1H), 3.61 (s, 3H), 2.78±2.86
(m, 1H), 2.48 (s, 3H), 2.40±2.44 (m, 1H), 2.25 (ddd,
J=14.4, 4.4, 2.4, 1H), 1.84±1.94 (m, 1H), 1.60±1.82 (m,
6H), 1.18±1.30 (m, 3H); 13C NMR (CDCl3): d 141.45,
138.66, 128.80, 127.10, 123.59, 122.30, 104.02, 96.30,
83.90, 56.23, 45.59, 37.82, 33.58, 32.72, 27.35, 25.45,
23.35, 16.03. HRMS calcd for C18H25O4S m/z (M+):
ether (20 mL) at 78 ꢂC was then treated with t-butyl-
lithium (1.7 M in pentane, 7.20 mL, 12.24 mmol, 2.4
equiv). After 45 min a solution of nitrile 18 (688 mg,
3.84 mmol, 1.0 equiv)5 in diethyl ether (10 mL) at
78 ꢂC was added to the reaction via cannula over 5
min. The reaction was continued overnight and then
quenched with water (5 mL), transferred to a separatory
funnel and extracted with diethyl ether (3Â15 mL),
washed with brine, dried over MgSO4 and concentrated
under reduced pressure. The crude product was puri®ed
by silica gel chromatography (10% EtOAc in hexanes)
to yield 686 mg of p-methylthiophenyl ketone 19 (2.27
mmol, 59%) as a yellow oil which solidi®ed upon
1
336.1395, found 336.1392. 9a, 12-b: H NMR (CDCl3):
d 7.46 (t, J=1.2 Hz, 1H), 7.26±7.33 (m, 2H), 7.22 (dt,
J=6.4, 2 Hz, 1H), 5.13 (d, J=1.2 Hz, 1H), 3.65 (s, 3H),
2.75 (ddd, J=13.2, 10.2, 3.6 Hz, 1H), 2.49 (s, 3H), 2.22±
2.31 (m, 1H), 1.84±2.00 (m, 2H), 1.60±1.81 (m, 8H),
1.22±1.36 (m, 1H); 13C NMR (CDCl3): d 141.73, 138.68,
128.68, 126.99, 123.47, 122.16, 105.25, 105.08, 84.09,
57.39, 47.62, 39.41, 35.82, 30.99, 26.99, 25.22, 24.01,
16.03. HRMS calcd for C18H25O4S m/z (M+): 336.1395,
found 336.1395.
refrigeration at 10 ꢂC. H NMR (CDCl3): d 7.85±7.88
1
(m, 2H), 7.24±7.26 (m, 2H), 5.79 (d, J=2 Hz, 1H), 3.42
(s, 3H), 2.80±2.95 (m, 3H), 2.51 (s, 3H), 1.95±2.05 (m,
2H), 1.50±1.76 (m, 7H), 1.14±1.28 (m, 1H); 13C NMR
(CDCl3): d 199.87, 145.06, 140.36, 133.61, 128.39,
124.83, 119.03, 59.06, 36.61, 32.59, 31.62, 28.23, 26.40,
25.87, 21.51, 14.73. HRMS calcd for C18H24O2S m/z
(M+): 304.1497, found 304.1491.
Sulfone trioxanes 9b. A solution of trioxane 9a, 12-a
(5.5 mg, 16 mmol, 1.0 equiv) in CH2Cl2 (3 mL) at 0 ꢂC
was treated with m-CPBA (repuri®ed from tech. grade,
12 mg, 68 mmol, 4.3 equiv). The reaction was stirred at
0 ꢂC for 1 h, warmed to room temperature, and stirred
for an additional 30 min. The reaction was diluted with
diethyl ether, washed with satd NaHCO3 (aq), satd
NaHSO3 (aq), NaHCO3 (aq), brine, dried over Na2SO4
and concentrated under reduced pressure. The crude
product was puri®ed by silica gel chromatography (25%
EtOAc in hexane) to yield 4 mg of 9b, 12-a (11 mmol,
68%). 1H NMR (CDCl3): d 8.17 (t, J=1.6 Hz, 1H), 7.92
(ddd, J=8, 2, 1.2 Hz, 1H), 7.83 (ddd, J=8, 2, 1.2 Hz,
1H), 7.58 (t, J=7.6 Hz, 1H), 5.20 (s, 1H), 3.62 (s, 3H),
3.04 (s, 3H), 2.82±2.90 (m, 1H), 2.40±2.44 (m, 1H), 2.23
(ddd, J=14.8, 4.4, 2 Hz, 1H), 1.88±1.94 (m, 2H), 1.70±
1.84 (m, 4H), 1.20±1.31 (m, 4H); 13C NMR (CDCl3): d
142.60, 140.85, 130.87, 129.63, 127.82, 124.73, 103.52,
96.51, 84.29, 56.51, 45.50, 44.68, 37.74, 33.53, 32.68,
27.21, 25.39, 23.32. A solution of trioxane 9a, 12-b (30
mg, 89 mmol, 1.0 equiv) in CH2Cl2 (10 mL) at 0 ꢂC was
treated with m-CPBA (repuri®ed from tech. grade, 62
mg, 360 mmol, 4.0 equiv). The reaction was stirred at
0 ꢂC for 1 h, warmed to RT, and stirred for an addi-
tional 30 min. The reaction was diluted with diethyl
ether, washed with satd NaHCO3 (aq), satd NaHSO3
(aq), NaHCO3 (aq), brine, dried over Na2SO4 and con-
centrated under reduced pressure. The crude product
was puri®ed by silica gel chromatography (25% EtOAc
in hexane) to yield 27.5 mg of 9b, 12-b (75 mmol, 84%).
1H NMR (CDCl3): d 8.14 (t, J=1.6 Hz, 1H), 7.92 (ddd,
J=8, 1.6, 0.8 Hz, 1H), 7.82 (ddd, J=8, 1.6, 0.8 Hz, 1H),
7.57 (t, J=7.6 Hz, 1H), 5.14 (d, J=1.6 Hz, 1H), 3.66 (s,
3H), 3.05 (s, 3H), 2.79 (ddd, J=14.4, 13.2, 8 Hz, 1H),
2.25 (ddd, J=10.8, 4.4, 3.2 Hz, 1H), 1.88±2.02 (m, 2H),
1.58±1.82 (m, 6H), 1.14±1.36 (m, 3H); 13C NMR
(CDCl3): d 142.82, 140.82, 130.83, 129.60, 127.79, 124.48,
105.32, 104.55, 84.36, 57.51, 47.52, 44.65, 39.34, 35.77,
30.93, 26.83, 25.11, 23.95. HRMS calcd for C18H28
NO6S m/z (M+NH+4 ): 386.1637, found 386.1634.
p-Sul®de trioxanes 9 via singlet oxygen. p-Methylthio-
phenyl ketone 19 (144 mg, 0.474 mmol, 1.0 equiv) was
treated according to General procedure 1. TMSOTf (1.2
equiv) was used to eect rearrangement. The crude
product was puri®ed by silica gel chromatography (10%
EtOAc in hexanes) and the diastereomers were further
puri®ed on silica gel semi-prep HPLC (2% EtOAc in
hexanes, 3 mL/min) to yield 4 mg trioxane 9c, 12-a
(0.012 mmol, 2.5%) and 10 mg trioxane 9c, 12-b(0.030
mmol, 6.3%). 9c, 12-a1H NMR (CDCl3): d 7.45±7.48
(m, 2H), 7.21±7.23 (m, 2H), 5.17 (s, 1H), 3.61 (s, 3H),
2.78±2.85 (m, 1H), 2.48 (s, 3H), 2.38±2.45 (m, 1H),
2.20±2.30 (m, 1H), 1.86±1.92 (m, 1H), 1.68±1.80 (m,
7H), 1.18±1.30 (m, 2H); 13C NMR (CDCl3): d 139.38,
137.22, 125.94, 125.88, 103.85, 96.15, 83.57, 56.09,
45.41, 37.47, 33.39, 32.53, 27.15, 25.26, 23.15, 15.52. 9c,
12-b1H NMR (CDCl3): d 7.45±7.49 (m, 2H), 7.21±7.25
(m, 2H), 5.13 (d, J=1.6 Hz, 1H), 3.64 (s, 3H), 2.73±2.82
(m, 1H), 2.48 (s, 3H), 2.35±2.43 (m, 1H), 1.86±2.02 (m,
3H), 1.60±1.80 (m, 5H), 1.17±1.35 (m, 3H); 13C NMR
(CDCl3): d 139.56, 137.72, 126.17, 126.00, 105.33,
105.11, 83.97, 57.36, 47.65, 39.20, 35.81, 31.00, 27.00,
25.23, 24.03, 15.80. HRMS calcd for C18H25O4S m/z
(M+H+): 337.1474, found 337.1474.
p-Sul®de trioxane 9 via triphenylphosphite ozonide. p-
Methylthiophenyl ketone 19 (136 mg, 0.448 mmol, 1.0
equiv) in CH2Cl2 (7 mL) was treated according to Gen-
eral procedure 2 utilizing triphenyl phosphite (295 mg,
0.951 mmol, 2.1 equiv) in CH2Cl2 (30 mL). TMSOTf
(1.2 equiv) in CH2Cl2 was used to eect rearrangement
and the reaction was quenched with sodium methoxide
(3.2 equiv, 25 wt% in methanol). After work up, the
crude product was puri®ed by silica gel chromatography
(10% EtOAc in hexane) to yield 10 mg of 9c, 12-a
(0.030 mmol, 7%) and 1 mg 9c, 12-b (0.003 mmol,
0.7%). Spectral data as reported above.
Preparation of trioxanes 9c and 9d:
Trioxanes 9d, 12-ꢁ. A solution of trioxane 9c, 12-b (5 mg,
15 mmol, 1.0 equiv) in CH2Cl2 (4 mL) at 0 ꢂC was trea-
ted with m-CPBA (repuri®ed from tech. grade, 11 mg,
p-Methylthiophenyl ketone 19. A solution of 4-bromo-
thioanisole (1.02 g, 5.01 mmol, 1.3 equiv) in diethyl