4238 J . Org. Chem., Vol. 61, No. 13, 1996
Refvik and Schwan
LDA. To a solution of LDA (0.96 mmol, 1.1 equiv) in THF
(5 mL) was added thiophthalimide 7b (227 mg, 0.88 mmol) in
THF (2 mL) at -78 °C. The mixture was warmed to rt over
0.5 h. At this time water (10 mL) and ether (20 mL) were
added. The layers were separated, and the aqueous layer was
extracted with ether (2 × 10 mL). The combined organic layers
were washed with water (3 × 10 mL) and brine and were dried
over Na2SO4. Filtration and concentration of the mixture
afforded crude alkenesulfenamide 8f (46%). Crude yields for
all systems are reported in Table 1.
MCP BA Oxid a tion of Cr u d e 1-Alk en esu lfen a m id es 8.
The following is based on a method previously reported for
sulfinamide to sulfonamide oxidation.28 To a solution of
sulfenamide 8 in CH2Cl2 (15 mL) at 0 °C was added anhydrous
K2CO3 (3 equiv), followed by dried MCPBA (3 equiv) in CH2Cl2
(5-10 mL). The mixture was warmed to rt and was stirred
for 3 days. At this time, the mixture was impinged with
anhydrous NH323,39 at rt, and the mixture was suction filtered
through Celite to remove some ammonium m-chlorobenzoate.
The NH3 treatment and filtration was repeated at -78 °C. The
filtrate was concentrated and chromatographed on basic
alumina (I) (EtOAc in hexanes and/or EtOAc only) to afford
pure alkenesulfonamide.
N-Ben zyl-(E)-1-h exen esu lfon a m id e (9a ): 67%, oil. 1H
NMR (400 MHz), δ 7.36-7.27 (m, 5H), 6.74 (dt, J ) 15.0, 6.8
Hz, 1H), 6.11 (d, J ) 15.0 Hz, 1H), 4.71 (t(br), J ) 6.0 Hz,
1H), 4.18 (d, J ) 6.0 Hz, 2H), 2.18 (q, J ) 6.8 Hz, 2H), 1.44-
1.28 (m, 4H), 0.91 (t, J ) 7.0 Hz, 3H); 13C NMR (100.6 MHz),
δ 146.2, 136.7, 128.7 (2 C’s), 127.9 (2 C’s), 47.0, 30.9, 29.8, 22.1,
13.7. Anal. Calcd for C13H19NO2S: C, 61.63; H, 7.56; N, 5.53.
Found: C, 61.66; H, 7.58; N, 5.77.
N-Ben zyl-N-m eth yl-(E)-1-h exen esu lfon am ide (9b): 73%,
oil. 1H NMR (400 MHz), δ 7.38-7.29 (m, 5H), 6.78 (dt, J )
15.1, 7.0 Hz, 1H), 6.11 (dt, J ) 15.1, 1.2 Hz, 1H), 4.22 (s, 2H),
2.66 (s, 3H), 2.27 (dq, J )7.0, 1.2 Hz, 2H), 1.46 (m, 2H), 1.36
(m, 2H), 0.93 (t, J ) 7.2 Hz, 3H); 13C NMR (100.6 MHz), δ
147.2, 135.8, 128.6, 128.4, 127.9, 124.8, 53.8, 34.1, 31.2, 30.0,
22.1, 13.7. Anal. Calcd for C14H21NO2S: C, 62.89; H, 7.92;
N, 5.24. Found: C, 62.65; H, 7.76; N, 5.26.
N-Allyl-(E)-1-h exen esu lfon a m id e (9c): 53%, oil. 1H NMR
(400 MHz), δ 6.77 (ddt, J ) 15.1, 7.0, 2.2 Hz, 1H), 6.18 (d, J )
15.1, 1H), 5.84 (m, 1H), 5.26 (dt, J ) 17.1, 1.3 Hz, 1H), 5.18
(dt, J ) 11.1, 1.2 Hz, 1H), 4.41 (s(br), 1H), 3.64 (s, 2H), 2.26
(q, J ) 7.0 Hz, 2H), 1.50-1.42 (m, 2H), 1.40-1.31 (m, 2H),
0.92, (t, J ) 7.1 Hz, 3H); 13C NMR (100.6 MHz), δ 146.2, 133.4,
127.9, 117.6, 45.5, 31.0, 29.9, 22.1, 13.7. HRMS Calcd for
C9H17NO2S: 203.0980. Found: 203.0961.
N-Allyl-N-p h en yl-(E)-1-h exen esu lfon a m id e (9d ): 35%,
oil. 1H NMR (400 MHz), δ 7.37-7.27 (m, 5H), 6.65 (dt, J )
15.1, 7.0 Hz, 1H), 6.19 (d, J ) 15.1 Hz, 1H), 5.81 (m, 1H), 5.14
(d, J ) 17.1 Hz, 1H), 5.09 (d, J ) 10.2 Hz, 1H), 4.20 (d, J )
6.1 Hz, 1H), 2.20 (q, J ) 7.0 Hz, 1H), 1.42 (m, 2H), 1.32 (m,
2H), 0.90 (t, J ) 7.2 Hz, 3H); 13C NMR (100.6 MHz), δ 146.9,
139.4, 133.1, 129.0, 128.7, 127.7, 126.1, 118.7, 53.5, 31.1, 29.9,
22.0, 13.7. Anal. Calcd for C15H21NO2S: C, 64.48; H, 7.58;
N, 5.01. Found: C, 64.31; H, 7.48; N, 4.94.
N-(4-P h en yl-(E)-1-bu ten esu lfon yl)m or ph olin e (9e): 63%,
mp 96-96.5 °C. 1H NMR (400 MHz), δ 7.33-7.16 (m, 5H),
6.75 (dt, J ) 15.2, 6.8 Hz, 1H), 6.03 (d, J ) 15.2 Hz, 1H), 3.70
(t, J ) 4.6 Hz, 4H), 2.94 (t, J ) 4.6 Hz, 4H), 2.83 (t, J ) 7.3
Hz, 2H), 2.62 (dt, J ) 7.3, 6.8 Hz, 2H); 13C NMR (100.6 MHz),
δ 147.5, 139.8, 128.6, 128.3, 126.5, 124.1, 66.1, 45.5, 34.0, 33.0.
Anal. Calcd for C14H19NO3S: C, 59.76; H, 6.81; N, 4.98.
Found: C, 59.89; H, 6.67; N, 4.97.
N,N-Bis(2-m eth yleth yl)-1-cycloh exen esu lfon am ide (9f):
25%, oil. 1H NMR (400 MHz), δ 6.81 (m, 1H), 3.58 (septet, J
) 6.7 Hz, 2H), 2.31 (m, 2H), 2.23 (m, 2H), 1.74-1.68 (m, 2H),
1.63-1.58 (m, 2H), 1.30 (d, J ) 6.7 Hz, 12H); 13C NMR (100.6
MHz), δ: 138.8, 136.7, 48.0, 25.3, 23.1, 22.3, 22.1, 21.1. HRMS
Calcd for C12H23NO2S: 245.1450. Found: 245.1446.
4.6 Hz, 1H), 1.76 (m, 2H), 1.67 (m, 2H), 1.31 (d, J ) 5.8 Hz,
3H); 13C NMR (100.6 MHz), δ 138.3, 137.6, 35.1, 34.2, 25.3,
23.5, 21.8, 20.8, 16.9. Anal. Calcd for C9H15NO2S: C, 53.70;
H, 7.51; N, 6.96. Found: C, 53.86; H, 7.32; N, 6.98.
N-Cycloh exyl-1-cycloh exen esu lfon a m id e (9h ): 67%, mp
90-90.5 °C. 1H NMR (400 MHz), δ 6.81 (m, 1H), 4.61 (d, J )
7.6 Hz, 1H), 3.07 (m, 1H), 2.32 (m, 2H), 2.24 (m, 2H), 1.89 (m,
2H), 1.76-1.53 (m, 6H), 1.38-1.17 (m, 6H); 13C NMR (100.6
MHz), δ 138.5, 136.2, 52.3, 34.1, 25.2, 25.1, 24.7, 23.0, 21.9,
21.0. Anal. Calcd for C12H21NO2S: C, 59.22; H, 8.70; N, 5.76.
Found: C, 59.40; H, 8.88; N, 5.79.
N,N-Dim eth yl-1-cycloh exen esu lfen a m id e (8j). A mix-
ture of thiophthalimide 7g (2.15 g, 8.30 mmol) and dimethyl-
amine (0.7 mL, 10.6 mmol) was stirred in benzene (50 mL) at
rt for 2 h. The mixture was suction filtered, and the solid was
rinsed with pentane (3 × 10 mL). The filtrate and the pentane
washes were combined and concentrated. The residue was
triturated into pentane (20 mL) and was suction filtered. The
solid as rinsed with pentane (3 × 10 mL). The filtrate and
the pentane washes were combined and concentrated to afford
crude alkenesulfenamide 8j (96% crude). Distillation (42-46
°C/1.2 mm) afforded pure sulfenamide 8j (1.02 g, 78%). 1H
NMR (400 MHz), δ 5.84 (m, 1H), 2.76 (s, 6H), 2.18-2.10 (m,
4H), 1.69 (m, 2H), 1.59 (m, 2H); 13C NMR (100.6 MHz), δ 135.1,
125.6, 48.8, 29.4, 26.1, 23.1, 22.0. HRMS Calcd for C9H15NS:
157.0925. Found: 157.0926.
P r ep a r a tion of [(Alk en ylth io)im in o]p h th a lid es 11. To
a flame-dried flask under N2 were added sulfenamide 4 (4.09-
4.28 g, 15-15.5 mmol), 4 Å molecular sieves (2 g), and dry
THF (110 mL). The flask was cooled to 0 °C, and TBAF (1
mol equiv, 1 M in THF) was added dropwise over 5 min. Then
Et3N (4 equiv) was added followed by phthaloyl dichloride (2
equiv) over 5 min. The mixture turns bright yellow, and a
precipitate forms. After 5 min, saturated aqueous NH4Cl (100
mL) and ether (50 mL) were added. After transfer to a
separatory funnel, the layers were separated and the aqueous
layer was extracted with ether (3 × 30 mL). The combined
organic extracts were washed with water (2 × 30 mL) and
brine (30 mL). The organic layer was dried over Na2SO4.
Filtration, concentration, and immediate flash chromatography
(silica gel, 30% EtOAc in hexanes) afforded compounds 11
followed by isomers 7 (10-12%). Recrystallization from
EtOAc/hexanes afforded analytically pure thioiminophthalides
11.
3-[(E)-(1-Hexen ylth io)im in o]p h th a lid e (11a ): 61%, oil.
1H NMR (400 MHz), δ 7.90 (d, J ) 7.6 Hz, 1H), 7.86 (d, J )
7.6 Hz, 1H), 7.76 (dt, J ) 7.6, 0.9 Hz, 1H), 7.64 (dt, J ) 7.6,
0.9 Hz, 1H), 6.52 (dt, J ) 15.3, 1.4 Hz, 1H), 6.01 (dt, J ) 15.3,
7.2 Hz, 1H), 2.21 (dq, J ) 7.2, 1.4 Hz, 2H), 1.45 (m, 2H), 1.37
(m, 2H), 0.92 (t, J ) 7.2 Hz, 3H); 13C NMR (100.6 MHz), δ
163.6, 145.4, 135.3, 135.1, 131.9, 131.8, 126.9, 125.3, 124.5,
122.2, 32.4, 31.0, 22.1, 13.8; UV/vis (95% ethanol), λmax: 356
nm (log ꢀ ) 3.0). Anal. Calcd for C14H15NO2S: C, 64.34; H,
5.79; N, 5.36. Found: C, 64.59; H, 5.68; N, 5.27.
3-[(1-Cycloh exen ylth io)im in o]p h th a lid e (11b): 67%,
oil. 1H NMR (400 MHz), δ 7.90 (d, J ) 7.6 Hz, 1H), 7.86 (d, J
) 7.6 Hz, 1H), 7.75 (dt, J ) 7.6, 1.0 Hz, 1H), 7.64 (dt, J ) 7.6,
1.0 Hz, 1H), 6.17 (m, 1H), 2.48 (m, 2H), 2.20 (m, 2H), 1.82 (m,
2H), 1.69 (m, 2H); 13C NMR (100.6 MHz), δ 163.8, 144.9, 135.3,
135.2, 134.1, 131.6, 126.9, 126.8, 125.3, 122.2, 27.4, 26.1, 23.0,
21.8. UV/vis (95% ethanol), λmax: 357 nm (log ꢀ ) 3.7). Anal.
Calcd for C14H13NO2S: C, 64.84; H, 5.05; N, 5.40. Found: C,
64.64; H, 4.95; N, 5.35.
Rea ction s of [(Alk en ylth io)im in o]p h th a lid es 11 w ith
Am in es. A mixture of thioiminophthalide 11 (205-248 mg,
0.66-0.95 mmol) and alkyl- or dialkylamine (1 equiv) was
stirred in benzene (5 mL) under the conditions indicated in
Table 2.
Tr a n sa m in a tion s. The mixture was diluted with pentane
(5 mL) and was suction filtered. The solid was rinsed with
pentane (3 × 10 mL). The filtrate and the pentane washes
were combined and concentrated to afford crude 1-alkene-
sulfenamide 8 which was oxidized as above to afford 1-alk-
enesulfonamides 9.
N-(1-Cycloh exen esu lfon yl)-2-m eth ylazir idin e (9g): 60%,
oil. 1H NMR (400 MHz), δ 6.88 (s(br), 1H), 2.74 (m, 1H), 2.56
(d, J ) 7.1 Hz, 1H), 2.49 (m, 2H), 2.28 (m, 2H), 2.02 (d, J )
Rin g-Op en in gs. The mixture was diluted with pentane
(5 mL) and was suction filtered. The solid was recrystallized
(39) Kondo, K.; Negishi, A. Tetrahedron, 1971, 27, 4821.