Synthesis of Six- to Nine-Membered Ring Oximinoorthodithiolactones
FULL PAPER
(weak, CϭNϪOH), 1827, 2935, 3007, 3276 (br. band, OH), 3564
1
(oxime, OH). Ϫ H NMR ([D6]DMSO/CDCl3): δ ϭ 2.07 (s, 3 H,
1H NMR (room temp./TMS, [D4]MeOH): δ ϭ 2.83 (s,
3 H, SϪCH3), 4.52 (s, 2 H, PhϪCH2ϪS), 7.19 (d, J ϭ 6.4 Hz, 1 o-
H), 7.26 (dd, J ϭ 7.8, 7.8 Hz, 1 H), 7.35 (dd, J ϭ 7.8, 7.8 Hz, 1
H), 7.79 (d, J ϭ 8 Hz, 1 o-H). Ϫ 13C NMR: δ ϭ 24.2 (SCH3), 40.7
(benzylic CH2), 117.7 (ipso-C), 129.1, 130.7 and 132.1 (aromatic
CH), 135.4 (ipso-C), 137.7 (aromatic CH), 149.2 (ϾCϭNϩϽ),
212.3 (ϾCϩ).
SCH3), 3.20 (s, 3 H, OCH3), 3.65 (d, J ϭ 15.9 Hz, 1 H, axial
benzylic H), 4.20 (d, J ϭ 15.9 Hz, 1 H, equatorial benzylic H),
7.15Ϫ7.35 (m, 3 H, aromatic H), 8.12 (dd, J ϭ 7.5 and 1.7 Hz, 1
H, o-H), 11.37 (s, 1 H, ϭNϪOH). Ϫ 13C NMR ([D6]DMSO/
CDCl3): δ ϭ 11.9 (SCH3), 30.2 (CH2), 51.5 (OCH3), 93.5 (orthodi-
thioester C), 125.9 and 127.1 (aromatic CH), 127.1 (ipso-C), 128.9
and 131.0 (aromatic CH), 135.6 (ipso-C), 148.9 (ϾCϭNϪOH). Ϫ
MS (70 eV); m/z (%): 224 (1) [Mϩ Ϫ CH3O], 208 (70) [Mϩ
Ϫ
1H NMR (room temp.): δ ϭ 1.89 (br. s, 2 H, CH2Ͻ),
2.50 (br. s, 2 H, benzylic H), 2.89 (br. s, 3 H, SCH3), 3.54 (br. s, 2
H, SCH2), 6.91 (d, J ϭ 7.7 Hz, 1 H), 6.97 (t, J ϭ 7.7 Hz, 1 H),
7.16 (t, J ϭ 7.7 Hz, 1 H), 7.21 (d, J ϭ 8.5 Hz, 1 H). Ϫ 13C NMR:
δ ϭ 23.7 (SCH3), 31.5 (CH2), 36.5 (CH2), 118.1 (ipso-C), 128.3,
129.1 and 132.5 (aromatic CH), 136.9 (ipso-C), 138.2 (aromatic
CH), 158.3 (ϾCϭNϩϽ), 220.1 (CϩϽ).
CH3S], 176 (5) [Mϩ Ϫ CH3S Ϫ CH3OH], 148 (20), 134 (32), 116
(70) [C4H6ONSϩ], 89 (65) [C3H5OSϩ], 75 (100) [C2H3OSϩ]. Ϫ
C11H13NO2S2 (255.34): calcd. C 51.74, H 5.13, N 5.49, S 25.11;
found C 51.64, H 5.16, N 5.35, S 24.36.
d
From nitroethylene derivative (312 mg, 1.22 mmol)
in TFSA (4.0 mL, 45 mmol) at room temp. for 1 h. Flash chroma-
tography (CH2Cl2/AcOEt/iPrOH, 95:5:0.5) afforded compound
(244 mg, 74%). Ϫ M.p. 181Ϫ3 °C (dec.). Ϫ 1H NMR
([D6]DMSO/CDCl3): δ ϭ 2.04 (s, SMe), 2.70 (m, 1 H), 3.05 (m, 3
H), 3.35 (s, 3 H, OMe), 7.14 (m, 2 H), 7.24 (m, 2 H), 11.08 (s, 1
H, ϭNϪOH). Ϫ 13C NMR ([D6]DMSO/CDCl3): δ ϭ 12.1 (SCH3),
27.4 (br. and weak signal for both CH2 groups), 50.8 (OCH3), 96.6
(orthodithioester C), 125.3, 128.3, 129.2 and 129.8 (aromatic CH),
132.9 (ipso-C), 136.5 (ipso-C), 156.6 (ϾCϭN). Ϫ MS (70 eV); m/z
(%): 269 (Ͻ 1) [Mϩ], 252 (5) [Mϩ Ϫ OH], 238 (2) [Mϩ Ϫ OCH3],
222 (100) [Mϩ Ϫ SCH3], 130 (20), 116 (20) [C4H6ONSϩ], 89 (17)
[C3H5OSϩ], 75 (58) [C2H5OSϩ]. Ϫ C12H15NO2S2 (269.38): calcd.
C 53.51, H 5.61, N 5.20, S 23.81; found C 53.44, H 5.44, N 5.39,
S 22.92.
1H NMR (255 K): δ ϭ 1.85 (br. s, 2 H, CH2), 2.47 (br.
s, 2 H, CH2), 2.86 (s, 3 H, SϪCH3), 3.51 (br. s, 2 H, CH2), 7.01
(m, 1 H), 7.20 (br. s, 1 H), 7.56 (br. s, 1 H), 6.92 (m, 1 H). Ϫ 13C
NMR: δ ϭ 26.2 (SϪCH3), 29.6, 33.4 and 44.6 (CH2), 122.5, 129.5
(ϭCϪH), 134.5, 140.0, 158.5 (ϾCϭNϩϽ), 220.1 (CϩϽ).
1H NMR (254 K): δ ϭ 4.31 (s, 2 H, CH2), 4.37 (s, 2 H,
CH2), 6.6 to 6.9 (br. m, 5 H, Ph), 7.17 (d, J ϭ 7.6 Hz, 1 H, ortho-
H), 7.21 (dd, J ϭ 7.6 and 8 Hz, 1 H), 7.34 (dd, J ϭ 7.7 and 7.7 Hz,
1 H), 7.77 (d, J ϭ 8 Hz, 1 H, ortho-H). Ϫ 13C NMR (room temp.):
δ ϭ 41.0 (benzylic C), 48.4, 117.7 (ipso-C), 125.6, 129.0 (br. s, aro-
matic CH), 129.4 (aromatic CH), 129.6, 130.4, 135.3 (ipso-C), 148.2
(ϾCϭNϩϽ), 209.0 (ϾCϩ).
1H NMR (255 K): δ ϭ 2.62 (m, 2 H, CH2CH2CH2),
2.82 (m, 2 H, CH2CH2CH2), 3.19 (br. d, 1 H), 3.40 (m, 2 H), 3.65
(t, J ϭ 14 Hz, 1 H, CH2S), 6.56 (m, 5 H), 6.92 (d, J ϭ 7.8 Hz, 1
H), 6.98 (t, J ϭ 7.7 Hz, 1 H), 7.16 (d, J ϭ 7.6 Hz, 1 H) 7.19 (t,
J ϭ 7.8 Hz, 2 H), 12.70 (v br. s, ϭNHϩϪOH). Ϫ 13C NMR: δ ϭ
32.3, 32.5, 37.2, 46.8 (br. s), 119.1, 128.8, 129.2, 129.4, 129.9, 130.0,
133.5, 136.2, 137.8, 139.3, 159.0 (ϾCϭNϩϽ), 216.6 (ϾCϩ).
H
d
From nitroethylene derivative
(241 mg,
0.896 mmol) in TFSA (4.9 mL, 55 mmol) for 2 h at 0Ϫ5 °C. Flash
chromatography (CH2Cl2/EtOH, 99:1) afforded compound
(184 mg, 82%) as white crystals. Ϫ M.p. 191Ϫ193 °C (dec.). Ϫ H
1
NMR ([D6]DMSO/CDCl3, 4:1) mixture of isomers in 3:2 ratio
(main signal with *): δ ϭ 1.5Ϫ1.9 (m, 1.7 H), 1.9Ϫ2.1 (m, 0.3 H),
2.03 and 2.05* (s, 3 H, SCH3), 2.15Ϫ2.3 (m, 0.7 H), 2.4Ϫ2.8 (m,
3.4 H), 3.38* and 3.40 (s, OCH3), 6.88* and 7.03 (d, J ϭ 7.2 Hz
and J ϭ 7.0 Hz, 1 H, ortho-H), 7.1Ϫ7.3 (m, 3 H, aromatic H),
11.13 and 11.17* (s, 1 H, NϪOH). Ϫ 13C NMR ([D6]DMSO/
CDCl3) (two isomers, main signal with *): δ ϭ 11.4 and 12.4*
(SCH3), 26.5 and 29.5* (CH2S), 30.5 and 31.1* (benzylic CH2),
32.2* and 34.1 (CH2ϪCH2ϪCH2), 50.6 and 50.4* (OCH3), 99.2
and 99.9* (dithioorthoester C), 124.8 and 125.3* (aromatic CH),
127.5* and 127.7 (aromatic CH), 128.3* and 128.4 (aromatic CH),
128.6 (aromatic CH), 134.1 and 134.3* (ipso-C), 137.9 and 140.6*
(ipso-C), 156.1 and 157.3* (ϾCϭNϪOH). Ϫ MS (70 eV); m/z (%):
283 (2) [Mϩ], 266 (9) [Mϩ Ϫ OH], 252 (55) [Mϩ Ϫ OCH3], 236
(100) [Mϩ Ϫ SCH3], 204 (20) [Mϩ Ϫ SCH3 Ϫ CH3OH], 116 (50)
[C8H6N]. Ϫ C13H17NO2S2 (283.40): calcd. C 55.10, H 6.05, N 4.94,
S 22.63; found C 55.57, H 6.20, N 5.31, S 22.43.
1H NMR (255 K):
δ ϭ 1.80 (br. s, 4 H, 2
CH2ϪCH2ϪCH2), 2.22 (br. s, 2 H, benzylic H), 2.30 (br. s, 2 H
benzylic H), 3.21 (br. s, 2 H, CH2S), 3.33 (br. s, 2 H, CH2S), 6.12
(br. s, 1 H, aromatic H), 6.33 (br. s, 2 H, aromatic H), 6.50 (br. s,
2 H, aromatic H), 6.96 (br. s, 2 H, aromatic H), 7.23 (br. s, 1 H,
aromatic H), 7.60 (br. s, 1 H, aromatic H). Ϫ 13C NMR: δ ϭ 27.3,
29.2, 33.0, 34.4, 43.1 and 45.0 (CH2ϪS), 122.8, 128.0, 128.7, 129.7,
130.0, 133.5, 134.8, 139.5, 143.9, 155.7 (ϾCϭNϩϽ), 214.3 (CϩϽ).
Mostly broadened signals and slow decomposition at 255 K.
؊
؊
Nitroethylene derivative
(322 mg, 1.33 mmol) was dissolved in TFSA (5.0 mL, 56 mmol)
at a temperature between Ϫ10 and ϩ2 °C, and left for 40 min. The
solution was quenched with MeOH/CH2Cl2 (18:52, 70 mL) at a
temperature between Ϫ60 and Ϫ80 °C, and then CH2Cl2 (100 mL)
was added. At a temperature between Ϫ10 and 0 °C, the resulting
organic phase was washed with water (30 mL), then brine (20 mL),
From nitroethylene derivative
and finally with brine containing NaHCO3. The organic phase was (517 mg, 1.83 mmol) in TFSA (9 mL, 101 mmol) for 30 min at 0Ϫ5
dried with MgSO4 and the solvent was evaporated under vacuum
to afford a crystallized product. Flash chromatography led to the
recovery of some starting material (petroleum ether/AcOEt, 9:1, tion from AcOEt/hexane. Ϫ M.p. 173Ϫ174 °C (dec.). Ϫ H NMR
°C. Flash chromatography (CH2Cl2/EtOH, 98:2) afforded com-
pound (152 mg, 28%) as light yellow crystals after crystalliza-
1
9 mg, 2.7%). Further elution (petroleum ether/AcOEt/CH2Cl2,
40:7:3) afforded the cyclic derivative (236 mg; 70%), which was
further crystallized from AcOEt as white crystals. Ϫ M.p. 134Ϫ136
(CDCl3), mixture of two isomers (1:7 ratio): δ ϭ 1.28 (m, 2 H) and
1.86 (m, 4 H), 2.10 (CH3S) and 2.69 (m, 4 H), 3.48 (CH3O), 7.26
(d, J ϭ 7.4 Hz, 2 H), 7.35 (d, J ϭ 7.4 Hz, 1 H), 7.47 (d, J ϭ 7.4 Hz,
°C (dec.). Ϫ IR (CHCl3) ν˜ ϭ 940, 1059, 2860 1454, 1495, 1602 1 H), 9.02, (s, ϭNϪOH). Ϫ 13C NMR (CDCl3): δ ϭ 12.2 (SCH3),
Eur. J. Org. Chem.
, 1525Ϫ1531
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