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Synlett 2010(12): 1766-1770  
DOI: 10.1055/s-0030-1258119
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

MoO2Cl2(dmf)2-Catalyzed Domino Reactions of ω-Nitro Alkenes to 3,4-Dihydro-2H-1,4-benzothiazines and Other Heterocycles

Chandi C. Malakar, Elena Merisor, Jürgen Conrad, Uwe Beifuss*
Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany
Fax: +49(711)45922951; e-Mail: ubeifuss@uni-hohenheim.de;
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Publication History

Received 6 April 2010
Publication Date:
30 June 2010 (online)

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Abstract

Using the transformation of allyl 2-nitrophenyl thio­ethers to 3,4-dihydro-2H-1,4-benzothiazines as an example the reductive cyclization of ω-nitroalkenes to saturated N-heterocycles can be performed highly selective and with high yields if a combination of MoO2Cl2(dmf)2 as a catalyst and Ph3P as reducing agent are employed.

Key words

catalysis - domino reaction - heterocycles - nitroso ene reaction - reductive cyclization

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General Procedure for the Synthesis of Thioethers 7a-d In an oven dried 250 mL three-necked round-bottom flask
2-nitro thiophenol 9 (16.11 mmol) was dissolved in freshly distilled dry THF (50 mL) under Ar. Sodium hydride (80%) (24.16 mmol) was added in several portions at 0 ˚C during 10 min, and after complete addition the reaction mixture was stirred for 30 min at 0 ˚C. Freshly distilled allyl bromide (64.44 mmol) was added dropwise at 0 ˚C; after complete addition the reaction mixture was allowed to stir at r.t. for 12.5 h. Then the reaction mixture was poured into sat. NH4Cl (100 mL) and extracted with TBME (3 × 100 mL). The combined organic phases were washed with brine (100 mL) and dried over anhyd MgSO4. The solvents were removed under reduced pressure, and the crude product was purified by Kugelrohr distillation or by flash column chromatog-raphy on silica gel (cyclohexane-EtOAc, 20:1).

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General Procedure for the (EtO) 3 P-Mediated Domino Reaction under Microwave Conditions A 10 mL process vial was charged with a mixture of 7 (1 mmol), (EtO)3P (1.07 mL, 6 mmol) and toluene (3 mL). The vial was sealed, placed into the cavity of the microwave reactor, and irradiated with microwaves at 200 ˚C for 30-35 min, after removing (EtO)3P and (EtO)3PO by Kugelrohr distillation under reduced pressure, the remaining residue was diluted with hot EtOAc (50 mL). The organic phase was washed with brine (3 × 20 mL) and dried over MgSO4. Solvent was removed under reduced pressure, and the remaining residue was purified by flash chromatography on silica gel (cyclohexane-EtOAc, 20:1).

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General Procedure for the Mo(VI)-Catalyzed Domino Reaction under Microwave Conditions with Ph 3 P as a Reagent A 10 mL process vial was charged with a mixture of 7 (1 mmol), Ph3P, MoO2Cl2(dmf)2, and toluene (3 mL). The vial was sealed, placed into the cavity of the microwave reactor, and irradiated with microwaves at 200 ˚C for 30-240 min, after filtration and removal of the solvent the reaction mixture was poured into H2O (100 mL) and extracted with EtOAc (3 × 50 mL). The combined organic phases were washed with brine (3 × 20 mL), dried over MgSO4, and the solvent was removed under reduced pressure. The remaining residue was purified by flash chromatography on silica gel (cyclohexane-EtOAc, 20:1). Alternatively, the reaction mixture can also be purified by flash column chroma-tography without any workup procedure.

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Selected Data for 1-(3-Methylbut-2-enylsulfanyl)-2-nitrobenzene (7a, Figure 2) R f = 0.52 (cyclohexane-EtOAc, 20:1). UV/vis (MeCN):
λmax (log ε) = 245 (4.20), 380 (3.43) nm. IR (ATR): 2914, 1593, 1565, 1508, 1452, 1376, 1333, 1303, 1252, 1170, 1103, 1061, 1044, 981, 852, 780, 730 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.74 (br s, 3 H, 4′-H), 1.76 (br s, 3 H, 5′-H), 3.60 (d, ³ J = 7.8 Hz, 2 H, 1′-H), 5.31 (sept, ³ J = 7.6 Hz, 4 J = 1.4 Hz, 1 H, 2′-H), 7.24 (ddd, ³ J = 7.2 Hz, ³ J = 8.2 Hz, 4 J = 1.4 Hz, 1 H, 4-H), 7.41 (dd, ³ J = 8.2 Hz, 4 J = 1.2 Hz,
1 H, 6-H), 7.54 (ddd, ³ J = 7.2 Hz, ³ J = 8.2 Hz, 4 J = 1.5 Hz,
1 H, 5-H), 8.19 (dd, ³ J = 8.2 Hz, 4 J = 1.5 Hz, 1 H, 3-H). ¹³C NMR (75.4 MHz, CDCl3): δ = 18.25 (C-5′), 26.00 (C-4′), 31.27 (C-1′), 117.18 (C-2′), 124.65 (C-4), 126.33 (C-3), 127.29 (C-6), 133.61 (C-5), 138.80 (C-1), 139.03 (C-3’), 146.25 (C-2). MS (EI, 70 eV): m/z (%) = 223 (20) [M+], 206 (5), 155 (36), 139 (100), 138 (23), 125 (8), 117 (3), 69 (1). HRMS (EI): m/z [M+] calcd for C11H13NO2S: 223.0667; found: 223.0664. Anal. Calcd for C11H13NO2S: C, 59.17; H, 5.87; N, 6.27. Found: C, 59.18; H, 5.92; N, 6.62.

Figure 2

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Selected Data for 3-Isopropenyl-3,4-dihydro-2 H -benzo[1,4]thiazine (8a, Figure 3)
R f = 0. 54 (cyclohexane-EtOAc, 20:1). UV/vis (C2H5OH): λmax (log ε) = 230 (4.36), 313 (3.67) nm. IR (ATR): 3397, 2927, 1647, 1589, 1477, 1417, 1306, 1263, 1237, 1156, 1107, 1075, 1033, 957, 899, 838, 738 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.83 (s, 3 H, 3′-H), 2.98 (overlapped, 1 H, 3-H), 2.98 (dd, ³ J = 3.9 Hz, ² J = 12.5 Hz, 1 H, 2b-H), 3.04 (dd, ³ J = 7.3 Hz, ² J = 12.5 Hz, 1 H, 2a-H), 4.08 (br dd, ³ J = 3.9 Hz, ³ J = 7.2 Hz, 1 H, 3-H), 5.03 (br s, 1 H, 2′-H), 5.11 (br s, 1 H, 2′-H), 6.54 (dd, ³ J = 8.0 Hz, ² J = 1.3 Hz, 1 H, 5-H), 6.64 (ddd, ³ J = 7.5 Hz, ³ J = 7.5 Hz, ² J = 1.3 Hz, 1 H, 7-H), 6.93 (ddt, ³ J = 7.3 Hz, ³ J = 8.0 Hz, ² J = 1.6 Hz, 1 H, 6-H), 7.02 (dd, ³ J = 7.8 Hz, ² J = 1.5 Hz, 1 H, 8-H). ¹³C NMR (75 MHz, CDCl3): δ = 19.22 (C-3′), 30.19 (C-2), 57.16 (C-3), 112.95 (C-2′), 115.66 (C-5), 115.88 (C-9), 118.5 (C-7), 125.93 (C-6), 127.74 (C-8), 142.01 (C-10), 145.81 (C-1′). MS (EI, 70 eV): m/z (%) = 191 (100) [M+], 163 (18), 150 (46), 117 (21), 109 (11), 65 (5). HRMS (EI): m/z [M+] calcd for C11H13NS: 191.0769; found: 191.0783. Anal. Calcd for C11H13NS: C, 69.07; H, 6.85; N, 7.32. Found: C, 69.15; H, 6.90; N, 7.27.

Figure 3