Rh2(OAc)4-Mediated Diazo Decomposition of δ-(N-Tosyl)amino-β-keto-α-diazo Carbonyl Compounds: A Novel Approach to Pyrrole Derivatives

Guisheng  Deng; Nan  Jiang; Zhihua  Ma; Jianbo  Wang

doi:10.1055/s-2002-34888

LETTER

Rh₂(OAc)₄-Mediated Diazo Decomposition of δ-(N-Tosyl)amino-β-keto-α-diazo Carbonyl Compounds: A Novel Approach to Pyrrole Derivatives

Guisheng Deng, Nan Jiang, Zhihua Ma, Jianbo Wang*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry, Peking University, Beijing 100871, P. R. China
Fax: +86(10)62751708; e-Mail: wangjb@pku.edu.cn;

Abstract

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Abstract

(N-Tosyl)amino substituted β-keto diazo carbonyl compounds have been prepared by reaction of titanium enolate of β-ketodiazoester or -ketone with an activated N-tosylimine. Rh₂(OAc)₄-catalyzed reaction of the (N-tosyl)amino substituted α-diazocarbonyl compounds leads to the efficient formation of pyrrole derivatives.

Key words

pyrroles - diazo compounds - Ti(IV) enolate - nucleophilic additions - Rh(II) carbene

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References

1 Comprehensive Heterocyclic Chemistry Vol. 2: Bird CW. Pergamon Press; Oxford: 1996.

For recent examples of pyrrole syntheses based on Paal-Knorr reaction, see:

2a Hewton CE. Kimber MC. Taylor DK. Tetrahedron Lett. 2002, 43: 3199

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3a Chen N. Lu Y. Gadamasetti K. Hurt CR. Norman MH. Fotsch C. J. Org. Chem. 2000, 65: 2603

3b Katritzky AR. Huang T.-B. Voronkov MV. Wang M. Kolb H. J. Org. Chem. 2000, 65: 8819

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5c Calter MA. Zhu C. J. Org. Chem. 1999, 64: 1415

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General procedure for the TiCl₄-promoted condensation of α-diazo-β-ketoester 1 with N-tosylimine: To a solution of 2a (10.0 mmol) in anhydrous CH₂Cl₂ (20 mL) at -41 °C were added dropwise TiCl₄ (11.0 mmol) and Et₃N (11.0 mmol). After the resulting red-dark solution was stirred at -41 °C for 1 h, a solution of N-tosylimine (4 mmol) in anhydrous CH₂Cl₂ (4 mL) was added dropwise. The reaction mixture was stirred at -41 °C for 9 h and then was quenched with saturated aqueous NH₄Cl (5 mL). The organic layer was separated and the aqueous layer was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic layers were washed with saturated aqueous NaHCO₃ (2 × 20 mL), and then dried over Na₂SO₄. The product was purified by flash chromatography to yield 3a (Ar = Ph) as white solid (1.03 g, 62%). Mp 140-142 °C; IR (KBr) 3223, 2152, 1748, 1625 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 1.32 (t, J = 7 Hz, 3 H), 2.37 (s, 3 H), 3.19 (dd, J = 15.6, 5.4 Hz, 1 H), 3.36 (dd, J = 15.6, 8 Hz, 1 H), 4.28 (q, J = 7 Hz, 2 H), 4.76-4.86 (m, 1 H), 5.69 (d, J = 7.8 Hz, 1 H), 7.14-7.20 (m, 7 H), 7.58 (d, J = 8.2 Hz, 2 H); ¹³C NMR (50 MHz, CDCl₃) δ 14.2, 21.4, 46.3, 54.5, 61.6, 76.8, 126.3, 127.0, 127.4, 128.4, 129.2, 137.4, 140.1, 143.0, 161.1, 189.8; MS m/z (FAB): 416 [(M+H)⁺, 13], 388 (3), 344 (2), 261 (11), 245 (69), 219 (20), 181 (12), 171 (49), 139 (23), 115 (38), 91 (100), 77 (22), 59 (38), 41 (53). Anal. Calcd for C₂₀H₂₁N₃O₅S: C, 57.82; H, 5.09; N, 10.11. Found: C, 57.85; H, 5.09; N, 10.01.

For examples of intramolecular N-H bond insertion, see:

7a Moyer MP. Feldman PL. Rapoport H. J. Org. Chem. 1985, 50: 5223

7b Wang J. Hou Y. J. Chem. Soc., Perkin Trans. 1 1999, 2277

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General procedure for the diazo decomposition of 3 with catalyst Rh₂(OAc)₄: A solution of 3a (Ar = Ph, 1.0 mmol) in benzene (30 mL) containing Rh₂(OAc)₄ (0.01 mmol) was heated under reflux for 10 min. The solution was cooled to room temperature and was concentrated. Purification by flash chromatography provided 4a (Ar = Ph, 75% yield) as white solid.
4a: Mp 138-140 °C; IR (KBr) 3453, 3304, 3278, 1692
cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 1.37 (t, J = 7.2 Hz, 3 H), 4.37 (q, J = 7.2 Hz, 2 H), 6.16 (d, J = 3.2 Hz, 1 H), 7.25-7.79 (m, 5 H), 7.91 (br, s, 1 H), 8.76 (br, d, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 14.6, 61.2, 95.9, 106.2, 124.9, 128.2, 128.6, 131.1, 136.0, 155.2, 162.0; MS m/z (EI) 231 (M⁺, 91), 203 (3), 185 (100), 156 (18), 129 (12), 102 (72), 77 (14), 51 (6); Anal. Calcd for C₁₃H₁₃NO₃: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.45; H, 5.59; N, 5.91.
4b: Mp 91-93 °C; IR (KBr) 3489, 3310, 1696, 1677 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 1.37 (t, J = 7.2 Hz, 3 H), 2.43 (s, 3 H), 4.35 (q, J = 7.2 Hz, 2 H), 5.98 (d, J = 2.6 Hz, 1 H), 7.23-7.37(m, 4 H), 7.76 (br, s, 1 H), 8.11 (br, s, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 14.5, 20.7, 60.0, 98.8, 105.5, 126.0, 128.3, 128.4, 130.9, 131.5, 135.7, 135.9, 153.7(br), 162.0(br); MS m/z (EI) 245 (M⁺, 100), 222 (3), 199 (93), 193 (28), 171 (12), 144 (12), 134 (12), 123 (28), 116 (63), 95 (7), 91 (6), 77 (6), 57 (6), 43 (7). Anal. Calcd for C₁₄H₁₅NO₃: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.45; H, 6.18; N, 5.61.
4c: Mp 203 °C; IR (KBr) 3501, 3337, 2227, 1669 cm^-1; ¹H NMR (200 MHz, CDCl₃/DMSO-d ₆) δ 1.41 (t, J = 7.2 Hz, 3 H), 4.39 (q, J = 7.2 Hz, 2 H), 6.17 (d, J = 2.8 Hz, 1 H), 7.44-7.56 (m, 2 H), 7.89-7.95 (m, 2 H), 8.15 (s, 1 H), 10.91 (br, s, 1 H); ¹³C NMR (50 MHz, CDCl₃/DMSO-d ₆) δ 14.1, 59.4, 95.7, 106.9, 112.0, 118.1, 128.0, 128.9, 129.9, 132.2, 132.5, 152.7, 161.4; MS m/z (EI) 256 (M⁺, 14), 241 (2), 210 (20), 178 (5), 171 (43), 155 (57), 127 (14), 107 (22), 91 (100), 65 (39), 57 (31), 39 (18); Anal. Calcd for C₁₄H₁₂N₂O₃: C, 65.62; H, 4.72; N, 10.93. Found: C, 65.81; H, 4.59; N, 10.83.
4d: Mp 150-152 °C; IR (KBr) 3269, 1680, 1661 cm^-1; ¹H NMR (200 MHz, CDCl₃/DMSO-d ₆) δ 1.37 (t, J = 7.2 Hz,
3 H), 4.34 (q, J = 7.2 Hz, 2 H), 5.94 (d, J = 2.8 Hz, 1 H), 6.88 (d, J = 16.4 Hz, 1 H), 7.06 (d, J = 16.4 Hz, 1 H), 7.21-7.44 (m, 5 H), 7.91 (s, 1 H), 11.0 (br s, 1 H); ¹³C NMR (50 MHz, CDCl₃/DMSO-d ₆) δ 14.0, 58.9, 94.8, 105.2, 117.6, 125.4, 126.9, 127.9, 128.3, 133.8, 136.0, 152.6, 161.1; MS m/z (EI) 257 (M⁺, 100), 210 (88), 183 (11), 182 (6), 167 (8), 154 (28), 128 (46), 102 (5), 77 (6), 51 (5), 29 (5); Anal. Calcd for C₁₅H₁₅NO₃: C, 70.02; H, 5.88; N, 5.44. Found: C, 70.22; H, 6.08; N, 5.29.
4e: Mp 131-133 °C; IR (KBr) 3306, 1667, 1564 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 1.38 (t, J = 7.2 Hz, 3 H), 4.38 (q, J = 7.2 Hz, 2 H), 6.06 (d, J = 2.6 Hz, 1 H), 6.45-6.47 (m, 1 H), 6.56 (d, J = 3.4 Hz, 1 H), 7.41-7.42 (m, 1 H), 7.92 (br s, 1 H), 8.59 (br s, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 14.5, 60.1, 94.6, 105.4, 106.2, 111.7, 126.8, 142.0, 146.5, 154.4, 162.1; MS m/z (EI) 221 (M⁺, 95), 193.3 (4), 175 (100), 147 (26), 139 (2), 119 (15), 92 (52), 91 (8), 63 (15), 39 (12); Anal. Calcd for C₁₁H₁₁NO₄: C, 59.73; H, 5.01; N, 6.33. Found: C, 59.65; H, 4.97; N, 6.13.
4f: Mp 129-130 °C; IR (KBr) 3502, 3289, 1677, 1574, 1539 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 1.38 (t, J = 7.2 Hz, 3 H), 4.37 (q, J = 7.2 Hz, 2 H), 5.99 (d, J = 3Hz, 1 H), 6.93-7.26 (m, 2 H), 8.08 (br s, 1 H), 8.84 (br, s, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 14.5, 60.3, 96.6, 123.7, 127.9, 129.7, 130.7, 131.9, 139.0, 144.5, 160.9; MS m/z (EI) 317 (M⁺, ⁸⁰Br, 74), 315 (M⁺, ⁷⁸Br, 71), 271 (100), 242 (12), 215 (9), 188 (37), 162 (76), 155 (17), 133 (14), 108 (19), 91 (40), 82 (9), 63 (14), 45 (5); Anal. Calcd for C₁₁H₁₀BrNO₃S: C, 41.79; H, 3.19; N, 4.43. Found: C, 41.85; H, 3.26; N, 4.40.
4g: Mp 139-142 °C; IR (KBr) 3320, 1590, 1567 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 6.14 (d, J = 2.4 Hz, 1 H), 6.50 (dd, J = 3.5, 1.7 Hz, 1 H), 6.66 (d, J = 3.5 Hz, 1 H), 7.44 (d, J = 1.7 Hz, 1 H), 7.50-7.59 (m, 3 H), 7.77-7.82 (m, 2 H), 8.26 (br s, 1 H), 10.43 (br s, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 94.8, 108.2, 112.1, 116.0, 127.5, 129.0, 129.8, 131.6, 137.7, 142.7, 145.9, 159.3, 184.0; MS m/z (EI) 253 (M⁺, 100), 236 (5), 224 (4), 196 (4), 176 (30), 147 (7), 120 (9), 105 (37), 92 (24), 91 (3), 77 (49), 65 (20), 51 (17), 39 (15); Anal. Calcd for C₁₅H₁₁NO₃: C, 71.14; H, 4.38; N, 5.53. Found: C, 70.98; H, 4.37; N, 5.46.
4h: Mp 159-161 °C; IR (KBr) 3322, 2261, 1626, 1592, 1550, 1503 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 6.10 (d, J = 2 Hz, 1 H), 6.79 (d, J = 16.5 Hz, 1 H), 7.00 (d, J = 16.5 Hz, 1 H), 7.28-7.54 (m, 8 H), 7.68-7.72 (m, 2 H), 8.41 (br s, 1 H), 10.40 (br s, 1 H); ¹³C NMR (50 MHz, CDCl₃) δ 96.3, 116.6, 117.3, 126.6, 127.5, 128.5, 128.8, 128.9, 131.6, 132.0, 135.9, 137.7, 138.0, 159.5, 183.8; MS m/z (EI) 289 (M⁺, 100), 288 (27), 270 (10), 212 (13), 156 (6), 128 (23), 105 (49), 77 (31), 51 (7); Anal. Calcd for C₁₉H₁₅NO₂: C, 78.87; H, 5.23; N, 4.84. Found: C, 78.80; H, 5.21; N, 4.74.
4i: Mp 178-180 °C(decomposed); IR (KBr) 3272, 1614, 1585, 1534 cm^-1; ¹H NMR (200 MHz, CDCl₃) δ 2.48 (s, 3 H), 3.85 (s, 3 H), 6.01 (d, J = 2.8 Hz, 1 H), 6.93 (d, J = 8.6 Hz, 2 H), 7.62 (d, J = 8.6 Hz, 2 H), 9.47 (br s, 1 H), 10.59 (br, s, 1 H); MS m/z (EI) 231 (M⁺, 100), 216 (93), 202 (9), 188 (5), 174 (8), 161 (15), 146 (4), 133 (18), 118 (7), 117 (8), 102 (3), 89 (12), 77 (4), 63 (6), 43 (13); Anal. Calcd for C₁₃H₁₃NO₃: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.41; H, 5.71; N, 6.01.

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p-Toluenesufinic acid was further converted to thiosulfonic ester, which is isolated and characterized.