5-endo-dig Cyclisations of homopropargylic sulfonamides: a new route to 2,3-dihydropyrroles and β-iodopyrroles

Abstract

5-endo-dig Iodocyclisations of the homopropargylic sulfonamides 12a–c and 13 give excellent yields of the iododihydropyrroles 14a–d and thence the β-iodopyrroles 15a–d, following base-catalysed elimination of sulfinic acid.

References

1. A. D. Jones and D. W. Knight, Chem. Commun., 1996, 915.
2. J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734 and 738.
3. S. H. Kang and S. B. Lee, Tetrahedron Lett., 1993, 34, 1995, 7579; J. M. Barks, D. W. Knight, C. J. Seaman and G. G. Weingarten, Tetrahedron Lett., 1994, 35, 7259; B. H. Lipshutz and T. Gross, J. Org. Chem., 1995, 60, 3572; K. Chibale and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1996, 1935; M. B. Berry, D. Craig, P. S. Jones and G. J. Rowlands, Chem. Commun., 1997, 2141; O. Andrey, L. Ducry, Y. Landais, D. Planchenault and V. Weber, Tetrahedron, 1997, 53, 4339; B. H. Lipshutz and T. Gross, J. Org. Chem., 1995, 60, 3572 and references cited therein in each.
4. D. W. Knight, A. L. Redfern and J. Gilmore, Synlett, 1998, 731.
5. S. P. Bew and D. W. Knight, Chem. Commun., 1996, 1007.
6. M. J. O'Donnell and R. L. Polt, J. Org. Chem., 1982, 47, 2663.
7. A. Lopez, M. Moreno-Manas, R. Pleixats, A. Roglans, J. Ezquerra and C. Pedregal, Tetrahedron, 1996, 52, 8365.
8. K. Sonogashira, Comp. Org. Synth., 1991, 3, 521.
9. Typical experimental procedure for 14b: The tosylamide 12b(70 mg, 0.20 mmol) was stirred in dry MeCN (1 ml) containing anhydrous K₂CO₃(84 mg, 0.61 mmol) and cooled in an ice bath. I₂(153 mg, 0.61 mmol) in MeCN (0.6 ml) was added dropwise and the resulting suspension stirred overnight without the addition of further coolant. Saturated aq. sodium thiosulfate was then added until the excess I₂ was decolourized and the organic layer separated. The aqueous layer was extracted with CH₂Cl₂(2 × 5 ml) and the combined organic solutions dried (MgSO₄) and evaporated. Column chromatography of the residue (6∶1 hexane–EtOAc) gave 14b(74 mg, 78%) as a pale yellow solid, mp 88–92 °C, v_max/cm^–1 2953, 1742, 1597, 1437, 1361, 1212, 1170, 1089, 1017; δ_H(CDCl₃; 400 MHz) 2.45 (3H, s, Ar-CH₃), 2.59 (1H, dd, J 17.1 and 9.7, 3-H_a), 2.85 (1H, dd, J 17.1 and 2.4, 3-H_b), 3.82 (3H, s, OCH₃), 4.83 (1H, dd, J 9.7 and 2.4, 2-H), 6.50 (1H, dd, J 3.4 and 1.8, 4′-H), 6.89 (1H, d, J 3.4, 3′-H), 7.31 (2H, d, J 8.2, 2 × Ar-H), 7.47 (1H, app. br s, 5′-H), 7.60 (2H, d, J 8.2, 2 × Ar-H); δ_C(CDCl₃; 100 MHz) 21.6 (Ar-CH₃), 43.5 (3-CH₂), 53.1 (OCH₃), 62.2 (2-CH), 77.6 (4-C), 111.0 (4′-CH), 113.9 (3′-CH), 127.8 (2 × Ar-CH), 129.6 (2 × Ar-CH), 133.5 (C), 135.8 (C), 143.1 (5′-CH), 144.6 (C), 144.8 (C) and 170.6 (CO); m/z(EI) 473 (M⁺, 27%), 318 (17), 191 (88), 159 (51), 132 (56), 104 (55), 91 (100)[Found: C, 42.8; H, 3.4; N, 3.1. C₁₇H₁₆INO₅S requires C, 43.1; H, 3.4; N, 3.0%]. For elimination of toluene-p-sulfinic acid: To a stirred solution of the 14(1 mmol) in dry DMF (5 ml) at ambient temperature, DBU (0.3 ml, 2.1 mmol) was added dropwise and the elimination followed by TLC. Upon completion (ca. 12 h), 2 M HCl (5 ml) was added and the resulting mixture extracted with hexane (4 × 20 ml). The combined extracts were dried (MgSO₄) and concentrated, then passed through a short silica plug; evaporation of the filtrate left the pure iodopyrrole 15. Selected data for 15b: pale yellow solid, mp 120–124 °C; v_max/cm^–1 3282, 2951, 1697, 1508, 1437, 1395, 1317, 1262, 1203; δ_H(CDCl₃; 400 MHz) 3.88 (3H, s, OCH₃), 6.53 (1H, dd, J 3.5 and 1.6, 4′-H), 7.07 (1H, d, J 2.7, 3-H), 7.21 (1H, d, J 3.5, 3′-H), 7.47 (1H, d, J 1.6, 5′-H), 9.45 (1H, br s, NH); δ_C(CDCl₃; 100 MHz) 5.19 (OCH₃), 65.2 (4-C), 107.8, 111.8, 124.5 (all Ar-CH), 129.0, 136.0, 140.5 (all Ar-C), 142.0 (Ar-CH), 162.5 (CO); m/z(EI) 317 (M⁺, 79%), 285 (59), 130 (70), 76 (79), 57 (100)[Found: M⁺, 316.9551. C₁₀H₈INO₃ requires M, 316.9551].
10. J. J. Wang and A. I. Scott, Tetrahedron Lett., 1995, 36, 7043 See also J. J. Wang and A. I. Scott, Tetrahedron Lett., 1996, 37, 3247.
11. A. Alvarez, A. Guzman, A. Ruiz, E. Velarde and J. M. Muchowski, J. Org. Chem., 1992, 57, 1653; P. A. Jacobi, J. S. Guo, S. Rajeswari and W. J. Zheng, J. Org. Chem., 1997, 62, 2907 and references cited therein.