Tandem Meinwald Rearrangement-Fischer Indolisation: A One-Pot Conversion of Epoxides into Indoles

Abstract

A tandem Sc(OTf)₃-mediated Meinwald epoxide re­arrangement-Fischer indole synthesis is reported. Optimisation and scope and limitation studies are described. In addition, preliminary investigations to develop a telescoped epoxidation-Meinwald re­arrangement-Fischer indole sequence are outlined.

Key words

aldehydes - epoxides - indoles - rearrangements - tandem reactions

References and Notes

• For recent examples, see:
• 1a Taylor RJK. Reid M. Foot JS. Raw SA. Acc. Chem. Res.  2005,  38:  851 ; and references cited therein
• 1b Robinson RS. Taylor RJK. Synlett  2005,  1003 
• 1c Cayley AN. Cox RJ. Ménard-Moyon C. Schmidt JP. Taylor RJK. Tetrahedron Lett.  2007,  48:  6556 
• 1d Donald JR. Edwards MG. Taylor RJK. Tetrahedron Lett.  2007,  48:  5201 
• 2a Meinwald J. Labana SS. Chadha MS. J. Am. Chem. Soc.  1963,  85:  582 
• 2b For a review, see: Rickborn B. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon; Oxford: 1991.  p.733 
• For recent examples, see:
• 3a Maruoka K. Murase N. Bureau R. Ooi T. Yamamoto H. Tetrahedron  1994,  50:  3663 
• 3b Suda K. Kikkawa T. Nakajima S. Takanami T. J. Am. Chem. Soc.  2004,  126:  9554 
• 3c Procopio A. Dalpozzo R. De Nino A. Nardi M. Sindona G. Tagarelli A. Synlett  2004,  2633 
• For recent examples, see:
• 4a Takanami T. Hirabe R. Ueno M. Hino F. Suda K. Chem. Lett.  1996,  1031 
• 4b Kulasegaram S. Kulawiec RJ. J. Org. Chem.  1997,  62:  6547 
• For recent examples, see:
• 5a Srikrishna A. Satyanarayana G. Prasad KR. Synth. Commun.  2007,  37:  1511 
• 5b Wilson MS. Woo JCS. Dake GR. J. Org. Chem.  2006,  71:  4237 
• 5c Vital P. Tanner D. Org. Biomol. Chem.  2006,  4:  4292 
• 5d For a review, see: Silva LF. Tetrahedron  2002,  58:  9137 ; and references cited therein
• For recent examples, see:
• 6a Wang L. Maddess ML. Lautens M. J. Org. Chem.  2007,  72:  1822 
• 6b Nokami J. Maruoka K. Souda T. Tanaka N. Tetrahedron  2007,  63:  9016 
• 6c Albert BJ. Koide K. J. Org. Chem.  2008,  73:  1093 
• 7 D’Ischia M. Napolitano A. Pezzella A. In Comprehensive Heterocyclic Chemistry III   Katritzky AR. Ramsden CA. Scriven EFV. Taylor RJK. Elsevier; Oxford: 2008.  p.Chap. 3.04 ; and references therein
• For recent reviews, see:
• 8a Hughes DL. Org. Prep. Proced. Int.  1993,  25:  607 
• 8b Robinson B. The Fischer Indole Synthesis   Wiley; Chichester: 1982. 
• 9 See, for example: Robinson MWC. Pillinger KS. Graham AE. Tetrahedron Lett.  2006,  47:  5919; and references therein 
• 10 Rodríguez JG. Lafuente A. García-Almaraz P. J. Heterocycl. Chem.  2000,  37:  1281 
• 11 Manabe K. Nobutou D. Kobayashi S. Bioorg. Med. Chem.  2005,  13:  5154 
• 12a Anderson AM. Blazek JM. Garg P. Payne BJ. Mohan RS. Tetrahedron Lett.  2000,  41:  1527 
• 12b Johnson AP. Luke RWA. Singh G. Boa AN. J. Chem. Soc., Perkin Trans. 1  1996,  907 
• 13 Blades CE. Wilds AL. J. Org. Chem.  1956,  21:  1013 
• 15a Brown DW. Graupner PR. Sainsbury M. Shertzer HG. Tetrahedron  1991,  47:  4383 
• 15b Armit JW. Robinson R. J. Chem. Soc. Trans.  1922,  121:  827 
• 16 Sanz R. Castroviejo MP. Guilarte V. Pérez A. Fañanás FJ. J. Org. Chem.  2007,  72:  5113 
• 17 Herrmann WA. Fischer RW. Marz DW. Angew. Chem., Int. Ed. Engl.  1991,  30:  1638 

14

All novel compounds were fully characterized.
3-(2′-Benzofuranyl) indole (6a)
Pale orange microcrystals; mp 162-163 ˚C (heptane); R _f  = 0.27 (PE-Et₂O, 4:1). ^¹H NMR (400 MHz, CDCl₃): δ = 8.33 (br s, 1 H), 8.05-8.00 (m, 1 H), 7.71 (d, J = 2.5 Hz, 1 H), 7.57-7.52 (m, 1 H), 7.49-7.45 (m, 1 H), 7.44-7.39 (m, 1 H), 7.29-7.24 (m, 2 H), 7.23-7.16 (m, 2 H), 6.91 (s, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 154.0, 152.9, 136.6, 129.9, 124.6, 123.3, 123.12, 123.08, 122.8, 121.1, 120.4, 120.3, 111.7, 110.8, 108.8, 99.7. IR (neat): ν_max = 3399, 2918, 2850, 1623, 1453, 1427, 1358, 1249, 1100 cm^-¹. MS (EI⁺): m/z (%) = 233 (97) [M⁺ ], 135 (38), 97 (37), 95 (50), 93 (37), 91 (52), 83 (37), 81 (63), 79 (50), 71 (51), 69 (71), 67 (100), 57 (73), 55 (91), 43 (48), 41 (52). HRMS (EI⁺): m/z calcd for C₁₆H₁₁NO: 233.0841; Found: 233.0842 [M⁺ ] (0.4 ppm error).
1-Methyl-3-(2′-benzofuranyl) indole (6b) Colourless microcrystals; mp 109-110 ˚C (i-PrOH); R _f  = 0.44 (PE-Et₂O, 7:3). ^¹H NMR (400 MHz, CDCl₃): δ = 8.06 (dd, J = 8.0, 1.0 Hz, 1 H), 7.62 (s, 1 H), 7.60-7.57 (m, 1 H), 7.54-7.49 (m, 1 H), 7.40 (dd, J = 7.5, 1.5 Hz, 1 H), 7.35 (app. td, J = 7.5, 1.5 Hz, 1 H), 7.31 (app. td, J = 7.5, 1.5 Hz, 1 H), 7.27-7.22 (m, 2 H), 6.91 (d, J = 0.5 Hz, 1 H) 3.85 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 154.0, 153.1, 137.5, 130.0, 127.7, 125.1, 123.1, 122.8, 122.6, 120.7, 120.5, 120.1, 110.7, 109.9, 107.0, 99.1, 33.2. IR (neat): ν_max = 3053, 2924, 2853, 1624, 1609, 1468, 1452, 1371, 1254, 1203, 1156, 1088, 1014 cm^-¹. MS (EI⁺): m/z (%) = 247 (100) [M⁺ ], 232 (26). HRMS (EI⁺): m/z calcd for C₁₇H₁₃NO: 247.0997; found: 247.0987 [M⁺ ] (4.0 ppm error). Anal. Calcd for C₁₇H₁₃NO: C, 82.57; H, 5.30; N, 5.66. Found: C, 82.39; H, 5.36; N, 5.57.
4,6-Dichloro-3-phenylindole (11) Orange oil; R _f  = 0.16 (PE-Et₂O, 4:1). ^¹H NMR (400 MHz, CDCl₃): δ = 8.30 (br s, 1 H), 7.50 (dd, J = 8.0, 1.5 Hz, 2 H), 7.42-7.36 (m, 3 H), 7.34 (d, J = 2.0 Hz, 1 H), 7.19 (d, J = 2.5 Hz, 1 H), 7.15 (d, J = 2.0 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 137.5, 134.5, 131.0, 128.1, 127.6, 127.2, 126.9, 124.9, 122.3, 121.9, 119.5, 110.1. IR (neat): ν_max = 3417, 3079, 2921, 2851, 1601, 1546, 1474, 1423, 1393, 1188, 1129, 1105, 1076 cm^-¹. MS (EI⁺): m/z (%) = 263 (64) [^³7Cl^³5ClM⁺ ], 261 (100) [^³5Cl^³5ClM⁺ ], 199 (25). HRMS (EI⁺): m/z calcd for C₁₄H₉NCl₂: 261.0112; found: 261.0108 [M⁺ ] (1.5 ppm error)].