Gold-Catalyzed Conjugate Addition Type Reaction of Indoles with α,β-Enones

Antonio Arcadi; Gabriele Bianchi; Marco Chiarini; Gaetano D’Anniballe; Fabio Marinelli

doi:10.1055/s-2004-822903

LETTER

Gold-Catalyzed Conjugate Addition Type Reaction of Indoles with α,β-Enones

Antonio Arcadi*^a, Gabriele Bianchi^a, Marco Chiarini^a, Gaetano D’Anniballe^b, Fabio Marinelli^a
^a Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università di L’Aquila, Via Vetoio, Coppito Due, 67010 L’Aquila, Italy
^b Dompé Research Center, Località Campo di Pile, 67100 L’Aquila, Italy
Fax: +39(0862)433753; e-Mail: arcadi@univaq.it;

Abstract

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Abstract

3-Unsubstituted indoles undergo regioselective alkylation at the 3-position of the indole nucleus through gold-catalyzed conjugated addition type reaction with α,β-enones. 3-Substituted indoles undergo C-2 alkylation. Sequential C-3/C-2 gold catalyzed alkylation of the indole with dibenzylidene acetone gives a polycyclic indole b-annulated with a seven-membered cycle.

Key words

gold catalysis - indoles - α,β-enones - conjugated addition

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References

<A NAME="RG02004ST-1A">1a</A> Joule JA. In Science of Synthesis Vol. 10: Thomas EJ. Thieme; Stuttgart: 2000. p.361-652

<A NAME="RG02004ST-1B">1b</A> Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000, 1045

<A NAME="RG02004ST-1C">1c</A> Lounasmaa M. Tolvanen A. Nat. Prod. Rep. 2000, 17: 75

<A NAME="RG02004ST-2A">2a</A> Sezen B. Sames D. J. Am. Chem. Soc. 2003, 125: 5274

<A NAME="RG02004ST-2B">2b</A> Beccalli EM. Broggini G. Tetrahedron Lett. 2003, 44: 1919

<A NAME="RG02004ST-3">3</A> Wang S.-Y. Ji S.-J. Loh T.-P. Synlett 2003, 2377

<A NAME="RG02004ST-4A">4a</A> Agnusdei M. Bandini M. Melloni A. Umani-Ronchi A. J. Org. Chem. 2003, 68: 7126

<A NAME="RG02004ST-4B">4b</A> Bandini M. Fagioli M. Melchiorre P. Melloni A. Umani-Ronchi A. Tetrahedron Lett. 2003, 44: 5843

<A NAME="RG02004ST-4C">4c</A> Jørgensen KA. Synthesis 2003, 1117

<A NAME="RG02004ST-4D">4d</A> Yadav JS. Reddy BVS. Satheesh G. Tetrahedron Lett. 2003, 44: 8331

<A NAME="RG02004ST-4E">4e</A> Evans DA. Scheidt KA. Fandrik KR. Wai Lam H. Wu J. J. Am. Chem. Soc. 2003, 125: 10780

<A NAME="RG02004ST-4F">4f</A> Bandini M. Fagioli M. Melloni A. Umani-Ronchi A. Synthesis 2003, 397

<A NAME="RG02004ST-4G">4g</A> Bandini M. Cozzi PG. Giacobini M. Melchiorre P. Selva S. Umani-Ronchi A. J. Org. Chem. 2002, 67: 3700

<A NAME="RG02004ST-4H">4h</A> Yadav JS. Reddy BVS. Abraham S. Sabitha G. Synlett 2002, 1550

<A NAME="RG02004ST-4I">4i</A> Harrington PE. Kerr MA. Synlett 1996, 1047

<A NAME="RG02004ST-5A">5a</A> Bartoli G. Bertolacci M. Bosco M. Foglia G. Giuliani A. Marcantoni E. Sembri L. Torregiani E. J. Org. Chem. 2003, 68: 4594

<A NAME="RG02004ST-5B">5b</A> Ji SH. Wang S.-Y. Synlett 2003, 2074

<A NAME="RG02004ST-5C">5c</A> Ji SH. Zhou M.-F. Gu D.-G. Wang S.-Y. Loh T.-P. Synlett 2003, 2077

<A NAME="RG02004ST-5D">5d</A> Reddy AV. Ravinder K. Goud TV. Krishnaiah P. Raju TV. Venkateswarlu Y. Tetrahedron Lett. 2003, 44: 6257

<A NAME="RG02004ST-5E">5e</A> Alam MM. Varala R. Adapa SR. Tetrahedron Lett. 2003, 44: 5115

<A NAME="RG02004ST-6">6</A> For a recent review on gold catalysis, see: Dyker G. Angew. Chem. Int. Ed. 2000, 39: 4237

<A NAME="RG02004ST-7A">7a</A> Casado R. Contel M. Laguna M. Romero P. Sanz S. J. Am. Chem. Soc. 2003, 125: 11925

<A NAME="RG02004ST-7B">7b</A> Dyker G. Hildebrandt D. Liu J. Merz K. Angew. Chem. Int. Ed. 2003, 42: 4399

<A NAME="RG02004ST-7C">7c</A> Asao N. Nogami T. Lee S. Yamamoto Y. J. Am. Chem. Soc. 2003, 125: 10921

<A NAME="RG02004ST-7D">7d</A> Hashmi AS. Ding L. Bats JW. Fischer P. Frey W. Chem.-Eur. J. 2003, 9: 4339

<A NAME="RG02004ST-7E">7e</A> Mizushima E. Hayashi T. Tanaka M. Org. Lett. 2003, 5: 3349

<A NAME="RG02004ST-7F">7f</A> Abbiati G. Arcadi A. Bianchi G. Di Giuseppe S. Marinelli F. Rossi E. J. Org. Chem. 2003, 68: 6959

<A NAME="RG02004ST-7G">7g</A> Arcadi A. Bianchi G. Di Giuseppe G. Marinelli F. Green Chem. 2003, 5: 64

<A NAME="RG02004ST-7H">7h</A> Arcadi A. Chiarini M. Di Giuseppe S. Marinelli F. Synlett 2003, 203

<A NAME="RG02004ST-7I">7i</A> Krause N. Hoffmann-Röder A. Canisius J. Synthesis 2002, 1759

<A NAME="RG02004ST-7J">7j</A> Arcadi A. Di Giuseppe S. Marinelli F. Rossi E. Tetrahedron: Asymmetry 2001, 12: 2715

<A NAME="RG02004ST-7K">7k</A> Arcadi A. Di Giuseppe S. Marinelli F. Rossi E. Adv. Synth. Catal. 2001, 343: 443

<A NAME="RG02004ST-7L">7l</A> Dankwardt JW. Tetrahedron Lett. 2001, 42: 5809

<A NAME="RG02004ST-8">8</A> Wei C. Li C.-J. J. Am. Chem. Soc. 2003, 125: 9584

<A NAME="RG02004ST-9">9</A> Fuchita Y. Utsunomiya Y. Yasutake M. J. Chem. Soc., Dalton Trans. 2001, 2330

<A NAME="RG02004ST-10">10</A> Zamora F. Zangrado E. Furlan M. Randaccio L. Lippert B. J. Organomet. Chem. 1998, 552: 127

<A NAME="RG02004ST-11">11</A> Zamora F. Amo-Ochoa P. Fischer B. Scimanski A. Lippert B. Angew. Chem. Int. Ed. 1999, 38: 2274

<A NAME="RG02004ST-12">12</A> Reetz MT. Sommer K. Eur. J. Org. Chem. 2003, 3485

<A NAME="RG02004ST-13">13</A> Hasmi ASK. Schwarz L. Choi J.-H. Frost TM. Angew. Chem. Int. Ed. 2000, 39: 2285

<A NAME="RG02004ST-14">14</A> Formation of 3-indolylaurate species by aminoauration of 2-alkynylanilines was suggested by: Iritani K. Matsubara S. Utimoto K. Tetrahedron Lett. 1988, 29: 1799

<A NAME="RG02004ST-15">15</A> Dyker G. Muth E. Hashmi ASK. Ding L. Adv. Synth. Catal. 2003, 345: 1247

General Procedure for the Synthesis of Indoles 3. To a 1:1 mol ratio solution of indole 1 and α,β-enone 2 in EtOH was added NaAuCl₄·2H₂O (5 mol%). The resulting mixture was allotted to react under stirring at r.t. or at 30 °C and the reaction was monitored by TLC or GC-MS. After completion, the solvent was removed by evaporation. To the residue, acetone (few mL) was added to precipitate the catalyst, which was separated by filtration. The filtrate was concentrated and the crude products were purified by chromatography on silica gel (230-400 mesh) eluting with n-hexane/EtOAc mixtures.

Selected data for 3b: IR (neat): 3420, 1725 cm^-1. ¹H NMR: δ = 8.25 (bs, 1 H), 7.64-7.60 (m, 1 H), 7.24-7.03 (m, 3 H), 6.80 (d, J = 2.3 Hz, 1 H), 3.47-3.40 (m, 1 H), 2.84-2.76 (m, 2 H), 1.95 (s, 3 H), 1.73-1.63 (m, 2 H), 1.25-1.15 (m, 4 H), 0.77 (t, J = 3.9 Hz, 3 H). ¹³C NMR: δ = 209.51, 136.39, 126.34, 121.55, 121.26, 119.02, 118.86, 118.38, 111.31, 50.07, 35.49, 32.73, 30.24, 29.63, 22.51, 13.89. MS: m/e (relative intensity) = 244 (100) [M + 1]⁺, 243 (35) [M⁺], 186 (63). 3c: IR (KBr): 3430, 1715 cm^-1. ¹H NMR (diastereomeric mixture, 2:1 ratio): δ = 7.80 (bs, 2 H), 7.39-7.03 (m, 18 H), 6.73 (bs, 2 H), 4.82 (t, J = 7.4 Hz, 2 H), 3.24 (dd, J = 16.3 and 7.4 Hz, 2 H), 3.09 (dd, J = 16.3 and 7.4 Hz, 2 H);(diastereoisomer) δ = 7.78 (bs, 2 H), 7.32-7.00 (m, 18 H), 6.69 (bs, 2 H), 4.82 (t, J = 7.4 Hz, 2 H), 3.19 (dd, J = 16.3 and 7.5 Hz, 2 H), 3.09 (dd, J = 16.3 and 7.5 Hz, 2 H). ¹³C NMR (diastereomeric mixture, 2:1 ratio): δ = 207.79, 143.97 136.65, 128.37, 127.66, 126.59, 126.19, 122.11, 121.62, 119.54, 119.45, 118.85, 111.09, 49.77, 38.12; (diastereoisomer) δ = 207.70, 144.15, 136.62, 128.43, 127.77, 126.64, 126.26, 122.11, 121.49, 119.50, 119.40, 118.78, 111.05, 49.90, 38.18. ESI-MS: m/e (relative intensity) = 469 (100) [M + 1⁺]. 3e: IR (KBr): 3360, 1720 cm^-1. ¹H NMR: δ = 8.28 (bs, 1 H), 7.44 (s, 1 H), 7.17 (s, 1 H), 7.04 (s, 1 H), 2.96 (t, J = 7.2 Hz, 2 H), 2.79 (t, J = 7.2 Hz, 2 H), 2.13 (s, 3 H). ¹³C NMR: δ = 208.03, 135.59, 132.11, 129.09, 123.61, 121.49, 116.21, 117.06, 43.73, 29.99, 19.07. MS: m/e (relative intensity) = 259 (10) [M⁺], 257 (63) [M⁺], 256 (63) [M + 1]⁺, 255 (100) [M⁺], 214 (34), 213 (49), 212 (19), 200(83), 199 (100), 198 (39). 3f: IR (KBr): 3400, 1710 cm^-1. ¹H NMR: δ = 8.20 (bs, 1 H), 7.57-7.14 (m, 9 H), 3.19-3.11 (m, 2 H), 2.79-2.71 (m, 2 H), 2.05 (s, 3 H). ¹³C NMR: δ = 208.93, 135.86, 134.44, 132.97, 128.86, 128.66, 127.89, 127.68, 122.27, 119.59, 118.82, 111.55, 110.97, 44.45, 29.90, 18.70. MS: m/e (relative intensity) = 264 (63) [M + 1]⁺, 207 (100). 3g: IR (KBr): 3360, 1710 cm^-1. ¹H NMR: δ = 8.15 (s, 1 H), 7.62-7.10 (m, 14 H), 5.09 (t, J = 7.4 Hz, 1 H), 3.46 (dd, J = 16.4 and 7.4 Hz, 1 H), 3.37 (dd, J = 16.4 and 7.4 Hz, 1 H), 1.97 (s, 3 H). ¹³C NMR: δ = 207.51, 144.45, 136.28, 135.73, 132.98, 128.81, 128.76, 128.43, 128.14, 127.70, 127.48, 126.05, 122.08, 120.61, 119.76, 114.03, 111.21, 49.31, 37.09, 30.31. MS: m/e (relative intensity) = 339 (23) [M⁺], 283 (100). 3h: IR (KBr): 3300, 1690 cm^-1. ¹H NMR: δ = 8.14 (s, 1 H), 7.84 (d, J = 7.9 Hz, 1 H), 7.50-7.46 (m, 4 H), 7.44-7.40 (m, 2 H), 7.24 (t, J = 7.9 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 3.46-3.40 (tt, J = 12.9 and 4.1 Hz, 1 H), 3.14 (t, J = 13.6 Hz, 2 H), 2.62-2.45 (m, 2 H), 2.21-1.66 (m, 4 H). ¹³C NMR: δ = 211.33, 136.29, 134.52, 132.97, 128.88, 128.75, 128.16, 126.94, 122.13, 120.10, 119.55, 115.11, 111.38, 48.11, 41.39, 37.14, 31.70, 25.87. MS: m/e (relative intensity) = 289 (100) [M⁺], 246 (49), 232 (74), 218 (58). 3i: IR (neat): 3360, 1715 cm^-1. ¹H NMR: δ = 8.25 (bs, 1 H), 7.57-7.10 (m, 7 H), 3.26-3.18 (m, 2 H), 2.83-275 (m, 2 H), 2.12 (s, 3 H). ¹³C NMR: δ = 207.45, 139.58, 132.00, 131.34, 130.88, 130.01, 128.72, 128.52, 127.89, 127.73, 126.25, 122.49, 120.59, 37.33, 32.91, 29.80. MS: m/e (relative intensity) = 269 (63) [M⁺], 213 (100). 3j: IR (KBr): 3400, 1710 cm^-1. ¹H NMR: δ = 8.13 (bs, 1 H), 7.52-7.06 (m, 9 H), 6.04 (bs, 1 H), 3.15-3.07 (m, 2 H), 2.80-2.72 (m, 2 H), 2.50-1.95 (m, 7 H), 2.13 (s, 3 H). ¹³C NMR: δ = 209.09, 146.37, 135.97, 135.13, 129.82, 128.65, 128.44, 127.15, 126.82, 126.19, 121.83, 119.30, 118.38, 110.63, 110.51, 44.79, 39.42, 33.67, 30.02, 29.83, 28.74, 19.10. MS: m/e (relative intensity) = 343 (100) [M⁺], 286 (86). 3k: IR (neat): 3440, 1730 cm^-1. ¹H NMR: δ = 7.92 (bs, 1 H), 7.46-7.01 (m, 14 H), 6.02 (bs, 1 H), 5.08-5.05 (m, 1 H), 3.43-3.36 (m, 2 H), 2.62-2.46 (m, 1 H), 2.16-2.08 (m, 4 H), 2.06 (s, 3 H), 2.04-1.96 (m, 2 H). MS: m/e (relative intensity) = 419 (38) [M⁺], 362 (100). 3l: IR (neat): 3380, 1680 cm^-1. ¹H NMR: δ = 7.92 (d, J = 7.9 Hz, 1 H), 7.54-7.04 (m, 14 H), 5.17 (t, J = 7.3 Hz, 1 H), 4.01 (dd, J = 16.7 and 6.9 Hz, 1 H), 3.93 (dd, J = 16.7 and 6.9 Hz, 1 H), 2.87-2.75 (m, 2 H), 1.62-1.58 (m, 2 H), 1.39-1.36 (m, 2 H), 0.92 (t, J = 7.3 Hz, 3 H). ¹³C NMR: δ = 199.08, 144.26, 137.09, 136.34, 135.54, 132.84, 128.41, 128.18, 128.01, 127.47, 125.78, 120.70, 119.36, 119.08, 113.27, 110.50, 43.84, 36.59, 31.83, 26.02, 22.52, 13.82. EI-MS: m/e (relative intensity) = 381 (30) [M⁺], 263 (100).

<A NAME="RG02004ST-18">18</A> Sundberg RJ. In Indoles Academic Press; London: 1996.

Temperatures are reported as bath temperature.

<A NAME="RG02004ST-20">20</A> Srivastava N. Banik BK. J. Org. Chem. 2003, 68: 2109

<A NAME="RG02004ST-21">21</A> Kobayashi S. Kakumoto K. Sugiura M. Org. Lett. 2002, 4: 1319

Sequential Procedure for the Preparation of 5a. To a solution of the indole 1a (0.072 g, 0.612 mmol) and the trans,trans-dibenzylidene acetone 2c (0.287 g, 1.22 mmol) in EtOH (3 mL) was added NaAuCl₄·2H₂O (0.012 g, 0.0306 mmol). The resulting mixture was allotted to react under stirring at 30 °C. After 2 h, the temperature was raised at 60 °C and the heating was continued for 3 h after which the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography eluting with n-hexane/EtOAc 90/10 v/v mixture to afford 4a (0.17 g, 80% yield). IR (KBr): 3440, 1720 cm^-1. ¹H NMR (diastereomeric mixture, 2.1:1 ratio): major isomer: δ = 7.56 (bs, NH, 1 H), 7.50-6.90 (m, C_sp2-H, 14 H), 4.82 (t, J = 4.5 Hz, 10-CH, 1 H), 4.54 (dd, J = 2.3 and 12.1 Hz, 6-CH, 1 H), 3.40 (d, J = 4.5 Hz, 9-CH, 2 H), 3.21 (dd, J = 12.1 and 15.5 Hz, 7-CH _a, 1 H) 2.73 (dd, J = 2.3 and 15.5 Hz, 7-CH _b, 1 H); minor isomer: δ = 7.68 (bs, NH, 1 H), 7.50-6.90 (m, C_sp2-H, 14 H), 4.86 (dd, X part of ABX system, 6-CH, 1 H), 4.78 (dd, J = 4.5 and 7.9 Hz, 10-CH, 1 H), 3.47 (dd, J = 8.3 and 14.0 Hz, 9-CH _a, 1 H), 3.08 (dd, J = 4.5 and 14.4 Hz, 9-CH _b, 1 H), 3.18-3.09 (m, AB part of ABX system 7-CH, 2 H). ¹³C NMR: (diastereomeric mixture, 2.1:1 ratio): major isomer: δ = 209.97 (8-CO), 143.43 (1-C_Pha), 141.78 (1-C_Phb), 136.57 (5a-C), 134.88 (4a-C), 129.26, 128.62 (10b-C), 128.60, 128.05, 127.71, 127.42, 126.45 (Pha and Phb), 122.13 (3-C), 119.71 (2-C), 118.63 (1-C), 113.65 (10a-C), 110.53 (4-C), 50.37 (7-C), 49.08 (9-C), 41.13 (6-C), 36.42 (10-C); minor isomer: δ = 209.43 (8-CO), 143.66 (1-C_Pha), 140.01 (1-C_Phb), 136.04 (5a-C), 134.76 (4a-C), 129.19, 128.47 (10b-C), 128.18, 128.05, 127.45, 126.49 (Pha and Phb), 121.97 (3-C), 119.65 (2-C), 118.65 (1-C), 112.86 (10a-C), 110.53 (4-C), 50.06 (4-C), 49.93 (7-C), 41.02 (6-C), 38.63 (10-C). MS: m/e (relative intensity) = 351 (100) [M⁺], 219 (47).

Selected data for 5b: IR (neat): 3400, 1710 cm^-1. ¹H NMR: δ = 8.19 (bs, 1 H), 7.52-7.47 (m, 1 H), 7.28-7.24 (m, 1 H), 7.17-7.05 (m, 2 H), 3.30-3.25 (m, 1 H), 2.52-2.28 (m, 4 H), 2.21 (s, 3 H), 2.13-1.73 (m, 4 H). ¹³C NMR: δ = 210.85, 136.03, 135.11, 129.01, 121.28, 119.08, 118.25, 110.43, 106.25, 47.09, 41.07, 36.34, 30.77, 25.33, 8.37. MS: m/e (relative intensity) = 227 (100) [M⁺]. 5c: IR (neat): 3390, 1710 cm^-1. ¹H NMR: δ = 8.39 (bs, 1 H), 7.57-7.09 (m, 8 H), 3.85 (s, 3 H), 3.55-3.35 (m, 1 H), 2.63-2.58 (m, 2 H), 2.41-2.16 (m, 2 H), 2.05-1.98 (m, 4 H). ¹³C NMR: δ = 210.28, 158.21, 136.53, 135.20, 130.77, 128.03, 127.01, 121.98, 119.98, 119.20, 114.13, 113.86, 110.64, 55.29, 47.76, 41.10, 36.26, 31.72, 25.23. MS: m/e (relative intensity) = 319 (100) [M⁺].

<A NAME="RG02004ST-24A">24a</A> Itahara T. Kawasaki K. Ouseto F. Synthesis 1984, 236

<A NAME="RG02004ST-24B">24b</A> Itahara T. Ikeda M. Sakakibara T. J. Chem. Soc., Perkin Trans. 1 1983, 1361

<A NAME="RG02004ST-25">25</A> Baker RT. Nguyen P. Marder TB. Westcott SA. Angew Chem., Int. Ed. Engl. 1995, 34: 1336

<A NAME="RG02004ST-26A">26a</A> Snider BB. Zeng H. J. Org. Chem. 2003, 68: 545

<A NAME="RG02004ST-26B">26b</A> Abbiati G. Beccalli EM. Broggini G. Zoni C. J. Org. Chem. 2003, 68: 7625