Total Synthesis of Horsfiline: A Palladium-Catalyzed Domino Heck-Cyanation Strategy

Abstract

A total synthesis of horsfiline has been accomplished featuring a key intramolecular palladium-catalyzed domino Heck-cyanation sequence for the formation of the 3,3′-disubstituted oxindole.

Key words

domino reaction - palladium - Heck - cyanation - oxindole - horsfiline

References and Notes

• For reviews, see:
• 1a Marti C. Carreira EM. Eur. J. Org. Chem.  2003,  2209 
• 1b Galliford CV. Sheidt KA. Angew. Chem. Int. Ed.  2007,  46:  8748 
• 2 James MNG. Williams GJB. Can. J. Chem.  1972,  50:  2407 
• 3a Cui CB. Kakeya H. Osada H. J. Antibiot.  1996,  49:  832 
• 3b Cui C.-B. Kakeya H. Ckada H. Tetrahedron  1996,  52:  12651 
• 4 Elderfield RC. Gilman RE. Phytochemistry  1972,  11:  339 
• 5 Pellegrin C. Weber M. Borschberg H.-J. Helv. Chim. Acta  1996,  79:  151 ; and references therein
• 6 Edmondson S. Danishefsky SJ. Sepp-Lorenzino L. Rosen N. J. Am. Chem. Soc.  1999,  121:  2147 
• 7 Jossang A. Jossang P. Hadi HA. Sevenet T. Bodo B. J. Org. Chem.  1991,  56:  6527 
• 8a Jones K. Wilkinson J. Chem. Commun.  1992,  1767 
• 8b Bascop S. Sapi J. Laronze J. Levy J. Heterocycles  1994,  38:  725 
• 8c Pellegrini C. Strässler C. Weber M. Borschberg H. Tetrahedron: Asymmetry  1994,  5:  1979 
• 8d Palmisano G. Annunziata R. Papeo G. Sisti M. Tetrahedron: Asymmetry  1996,  7:  1 
• 8e Lakshmaiah G. Kawabata T. Shang M. Fuji K. J. Org. Chem.  1999,  64:  1699 
• 8f Fischer C. Meyers C. Carreira EM. Helv. Chim. Acta  2000,  83:  1175 
• 8g Cravotto G. Giovenzana G. Pilati T. Sisti M. Palmisano G. J. Org. Chem.  2001,  66:  8447 
• 8h Kumar UKS. Illa H. Junjappa H. Org. Lett.  2001,  3:  4193 
• 8i Lizos D. Tripoli R. Murphy JA. Chem. Commun.  2001,  2732 
• 8j Selvakumar N. Azhagan AM. Srinivas D. Krishna GG. Tetrahedron Lett.  2002,  43:  9175 
• 8k Lizos DE. Murphy JA. Org. Biomol. Chem.  2003,  1:  117 
• 8l Chang MY. Pai C.-L. Kung Y.-H. Tetrahedron Lett.  2005,  46:  8463 
• 8m Murphy JA. Tripoli R. Khan TA. Mali UW. Org. Lett.  2005,  7:  3287 
• 8n Trost BM. Brennan MK. Org. Lett.  2006,  8:  2027 
• 9a Bonnaterre F. Bois-Choussy M. Zhu J. Org. Lett.  2006,  8:  4351 
• 9b Salcedo A. Neuville L. Zhu J. J. Org. Chem.  2008,  73:  3600 
• 9c Erb W. Neuville L. Zhu J. J. Org. Chem.  2009,  74:  3109 
• 10a Pinto A. Neuville L. Retailleau P. Zhu J. Org. Lett.  2006,  8:  4927 
• 10b Pinto A. Neuville L. Retailleau P. Zhu J. Angew. Chem. Int. Ed.  2007,  46:  3291 
• 10c Pinto A. Neuville L. Zhu J. Tetrahedron Lett.  2009,  50:  3602 
• For general reviews on the domino process, see:
• 11a Tietze LF. Chem. Rev.  1996,  96:  115 
• 11b Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 
• 11c For a recent book, see: Domino Reactions in Organic Synthesis   Tietze LF. Brasche G. Gericke K. Wiley-VCH; Weinheim: 2006. 
• 12 Pinto A. Jia X. Neuville L. Zhu J. Chem. Eur. J.  2007,  13:  961 
• For the seminal use of K₄[Fe(CN)₆] in palladium-mediated cyanation, see:
• 13a Schareina T. Zapf A. Beller M. Chem. Commun.  2004,  1388 
• See also:
• 13b Weissman SA. Zewge D. Chen C. J. Org. Chem.  2005,  70:  1508 
• 13c Gelman D. Grossman O. Org. Lett.  2006,  8:  1189 
• 13d Li LH. Pan Z.-L. Liang Y.-M. Synlett  2006,  2094 
• 13e Schareina T. Zapf A. Magerlein W. Muller N. Beller M. Tetrahedron Lett.  2007,  48:  1087 
• 13f For related domino palladium-catalyzed cyanation process, see: Mariampillai B. Alliot J. Li M. Lautens M. J. Am. Chem. Soc.  2007,  129:  15372 
• 13g Cheng Y.-N. Duan Z. Yu L. Li Z. Zhu Y. Wu Y. Org. Lett.  2008,  10:  901 
• 13h For a general review on palladium-catalyzed cross-coupling involving metal cyanides, see: Takagi K. In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol.1:  Negishi E. de Meijere A. Wiley; New York: 2002.  p.657-672  
• 14a Byun HS. Reddy KC. Bittman R. Tetrahedron Lett.  1994,  35:  1371 
• 14b Yu C. Liu B. Hu L. J. Org. Chem.  2001,  66:  5413 
• For reviews, see:
• 14c Basavaiah D. Rao AJ. Satyanarayana T. Chem. Rev.  2003,  103:  811 
• 14d Masson G. Housseman C. Zhu J. Angew. Chem. Int. Ed.  2007,  46:  4614 
• 15a Villieras J. Rambaud M. Synthesis  1982,  924 
• 15b Villieras J. Rambaud M. Org. Synth.  1988,  66:  220 
• 16 Kondo Y. Kojima S. Sakamoto T. J. Org. Chem.  1997,  62:  6507 
• 17 Bald E. Saigo K. Mukaiyama T. Chem. Lett.  1975,  4:  1163 
• 19 Such reduction product has been reported in a related domino Heck reaction recently: Ruck RT. Huffman MA. Kim MK. Shevlin M. Kandur WV. Davies IW. Angew. Chem. Int. Ed.  2008,  47:  4711 
• 20 Zawisza AM. Muzart J. Tetrahedron Lett.  2007,  48:  6738 ; and references cited herein
• 21a Satoh T. Suzuki S. Suzuki Y. Miyagi Y. Imai Z. Tetrahedron Lett.  1969,  4555 
• 21b Osby JO. Heinzman SW. Ganem B. J. Am. Chem. Soc.  1986,  108:  67 
• 21c Caddick S. Haynes AK. Judd DB. Williams MRV. Tetrahedron Lett.  2000,  41:  3513 
• 22a Appel R. Angew. Chem. Int. Ed.  1976,  14:  801 
• 22b Shishido Y. Kibayashi C. J. Org. Chem.  1992,  57:  2876 
• 22c Wittenberger SJ. McLaughlin MA. Tetrahedron Lett.  1999,  40:  7175 
• 22d Harris JM. Padwa A. J. Org. Chem.  2003,  68:  4371 

18

Experimental Procedure: To a degassed solution of iodoanilide 14 (1.90 g, 3.29 mmol, 1.0 equiv) in DMF (16 mL) were added K₄Fe(CN)₆˙3H₂O (306.0 mg, 0.72 mmol, 0.22 equiv), Na₂CO₃ (350.0 mg, 3.30 mmol, 1.0 equiv) and Pd(OAc)₂ (22.0 mg, 0.1 mmol, 0.03 equiv). After being stirred at 120 ˚C under an argon atmosphere for 3 h, the reaction mixture was quenched with H₂O and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na₂SO₄) and concentrated. The residue was purified by flash chromatography (SiO₂, heptane-EtOAc, 95:5 → 90:10) to give the corresponding oxindole 15 (0.94 g, 60%) as a light orange solid. Compound 15: ^¹H NMR (500 MHz, CDCl₃): δ = 7.06 (d, J = 2.6 Hz, 1 H), 7.02 (d, J = 8.6 Hz, 1 H), 6.88 (dd, J = 8.6, 2.6 Hz, 1 H), 5.17 (d, J = 11.0 Hz, 1 H), 5.11 (d, J = 11.0 Hz, 1 H), 3.92 (d, J = 9.7 Hz, 1 H), 3.80 (s, 3 H), 3.73 (d, J = 9.7 Hz, 1 H), 3.62-3.51 (m, 2 H), 3.02 (d, J = 16.7 Hz, 1 H), 2.79 (d, J = 16.7 Hz, 1 H), 0.92 (t, J = 8.2 Hz, 2 H), 0.84 (s, 9 H), 0.00 (s, 3 H), -0.01 (s, 3 H), -0.03 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 175.4, 156.4, 135.4, 129.1, 116.2, 114.3, 111.2, 110.6, 69.9, 66.5, 66.1, 55.8, 51.9, 25.7, 21.7, 18.1, 17.7, -1.4, -5.6, -5.7. HRMS (ES+): m/z [M + Na]⁺ calcd for C₂₄H₄₀N₂O₄Si₂Na: 499.2424; found: 499.2415.