Sequential Three-Component and Heck Reactions for the Synthesis of Phenanthridones

Abstract

A condensation-cycloaddition-cross-coupling reaction sequence has been applied to the synthesis of phenanthridone derivatives. This novel two-step procedure is based on a three-component reaction to give 2-halobenzamide-substituted cyclohexenes, which undergo palladium-catalyzed intramolecular Heck cyclizations.

Key words

domino reactions - Heck reactions - isomerizations - heterocycles - palladium

References

• For selected reviews on multicomponent and domino reactions, see:
• 1a Tietze LF. Haunert F. In Stimulating Concepts in Chemistry   Shibasaki M. Stoddart JF. Vögtle F. Wiley-VCH; Weinheim: 2000.  p.39 
• 1b Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 1c Bienaymé H. Hulme C. Oddon G. Schmitt P. Chem.-Eur. J.  2000,  6:  3321 
• 1d Multicomponent Reactions   1st ed.:  Zhu J. Bienaymé H. Wiley; New York: 2005. 
• 2 Jacobi von Wangelin A. Neumann H. Gördes D. Klaus S. Strübing D. Beller M. Chem. Eur. J.  2003,  9:  4283 
• 3a Beller M. Eckert M. Angew. Chem. Int. Ed.  2000,  39:  1010 
• 3b Gördes D. Neumann H. Jacobi von Wangelin A. Fischer C. Drauz K. Krimmer H.-P. Beller M. Adv. Synth. Catal.  2003,  345:  510 
• 3c Enzmann A. Eckert M. Ponikwar W. Polborn K. Schneiderbauer S. Beller M. Beck W. Eur. J. Inorg. Chem.  2004,  1330 
• 3d Beller M. Eckert M. Vollmüller F. Bogdanovic S. Geissler H. Angew. Chem., Int. Ed. Engl.  1997,  36:  1494 
• 4 Gördes D. Jacobi von Wangelin A. Klaus S. Neumann H. Strübing D. Hübner S. Jiao H. Baumann W. Beller M. Org. Biomol. Chem.  2004,  2:  845 
• 5a Neumann H. Jacobi von Wangelin A. Gördes D. Spannenberg A. Beller M. J. Am. Chem. Soc.  2001,  123:  8398 
• 5b Jacobi von Wangelin A. Neumann H. Gördes D. Spannenberg A. Beller M. Org. Lett.  2001,  3:  2895 
• 5c Neumann H. Jacobi von Wangelin A. Gördes D. Spannenberg A. Baumann W. Beller M. Tetrahedron  2002,  58:  2381 
• 6 Neumann H. Jacobi von Wangelin A. Gördes D. Klaus S. Jiao H. Spannenberg A. Beller M. Krüger T. Wendler C. Thurow K. Stoll N. Chem. Eur. J.  2003,  9:  2273 
• 7 Neumann H. Jacobi von Wangelin A. Klaus S. Strübing D. Gördes D. Beller M. Angew. Chem. Int. Ed.  2003,  42:  4503 
• 8 Neumann H. Klaus S. Klawonn M. Strübing D. Hübner S. Gördes D. Jacobi von Wangelin A. Lalk M. Beller M. Z. Naturforsch., B  2004,  59:  431 
• 9a Baldwin JE. J. Chem. Soc., Chem. Commun.  1976,  18:  734 
• 9b For total syntheses featuring intramolecular Heck reactions to fashion cis-decalins, see: Link JT. Overman LE. In Metal-catalyzed Cross-coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.231 
• 10a For a recent ortho-lithiation/Suzuki coupling approach toward Hippadine, see: Hartung CG. Fecher A. Chapell B. Snieckus V. Org. Lett.  2003,  5:  1899 
• 10b For a Heck-type biaryl synthesis, see: Garden SJ. Torres JC. Pinto AC. J. Braz. Chem. Soc.  2000,  11:  441 
• For Heck ring closure procedures toward Lycoricidine, see:
• 11a Chida N. Ohtsuka M. Ogawa S. Tetrahedron Lett.  1991,  32:  4525 
• 11b Martin SF. Tso H.-H. Heterocycles  1993,  35:  85 
• 11c Hudlicky T. Olivo HF. J. Am. Chem. Soc.  1992,  114:  9694 
• 11d Hudlicky T. Olivo HF. McKibben B. J. Am. Chem. Soc.  1994,  116:  5108 
• 11e McIntosh MC. Weinreb SM. J. Org. Chem.  1993,  58:  4823 
• 12 Tan Z. Negishi E.-I. In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol. 1:  Negishi E.-I. Wiley; New York: 2002.  Chap III.2.18.
• 16a SHELXS-86: Sheldrick GM. Acta Crystallogr., Sect. A  1990,  46:  467 
• 16b Sheldrick GM. SHELXL-93   University of Göttingen; Germany: 1993. 

13

See also Supporting Information of ref. 5a.

14

Suitable crystals of 10a were obtained by recrystallization from toluene-EtOAc (10:1).

15

X-ray data of 10a were collected with a STOE-IPDS diffractometer using graphite-monochromated Mo-K _α radiation (λ = 0.71069 Å). The structure was solved by direct methods [16a] and refined by full matrix least square techniques against F ^² . [16b] XP (Bruker AXS) was used for structure representation. All non-hydrogen atoms were refined anisotropically. The hydrogen atoms (except NH) were included at calculated positions and refined by the riding model. Crystal data for 10a: space group Pna2₁, orthorhombic, a = 13.328 (3), b = 9.314 (2), c = 18.207 (4) Å, V = 2260.2 (9) ų, Z = 8, ρ_calcd = 1.318 g cm^-3, 11205 reflections measured, 3580 were independent of symmetry and 2524 were observed [I > 2σ (I)], R1 = 0.043, wR2 (all data) = 0.091, 315 parameters.