A Study of Negishi Cross-Coupling Reactions with Benzylzinc Halides­ To Prepare Original 3-Ethoxypyrazoles

Abstract

The Negishi palladium-catalyzed cross-coupling reaction between 3-ethoxy-4-iodo-1H-pyrazole and various benzylzinc halides was extensively studied. Using simplified, robust, and optimized reaction conditions, a series of electron-poor benzylzinc halides were prepared and used to synthesize 4-benzyl-3-ethoxy-1H-pyrazoles derivatives. From these, iodination on C5 of the pyrazole nucleus led to the corresponding 4-benzyl-3-ethoxy-5-iodo-1H-pyrazoles, these are original building blocks for the preparation of libraries of new chemical entities.

Key words

cross-coupling - heterocycles - palladium - zinc - benzylation

• References

• 1 Guillou S, Bonhomme FJ, Janin YL. Synthesis 2008; 3504
• 2 Guillou S, Bonhomme FJ, Janin YL. Tetrahedron 2009; 65: 2660
• 3 Guillou S, Nesme O, Ermolenko MS, Janin YL. Tetrahedron 2009; 65: 3529
• 4 Guillou S, Bonhomme FJ, Chahine D, Nesme O, Janin YL. Tetrahedron 2010; 66: 2654
• 5 Guillou S, Janin YL. Chem. Eur. J. 2010; 16: 4669
• 6 Guillou S, Bonhomme FJ, Ermolenko MS, Janin YL. Tetrahedron 2011; 67: 8451
• 7 Salanouve E, Guillou S, Bizouarne M, Bonhomme FJ, Janin YL. Tetrahedron 2012; 68: 3165
• 8 Salanouve E, Retailleau P, Janin YL. Tetrahedron 2012; 68: 2135
• 9 Ermolenko MS, Guillou S, Janin YL. Tetrahedron 2013; 69: 257
• 10 King AO, Okukado N, Negishi E. J. Chem. Soc., Chem. Commun. 1977; 683
• 11 Negishi E, King AO, Okukado N. J. Org. Chem. 1977; 42: 1821
• 12 Erdik E. Tetrahedron 1987; 43: 2203
• 13 Nakamura E In Organometallics in Synthesis, A Manual . Schlosser M. John Wiley & Sons; Chichester: 2002: 579
• 14 Krasovskiy A, Malakhov V, Gavryushin A, Knochel P. Angew. Chem. Int. Ed. 2006; 45: 6040
• 15 Boudet N, Sase S, Sinha P, Liu C.-Y, Krasovskiy A, Knochel P. J. Am. Chem. Soc. 2007; 129: 12358
• 16 Ren H, Dunet G, Mayer P, Knochel P. J. Am. Chem. Soc. 2007; 129: 5376
• 17 Aerssens MH. P. J, Brandsma L. J. Chem. Soc., Chem. Commun. 1984; 735
• 18 Knochel P, Normant JF. Tetrahedron Lett. 1984; 25: 1475
• 19 Bellassoued M, Gaudemar M, Burgi AE, Baccar B. J. Organomet. Chem. 1985; 280: 165
• 20 Gawroński JK. Tetrahedron Lett. 1984; 25: 2605
• 21 Picotin G, Miginiac P. J. Org. Chem. 1987; 52: 4796
• 22 Takai K, Kakiuchi T, Utimoto K. J. Org. Chem. 1994; 59: 2671
• 23 Knochel P, Yeh MC. P, Berk SC, Talbert J. J. Org. Chem. 1988; 53: 2390
• 24 Rao SA, Knochel P. J. Am. Chem. Soc. 1991; 113: 5735
• 25 Rieke RD, Uhm SJ, Hudnall PM. J. Chem. Soc., Chem. Commun. 1973; 269
• 26 Rieke RD, Uhm SJ. Synthesis 1975; 452
• 27 Arnold RT, Kulenovic ST. Synth. Commun. 1977; 7: 223
• 28 Rieke RD, Hanson MV. Tetrahedron 1997; 53: 1925
• 29 Fleckenstein JE, Koszinowski K. Organometallics 2011; 30: 5018
• 30 Metzger A, Schade MA, Knochel P. Org. Lett. 2008; 10: 1107
• 31 Dong Z, Manolikakes G, Li J, Knochel P. Synthesis 2009; 681
• 32 Metzger A, Argyo C, Knochel P. Synthesis 2010; 882
• 33 Krasovskiy A, Knochel P. Synthesis 2006; 890