Acid-Free Silver-Catalyzed Cross-Dehydrogenative Carbamoylation of Pyridines with Formamides

Abstract

Primary pyridylcarboxamides are prevalent parent structures in bioactive molecules and have the apparent advantages over N-protected derivatives as synthetic building blocks. However, no practical methods have been developed for direct synthesis of this compound class from unfunctionalized pyridines. We herein present a general, safe, concise, acid-free, and highly selective method for the C2-carba­moylation of pyridines with unprotected formamide and N-methyl formamide through the cleavage of two C–H bonds.

Key words

pyridylcarboxamides - pyridines - C–H bonds functionalization - carbamoylation - formamides

• References and Notes

• 1a Haynes C, Kirkwood RC. Pestic. Sci. 1992; 35: 161
• 1b Regitano JB, Koskinen WC. J. Agric. Food Chem. 2008; 56: 5801
• 1c Babu YS, Rowland RS, Chand P, Kotian PL, El-Kattan Y, Niwas S. US Patent 6699994, 2004
• 2a Allen CL, Williams JM. J. Chem. Soc. Rev. 2011; 40: 3405
• 2b Valeur E, Bradley M. Chem. Soc. Rev. 2009; 38: 606
• 2c Constable DJ. C, Dunn PJ, Hayler JD, Humphrey GR, Leazer JL. Jr, Linderman RJ, Lorenz K, Manley J, Pearlman BA, Wells A, Zaks A, Zhang TY. Green Chem. 2007; 9: 411
• 2d Brunner H, Nuber B, Prommesberger M. J. Organomet. Chem. 1996; 523: 179
• 2e Mukkala V.-M, Liitti P, Hemmilae I, Takalo H, Matachescu C, Jouko K. Helv. Chim. Acta 1996; 79: 295

For a few examples of the use of CO and ammonia in palladium-catalyzed carbonylation of aryl halides, see:
• 3a Wu X.-F, Neumann H, Beller M. Chem. Asian J. 2010; 5: 2168
• 3b Wu X.-F, Neumann H, Beller M. Chem. Eur. J. 2010; 16: 9750
• 3c Alsabeh PG, Stradiotto M, Neumann H, Beller M. Adv. Synth. Catal. 2012; 354: 3065
• 4 Xu T, Alper H. Tetrahedron Lett. 2013; 54: 5496
• 5a Takács A, Abreu AR, Peixoto AF, Pereira M, Kollár L. Synth. Commun. 2009; 39: 1534
• 5b Csajági C, Borcsek B, Niesz K, Kovács I, Székelhidi Z, Bajko Z, Urge L, Darvas F. Org. Lett. 2008; 10: 1589
• 5c Wu X, Larhed M. Org. Lett. 2005; 7: 3327
• 5d Wannberg J, Larhed M. J. Org. Chem. 2003; 68: 5750
• 5e Salvadori J, Balducci E, Zaza S, Petricci E, Taddei M. J. Org. Chem. 2010; 75: 1841
• 5f Cardullo F, Donati D, Merlo G, Paio A, Petricci E, Taddei M. Synlett 2009; 47
• 5g Martinelli JR, Martinelli DA, Watson DM, Freckmann M, Barder TE, Buchwald SL. J. Org. Chem. 2008; 73: 7102
• 5h Tambade PJ, Patil YP, Bhanushali MJ, Bhanage BM. Synthesis 2008; 2347
• 5i Martinelli JR, Clark TP, Watson DA, Munday RH, Buchwald SL. Angew. Chem. Int. Ed. 2007; 46: 8460
• 5j Appukkuttan P, Axelsson L, Van der Eycken E, Larhed M. Tetrahedron Lett. 2008; 49: 5625
• 5k Wu X, Wannberg J, Larhed M. Tetrahedron 2006; 62: 4665
• 5l Morera E, Ortar G. Tetrahedron Lett. 1998; 39: 2835
• 6 Gadge ST, Bhanage BM. Synlett 2014; 25: 85
• 7 Nielsen DU, Tanning RH, Lindhardt AT, Gogsig TM, Skrydstrup T. Org. Lett. 2011; 13: 4454
• 8 Suresh AS, Baburajan P, Ahmed M. Tetrahedron Lett. 2015; 56: 4864
• 9a Wan Y, Alterman M, Larhed M, Hallberg A. J. Comb. Chem. 2003; 5: 82
• 9b Schnyder A, Beller M, Mehltretter G, Nsenda T, Studer M, Indolese AF. J. Org. Chem. 2001; 66: 4311

For recent reviews and highlights on oxidative cross dehydrogenative couplings, see:
• 10a Li C.-J. Acc. Chem. Res. 2009; 42: 335
• 10b You S.-L, Xia J.-B. Top. Curr. Chem. 2010; 292: 165
• 10c Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
• 10d Newhouse T, Baran PS. Angew. Chem. Int. Ed. 2011; 50: 3362
• 10e Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
• 10f McMurray L, O’Hara F, Gaunt MJ. Chem. Soc. Rev. 2011; 40: 1885
• 10g Han W, Ofial AR. Synlett 2011; 1951
• 10h Bugaut X, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 7479
• 10i Liu C, Zhang H, Shi W, Lei A. Chem. Rev. 2011; 111: 1780
• 10j Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
• 10k Girard SA, Knauber T, Li C.-J. Angew. Chem. Int. Ed. 2014; 53: 74
• 11a He T, Li HH. J, Li PH, Wang L. Chem. Commun. 2011; 47: 8946
• 11b Peng JL, Liu LY, Hu ZW, Huang JB, Zhu Q. Chem. Commun. 2012; 48: 3772
• 11c Xing Q, Shi LJ, Lang R, Xia CG, Li FW. Chem. Commun. 2012; 48: 11023
• 11d Velavan A, Sumathi S, Balasubramanian KK. Eur. J. Org. Chem. 2013; 3148

For recent reviews on direct C–H functionalization of unprotected pyridines, see:
• 12a Nakao Y. Synthesis 2011; 3209
• 12b Zhang BN, Zhou QZ, Chen RE, Jiang HJ. Chin. J. Org. Chem. 2012; 32: 1653
• 13 Yao B, Deng C.-L, Liu Y, Tang R.-Y, Zhang X.-G, Li J.-H. Chem. Commun. 2015; 51: 4097

For recent reviews on direct activation of protected formamide C–H bond, see:
• 14a Ding ST, Jiao N. Angew. Chem. Int. Ed. 2012; 51: 9226
• 14b Muzart J. Tetrahedron 2009; 65: 8313
• 15a For a review, see: Collins KD, Glorius F. Acc. Chem. Res. 2015; 48: 619
• 15b Collins KD, Glorius F. Nat. Chem. 2013; 5: 597
• 16a Minisci F, Gardini GP, Galli R, Bertini F. Tetrahedron Lett. 1970; 11: 15
• 16b Langhals E, Langhals H, Rüchardt C. Liebigs Ann. Chem. 1982; 930
• 16c Martin I, Vares L, Kühn I, Claesson A. Acta Chem. Scand. 1995; 49: 230
• 16d Minisci F, Recupero F, Punta C, Gambarotti C, Antonietti F, Fontana F, Pedulli GF. Chem. Commun. 2002; 2496
• 16e Amrollahi Biyouki MA, Smith RA. J, Bedford JJ, Leader JP. Synth. Commun. 1998; 28: 3817
• 17 Han W, Mayer P, Ofial AR. Angew. Chem. Int. Ed. 2011; 50: 2178

For studies on the solvent effect in the α and γ regioselectivity of pyridines, see:
• 18a Minisci F, Vismara E, Fontana F, Morini G, Serravalle M, Giordano C. J. Org. Chem. 1987; 52: 730
• 18b O’Hara F, Blackmond DG, Baran PS. J. Am. Chem. Soc. 2013; 135: 12122
• 19 General Procedure A 25 mL Schlenk flask was charged with AgNO₃ (17.2 mg, 20 mol% Ag), K₂S₂O₈ (408 mg, 1.5 mmol), and HCOONa (129 mg, 1.0 mmol) before standard cycles of evacuation and back-filling with dry and pure oxygen (three times). Corresponding pyridine 1m (40 μL, 0.5 mmol), formamide (2, 2 mL), and H₂O (0.4 mL) were added successively. The mixture was stirred at 80 °C for the indicated time (monitored by TLC). At the end of the reaction, the reaction mixture was cooled to room temperature, poured into a sat. aq NaCl solution (15 mL), and extracted with EtOAc (3 × 15 mL). The organic phases were combined, and the volatile components were evaporated in a rotary evaporator. The residue was purified by flash column chromatography on silica gel (eluent: PE–EtOAc–Et₃N) to afford the corresponding product 3m as white solid (57 mg, 94%); mp 102–103 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.62 (m, 1 H), 8.11 (br s, 1 H), 8.06 (dt, J = 7.6, 0.8 Hz, 1 H), 8.0 (td, J = 7.6, 1.6 Hz, 1 H), 7.64 (br s, 1 H), 7.61–7.57 (m, 1 H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 166.5, 150.7, 148.9, 138.1, 126.9, 122.4 ppm.
• 20 Wen P, Li YM, Zhou K, Ma C, Lan XB, Ma CW, Huang GS. Adv. Synth. Catal. 2012; 354: 2135
• 21 Mcgill CK, Rappa A. Adv. Heterocycl. Chem. 1988; 44: 1
• 22a Fier PS, Hartwig JF. Science 2013; 342: 956
• 22b Fier PS, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 10139
• 23a Xu P, Guo S, Wang LY, Tang PP. Angew. Chem. Int. Ed. 2014; 53: 5955
• 23b Anderson JM, Kochi JK. J. Am. Chem. Soc. 1970; 92: 1651