Bi(OTf)₃-Catalyzed Three-Component Synthesis of Amidomethylarenes and -Heteroarenes

Abstract

A highly efficient Bi(OTf)₃-catalyzed multicomponent synthesis of amidomethylated arenes and heteroarenes from readily available starting materials has been developed. This reaction proceeds under mild conditions, has a broad substrate scope, and in addition water is generated as only side product.

Key words

multicomponent reactions - bismuth - green chemistry - acylimines - amidoalkylation

• References and Notes

• 1a French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. J. Pharmacol. Exp. Ther. 2010; 133: 129
• 1b Belyk KM, Morrison HG, Jones P, Summa V. WO 2006060730, 2007
• 1c McIntyre JA, Castaner J. Drugs Future 2004; 29: 992
• 1d Ratti S, Quarato P, Casagrande C, Fumagalli R, Corsini A. Eur. J. Pharmacol. 1998; 355: 77
• 2 Science of Synthesis . Vol. 21. Weinreb SM. Thieme; Stuttgart: 2005
• 3 Montalbetti CA. G. N, Falque V. Tetrahedron 2005; 61: 10827
• 4a Molander GA, Shin I. Org. Lett. 2012; 14: 3138
• 4b Molander GA, Beaumard F. Org. Lett. 2011; 13: 1242
• 4c Molander GA, Shin I. Org. Lett. 2011; 13: 3956
• 4d Molander GA, Hiebel M.-A. Org. Lett. 2010; 12: 4876
• 5 Anastas PT, Warner JC. Green Chemistry: Theory and Practice . Oxford University Press; 2000:
• 6a Yazici A, Pyne SG. Synthesis 2009; 339
• 6b Petrini M, Torregiani E. Synthesis 2007; 159
• 6c Speckamp WN, Moolenaar MJ. Tetrahedron 2000; 56: 3817
• 6d Zaugg H. Synthesis 1984; 85
• 7a Salama TA. Synlett 2013; 24: 713
• 7b Jaratjaroonphong J, Krajangsri S, Reutrakul V. Tetrahedron Lett. 2012; 53: 2476
• 7c Nandi GC, Samai S, Kumar R, Singh MS. Tetrahedron Lett. 2009; 50: 7220
• 7d Shirakawa S, Kobayashi S. Org. Lett. 2006; 8: 4939
• 7e Ben-Ishai D, Altman J, Bernstein Z, Peled N. Tetrahedron 1977; 34: 467
• 8 Trost BM. Science 1991; 254: 1471
• 9 Typical procedures use at least 1 equiv of the acid (often >3 equiv). In some cases the acid is used as solvent (see ref. 6 and 7).

Reviews:
• 10a Bothwell JM, Krabbe SW, Mohan RS. Chem. Soc. Rev. 2011; 40: 4649
• 10b Gaspard-Iloughmane H, Le Roux C. Eur. J. Org. Chem. 2004; 2517

For some recent applications, see:
• 11a Zhang L, Li Z, Fan R. Org. Lett. 2013; 15: 2482
• 11b Li Z, Plancq B, Ollevier T. Chem. Eur. J. 2012; 18: 3144
• 11c Rubenbauer P, Herdtweck E, Strassner T, Bach T. Angew. Chem. Int. Ed. 2008; 47: 10106
• 11d Rueping M, Nachtsheim BJ, Kuenkel A. Org. Lett. 2007; 9: 825
• 11e Qin H, Yamagiwa N, Matsunaga S, Shibasaki M. Angew. Chem. Int. Ed. 2007; 46: 409
• 11f Rueping M, Nachtsheim BJ, Scheidt T. Org. Lett. 2006; 8: 3717

For Bi(OTf)₃-catalyzed Mannich-type amidoalkylation and Mannich-type reactions with reactive nucleophiles, see:
• 12a Pin F, Comesse S, Garrigues B, Marchalin S, Daïch A. J. Org. Chem. 2007; 72: 1181
• 12b Ollevier T, Nadeau E. Org. Biomol. Chem. 2007; 5: 3126
• 12c Ollevier T, Nadeau E. J. Org. Chem. 2004; 69: 9292
• 12d Ollevier T, Ba T. Tetrahedron Lett. 2003; 44: 9003
• 13 For the use of dbpy as mechanistic probe to determine between Lewis and Brønsted acid catalysis, see: Wabnitz TC, Yu J.-Q, Spencer JB. Chem. Eur. J. 2004; 10: 484
• 14 Dang TT, Boeck F, Hintermann L. J. Org. Chem. 2011; 76: 9353
• 15 See Supporting Information for experimental details.
• 16 Reactions with indoles not bearing electron-withdrawing N-protecting groups or other more reactive heterocycles such as furan or pyrrole led to the exclusive formation of bisheteroarylmethane derivatives.
• 17a Musher DM, Fainstein V, Young EJ. Antimicrob. Agents Chemother. 1980; 254
• 17b Campoli-Richards D, Lackner T, Monk J. Drug 1987; 34: 411
• 17c Kaczanowska K, Wiesmuller K.-H, Schaffner A.-P. ACS Med. Chem. Lett. 2010; 1: 530
• 18 This might be due to the decreased sterical shielding of 4ab.
• 19 Typical Procedure A 10 mL screw-cap vial was charged with Bi(OTf)₃ (5 mol%), amide (1.0 equiv), formaldehyde (1.2 equiv), (hetero)arene (3–4 equiv), and nitromethane and closed with a Teflon lined screw cap. The reaction mixture was stirred at 25–100 °C for the specified time. After cooling to r.t. the reaction mixture was diluted with EtOAc and filtered over a short plug of Celite and silica gel. The plug was rinsed with additional EtOAc. The combined filtrates were concentrated under reduced pressure. Purification of the crude residue by column chromatography (hexane–EtOAc) afforded the analytically pure product. Synthesis of N-(2,4,6-Trimethylbenzyl)benzamide (4b, Table 2 Entry 1) N-(2,4,6-Trimethylbenzyl)benzamide was synthesized according to the typical procedure from benzamide (242 mg, 2.0 mmol), paraformaldehyde (72 mg, 2.4 mmol), mesitylene (0.83 mL, 6.0 mmol, 3 equiv), and Bi(OTf)₃ (66 mg, 0.1 mmol) in MeNO₂ (4 mL) at 100 °C for 16 h. Purification by chromatography (hexane–EtOAc, 4:1) yielded the product as colorless solid (371 mg, 73%).