Palladium-Catalyzed N-Arylation of Amines and Amides with Aryltrimethylgermanes

Abstract

Described herein is a novel palladium-catalyzed C–N bond-formation reaction employing aryltrimethylgermanes as the new arylating reagents. Primary/secondary amines or even amides could be smoothly arylated to provide the corresponding N-arylation products in moderate to excellent yields.

Key words

N-arylation - amine - amide - aryltrimethylgermane

• References and Notes

• 1a Lawrence SA. Amines: Synthesis, Properties, and Application. Cambridge University Press; Cambridge: 2004
• 1b Quan ML, Lam PY. S, Han Q, Pinto DJ. P, He MY, Li R, Ellis CD, Clark CG, Teleha CA, Sun J.-H, Alexander RS, Bai S, Luettgen JM, Knabb RM, Wong PC, Wexler RR. J. Med. Chem. 2005; 48: 1729
• 1c Barchéchath SD, Tawatao RI, Corr M, Carson DA, Cottam HB. J. Med. Chem. 2005; 48: 6409
• 1d Voets M, Antes I, Scherer C, Müller-Vieira U, Biemel K, Barassin C, Marchais-Oberwinkler S, Hartmann RW. J. Med. Chem. 2005; 48: 6632
• 1e Davey DD, Adler M, Arnaiz D, Eagen K, Erickson S, Guilford W, Kenrick M, Morrissey MM, Ohlmeyer M, Pan G, Paradkar VM, Parkinson J, Polokoff M, Saionz K, Santos C, Subramanyam B, Vergona R, Wei RG, Whitlow M, Ye B, Zhao ZS, Devlin JJ, Phillips G. J. Med. Chem. 2007; 50: 1146
• 1f Ullmann F. Ann. 1904; 232: 38
• 1g Fanta PE. Chem. Rev. 1946; 38: 139
• 1h Kwong FY, Klapars A, Buchwald SL. Org. Lett. 2002; 4: 581
• 1i Ma D, Cai Q, Zhang H. Org. Lett. 2003; 5: 2453
• 2a Hartwig JF. Palladium-Catalyzed Amination of Aryl Halides and Related Reactions in Handbook of Organopalladium Chemistry for Organic Synthesis. Vol. 1. Negishi EI. Wiley-Interscience; New York: 2002: 1051.2
• 2b Muci AR, Buchwald SL. Practical Palladium Catalysts for CAN and CAO Bond Formation. In Topics in Current Chemistry. Vol. 219. Miyaura N. Springer; Berlin: 2002: 133
• 2c Fagan PJ, Hauptman E, Shapiro R, Casalnuovo A. J. Am. Chem. Soc. 2000; 122: 5043
• 2d Rao KS, Wu T.-S. Tetrahedron 2012; 68: 7735
• 2e Lin B, Liu M, Ye Z, Ding J, Wu H, Cheng J. Org. Biomol. Chem. 2009; 7: 869
• 3a Wolfe JP, Wagaw S, Marcoux J.-F, Buchwald SL. Acc. Chem. Res. 1998; 31: 805
• 3b Hartwig JF. Angew. Chem. Int. Ed. 1998; 37: 2046
• 4a Kumari AS, Pathak DD. Tetrahedron Lett. 2015; 56: 4135
• 4b Quach TD, Batey RA. Org. Lett. 2003; 5: 4397
• 4c Poonam R, Rajendra S. Tetrahedron Lett. 2014; 55: 5256
• 4d Islam SM, Salam N, Mondal P, Roy AS, Ghosh K, Tuhinac K. J. Mol. Catal. A: Chem. 2014; 387: 7
• 4e Chan DM. T, Monaco KL, Wang RP, Winters MP. Tetrahedron Lett. 1998; 39: 2933
• 4f Batey RA, Quach TD. Org. Lett. 2003; 5: 4397
• 4g Kantam ML, Venkanna GT, Sridhar C, Sreedhar B, Choudary BM. J. Org. Chem. 2006; 71: 9522
• 5a Mitchell TN In Metal-Catalyzed Cross-Coupling Reactions. Vol. 1. de Mejijere A, Diederich F. Wiley-VCH; Weinheim: 2004: 125-162
• 5b Kwong FY, Klapars A, Buchwald SL. Org. Lett. 2002; 4: 581
• 5c Wolfe JP, Wagaw S, Marcoux J.-F, Buchwald SL. Acc. Chem. Res. 1998; 31: 805
• 5d Hartwig JF. Angew. Chem. Int. Ed. 1998; 37: 2046
• 5e Kumari AS, Pathak DD. Tetrahedron Lett. 2015; 56: 4135
• 5f Quach TD, Batey RA. Org. Lett. 2003; 5: 4397
• 5g Poonam R, Rajendra S. Tetrahedron Lett. 2014; 55: 5256
• 5h Batey RA, Quach TD. Org. Lett. 2003; 5: 4397
• 6 Anctil EJ. G, Snieckus V In Metal-Catalyzed Cross-Coupling Reactions . Vol. 2. de Mejijere A, Diederich F. Wiley-VCH; Weinheim: 2004: 761-814
• 7a Moerlein SM. J. Org. Chem. 1987; 52: 664
• 7b Zhang Z, Pitteloud J.-P, Cabrera L, Liang Y, Toribio M, Wnuk SF. Org. Lett. 2010; 12: 816
• 8a Song RJ, Deng CL, Xie YX, Li JH. Tetrahedron Lett. 2007; 48: 7845
• 8b Lam PY. S, Deudon S, Averill KM, Li R, He MY, DeShong P, Clark CG. J. Am. Chem. Soc. 2000; 122: 7600
• 9 Zhang Q, Chen J, Liu M, Wu H, Cheng J, Qin C, Su W, Ding J. Synlett 2008; 935
• 10 Representative Procedure A Schlenk reaction tube was charged with phenyltrimethylgermane (2a, 194.9 mg, 1.0 mmol), 4-methoxyaniline (1m, 147.9 mg, 1.2 mmol), Pd(OAc)₂ (11.2 mg, 5 mol%), Ph₃P (13.1 mg, 5 mol%), NaOAc (164.1 mg, 2.0 mmol), toluene (2.0 mL), under argon atmosphere at 100 °C for 12 h. After completion of the reaction, as indicated by TLC, the reaction mixture was extracted with Et₂O (3 × 10 mL). The combined organic layer was washed by water and dried by Na₂SO₄. The solvent was removed in vacuo, and the residue was purified by a short column chromatography (silica gel 300–400 mesh, PE–EtOAc = 8:1) to give 3m in 87% isolated yield (173 mg); mp 102–103 °C. 4-Methoxy-N-Phenylaniline (3m) ¹H NMR (300 MHz, CDCl₃): δ = 7.25–7.18 (m, 3 H), 7.09–7.05 (m, 2 H), 6.92–6.83 (m, 4 H), 5.49 (s, 1 H), 3.81 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 135.7, 129.3, 124.3, 122.2, 119.5, 115.6, 114.6, 114.1, 55.6. MS (EI): m/z = 212. Anal. Calcd for C₁₃H₁₃NO: C, 78.35; H, 6.59; N, 7.02. Found: C, 78.22; H, 6.41; N, 6.95.