Methylaluminoxane (MAO)-Assisted Direct Amidation of Esters

Abstract

Aliphatic and aromatic esters are efficiently transformed into amides in good to excellent yields, under mild conditions using methylaluminoxane (MAO). This reaction can be performed either at room temperature or by applying microwave irradiation.

Key words

amidation - MAO - esters - amides - microwave

• References and Notes

• 1a Valeur E, Bradley M. Chem. Soc. Rev. 2009; 38: 606
• 1b Pattabiraman VR, Bode JW. Nature (London, U.K.) 2011; 480: 471
• 2a Gooβen LJ, Ohlmann DM, Lange PP. Synthesis 2009; 160
• 2b Veitch GE, Bridgwood KL, Ley SV. Org. Lett. 2008; 10: 3623
• 2c Kim BR, Lee H.-G, Kang S.-B, Sung GH, Kim J.-J, Park JK, Lee S.-G, Yoon Y.-J. Synthesis 2012; 44: 42
• 2d Huang Z, Reilly JE, Buckle RN. Synlett 2007; 1026
• 2e Al-Zoubi RM, Marion O, Hall DG. Angew. Chem. Int. Ed. 2008; 2876
• 2f Gernigon N, Al-Zoubi RM, Hall DG. J. Org. Chem. 2012; 77: 8386
• 2g Bao Y.-S, Zhaorigetu B, Angula B, Baiyin M, Jia M. J. Org. Chem. 2014; 79: 803
• 2h Han C, Lee JP, Lobkovsky E, Porco JA. J. Am. Chem. Soc. 2005; 127: 10039
• 2i Hosseini-Sarvari M, Sodagar E, Doroodmand MM. J. Org. Chem. 2011; 76: 2853
• 3a Basha A, Lipton M, Weinreb SM. Tetrahedron Lett. 1977; 48: 4171
• 3b Gustafsson T, Ponten F, Seeberger PH. Chem. Commun. 2008; 1100
• 3c Chung SW, Uccello DP, Choi H, Montgomery JI, Chen J. Synlett 2011; 2072
• 4a Chen EY.-X, Marks TJ. Chem. Rev. 2000; 100: 1391
• 4b Negureanu L, Hall RW, Butler LG, Simerall LA. J. Am. Chem. Soc. 2006; 128: 16816
• 5 Lipshutz BH, Butler T, Lower A. J. Am. Chem. Soc. 2006; 128: 15396
• 6 General ProceduresMethod A: To a mixture of ester (1 mmol) and amine (2 mmol) under an argon atmosphere was added a 10% solution of MAO in toluene (2 mL, 3 mmol). After 5 h at r.t., the solution was diluted with MTBE (3 mL) and quenched by addition of 10% aq NaOH (2 mL). The product was then extracted with MTBE (3×) and the combined organic layers were washed with a 1 M solution of HCl, dried over MgSO₄, filtered, and concentrated under reduced pressure to give usually the pure product (purity >90%). Less pure products were purified by flash chromatography on silica gel using a mixture of heptane and EtOAc.Method B: A mixture of ester (1 mmol) and amine (2 mmol) was placed in a MW vial under an argon atmosphere. A 10% solution of MAO in toluene (2 mL, 3 mmol) was then added, and the mixture was irradiated and stirred for 15 min at 110 °C. The solution was then cooled to r.t. and diluted with MTBE. The products were isolated in the same manner as in method A.