Reductive N-Arylethylation of Aromatic Amines and N-Heterocycles with Enol Ethers

Abstract

A convenient method for N-arylethylation of aromatic amines and heterocycles under mild reductive conditions was developed using (2-methoxyvinyl)(hetero)arenes as building blocks and triethylsilane/trifluoroacetic acid as reducing agent. This protocol is compatible with numerous functional groups, and aliphatic amines are inert due to protonation.

Key words

arylethylation - triethylsilane - aromatic amines - heterocycles - chemoselectivity

• References

• 1 Abdel-Magid AF. Mehrmann SJ. Org. Process Res. Dev. 2006; 10: 971
• 2 Wekesa FS. Phadke N. Jahier C. Cordes DB. Findlater M. Synthesis 2014; 46: 1046
• 3 Larrosa M. Guerrero C. Rodríguez R. Cruces J. Synlett 2010; 2101
• 4 Eisch JJ. Dua SK. Kovacs CA. J. Org. Chem. 1987; 52: 4437
• 5 Haddou TB. Béni S. Hosztafi S. Malfacini D. Calo G. Schmidhammer H. Spetea M. PLOS One 2014; 9: e99231
• 6 Eggler JF. Holland GF. Johnson MR. Volkmann RA. (Pfizer Inc.) US Patent 4738972, 1988
• 7a Müller TE. Beller M. Chem. Rev. 1998; 98: 675
• 7b Kumar K. Michalik D. Castro IG. Tillack A. Zapf A. Arlt M. Heinrich T. Böttcher H. Beller M. Chem. Eur. J. 2004; 10: 746
• 8 Jaspers D. Doye S. Synlett 2011; 1444
• 9 Munro-Leighton C. Delp SA. Alsop NM. Blue ED. Gunnoe TB. Chem. Commun. 2008; 111
• 10 Heutling A. Pohlki F. Bytschkov I. Doye S. Angew. Chem. Int. Ed. 2005; 44: 2951
• 11 Hamid MH. S. A. Williams JM. J. Chem. Commun. 2007; 725
• 12 Iranpoor N. Firouzabadi H. Nowrouzi N. Khalili D. Tetrahedron 2009; 65: 3893
• 13a Katritzky AR. Shobana N. Harris PA. Tetrahedron Lett. 1991; 32: 4247
• 13b Katritzky AR. Strah S. Belyakov SA. Tetrahedron 1998; 54: 7167
• 14 Katritzky AR. Saczewski F. Marson CM. J. Org. Chem. 1985; 50: 1351
• 15 Werner V. Ellwart M. Wagner AJ. Knochel P. Org. Lett. 2015; 17: 2026
• 16 Patel JP. Li A.-H. Dong H. Korlipara VL. Mulvihill MJ. Tetrahedron Lett. 2009; 50: 5975
• 17 Righi M. Bedini A. Piersanti G. Romagnoli F. Spadoni G. J. Org. Chem. 2011; 76: 704
• 18 Popp TA. Uhl E. Ong DN. Dittrich S. Bracher F. Tetrahedron 2016; 72: 1668
• 19 Popp TA. Bracher F. Synthesis 2015; 47: 3333
• 20 Righi M. Topi F. Bartolucci S. Bedini A. Piersanti G. Spadoni G. J. Org. Chem. 2012; 77: 6351
• 21 Appleton JE. Dack KN. Green AD. Steele J. Tetrahedron Lett. 1993; 34: 1529
• 22 Cabrero-Antonino JR. Adam R. Junge K. Beller M. Chem. Sci. 2017; 8: 6439
• 23 Xiao Y. Araldi GL. Zhao Z. Reddy A. Karra S. Brugger N. Fischer D. Palmer E. Bao B. McKenna SD. Bioorg. Med. Chem. Lett. 2008; 18: 821
• 24 Brown CE. McNulty J. Bordon C. Yolken R. Jones-Brando L. Org. Biomol. Chem. 2016; 14: 5951
• 25 Xiao Y. Araldi GL. Zhao Z. Reddy A. Karra S. Brugger N. Fischer D. Palmer E. Bao B. Mckenna SD. Bioorg. Med. Chem. Lett. 2008; 18: 821
• 26 Winterfeldt E. Chem. Ber. 1963; 96: 3349
• 27 Clarke D. Gilbert BC. Hanson P. Kirk CM. J. Chem. Soc., Perkin Trans. 2 1978; 1103
• 28 El-Hamamy AA. Hill J. Townend J. J. Chem. Soc., Perkin Trans. 1 1983; 573
• 29 Wekesa FS. Phadke N. Jahier C. Cordes DB. Findlater M. Synthesis 2014; 46: 1046
• 30 Mokrosz JL. Bojarski AJ. Charakchieva-Minol S. Duszynska B. Mokrosz MJ. Paluchowska MH. Arch. Pharm. (Weinheim) 1995; 328: 604
• 31 Albright JD. DeVries VG. Largis EE. Miner TG. Reich MF. Schaffer SA. Shepherd RG. Upeslacis J. J. Med. Chem. 1983; 26: 1378
• 32 Manning RE. US Patent 3963780 A, 1976