A Simplified Synthesis of Takemoto’s Catalyst

Abstract

A facile two-step procedure for the preparation of Takemoto’s catalyst is reported. The thiourea moiety was obtained by condensation of 3,5-bis(trifluoromethyl)aniline with phenyl chlorothioformate and in situ substitution of phenol by trans-1,2-diaminocyclohexane. Subsequent reductive dimethylation using formaldehyde/zinc afforded Takemoto’s catalyst.

Key words

organocatalyst - thiourea - amine - bifunctional

References

• 1a Okino T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc.  2003,  125:  12672 
• 1b Okino T. Hoashi Y. Furukawa T. Yu X. Takemoto Y. J. Am. Chem. Soc.  2005,  127:  119 
• 2a Okino T. Hoashi Y. Takemoto Y. Angew. Chem. Int. Ed.  2005,  44:  4032 
• 2b Inokuma T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc.  2006,  128:  9413 
• 3 Takemoto Y. Miyabe H. Chimia  2007,  61:  269 
• 4 Okino T. Nakamura S. Furukawa T. Takemoto Y. Org. Lett.  2004,  6:  625 
• 5a Berkessel A. Cleemann F. Mukherjee S. Müller TN. Lex J. Angew. Chem. Int. Ed.  2005,  44:  807 
• 5b Berkessel A. Mukherjee S. Cleemann F. Müller TN. Lex J. Chem. Commun.  2005,  1898 
• 5c Berkessel A. Mukherjee S. Müller TN. Cleemann F. Roland K. Brandenburg M. Neudörfl J.-M. Lex J. Org. Biomol. Chem.  2006,  4:  4319 
• 6 Kaik M. Gawronski J. Tetrahedron: Asymmetry  2003,  14:  1559 
• 7 Bied C. Moreau JJE. Chi Man MW. Tetrahedron: Asymmetry  2001,  12:  329 
• 8 Touchard F. Fache F. Lemaire M. Tetrahedron: Asymmetry  1997,  8:  3319 
• 9 Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Chem. Pharm. Bull.  2004,  52:  477 
• 10 Menche D. Böhm S. Li J. Rudolph S. Zander W. Tetrahedron Lett.  2007,  48:  365 
• 11a Procuranti and Connon reported the formation of monothiourea 4 from isothiocyanate 7 and diamine 3 in 49% yield: Procuranti B. Connon SJ. Chem. Commun.  2007,  1421 
• 11b

  However, in our hands, the corresponding bis-thiourea was obtained as the major product from equimolar amounts of 4 and 7.

• 12 da Silva RA. Estevam IHS. Bieber L. W. Tetrahedron Lett.  2007,  48:  7680 
• 13 Loibner H. Pruckner A. Stütz A. Tetrahedron Lett.  1984,  25:  2535 
• 14 Mitchell JM. Finney NS. Tetrahedron Lett.  2000,  41:  8431 
• 15 Mukherjee S. PhD Dissertation, Universität Köln; Germany: 2005.