Diarylprolinol in the Direct Asymmetric Aldol Reaction of Trifluoromethylacetaldehyde Ethyl Hemiacetal with Aldehyde

Abstract

Asymmetric direct aldol reaction of trifluoromethylacet­aldehyde with aldehyde using diarylprolinol as a catalyst, to afford a synthetically useful β-trifluoromethyl-β-hydroxy aldehyde with excellent enantioselectivity, was developed. Commercially available trifluoromethylacetaldehyde ethyl hemiacetal was used directly as a precursor of trifluoromethylacetaldehyde without acid pyrolysis or distillation prior to use.

Key words

asymmetric synthesis - aldol reactions - organocatalyst - diarylprolinol - trifluoromethylacetaldehyde

References and Notes

• 1a Enantiocontrolled Synthesis of Fluoro-Organic Compounds   Soloshonok VA. Wiley; Chichester: 1999. 
• 1b Kirsch P. Modern Fluoroorganic Chemistry   Wiley-VCH; Weinheim: 2004. 
• 1c Uneyama K. Organofluorine Chemistry   Blackwell; Oxford: 2006. 
• 1d Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology   Blackwell; Oxford: 2009. 
• 2 Review, see: Modern Aldol Reactions   Vol. 1 and 2:  Mahrwald R. Wiley-VCH; Weinheim: 2004. 
• 3 Iseki K. Oishi S. Kobayashi Y. Tetrahedron  1996,  52:  71 
• 4 List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 
• For selected reviews on organocatalysis, see:
• 5a Dalko
  PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
• 5b Asymmetric Organocatalysis   Berkessel A. Groger H. Wiley-VCH; Weinheim: 2005. 
• 5c Hayashi Y.
  J. Synth. Org. Chem. Jpn.  2005,  63:  464 
• 5d List B. Chem. Commun.  2006,  819 
• 5e Marigo M. Jørgensen KA. Chem. Commun.  2006,  2001 
• 5f Gaunt MJ. Johansson CCC. McNally A. Vo NT. Drug Discov. Today  2007,  12:  8 
• 5g Enantioselective Organocatalysis   Dalko PI. Wiley-VCH; Weinheim: 2007. 
• 5h Mukherjee S. Yang JW. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
• 5i Walji AM. MacMillan DWC. Synlett  2007,  1477 
• 5j MacMillan DWC. Nature (London)  2008,  455:  304 
• 5k Barbas CF. Angew. Chem. Int. Ed.  2008,  47:  42 
• 5l Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
• 5m Melchiorre P. Marigo M. Carlone A. Bartoli G. Angew. Chem. Int. Ed.  2008,  47:  6138 
• 5n Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
• 6 Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed.  2004,  43:  1983 
• 7 Funabiki K. Yamamoto H. Nagaya H. Matsui M. Tetrahedron Lett.  2006,  47:  5507 
• 8 Northrup AB. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  6978 
• Selected examples of organocatalytic cross-aldol reaction of aldehydes, see:
• 9a Chowdari NS. Ramachary DB. Cordova A. Tetrahedron Lett.  2002,  43:  9591 
• 9b Pihko PM. Erkkila A. Tetrahedron Lett.  2003,  44:  7607 
• 9c Pidathala C. Hoang L. Vignola N. List B. Angew. Chem. Int. Ed.  2003,  42:  2785 
• 9d Mase N. Tanaka F. Barbas CF. Org. Lett.  2003,  5:  4369 
• 9e Mans DM. Pearson WH. Org. Lett.  2004,  6:  3305 
• 9f Thayumanavan R. Tanaka F. Barbas FC. Org. Lett.  2004,  6:  3541 
• 9g Northrup AB. Mangion IK. Hettche F. MacMillan DWC. Angew. Chem. Int. Ed.  2004,  43:  2152 
• 9h Mase N. Tanaka F. Barbas CF. Angew. Chem. Int. Ed.  2004,  43:  2420 
• 9i Mangion IK. Northrup AB. MacMillan DWC. Angew. Chem. Int. Ed.  2004,  43:  6722 
• 9j Storer RI. MacMillan DWC. Tetrahedron  2004,  60:  7705 
• 9k Northrup AB. Macmillan DWC. Science  2004,  305:  1752 
• 9l Reyes E. Cordova A. Tetrahedron Lett.  2005,  46:  6605 
• 9m Casas J. Engqvist M. Ibrahem I. Kaynak B. Cordova A. Angew. Chem. Int. Ed.  2005,  44:  1343 
• 9n Cordova A. Engqvist M. Ibrahem I. Casas J. Sunden H. Chem. Commun.  2005,  2047 
• 9o Cordova A. Ibrahem I. Casas J. Sunden H. Engqvist M. Reyes E. Chem. Eur. J.  2005,  11:  4772 
• 9p Hayashi Y. Aratake S. Okano T. Takahashi J. Samiya T. Shoji M. Angew. Chem. Int. Ed.  2006,  45:  5527 
• 9q Hayashi Y. Itoh T. Aratake S. Ishikawa H. Angew. Chem. Int. Ed.  2008,  47:  2082 
• 10 Hayashi Y. Itoh T. Aratake S. Ishikawa H. Angew. Chem. Int. Ed.  2008,  47:  2082 
• 11 Urushima T. Yasui Y. Ishikawa H. Hayashi Y. Org. Lett.  2010,  12:  2966 

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TCI, catalog number T0791.

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When the reaction was performed in 72 h, the yield increased to 49% but the anti/syn ratio decreased to 3.5:1, which indicates that the partial isomerization occurred during the reaction.