An Efficient Synthesis of Thalifoline

Abstract

An efficient multi-step approach for the synthesis of the isoquinolin-1-one alkaloid thalifoline (1) is described. The key intermediate carbamate 8a underwent a modified Bischler-Napieralski-type cyclization using Banwell’s Tf₂O/DMAP conditions to form the lactam 9a under mild conditions and in excellent yield.

Key Words

alkaloids - thalifoline - quinolines - heterocycles - isoquinoline - ring closure - cyclizations

References

• 1 Doskotch RW. Schiff PL. Beal JL. Tetrahedron  1969,  25:  469 
• 2 Cava MP. Bessho K. Douglas B. Markey S. Weisbach JA. Tetrahedron Lett.  1966,  36:  4279 
• 3 Cava MP. Buck KT. Tetrahedron  1969,  25:  2795 
• 4 Shamma M. Foy JE. Miana GA. J. Am. Chem. Soc.  1974,  96:  7809 
• 5a Suau R. Rico R. Lopez-Romfro JM. Najera F. Cuevas A. Phytochemistry  1998,  49:  2545 
• 5b For a recently reported enantioselective synthesis of (-)-tejedine see: Wang Y.-C. Georghiou PE. Org. Lett.  2002,  4:  2675 
• 6a Banwell MG. Cowden CJ. Gable RR. J. Chem. Soc., Perkin Trans. 1  1994,  3515 
• 6b Banwell MG. Bissett BD. Busato S. Cowden CJ. Hockless DCR. Holman JW. Read RW. Wu AW. J. Chem. Soc., Chem. Commun.  1995,  2551 
• 7 Worrall DE. Org. Synth., Coll. Vol. 1   J. Wiley and Sons; Chichester: 1941.  p.413 
• 8 Hey DH. Palluel AL. J. Chem. Soc.  1957,  2926 
• 9 Dauzonne D. Royer R. Synthesis  1984,  12:  1054 
• 10 Finkelstein J. J. Am. Chem. Soc.  1951,  73:  550 
• 11 Takahashi H. Suzuki Y. Chem Pharm. Bull.  1983,  31:  4295 
• 12 Brown HC. Choi YM. Narisimhan S. J. Org. Chem.  1982,  47:  3153 
• 13 Schultz AG. Guzi TJ. Larsson E. Rahm R. Thakkar K. Bidlack JM. J. Org. Chem.  1998,  63:  7795 
• 14 Wang X. Tan J. Grozinger K. Tetrahedron Lett.  1998,  39:  6609 
• 15 Hutchinson JH. Cook JJ. Brashear KM. Breslin MJ. Glass JD. Gould RJ. Halczenko W. Holahan MA. Lynch RJ. Sitko GR. Stranieri MT. Hartman GD. J. Med. Chem.  1996,  39:  4583 
• 16 Martin SF. Tu C. J. Org.Chem.  1981,  46:  3763 
• 17 Eaton PE. Carlson GR. Lee JT. J. Org. Chem.  1973,  38:  4071 
• 18 Kametani T. Koizumi M. Fukumoto K. J. Chem. Soc. C.  1971,  1792 
• 19 Irie H. Shiina A. Fushimi T. Katakawa J. Fujii N. Yajima H. Chem. Lett.  1980,  875 
• 21 Lange NA. Hambourger WE. J. Am. Chem. Soc.  1931,  53:  3865 

20

In ref. [10] J. Finkelstein reported this compound using a different procedure but did not quote a melting point. Sigma-Aldrich lists this compound as having a mp of 61-64 °C.