Convenient One-Pot Synthesis of Chiral Tetrahydropyridines via a Multicomponent Reaction

Abstract

The multicomponent condensation of various β-dicarbonyl compounds, acrolein and (S)-2-phenylglycinol was found to provide a one-pot access to chiral 6-carbonyl-3-phenyl-2,3,8,8a-tetrahydro-7H-[1,3]oxazolo[3,2-a]pyridines. The value of this methodology is illustrated by the short and efficient synthesis of (-)-lupinine.

Key words

multicomponent reaction - tetrahydropyridines - oxazolidine - asymmetric synthesis - alkaloids

References

• 1 Boiteau L. Boivin J. Liard A. Quiclet-Sire B. Zard SZ. Angew. Chem. Int. Ed.  1998,  37:  1128 
• 2 Botuha C. Galley CMS. Gallagher T. Org. Biomol. Chem.  2004,  2:  1825 
• 3 Paulvannan K. Stille JR. J. Org. Chem.  1994,  59:  1613 
• 4 Noël R. Vanucci-Bacqué C. Fargeau-Bellassoued M.-C. Lhommet G. Eur. J. Org. Chem.  2007,  476 
• 5 Noël R. Vanucci-Bacqué C. Fargeau-Bellassoued M.-C. Lhommet G. J. Org. Chem.  2005,  70:  9044 
• 6a Simon C. Peyronel J.-F. Rodriguez J. Org. Lett.  2001,  3:  2145 
• 6b Liéby-Muller F. Constantieux T. Rodriguez J. Synlett  2007,  1323 
• 7 For a review on MCRs using β-dicarbonyl derivatives, see: Simon C. Constantieux T. Rodriguez J. Eur. J. Org. Chem.  2004,  4957 
• 9 Calvet S. David O. Vanucci-Bacqué C. Fargeau-Bellassoued M.-C. Lhommet G. Tetrahedron  2003,  59:  6333 
• 10 Agami C. Dechoux L. Hebbe S. Ménard C. Tetrahedron  2004,  60:  5433 
• 13 Cimarelli C. Palmieri G. J. Org. Chem.  1996,  61:  5557 
• 14 Agami C. Dechoux L. Ménard C. Hebbe S. J. Org. Chem.  2002,  67:  7573 
• 15 Banwell MG. Crasto CF. Easton CJ. Karoli T. March DR. Nairn MR. O’Hanlon PJ. Oldman MD. Willis AC. Yue W. Chem. Commun.  2001,  2210 
• 16 Kinghorn AD. Balandrin MF. In Alkaloids: Chemical and Biological Perspectives   Vol. 2:  Pelletier SW. John Wiley & Sons; New York: 1984.  p.105 
• 17 Ledoux S. Marchalant E. Célérier J.-P. Lhommet G. Tetrahedron Lett.  2001,  42:  5397 

8

The use of methyl vinyl ketone always led to intractable mixtures, with only a trace of the expected tetrahydro-pyridines.

11

The diastereomers were inseparable by column chromato-graphy, except for compounds 1a and 1h.⁵

12

Improved yield was obtained by the addition of 0.5 more equivalents of (S)-2-phenylglycinol after reaction for 24 hours; under these conditions, the expected compound 1g was isolated in 53% yield and the presence of compound 4g was not detected.