Cinchona alkaloids OMe OMe H N OH MOH N R 8S, 9R-quinine 8R, 9s-quinidine Enantiomeric B-hydroxyamine functionality Nucleophilic catalysts Wynberg, H Top. Stereochem. 1986, 16, 87
Cinchona Alkaloids • Enantiomeric b-hydroxyamine functionality • Nucleophilic catalysts Wynberg, H. Top. Stereochem. 1986, 16, 87. S H N N OMe OH H N H H OH N OMe R 8S, 9R - quinine 8R, 9S - quinidine
ASymmetricβ- Lactones H H 1-2 mol% quinidine Clc H toluene,-25°C O 89% yield Clc (S)98%ee Requires electron deficient aldehydes and aromatic ketones 68-98%yied 89-98%ee Alkyl aryl ketones react in trace amounts Staring, E.G.J.: Wynberg, H.J. Am. Chem. Soc. 1982, 104, 166 Staring, E.G. J; Wynberg, H J. Org. Chem. 1985, 50, 1977
Asymmetric b-Lactones Staring, E. G. J.; Wynberg, H. J. Am. Chem. Soc. 1982, 104, 166. Staring, E. G. J.; Wynberg, H. J. Org. Chem. 1985, 50, 1977. O Cl 3 C H O H H O O Cl 3 C + 1-2 mol% quinidine toluene, -25 °C 89% yield (S) 98% ee Requires electron deficient aldehydes and aromatic ketones 68 – 98% yield 89 – 98% ee Alkyl aryl ketones react in trace amounts
Aldol- lactonization mechanism NR NR CCI 3 0 OAC NR OCH Re face of enolate blocked Aldehyde approaches the si face of enolate Dijkstra, G. D. H. Kellog, R. M; Wynberg, H. Svendsen, J. S; Marko, I; Sharpless, K. B J.Am.chem.Soc.1989.111.8069 Cortez, G.S., Tennyson, R L Romo, D.J. Am. Chem. Soc. 2001, 123, 7945
Aldol - Lactonization Mechanism Dijkstra, G. D. H.; Kellog, R. M.; Wynberg, H.; Svendsen, J. S.; Marko, I.; Sharpless, K. B. J. Am. Chem. Soc. 1989, 111, 8069. Cortez, G. S.; Tennyson, R. L.; Romo, D. J. Am. Chem. Soc. 2001, 123, 7945. NR3 O H H O NR3 H H O H CCl3 O H NR3 O Cl3C NR3 O O Cl3C O O NR3 Cl3C H N H OAc H N H OCH3 O + * * * * Aldehyde approaches the Si face of enolate * Re face of enolate blocked
Methyl Ketene Dimerization Me Zn 1 mol%amine Me Br THF,-78°C Br MeH Me OH LIAIH Me 20% yield Me Me uridine (R)98%ee (trimethyl quInine (S)93%ee Calter, M. A.J. Org. Chem. 1996, 61, 8006
Methyl Ketene Dimerization Calter, M. A. J. Org. Chem. 1996, 61, 8006. O Br Me Br Zn O Me H O O Me Me LiAlH4 (S) 93% ee (R) 98% ee O Me Me OH O R3 N Me O Me 1 mol% amine THF, -78 °C * * quinidine (trimethylsilyl)quinine 20% yield * *
Polypropionate Synthesis 0.3mo% 500° quinidine THF.-78°C Me - OLi Meo Me N MeMe THF,-78° Me Me THF,-78°C oO OH Meo OHC N MeMe MeMe Me Me MeMeMeMe 55% yield siphonarienal Guo, X ; Liao, W; Calter, M. A. Org. Lett. 2001, 3, 1499
Polypropionate Synthesis Guo, X.; Liao, W.; Calter, M. A. Org. Lett. 2001, 3, 1499. O Me O Me N MeO Li O Me H Me N O MeO Me OLi Me O H Me Me O O Me Me Me Me Me Me N O MeO Me O OH Me OHC Me Me Me Me 55% yield siphonarienal THF, -78 °C THF, -78 °C THF, -78 °C 0.3 mol% quinidine 2 500 °C