3

Aldol condensation
Condensation of a carbonyl with an enolate or an enol. A simple case is addition of an enolate to an aldehyde to afford an alcohol, thus the name aldol.

O R R1 2.

1. base O R
2

R OH O R3 R R1

O R H B: R1 deprotonation R R
3

O R1 R2 O condensation

R2 O O R3 R
Example 13

acidic R
1

R2 OH O R3 R R1

workup

O OTMS

LDA, THF, then MgBr2, 110 C, then

OHC OH BnO O O

OBn

OTMS

85% yield

Example 212

LDA, THF, 78 to 40 oC, then aldehyde, 1 h, 83%, 3:2 de O CO2H OTBS H O

HO CO2H OTBS

O
References
1.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Wurtz, C. A. Bull. Soc. Chim. Fr. 1872, 17, 436. Charles Adolphe Wurtz (1817 1884) was born in Strasbourg, France. After his doctoral training, he spent a year under Liebig in 1843. In 1874, Wurtz became a chair of organic chemistry at the Sorbonne, where he educated many illustrous chemists such as Crafts, Fittig, Friedel, and vant Hoff. The Wurtz reaction is no longer considered synthetically useful, although the aldol reaction that Wurtz discovered in 1872 has become a staple in organic synthesis. Nielsen, A. T.; Houlihan, W. J. Org. React. 1968, 16, 1 438. (Review). Still, W. C.; McDonald, J. H., III. Tetrahedron Lett. 1980, 21, 1031, 1035. Mukayama, T. Org. React. 1982, 28, 203 331. (Review). Mukayama, T.; Kobayashi, S. Org. React. 1994, 46, 1 103. (Review on Tin(II) enolates). Saito, S.; Yamamoto, H. Chem. Eur. J. 1999, 5, 1959 1962. (Review). Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325 335. (Review). Denmark, S. E.; Stavenger, R. A. Acc. Chem. Res. 2000, 33, 432 440. (Review). Nicolaou, K. C.; Ritzn, A.; Namoto, K. Chem. Commun. 2001, 1523. Palomo, C.; Oiarbide, M.; Garca, J. M. Chem. Eur. J. 2002, 8, 36 44. (Review). Alcaide, B.; Almendros, P. Eur. J. Org. Chem. 2002, 1595 1601. (Review). Wei, H.-X.; Hu, J.; Purkiss, D. W.; Par, P. W. Tetrahedron Lett. 2003, 44, 949. Bravin, F. M.; Busnelli, G.; Colombo, M.; Gatti, F.; Manzoni, L.; Scolastico, C. Synthesis 2004, 353. Mahrwald, R. (ed.) Modern Aldol Reactions, Wiley VCH: Weinheim, Germany, 2004. (Book).