Mannich Reaction

Schematic representation of the Mannich Reaction.

Mechanism of the Mannich Reaction

Mechanism of the Mannich Reaction

Original publication	Archiv Pharm.. 1912, 250, 647.
Reviews	Acc. Chem. Res.. 2004, 37, 102. Angew. Chem. Int. Ed.. 1998, 37, 1044. Chem. Soc. Rev.. 2004, 37, 29. Comp. Org. Syn.. 1991, 2, 1007. Comp. Org. Syn.. 1991, 2, 893. Org. React.. 1942, 1, 303. Tetrahedron. 1990, 46, 1791.

Sample reactions

intermediate structure

AcOH, CH2O, Me2NH

Dioxane , H2O

RT, 2 h, 92%

intermediate structure

intermediate structure

(CF3CO)2O

CF3CO2H

Reflux, 14 h, 67% (2 steps)

intermediate structure

intermediate structure

2,6-Di-tert-butyl-4-methylpyridine, BCl3

CH2Cl2

RT, 15 h, 85%

intermediate structure

intermediate structure

intermediate structure

TMS2NLi

Et2O

-78 °C, 3 h, 78%

"Also isolated was the C5-epimer (8 % yield)."

intermediate structure

intermediate structure

TsOH

PhH

RT, 40 h, 58% (3 steps)

"Also isolated was the C2-epimer (18% yield)."

intermediate structure

intermediate structure

(CH2O)n

3-Methyl-1-butanol

Reflux, 20 h

intermediate structure

intermediate structure

Dess-Martin Periodinane, Et3N, NaHCO3, H2CN+Me2 I-

CH2Cl2

RT, ON, 97%

intermediate structure

intermediate structure

intermediate structure

DMF

100 °C

intermediate structure

intermediate structure

BF3.OEt2, HgO

MeOH

intermediate structure

intermediate structure

intermediate structure

i-PrN(Cy)Li, H2CN+Me2 I-

THF

-78 to 0 °C, 8 h, 15%

intermediate structure

intermediate structure

intermediate structure

intermediate structure

CF3CO2H

CH2Cl2

-78 °C to RT, 5.5 h, 78%

intermediate structure

intermediate structure

intermediate structure

Et3N, ZnCl2, t-BuOCl

THF

-78 °C to RT, ON

intermediate structure

intermediate structure

intermediate structure

THF

-78 °C to RT, 13 h, 83% (2 steps)

intermediate structure

intermediate structure

intermediate structure

intermediate structure

THF

-78 °C to RT, 2 h, 79%

intermediate structure

intermediate structure

TMS2NLi

THF

-15 °C to RT, 3.5 h, 26%

intermediate structure

intermediate structure

TMS2NK, 2-Butanone

Et2O

-78 °C, 90 min, 84%

intermediate structure

intermediate structure

TsOH

PhH

60 °C, 4 h, 74%

intermediate structure

intermediate structure

H2CN+Me2 I-

CH2Cl2

35 °C, 48 h

intermediate structure

intermediate structure

CH2O, Me2NH

AcOH

RT, 2 h

intermediate structure