Pictet-Spengler Reaction

Schematic representation of the Pictet-Spengler Reaction.

Mechanism of the Pictet-Spengler Reaction

Mechanism of the Pictet-Spengler Reaction

Original publication	Ber. Dtsch. Chem. Ges.. 1911, 44, 2030. Org. Lett.. 2003, 5, 43.
Reviews	Angew. Chem. Int. Ed.. 2011, 50, 8538. Arkivoc. 2005, 12, 98. Chem. Rev.. 1995, 95, 1797. Chem. Rev.. 2004, 104, 1431. Org. Prep. Proced. Int.. 1996, 28, 1.

Sample reactions

intermediate structure

intermediate structure

Dioxane , PhH

Reflux

intermediate structure

intermediate structure

H3PO4, NaIO4

Acetone, H2O

60-70 °C, 20 min, 60%

intermediate structure

intermediate structure

intermediate structure

t-BuCO2H

PhMe

Reflux, 50 min, 53%

"Also isolated was the C3-epimer (37 % yield)."

intermediate structure

intermediate structure

HCl

H2O, THF

RT, 30 h, 92%

intermediate structure

intermediate structure

intermediate structure

Cl2CHCO2H

PhMe

0 °C, 15 min, 100%

intermediate structure

intermediate structure

Me2S, CF3CO2H, PhSH, Cs2CO3

CH2Cl2

RT to 50 °C, 7.5 h, 84% (2 steps)

intermediate structure

intermediate structure

intermediate structure

BzOH, Hydroquinone

Dean-Stark

PhH

Reflux, 10 h, 84%

intermediate structure

intermediate structure

intermediate structure

BF3.OEt2

4 Å MS, Dean-Stark

PhMe

Reflux, 18 h

intermediate structure

intermediate structure

HCl

MeOH

RT, 30 h, 85%

intermediate structure

intermediate structure

intermediate structure

AcOH, CH2Cl2

0 °C to RT, ON

intermediate structure

intermediate structure

Camphorsulfonic acid

PhMe

80 °C, , 69%

intermediate structure

intermediate structure

intermediate structure

AcOH

PhMe

80 °C, 2 h, 26%

"Also isolated, 38 % isomer"

intermediate structure