[184304-16-3] · C10H12N2O · (MW 176.23)
(catalyst used for the selective methanolysis of a-hydroxy esters)
Physical Data: light-yellow crystalline solid; mp 98-99 °C.
Solubility: soluble in most common organic solvents. Not soluble in water.
Form Supplied in: not commercially available.
Analysis of Reagent Purity: 1H NMR, 13C NMR.
Preparative Methods: this catalyst has been prepared from the isopropyl amide of 2-picolinic acid by metalation with n-BuLi and trapping with iodine, followed by an halogen-dance reaction with LDA to provide the 4-iodo derivative. Nucleophilic aromatic substitution of the iodide for a pyrrolidine in refluxing pyrrolidine is followed by DIBAL reduction of the amide to provide the aldehyde in 34% overall yield for the four steps.1 Alternatively, it can be prepared from 4-pyrrolidino pyridine (PPY) by metalation of the BF3 complex and trapping with DMF.2
Purification: flash chromatography.
Handling, Storage, and Precautions: no special instructions for storage and handling are mentioned in the literature. Use in a fume hood.
2-Formyl-4-pyrrolidino pyridine (FPP, 1) has been used for the hydroxyl-directed methanolysis of a-hydroxy esters.1 The preference for the methanolysis of para-nitrophenyl glycolate over para-nitrophenyl methoxyacetate is 96:1 in competition reactions (
The reagent was designed as a nucleophilic catalyst with two sites, one a binding site (the aldehyde), the other a catalytic site (the pyridine nitrogen). Hydroxyl direction occurs by the formation of a hemiacetal between the hydroxyl group of the substrate and the aldehyde of the catalyst. An extensive examination of the mechanism of the reaction revealed that the pyridine nitrogen acts as a base. Its role is to deprotonate the hydroxyl oxygen of the hemiacetal which acts as a nucleophile, attacks the carbonyl of the substrate, and forms the unusual dioxolanone 3 (
Within this class of catalysts, others are more selective, most notably, the ketone-derived catalysts 7-10.4 These compounds display comparable activity, but significantly greater selectivity for the methanolysis of para-nitrophenyl glycolate over para-nitrophenyl methoxyacetate than the aldehyde-derived catalysts (1700:1 or greater,
DMAP, 4-dimethylamino pyridine;
University of Colorado, Boulder, Colorado, USA