title: Enhanced selectivities for the hydroxyl-directed methanolysis of esters using the 2-acyl-4-aminopyridine class of acyl transfer catalysts: ketones as binding sites.
abstract: In this paper we describe the preparation of a series of 2-acyl-4-aminopyridines, and their use as catalysts for the hydroxyl-directed methanolysis of alpha-hydroxy esters in preference to alpha-methoxy esters. Hydroxyl-direction with these catalysts, which contain ketones at the 2-position of the pyridine, is achieved by reversible addition of the alcohol of the hydroxy ester to the ketone to provide the corresponding hemiketal. Their activity is compared to that of the previously described catalyst 2-formyl-4-pyrrolidinopyridine (FPP), which contains an aldehyde at the 2-position of the pyridine. The catalysts which contain ketones at the 2-position range in reactivity from 10 times slower to slightly faster than FPP, and certain of these are much more selective for the methanolysis of hydroxy esters than FPP. This increase in selectivity is ascribed to a decrease in the rate of the nondirected methanolysis reaction with the ketone-derived catalysts. The evidence suggests that the nondirected reaction does not proceed by an intermolecular general base mechanism, but rather via a nucleophilic catalysis mechanism in which the hydroxyl group of the hemiacetal formed upon addition of methanol to the aldehyde of FPP acts as the nucleophile. Since the hydroxyl group derived from a hemiketal is more hindered and less nucleophilic than that derived from a hemiacetal, the nondirected reaction is much slower for the catalysts containing ketones as binding sites.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sammakia
authors.forename: T B
authors.initials: TB
authors.lastname: Hurley
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D004952:Esters / Q000737:chemistry* / Q000378:metabolism*; D006868:Hydrolysis; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008697:Methane / Q000378:metabolism*; D011759:Pyrrolidines / Q000737:chemistry
chemical_list: D004952:Esters; D007659:Ketones; D011759:Pyrrolidines; D015761:4-Aminopyridine; D008697:Methane