Synthesis of new chiral pyrylium salts and their phosphinine and pyridine derivatives

Despite their versatility, chiral pyryliums are almost unknown in the literature. Reported here is the synthesis of several new chiral pyrylium salts and the corresponding pyridines and phosphinines. This work more than doubles the number of reported chiral pyryliums, and also represents the first racemizable/epimerizable pyryliums. The derived phosphinines and pyridines represent rare α-chiral ligands for transition metals. © 2012 Elsevier Ltd. All rights reserved

Kinetic studies of the epimerization of diastereomeric pyrylium salts

Chiral pyrylium salts are almost unknown in the literature, and none that are epimerizable have been reported prior to our work. Herein, we report two new epimerizable pyryliums and the kinetics of the diastereomeric equilibration of these and one other example. All of these required a careful analysis of the 1H NMR spectrum to identify the stereoisomers, particularly for one of them. The temporal evolution of the relative isomeric concentrations was determined through acquisition of progressive NMR spectra. The base-catalyzed isomerization kinetics were successfully modeled as sequential, pseudo-first-order reactions that transition through a long-lived intermediate. These results suggest that the pseudobase intermediate is the operative catalyst when epimerizations are initiated with amines with pKa 7.4 or greater. Given the bulky nature of the operative acid (pyrylium) and base (pseudobase), the rate of these epimerizations is sensitive to steric bulk in the pyrylium. Thus, the reaction kinetics slow by a factor of 25 when substituents are placed at the ortho versus para position on the pyrylium cyclohexane ring. This is likely due to the difficulty of pseudobase attack at the sterically crowded pyrylium acidic hydrogen position. © 2013 American Chemical Society

Kinetic Studies of the Epimerization of Diastereomeric Pyrylium Salts

Chiral pyrylium salts are almost unknown in the literature, and none that are epimerizable have been reported prior to our work. Herein, we report two new epimerizable pyryliums and the kinetics of the diastereomeric equilibration of these and one other example. All of these required a careful analysis of the ¹H NMR spectrum to identify the stereoisomers, particularly for one of them. The temporal evolution of the relative isomeric concentrations was determined through acquisition of progressive NMR spectra. The base-catalyzed isomerization kinetics were successfully modeled as sequential, pseudo-first-order reactions that transition through a long-lived intermediate. These results suggest that the pseudobase intermediate is the operative catalyst when epimerizations are initiated with amines with p<i>K</i>_a 7.4 or greater. Given the bulky nature of the operative acid (pyrylium) and base (pseudobase), the rate of these epimerizations is sensitive to steric bulk in the pyrylium. Thus, the reaction kinetics slow by a factor of 25 when substituents are placed at the ortho versus para position on the pyrylium cyclohexane ring. This is likely due to the difficulty of pseudobase attack at the sterically crowded pyrylium acidic hydrogen position