A series of four new azulene-1,5-diol diastereomers were prepared and found to exhibit large differences (ΔRf 0.22–0.46) in silica TLC mobilities despite having stereocenters four bonds apart. The stereoisomers were identified by X-ray crystallography, and in all cases the RR/SS diastereomers were less strongly retained than the RS/SR diastereomers. The crystal structures suggested that this is due to a conformational preference for the CF3 groups to be nearly perpendicular to the plane of the azulene ring, which caused the dihedral angle between the OH groups to be larger (in the RR/SS diastereomers) or smaller (in the RS/SR diastereomers). The smaller dihedral angles allow the RS/SR diastereomers to simultaneously bind to a silica surface and thus be more strongly retained. Two similar benzene derivatives and several cycloalkanediols with more proximate stereocenters showed little or no difference in mobilities between diastereomers, though the NMR differences were greater. Thus, the azulene ring is an important factor in enforcing the conformational preferences, either through steric interactions with the 4/8 substituents (H or methyl) or its significant dipole moment, or both.

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.

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.

The synthesis of 2,6-bis-hydrazonopyridines from 2,6-bis-hydrazinopyridine and the conversion of these bis-hydrazones into 2,6-bis-indazol-1-ylpyridines were studied. The conversion of bis-haloarylhydrazones to bis-indazoles was systematically optimized using iron and copper mediated reactions and various bases and ligands. By varying solvent, base, transition metal, and ligand, a novel regiospecific route to the 2,6-bis-indazol-1-ylpyridine class of ligands was developed.