Computational Studies on the Diastereospecific Lithium Variant of Oppenauer Oxidation of a Tofisopam Intermediate.

During the synthesis of tofisopam drug substance, an interesting diastereospecific lithium variant of Oppenauer oxidation was observed and investigated by density functional theory (DFT) calculations. The computations revealed energetic differences caused by steric differences between the diastereomers that might provide an explanation for the experimentally formed products. In addition, the trend in the measured NMR shifts was also in line with the computed values, which allowed the assignment of the absolute configuration of the diastereomers.

Chiroptical properties of cation complexes of chiral phenazino-18-crown-6 ether-type hosts.

Herein we report CD spectroscopic studies on complexes of (R,R)-dimethyl-, (R,R)-diisobutyl-, and (S,S)-di-sec-butyl-phenazino-18-crown-6 ligands (Scheme 1) with selected alkali (Na+, K+), alkaline earth (Mg2+, Ca2+), and transition-metal (Ag+, Zn2+, Ni2+, Cd2+, Pb2+) cations. The complexation was monitored in the 300- to 240-nm region of the CD spectra comprising mainly the 1Bb band of the heteroaromatic subunit. The CD spectra of the complexes showed an unexpected diversity.