Stereoselective oxidation of phenoxathiin-based thiacalix[4]arenes - stereomutation of sulfoxide groups

A phenoxathiin-based macrocycle represents an inherently chiral building block, well accessible in two steps from the starting thiacalix[4]arene. The oxidized derivatives bearing one sulfoxide group and three sulfonyl groups were found to exhibit unexpected stereochemical preferences of the sulfoxide group during transformations. The sulfoxide moiety is always pointing out of the cavity (S=O out ), while the opposite (S=O in) configuration was never obtained by direct oxidation. In order to achieve full oxidation to sulfone, the configuration of the sulfoxide group must first be changed by a photochemical inversion before the final oxidation occurs. The phenomenon of stereomutation of the sulfoxide group in the thiacalixarene series was studied using a combination of experimental (NMR and single crystal X-ray analysis) and theoretical (DFT) approaches.

Automated summary

A phenoxathiin-based macrocycle, accessible from thiacalix[4]arene in two steps, is found to be inherently chiral. During transformations, oxidized derivatives with one sulfoxide group and three sulfonyl groups show unexpected stereochemical preferences. The sulfoxide moiety always points out of the cavity (S=O out), and the opposite (S=O in) configuration is never obtained by direct oxidation. Achieving full oxidation to sulfone requires photochemical inversion of the sulfoxide group prior to the final oxidation. The stereomutation of the sulfoxide group in the thiacalixarene series is studied using experimental (NMR and single crystal X-ray analysis) and theoretical (DFT) approaches.