Intertwined Processes in the Pummerer-Type Rearrangement Affording α-Trifluoromethoxylated Thioethers and the Corresponding Highly Enantioenriched Sulfoxides.

A method to access racemic or highly stereoenriched α-trifluoromethoxylated sulfoxides through the Pummerer rearrangement of aryl methyl sulfoxides followed by the oxidation of the resulting trifluoromethoxylated sulfides is described. Among the three reagents selected as both rearrangement activators and F3CO- anion sources, 2,4-dinitro-1-(trifluoromethoxy)benzene (DNTFB) was found to be the most effective. In each case, the OCF3-source was shown to play diverse key roles in the rearrangement. Enantioenriched trifluoromethoxy-sulfoxides (up to 95% enantiomeric excess) were obtained using an oxaziridinium salt derived from cholesterol. The configurational stability of these sulfoxides was investigated by thermal enantiomerization followed by enantioselective chromatography. Finally, the acidity of the protons in α-position of the sulfinyl group was determined in DMSO (pKa value 20.3) suggesting the potency of this new scaffold for preparing trifluoromethoxylated trisubstituted C-sp3 centers via a deprotonation/alkylation sequence.