Highly Stereoselective Asymmetric Pummerer Reactions That Incorporate Intermolecular and Intramolecular Nonbonded S···O Interactions

New chiral sulfoxides (RS,S)-3, (SS,S)-3, (RS,S)-4, and (SS,S)-4 and known chiral sulfoxides (RS)-5, (RS)-6, and (RS)-7 were synthesized, and the stereochemistry of the new sulfoxides (RS,S)-3 and (RS,S)-4 was determined by X-ray crystallographic analysis. In their crystallographic structures, the intramolecular nonbonded S···O close contacts were recognized. Analyses of several sulfoxide complexes including rac-11 with N,N-dimethylacetamide (DMAC) or N-methyl-2-pyrrolidone (NMP) in a MeOH solution utilizing cold-spray ionization mass spectrometry provided, for the first time, direct information for intermolecular nonbonded S···O interactions between sulfoxides and amide (or lactam) in a solution. Highly diastereoselective and enantioselective Pummerer reactions based on the concept of intermolecular and intramolecular nonbonded S···O interactions were performed by treatment of several chiral sulfoxides (RS, S)-3, (SS, S)-3, (RS, S)-4, (SS, S)-4, (RS)-5, (RS)-6, and (RS)-7 with acetic anhydride and trimethylsilyl triflate (TMSOTf) in DMAC, NMP, N,N-dimethylformamide, and N-formylpiperidine. Mechanistic studies on these facile stereoselective Pummerer reactions revealed the necessity for the amide/TMSOTf complex, such as 26 or 27, to be an efficient activation reagent for Ac2O and a trapping reagent for the released acetate ion, and that DMAC and NMP had a positive effect on this highly stereoselective chiral transfer reaction.