title: Highly stereoselective asymmetric Pummerer reactions that incorporate intermolecular and intramolecular nonbonded S...O interactions.
abstract: New chiral sulfoxides (R(S),S)-3, (S(S),S)-3, (R(S),S)-4, and (S(S),S)-4 and known chiral sulfoxides (R(S))-5, (R(S))-6, and (R(S))-7 were synthesized, and the stereochemistry of the new sulfoxides (R(S),S)-3 and (R(S),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 (R(S), S)-3, (S(S), S)-3, (R(S), S)-4, (S(S), S)-4, (R(S))-5, (R(S))-6, and (R(S))-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 Ac(2)O 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.
authors.affiliation: Contribution from the Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nagao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Hiroe
authors.initials: H
authors.lastname: Takeshige
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sano
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sei