Chiral Brønsted Acid Catalyzed Enantioconvergent Propargylic Substitution Reaction of Racemic Secondary Propargylic Alcohols with Thiols

• Published in: Chemistry : a European journal 2020-09, Vol.26 (49), p.11124-11128
• Main Authors: Kikuchi, Jun, Takano, Kyohei, Ota, Yusuke, Umemiya, Shigenobu, Terada, Masahiro
• Format: Article
• Language: English
• Subjects: Alcohols; Brønsted acids; Catalysts; Enantiomers; enantioselectivity; Functional groups; Information processing; organocatalysis; Phosphoric acid; Substitution reactions; Sulfur; thioethers; Thiols
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202001609

Despite the significant progress of the enantioselective reaction using chiral catalysts, the enantioselective nucleophilic substitution reaction at the chiral sp3‐hybridized carbon atom of a racemic electrophile has not been largely explored. Herein, we report the enantioconvergent propargylic substitution reaction of racemic propargylic alcohols with thiols using chiral bis‐phosphoric acid as the chiral Brønsted acid catalyst. The substitution products were formed in high yields with high enantioselectivities in most cases. The cation‐stabilizing effect of the sulfur functional group introduced at the alkynyl terminus is the key to achieving the efficient enantioconvergent process, in which chiral information originating from not only the racemic stereogenic center but also the formed contact ion pair is completely eliminated from the present system. An enantioconvergent propargylic substitution reaction of a racemic propargyl alcohol with a thiol was established using chiral bis‐phosphoric acid as the chiral Brønsted acid catalyst. The cation‐stabilizing effect of the sulfur functional group introduced at the alkynyl terminus is the key to achieving the efficient enantioconvergent process.