Catalytic Enantioselective Synthesis of Highly Functionalized Pentafluorosulfanylated Pyrrolidines

Abstract

The first catalytic asymmetric synthesis of highly functionalized pentafluorosulfanylated pyrrolidines is described. The method, based on a 1,3-dipolar cycloaddition reaction of aryl and heteroaryl-substituted glycine Schiff bases with pentafluorosulfanyl acrylic esters, gave access to a broad range of pyrrolidines bearing aryl, naphtyl, and heteroaryl groups. By using Xing-Phos as a catalyst, the corresponding products were obtained in good yields, good to high regioselectivity, and excellent diastereo- and enantioselectivities (up to 98 % ee). This methodology allowed the preparation of enantioenriched SF compounds for the first time using an enantioselective approach.

Ligand-Controlled Inversion of Diastereo- and Enantioselectivity in Silver-Catalyzed Azomethine Ylide–Imine Cycloaddition of Glycine Aldimino Esters with Imines

“…In particular for aliphatic imine 2c with a branched i -Pr group, higher yield (70%) and better enantioselectivity (97% ee) than that for linear aliphatic imines were observed. This result supported the magic effect of the multiple stereogenic substituents on syn -( R, R s )-Xing-Phos , in the silver-mediated AYI cycloaddition reactions under conditions A. Notably, the stereochemical and configuration assignment of syn - 3ag was determined by X-ray analysis (Figure ) in which the structure of syn -products 3 was further confirmed with good syn -selectivity in this Xing-Phos-controlled AYI cycloaddition reaction.…”

Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

“…Scheme 22 Catalytic enantioselective synthesis of SF5-pyrrolidines 25 Indoles represent one of the most widely used classes of heterocyclic compounds in medicinal chemistry. Bizet et al described an efficient and scalable strategy to access 2-SF5 (aza)indoles.…”

The Discovery of Multifunctional Chiral P Ligands for the Catalytic Construction of Quaternary Carbon/Silicon and Multiple Stereogenic Centers

“…Notably, Xing-Phos has been proved to be highly efficient in promoting the asymmetric cycloaddition of glycine aldimino esters with various activated alkenes (Scheme ), ,, including nitroalkenes, maleimides, chalcones, and less-reactive methyl cinnamates, giving the corresponding enantioenriched pyrrolidines with multiple stereogenic centers in good yields and diastereoselectivities (up to >98:2 dr) as well as excellent enantioselectivities (up to 99% ee). Recently, Jubault, Bouillon, and co-workers also revealed the excellent performance of Xing-Phos in the catalytic asymmetric synthesis of highly functionalized pentafluorosulfanyl (SF 5 )-substituted pyrrolidines (up to 98% ee) …”