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Chiral Binaphthyl‐Based Iodonium Salt (Hypervalent Iodine(III)) as Hydrogen‐ and Halogen‐Bonding Bifunctional Catalyst: Insight into Abnormal Counteranion Effect and Asymmetric Synthesis of <i>N</i>,<i>S</i>‐Acetals

Yasushi Yoshida, Tappei Fujimura, Takashi Mino, Masami Sakamoto

2022Advanced Synthesis & Catalysis54 citationsDOI

Abstract

Abstract Asymmetric construction of chiral N , S ‐acetal skeletons is important because they are widely present in natural products and pharmaceuticals. Halogen‐bonding is a unique interaction that has been an organic synthesis focus, although research into chiral variants is limited. Halonium salts have been found to act as halogen‐bonding catalysts and asymmetric catalysis using chiral bromonium salts under basic conditions was recently discovered by our group. Herein, we report the asymmetric syntheses of chiral N , S ‐acetals in good‐to‐excellent yields and enantioselectivities (82–97% ee) through bulky thiol additions to imines catalysed by a chiral iodonium salt under neutral conditions. The reaction mechanism was studied using NMR experiments and DFT calculations of a plausible intermediate, which revealed that the imine substrate is activated by the catalyst in a bidentate manner. The abnormal counteranion effect observed for the tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate anion in the present system was examined by 1 H NMR spectroscopy. magnified image

Topics & Concepts

ChemistryHalogen bondCatalysisBifunctionalTrifluoromethylImineHalogenMedicinal chemistryDenticityOrganocatalysisEnantioselective synthesisAsymmetric hydrogenationHydrogen bondStereochemistryOrganic chemistryMoleculeCrystal structureAlkylAsymmetric Synthesis and CatalysisAlkaloids: synthesis and pharmacologySynthesis and Catalytic Reactions
Chiral Binaphthyl‐Based Iodonium Salt (Hypervalent Iodine(III)) as Hydrogen‐ and Halogen‐Bonding Bifunctional Catalyst: Insight into Abnormal Counteranion Effect and Asymmetric Synthesis of <i>N</i>,<i>S</i>‐Acetals | Litcius