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 1H NMR spectroscopy.

The front cover picture, prepared by Dr Y. Yoshida, illustrates the asymmetric syntheses of N,S‐acetals catalysed by their originally‐designed chiral iodonium salts. The 1,2‐addition reaction of bulky thiols to isatin‐derived ketimines were catalysed by the chiral iodonium salts in excellent yields and enantioselectivities under neutral conditions. The reaction mechanism was studied using NMR experiments and DFT calculations of a plausible intermediate, which revealed that the imine substrate was activated by the catalyst in a hydrogen‐ and halogen‐bonding bidentate activation manner. Details can be found in the Research Article by Yoshida and co‐workers. (Y. Yoshida, T. Fujimura, T. Mino, M. Sakamoto, Adv. Synth. Catal. 2022, 364, 1091‐1097; DOI: 10.1002/adsc.202101380)