Ru(II)/Chiral Carboxylic Acid-Catalyzed Asymmetric [4+3] Annulation of Sulfoximines with α,β-Unsaturated Ketones

Sulfur-stereogenic containing benzo-fused heterocycles have gained much attention in drug discovery. However, the asymmetric synthesis of these chiral molecules with structural diversity is very challenging. Herein, we report the synthesis of chiral benzothiadiazine-1-oxides with a seven-membered ring via achiral Ru(II)-catalyzed asymmetric [4 + 3] annulation of sulfoximines with alpha,beta-unsaturated ketones assisted by chiral carboxylic acid (CCA). A broad range of chiral benzothiadiazepine-1-oxides bearing various functional groups could be prepared in up to 90% yield with up to >99% ee, expanding the chemical space of chiral sulfoximines. Notably, the oxidative cleavage of the double bonds in the products gave chiral N-benzoyl sulfoximines with a C-S chiral axis.

Automated summary

Chiral benzothiadiazine-1-oxides are sulfur-stereogenic compounds with structural diversity that have gained significant attention in drug discovery. This study reports the synthesis of these chiral molecules through an asymmetric [4 + 3] annulation reaction of sulfoximines with alpha,beta-unsaturated ketones, catalyzed by an achiral Ru(II) complex and assisted by a chiral carboxylic acid (CCA). The method allows for the preparation of a wide range of chiral benzothiadiazepine-1-oxides with various functional groups in high yields and excellent enantioselectivity, expanding the chemical space of chiral sulfoximines. Importantly, the oxidative cleavage of the products yields chiral N-benzoyl sulfoximines with a C-S chiral axis.