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Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C-H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cp-x ligand selectively participates in conjunction with phthaloyl phenylalanine in the C-H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2-benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2-benzothiazines were obtained in high yields and excellent enantioselectivity, with s-values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.
Philippe Schwaller, Michael Alexander Skinnider, Florian Huber, Albert Hofstetter