Enantioselective Synthesis of Chiral‐at‐Sulfur 1,2‐Benzothiazines by Cp^xRh^III‐Catalyzed C−H Functionalization of Sulfoximines

Abstract

Sulfoximines with stereogenic sulfur atoms are attractive structural motifs in drug discovery.Adirect catalytic enantioselective method for the synthesis of sulfur-chiral 1,2benzothiazines from readily accessible diaryl sulfoximines is presented. Rhodium(III) complexes equipped with chiral cyclopentadienyl ligands and paired with suitable carboxylic acid additives engage in an enantiodetermining C À Hactivation directed by the sulfoximine group.Subsequent trapping of the rhodacycle with abroad range of diazoketones gives access to S-chiral 1,2-benzothiazines with synthetically highly attractive substitution patterns in good yields and enantioselectivities. Scheme 3. Diazo substrate scope of the sulfoximine functionalization. Reaction conditions: 0.1 mmol 1a,0.1 mmol 2,2 .5 mmol Rh5,3 0mmol A4,50mmol NaSbF 6 ,0 .2 m in tBuOH at 35 8 8Cfor 24-72 h.Scheme 4. Parallel kinetic resolution of racemic diaryl sulfoximine rac-4. Scheme 5. Suggestedm echanism and steps that are potentially critical for the enantioselectivity.Angewandte Chemie Communications

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

“…[1,2] We have reported several classes of chiral Cp x ligands [3] and illustrated their potential for asymmetric Rh III catalysis [4] as well as with other transition metals. [1,2] We have reported several classes of chiral Cp x ligands [3] and illustrated their potential for asymmetric Rh III catalysis [4] as well as with other transition metals.…”

“…Rh III complexes has emerged over the past few years as an increasingly robust tool for enantioselective C À Hb ond functionalizations. [1,2] We have reported several classes of chiral Cp x ligands [3] and illustrated their potential for asymmetric Rh III catalysis [4] as well as with other transition metals. [5] Additionally,t he groups of You, [6] Antonchick and Waldmann, [7] and Perekalin [8] reported chiral Cp x ligands and subsequently applied them in asymmetric Rh III -catalyzed C À Hf unctionalizations.Acomplementary metallo-enzymatic approach based on supramolecular engineering was developed by the groups of Ward and Rovis.…”