Asymmetric Syntheses of S,S-Dialkyl-Substituted Sulfoximines and Related Heterocycles

Abstract

Enantiomerically enriched forms of a sulfoximine-based myristic acid analogue are prepared using either an asymmetric desymmetrization with a chiral base, or an enantioselective oxidation procedure as key steps. Additionally, a variety of 2-oxa-2-alkyl 3,4-dihydro 2,1-benzothiazines are synthesized via intramolecular metal­-catalyzed N-arylation of appropriately functionalized sulfoximines with tethered 2-bromoaryl substituents. In turn, the sulfoximines are prepared by lithiation-alkylation sequences including enantioselective deprotonation steps or the use of an optically active sulfoxide. Using this methodology, the range of accessible 3,4-dihydro 2,1-benzothiazine derivatives is expanded.

Key words

alkyl sulfoximines - dihydro benzothiazines - desymmetrization - cyclizations - copper

References

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21

The relative configuration of diastereoisomeric 4-methyl substituted benzothiazines 9b and 9b′ was assigned by comparison with the NMR patterns of reported 4-alkyl substituted analogues (see reference 11a). Accordingly, the relative configuration of their precursors 8b and 8b′ was also established.

23

The enantiomeric ratio of 19 was determined by HPLC: Daicel Chiralpack AS, heptane-i-PrOH, 97:3, 0.9 mL˙min^-¹, 254 nm, t _R1 = 6.3 min, t _R2 = 7.7 min.

25

The absolute configuration of 7e could be deduced by considering that the nucleophilic substitution of 19 proceeded with inversion of configuration and that the imination occurred under retention. For respective details, see references 22 and 24.