The use of chiral lithium amides in the desymmetrisation of N-trialkylsilyl dimethyl sulfoximines

Matthew J Mcgrath,Carsten Bolm

doi:10.1186/1860-5397-3-33

Abstract

BackgroundChiral base desymmetrisation of dimethyl sulfoximines could provide a general route to chiral, enantioenriched dialkyl sulfoximines with potential for use in asymmetric catalysis.ResultsAsymmetric deprotonation of N-trialkylsilyl dimethyl sulfoximines with either enantiomer of lithium N,N-bis(1-phenylethyl)amide in the presence of lithium chloride affords enantioenriched sulfoximines on electrophilic trapping. Ketones, ketimines, trialkylsilyl chlorides and activated alkyl halides may be used as electrophiles in the reaction. Furthermore, a modified Horner-Emmons methodology was investigated.ConclusionSimple chiral lithium amides afford products with enantiomeric excesses of up to 70%, illustrating that chiral base desymmetrisation of dimethyl sulfoximines is possible.

Highlights

The preparation of enantioenriched sulfoximines is an important goal in synthesis as these S-chiral compounds make interesting ligands for asymmetric catalysis and have been used in the construction of pseudopeptides. [1,2,3,4] Enantiomerically enriched aryl-alkylsulfoximines are generally prepared by resolution with camphorsulfonic acid but this method is not applicable to dialkyl sulfoximines. [5,6,7]Imination of enantioenriched sulfoxides and derivatisation of sulfoximines with enantiomerically pure amino acid derivativesPage 1 of 6 (page number not for citation purposes)Beilstein Journal of Organic Chemistry 2007, 3, No 33.Scheme 2: Preparation of N-trialkylsilyl dimethyl sulfoximine derivativesScheme 1: Desymmetrisation of N-trialkylsilyldimethylsulfoximines using chiral bases provide enantioenriched S-chiral sulfoximines but both methods lack generality due to the limited availability of the appropriate chiral sulfoxides and the limited scope for cleavage of the chiral auxiliary in the latter process. [6,7,8,9,10,11,12,13,14,15]Selective substitution of one of the enantiotopic methyl groups in a dimethylsulfoximine derivative 1, by treatment with a chiral base followed by electrophilic trapping of the resultant anion, would provide an alternative access to enantioenriched sulfoximines of type 2, which are not readily accessible by other means (Scheme 1). [16,17,18,19]
Simple chiral lithium amides afford products with enantiomeric excesses of up to 70%, illustrating that chiral base desymmetrisation of dimethyl sulfoximines is possible
The preparation of enantioenriched sulfoximines is an important goal in synthesis as these S-chiral compounds make interesting ligands for asymmetric catalysis and have been used in the construction of pseudopeptides. [1,2,3,4] Enantiomerically enriched aryl-alkylsulfoximines are generally prepared by resolution with camphorsulfonic acid but this method is not applicable to dialkyl sulfoximines. [5,6,7]

Summary

Introduction

The preparation of enantioenriched sulfoximines is an important goal in synthesis as these S-chiral compounds make interesting ligands for asymmetric catalysis and have been used in the construction of pseudopeptides. [1,2,3,4] Enantiomerically enriched aryl-alkylsulfoximines are generally prepared by resolution with camphorsulfonic acid but this method is not applicable to dialkyl sulfoximines. [5,6,7]Imination of enantioenriched sulfoxides and derivatisation of sulfoximines with enantiomerically pure amino acid derivativesPage 1 of 6 (page number not for citation purposes)Beilstein Journal of Organic Chemistry 2007, 3, No 33.Scheme 2: Preparation of N-trialkylsilyl dimethyl sulfoximine derivativesScheme 1: Desymmetrisation of N-trialkylsilyldimethylsulfoximines using chiral bases provide enantioenriched S-chiral sulfoximines but both methods lack generality due to the limited availability of the appropriate chiral sulfoxides and the limited scope for cleavage of the chiral auxiliary in the latter process. [6,7,8,9,10,11,12,13,14,15]Selective substitution of one of the enantiotopic methyl groups in a dimethylsulfoximine derivative 1, by treatment with a chiral base followed by electrophilic trapping of the resultant anion, would provide an alternative access to enantioenriched sulfoximines of type 2, which are not readily accessible by other means (Scheme 1). [16,17,18,19]. Simple chiral lithium amides afford products with enantiomeric excesses of up to 70%, illustrating that chiral base desymmetrisation of dimethyl sulfoximines is possible.

Results

Conclusion