Michael addition with Evans’ oxazolidinones

Michael additions with 8-phenylmenthyl esters of unsaturated acids Chiral auxiliaries attached elsewhere in asymmetric Michael additions Other Chiral Auxiliaries in Conjugate Addition The Evans oxazolidinones Chiral sulfoxides Asymmetric Birch Reduction Birch reduction of benzene Asymmetric Birch reduction of heterocycles... 

Merck has used the L-phenylalanine-derived Evans oxazolidinone to make matrix metalloproteinase inhibitors such as 45 (Scheme 23.14) (see also Chapter 2).62 The mixed anhydride of 4-butyric acid was reacted with the lithium anion of the oxazolidinone. This was enolized with the standard titanium reagents. An enantioselective Michael addition was then carried out by the addition of t-butyl acrylate at low temperature. The auxiliary was removed with LiOH/peroxides to give the acid, which was further derivatized over multiple steps to yield the desired drug. 

Inspired by their previous work dealing with enantioselective conjugate addition of t-butyl acetoacetate to crotonoylthiazolidinethione catalysed by a preformed nickel catalyst from/>-To 1-BINAP ligand 30, and by those of Kane-masa on enantioselective nickel-catalysed additions of thiols and 1,3-dike-tones to unsaturated acylpyrazoles and oxazolidinones with a chiral amine ligand, Evans et al. investigated the scope of enantioselective Michael... 

In any treatment of auxiliary-based alkylations (as well as aldol additions, enolate oxidations, Mannich and Michael reactions), clearly, the carboximide enolates pioneered by the group of Evans are the center of attention. Developed in the early 1980, JV-acyl derivatives of oxazolidinones 45-47 (Scheme 4.9) became the epitomes of chiral auxiliaries [7,28] with countless applications in natural products and drug syntheses. The enantiomeric oxazolidinones (S)- and (R)-47 derived from the corresponding enantiomer of phenylalanine have the advantage that, when used for various transformations, the corresponding products have a higher tendency to crystallization and were shortly later added [29] to this collection of classics. 

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