Reactions of Chiral Ammonium Ketene Enolates as Nucleophiles with Different Electrophiles

Reactions of Chiral Ammonium Ketene Enolates as Nucleophiles with Different Electrophiles 

1 Lewis Acid Assisted Nucleophilic Addition of Ketenes (or Sulfenes) to Aldehydes -Lactone and (i-Sultone Synthesis 

In 1982, Wynberg and coworkers discovered the cinchona alkaloid catalyzed enantioselective aldol lactonization of ketenes with chloral or trichloroacetone [35], in which the zwitterionic acyl ammonium enolate provides the carbon nucleophile. This work is probably one of the most important early contributions to enantioselective organocatalysis [36], One drawback associated with this process is the severe substrate limitations. The aldehydes should be highly reactive, presumably due to the relatively limited nudeophilicity of ammonium enolates. Nelson and coworkers first addressed the scope and reactivity problems associated with Wynberg s original protocol by combining a cinchona alkaloid derivative (O-trimethylsilylquinine (12) or O-trimethylsilylquinidine (13)) with a metal Lewis acid as a cocatalyst to 

Quite recently, Doyle and coworkers found that dirhodium(II) complexes such as rhodium(II) acetate and Rh2(4S-MEAZ)4 (14) also act as highly active Lewis addcatalysts (1 mol%) for the reaction of trimethylsilylketene and ethyl glyoxalate, affording the P-lactonel5 (Table4.6) [42]. However, theuseofthechiral Rh-complex, Rh2(4S-M EAZ)4, alone afforded almost no asymmetric induction (5% ee for (S)-isomer) (entry 2). The use of quinine (10 mol%) as a cobase catalyst to activate the ketene simultaneously provided exceptional enantiocontrol (99% ee) and enhanced reactivity (entry 5). 

Asa logical extension to the discrete bifunctional catalytic systems described above, Lin et al. developed a catalyst containing two catalytic moieties (i.e., an alkaloid as a 

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