Asymmetric Deprotonation Using Polymer-Supported Chiral Lithium Amides

Significance

Polymer-supported chiral lithium amides were prepared and used as chiral bases in the asymmetric deprotonation of prochiral cyclic ketones. The reaction of Merrifield resin 1 with chiral amines 2 in the presence of NaHCO₃ gave the polymer-supported amines 3a and 3b (eq. 1). The polymer-supported chiral lithium amide 3a-Li was generated in situ from amine 3a with BuLi. The deprotonation of the prochiral cyclic ketones 4 with the chiral lithium amide 3a-Li and the reaction of the resulting lithium enolates with trimethylsilyl chloride gave the trimethylsilyl enol ethers 5 in 86-94% yield with moderate enantioselectivity (31-41% ee) (eq. 2). The reaction of 6 with 3-Li gave (S)-7 with high enantioselectivity (3a: 71% ee, 3b: 81% ee) (eq. 3). The polymer-supported amine 3b was recovered and reused five times.