Parallel Kinetic Resolution of Acyclic γ-Amino-α,β-unsaturated Esters: Application to the Asymmetric Synthesis of 4-Aminopyrrolidin-2-ones

Conjugate addition of a 50:50 pseudoenantiomeric mixture of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(α-methylbenzyl)amide to a range of racemic acyclic γ-amino-α,β-unsaturated esters (derived from the corresponding α-amino acids) effects their efficient parallel kinetic resolution, allowing the preparation of enantiopure β,γ-diamino esters. The β,γ-diamino ester products of these reactions are readily converted into the corresponding substituted 4-aminopyrrolidin-2-ones via N-debenzylation and cyclization.

将锂(R)-N-苄基-N-(α-甲基苄基)氨基锂与锂(S)-N-3,4-二甲氧基苄基-N-(α-甲基苄基)氨基锂按50:50的比例配制成假对映体混合物（pseudoenantiomeric mixture），将该混合物与一系列由相应α-氨基酸衍生得到的外消旋无环γ-氨基-α,β-不饱和酯进行共轭加成（conjugate addition）反应，可实现该类底物的高效平行动力学拆分（parallel kinetic resolution），进而制备得到对映纯的β,γ-二氨基酯。上述反应得到的β,γ-二氨基酯产物可通过N-脱苄基（N-debenzylation）与环化（cyclization）步骤，便捷地转化为对应的取代4-氨基吡咯烷-2-酮。