可见光氧化还原催化的不对称Smiles重排反应研究

本项目主要内容为实现可见光氧化还原催化的不对称Smiles重排反应，并由此制备一系列由传统方法较难制备的含有季碳手性中心的光学纯苯甘氨酸衍生物。通过两种不同的单电子转移途径可以实现这一目标，第一条途径包含了光氧化还原催化条件下自由基物种对脱氢丙氨酸衍生物的自由基加成以及辅基控制的分子间芳基亲核取代。第二条途径是通过激发态光敏剂对苯甘氨酸衍生物上富电子芳环的单电子氧化和苄位离去质子后的芳构化作为关键步骤来进行的。这两条途径都巧妙利用了光氧化还原催化的自由基Giese反应中所形成的碳负离子(烯醇盐)中间体来进行手性辅基控制的分子内芳基亲核取代，解决了传统的不对称Smiles重排反应中需要加入强碱来生成碳负离子这一局限性。因此，该策略将有较好的官能团兼容性和底物多样性，并且反应条件温和可控，有望实现含季碳的光学纯苯甘氨酸衍生物的多样化制备。

Optical pure α-amino acids with a quaternary carbon center have wide applications in modification of peptide structures and biological functions. Therefore, the development of general and efficient methods for their preparation has been drawing intensive research interests to synthetic chemists. In this proposal, we introduce a convenient method to prepare optical pure phenylglycines with a quaternary carbon center through visible light promoted, chiral auxiliary controlled diastereoselective Smiles rearrangement. Two distinct approaches are conceived to achieve this research target. The first approach starts with radical addition to a dehydroalanine (Dha) derivative. Subsequent radical reduction gives an enolate intermediate, followed by intramolecular nucleophilic aromatic substitution (SNAr), produceing a quaternary center. The diastereoselectivity in this cascade is controlled by a chiral auxiliary. In another approach, a phenylglycine derivative undergoes single electron oxidation of the electron-rich aromatic ring by a photo-excited redox catalyst, leading to a benzylic carboanion after deprotonation, aromatization and SET reduction. The absence of a strong base that is indispensable in previous examples of asymmetric Smiles rearrangement allows the preparation of diverse optical pure phenylglycines in mild conditions with good functional group tolerance.