过渡金属催化合成手性氨基酸酯类衍生物的研究

Chiral amino acids derivatives are a kind of useful compounds which are widely used as the buildingblock for cores of peptides, proteins, and pharmaceutical agents. Meanwhile, these amino acids also have been used in organic chemistry to synthesize natural products, chiral catalysts, and ligands. However, the main methods previously reported to synthesize chiral amino acid derivatives were the nucleophiles addition to imines, which limited and suffer from the necessity of using complicated starting materials and narrow functional group compatibility. We previously have developed a novel cascade reaction for the synthesis of chiral α-amino acid derivatives. Based on our previous work, we propose to combine direct C-H bond oxidation and transition metal catalyzed asymmetric addition to imine strategies to accomplish the synthesis of a series of chiral amino acid ester derivatives. At the same time, a systematic investigation will be carried out on reaction factors, including different types of substrate reaction system and mechanism of this reaction will be studied. This work will establish a novel pattern for the synthesis of series chiral α-amino acid derivatives via a potential pathway of enantioselective Csp3-C bond formations by direct C-H oxidative, and provide insights of transition metal catalyzed cascade reactions.

手性氨基酸衍生物是一种很重要的化合物，广泛存在于蛋白质和药物中间体中。这些氨基酸也被用于合成天然产物，催化剂或配体。但是，目前报道的方法通常是亲核试剂对亚胺的加成合成手性氨基酸衍生物。这种合成方法局限性大，产物的取代类型单一。基于前期工作，结合目前手性氨基酸酯衍生物的合成研究现状，本项目计划利用C-H键氧化和过渡金属催化的不对称亚胺加成相结合的策略，发展一类新型的以过渡金属为催化剂，通过C-H氧化原位生成亚胺合成一系列手性氨基酸酯衍生物的方法。同时，对不同类型底物反应体系的研究和机理探索，进一步深入理解和扩展这类反应，为通过C-H氧化构建Csp3-C键从而合成手性氨基酸酯衍生物提供一定的实验依据和理论基础。

氨基羰基化合物是一种重要的骨架，广泛存在于蛋白质和药物中间体中。本项目以α-氨基羰基化合物为原料，利用C-H键原位氧化亚胺和过渡金属催化相结合的策略，发展了一类新型的合成α-氨基取代衍生物的方法。有机磷化合物在医药、农业化学和材料化学等领域有着广泛的应用。我们以酮为原料，在路易斯酸促进下，与亲核磷试剂通过Phospha-Aldol-Elimination串联反应构建C-P键合成了烯基膦酸酯和9-膦酰基芴类化合物。在本项目的支持下，发表论文9篇，申请专利4项。