Innovational Asymmetric Catalysis縲廾ptimization and New Development

我们开发了一种实用的葡萄糖衍生配体催化氯胺酮的不对称Strecker反应。针对工业应用，我们使用非手性质子添加剂将催化剂的周转效率提高了100倍。廉价的HCN可用作该反应的氰化物源。这是迄今为止最普遍、最实用的酮胺催化不对称Strecker反应。此外，我们还开发了一种新的高效的手性配体合成途径，使我们能够合成该配体的两个对映体。该催化剂可促进中杂氮嘧啶与TMSN_3的高对映选择性开环反应。这一反应为合成抗流感药物达菲提供了平台。Et_2Zn/联联binol催化剂促进了羟基酮的反选择性和顺选择性直接Mannich反应。产物的两种非对映体均可根据反应条件合成，ee最高可达99%。催化剂负载降至0.01 mol %，是不对称曼尼希反应中最低的催化剂负载。同样的催化剂在最少用量的情况下也能促进醛醇反应和迈克尔反应。最近研制出一种手性稀土金属酰胺催化剂，在不对称动化反应中具有良好的催化效果。这一发现导致开发了一种实用的合成路线，雷尼司他，一种抗糖尿病药物。

We developed a practical catalytic asymmetric Strecker reaction of ketimines using glucose-derived ligands. Directing toward industrial application, we improved the catalyst turnover efficiency in 100 times using an achiral protic additive. Inexpensive HCN can be used as a cyanide source in this reaction. This is the most general and practical catalytic asymmetric Strecker reacton of ketimines to date. In addition, we developed a new efficient synthetic route of the chiral ligand, which allowed us to synthesize both enantiomers of the ligand. The related catalyst can promote highly enantioselective ring-opening reaction of meso-aziridines with TMSN_3. This reaction was a platform for the synthesis of anti-influenza drug, Tamiflu.Et_2Zn/linked-BINOL catalyst promoted both anti-and syn-selective direct Mannich reaction of hydroxy ketones. Both diastereomers of the products can be synthesized depening on the reaction conditions with up to 99% ee. The catalyst loading was reduced to 0.01 mol %, which is the far lowest catalyst loading in asymmetric Mannich reaction. The same catalyst also promoted aldol reaction and Michael reaction using the minimum amount of the catalyst.A chiral rare earth metal-amide catalyst was recently developed, and found to be effective in asymmetric animation reactions. This finding led to develop a practical synthetic route of ranirestat, an anti-diabetic agent.