Innovational Asymmetric Catalysis縲廾ptimization and New Development

我们发展了一个实用的催化酮亚胺的不对称Strecker反应使用葡萄糖衍生的配体。针对工业应用，我们使用非手性质子添加剂将催化剂的转换效率提高了100倍。在该反应中，廉价的HCN可用作氰化物源。这是迄今为止酮亚胺的最普遍和最实用的催化不对称Strecker反应。此外，我们还开发了一条新的高效合成路线，使我们能够同时合成手性配体的两种对映体。该催化剂能促进TMSN_3与meso-氮杂环丙烷的高对映选择性开环反应。该反应为抗流感药物Tamiflu的合成提供了一个平台。Et_2Zn/linked-BINOL催化剂促进了羟基酮的反式和顺式选择性直接Mannich反应。反应条件对产物的两种非对映异构体的合成均有影响，ee值可达99%，催化剂用量降至0.01mol%，是不对称Mannich反应中最低的催化剂用量。该催化剂还能以最小的用量促进Aldol反应和Michael反应。最近开发了一种手性稀土金属酰胺催化剂，并发现其在不对称胺化反应中是有效的。这一发现导致开发了抗糖尿病药物ranirestat的实用合成路线。

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.