Menche Dirk, Arikan Fatih, Li Jun, Rudolph Sven
Gesellschaft für Biotechnologische Forschung mbH, Medizinische Chemie, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Org Lett. 2007 Jan 18;9(2):267-70. doi: 10.1021/ol062715y.
An efficient procedure for the directed reductive amination of beta-hydroxy-ketones (3) for the stereoselective preparation of 1,3-syn-amino alcohols (6) is reported. The operationally simple protocol uses Ti(iOPr)4 for coordination of the intermediate imino alcohol (5) and PMHS as the reducing agent. The method was expanded to an asymmetric aldol reductive amination sequence to allow a highly convergent synthesis of the hydroxy-amine core of the HIV-protease inhibitors ritonavir and lopinavir. [reaction: see text].
报道了一种用于β-羟基酮（3）定向还原胺化以立体选择性制备1,3-顺式氨基醇（6）的有效方法。该操作简单的方案使用四异丙氧基钛（Ti(iOPr)4）来配位中间体亚氨基醇（5），并使用聚甲基氢硅氧烷（PMHS）作为还原剂。该方法扩展至不对称羟醛还原胺化序列，以实现对HIV蛋白酶抑制剂利托那韦和洛匹那韦的羟基胺核心进行高度汇聚式合成。[反应：见正文]
