The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions.
The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions.
复制标题
DOI：
10.1002/chem.201502090
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Dagmar Scharnagel;A. Müller;Felix Prause;M. Eck;Jessica Goller;W. Milius;M. Breuning
中科院分区：
文献类型：
--
作者：
Dagmar Scharnagel;A. Müller;Felix Prause;M. Eck;Jessica Goller;W. Milius;M. Breuning
采用“由内而外”的方法，首次实现了核手性双吡啶的模块化灵活合成。以手性修饰的β-氨基酸和2-(乙酰氧甲基)丙烯腈为原料，经5步反应合成了关键中间体--NBOC激活的双吡啶内酰胺，产率为48%。一种简单的加成-还原方案允许高内选择性地引入取代基，从而快速和可变地获得2-内基取代和2-内基，N-稠合的双环和三环双吡啶。新的二胺作为不对称Henry反应中的手性配体进行了评价。由2-内基，N-(3，3-二甲基吡咯烷)-双吡啶修饰的铜(II)络合物具有高达99%的对映体选择性和高达86：14的良好的非对映异构体比。它的性能优于著名的双吡啶(-)-司马汀和(+)-司马汀替代物。
The first modular and flexible synthesis of core-chiral bispidines was achieved by using an "inside-out" strategy. The key intermediate, a NBoc-activated bispidine lactam, was constructed in enantiomerically pure form from a chirally modified β-amino acid and 2-(acetoxymethyl)acrylonitrile in just five steps and good 48% yield. A simple addition-reduction protocol permitted a highly endo-selective introduction of substituents and, thus, a fast and variable access to 2-endo-substituted and 2-endo,N-fused bi- and tricyclic bispidines. The new diamines were evaluated as the chiral ligands in asymmetric Henry reactions. Excellent enantioselectivities of up to 99% ee and good diastereomeric ratios of up to 86:14 were reached with a copper(II) complex modified by a 2-endo,N-(3,3-dimethylpyrrolidine)-annelated bispidine. Its performance is superior to that of the well-known bispidines (-)-sparteine and the (+)-sparteine surrogate.