Palladium-catalyzed coupling of optically active amines with aryl bromides
Palladium-catalyzed coupling of optically active amines with aryl bromides
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DOI：
10.1021/ja971583o
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发表时间：
1997-09-10
影响因子：
15
通讯作者：
Buchwald, SL
中科院分区：
文献类型：
--
作者：
Wagaw, S;Rennels, RA;Buchwald, SL
对映体富集的胺与芳基溴的偶联产生相应的N-芳基衍生物。钯催化偶联反应中配体的选择对于苯胺的形成而不损失对映体纯度至关重要。LnPd（L = P（o-tolyl）（3））成功地催化了α-取代光学纯胺的分子内芳基胺化反应，在此催化体系下的分子间偶联反应得到了外消旋产物。相比之下，使用LnPd（L =（+/-）-BINAP）的分子间N-芳基化以良好的产率得到产物，对映体纯度没有受到侵蚀。提出了所观察到的外消旋化的机制。分子内过程的效用通过5的合成来证明，5是6的正式合成中的中间体，6是一种有效的ACE抑制剂。
The coupling of enantiomerically enriched amines with aryl bromides produces the corresponding N-aryl derivatives. The choice of ligand in the palladium-catalyzed coupling is critical to the formation of the anilines without loss of enantiomeric purity. While LnPd (L = P(o-tolyl)(3)) successfully catalyzes the intramolecular aryl amination of alpha-subsituted optically pure amines, intermolecular coupling reactions with this catalyst system gives racemized products. In contrast, intermolecular N-arylations employing LnPd (L = (+/-)-BINAP) gives products in good yields with no erosion of enantiopurity. A mechanism for the observed racemization is proposed. The utility of the intramolecular process is demonstrated by the synthesis of 5, an intermediate in the formal synthesis of 6, a potent ACE inhibitor.