Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Am Chem Soc. 2012 Oct 17;134(41):17003-6. doi: 10.1021/ja308460z. Epub 2012 Oct 5.
We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline-oxazoline ligand furnishes excellent ee's and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile.
我们开发了一种镍催化的方法，用于立体选择性地实现仲亲电试剂与仲亲核试剂的交叉偶联，具体来说，是外消旋苄基溴与手性环烷基锌试剂的 Negishi 反应。与大多数之前对非对映选择性 Negishi 交叉偶联的研究不同，三齿 pybox 配体在此过程中无效；然而，一种新的、易于获得的双齿异喹啉-恶唑啉配体提供了出色的对映选择性和良好的产率。使用无环烷基锌试剂作为偶联试剂，发现了一种非常不寻常的异构化反应，它能够从无支化亲核试剂中生成大量支化的交叉偶联产物。
