Ionic and Radical Cross-Couplings for Carbon-Silicon Bond Formation

通过双分子亲核取代(SN2)与硅亲核试剂在饱和碳原子上形成C-Si键似乎是一个长期解决的合成问题。然而，有效的方法直到去年才被披露。研究发现，根据离位基团的不同，位移可能是通过离子机制发生的，也可能是通过自由基过程发生的。催化生成的铜基硅亲核试剂在Sn2气氛下以三氟酸盐为离开基团，而相同的亲核剂以卤代烷为亲电剂，采用逐级自由基反应机理。以不对称方式进行这些C(SP3)-Si偶联反应是下一个目标。对于手性烷基三氟化物，从容易获得的富含对映体的醇中衍生，亲核取代将是对映体专一性的。相反，烷基卤化物的交叉偶联是从外消旋物质开始的，因此是一种对映体选择性转化。在自由基反应中实现高对映选择性是一项艰巨的挑战。然而，初步实验已经表明，离子对映异构体和自由基对映体选择性偶联与硅亲核试剂都是可能的。本项目旨在系统地研究这些新的不对称C(SP3)-Si键的形成。此外，铜基硅亲核试剂作为单电子还原剂的能力也可能为重氮离子前所未有的C(Sp2)-Si交叉偶联反应打开大门。

The formation of C-Si bonds at saturated carbon atoms by bimolecular nucleophilic substitution (SN2) with silicon nucleophiles seems like a long-solved synthetic problem. Effective methods were, however, only disclosed last year. It was found that, depending on the leaving group, the displacement occurs either by an ionic mechanism or by a radical process. With triflate as leaving group, the catalytically generated copper-based silicon nucleophile reacts under SN2 whereas the same nucleophile engages in a stepwise radical mechanism with alkyl halides as electrophiles. Performing these C(sp3)-Si coupling reactions in asymmetric fashion is the next goal. With chiral alkyl triflates derived from readily available enantioenriched alcohols, the nucleophilic displacement would be enantiospecific. Conversely, the cross-coupling of alkyl halides would start from racemic material and is, as such, an enantioselective transformation. Achieving high enantioselectivity in a radical reaction is a formidable challenge. However, preliminary experiments have already shown that both ionic enantiospecific and radical enantioselective couplings with silicon nucleophiles are possible. This project aims at the systematic investigation of these new asymmetric C(sp3)-Si bond formations. Moreover, the ability of the copper-based silicon nucleophile to act as a one-electron reductant could also open a door to an unprecedented C(sp2)-Si cross-coupling reaction of diazonium ions.