Silyl groups as a steering element in enantioconvergent, nickel-catalyzed C(spn)-C(spm) cross-coupling of racemic silylated/germylated electrophiles

涉及自由基中间体的对映选择性镍催化已经成为以对映聚合方式锻造C(SPN)-C(SPM)键(w/n=主要为3，m=3，2和1)的关键技术。从外消旋亲电体和广泛的锌基亲核试剂开始，近年来已经实现了大量困难的键形成。随着我们对硅化学的兴趣，我们问自己，亲电成分中的硅基取代会对这些交叉偶联反应产生什么影响。对于α硅化的卤代烷基化合物，我们发现硅基使对映体聚合体C(Sp3)-C(Sp3)与伯烷基锌试剂偶联；硅稳定的自由基的中间体是至关重要的。此外，硅基对传统的烯丙基取代的区域选择性有很大的影响，我们已经能够设计出硅烷化的烯丙基亲电化合物(烯丙基取代)的对映体聚合型和区域可控的C(SP3)-C(SP3)偶联和硅烷化的炔丙基亲电化合物的C(Sp2)-C(SP3)偶联(炔丙基取代)。这些新方法允许用硅基作为后续官能团操纵的额外手柄来对映体选择性地合成本来难以制造的碳骨架。这个项目建立在这一初步成功的基础上，目标基本上是在硅基的指导下进行数十次前所未有的转变。此外，与硅原子相连的直接给体基团可以增强硅化亲电试剂的反应活性，甚至逆转烯丙基和丙叉基位移的区域选择性。例如，二级(非手性和手性)烷基锌试剂或“三级”硅烷化亲电试剂的使用属于这一长期努力的目标。同样的方法将被应用于Germyl基团，最终合成富含对映体的含Ge的构建块。有希望的实验已经证实了镍催化这种不同寻常的延伸的可行性，为较少被探索的锗化学领域增加了新的合成工具。含硅和锗的产品将主要通过交叉耦合技术转化回碳化学。

Enantioselective nickel catalysis involving radical intermediates is already a key technology for forging C(spn)-C(spm) bonds (w/ n = mainly 3 and m = 3, 2 and 1) in an enantioconvergent fashion. Starting from racemic electrophiles and a broad range of zinc-based nucleophiles, an impressive number of difficult bond formations has been realized in recent years. With our interest in silicon chemistry, we asked ourselves what the effect of silyl substitution in the electrophilic component would have on the course of those cross-coupling reactions. With regard to α-silylated alkyl halides, we found out that the silyl group enables enantioconvergent C(sp3)-C(sp3) coupling with primary alkylzinc reagents; the intermediacy of a silicon-stabilized radical was crucial. Moreover, the silyl group exerts a strong influence on the regioselectivity of conventional allylic substitutions, and we have been able to design enantioconvergent and regiocontrolled C(sp3)-C(sp3) couplings of silylated allyl electrophiles (allylic substitution) and C(sp2)-C(sp3) couplings of silylated propargyl electrophiles (propargylic substitution), respectively. These new methods allows for the enantioselective synthesis of otherwise difficult-to-make carbon skeletons with silyl groups as an additional handle for subsequent functional-group manipulation. This project builds on this preliminary success, aiming at essentially dozens of unprecedented transformations steered by a silyl group. Furthermore, a directing donor group tethered to the silicon atom could enhance the reactivity of the silylated electrophile or even reverse the regioselectivity of allylic and propargylic displacements. For example, the use of secondary (achiral and chiral) alkylzinc reagents or "tertiary" silylated electrophiles belongs to the goals of this long-term endeavor. The same approach will be applied to germyl groups to eventually synthesize enantioenriched, germanium-containing building blocks. Promising experiments have already confirmed the viability of this unusual extension of nickel catalysis, adding new synthetic tools to the less explored field of germanium chemistry. The silicon- and germanium-containing products will be translated back into carbon chemistry by mainly cross-coupling techniques.