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

甲硅烷基作为外消旋甲硅烷基化/锗基化​​亲电子试剂的对映体聚合、镍催化的 C(spn)-C(spm) 交叉偶联中的转向元件

• 批准号: 497222168
• 负责人: Professor Dr. Martin Oestreich
• 金额: --
• 依托单位: Institut für Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/497222168?language=en
• 关键词: Silyl; groups; steering; element; enantioconvergent

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.

涉及自由基中间体的对映选择性镍催化已经是以对映会聚方式形成C（spn）-C（spm）键（w/ n主要= 3和m = 3，2和1）的关键技术。从外消旋亲电试剂和广泛的锌基亲核试剂开始，近年来已经实现了令人印象深刻的许多困难的键形成。由于我们对硅化学的兴趣，我们问自己亲电组分中的甲硅烷基取代对这些交叉偶联反应的过程有什么影响。关于α-甲硅烷基化的烷基卤化物，我们发现甲硅烷基能够与伯烷基锌试剂进行对映会聚的C（sp3）-C（sp3）偶联;硅稳定的自由基的中间性是至关重要的。此外，甲硅烷基对传统烯丙基取代的区域选择性产生强烈的影响，我们已经能够分别设计甲硅烷基化的烯丙基亲电试剂的对映收敛和区域控制的C（sp3）-C（sp3）偶联（烯丙基取代）和甲硅烷基化的炔丙基亲电试剂的C（sp2）-C（sp3）偶联（炔丙基取代）。这些新的方法允许对映选择性合成，否则难以使碳骨架与甲硅烷基作为后续官能团操作的额外处理。该项目建立在这一初步成功的基础上，旨在实现由甲硅烷基引导的数十种前所未有的转化。此外，定向供体基团拴系到硅原子上可以增强甲硅烷基化亲电试剂的反应性，甚至逆转烯丙基和炔丙基置换的区域选择性。例如，使用仲（非手性和手性）烷基锌试剂或“叔”甲硅烷基化亲电试剂属于这一长期奋进的目标。同样的方法将应用于锗基，最终合成对映体富集的含锗结构单元。有希望的实验已经证实了镍催化的这种不寻常的延伸的可行性，为锗化学的探索较少的领域增加了新的合成工具。含硅和锗的产物将主要通过交叉偶联技术转化回碳化学。