Persistent organonickel complexes as general platforms for Csp2-Csp3 coupling reactions.
Persistent organonickel complexes as general platforms for Csp2-Csp3 coupling reactions.
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DOI：
10.1038/s41557-024-01528-7
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发表时间：
2024-04
期刊：
影响因子：
21.8
通讯作者：
Long P. Dinh;Hunter F Starbuck;Taylor B. Hamby;Matthew J. LaLama;C. Q. He;D. Kalyani;C. Sevov
中科院分区：
文献类型：
--
作者：
Long P. Dinh;Hunter F Starbuck;Taylor B. Hamby;Matthew J. LaLama;C. Q. He;D. Kalyani;C. Sevov
构建Csp 2-Csp 3键的重要性推动了电化学、光化学和热活化方法的发展，以还原偶联丰富的芳基和烷基亲电试剂。然而，这些方法仅限于非常特定的底物类别的偶联，并且需要专门的催化剂和反应装置。在这里，我们将这些无数的策略整合成一组条件，使可靠的烷基-芳基偶联，包括那些以前未知的。这些反应依赖于发现异常持久的有机镍配合物，作为化学计量平台的C（sp2）-C（sp3）耦合。Ni的芳基、杂芳基或乙烯基络合物可以通过从相应的C（sp2）亲电试剂的温和电还原以数克规模廉价地制备。有机镍复合物可以被分离和储存或直接压缩，以可靠地使药物样分子多样化。最后，通过整合可溶性电池化学物质作为氧化还原引发剂，将该过程小型化至微摩尔尺度，从而实现对底物多样性的高通量探索。
The importance of constructing Csp2–Csp3bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl–aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp2)–C(sp3) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp2) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity.