Gesmundo Nathan J, Tu Noah P, Sarris Kathy A, Wang Ying
AbbVie, Inc., 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
ACS Med Chem Lett. 2023 Mar 16;14(4):521-529. doi: 10.1021/acsmedchemlett.2c00538. eCollection 2023 Apr 13.
Enthusiasm surrounding nickel/photoredox C(sp)-C(sp) cross-couplings is very high; however, these methods are sometimes challenged by complex drug-like substrates in discovery chemistry. In our hands this has been especially true of the decarboxylative coupling, which has lagged behind other photoredox couplings in internal adoption and success. Herein, the development of a photoredox high-throughput experimentation platform to optimize challenging C(sp)-C(sp) decarboxylative couplings is described. Chemical-coated glass beads (ChemBeads) and a novel parallel bead dispenser are used to expedite the high-throughput experimentation process and identify improved coupling conditions. In this report, photoredox high-throughput experimentation is utilized to dramatically improve low-yielding decarboxylative C(sp)-C(sp) couplings, and libraries, using conditions not previously identified in the literature.
围绕镍/光氧化还原C(sp)-C(sp)交叉偶联反应的热情非常高涨；然而，在药物研发化学中，这些方法有时会受到复杂类药物底物的挑战。在我们的研究中，脱羧偶联反应尤其如此，其在内部应用和成功率方面落后于其他光氧化还原偶联反应。本文描述了一个用于优化具有挑战性的C(sp)-C(sp)脱羧偶联反应的光氧化还原高通量实验平台的开发。化学涂层玻璃珠（ChemBeads）和一种新型平行珠分配器被用于加快高通量实验过程并确定改进的偶联条件。在本报告中，利用光氧化还原高通量实验显著改善了低产率的脱羧C(sp)-C(sp)偶联反应，并使用了文献中未曾报道过的条件构建了文库。
