Late-Stage Carbon Isotope Exchange of Aryl Nitriles through Ni-Catalyzed C-CN Bond Activation.
Late-Stage Carbon Isotope Exchange of Aryl Nitriles through Ni-Catalyzed C-CN Bond Activation.
复制标题
通过 Ni 催化 C-CN 键活化进行芳基腈的后期碳同位素交换。
DOI：
10.1021/jacs.1c01454
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发表时间：
2021
影响因子：
15
通讯作者：
N. Strotman
中科院分区：
文献类型：
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作者：
S. Reilly;Yu;S. Ren;N. Strotman
描述了使用 Ni 膦催化剂和 BPh3 与芳基、杂芳基和烯基腈进行 13CN 和 14CN 交换的简便一锅策略。这种后期碳同位素交换 (CIE) 策略采用标记的 Zn(CN)2 来促进使用未标记的母体化合物作为起始材料的富集，从而消除了前体开发的从头合成。公开了涵盖多种药物的广泛底物范围，包括[14C]belzutifan的制备，以说明该标记方法的特殊官能团耐受性和实用性。初步实验和计算研究表明路易斯酸 BPh3 对于氧化加成步骤并不重要，而是在促进 Ni 上的 CN 交换中发挥作用。这种 CIE 方法极大地减少了临床开发用 14C 标记示踪剂制备过程中涉及的合成步骤和放射性废物。
A facile one-pot strategy for 13CN and 14CN exchange with aryl, heteroaryl, and alkenyl nitriles using a Ni phosphine catalyst and BPh3 is described. This late-stage carbon isotope exchange (CIE) strategy employs labeled Zn(CN)2 to facilitate enrichment using the nonlabeled parent compound as the starting material, eliminating de novo synthesis for precursor development. A broad substrate scope encompassing multiple pharmaceuticals is disclosed, including the preparation of [14C] belzutifan to illustrate the exceptional functional group tolerance and utility of this labeling approach. Preliminary experimental and computational studies suggest the Lewis acid BPh3 is not critical for the oxidative addition step and instead plays a role in facilitating CN exchange on Ni. This CIE method dramatically reduces the synthetic steps and radioactive waste involved in preparation of 14C labeled tracers for clinical development.
影响因子：
15
作者：
Kingston, Cian;Wallace, Michael A.;Baran, Phil S.
通讯作者：
Baran, Phil S.