Ward Robert M, Hu Yun, Tu Noah P, Schomaker Jennifer M
Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA.
Discovery Chemistry and Technology, AbbVie Inc., 1 N. Waukegan Rd., North Chicago, Illinois, 60064, USA.
ChemSusChem. 2024 Jan 8;17(1):e202300964. doi: 10.1002/cssc.202300964. Epub 2023 Nov 3.
Transition metal-catalyzed, non-enzymatic nitrene transfer (NT) reactions to selectively transform C-H and C=C bonds to new C-N bonds are a powerful strategy to streamline the preparation of valuable amine building blocks. However, many catalysts for these reactions use environmentally unfriendly solvents that include dichloromethane, chloroform, 1,2-dichloroethane and benzene. We developed a high-throughput experimentation (HTE) protocol for heterogeneous NT reaction mixtures to enable rapid screening of a broad range of solvents for this chemistry. Coupled with the American Chemical Society Pharmaceutical Roundtable (ACSPR) solvent tool, we identified several attractive replacements for chlorinated solvents. Selected catalysts for NT were compared and contrasted using our HTE protocol, including silver supported by N-dentate ligands, dinuclear Rh complexes and Fe/Mn phthalocyanine catalysts.
过渡金属催化的非酶氮烯转移（NT）反应可将碳氢键和碳碳双键选择性地转化为新的碳氮键，这是简化制备有价值胺类结构单元的有力策略。然而，这些反应的许多催化剂使用的是对环境不友好的溶剂，包括二氯甲烷、氯仿、1,2 - 二氯乙烷和苯。我们开发了一种用于多相NT反应混合物的高通量实验（HTE）方案，以便能够快速筛选适用于该化学过程的多种溶剂。结合美国化学学会药物圆桌会议（ACSPR）溶剂工具，我们确定了几种有吸引力的氯化溶剂替代品。使用我们的HTE方案对NT反应的选定催化剂进行了比较和对比，包括由N齿配体负载的银、双核铑配合物和铁/锰酞菁催化剂。
