Merging Directed C−H Activations with High-Throughput Experimentation: Development of Predictable Iridium-Catalyzed C−H Aminations Applicable to Late-Stage Functionalization

07 December 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Herein, we report an iridium-catalyzed directed C−H amination methodology developed using a high-throughput experimentation (HTE)-based strategy, applicable for the needs of automated modern drug discovery. The informer library approach for investigating accessible directing group chemical space for the reaction, in combination with functional group tolerance screening and substrate scope investigations, allowed for the generation of an empirical predictive model to guide future users. Applicability to late-stage functionalization of complex drugs and natural products, in combination with multiple deprotection protocols leading to the desirable aniline matched pairs, serve to demonstrate the utility of the method for drug discovery. Finally reaction miniaturization to a nano molar range highlights the opportunities for more sustainable screening with decreased material consumption.


C-H activation
C-H amination
C-H functionalization
High-throughput experimentation
Late-stage functionalization

Supplementary materials

Supporting information; Merging Directed C-H Activations with High-throughput Experimentation: Development of Predictable Iridium-catalyzed C-H Aminations Applicable to Late-stage Functionalization
Supporting information


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