Exploring Homogeneous Conditions for Mild Buchwald-Hartwig Amination in Batch and Flow

10.26434/chemrxiv.10094048 ◽

2020 ◽

Author(s):

Saeed K. Kashani ◽

Jacob E. Jessiman ◽

Stephen Newman

Keyword(s):

High Throughput ◽

Functional Group ◽

Sonogashira Coupling ◽

High Throughput Experimentation ◽

Reac Tions ◽

Base Application

We describe the use of high throughput experimentation to identify a number of conditions that enable Buchwald-Hartwig reactions to be carried out using readily available ligands (e.g. XantPhos) with DBU as a soluble, functional group tolerant, homogeneous base. Application of this system to diverse aminations in batch and flow are demonstrated, as is the translation of this technique to performing continuous Mizoroki-Heck and Sonogashira coupling reac-tions.

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Exploring Homogeneous Conditions for Mild Buchwald-Hartwig Amination in Batch and Flow

10.26434/chemrxiv.10094048.v2 ◽

2020 ◽

Author(s):

Saeed K. Kashani ◽

Jacob E. Jessiman ◽

Stephen Newman

Keyword(s):

High Throughput ◽

Functional Group ◽

Sonogashira Coupling ◽

High Throughput Experimentation ◽

Reac Tions ◽

Base Application

We describe the use of high throughput experimentation to identify a number of conditions that enable Buchwald-Hartwig reactions to be carried out using readily available ligands (e.g. XantPhos) with DBU as a soluble, functional group tolerant, homogeneous base. Application of this system to diverse aminations in batch and flow are demonstrated, as is the translation of this technique to performing continuous Mizoroki-Heck and Sonogashira coupling reac-tions.

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

10.26434/chemrxiv-2021-vp0kl ◽

2021 ◽

Author(s):

Erik Weis ◽

Maria Johansson ◽

Pernilla Korsgren ◽

Belén Martín-Matute ◽

Magnus J Johansson

Keyword(s):

Drug Discovery ◽

High Throughput ◽

Late Stage ◽

Functional Group ◽

Chemical Space ◽

Material Consumption ◽

Modern Drug ◽

High Throughput Experimentation ◽

Directing Group ◽

Group Chemical

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.

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