Using High-Throughput Iridium-Catalyzed C─H Borylations for Rapid Investigation of Heterocyclic Fragments in Discovery Chemistry

Abstract

This study presents a workflow for rapidly assessing the applicability of Ir-catalyzed C─H borylation across structurally diverse heterocyclic fragments relevant to discovery chemistry. Leveraging cheminformatics, we have selected different N-containing bicyclic scaffolds and evaluated various reaction conditions via a high-throughput experimentation (HTE) platform. The diversified screening approach revealed suitable substrate-specific catalytic systems. The workflow integrates several key steps: 1) defining a focused subset of relevant heterocyclic scaffolds, 2) selecting structurally diverse scaffolds using clustering algorithms, 3) conducting HTE screening with multiple catalytic systems, and 4) scaling up promising hits in a high-throughput fashion. This approach enabled rapid exploration of reaction scope and identification of suitable conditions for various substrates. The study demonstrates the power of combining cheminformatics, HTE, and strategic experimental design to accelerate the evaluation and optimization of synthetic methodologies, with potential future implications for lead optimization in drug discovery and agrochemical development.