Breaking Technological Limits in HT Synthesis: A Platform Concept to Unlock Phase‐Transfer Catalysis in Microplate‐Based S N 2 Automation
Year: 2025
Type: article
Abstract: We report a covalently immobilized crown ether‐based platform that enables phase‐transfer‐catalyzed S N 2 reactions under fully automated microplate conditions. This regenerable system overcomes key limitations of HT synthesis—solubility mismatches, mixing constraints, and purification demands—offering a zero‐waste solution for expanding the accessible reaction space in robotized synthetic workflows. The approach relies on silanized glass microvials bearing dibenzo‐18‐crown‐6 functionalities, providing a well‐defined catalytic interface between immiscible organic and aqueous phases. The dynamic movement of the phase boundary during orbital shaking ensures continuous reagent exchange without the need for mechanical stirring. Model transformations using benzyl chloride and alkali metal salts (KCN, NaSCN) validated the efficiency of the immobilized phase‐transfer system, showing comparable or superior yields relative to homogeneous conditions. The covalently anchored catalysts remained active over multiple cycles, demonstrating excellent stability and reusability. The results establish a generalizable strategy for integrating biphasic reactions into automated high‐throughput synthesis workflows by eliminating the need for free phase‐transfer catalysts.
Source: Advanced Synthesis & Catalysis
DOI: 10.1002/adsc.70256
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4416934968