New Fluorogenic Probes for Oxygen and Carbene Transfer:  A Sensitive Assay for Single Bead-Supported Catalysts

Abstract

A high-throughput screening assay for atom transfer catalysis has been developed. This assay is based on two probes, developed herein, which generate highly fluorescent products upon carbene or oxygen atom transfer. The emission wavelength of probes 1 and 5 shift significantly (up to 90 nm) upon epoxidation, allowing detection of product at 3% conversion. Probe 7 is not fluorescent, while fluorescence emission by carbene insertion/rearrangement product 8 allows detection at less than 1% conversion. Such sensitivity allows for examination of single-bead reactions in a high throughput array format (1536 wells per plate), and provides a broad detection window ranging from single to high turnover numbers. Thousands of metal complexes are evaluated in a single screening experiment. Preliminary screening of a diverse ligand library with probe 7 in the presence of Rh(II) uncovered new catalysts capable of cyclopropanation and C-H insertion.

Mini-ISES identifies promising carbafructopyranose-based salens for asymmetric catalysis: Tuning ligand shape via the anomeric effect

“…More recently, microfluidic approaches have been invoked to address throughput ( 21 – 23 ). Optical sensing methods continue to be invoked and include fluorescence resonance energy transfer ( 24 ), indicator-displacement assays ( 16 , 25 ), substrate chromophore induction ( 26 ), and optical rotatory dispersion ( 27 ). Mass spectrometric methods have proven invaluable to enhance throughput ( 4 , 28 ) and provide information on reactivity ( 29 ) and stereoselectivity ( 30 , 31 ).…”

High Throughput Screening Methods for Asymmetric Synthesis

“…In 2001, Sames reported a high-throughput screening assay for atom transfer catalysis [58]. It was not intended to be a general assay as it was designed for this sole purpose.…”

Late‐Stage Functionalization and Characterization of Drugs by High‐Throughput Desorption Electrospray Ionization Mass Spectrometry

“…Recently, highthroughput experimentation (HTE) has emerged as a rapid and systematic method for synthetic route screening for conventional reactions using small quantities of reagents in an array format. [8][9][10][11][12][13][14][15][16][17] HT methods can be utilized to assess product yields as a function of such reaction parameters as the choice of reactants, pH, catalyst, ligand, stoichiometric ratio, order of addition, temperature, solvent, and substrate. Extensive studies of this kind are challenging because of the time required for synthesis and analysis but HT systems overcome this limitation.…”