A Mass Spectrometric Labeling Strategy for High-Throughput Reaction Evaluation and Optimization: Exploring C−H Activation

Use of Ambient Ionization High-Resolution Mass Spectrometry for the Kinetic Analysis of Organic Surface Reactions

“… Thus, the ester bond was selected as a labile linker that couples the reactive BCN group with a MS tag, which was chosen to be a para -substituted benzoic acid derivative with a fluorinated butyl chain (highlighted in green in Scheme ). Such a labeling approach has been widely studied; , however, to the best of our knowledge, this is the first time an ionizable MS tag is used for interfacial kinetics elucidation. This design has three additional advantages: (1) the fluorinated alkyl chain increases the volatility of the benzoic acid group, allowing a rapid surface desorption; (2) the electron-withdrawing perfluorobutyl group weakens the ester bond and stabilizes the carboxylate anion; (3) F signals are easily detected by XPS, thus providing a label for an independent quantitative analysis.…”

Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization

“…1A ). While the use of MS labeling approach to facilitate the ionization process has been recognized ( 14 - 18 ) and used to optimize at least two established reactions ( 16 , 18 ), this powerful concept has not been employed for high-throughput discovery of new chemical transformations.…”

Laser desorption ionization mass spectrometry: Recent progress in matrix‐free and label‐assisted techniques

“…The importance of a polyaromatic moiety to impart selective ionization was first demonstrated by Senkan, who used resonance‐enhanced multi‐photon ionization (REMPI) TOF‐MS to selectively identify benzene in the presence of cyclohexane . Limbach and coworkers also showed that when a polyaromatic molecule like anthracene is used as matrix in MALDI‐MS, it plays a direct and active role in ionization. Unlike other conventional matrices, which ionize the analyte by proton transfer or ion transfer reaction, an electron transfer mechanism has been proposed by which the photo‐ionized molecule ion of the matrix (M •+ ) ionizes the analyte molecules (A) by accepting an electron.…”

“…This tag can absorb laser power to assist desorption/ionization to exclude the need of external matrix.The importance of a polyaromatic moiety to impart selective ionization was first demonstrated by Senkan, who used resonance-enhanced multi-photon ionization (REMPI) TOF-MS to selectively identify benzene in the presence of cyclohexane 51. Limbach and coworkers also showed that when a polyaromatic molecule like anthracene is used as matrix in MALDI-MS,52,53 it plays a direct and active role in ionization. Unlike other conventional matrices, which ionize the analyte by proton transfer or ion transfer reaction, an electron transfer mechanism has been proposed by which the photo-ionized molecule ion of the matrix (M •+ ) ionizes the analyte molecules (A) by accepting an electron.M þ nhv → M •þ ðphoto ionization processÞ M •þ þ A → M þ A •þ ðelectron transfer processÞPolyaromatic moieties are most versatile in this regard because they have high molar absorptivity that allows efficient absorption of laser radiation and also for their facile ability to form molecular ions.Kozmin et al in a landmark paper first reported the use of pyrene as a polyaromatic MS tag and established a general and powerful method for reaction optimization and discovery with LALDI-TOF-MS 54.…”