Capturing Reactive Carbanions by Microdroplets

Abstract

Carbanions appear in many organic or biological reactions as fleeting intermediates, prohibiting direct observation or spectroscopic measurement. An aqueous environment is known to rapidly annihilate a carbanion species, reducing its lifetime to as short as picoseconds. We report that aqueous microdroplets can capture and stabilize reactive carbanion intermediates isolated from four classic organic reactions, aldol and Knoevenagel condensations, alkyne alkylation, and the Reimer–Tiemann reaction, enabling the detection of their carbanion intermediates by desorption electrospray ionization mass spectrometry. This is accomplished in real time of the reaction, allowing new insights into reaction mechanisms to be obtained. The efficacy of microdroplets in capturing such elusive species was examined by varying the solvent and the microdroplet negative charge density. We observed that microdroplets composed of water–methanol outperform other solvents, such as pure water, in capturing carbanions, which is in contrast to the earlier report that presented the highest performance of pure water microdroplets in capturing carbocations. We offer some mechanistic insights to explain the discriminatory behavior of these two oppositely charged species in microdroplets.

Efficient Desorption and Capture of Reactive Carbocations from Positively Charged Glass Surface Bombarded with High-Speed Water Microdroplets

“…When we impacted a carbocation intermediate generating reaction aliquot using H 2 O 18 (99 atom % O 18 -water) microdroplets in the DESI source, we could detect a trace ion signal (sodium adduct) of the corresponding O 18 -labeled alcohol along with an intense ion signal of the carbocation (Figure S2). This result suggests the survival of a significant fraction of the reactive carbocation in the DESI secondary microdroplets, despite a small fraction of the carbocation annihilation by the nucleophilic attack of water (H 2 O 18 ). This result is in line with the proposal that carbocations primarily span life at or near the air/water interface, 11 which is effectively water-poor.…”

“…Desorption Electrospray Ionization Mass Spectrometry (DESI-MS). The DESI-MS studies were performed using a custom-built DESI source (Figure 1a) 5,6,18 coupled with a high-resolution mass spectrometer (Orbitrap Elite hybrid ion trap-Orbitrap mass spectrometer, ThermoFisher Scientific, Newington, NH, USA). The DESI source was built with an inner fused silica capillary (100 μm i.d.…”

Microdroplet Chemistry Accelerating a Three-Component Passerini Reaction for α-Acyloxy Carboxamide Synthesis

“…Microdroplet chemistry is an emerging research field that attracts extensive interest in analytical, organic, and biological communities because of its amazing power in reaction acceleration. − In addition to astonishing rate acceleration, microdroplet chemistry is striking us in making conditions mild (i.e., avoiding catalysts and high temperature), − decreasing energy barrier, − facilitating spontaneous redox reactions, − stabilizing transient intermediates, − and providing novel reactivities. − The role versatility and format diversity of microdroplet chemistry open new windows for analytical derivatization, , biotic and abiotic synthesis, ,,,− and mainly organic applications (mechanistic studies, ,,, reaction screening, − rapid gram-scale organic synthesis, − etc.). Organic reactions by microdroplet chemistry and acceleration mechanisms have been comprehensively summarized in three review papers by Cooks’s group. − …”

OH radical-initiated single-electron transfer for accelerated degradation via carbocation intermediates

“…Beyond instantaneous molecular information, the continuous monitoring of dynamic changes or transformations of different reactive intermediates (radical cations and carbocations) would also offer signicant benets to in-depth SET studies. 9,10 Taking green and efficient degradation by plasma catalysis as an example, the SET process was predicated on the coupling of heterogeneous catalysts with non-thermal plasma. Generated by air discharge, the plasma normally contains active species.…”