Suzuki C–C Coupling in Paper Spray Ionization: Microsynthesis of Biaryls and High-Sensitivity MS Detection of Aryl Bromides

Abstract

Suzuki–Miyaura cross-coupling is one of the most powerful strategies for constructing biaryl compounds. However, classic Suzuki–Miyaura coupling suffers from hour-scale reaction time and competitive protodeboronation. To address these problems, a mild nonaqueous potassium trimethylsilanolate (TMSOK)-assisted Suzuki–Miyaura coupling strategy was designed for the microsynthesis of biaryls in paper spray ionization (PSI). Due to the acceleration power facilitated by microdroplet chemistry in reactive PSI, the microsynthesis of biaryls by reactive PSI was accomplished within minutes with comparable yields to the bulk, showing good substrate applicability from 32 Suzuki–Miyaura reactions of aryl bromides and aryl boronic acid/borates bearing different substituents. Based on the above TMSOK-assisted Suzuki–Miyaura coupling strategy, we further developed a high-sensitivity and selective PSI mass spectrometry (MS) method for quantitative analysis of aryl bromides, a class of environmentally persistent organic pollutants that cannot be directly detected by ambient mass spectrometry due to their low ionization efficiency. In situ derivatization of aryl bromides was achieved with aryl borates bearing quaternary ammonium groups in PSI. The proposed PSI-MS method shows good linearity over the 0.01–10 μmol L–1 range with low detection limits of 1.8–4.8 nmol L–1 as well as good applicability to the rapid determination of six aryl bromides in three environmental water samples. The proposed PSI-MS method also shows good applicability to brominated flame retardants (polybrominated diphenyls/diphenyl esters). Overall, this study provides a simple, rapid, low-cost, high-sensitivity, and high-selectivity strategy for trace aryl bromides and other brominated pollutants in real samples with minimal/no sample pretreatment.

Mild Diarylmethylation of Indoles through Regioselective 1,6-Hydroarylation of para-Quinone Methides in Microdroplets/Thin Film

“…In our previous studies, ,,,,− both the reaction and collection temperature play essential roles in many microdroplet/thin film reactions, leading to a necessity to optimize the two temperatures. According to our investigation into the reaction temperature (entry 12 of Table and Table S4), high reaction temperatures were unbeneficial to the microdroplet/thin film conversion.…”

Is Reaction Acceleration of Microdroplet Chemistry Favorable to Controlling the Enantioselectivity?

“…Reaction of the Ketones to Be Stereoselectively Converted into Chiral Alcohols by Photochemical Enzymatic Catalysis in the Bulk Phase. The enzymatic synthesis of (S)-1-(2,6-dichloro-3fluorophenyl) ethanol (11) in bulk phase was carried out with 2,5didehydrogluconate reductase-alcohol dehydrogenase (DkgA-ADH, 20 mg•mL −1 ) which was suspended in 3 mL of PBS (200 Mm, pH 7.0) containing 2 mg•mL −1 NADP + , 1-(2,6-dichloro-3-fluorophenyl)ethan-1-one (10, 20 mM), and isopropanol (60 μL) and the solution was stirred for 20 min and 2 h at 25 °C (water bath). The collected crude product was extracted with ethyl acetate.…”

“…After being diluted and filtered by a 0.22 μm filter, the organic phase was analyzed by RP-HPLC, and the yield was calculated by the external standard method. The crude product from the scaled microdroplet reaction was purified by column chromatography using petroleum ether/ethyl acetate as eluent to produce the desired chiral alcohol product (11) for NMR characterization, monitoring ee values.…”

“…As an emerging research field derived from mass spectrometric analysis in the past two decades, microdroplet chemistry has attracted extensive attention beyond the analytical community because of its strong power in reaction acceleration. − Development of microdroplet chemistry not only stimulates huge profit in the analytical community but also provides countable benefits in many other scientific communities. By taking advantage of microdroplet chemistry, analysts can efficiently achieve structural characterization − and high-sensitivity quantification − while material chemists can construct diverse micro- and nanostructures (nanoparticles, nanorod, nanowire, etc. ). − Biological chemists can utilize microdroplets to conduct many thermodynamically unfavorable conversions and processes in cellular compartments − while environmental chemists can make use of microdroplet chemistry to simulate and predict many important atmospheric processes. − Last but not least, synthetic chemists can develop not only a variety of mild, green, efficient, and gram-scale methodologies − but also discover several unique chemoselective conversions based on microdroplet chemistry. − Organic chemists may further benefit from microdroplet chemistry with respect to mechanistic studies (probing fleeting intermediates) − and predictable guidance to flow chemistry. − …”

Enhanced Compound Analysis Using Reactive Paper Spray Mass Spectrometry: Leveraging Schiff Base Reaction for Amino Acid Detection

“… 11 Various reactions like the Katrizky reaction, 12 Haloform reaction, 13 and nucleophilic substitution reactions, 14 have been explored within this realm. Reactive PS-MS innovatively leverages these diverse chemical reactions to enhance the detection and quantification of analytes, spanning estrogens, 15 aldehydes, 16 , 17 aryl bromides, 18 amino acid (AA) neurotransmitters, 19 among others.…”