Accelerated five-component spiro-pyrrolidine construction at the air–liquid interface

Kuai, Dacheng; Cheng, Heyong; Kuan, Kai-Yuan; Yan, Xingru

doi:10.1039/d1cc00574j

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…Microdroplet chemistry is an emerging field in chemistry due to the remarkable reaction acceleration ( Girod et al, 2011 ; Müller et al, 2012 ; Yan et al, 2016 , 2017 ; Lee et al, 2017 ; Nam et al, 2017 ; Cooks and Yan, 2018 ; Sahota et al, 2019 ; Zhang et al, 2019 , Zhang et al, 2021 Y. ; Wei et al, 2020 , 2022 ; Cao et al, 2020 ; Kuai et al, 2021 ; Vannoy et al, 2021 ; Zheng et al, 2021 ), and the unique properties of the reaction environment ( Li et al, 2014 ; Lee et al, 2019a , 2019b ; Gao et al, 2019 ; Huang et al, 2021 ; Wang et al, 2021 ; Gong et al, 2022 ; Qiu et al, 2022 ). These features give rise to numerous applications ( Wei et al, 2017 ; Yan et al, 2018 ; Zhu et al, 2019 ; Nie et al, 2020 ; Li Z. et al, 2021 ; Gunawardena et al, 2021 ; Yan, 2021 ; Zhang, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets

et al. 2022

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Spontaneous oxidation of compounds containing diverse X=Y moieties (e.g., sulfonamides, ketones, esters, sulfones) occurs readily in organic-solvent microdroplets. This surprising phenomenon is proposed to be driven by the generation of an intermediate species [M+H2O]+·: a covalent adduct of water radical cation (H2O+·) with the reactant molecule (M). The adduct is observed in the positive ion mass spectrum while its formation in the interfacial region of the microdroplet (i.e., at the air-droplet interface) is indicated by the strong dependence of the oxidation product formation on the spray distance (which reflects the droplet size and consequently the surface-to-volume ratio) and the solvent composition. Importantly, based on the screening of a ca. 21,000-compound library and the detailed consideration of six functional groups, the formation of a molecular adduct with the water radical cation is a significant route to ionization in positive ion mode electrospray, where it is favored in those compounds with X=Y moieties which lack basic groups. A set of model monofunctional systems was studied and in one case, benzyl benzoate, evidence was found for oxidation driven by hydroxyl radical adduct formation followed by protonation in addition to the dominant water radical cation addition process. Significant implications of molecular ionization by water radical cations for oxidation processes in atmospheric aerosols, analytical mass spectrometry and small-scale synthesis are noted.

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Section: Introductionmentioning

confidence: 99%

Spontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets

et al. 2022

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“…Microdroplets and thin films have been employed to carry out several different types of synthetic chemical reactions including Girard reactions, , Michael additions, , Mannich and Claisen–Schmidt condensations, ,,, Pomeranz–Fritsch synthesis, Katritzky reactions, , and even five-component spiropyrrolidine synthesis …”

Section: Introductionmentioning

confidence: 99%

“…1−4,7,13−20 Microdroplets and thin films have been employed to carry out several different types of synthetic chemical reactions including Girard reactions, 1,7 Michael additions, 1,13 Mannich and Claisen−Schmidt condensations, 7,11,13,19 Pomeranz− Fritsch synthesis, 11 Katritzky reactions, 21,22 and even fivecomponent spiropyrrolidine synthesis. 23 For this work, we seek to leverage the rate acceleration afforded by thin films and electrospray microdroplets to carry out online, in-source chemical derivatization using a unique, coaxial flow contained-electrospray ion source (contained-ESI). 24,25 The contained-ESI source is a modified electrospray platform that allows for the introduction of liquid and/or vapor phase reagents directly into the ion source.…”

Section: ■ Introductionmentioning

confidence: 99%

In-Source Microdroplet Derivatization Using Coaxial Contained-Electrospray Mass Spectrometry for Enhanced Sensitivity in Saccharide Analysis

Heiss

Badu‐Tawiah

2021

Anal. Chem.

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Online, droplet-based in-source chemical derivatization is accomplished using a coaxial-flow contained-electrospray ionization (contained-ESI) source to enhance sensitivity for the mass spectrometric analysis of saccharides. Derivatization is completed in microseconds by exploiting the reaction rate acceleration afforded by electrospray microdroplets. Significant improvements in method sensitivity are realized with minimal sample preparation and few resources when compared to traditional benchtop derivatizations. For this work, the formation of easily ionizable phenylboronate ester derivatives of several mono-, di-, and oligosaccharides is achieved. Various reaction parameters including concentration and pH were evaluated, and a Design of Experiments approach was used to optimize ion source parameters. Signal enhancements of greater than two orders of magnitude were observed for many mono-and disaccharides using in-source phenylboronic acid derivatization, resulting in partsper-trillion (picomolar) limits of detection. In addition, amino sugars such as glucosamine, which do not ionize in negative mode, were detected at low parts-per-billion concentrations, and isobaric sugars such as lactose and sucrose were easily distinguished. The new in-source derivatization approach can be employed to expand the utility of ESI-MS analysis for compounds that historically experience limited sensitivity and detectability, while avoiding resource-intensive, bulk-phase derivatization procedures.

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“…There was hardly any product formation at 0 h, without any time delay. Reactions in microdroplet are known to be accelerated, [28][29][30][31][32][33][34][35][36][37] however no such phenomenon was observed on the scale used here. HT-based DESI-MS analysis was also conducted to check the effect of different catalysts (Pd(acac) 2 , Pd(OAc) 2 , NiCl 2 , and CuCl 2 ) selecting the reaction between ethyl acrylate and Ezetimibe.…”

Section: Cà H Alkenylation Reaction On Ezetimibe (E) Using Ht-based Desi-ms Analysismentioning

confidence: 70%

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

Huang

Ghosh

et al. 2022

ChemPlusChem

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Late-stage functionalization (LSF) of drug molecules is an approach to generate modified molecules that retain functional groups present in the active drugs. Here, we report a study that seeks to characterize the potential value of high-throughput desorption electrospray ionization mass spectrometry (HT DESI-MS) for small-scale rapid LSF. In conventional route screening, HT-based DESI-MS provides contactless, rapid analysis, reliable and reproducible data, minimal sample requirement, and exceptional tolerance to high salt concentrations. Ezetimibe (E),[a] K.

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Accelerated five-component spiro-pyrrolidine construction at the air–liquid interface

Abstract: Multi-component reactions assemble complex molecules in a highly effective way, however they often suffer from long reaction times. We demonstrate that acceleration of a five-component spiro-pyrrolidine construction can be achieved...

Cited by 17 publications

References 40 publications

Spontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets

Spontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets

In-Source Microdroplet Derivatization Using Coaxial Contained-Electrospray Mass Spectrometry for Enhanced Sensitivity in Saccharide Analysis

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

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