First Example of a Continuous-Flow Carbonylation Reaction Using Aryl Formates as CO Precursors

Alonso, Nerea; Muñoz, Juan de M.; Egle, Brecht; Vrijdag, Johannes; Borggraeve, Wim M. De; Hoz, Antonio de la; Díaz‐Ortiz, Ángel; Alcázar, Jesús

doi:10.1556/jfc-d-14-00005

Cited by 18 publications

(12 citation statements)

References 33 publications

(2 reference statements)

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“…[11][12][13] Although this technique has not been used as widely in flow as in batch carbonylations there are some examples. 2,4,6-Trichlorophenyl formate has been reported as a CO surrogate in the Pd catalyzed synthesis of (hetero)aromatic 2,4,6-trichlorophenol esters, 14 and the dehydration of formic acid by concentrated H 2 SO 4 has been employed as an in situ CO source for the Koch-Haaf reaction in a specialist hastelloy microreactor. 15 The main limitation of these kinds of surrogates is that the chemistry must be compatible with both the surrogate itself and the conditions needed for CO release.…”

Section: Introductionmentioning

confidence: 99%

Controlled generation and use of CO in flow

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Controlled generation and use of CO in flow

et al. 2016

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“…In addition, since some CO surrogates developed in our laboratory are now commercially available at reasonable prices, 104) they have begun to be applied in the fields of medicinal chemistry, 105,106) total syntheses of natural bioactive compounds, 107,108) and flow chemistry. 109,110) For the development of truly useful reactions, the practical aspects of the organic reactions in question need to be considered during their development and application. The substitution of toxic gases for their surrogates in synthetic organic reactions is attractive; the resulting ready-to-use reactions may result in paradigm-shifting protocols for conducting reactions with toxic gases.…”

Section: Resultsmentioning

confidence: 99%

Creation of Novel Toxic Gas Surrogates and the Development of Safe and Facile Catalytic Reactions

Konishi

2018

Chem. Pharm. Bull.

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The use of toxic gas surrogates in organic reactions instead of the gas itself contributes to enhancing the safety, practicality, and efficiency of the reactions involved. Our efforts toward the creation of toxic gas surrogates and the development of a series of catalytic reactions using these surrogates are described. Improvements in substrate scope during the hydroesterification of alkenes using formates facilitated by the Ru-imidazole catalyst system provided the opportunity to discover that phenyl formate is a useful carbon monoxide (CO) surrogate for the generation of CO and phenol under weakly basic conditions. This discovery triggered the development of highly reactive but stable CO surrogates and a variety of Pd-catalyzed carbonylative transformations. N-Formylsaccharin facilitated the use of additional nucleophiles in carbonylation reactions that provided access to a variety of carbonyl compounds. Detailed experimental and theoretical mechanistic studies into the generation of CO from phenyl formate suggest that CO generation proceeds via a concerted E2 α-elimination. Furthermore, a known surrogate of sulfur dioxide was applied for the first time to the selective syntheses of cyclic sulfonamides and sulfinamides, confirming that the surrogate operates as an "S O" source. Notably, the reactions described herein are scalable and can be performed without the use of external toxic gases and specialized reaction vessels; they are easy and simple to perform and demonstrate enormous potential for industrial application.

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“…gas cylinder, thus furnishing N-(pyridin-4-yl)benzamide in 65 % yield. [77] Raston and co-workers, in 2015, reported a continuous-flow approach for the amide synthesis using a novel thin film vortex fluidic device (VFD) (Table 1, entry 4; Scheme 3). [69] The reagents were introduced into the inclined rapidly rotating tube and proceeded up to the walls of the tube for exiting.…”

Section: Chemsuschemmentioning

confidence: 99%

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

2022

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Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small-molecule active pharmaceutical ingredients, in linear or cyclic oligo-and polypeptidic actives, including pseudopeptides, has led to the development of dedicated synthetic approaches for the formation of amide bonds starting from, if necessary, suitably protected amino acids. While the use of solid supported reagents is common in traditional peptide synthesis, similar approaches targeting amide bond formation in continuous-flow mode took off more significantly, after a first publication in 2006, only a couple of years ago. Most efforts rely upon the transition of traditional approaches in flow mode, or the combination of solid-phase peptide synthesis principles with flow chemistry, and advantages are mainly seen in improving space-time yields. This Review summarizes and compares the various approaches in terms of basic amide formation, peptide synthesis, and pseudopeptide generation, describing the technological approaches and the advantages that were generated by the specific flow approaches. A final discussion highlights potential future needs and perspectives in terms of greener and more sustainable syntheses.

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First Example of a Continuous-Flow Carbonylation Reaction Using Aryl Formates as CO Precursors

Cited by 18 publications

References 33 publications

Controlled generation and use of CO in flow

Controlled generation and use of CO in flow

Creation of Novel Toxic Gas Surrogates and the Development of Safe and Facile Catalytic Reactions

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

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