The Eschenmoser coupling reaction under continuous-flow conditions

The Eschenmoser coupling is a useful carbon–carbon bond forming reaction which has been used in various different synthesis strategies. The reaction proceeds smoothly if S-alkylated ternary thioamides or thiolactames are used. In the case of S-alkylated secondary thioamides or thiolactames, the Eschenmoser coupling needs prolonged reaction times and elevated temperatures to deliver valuable yields. We have used a flow chemistry system to promote the Eschenmoser coupling under enhanced reaction conditions in order to convert the demanding precursors such as S-alkylated secondary thioamides and thiolactames in an efficient way. Under pressurized reaction conditions at about 220 °C, the desired Eschenmoser coupling products were obtained within 70 s residence time. The reaction kinetics was investigated and 15 examples of different building block combinations are given.

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Dimeric cyclobutane formation under continuous flow conditions using organophotoredox catalysed [2+2]-cycloaddition

10.33774/chemrxiv-2021-1c8zv ◽

2021 ◽

Author(s):

Helena Grantham ◽

Marc Kimber

Keyword(s):

Natural Products ◽

Continuous Flow ◽

Reaction Times ◽

Functional Materials ◽

Synthetic Route ◽

Flow Conditions ◽

Reaction Conditions ◽

New Class ◽

Cyclobutane Dimers ◽

Flow Study

Radical cation-initiated dimerization of electron rich alkenes is an expedient method for the synthesis of cyclobutanes. By merging organophotoredox catalysis and continuous flow technology a batch versus continuous flow study has been performed providing a convenient synthetic route to an important carbazole cyclobutane material dimer t-DCzCB using less only 0.1 mol% of an organophotoredox catalyst. The scope of this methodology was explored giving a new class of functional materials, as well as an improved synthetic route to styrene based lignan dimeric natural products. The cyclobutane dimers could be isolated in higher chemical yields under continuous flow conditions and reaction times were reduced significantly compared to traditional batch reaction conditions.

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Cobalt-catalyzed deoxygenative triborylation of allylic ethers to access 1,1,3-triborylalkanes

Nature Communications ◽

10.1038/s41467-020-19039-7 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Wei Jie Teo ◽

Xiaoxu Yang ◽

Yeng Yeng Poon ◽

Shaozhong Ge

Keyword(s):

Building Blocks ◽

Mechanistic Studies ◽

Deuterium Labeling ◽

Bond Forming ◽

Carbon Carbon Bond ◽

Synthetic Utility ◽

Reaction Proceeds ◽

Site Selective ◽

And Control ◽

Allylic Ethers

Abstract Polyborylated organic compounds have been emerging as versatile building blocks in chemical synthesis. Here we report a selective cobalt-catalyzed deoxygenative 1,1,3-triborylation reaction of allylic ethers with pinacolborane to prepare 1,1,3-triborylalkane compounds. With naturally abundant and/or synthetic cinnamic methyl ethers as starting materials, we have achieved the synthesis of a variety of 1,1,3-triborylalkanes (25 examples). The synthetic utility of these 1,1,3-triborylalkanes is demonstrated through site-selective allylation, protodeborylation, and consecutive carbon-carbon bond-forming reactions. Mechanistic studies including deuterium-labeling and control experiments suggest that this 1,1,3-triborylation reaction proceeds through initial cobalt-catalyzed deoxygenative borylation of allylic ethers to form allylic boronates followed by cobalt-catalyzed 1,1-diborylation of the resulting allylic boronates.

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Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis

Synthesis ◽

10.1055/s-0040-1707212 ◽

2020 ◽

Vol 52 (23) ◽

pp. 3511-3529 ◽

Cited By ~ 1

Author(s):

Peter Koóš ◽

Martin Markovič ◽

Pavol Lopatka ◽

Tibor Gracza

Keyword(s):

Organic Synthesis ◽

Continuous Flow ◽

Palladium Catalysis ◽

Flow Chemistry ◽

Cross Coupling ◽

Coupling Reactions ◽

Flow Conditions ◽

Cross Coupling Reactions ◽

Continuous Flow Chemistry ◽

Oxidative Transformations

Considerable advances have been made using continuous flow chemistry as an enabling tool in organic synthesis. Consequently, the number of articles reporting continuous flow methods has increased significantly in recent years. This review covers the progress achieved in homogeneous palladium catalysis using continuous flow conditions over the last five years, including C–C/C–N cross-coupling reactions, carbonylations and reductive/oxidative transformations.1 Introduction2 C–C Cross-Coupling Reactions3 C–N Coupling Reactions4 Carbonylation Reactions5 Miscellaneous Reactions6 Key to Schematic Symbols7 Conclusion

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N-Methyl-D-Glucoseimine Synthesis Reaction Thermodynamic Properties Calculation

Bulletin of Science and Practice ◽

10.33619/2414-2948/60/04 ◽

2020 ◽

Vol 6 (11) ◽

pp. 40-46

Author(s):

S. Mikhailov ◽

R. Brovko ◽

S. Mushinskii ◽

M. Sulman

Keyword(s):

Elevated Temperatures ◽

Equilibrium Constants ◽

Thermodynamic Calculations ◽

Process Conditions ◽

Reaction Conditions ◽

Formation Reaction ◽

Reaction Proceeds ◽

Energy Equilibrium ◽

Reversible Formation ◽

Pharmaceutical Practice

The presented article is devoted to thermodynamic calculations of the N-methyl-D-glucosimine reversible formation reaction, an intermediate product for N-methyl-D-glucosamine synthesis, which is widely used in pharmaceutical practice as a ballast or counterion that improves the bioavailability of the main active substance. N-methyl-D-glucosimine is synthesized as a result of the interaction of D-glucose with methylamine in organic solvents, the reaction is reversible, and the yield of the target product depends entirely on the reaction conditions. The use of thermodynamic calculations makes it possible to evaluate the influence of the chemical process conditions on the yield of target products, which in turn contributes to a deeper understanding of the chemical reactions mechanisms. In chemical equilibrium, direct and reverse reactions proceed at equal rates, while the concentrations of products and reagents remain constant. When the reaction proceeds in a closed system, after a certain time, a state of equilibrium occurs, while the reaction does not proceed with a complete transformation of the reagents. This article presents the results of thermodynamic calculations of the reaction for the synthesis of N-methyl-D-glucosimine by the Van Kravlen – Cheremnov method. The Gibbs energy, equilibrium constants, and D-glucose conversion were calculated as activity function of reacting substances. It was shown that an increase in the temperature of the reaction mixture from 20 to 160 °C promotes an increase in the conversion of D-glucose from 3 to 32%, and therefore it is possible to recommend carrying out this reaction at elevated temperatures.

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The influence of mixing on chain extension by photo-controlled/living radical polymerization under continuous-flow conditions

Polymer Chemistry ◽

10.1039/c9py01063g ◽

2019 ◽

Vol 10 (35) ◽

pp. 4879-4886 ◽

Cited By ~ 6

Author(s):

Fuyao Zhong ◽

Yang Zhou ◽

Mao Chen

Keyword(s):

Radical Polymerization ◽

Continuous Flow ◽

Flow Chemistry ◽

Polymer Synthesis ◽

Living Radical Polymerization ◽

Chain Extension ◽

Flow Conditions ◽

Continuous Flow Chemistry ◽

Controlled Living Radical Polymerization

Continuous-flow chemistry holds powerful potential for polymer synthesis, and has attracted increasing attention in recent years.

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Breaking Molecular Symmetry through Biocatalytic Reactions to Gain Access to Valuable Chiral Synthons

Symmetry ◽

10.3390/sym12091454 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1454

Author(s):

Angela Patti ◽

Claudia Sanfilippo

Keyword(s):

Bioactive Compounds ◽

Continuous Flow ◽

Molecular Diversity ◽

Molecular Symmetry ◽

Flow Conditions ◽

Reaction Conditions ◽

Whole Cells ◽

Efficient Approach ◽

Substrate Tolerance ◽

Gain Access

In this review the recent reports of biocatalytic reactions applied to the desymmetrization of meso-compounds or symmetric prochiral molecules are summarized. The survey of literature from 2015 up to date reveals that lipases are still the most used enzymes for this goal, due to their large substrate tolerance, stability in different reaction conditions and commercial availability. However, a growing interest is focused on the use of other purified enzymes or microbial whole cells to expand the portfolio of exploitable reactions and the molecular diversity of substrates to be transformed. Biocatalyzed desymmetrization is nowadays recognized as a reliable and efficient approach for the preparation of pharmaceuticals or natural bioactive compounds and many processes have been scaled up for multigram preparative purposes, also in continuous-flow conditions.

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Copper-Catalyzed C(sp3)–H Azidation of 1,3-Dihydro-2H-indol-2-ones Under Mild Conditions

Synlett ◽

10.1055/s-0037-1610672 ◽

2018 ◽

Vol 30 (01) ◽

pp. 109-113 ◽

Cited By ~ 3

Author(s):

Wen-Ting Wei ◽

Yan-Yun Liu ◽

Wen-Hui Bao ◽

Le-Han Gao ◽

Wei-Wei Ying ◽

...

Keyword(s):

Biological Activity ◽

Reaction Times ◽

Reaction Conditions ◽

Mild Conditions ◽

Trimethylsilyl Azide ◽

Reaction Proceeds ◽

The Rich ◽

Enol Tautomer

A simple and economical synthesis of 3-substituted 3-azido-1,3-dihydro-2H-indol-2-ones has been realized under mild conditions through copper-catalyzed C(sp3)–H azidation of the corresponding 1,3-dihydro-2H-indol-2-ones with trimethylsilyl azide. The reaction proceeds by an efficient pathway involving the addition of a N3 radical to the enol tautomer and consecutive C(sp3)−N bond formations. The method is valuable because of its mild reaction conditions, short reaction times, and broad substrate scope, and because of the rich biological activity of the resulting 3-substituted 3-azido-1,3-dihydro-2H-indol-2-one products.

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