A Brief Introduction to Chemical Reaction Optimization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(6), P. 3089 - 3126

Published: Feb. 23, 2023

From the start of a synthetic chemist's training, experiments are conducted based on recipes from textbooks and manuscripts that achieve clean reaction outcomes, allowing scientist to develop practical skills some chemical intuition. This procedure is often kept long into researcher's career, as new developed similar protocols, intuition-guided deviations through learning failed experiments. However, when attempting understand systems interest, it has been shown model-based, algorithm-based, miniaturized high-throughput techniques outperform human intuition optimization in much more time- material-efficient manner; this covered detail paper. As many chemists not exposed these undergraduate teaching, leads disproportionate number scientists wish optimize their reactions but unable use methodologies or simply unaware existence. review highlights basics, cutting-edge, modern well its relation process scale-up can thereby serve reference for inspired each techniques, detailing several respective applications.

Language: Английский

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Multicomponent Pyrazole Synthesis from Alkynes, Nitriles, and Titanium Imido Complexes via Oxidatively Induced N–N Bond Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(9), P. 4390 - 4399

Published: Feb. 11, 2020

Pyrazoles are an important class of heterocycles found in a wide range bioactive compounds and pharmaceuticals. Pyrazole synthesis often requires hydrazine or related reagents where intact N–N bond is conservatively installed into pyrazole precursor fragment. Herein, we report the multicomponent oxidative coupling alkynes, nitriles, Ti imido complexes for multisubstituted pyrazoles. This modular method avoids potentially hazardous like hydrazine, instead forming final step via oxidation-induced on Ti. The mechanism this transformation has been studied in-depth through stoichiometric reactions key diazatitanacyclohexadiene intermediate, which can be accessed imidos with nitriles ring opening 2-imino-2H-azirines, direct metalation 4-azadiene-1-amine derivatives. critical reaction 2-electron rare example formal metal center, likely occurs electrocyclic analogous to Nazarov cyclization. Conveniently, these 2-electron-oxidized intermediates disproportionation 1-electron-oxidized species, allows utilization weak oxidants such as TEMPO

Language: Английский

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The clean preparation of multisubstituted pyrroles under metal- and solvent-free conditions

Green Chemistry, Journal Year: 2019, Volume and Issue: 22(1), P. 118 - 122

Published: Nov. 29, 2019

A practical method for the clean preparation of multisubstituted pyrroles via an iodine-catalyzed multicomponent reaction under metal- and solvent-free conditions was developed. In gram-scale synthesis, can be easily collected through simple extraction.

Language: Английский

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Synthesis of Pyrroles through the CuH-Catalyzed Coupling of Enynes and Nitriles

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(22), P. 9908 - 9914

Published: May 12, 2020

Herein, we describe an efficient method to prepare polysubstituted pyrroles via a copper hydride (CuH)-catalyzed enyne-nitrile coupling reaction. This protocol accommodates both aromatic and aliphatic substituents broad range of functional groups, providing variety N-H in good yields with high regioselectivity. We propose that the Cu-based catalyst promotes initial reductive subsequent cyclization steps. Density theory (DFT) calculations were performed elucidate reaction mechanism.

Language: Английский

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Reactivity of terminal imido complexes of group 4–6 metals: Stoichiometric and catalytic reactions involving cycloaddition with unsaturated organic molecules

Coordination Chemistry Reviews, Journal Year: 2020, Volume and Issue: 407, P. 213118 - 213118

Published: Jan. 14, 2020

Language: Английский

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Highly Regioselective Synthesis of Multisubstituted Pyrroles via Ag-Catalyzed [4+1C]^insert Cascade

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(6), P. 3733 - 3740

Published: Feb. 6, 2020

An efficient [4+1C]insert approach to the coupling of enaminones with donor/acceptor or donor/donor carbenes by AgOTf-catalyzed C–C bond carbenoid formal insertion/cyclization/[1,5]-shift cascade reaction was successfully developed, providing distinct chemo- and regioselective multisubstituted pyrroles. The plausible mechanism involves two catalytic cycles: in first one, silver ions regioselectively catalyze insertion reaction; second control cyclization [1,5]-shift reactions. This method not only provides convenience applies atom economy synthesis pyrroles but also presents an entry point for further pyrrole diversification via facile modification resulting 4H-pyrrole products, as displayed a short natural product lamellarin L.

Language: Английский

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Modular Domino Process toward Highly Functionalized Pyrroles via Pd-Catalyzed [4 + 1] Annulation under Mild Conditions

Organic Letters, Journal Year: 2021, Volume and Issue: 23(6), P. 2013 - 2018

Published: Feb. 25, 2021

A Pd-catalyzed decarboxylative approach for the modular synthesis of highly functionalized pyrroles is presented. This protocol utilizes readily available cyclic carbonates and amines as reaction partners only generates CO2 H2O byproducts. methodology could be operated at room temperature open to air, thus serving an ideal means derivatization bioactive compounds. Mechanism investigations suggested that stereoselective formation (Z)-configured γ-amino ketone intermediate crucial success reaction.

Language: Английский

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Metal-coordinated azoaromatics: Strategies for sequential azo-reduction, isomerization and application potential

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 475, P. 214895 - 214895

Published: Oct. 21, 2022

Language: Английский

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Molecular Editing of Pyrroles via a Skeletal Recasting Strategy

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(9), P. 1758 - 1767

Published: Aug. 15, 2023

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization allow for peripheral modifications of heterocyclic motifs, often being specific taking place at multiple sites. The past few years seen the quick emergence exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion structural diversification, as well scaffold hopping. construction heterocycles via deconstruction simple is unknown. Herein, we disclose a new method which name recasting strategy. Specifically, by tapping on 1,3-dipolar property azoalkenes, recast pyrroles to fully substituted pyrroles, phosphoric acid-promoted one-pot reaction consisting dearomative rearomative reconstruction steps. allows easy access synthetically challenging tetra-substituted otherwise difficult synthesize. Furthermore, construct N-N axial chirality our pyrrole products, accomplish facile synthesis anticancer drug, Sutent. potential application this other has also demonstrated.

Language: Английский

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Photoinduced Difunctionalization of Diazenes Enabled by N–N Radical Coupling

Organic Letters, Journal Year: 2023, Volume and Issue: 25(36), P. 6671 - 6676

Published: Aug. 29, 2023

In this study, a metal-free difunctionalization strategy for diazenes was developed using range of bifunctionalization reagents. This involves unique N(sp3)–N(sp2) radical coupling between the hydrazine and imine radical. More than 30 triazane core motifs were constructed by installing imines various functional groups, including alkyl, phenyl, cyanoalkyl, sulfonyl on both ends nitrogen–nitrogen bond in an efficient manner.

Language: Английский

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