Site-Selective C(sp3)–H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals

Synthesis, Journal Year: 2021, Volume and Issue: 54(06), P. 1461 - 1477

Published: Oct. 25, 2021

Abstract Amines and amides, as N-containing compounds, are ubiquitous in pharmaceutically-active scaffolds, natural products, agrochemicals, peptides. Amides nature bear a key responsibility for imparting three-dimensional structure, such proteins. Structural modifications to amines especially at their positions α N, bring about profound changes biological activity oftentimes leading more desirable pharmacological profiles of small drug molecules. A number recent developments synthetic methodology the functionalizations amides omit need directing groups or pre-functionalizations, achieving direct activation otherwise relatively benign C(sp3)–H bonds N. Among these, hydrogen atom transfer (HAT) has proven very powerful platform selective α-amino α-amido radicals, which can then be employed furnish C–C C–X (X = heteroatom) bonds. The abilities both form these radicals control reactivity site-selective manner is utmost importance chemistries witness applications late-stage functionalization. Therefore, this review captures contemporary HAT strategies realize chemo- regioselective amine amide α-C(sp3)–H functionalization, based on bond strengths, polarities, reversible equilibria, traceless electrostatic-directing auxiliaries, steric effects situ-generated agents. 1 Introduction 2 Functionalizations 3 Carbamates 4 5 Conclusion

Language: Английский

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Oxidative lactonization of C(sp3)-H bond in methyl aromatic alcohols enabled by proton-coupled electron transfer

Science China Chemistry, Journal Year: 2022, Volume and Issue: 65(8), P. 1526 - 1531

Published: July 18, 2022

Language: Английский

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Selective and Functional-Group-Tolerant Photoalkylation of Imines by Energy-Transfer Photocatalysis

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(21), P. 15209 - 15217

Published: Oct. 24, 2023

Basic amines show broad bioactivity and remain a promising source of new medicines. The direct photoalkylation imines offers strategy for complex amines. However, the lack efficient imine photoreactivity hinders this reaction remains fundamental limitation in organic photochemistry. We report an that provides primary directly without protecting or leaving groups. transformation effects C-H addition across N-H under energy-transfer photocatalysis by ketone. Our method is distinguished from organometallic, metal-catalyzed, photoredox approaches to alkylation its groups scope, which includes unactivated alkanes, protic substrates, basic amines, heterocycles, ketone imines. highlight scope through condensation two pharmaceutical ketones, providing succinctly. mechanistic analysis supports three-step process, involving hydrogen-atom transfer triplet excited state, intersystem crossing, radical recombination, with photocatalytic enhancement energy transfer. further are more photoreactive than N-substituted imines, distinction partially explained sterics side reactions. To fully explain distinction, we introduce thermodynamic parameter excited-state affinity, highly effective at predicting

Language: Английский

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Continuous‐Flow Photochemistry: The Synthesis of Marketed Pharmaceutical Compounds

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(47)

Published: Dec. 1, 2024

Abstract Chemistry professionals from all kinds of fields and disciplines in the academic commercial sectors have recently shown a great deal interest continuous‐flow chemistry. Flow methods are used nowadays for rapid optimization assessment, as well production scale‐up, reaction discovery, methodology. Photochemical processes currently receiving lot attention scientific community, application flow these approaches has advantages chemistry its importance modern industry worldwide. This study illustrates most recent advancements benefits continuous photochemical reactions relation to synthesis active pharmaceutical compounds recommended frameworks.

Language: Английский

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Sustainable Photooxidation using a Subpart-per-million Heavy-Metal-Free Red-Light Photocatalyst

ACS Sustainable Chemistry & Engineering, Journal Year: 2023, Volume and Issue: 11(43), P. 15674 - 15684

Published: Oct. 15, 2023

Photochemical activation using red or near-infrared light has recently emerged as a potential remedy for solving fundamental issues in photochemistry such selectivity and scale up. However, this is particularly challenging the case of photooxidation chemistry due to low resistance photobleaching poor solubility photocatalysts absorbing region electromagnetic spectrum. In study, we report use commercially available Si-phthalocyanines robust environmentally friendly class soluble photosensitizers activated under light. Interestingly, while exhibit lower singlet oxygen generation (ϕΔ) quantum yields compared classical photosensitizers, their high stability enables us achieve comparable efficiencies at ultralow catalytic loadings (ppb range). This unique feature provides performances range photooxidative processes substrate concentrations ultimately leading safe efficient solvent-free continuous flow applied multigram-scale synthesis.

Language: Английский

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