Green chemistry meets medicinal chemistry: a perspective on modern metal-free late-stage functionalization reactions

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(19), P. 10955 - 10982

Published: Jan. 1, 2021

This review summarizes the most recent advances of metal-free late-stage functionalization (LSF) pharmaceutically relevant molecules. Particular emphasis is placed on C – H activation as well use endogenous functional groups.

Language: Английский

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Hydrogen Atom Transfer-Driven Enantioselective Minisci Reaction of Amides

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(13), P. 4928 - 4934

Published: March 29, 2021

Minisci-type reactions constitute one of the most powerful methods for building up complexity around basic heteroarenes. The desirable variants involve formal oxidative coupling a C–H bond on each partner, leading back to simplest possible starting materials. We herein disclose method that enables such linear amides and heteroarenes with full control enantioselectivity at newly formed stereocenter as well site selectivity both heteroarene amide. This is achieved by use chiral phosphoric acid catalyst in conjunction diacetyl combined hydrogen atom transfer reagent oxidant. Diacetyl directly photoexcitable, thus, no extraneous photocatalyst required: an added feature contributes simplicity practicality protocol.

Language: Английский

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Time-Resolved EPR Revealed the Formation, Structure, and Reactivity of N-Centered Radicals in an Electrochemical C(sp³)–H Arylation Reaction

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(49), P. 20863 - 20872

Published: Dec. 1, 2021

Electrochemical synthesis has been rapidly developed over the past few years, while a vast majority of reactions proceed through radical pathway. Understanding properties intermediates is crucial in mechanistic study electrochemical transformations and will be beneficial for developing new reactions. Nevertheless, it rather difficult to determine "live" due their high reactivity. In this work, formation structure sulfonamide N-centered radicals have researched directly by using time-resolved electron paramagnetic resonance (EPR) technique under conditions. Supported EPR results, reactivity as mediator hydrogen atom transfer (HAT) approach discussed. Subsequently, these results successfully utilized discovery an unactivated C(sp3)–H arylation reaction. The kinetic experiments revealed rate-determined step anodic oxidation sulfonamides.

Language: Английский

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Cross-Dehydrogenative Coupling of Strong C(sp³)–H with N-Heteroarenes through Visible-Light-Induced Energy Transfer

Organic Letters, Journal Year: 2020, Volume and Issue: 22(19), P. 7709 - 7715

Published: Sept. 17, 2020

The sustainable cross-dehydrogenative coupling of strong C(sp3)-H with N-heteroarenes has been developed using an efficient organic photocatalyst. It features atomic- and step-economy, acid-free conditions. Mechanism studies suggest a previous elusive energy transfer pathway from photocatalyst to oxidants.

Language: Английский

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Photochemical C–H Silylation and Hydroxymethylation of Pyridines and Related Structures: Synthetic Scope and Mechanisms

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(22), P. 13710 - 13717

Published: Nov. 10, 2020

Considering the synthetic relevance of heteroarenes in various areas ranging from organic synthesis to medicinal chemistry, developing practically simple methodologies access functionalized is a significant value. Described herein an efficient approach for C–H silylation and hydroxymethylation pyridines related heterocycles by combination silanes or methanol with readily available N-methoxypyridinium ions low catalyst loading (2 mol %) under blue light irradiation. The importance developed reactions demonstrated biologically relevant compounds. Electron paramagnetic resonance spectroscopy, quantum yield measurements, density-functional theory calculations allowed us understand reaction mechanisms both photocatalytic reactions.

Language: Английский

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Photo-induced direct alkynylation of methane and other light alkanes by iron catalysis

Green Chemistry, Journal Year: 2021, Volume and Issue: 23(23), P. 9406 - 9411

Published: Jan. 1, 2021

An iron-catalysed photoredox alkynylation of methane, ethane, and other light alkanes is developed as a concise efficient approach to valuable internal alkyne synthesis.

Language: Английский

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Electrophotocatalytic C−H Functionalization of N‐Heteroarenes with Unactivated Alkanes under External Oxidant‐Free Conditions

ChemSusChem, Journal Year: 2021, Volume and Issue: 15(6)

Published: Dec. 30, 2021

The Minisci alkylation of N-heteroarenes with unactivated alkanes under external oxidant-free conditions provides an economically attractive route to access alkylated but remains underdeveloped. Herein, a new electrophotocatalytic strategy alkyl radicals from strong C(sp3 )-H bonds was reported for the following reactions in absence chemical oxidants. This realized first example cerium-catalyzed reaction directly abundant excellent atom economy. It is anticipated that general design principle would enrich catalytic strategies explore functionalizations H2 evolution.

Language: Английский

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Iron-Catalyzed Photoredox Functionalization of Methane and Heavier Gaseous Alkanes: Scope, Kinetics, and Computational Studies

Organic Letters, Journal Year: 2022, Volume and Issue: 24(10), P. 1901 - 1906

Published: March 7, 2022

Herein, we report the development of photocatalytic C-H functionalization methane, ethane, and heavier gaseous alkanes with good yields selectivity, broad scope (57 examples), mild conditions, low cost. Kinetics density functional theory calculations were investigated for key photoinduced ligand-to-metal charge transfer hydrogen atom processes to reveal detailed mechanism iron photocatalysis. This work may bring novel ideas feedstock upgrading catalyst design.

Language: Английский

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Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(10)

Published: Nov. 15, 2021

The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development carboxyl deoxygenative functionalizations, highlighting some representative significant contributions this field. These advances are categorized based on reactivity patterns oxygenated feedstock compounds, including aldehydes, ketones carboxylic acids. Four types reactive intermediates arising from aldehydes during deoxygenation, namely, bis-electrophiles, carbenoids, bis-nucleophiles alkyl radical equivalents, presented, while acids mainly behave as tris-electrophiles when deoxygenated. In each subcategory, selected examples organized according to type bond formation discussed a generalized mechanistic perspective.

Language: Английский

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Development of a Quinolinium/Cobaloxime Dual Photocatalytic System for Oxidative C–C Cross-Couplings via H₂ Release

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(22), P. 14148 - 14158

Published: Nov. 8, 2021

Designing molecular photocatalysts for potent photochemical reactivities ranks among the most challenging but rewarding endeavors in synthetic photochemistry. Herein, we document a quinoline-based organophotoredox catalyst, 2,4-bis(4-methoxyphenyl)quinoline (DPQN2,4-di-OMe), that could be assembled via facile aldehyde–alkyne–amine (A3) couplings. Unlike reported photocatalysts, which impart their photoreactivities as covalently linked entities, our mechanistic studies suggested distinct proton activation mode of DPQN2,4-di-OMe. Simply upon protonation, DPQN2,4-di-OMe reach highly oxidizing excited state under visible-light irradiation (E*1/2 = +1.96 V vs standard calomel electrode, SCE). On this basis, synergistic merger and cobaloxime formulated an oxidative cross-coupling platform, enabling Minisci alkylation various C–C bond-forming reactions with diverse pool radical precursors absence chemical oxidants. The catalytic loading minimized to 0.025 mol % (TON 3360), polymer-supported photocatalyst, DPQN2,4-di-OR@PS, was prepared facilitate catalyst recycling (at 0.50 mmol up five times without significant loss photosynthetic efficiency).

Language: Английский

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