Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4237 - 4352

Опубликована: Янв. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Язык: Английский

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A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июнь 29, 2021

Abstract Hydrogen atom abstraction (HAT) from C( sp 3 )–H bonds of naturally abundant alkanes for alkyl radical generation represents a promising yet underexplored strategy in the alkylation reaction designs since involving stoichiometric oxidants, excessive alkane loading, and limited scope are common drawbacks. Here we report photo-induced chemical oxidant-free cross-dehydrogenative coupling (CDC) between heteroarenes using catalytic chloride cobalt catalyst. Couplings strong bond-containing substrates complex heteroarenes, have been achieved with satisfactory yields. This dual platform features situ engendered chlorine exploits cobaloxime catalyst to enable hydrogen evolution turnover. The practical value this protocol was demonstrated by gram-scale synthesis alkylated heteroarene merely equiv. loading.

Язык: Английский

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Formation and degradation of strongly reducing cyanoarene-based radical anions towards efficient radical anion-mediated photoredox catalysis

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 6, 2023

Cyanoarene-based photocatalysts (PCs) have attracted significant interest owing to their superior catalytic performance for radical anion mediated photoredox catalysis. However, the factors affecting formation and degradation of cyanoarene-based PC (PC•‒) are still insufficiently understood. Herein, we therefore investigate PC•‒ under widely-used photoredox-mediated reaction conditions. By screening various PCs, elucidate strategies efficiently generate with adequate excited-state reduction potentials (Ered*) via supra-efficient generation long-lived triplet excited states (T1). To thoroughly behavior in actual reactions, a reductive dehalogenation is carried out as model identified dominant photodegradation pathways PC•‒. Dehalogenation coexistent depending on rate electron transfer (ET) substrate strongly depends electronic steric properties PCs. Based understanding both PC•‒, demonstrate that efficient highly reducing allows catalyzed aryl/alkyl halides at loading low 0.001 mol% high oxygen tolerance. The present work provides new insights into reactions reactions.

Язык: Английский

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Photocatalytic Three-Component Reductive Coupling Synthesis of gem-Difluorohomoallyl Secondary Amines

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

gem-Difluorohomoallyl amines, an important class of gem-difluoroalkenes, are prevalent moieties in many bioactive compounds. However, limited methods suitable for the synthesis this type compound containing secondary amines. Here, we display a photocatalytic multicomponent protocol gem-difluoroalkenes which makes use readily available materials: arylamines, alkyl aldehydes, and α-trifluoromethyl alkenes. Moreover, ketones amines also substrates. Preliminary mechanistic experiments indicate that key α-amino radical was involved, generated from reduction situ-formed imines (or iminium ions) by reduced photocatalyst. Subsequent addition to alkenes β-F elimination deliver desired products.

Язык: Английский

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Minimization of Back‐Electron Transfer Enables the Elusive sp³ C−H Functionalization of Secondary Anilines

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(14), С. 7669 - 7674

Опубликована: Янв. 18, 2021

Abstract Anilines are some of the most used class substrates for application in photoinduced electron transfer. N,N‐Dialkyl‐derivatives enable radical generation α to N‐atom by oxidation followed deprotonation. This approach is however elusive monosubstituted anilines owing fast back‐electron transfer (BET). Here we demonstrate that BET can be minimised using photoredox catalysis presence an exogenous alkylamine. synergistically aids aniline SET and then accelerates following In this way, α‐anilinoalkyl radicals now possible these species a general sense achieve divergent sp 3 C−H functionalization.

Язык: Английский

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Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(39), С. 15936 - 15945

Опубликована: Сен. 20, 2021

Catalytic, intermolecular hydroaminoalkylation (HAA) of styrenes provides a powerful disconnection for pharmacologically relevant γ-arylamines, but current methods cannot utilize unprotected primary alkylamines as feedstocks. Metal-catalyzed HAA protocols are also highly sensitive to α-substitution on the amine partner, and no catalytic solutions exist α-tertiary γ-arylamine synthesis via this approach. We report solution these problems using organophotoredox catalysis, enabling direct, modular, sustainable preparation α-(di)substituted including challenging electron-neutral moderately electron-rich aryl groups. A broad range functionalities tolerated, reactions can be run multigram scale in continuous flow. The method is applied concise, protecting-group-free blockbuster drug Fingolimod, well phosphonate mimic its vivo active form (by iterative α-C–H functionalization ethanolamine). reaction sequenced with an intramolecular N-arylation provide general modular access valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines 1,2,3,4-tetrahydronaphthyridines. Mechanistic kinetic studies support irreversible hydrogen atom transfer activation alkylamine by azidyl radical some contribution from chain. photon-limited exhibits zero-order dependence amine, azide, photocatalyst, first-order styrene.

Язык: Английский

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Understanding Ir(III) Photocatalyst Structure–Activity Relationships: A Highly Parallelized Study of Light-Driven Metal Reduction Processes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(3), С. 1431 - 1444

Опубликована: Янв. 13, 2022

High-throughput synthesis and screening methods were used to measure the photochemical activity of 1440 distinct heteroleptic [Ir(C^N)2(N^N)]+ complexes for photoreduction Sn(II) Zn(II) cations their corresponding neutral metals. Kinetic data collection was carried out using home-built photoreactors measured initial rates, obtained through an automated fitting algorithm, spanned between 0–120 μM/s Sn(0) deposition 0–90 Zn(0) deposition. Photochemical reactivity compared photophysical properties previously such as deaerated excited state lifetime emission spectral these same complexes; however, no clear correlations among features observed. A formal rate law then developed help elucidate observed reactivity. Initial rates found be directly correlated product incident photon flux with three reaction elementary efficiencies: (1) fraction light absorbed by photocatalyst, (2) species that are quenched electron donor, (3) cage escape efficiency. The most active catalysts exhibit high efficiencies all steps, catalyst engineering requirements maximize postulated. kinetic treatment provided mechanistic information needed decipher structure/function trends in high-throughput work.

Язык: Английский

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Straightforward synthesis of functionalized γ-Lactams using impure CO2 stream as the carbon source

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 22, 2023

Abstract Direct utilization of CO 2 into organic synthesis finds enormous applications to synthesize pharmaceuticals and fine chemicals. However, pure gas is essential achieve these transformations, the purification highly cost energy intensive. Considering this, we describe a straightforward synthetic route for γ-lactams, pivotal core structure bioactive molecules, by using commercially available starting materials (alkenes amines) impure stream (exhaust collected from car) as carbon source. This blueprint features broad scope, excellent functional group compatibility application late-stage transformation existing natural products functionalized γ-lactams. We believe that our strategy will provide direct access γ-lactams in very sustainable way also enhance Carbon Capture Utilization (CCU) strategy.

Язык: Английский

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Photoredox-Catalyzed Site-Selective Generation of Carbanions from C(sp³)–H Bonds in Amines

ACS Catalysis, Год журнала: 2022, Номер 12(7), С. 3974 - 3984

Опубликована: Март 15, 2022

The selective activation of sp3 carbon–hydrogen bonds in the presence multiple C–H is challenging and remains supreme importance chemical research. Late-stage modification complex molecules via high prevalence organic synthesis. Herein, we describe a C(sp3)–H bond α-position to an amine carbanion intermediate. In several α-amine sites, only one specific position selectively activated. Applying this protocol, proposed intermediate was effectively trapped with different electrophiles such as deuterium (D+), tritium (T+), or carbonyl compounds compiling over 50 examples. Further, methodology used install drug-derivatives (>10 drugs) at selected late-stage functionalization. addition, protocol suitable for gram-scale synthesis, detailed mechanistic investigation has been carried out support our hypothesis.

Язык: Английский

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N-Dealkylation of Amines

Molecules, Год журнала: 2022, Номер 27(10), С. 3293 - 3293

Опубликована: Май 20, 2022

N-dealkylation, the removal of an N-alkyl group from amine, is important chemical transformation which provides routes for synthesis a wide range pharmaceuticals, agrochemicals, bulk and fine chemicals. N-dealkylation amines also in vivo metabolic pathway metabolism xenobiotics. Identification drug metabolites such as N-dealkylated are necessary throughout all phases development studies. In this review, different approaches including chemical, catalytic, electrochemical, photochemical enzymatic methods will be discussed.

Язык: Английский

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