Photocatalytic Carboxylation of C−N Bonds in Cyclic Amines with CO₂ by Consecutive Visible‐Light‐Induced Electron Transfer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(11)

Published: Jan. 21, 2023

Abstract Visible‐light photocatalytic carboxylation with CO 2 is highly important. However, it still remains challenging for reluctant substrates low reduction potentials. Herein, we report a novel of C−N bonds in cyclic amines via consecutive photo‐induced electron transfer (ConPET). It also the first reductive ring‐opening reaction azetidines, pyrrolidines and piperidines. This strategy practical to transform variety easily available valuable β‐, γ‐, δ‐ ϵ‐amino acids moderate‐to‐excellent yields. Moreover, method features mild transition‐metal‐free conditions, high selectivity, good functional‐group tolerance, facile scalability product derivations. Mechanistic studies indicate that ConPET might be key generating reactive photocatalysts, which enable activation generate carbon radicals carbanions as intermediates.

Language: Английский

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Photocatalytic Alkylation of C(sp³)−H Bonds Using Sulfonylhydrazones**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(3)

Published: Nov. 17, 2022

The ability to construct C(sp3 )-C(sp3 ) bonds from easily accessible reagents is a crucial, yet challenging endeavor for synthetic organic chemists. Herein, we report the realization of such cross-coupling reaction, which combines N-sulfonyl hydrazones and )-H donors through diarylketone-enabled photocatalytic hydrogen atom transfer subsequent fragmentation obtained alkylated hydrazide. This mild metal-free protocol was employed prepare wide array alkyl-alkyl cross-coupled products tolerant variety functional groups. application this chemistry further provides preparatively useful route various medicinally-relevant compounds, as homobenzylic ethers, aryl ethyl amines, β-amino acids other moieties are commonly encountered in approved pharmaceuticals, agrochemicals natural products.

Language: Английский

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Late‐Stage Modification of Oligopeptides by Nickel‐Catalyzed Stereoselective Radical Addition to Dehydroalanine

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(48)

Published: Sept. 30, 2022

Radical addition to dehydroalanine (Dha) represents an appealing, modular strategy access non-canonical peptide analogues for drug discovery. Prior studies on radical the Dha residue of peptides and proteins have demonstrated outstanding functional group compatibility, but lack stereoselectivity has limited synthetic utility this approach. Herein, we address challenge by employing chiral nickel catalysts control oligopeptides. The conditions accommodate a variety primary secondary electrophiles introduce polyethylene glycol, biotin, halo-tag, hydrophobic hydrophilic side chains peptide. reaction features catalyst largely override substrate-based stereochemical outcome modification short peptides. We anticipate that discovery complexes confer will allow rapid, late-stage featuring nonnatural sidechains.

Language: Английский

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Π–Π Stacking Complex Induces Three‐Component Coupling Reactions To Synthesize Functionalized Amines

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(49)

Published: Oct. 13, 2022

π-π stacking and ion-pairing interactions induced the generation of α-amino radicals under irradiation visible light without requirement an expensive photocatalyst. This strategy enabled construction functionalized amines via three-component coupling reactions with broad scope (we report >50 examples up to 90 % yield). synthetic pathway also delivered complex a very high yield. Quantum chemistry Density Functional Theory (DFT) calculations identified stacked ionic complexes; time-dependent DFT was employed simulate absorption spectra, nudged elastic band (NEB) methodology provided possible interaction/reaction picture selected species.

Language: Английский

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Switchable, Reagent‐Controlled Diastereodivergent Photocatalytic Carbocyclisation of Imine‐Derived α‐Amino Radicals

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(45), P. 24116 - 24123

Published: Aug. 27, 2021

A reagent-controlled stereodivergent carbocyclisation of aryl aldimine-derived, photocatalytically generated, α-amino radicals possessing adjacent conjugated alkenes, affording either bicyclic or tetracyclic products, is described. Under net reductive conditions using commercial Hantzsch ester, the radical species underwent a single stereoselective cyclisation to give trans-configured amino-indane structures in good yield, whereas substituted ester as milder reductant afforded cis-fused tetrahydroquinoline frameworks, resulting from two consecutive cyclisations. Judicious choice reaction allowed libraries both and dual products be synthesised with high selectivity, notable predictability, good-to-excellent yields. Computational analysis employing DFT revealed pathway mechanistic rationale behind this finely balanced yet readily controlled photocatalytic system.

Language: Английский

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Electroreductive Cross‐Coupling of Trifluoromethyl Alkenes and Redox Active Esters for the Synthesis of Gem‐Difluoroalkenes

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 28(2)

Published: Nov. 11, 2021

An electroreductive access to gem-difluoroalkenes has been developed through the decarboxylative/defluorinative coupling of N-hydroxyphtalimides esters and α-trifluoromethyl alkenes. The electrolysis is performed under very simple reaction conditions in an undivided cell using cheap carbon graphite electrodes. This metal-free transformation features broad scope with good excellent yields. Tertiary, secondary as well primary alkyl radicals could be easily introduced. α-aminoacids L-aspartic L-glutamic acid-derived redox active were reactive partners furnishing potentially relevant gem-difluoroalkenes. In addition, it demonstrated that our electrosynthetic approach toward synthesis use prepared Kratitsky salt radical precursor via a deaminative/defluorinative carbofunctionalization trifluoromethylstyrene.

Language: Английский

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Metal‐Catalyzed C(sp²)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

European Journal of Inorganic Chemistry, Journal Year: 2021, Volume and Issue: 2021(29), P. 2928 - 2941

Published: June 14, 2021

Abstract The site‐selective chemical diversification of biomolecules constitutes an unmet challenge capital importance within medicinal chemistry and biology. functionalization otherwise unreactive C−H bonds holds great promise for reducing the reliance on existing functional groups, thereby streamlining syntheses. Over last years, a myriad peptide labelling techniques featuring metal‐catalyzed reactions have been developed. Despite wealth reports in field, modification both phenylalanine (Phe) tyrosine (Tyr) compounds upon metal catalysis remain comparatively overlooked. This review highlights these promising tagging strategies, which generally occur through formation challenging 6‐membered metallacycles enable late‐stage peptides tailored fashion.

Language: Английский

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A Vitamin B₂‐Photocatalysed Approach to Methionine Analogues

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(50)

Published: Oct. 17, 2022

Access to new non-canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the methionine have been far less explored-despite their use in biochemistry, pharmacology peptide bioconjugation. This largely due limited synthetic access. Herein, we exploit a disconnection access non-natural methionines through development photochemical method radical α-C-H functionalization sulfides with alkenes, water, using inexpensive commercially-available riboflavin (vitamin B

Language: Английский

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Radical‐Mediated C−H Alkylation of Glycine Derivatives: A Straightforward Strategy for Diverse α‐Unnatural Amino Acids

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(45)

Published: Sept. 8, 2022

Abstract Unnatural amino acids are important scaffolds for novel drug candidates, and especially α‐alkyl have emerged as a valuable variant. This is due to the ubiquity of alkyl groups, which pervasive key motifs in natural products, biological pharmaceutical molecules. The development radical‐based approaches organic synthesis has expanded dramatically recent years. It enabled site‐ region‐specific installation variety functionalities small molecules, been spontaneously applied preparation versatile acid building blocks. glycine motif backbone gained significant attention allowing access complex α‐unnatural via radical‐mediated α‐C−H alkylation. review summarizes last decade's alkylation derivatives provide unnatural α‐amino acids. advantages, current limitations, perspectives glycine‐based also discussed.

Language: Английский

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Site‐Selective Itaconation of Complex Peptides by Photoredox Catalysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(5)

Published: Nov. 30, 2021

Site-selective peptide functionalization provides a straightforward and cost-effective access to diversify peptides for biological studies. Among many existing non-invasive conjugations methodologies, photoredox catalysis has emerged as one of the powerful approaches site-specific manipulation on native peptides. Herein, we report highly N-termini-specific method rapidly itaconated their derivatives through combination transamination conditions. This strategy exploits facile reactivity peptidyl-dihydropyridine in complex settings, complementing bioconjugations with excellent selectivity under mild Distinct from conventional methods, this utilizes reactive carbamoyl radical derived peptidyl-dihydropyridine. In addition, can be further functionalized Michael acceptor corresponding peptide-protein conjugate.

Language: Английский

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