Electron Donor‐Acceptor (EDA) Complex Enabled C−C Cross‐Coupling Reactions of α‐Amino Radicals DOI

Padmanava Barik,

Subhra Sriharsa Behera,

Santosh K. Nanda

et al.

Asian Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 13(6)

Published: April 18, 2024

Abstract Electron‐donor acceptor (EDA) complex has been an integral part of visible‐light photocatalysis and is different from the traditional photoredox catalysis, which requires exogenous photocatalyst, typically a colored compound to initiate photocatalytic cycle. Interestingly, EDA‐complex photochemistry found profound use in activating inert α‐C−H bonds amines. The strategy relied upon formation between donor (amine) (Lewis acid), harvesting light energy perform SET process generate radical cation anion intermediates. then loses activated acidic proton (because SET, acidity α‐proton increases by lowering BDE) form α‐amino radical, participates various C−C coupling cascades. In this review, conceptual approaches for generation radicals their bond‐forming reaction under triggered will be discussed with particular emphasis on mechanism 2018 onwards.

Language: Английский

Photocatalytic Late-Stage C–H Functionalization DOI
Peter Bellotti, Huan‐Ming Huang,

Teresa Faber

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 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.

Language: Английский

Citations

324
Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible-Light-Induced Energy Transfer DOI
Yujie Liang,

Roman Kleinmans,

Constantin G. Daniliuc

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(44), P. 20207 - 20213

Published: Oct. 27, 2022

Synthesis of bicyclic scaffolds has attracted growing interest because they are high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy transfer catalysis. The process is proposed involve formal [2π + 2σ] photocycloaddition/backbone C-H abstraction/aryl group migration sequence. A diverse range (hetero)aryl groups successfully underwent the backbone (C2) position provide previously inaccessible molecules, ester product can serve as handle for downstream manipulation, thus offering opportunities rapidly build up molecular complexity new sp3-rich chemical space.

Language: Английский

Citations

124
Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects DOI
Debasish Mandal,

Sumali Roychowdhury,

Jyoti Prasad Biswas

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(17), P. 7358 - 7426

Published: Jan. 1, 2022

Transition metal catalysis has contributed immensely to C-C bond formation reactions over the last few decades, and alkylation is no exception. The superiority of such methodologies traditional evident from minimal reaction steps, shorter times, atom economy while also allowing control regio- stereo-selectivity. In particular, hydrocarbonation alkenes grabbed increased attention due its fundamental ability effectively selectively synthesise a wide range industrially pharmaceutically relevant moieties. This review attempts provide scientific viewpoint systematic analysis recent developments in transition-metal-catalyzed various C-H bonds using simple activated olefins. key features mechanistic studies involved these transformations are described briefly.

Language: Английский

Citations

81
Photocatalytic C(sp3) radical generationviaC–H, C–C, and C–X bond cleavage DOI Creative Commons
Chia‐Yu Huang, Jianbin Li, Chao‐Jun Li

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(19), P. 5465 - 5504

Published: Jan. 1, 2022

C(sp 3 ) radicals (R˙) are of broad research interest and synthetic utility.

Language: Английский

Citations

75
Identification of Alkoxy Radicals as Hydrogen Atom Transfer Agents in Ce-Catalyzed C–H Functionalization DOI
Qing An, Yang‐Yang Xing, Ruihua Pu

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 359 - 376

Published: Dec. 20, 2022

The intermediacy of alkoxy radicals in cerium-catalyzed C–H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)–alkoxide complexes have synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified as the sole heteroatom-centered radical species generated ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom (HAT) verified kinetic analysis, density functional theory (DFT) calculations, reactions under strictly chloride-free conditions. These experimental findings establish critical role Ce-LMCT catalysis definitively preclude involvement chlorine radical. This study also reinforced necessity a high relative ratio alcohol vs Ce for selective alkoxy-radical-mediated HAT, seemingly trivial changes can lead to drastically different mechanistic pathways. Importantly, previously proposed radical–alcohol complex, postulated explain alkoxy-radical-enabled selectivities this system, examined scrutiny ruled out regioselectivity studies, experiments, high-level calculations. Moreover, peculiar selectivity generation LMCT homolysis heteroleptic analyzed back-electron (BET) may regulated efficiency formation ligand-centered radicals.

Language: Английский

Citations

72
Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis DOI Creative Commons
Xiaomin Shu,

De Zhong,

Qian Huang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 9, 2023

Abstract Site- and enantioselective cross-coupling of saturated N -heterocycles carboxylic acids—two the most abundant versatile functionalities—to form pharmaceutically relevant α-acylated amine derivatives remains a major challenge in organic synthesis. Here, we report general strategy for highly site- α-acylation with situ-activated acids. This modular approach exploits hydrogen-atom-transfer reactivity photocatalytically generated chlorine radicals combination asymmetric nickel catalysis to selectively functionalize cyclic α-amino C−H bonds presence benzylic, allylic, acyclic α-amino, α-oxy methylene groups. The mild scalable protocol requires no organometallic reagents, displays excellent chemo-, enantioselectivity, is amenable late-stage diversification, including synthesis previously inaccessible Taxol derivatives. Mechanistic studies highlight exceptional versatility chiral catalyst orchestrating (i) catalytic elimination, (ii) alkyl radical capture, (iii) cross-coupling, (iv) induction.

Language: Английский

Citations

56
Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol DOI

Shaokun Cai,

Hong Tang,

Bo Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(9), P. 5952 - 5963

Published: Feb. 26, 2024

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular transfer reactions mild conditions. Besides transformations small molecules, these enable unique late-stage modification complex peptides. Mechanistic investigations uncover the key processes lies accommodating conformation solvent-mediated macrocyclic transition states, where aggregates HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between lone electron pair nitrogen and antibonding orbital amine's α C-H bond plays a critical role activation, promoting its liberation.

Language: Английский

Citations

17
Photocatalytic Three-Component Reductive Coupling Synthesis of gem-Difluorohomoallyl Secondary Amines DOI

Bingbing Feng,

Meifang Tang,

Rui Xiao

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

2
A Change from Kinetic to Thermodynamic Control Enables trans-Selective Stereochemical Editing of Vicinal Diols DOI

Yu‐An Zhang,

Xin Gu, Alison E. Wendlandt

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 144(1), P. 599 - 605

Published: Dec. 20, 2021

Here, we report the selective, catalytic isomerization of

Language: Английский

Citations

62
Functional-group translocation of cyano groups by reversible C–H sampling DOI
K. Chen,

Qingrui Zeng,

L. XIE

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7976), P. 1007 - 1012

Published: June 26, 2023

Language: Английский

Citations

40