Fe‐Catalyzed α‐C(sp3)–H Amination of N‐Heterocycles DOI Creative Commons
Andrea Geraci, Olivier Baudoin

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Nitrogen‐heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C−H amination reactions furnish unconventional straightforward approaches for construction of C−N bonds. Yet, most known methods rely on precious metal catalysts. Herein we report a site‐selective intermolecular C(sp 3 )−H N‐heterocycles, catalyzed by inexpensive FeCl 2, which allows functionalization wide range pharmaceutically relevant cyclic amines. The occurs site‐selectively α‐position to nitrogen atom, even when weaker bonds present, furnishes Troc‐protected aminals or amidines. method employs N‐heterocycle as limiting reagent is applicable late‐stage complex molecules. Its synthetic potential was further illustrated through derivatization α‐aminated products application concise total synthesis reported structure senobtusin. Mechanistic studies allowed propose plausible reaction mechanism involving turnover‐limiting Fe‐nitrene generation followed fast H atom transfer radical rebound.

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
Photocatalytic Hydrogen Atom Transfer-Induced Arbuzov-Type α-C(sp3)–H Phosphonylation of Aliphatic Amines DOI Open Access
Zhexuan Lei, Weigang Zhang, Jie Wu

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(24), P. 16105 - 16113

Published: Dec. 5, 2023

Despite remarkable progress in photocatalytic hydrogen atom transfer (HAT)-induced C(sp3)–H functionalization, achieving to C(sp3)–P transformation by the HAT process remains highly challenging due P-reagents' compatibility issues. α-Aminophosphonic acids have shown great potential medicinal chemistry, yet their synthesis is hindered limited substrate scopes, poor functional group tolerance, and reliance on prefunctionalized substrates, restricting broad applications. Herein, we report HAT-induced α-C(sp3)–H phosphonylation of aliphatic amines, providing rapid access structurally diverse α-aminophosphonates from abundant amines. Leveraging intramolecular HAT, radical polar crossover, an Arbuzov-type cascade, challenges associated with were overcome. This protocol features base-free, redox-neutral, mild conditions employing amines as limiting reagents, allows for late-stage complex drug molecules possessing amine moieties.

Language: Английский

Citations

26
Blue Light Irradiated Metal-, Oxidant-, and Base-Free Cross-Dehydrogenative Coupling of C(sp2)–H and N–H Bonds: Amination of Naphthoquinones with Amines DOI
Raushan Kumar Jha, Monojit Batabyal, Sangit Kumar

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(11), P. 7401 - 7424

Published: May 12, 2023

Herein, we report a blue-light-driven amination of C(sp2)-H bond naphthoquinones and quinones with the N-H primary secondary amines for synthesis 2-amino-naphthoquinones 2-amino-quinones. The coupling wide array aliphatic, aromatic, chiral, primary, having electron donating (-CH3, -OCH3, -SCH3), withdrawing (-F, -Cl, -Br, -I), CO2H, -OH, -NH2 groups acidic protons selectively occurred to afford C-N coupled in 60-99% yields hydrogen gas as byproduct methanol solvent without using any additional reagents, additives, oxidant under blue light irradiation. Mechanistic insight by DFT computation, controlled experiments, kinetic isotopic effect, substitution effect substrates suggest that reaction proceeds radical pathway which naphthoquinone forms highly oxidizing naphthoquinonyl biradical upon irradiation (457 nm). Consequently, transfer from electron-rich amine an leads anion aminyl cation, followed proton delocalization leading carbon-centered radical. cross-coupling nitrogen radicals bond, subsequent elimination (which was also confirmed GC-TCD), affording 2-amino-1,4-naphthoquinone metal-, reagent-, base-, oxidant-free conditions.

Language: Английский

Citations

22
Nickel‐Catalyzed Site‐Selective Intermolecular C(sp3)−H Amidation DOI
Jinhong Chen, Hao Wang, Craig S. Day

et al.

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

Published: Oct. 18, 2022

A nickel-catalyzed site-selective intermolecular amidation of saturated C(sp3 )-H bonds is reported. This mild protocol exhibits a predictable reactivity pattern to incorporate amide functions at sites adjacent nitrogen and oxygen atoms in either cyclic or acyclic frameworks, thus offering complementary profile existing oxidative-type processes metal-catalyzed )-N bond-forming reactions operating via two-electron manifolds.

Language: Английский

Citations

27
γ-Amino C(sp3)–H Functionalization of Aliphatic Amines through a Light-Driven Triple Catalysis DOI

Masanari Nakagawa,

Kazunori Nagao, Hirohisa Ohmiya

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(10), P. 8005 - 8012

Published: May 9, 2024

We report intra- and intermolecular γ-amino C(sp3)–H functionalization of aliphatic amines using a vinylsulfone-based HAT (hydrogen atom transfer) auxiliary triple catalysis, which is composed photoredox, cobalt, Brønsted acid catalysts under visible light irradiation. The process accomplishes four elementary steps: (i) electrophilic carbon-centered radical formation on the via MHAT (metal hydride hydrogen reaction, (ii) generation through 1,6-HAT (iii) single-electron oxidation to carbocation equivalents, (iv) nucleophilic substitution with internal or external nucleophiles. As result, this afforded γ-amino-functionalized products, such as azetidines, 1,3-diamine, 1,3-aminoalcohol derivatives.

Language: Английский

Citations

4
Electrochemical direct α-amidation and α-pyrazolation of N-alkoxy- and N-aryloxycarbonyl pyrrolidines DOI

Zhuang Wang,

Yuxiu Liu, Hongjian Song

et al.

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(12), P. 7419 - 7423

Published: Jan. 1, 2024

We have developed a straightforward electrochemical protocol for direct α-amidation and α-pyrazolation of N -alkoxy- -aryloxycarbonyl pyrrolidines with amides or pyrazoles.

Language: Английский

Citations

4
A Voltage-Controlled Strategy for Modular Shono-Type Amination DOI
Siyuan Su, Yahui Guo, Bryan Parnitzke

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(42), P. 28663 - 28668

Published: Oct. 14, 2024

Shono-type oxidation to generate functionalized heterocycles is a powerful method for late-stage diversification of relevant pharmacophores; however, development beyond oxygen-based nucleophiles remains underdeveloped. The limited scope can often be ascribed constant current electrolysis resulting in potential drifts that oxidize desired nucleophilic partner. Herein, we report voltage-controlled strategy selectively broad substrates, enabling modular C-N bond formation from protected amine nucleophiles. We implement an electroanalytically guided workflow using cyclic voltammetry (CV) and differential pulse (DPV) identify potentials across range heterocyclic substrates. Controlled (CPE) generates α-functionalized products moderate good yields carbamate-, sulfonamide-, benzamide-derived importance voltage control further exemplified through systematic study comparing our developed CPE (CCE) protocols. Voltage-guided CCE traditionally optimized reveal the maintaining high selectivity over scope; case with morpholine-derived substrate illustrates negative impact drifting under CCE. Sulfonamide drugs, which have significant overlap model are rendered competent CPE. Lastly, sequential C-O functionalization difunctionalized pyrrolidines broadening utility this reaction.

Language: Английский

Citations

4
Photocatalytic Oxidative C(sp3)-H/N–H Cross-Dehydrogenative Coupling of Tertiary Anilines with Amides/Imides: Synthesis of N-Mannich Bases DOI

Qiaerbati Adelibieke,

Bulunuer Yusan,

Xiong Wang

et al.

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

Published: April 30, 2025

A photocatalytic method for the synthesis of N-Mannich bases has been developed through C(sp3)-H/N-H cross-dehydrogenative coupling N,N-dimethylanilines with amides/imides. This process utilizes 2,4,6-triphenylpyrylium tetrafluoroborate (TPT) as photocatalyst and is conducted at ambient temperature atmospheric air. Various aromatic, heteroaromatic aliphatic (cyclic) amides, well imides were successfully employed, yielding moderate to good results. Preliminary mechanistic isotope-labeling studies indicate that reaction likely proceeds via a single electron transfer pathway involves an α-aminoalkyl radical intermediate.

Language: Английский

Citations

0
Amidative β-Scission of Alcohols Enabled by Dual Catalysis of Photoredox Proton-Coupled Electron Transfer and Inner-Sphere Ni-Nitrenoid Transfer DOI
Hyeyun Keum,

Harin Ryoo,

Dongwook Kim

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 1001 - 1008

Published: Dec. 18, 2023

The photoredox/Ni dual catalysis is an appealing strategy to enable unconventional C-heteroatom bond formation. While significant advances have been achieved using this system, intermolecular C(sp

Language: Английский

Citations

10
Alicyclic‐Amine‐Derived Imine‐BF3 Complexes: Easy‐to‐Make Building Blocks for the Synthesis of Valuable α‐Functionalized Azacycles DOI

Subhradeep Dutta,

Jae Hyun Kim, Kamal Bhatt

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(1)

Published: Nov. 1, 2023

A new strategy to access α-functionalized alicyclic amines via their corresponding imine-BF

Language: Английский

Citations

8