Advances in Pyridine C – H Functionalizations: Beyond C2 Selectivity DOI
Sachin Balaso Mohite, Yafia Kousin Mirza, Partha Sarathi Bera

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(2)

Published: Nov. 28, 2024

The pyridine core is a crucial component in numerous FDA-approved drugs and Environmental Protection Agency (EPA) regulated agrochemicals. It also plays significant role ligands for transition metals, alkaloids, catalysts, various organic materials with diverse properties, making it one of the most important structural frameworks. However, despite its significance, direct selective functionalization still relatively underdeveloped due to electron-deficient nature strong coordinating ability nitrogen. Among variety synthetic transformation, C-H bond straightforward atom economical approach it's advantageous late-stage containing drugs. In recent years, innovative strategies regioselective pyridines azines have emerged, offering benefits such as high regioselectivity, mild conditions, enabling transformations that were challenging traditional methods. This review emphasizes latest advancements meta para-C-H through approaches, including phosphonium salts, photocatalytic methods, temporary de-aromatization, Minisci-type reactions, metal-catalyzed activation techniques. We discuss advantages limitations these current methods aim inspire further progress this field.

Language: Английский

C3 Selective Hydroxylation of Pyridines via Photochemical Valence Isomerization of Pyridine N-Oxides DOI

Chen-Yan Cai,

Si-Jie Chen,

Rohan R. Merchant

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(35), P. 24257 - 24264

Published: Aug. 22, 2024

The C–H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains great challenge due to inherent electronic properties this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal selective pyridines via photochemical valence isomerization N-oxides. This metal-free features operational simplicity compatibility with diverse array functional groups, resulting hydroxylated products are amenable further elaboration synthetically useful building blocks. synthetic utility strategy demonstrated effective late-stage functionalization pyridine-containing medicinally relevant molecules versatile derivatizations 3-pyridinols.

Language: Английский

Citations

5
Formal meta-C–H-Fluorination of Pyridines and Isoquinolines through Dearomatized Oxazinopyridine Intermediates DOI
Malte Haring, Kuruva Balanna, Qiang Cheng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 30758 - 30763

Published: Nov. 1, 2024

Organofluorine compounds, including fluorinated pyridines and isoquinolines, play a crucial role in pharmaceuticals, agrochemicals, materials science. However, step-economic selective C-H-functionalization to access these azaarenes is still underexplored, with

Language: Английский

Citations

5
C3 Selective chalcogenation and fluorination of pyridine using classic Zincke imine intermediates DOI Creative Commons
Shun Li, Juan Tang,

Yonglin Shi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 28, 2024

Regioselective C-H functionalization of pyridines remains a persistent challenge due to their inherent electronically deficient properties. In this report, we present strategy for the selective pyridine C3-H thiolation, selenylation, and fluorination under mild conditions via classic N-2,4-dinitrophenyl Zincke imine intermediates. Radical inhibition trapping experiments, as well DFT theoretical calculations, indicated that thiolation selenylation proceeds through radical addition-elimination pathway, whereas two-electron electrophilic substitution pathway. The pre-installed electron-deficient activating N-DNP group plays crucial positive role, with additional benefit recyclability. practicability protocol was demonstrated in gram-scale synthesis late-stage modification pharmaceutically relevant pyridines.

Language: Английский

Citations

4
Visible-light-induced meta-selective sulfonylation of pyridine via an EDA complex DOI

Yong-Qing Ye,

Zhipeng Ye,

Meng Guo

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Pyridine is a versatile structural unit found in broad spectrum of pharmaceuticals, agrochemicals, and materials. Achieving selective meta-functionalization under mild conditions remains challenging due to its inherent electronic properties. In this work, we accomplished photoinduced method for meta-selective sulfonylation pyridines, facilitated by an electron donor-acceptor (EDA) complex between iodide ions sulfonyl chlorides. The reaction proceeds via oxazino-pyridine intermediate, with chloride acting as the radical precursor. This protocol stands out mild, photocatalyst-free conditions, high C5-selectivity, good scalability, offering promising approach synthesis meta-sulfonylated pyridines.

Language: Английский

Citations

0
Advances in Pyridine C – H Functionalizations: Beyond C2 Selectivity DOI
Sachin Balaso Mohite, Yafia Kousin Mirza, Partha Sarathi Bera

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(2)

Published: Nov. 28, 2024

The pyridine core is a crucial component in numerous FDA-approved drugs and Environmental Protection Agency (EPA) regulated agrochemicals. It also plays significant role ligands for transition metals, alkaloids, catalysts, various organic materials with diverse properties, making it one of the most important structural frameworks. However, despite its significance, direct selective functionalization still relatively underdeveloped due to electron-deficient nature strong coordinating ability nitrogen. Among variety synthetic transformation, C-H bond straightforward atom economical approach it's advantageous late-stage containing drugs. In recent years, innovative strategies regioselective pyridines azines have emerged, offering benefits such as high regioselectivity, mild conditions, enabling transformations that were challenging traditional methods. This review emphasizes latest advancements meta para-C-H through approaches, including phosphonium salts, photocatalytic methods, temporary de-aromatization, Minisci-type reactions, metal-catalyzed activation techniques. We discuss advantages limitations these current methods aim inspire further progress this field.

Language: Английский

Citations

3