Synlett 2021; 32(02): 159-178
DOI: 10.1055/s-0040-1706552
cluster
Modern Heterocycle Synthesis and Functionalization

Recent Developments in Transition-Metal-Free Functionalization and Derivatization Reactions of Pyridines

Fei-Yu Zhou
,
Lei Jiao
Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Email: leijiao@mail.tsinghua.edu.cn
› Author Affiliations
Financial support from the National Natural Science Foundation of China (Grants Nos. 21772110 and 21822304) is acknowledged.


Abstract

Pyridine is an important structural motif that is prevalent in natural products, drugs, and materials. Methods that functionalize and derivatize pyridines have gained significant attention. Recently, a large number of transition-metal-free reactions have been developed. In this review, we provide a brief summary of recent advances in transition-metal-free functionalization and derivatization reactions of pyridines, categorized according to their reaction modes.

1 Introduction

2 Metalated Pyridines as Nucleophiles

2.1 Deprotonation

2.2 Halogen–Metal exchange

3 Activated Pyridines as Electrophiles

3.1 Asymmetric 2-Allylation by Chiral Phosphite Catalysis

3.2 Activation of Pyridines by a Bifunctional Activating Group

3.3 Alkylation of Pyridines by 1,2-Migration

3.4 Alkylation of Pyridines by [3+2] Addition

3.5 Pyridine Derivatization by Catalytic In Situ Activation Strategies

3.6 Reactions via Heterocyclic Phosphonium Salts

4 Radical Reactions for Pyridine Functionalization

4.1 Pyridine Functionalization through Radical Addition Reactions

4.2 Pyridine Functionalization through Radical–Radical Coupling Reactions

5 Derivatization of Pyridines through the Formation of Meisenheimer-Type Pyridyl Anions

6 Conclusion



Publication History

Received: 13 July 2020

Accepted after revision: 30 September 2020

Article published online:
28 October 2020

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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