Transition Metal-Catalyzed Pyridine Synthesis

Transition Metal-Catalyzed Heterocycle Synthesis Series

Xiao-Feng Wu

• Publisher: Elsevier
• Year: 2016
• ISBN:
  9780128093689
• Topic: Physical Sciences
• Subtopic: Organic Chemistry

Transition Metal-Catalyzed Pyridine Synthesis provides an overview of pyridines, describing properties of these heterocycle compounds and describing traditional synthetic procedures for them. The book then explores catalyzed procedures for pyridine synthesis in greater detail and depth than is currently available in published Review articles.

The short series Transition Metal-Catalyzed Heterocycles Synthesis, authored by Xiao-Feng Wu, summarizes recent achievements on heterocycles synthesis with transition metal as the catalysts, with each volume dedicated to one heterocycle compound.

• Brief, focused review of this active research area, Pyridine synthesis via transition metal catalysis
• Useful coverage of Pyridine properties and both intermolecular and intramolecular cyclization
• Volume Two in Elsevier's short work series, "Transition Metal-Catalyzed Heterocycles Synthesis"

Chapter 1

Introduction

Abstract

A short introduction on pyridine derivative has been given.

Keywords

Pyridine; biological active; organic synthesis

Pyridine is an important class of nitrogen-containing heterocycles found in various natural products, pharmaceuticals, and materials (Scheme 1.1). Based on its importance, numerous synthetic procedures have been developed for their preparation [1]. In this book volume, the main achievements on transition metal-catalyzed pyridines synthesis are discussed. Based on the reaction types, the whole volume is catalogued by intramolecular cyclization and intermolecular cyclization reactions.

Scheme 1.1 Selected examples of bio-active pyridine derivatives.

Reference

1. Reviews on pyridines synthesis see:.

a. Gromov SP, Fomina MV. Russ Chem Rev. 2008;77:1055–1077.

b. Chopade PR, Louie J. Adv Synth Catal. 2006;348:2307–2327.

c. Bönnemann H. Angew Chem Int Ed Engl. 1985;24:248–262.

d. Heller B, Hapke M. Chem Soc Rev. 2007;36:1085–1094.

e. Baumann M, Baxendale IR. Beilstein J Org Chem. 2013;9:2265–2319.

f. Weding N, Hapke M. Chem Soc Rev. 2011;40:4525–4538.

g. Domínguez G, Pérez-Castells J. Chem Soc Rev. 2011;40:3430–3444.

h. Neely JM, Rovis T. Org Chem Front. 2014;1:1010–1015.

i. Hill MD. Chem Eur J. 2010;16:12052–12062.

j. Varela JA, Saá C. Chem Rev. 2003;103:3787–3801.

k. Bull JA, Mousseau JJ, Pelletier G, Charette AB. Chem Rev. 2012;112:2642–2713.

l. Gulevich AV, Dudnik AS, Chernyak N, Gevorgyan V. Chem Rev. 2013;113:3084–3213.

m. Allais C, Grassot J-M, Rodriguez J, Constantieux T. Chem Rev. 2014;114:10829–10868.

n. Amatore M, Aubert C. Eur J Org Chem. 2015;265–286.

o. Henry GD. Tetrahedron. 2004;60:6043–6061.

p. Kotha S, Brahmachary E, Lahiri K. Eur J Org Chem. 2005;4741–4767.

q. Pla-Quintana A, Roglans A. Molecules. 2010;15:9230–9251.

r. Varela J, Saá C. Synlett 2008;2571–2578.

Chapter 2

Synthesized by Intramolecular Cyclizations

Abstract

The procedures based on transition metal-catalyzed intramolecular cyclizations to prepare pyridines have been discussed here.

Keywords

Pyridine; intramolecular cyclization; organic synthesis; synthetic methodology; carbonylation; coupling

Intramolecular cyclization of substrates to the corresponding pyridine derivatives is the most straightforward pathway. By intramolecular version reaction, the positions of substituents are fixed and easier to control, such as N-propargylic β-enaminones in pyridines and pyrroles synthesis. In 2008, Cacchi et al. reported a copper-catalyzed synthesis of polysubstituted pyridines from N-propargylic β-enaminones [1]. By using DMSO as the solvent, pyrroles can be produced in good to high yields in the presence of only Cs₂CO₃ at room temperature, while pyridines can be formed under the assistant of CuBr at 60–80°C (Scheme 2.1). Here, the N-propargylic β-enaminones can be prepared via the following sequences: (1) cross-coupling of terminal alkynes with acyl chlorides; (2) followed by the conjugate addition of propargylamine with the resultant α,β-enones; (3) further Sonogashira cross-coupling of the propargyl derivative with aryl halides.

Scheme 2.1

A Carousel Tube Reactor (Radley Discovery), equipped with a magnetic stirrer, was charged with substrate (0.23 mmol) and recrystallized CuBr (13 mg, 0.09 mmol) in anhydrous DMSO (3 mL) was stirred for 1.5 h under argon at 60°C. Ethyl acetate was added to the reaction mixture and the resulting mixture was washed first with a 0.1 N HCl solution, then with a saturated NaCl solution, and finally dried over Na₂SO₄. The solvent was removed under vacuum and the residue was purified by chromatography (SiO₂, 30 g, n-Hexane/AcOEt 70/30 v/v) to give the corresponding pyridine derivative.

Scheme 2.1 CuBr-catalyzed pyridines synthesis from N-propargylic β-enaminones.

A procedure by using enamino ester and alkynone as the substrates was developed as well [2]. 2,3,4,6-Tetrasubstituted pyridines were prepared in a single step. Various acids, such as acetic acid, Amberlyst 15 ion exchange resin, zinc(II) bromide or ytterbium(III) triflate, can be applied as promoter for the cyclization step of the Michael addition adduct. 4-(3-Oxoalkyl)isoxazoles found could be applied as starting material for pyridine synthesis as well [3].

In 2013, Kim and coworkers reported a palladium-catalyzed domino cyclization of N-(2-bromoallyl)-N-cinnamyltosylamides for the construction of pyridines [4]. The reaction proceeds via a domino 5-exo/3-exo carbopalladation, ring expansion by palladium rearrangement, and an aromatization. Various 4-arylnicotinate derivatives were produced in good yields (Scheme 2.2).

Scheme ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Chapter 1. Introduction
• Chapter 2. Synthesized by Intramolecular Cyclizations
• Chapter 3. Synthesized by Intermolecular Cyclizations
• Chapter 4. Summary and Outlook