Electron-Deficient Acetylenes as Three-Modal Adjuvants in SNH Reaction of Pyridinoids with Phosphorus Nucleophiles.

Boris A Trofimov,Pavel A Volkov,Anton A Telezhkin

doi:10.3390/molecules26226824

Boris A Trofimov, Pavel A Volkov + Show 1 more

Open Access

https://doi.org/10.3390/molecules26226824

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Abstract

Publications covering a new easy metal-free functionalization of pyridinoids (pyridines, quinolines, isoquinolines, acridine) under the action of the system of electron-deficient acetylenes (acetylenecarboxylic acid esters, acylacetylenes)/P-nucleophiles (phosphine chalcogenides, H-phosphonates) are reviewed. Special attention is focused on a SNH reaction of the regioselective cross-coupling of pyridines with secondary phosphine chalcogenides triggered by acylacetylenes to give 4-chalcogenophosphorylpyridines. In these processes, acetylenes act as three-modal adjuvants (i) activating the pyridine ring towards P-nucleophiles, (ii) deprotonating the P-H bond and (iii) facilitating the nucleophilic addition of the P-centered anion to a heterocyclic moiety followed by the release of the selectively reduced acetylenes (E-alkenes).

Highlights

Phosphorylated heterocyclic compounds have attracted steadily growing attention as perspective pharmaceuticals or their precursors [1,2,3], multipurpose ligands for the design of biologically active metal complexes [4,5,6,7] and catalysts [8,9,10,11], as well as building blocks for organic synthesis [12,13,14,15]
Significant endeavors have been directed towards the synthesis of such compounds, a transition metal-free nucleophilic substitution of hydrogen in a heteroaromatic ring (SN H reaction) by phosphorus-centered nucleophiles being one of the most dynamically developing approaches because of its apparent benefits
Reactions of a new type, electron-deficient acetylenes play a role of three-modal adjuvants triggering and further driving the whole process

Summary

Introduction

Phosphorylated heterocyclic compounds have attracted steadily growing attention as perspective pharmaceuticals or their precursors [1,2,3], multipurpose ligands for the design of biologically active metal complexes [4,5,6,7] and catalysts [8,9,10,11], as well as building blocks for organic synthesis [12,13,14,15]. A short time ago [37,38,39,40], the nucleophilic substitution of hydrogen (SN H reaction) in non-activated pyridines and their fused derivatives by secondary phosphine chalcogenides (synthesized from red phosphorus [41,42,43,44]) in the presence of electron-deficient terminal and internal acetylenes was disclosed. SN H Phosphorylation of Pyridines Triggered and Driven by Electrophilic Acetylenes

One-Step SN H Phosphorylation

SN H Phosphorylation of Quinolines and Isoquinolines

SN H Phosphorylation of Acridines

Findings

Conclusions and Outlook