The Aryne Phosphate Reaction.

Thomas M Haas,Tobias Dürr‐Mayer,Alexander Ripp,Henning J Jessen,Stefan Wiesler,Danye Qiu,Paraskevi Fouka

doi:10.1002/anie.202113231

Thomas M Haas, Tobias Dürr‐Mayer + Show 5 more

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https://doi.org/10.1002/anie.202113231

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Abstract

Condensed phosphates are a critically important class of molecules in biochemistry. Non‐natural analogues are important for various applications, such as single‐molecule real‐time DNA sequencing. Often, such analogues contain more than three phosphate units in their oligophosphate chain. Consequently, investigations into phosphate reactivity enabling new ways of phosphate functionalization and oligophosphorylation are essential. Here, we scrutinize the potential of phosphates to act as arynophiles, paving the way for follow‐up oligophosphorylation reactions. The aryne phosphate reaction is a powerful tool to—depending on the perspective—(oligo)phosphorylate arenes or arylate (oligo‐cyclo)phosphates. Based on Kobayashi‐type o‐silylaryltriflates, the aryne phosphate reaction enables rapid entry into a broad spectrum of arylated products, like monophosphates, diphosphates, phosphodiesters and polyphosphates. The synthetic potential of these new transformations is demonstrated by efficient syntheses of nucleotide analogues and an unprecedented one‐flask octaphosphorylation.

Highlights

Arynes are “highly reactive, short-lived intermediates that can undergo a variety of chemical transformations.”[1]
Phosphate esters metaphosphates), leading to storable arylated cyclophosphate and anhydrides are arynophiles, which can be converted into O- species (24) of controllable ring-size, which have rarely been arylated phosphate derivatives
In 2017 Garg stated about arynes that “their high reactivity has seemingly steered chemists away from using them to assemble [...] complex scaffolds. [But] arynes can and should be used strategically to enable the synthesis of complex molecules with motifs that have conventionally been viewed as challenging.”[47]. In the present paper, we meet this suggestion by introducing the aryne phosphate reaction that accesses highly challenging arylated organophosphorous compounds with Kobayashi-type precursors

Summary

Introduction

Arynes are “highly reactive, short-lived intermediates that can undergo a variety of chemical transformations.”[1]. Based on Kobayashi-type o-silylaryltriflates, the aryne phosphate reaction enables rapid entry into a broad spectrum of arylated products, like monophosphates, diphosphates, phosphodiesters and polyphosphates. C: Synthetic concept of the aryne phosphate reaction including potentially accessible product groups.

Results

Conclusion