An Alkyne Diboration/6π‐Electrocyclization Strategy for the Synthesis of Pyridine Boronic Acid Derivatives

We demonstrate that a diboration‐electrocyclization sequence provides access to a range of pyridine‐fused, small‐molecule boronic ester building blocks, and that these are amenable to high‐throughput synthesis leading to biaryl and ether‐linked compound libraries. Moreover, the implementation of an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds for application in drug‐discovery projects.

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“…General . Characterization and synthetic procedures for compounds 1 , 2 , 5 , 7 , 8 are reported elsewhere [10b,c] …”

Section: Methodsmentioning

confidence: 99%

Design and Synthesis of Fused Pyridine Building Blocks for Automated Library Generation

et al. 2020

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“…Recent studies in our lab have demonstrated that aromatic oxime ethers bearing an ortho ‐alkyne group can be transformed into isoquinoline boronic esters via a diboration/6π‐electrocyclization sequence . We therefore began our studies by investigating the applicability of this transformation for the synthesis of borylated thienopyridines as this would deliver a novel class of heteroaromatic boronic ester scaffolds .…”

Section: Methodsmentioning

confidence: 99%

Synthetic and Mechanistic Investigation of an Oxime Ether Electrocyclization Approach to Heteroaromatic Boronic Acid Derivatives

Mora-Radó

Sotorríos

Ball‐Jones

et al. 2018

Chemistry A European J

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A range of functionalized heteroaromatic boronic acid derivatives are readily accessed by a diboration/6π-electrocyclization sequence. This study revealed the surprising observation that there is a direct relationship between oxime ether stereochemistry and reactivity towards electrocyclization. Specifically, E-oxime ethers are found to be significantly more reactive than their Z-counterparts (stereochemistry relative to azatriene scaffold). In contrast, the configuration at the azatriene alkene terminus has little impact on reaction rates. Computational analysis offers a rationale for this observation; a N →C=C π* orbital interaction lowers the energy of the transition state in the electrocyclization of E-oxime ethers. Finally, unreactive Z-oxime ethers can be converted to the corresponding heterocyclic products by a photolytically promoted E→Z isomerization and electrocyclization sequence.

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“…Organoboron compounds play an important role in organic chemistry as they can be converted into a wide variety of functional groups [1,2,3,4,5,6,7,8,9,10,11,12,13]. Thus, the synthesis of different types of organoboron compounds continues to be an important research field [14,15,16,17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Recent Synthesis Developments of Organoboron Compounds via Metal-Free Catalytic Borylation of Alkynes and Alkenes

et al. 2018

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Diboron reagents have been traditionally regarded as “Lewis acids”, which can react with simple Lewis base to create a significant nucleophilic character in one of boryl moieties. In particular, bis(pinacolato)diboron (B2pin2) reacts with simple Lewis bases, such as N-heterocyclic carbenes (NHCs), phosphines and alkoxides. This review focuses on the application of trivalent nucleophilic boryl synthon in the selective preparation of organoboron compounds, mainly through metal-free catalytic diboration and the β-boration reactions of alkynes and alkenes.

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An Alkyne Diboration/6π‐Electrocyclization Strategy for the Synthesis of Pyridine Boronic Acid Derivatives

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Cited by 33 publications

References 29 publications

Design and Synthesis of Fused Pyridine Building Blocks for Automated Library Generation

Design and Synthesis of Fused Pyridine Building Blocks for Automated Library Generation

Synthetic and Mechanistic Investigation of an Oxime Ether Electrocyclization Approach to Heteroaromatic Boronic Acid Derivatives

Recent Synthesis Developments of Organoboron Compounds via Metal-Free Catalytic Borylation of Alkynes and Alkenes

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