Cleavage of the N-N bond in 1-substituted indazoles under the influence of aryllithium compounds

Tertov, B. A.; Onishchenko, P. P.; Koshchienko, Yu. V.; Suvorova, G. M.; Малышева, Е. Н.

doi:10.1007/bf00506587

Cited by 3 publications

(1 citation statement)

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“…During the course of an ongoing medicinal chemistry program, we observed an undesirable ring-opening isomerization reaction of N1-substituted indazoles. Presumably, basic organometallic reagents can rapidly deprotonate an acidic C–H bond at the C3 position, − and owing to the thermodynamic favorability of nitrile formation, these anions rapidly undergo Kemp-type eliminations to afford their corresponding ring-opened o -aminobenzonitrile byproducts (Figure ). , This reactivity is sparsely documented in the literature, particularly in the context of modern transition metal catalysis wherein strong bases are frequently used, and is underappreciated as a parasitic side reaction.…”

Section: Introductionmentioning

confidence: 99%

Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base

Ganley

Yeung

2017

J. Org. Chem.

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Indazoles represent a privileged scaffold in medicinal chemistry. In the presence of strong base, however, N-protected indazoles are prone to an undesirable ring-opening reaction to liberate o-aminobenzonitriles. By employing unprotected indazoles with a free N-H bond, isomerization is averted because the heterocycle is deprotonated in situ. We herein report functional group-tolerant and robust C-S couplings of bromoindazoles with thiols of varying electronic nature in the presence of lithium bis(trimethylsilyl)amide at elevated temperatures.

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Section: Introductionmentioning

confidence: 99%

Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base

Ganley

Yeung

2017

J. Org. Chem.

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Surprising Reactivity in NiXantphos/Palladium-Catalyzed α-Arylation of Substituted Cyclopropyl Nitriles

Wright

Ardolino

2018

J. Org. Chem.

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α-Arylations of cyclopropyl and related nitriles provide access to important synthetic intermediates and pharmacophores for biologically active molecules. However, robust methods for coupling of sterically encumbered partners have remained elusive. Through optimization using high-throughput experimentation (HTE), the NiXantphos ligand was found to be effective in the coupling of sterically hindered β-substituted cyclopropyl nitriles with a number of aryl groups and heterocycles, including those containing acidic N–H and O–H bonds.

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Oxidant-controlled divergent transformations of 3-aminoindazoles for the synthesis of pyrimido[1,2-b]-indazoles and aromatic nitrile-derived dithioacetals

2019

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Cleavage of the N-N bond in 1-substituted indazoles under the influence of aryllithium compounds

Cited by 3 publications

References 1 publication

Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base

Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base

Surprising Reactivity in NiXantphos/Palladium-Catalyzed α-Arylation of Substituted Cyclopropyl Nitriles

Oxidant-controlled divergent transformations of 3-aminoindazoles for the synthesis of pyrimido[1,2-b]-indazoles and aromatic nitrile-derived dithioacetals

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