An Efficient and Regioselective Difluoromethylation of 3-Iodoindazole with Chlorodifluoromethane

Pelc, Matthew J.; Wei, Huang; Trujillo, John I.; Baldus, John; Turner, S. D.; Kleine, Pete; Yang, Shengtian; Thorarensen, Atli

doi:10.1055/s-0029-1218559

Cited by 10 publications

(4 citation statements)

References 2 publications

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“…Nonfluorinated aliphatic alcohols remain problematic substrates for difluoromethylation and often give rise to low yields 218. Likewise, nitrogenous nucleophiles such as azoles,219 2‐mercaptoazoles,220 sulfonamides,221 sulfanyltetrazoles,222 benzotriazoles and tetrazoles,223 2‐acetaminopyridine,224 and indazoles225 can be converted into N ‐difluoromethylated products. Historically, other reagents used in N ‐difluoromethylations include Zn(CF 3 )Br,226 Cd(CF 3 ) 2 ,226a,b,d, 227 and Bi(CF 3 ) 3 /AlCl 3 ,226d all of which react through difluorocarbene intermediates.…”

Section: Difluoromethylationmentioning

confidence: 99%

Introduction of Fluorine and Fluorine‐Containing Functional Groups

Liang¹,

Neumann²,

Ritter³

2013

Angew Chem Int Ed

2,303

856

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Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo‐ and transition‐metal catalysis. The most challenging transformation remains the formation of the parent CF bond, primarily as a consequence of the high hydration energy of fluoride, strong metal—fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost‐efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

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Section: Difluoromethylationmentioning

confidence: 99%

Introduction of Fluorine and Fluorine‐Containing Functional Groups

Liang¹,

Neumann²,

Ritter³

2013

Angew Chem Int Ed

2,303

856

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“…Nicht-fluorierte aliphatische Alkohole sind noch immer schwierige Substrate für diese Reaktion und ergeben oft niedrige Ausbeuten. [218] Auf ähnliche Weise lassen sich Stickstoffnucleophile wie Azole, [219] 2-Mercaptoazole, [220] Sulfonamide, [221] Sulfanyltetrazole, [222] Benzotriazole und Tetrazole, [223] 2-Acetaminopyridin [224] und Indazole [225] in N-difluormethylierte Produkte überführen. Früher wurden Difluormethylierungen mit Reagentien wie Zn(CF 3 )Br, [ [228] und Chlordifluormethylphenylsulfon (Schema 49) [229] Reagens, was sich mit dessen Zerfall durch Abspaltung des aciden Protons an der Difluormethylgruppe in Gegenwart des Nucleophils erklären ließe.…”

Section: Elektrophile Difluormethylierung üBer Carbenzwischenstufenunclassified

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

2013

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Die wichtigsten konzeptionellen Fortschritt auf dem Gebiet der Fluorierungen der letzten zehn Jahre wurden durch die Organo‐ und Übergangsmetallkatalyse ermöglicht. Die schwierigste Umwandlung ist weiterhin die Bildung der C‐F‐Stammbindung, was in erster Linie eine Folge der hohen Hydratationsenergie von Fluorid, starker Metall‐Fluor‐Bindungen und der hoch polarisierten Bindungen zu Fluor ist. Den meisten Fluorierungen fehlt es immer noch an Allgemeingültigkeit, Vorhersagbarkeit und Kosteneffizienz. Trotz der Einschränkungen sind fluorierte Verbindungen mit modernen Fluorierungsmethoden leichter zugänglich als je zuvor. Vor allem beginnen sich die modernen Methoden auf Forschungsgebiete auszuwirken, die keine großen Materialmengen benötigen, z. B. die Wirkstoffentwicklung und die Positronenemissionstomographie. Diese Entwicklungen werden in diesem Aufsatz zusammengefasst und vor dem Hintergrund konventioneller Fluorierungsmethoden diskutiert.

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“…Imidazoles 1 and benzimidazoles 2 [ 34 , 35 , 36 ], pyrazoles 3 [ 37 , 38 ], indazoles 4 and 5 [ 35 , 39 ], benzotriazole 6 [ 34 , 35 , 36 ] were reported. Related compounds 9 – 12 with CXF 2 substituents are described in reference [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

19F‐NMR Diastereotopic Signals in Two N-CHF2 Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole

et al. 2017

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In this paper, we report the anisochrony of the fluorine atoms of a CHF2 group when linked to a pyrazole ring. The pyrazole is part of (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole also known as (4S,7R)-campho[2,3-c]pyrazole, which has two stereogenic centers. Gauge-Independent Atomic Orbital (GIAO)/Becke, 3-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,f) calculated 19F chemical shifts of the minimum energy conformations satisfactorily agree with the experimental data. The energy differences between minima need to consider solvent effects (continuum model) to be satisfactorily reproduced.

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An Efficient and Regioselective Difluoromethylation of 3-Iodoindazole with Chlorodifluoromethane

Abstract: D i f l u o r o m e t h y l a t i o n o f 3 -I o d o i n d a z o l e w i t h C h l o r o d i f l u o r o m e t h a n e

Cited by 10 publications

References 2 publications

Introduction of Fluorine and Fluorine‐Containing Functional Groups

Introduction of Fluorine and Fluorine‐Containing Functional Groups

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

19F‐NMR Diastereotopic Signals in Two N-CHF2 Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole

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