Denitrogenative hydrofluorination of aromatic aldehyde hydrazones using (difluoroiodo)toluene

Kulkarni, Kaivalya G.; Miokovic, Boris; Sauder, Matthew; Murphy, Graham K.

doi:10.1039/c6ob02074g

“…Based on these results, we reasoned that the hydrazones are not initially oxidized to diazo compounds in this process . We anticipated that 6 would not lead to 1 b , given its inability to expel nitrogen gas, but we were surprised that 5 also failed, as p ‐tosylhydrazones were previously found to be interchangeable with hydrazones (for example, 5 vs. 3 b ) in various HVI‐mediated denitrogenation reactions . The differing reactivity observed here is attributed to the decreased nucleophilicity of the hydrazone possessing the p ‐Ts group.…”

Section: Methodsmentioning

confidence: 69%

“…Subjecting diazo compound 4 to the reaction conditions failed to give 1 b , as did p ‐toluenesulfonyl hydrazone 5 and phenylhydrazone 6 (Scheme a). Based on these results, we reasoned that the hydrazones are not initially oxidized to diazo compounds in this process . We anticipated that 6 would not lead to 1 b , given its inability to expel nitrogen gas, but we were surprised that 5 also failed, as p ‐tosylhydrazones were previously found to be interchangeable with hydrazones (for example, 5 vs. 3 b ) in various HVI‐mediated denitrogenation reactions .…”

Section: Methodsmentioning

confidence: 98%

Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2‐Trifluoroethyl)arenes

Zhao

¹

,

Kevin

²

,

Legault

³

et al. 2019

Chemistry A European J

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Reacting hydrazones of arylaldehydes with To gni's CF 3 -benziodoxolone reagent, in the presenceo f potassium hydroxide and cesium fluoride, induces ad enitrogenative hydrotrifluoromethylation eventt op roduce (2,2,2-trifluoroethyl)arenes. This novel reactionw as tolerant to many electronically-diverse functionalg roups and substitution patterns, as well as naphthyl-and heteroarylderivedsubstrates. Advantages of this processi nclude the easy access to hydrazone precursors on al arge scale, speed and operational simplicity,a nd being transition metal-free.Organofluorine compounds play criticalr oles in many areas of modernr esearch,f rom medicinal chemistry to agrochemistry, and from materials science to medical imaging, [1] so the continued development of new fluorination methodologies is critical. Amongt he myriad important organofluorine motifs, (2,2,2-trifluoroethyl)arenes( 1)h ave received considerable attention from the synthetic community,d ue to their favorable biological properties including their increased metabolic stability over alkyl groups. [2] Efforts towards this motif are plentiful and span aw ide range of general synthetics trategies. They are prepared from aldehydes by am ulti-step sequence involving trifluoromethylation and deoxygenation (Scheme 1a,i ), [3,4] and also from b,b-difluorostyrenes by hydrofluorination( Scheme 1a, ii). [5] Nucleophilic displacementonavariety of activated benzylic compounds is achieved with in situ-generated "CuCF 3 " [6,7] (Scheme 1a,i ii). Metal-mediated cross-coupling strategies [8] between arenes or heteroarenes and (2,2,2-trifluoroethyl)-based reagents have been achieved with Cu-, [9] Ni-, [10] Co-, [11] Zn-, [12] Ir-, [13] and Pd-based [14,15] catalysts( Scheme 1a,i v) and arylboronic acids have also been effectively coupled with 2,2,2trifluorodiazoethane (Scheme 1a,v ). [16] Over the past few decades, the use of hypervalenti odine(III) (HVI) reagents in organic chemistry has undergone tremendous growth,d ue to the advantageso fm ild reactionc onditions and broad reactivity,a nd of recyclable,e nvironmentallybenignb y-products. [17] The synthesis of (2,2,2-trifluoroethyl)arenes has recently been accomplished with mesityl( 2,2,2-trifluoroethyl)-iodoniums alts, by electrophilicc oupling with arenes( Scheme 1b,i ). [18] Togni's CF 3 -containing HVI reagent (2) [19] has also been used in the synthesis of 1,throughthe radical trifluoromethylation of benzylic CÀHb onds (Scheme 1b, ii). [20] We were interested in exploitingt he electrophilic nature of 2 [21] to develop at ransitionmetal-free synthesis of 1,b ye xposingi tt oas uitable benzylic nucleophile such as ah ydrazone. [22] Arylaldehyde-derivedh ydrazones readily undergo trifluoromethylation at the azomethine carbon, [23] but to the best of our knowledge,t his reactivity has not been coupled with a denitrogenation event. Given our interest in HVI-mediated gem-difunctionalization reactions of diazo compounds and hydrazones, [24] we aimed to interrupt aW olff-Kishner reduction by having an anionic intermediat...

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“…To demonstrate the chemical feasibility of the reaction of a hydrazone with an iodane, Murphy et al. developed several operationally simple protocols to prepare benzyl fluorides ( 11.7 ), [77] difluorides ( 11.8 ) [78] and dichlorides ( 11.9 ) [78] from the corresponding benzaldehyde hydrazones in the absence of transition metals. Afterward, Li's group disclosed a hydrotrifluoromethylation reaction with hydrazone and Tongi's reagent II, allowing the synthesis of a large number of electronically and sterically diverse (2,2,2‐trifluoroethyl)arenes ( 11.10 ) [79] .…”

Section: Deoxygenative Functionalizations Of Aldehydes and Ketonesmentioning

confidence: 99%

“…Along this line,h ypervalent iodines were considered as promising candidates since they could serve as oxidants as well as group-transfer reagents.In addition, most of the hypervalent iodines are commercially available and easily synthesized, and ab road range of oxidation potentials can be achieved by adjusting their substitution patterns. [76] To demonstrate the chemical feasibility of the reaction of ahydrazone with an iodane,Murphy et al developed several operationally simple protocols to prepare benzyl fluorides (11.7), [77] difluorides (11.8) [78] and dichlorides (11.9) [78] from the corresponding benzaldehyde hydrazones in the absence of transition metals.A fterward, Lisg roup disclosed ah ydrotrifluoromethylation reaction with hydrazone and Tongis reagent II, allowing the synthesis of al arge number of electronically and sterically diverse (2,2,2-trifluoroethyl)arenes (11.10). [79] Almost concurrently,M urphysg roup reported similar hydrotrifluoromethylation conditions for the denitrogenative hydrotrifluoromethylation of benzaldehyde hydrazones.…”

Section: Catalyst-free Transformations With Hydrazonesmentioning

confidence: 99%

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Li

¹

,

Li

²

,

Huang

³

2022

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The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis‐electrophiles, carbenoids, bis‐nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris‐electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective.

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“…Along this line,h ypervalent iodines were considered as promising candidates since they could serve as oxidants as well as group-transfer reagents.In addition, most of the hypervalent iodines are commercially available and easily synthesized, and ab road range of oxidation potentials can be achieved by adjusting their substitution patterns. [76] To demonstrate the chemical feasibility of the reaction of ahydrazone with an iodane,Murphy et al developed several operationally simple protocols to prepare benzyl fluorides (11.7), [77] difluorides (11.8) [78] and dichlorides (11.9) [78] from the corresponding benzaldehyde hydrazones in the absence of transition metals.A fterward, Lisg roup disclosed ah ydrotrifluoromethylation reaction with hydrazone and Tongis…”

Section: Catalyst-free Transformations With Hydrazonesmentioning

confidence: 99%

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Li

¹

,

Huang

²

,

Li

³

2022

View full text Add to dashboard Cite

The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis‐electrophiles, carbenoids, bis‐nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris‐electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective.

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Denitrogenative hydrofluorination of aromatic aldehyde hydrazones using (difluoroiodo)toluene

Cited by 11 publications

References 82 publications

Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2‐Trifluoroethyl)arenes

Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2‐Trifluoroethyl)arenes

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

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