Chemoselective α,β‐Dehydrogenation of Saturated Amides

Teskey, Christopher J.; Adler, Pauline; Gonçalves, Carlos R.; Maulide, Nuno

doi:10.1002/anie.201808794

Cited by 57 publications

(28 citation statements)

References 65 publications

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“…Therefore, this work represents a step change in developing a direct, green synthesis route for para -aromatic aldehydes and guides the design of more efficient heterogeneous catalysts for this reaction. More importantly, this report shows an experimental example of an organic amine-catalyzed dehydrogenation reaction, which is different to the reported metal-dehydrogenation and stoichiometric-dehydrogenation processes ( Gnaim et al., 2021 ; Teskey et al., 2019 ; Mukaiyama et al., 2000 ).…”

Section: Resultscontrasting

confidence: 98%

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

et al. 2021

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Summary p -Methyl benzaldehyde ( p -MBA) is a class of key chemical intermediates of pharmaceuticals. Conventional industrial processes for p -MBA production involve the consecutive photochlorination, amination, and acid hydrolysis of petroleum-derived p -xylene, while producing vast pollutants and waste water. Herein, we report a direct, green route for selective synthesis of p -MBA from acetaldehyde using a diphenyl prolinol trimethylsilyl ether catalyst. The optimized p -MBA selectivity is up to 90% at an acetaldehyde conversion as high as 99.8%. Intermediate structure and 18 O-isotope data revealed that the conversion of acetaldehyde to p -methylcyclohexadienal intermediates proceeds in an enamine-iminium intermediate mechanism. Then, controlled experiments and D-isotope results indicated that the dehydrogenation of p -methylcyclohexadienal to p -MBA and H 2 is catalyzed by the same amines through an iminium intermediate. This is an example that metal-free amines catalyze the dehydrogenation (releasing H 2 ), rather than using metals or stoichiometric oxidants.

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Section: Resultscontrasting

confidence: 98%

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

et al. 2021

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“…Metal-catalyzed dehydrogenative β -C(sp 3 )–H functionalization reactions via dehydrogenative desaturation 28,29 were also amenable to esters 30–34 , lactams 35 , and other substrates 36–48 , demonstrating the ability of this type of reaction to rapidly construct complex molecule from simple substrates. Such reactions will continue to flourish in the future in view of the recent advance in the development of catalytic methods for generation of unsaturated compounds via dehydrogenation 39–49 as well as the versatility of unsaturated compounds as synthetic intermediates. Recently, we have discovered a Cu-catalyzed successive dehydrogenation of aliphatic ketones to furnish dienketones or polyenketones 50 .…”

Section: Introductionmentioning

confidence: 99%

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Chen

Zhang

et al. 2019

Nat Commun

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Metal-catalyzed β -C-H functionalization of saturated carbonyls via dehydrogenative desaturation proved to be a powerful tool for simplifying synthesis of valuable β -substituted carbonyls. Here, we report a copper-catalyzed dehydrogenative γ -C(sp 3 )-H amination of saturated ketones that initiates the three-component coupling of saturated ketones, amines and N -substituted maleimides to construct polysubstituted anilines. The protocol presented herein enables both linear and α -branched butanones to couple a wide spectrum of amines and various N -substituted maleimides to produce diverse tetra- or penta-substituted anilines in fair-to-excellent yields with good functional group tolerance. The mechanism studies support that this ketone dehydrogenative γ -C(sp 3 )-H amination was triggered by the ketone α,β -dehydrogenation desaturation that activates the adjacent γ -C(sp 3 )-H bond towards functionalization. This α,β -dehydrogenation desaturation-triggered cascade sequence opens up a new avenue to the remote C(sp 3 )-H functionalization of saturated ketones and has the potential to enable the rapid syntheses of complex compounds from simple starting materials.

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“…Till now, seleninic acids have found several application routes, including their utilization as ligands [6][7][8][9][10] and reagents in oxidation [11][12][13][14], dehydrogenation [15] and oxidative deoximation reactions [16]. However, their applicability in medicinal chemistry seems to be still an unexplored field with promising perspectives.…”

Section: Introductionmentioning

confidence: 99%

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

et al. 2020

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Organoselenium compounds are well-known glutathione peroxidase (GPx) mimetics that possess antioxidants/prooxidant properties and are able to modulate the concentration of reactive oxygen species (ROS), preventing oxidative stress in normal cells or inducing ROS formation in cancer cells leading to apoptosis. The purpose of this study was the synthesis of potent GPx mimics with antioxidant and anticancer activity along with improved bioavailability, as a result of good solubility in protic solvents. As a result of our research, glutathione peroxidase (GPx) mimetics in the form of water-soluble benzeneseleninic acid salts were obtained. The procedure was based on the synthesis of 2-(N-alkylcarboxyamido)benzeneselenenic acids, through the oxidation of benzisoselenazol-3(2H)-ones or analogous arenediselenides with an amido group, which were further converted to corresponding potassium salts by the treatment with potassium tert-butanolate. All derivatives were tested as potential antioxidants and anticancer agents. The areneseleninic acid salts were significantly better peroxide scavengers than analogous acids and the well-known organoselenium antioxidant ebselen. The highest activity was observed for the 2-(N-ethylcarboxyamido)benzeneselenenic acid potassium salt. The strongest cytotoxic effect against breast cancer (MCF-7) and human promyelocytic leukemia (HL-60) cell lines was found for 2-(N-cyclohexylcarboxyamido)benzeneselenenic acid potassium salt and the 2-(N-ethylcarboxyamido)benzeneselenenic acid, respectively. The structure–activity correlations, including the differences in reactivity of benzeneseleninic acids and corresponding salts were evaluated.

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Chemoselective α,β‐Dehydrogenation of Saturated Amides

Cited by 57 publications

References 65 publications

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

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