scholarly journals The Programmed Multiple C–H Bond Functionalization of 4-Hydroxyquinoline and Its Medicinal Potential

2021 ◽  
Author(s):  
Quentin Ronzon ◽  
Wei Zhang ◽  
Nicolas Casaretto ◽  
Elizabeth Mouray ◽  
Isabelle Florent ◽  
...  
Keyword(s):  
Carbonyl Group ◽  
Multiple Site ◽  
Fries Rearrangement ◽  
Bond Functionalization ◽  
Chemical Libraries ◽  
Biologically Relevant ◽  
Directing Group ◽  
Metal Catalyzed ◽  
Site Selective

<p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalization of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalization, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an <i>O</i>-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C–H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p>

scholarly journals Programmed multiple C–H bond functionalisation of the privileged 4-hydroxyquinoline template

2021 ◽  
Author(s):  
Quentin Ronzon ◽  
Wei Zhang ◽  
Nicolas Casaretto ◽  
Elizabeth Mouray ◽  
Isabelle Florent ◽  
...  
Keyword(s):  
Carbonyl Group ◽  
Multiple Site ◽  
Fries Rearrangement ◽  
Chemical Libraries ◽  
Biologically Relevant ◽  
Directing Group ◽  
Metal Catalyzed ◽  
Site Selective

<div> <p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalisation. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalisation of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalisation, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalise position 5. Our study highlights the power of multiple C–H functionalisation to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p></div>

scholarly journals Programmed multiple C–H bond functionalisation of the privileged 4-hydroxyquinoline template

2021 ◽  
Author(s):  
Quentin Ronzon ◽  
Wei Zhang ◽  
Nicolas Casaretto ◽  
Elizabeth Mouray ◽  
Isabelle Florent ◽  
...  
Keyword(s):  
Carbonyl Group ◽  
Multiple Site ◽  
Fries Rearrangement ◽  
Chemical Libraries ◽  
Biologically Relevant ◽  
Directing Group ◽  
Metal Catalyzed ◽  
Site Selective

<div> <p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalisation. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalisation of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalisation, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalise position 5. Our study highlights the power of multiple C–H functionalisation to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p></div>

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

2017 ◽  
Author(s):  
Haibo Ge ◽  
Lei Pan ◽  
Piaoping Tang ◽  
Ke Yang ◽  
Mian Wang ◽  
...  
Keyword(s):  
Bond Activation ◽  
Theoretical Calculations ◽  
Experimental Studies ◽  
Bond Functionalization ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Mechanistic Investigation ◽  
Palladium Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

scholarly journals N-Benzo[c][1,2,5]thiazol-4-yl-3-trifluoromethylbenzamide

Molbank ◽  
10.3390/m1075 ◽  
2019 ◽  
Vol 2019 (3) ◽  
pp. M1075 ◽  
Author(s):  
Hamad H. Al Mamari ◽  
Nasser Al Awaimri ◽  
Yousuf Al Lawati
Keyword(s):  
1H Nmr ◽  
Elemental Analysis ◽  
13C Nmr ◽  
Title Compound ◽  
Structural Motif ◽  
Spectroscopic Methods ◽  
Bond Functionalization ◽  
Directing Group ◽  
Metal Catalyzed

The title compound, N-benzo[c][1,2,5]thiazol-4-yl-3-trifluoromethylbenzamide (1) was synthesized by reacting 3-trifluoromethylbenzoyl chloride (4) and 4-aminobenzo[c][1,2,5]thiadiazole (5). The compound was characterized by various spectroscopic methods (1H NMR, 13C NMR, IR, GC-MS) and its composition confirmed by elemental analysis. The importance of this compound lies in its possession of an N,N-bidentate directing group. Such a structural motif is potentially suitable for metal-catalyzed C-H bond functionalization reactions.

scholarly journals Diverse secondary C(sp3)–H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines

2018 ◽  
Vol 9 (30) ◽  
pp. 6374-6378 ◽  
Author(s):  
Yongzhen Tang ◽  
Yuman Qin ◽  
Dongmei Meng ◽  
Chaoqun Li ◽  
Junfa Wei ◽  
...  
Keyword(s):  
Aliphatic Amine ◽  
Aliphatic Amines ◽  
Coinage Metal ◽  
Bond Functionalization ◽  
Metal Catalyzed ◽  
Site Selective

A coinage-metal-catalyzed site-selective trifluoroacetoxylation of remote secondary C(sp3)–H bonds for aliphatic amine substrates was developed.

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

2017 ◽  
Author(s):  
Haibo Ge ◽  
Lei Pan ◽  
Piaoping Tang ◽  
Ke Yang ◽  
Mian Wang ◽  
...  
Keyword(s):  
Bond Activation ◽  
Theoretical Calculations ◽  
Experimental Studies ◽  
Bond Functionalization ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Mechanistic Investigation ◽  
Palladium Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

scholarly journals N-(2-Hydroxy-1,1-dimethylethyl)-3-methylbenzamide

Molbank ◽  
10.3390/m1099 ◽  
2019 ◽  
Vol 2020 (1) ◽  
pp. M1099 ◽  
Author(s):  
Hamad H. Al Mamari ◽  
Yousuf Al Lawati
Keyword(s):  
Elemental Analysis ◽  
13C Nmr ◽  
Present Report ◽  
Structural Motif ◽  
Spectroscopic Methods ◽  
Target Compound ◽  
Bond Functionalization ◽  
X Ray ◽  
Directing Group ◽  
Metal Catalyzed

The title compound, N-(2-hydroxy-1,1-dimethylethyl)-3-methylbenzamide was synthesized by reacting 3-methylbenzoyl chloride or 3-methylbenzoic acid with 2-amino-2-methyl-1-propanol. In the present report, the synthesized target compound was fully characterized by various spectroscopic methods (1H NMR, 13C NMR, IR, GC-MS), its composition confirmed by elemental analysis, and its structure determined and confirmed by X-ray analysis. The importance of this compound lies in its possession of an N,O-bidentate directing group. Such a structural motif is potentially suitable for metal-catalyzed C–H bond functionalization reactions.

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