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 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>

Arene diversification through distal C(sp2)−H functionalization

Science ◽  
2021 ◽  
Vol 372 (6543) ◽  
pp. eabd5992
Author(s):  
Uttam Dutta ◽  
Sudip Maiti ◽  
Trisha Bhattacharya ◽  
Debabrata Maiti
Keyword(s):  
Transition Metal ◽  
Noncovalent Interactions ◽  
Catalyst Design ◽  
Selective Functionalization ◽  
Directing Group ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal–catalyzed aryl C−H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal ortho-C−H activation, distal (meta- and/or para-) C−H activation remains more challenging due to the inaccessibility of these sites in the formation of energetically favorable organometallic pretransition states. Directing the catalyst toward the distal C−H bonds requires judicious template engineering and catalyst design, as well as prudent choice of ligands. This review aims to summarize the recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, and catalyst and/or ligand selection to control distal C−H activation.

γ-C(sp2)–H Arylation of Allylamines Using PdII and CO2 as a Transient Directing Group

2020 ◽  
Author(s):  
Vinod Landge ◽  
Justin Maxwell ◽  
Pratibha Chand-Thakuri ◽  
Mohit Kapoor ◽  
Evan Diemler ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Transition Metal ◽  
Complex Molecules ◽  
Dry Ice ◽  
Biologically Relevant ◽  
Mild Conditions ◽  
Directing Group ◽  
Key Features ◽  
Catalyzed Reactions ◽  
Metal Catalyzed

Although C–H activation has become a powerful tool in the synthesis of complex molecules from simple precursors, transition metal-catalyzed reactions involving free alkenes often lead to insertion-type reactions. Herein we demonstrate that the addition of carbon dioxide in the form of dry ice allows the C(<i>sp</i><sup>2</sup>)–H arylation of both secondary and primary allylamines in the presence of a Pd<sup>II</sup> catalyst. Notably, the product 3,3’-diarylallylamine motif is prevalent in a variety of biologically-relevant structures, and this method represents the most straightforward synthesis of these targets to date. Key features of the method are the ability to access relatively mild conditions that facilitate a broad substrate scope, as well as direct diarylation of terminal allylamine substrates. In addition, several complex and therapeutically-relevant molecules are included to demonstrate the utility of the transformation.

scholarly journals Site-selective Ru-catalyzed C–H bond alkenylation with biologically relevant isoindolinones: a case of catalyst performance controlled by subtle stereo-electronic effects of the weak directing group

2019 ◽  
Vol 9 (17) ◽  
pp. 4711-4717 ◽  
Author(s):  
Yu-Chao Yuan ◽  
Christian Bruneau ◽  
Thierry Roisnel ◽  
Rafael Gramage-Doria
Keyword(s):  
Electronic Effects ◽  
Biologically Relevant ◽  
Directing Group ◽  
Site Selective

A general regio- and site-selective ruthenium-catalyzed C–H bond alkenylation with the biologically relevant isoindolinone fragment serving as a weak directing group is presented.

para-Selective Cyanation of Arenes by H-Bonded Template

2019 ◽  
Author(s):  
Sandeep Pimparkar ◽  
Trisha Bhattacharya ◽  
Arun Maji ◽  
Argha Saha ◽  
Ramasamy Jayarajan ◽  
...  
Keyword(s):  
Selective Functionalization ◽  
Directing Group ◽  
Product Utility ◽  
Site Selective

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work we demonstrate the <i>para</i>-selective introduction of versatile nitrile moiety, enabled by detachable and reusable H-bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools heralds the inception of <i>para</i>-deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications

para-Selective Cyanation of Arenes by H-Bonded Template

2019 ◽  
Author(s):  
Sandeep Pimparkar ◽  
Trisha Bhattacharya ◽  
Arun Maji ◽  
Argha Saha ◽  
Ramasamy Jayarajan ◽  
...  
Keyword(s):  
Selective Functionalization ◽  
Directing Group ◽  
Product Utility ◽  
Site Selective

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work we demonstrate the <i>para</i>-selective introduction of versatile nitrile moiety, enabled by detachable and reusable H-bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools heralds the inception of <i>para</i>-deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications

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.

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