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>

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>

Palladium-catalyzed site-selective arylation of aliphatic ketones enabled by a transient ligand

2018 ◽  
Vol 54 (22) ◽  
pp. 2759-2762 ◽  
Author(s):  
Lei Pan ◽  
Ke Yang ◽  
Guigen Li ◽  
Haibo Ge
Keyword(s):  
Functional Group ◽  
Direct Arylation ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Palladium Catalyzed ◽  
High Site ◽  
Site Selective

A direct arylation of C–H bonds of ketones enabled by a cheap and commercially available transient ligand with high site-selectivity and functional group compatibility is reported.

Non-directed highly para-selective C-H functionalization of TIPS-protected phenols promoted by a proton shuttle

2021 ◽  
Author(s):  
Jingyao Geng ◽  
Zhang Fang ◽  
Guangliang Tu ◽  
Yingsheng Zhao
Keyword(s):  
Bioactive Molecules ◽  
Protecting Group ◽  
Mechanism Study ◽  
Phenol Derivatives ◽  
Site Selectivity ◽  
Palladium Catalyzed ◽  
Direct Functionalization ◽  
Poor Site ◽  
Site Selective ◽  
First Time

Abstract Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application. Herein, it is reported for the first time that the proton shuttle of 3,5-dimethyladamantane-1-carboxylic acid (1-DMAdCO2H) can affect the site selectivity during the C-H activation step in palladium-catalyzed non-directed C-H functionalization, leading to highly para-selective C-H olefination of TIPS-protected phenols. This transformation displayed good generality in realizing various other para-selective C-H functionalization reactions such as hydroxylation, halogenation, and allylation reactions. A wide variety of phenol derivatives including bioactive molecules of triclosan, thymol, and propofol, were compatible substrates, leading to the corresponding para-selective products in moderate to good yields. A preliminary mechanism study revealed that the spatial repulsion factor between proton shuttle and bulky protecting group resulted in the selective C-H activation at the less sterically hindered para-position. This new model non-directed para-selective C-H functionalization can provide a straightforward route for remote site-selective C-H activations.

scholarly journals Recent Advances in Palladium-Catalyzed Bridging C–H Activation by Using Alkenes, Alkynes or Diazo Compounds as Bridging Reagents

Synthesis ◽  
2020 ◽  
Vol 53 (02) ◽  
pp. 238-254
Author(s):  
Fulin Zhang ◽  
Luoting Xin ◽  
Saihu Liao ◽  
Xueliang Huang ◽  
Yinghua Yu
Keyword(s):  
Bond Distance ◽  
Short Review ◽  
Diazo Compounds ◽  
Bond Functionalization ◽  
Migratory Insertion ◽  
Intramolecular Reactions ◽  
Palladium Catalyzed ◽  
Direct Functionalization ◽  
Intermolecular Reactions ◽  
Metal Catalyzed

AbstractTransition-metal-catalyzed direct inert C–H bond functionalization has attracted much attention over the past decades. However, because of the high strain energy of the suspected palladacycle generated via C–H bond palladation, direct functionalization of a C–H bond less than a three-bond distance from a catalyst center is highly challenging. In this short review, we summarize the advances on palladium-catalyzed bridging C–H activation, in which an inert proximal C–H bond palladation is promoted by the elementary step of migratory insertion of an alkene, an alkyne or a metal carbene intermediate.1 Introduction2 Palladium-Catalyzed Alkene Bridging C–H Activation2.1 Intramolecular Reactions2.2 Intermolecular Reactions3 Palladium-Catalyzed Alkyne Bridging C–H Activation3.1 Intermolecular Reactions3.2 Intramolecular Reactions4 Palladium-Catalyzed Carbene Bridging C–H Activation5 Conclusion and Outlook

Carbon Dioxide-Driven Palladium-Catalyzed C–H Activation of Amines: A Unified Approach for the Arylation of Aliphatic and Aromatic Primary and Secondary Amines

Synlett ◽  
2019 ◽  
Vol 30 (05) ◽  
pp. 519-524 ◽  
Author(s):  
Michael Young ◽  
Mohit Kapoor ◽  
Pratibha Chand-Thakuri ◽  
Justin Maxwell ◽  
Daniel Liu ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Bond Activation ◽  
Secondary Amines ◽  
Activation Process ◽  
Unified Approach ◽  
Benzylic Amines ◽  
Palladium Catalyzed ◽  
Group A ◽  
Directing Group ◽  
Site Selective

Amines are an important class of compounds in organic chemistry and serve as an important motif in various industries, including pharmaceuticals, agrochemicals, and biotechnology. Several methods have been developed for the C–H functionalization of amines using various directing groups, but functionalization of free amines remains a challenge. Here, we discuss our recently developed carbon dioxide driven highly site-selective γ-arylation of alkyl- and benzylic amines via a palladium-catalyzed C–H bond-activation process. By using carbon dioxide as an inexpensive, sustainable, and transient directing group, a wide variety of amines were arylated at either γ-sp3 or sp2 carbon–hydrogen bonds with high selectivity based on substrate and conditions. This newly developed strategy provides straightforward access to important scaffolds in organic and medicinal chemistry without the need for any expensive directing groups.1 Introduction2 C(sp3)–H Arylation of Aliphatic Amines3 C(sp2)–H Arylation of Benzylamines4 Mechanistic Questions5 Future Outlook

scholarly journals Advances in the Synthesis of Fluorinated Scaffolds by Transition Metal-Catalyzed C–H Bond Activation

2020 ◽  
Vol 74 (11) ◽  
pp. 871-877
Author(s):  
Sara Mazeh ◽  
Maria Ivana Lapuh ◽  
Tatiana Besset
Keyword(s):  
Transition Metal ◽  
Fluorine Atom ◽  
Bond Activation ◽  
Value Added ◽  
Bond Functionalization ◽  
Present Account ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed

Thanks to the unique features of the fluorine atom and the fluorinated groups, fluorine-containing molecules are essential. Therefore, the search for new fluorinated groups as well as straightforward and original methodologies for their installation is of prime importance. Especially, the combination of organofluorine chemistry with transition metal-catalyzed C–H bond functionalization reactions offered straightforward tools to access original fluorinated scaffolds. In this context, over the last years, our group focused on the development of original methodologies to synthesize fluorine-containing molecules with a special attention to emergent fluorinated groups. The present account highlights our recent contributions to the synthesis of highly value-added fluorine-containing compounds by transition metal-catalyzed C–H bond activation.

scholarly journals Site-Selective A-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis

2021 ◽  
Author(s):  
Yangyang Shen ◽  
Franziska Schoenebeck ◽  
Ignacio Funes-Ardoiz ◽  
Tomislav Rovis
Keyword(s):  
Drug Discovery ◽  
Hydrogen Atom ◽  
Late Stage ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer ◽  
Bond Functionalization ◽  
Carbon Centers ◽  
Radical Trapping ◽  
Site Selectivity ◽  
Site Selective

Trialkylamines are widely found in naturally-occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and pre-clinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective a-C(sp3 )–H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between a-amino C(sp3 )-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3 )-C(sp3 ) bond with the more-crowded a-amino radical, with the overall selectivity guided by Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C– C bonds from a diverse set of trialkylamines with high levels of site-selectivity and preparative utility. Simple correlation of site-selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, holds tremendous potential to streamline complex trialkylamine synthesis and accelerate drug discovery

Palladium catalyzed chemo- and site-selective C–H acetoxylation and hydroxylation of oxobenzoxazine derivatives

2019 ◽  
Vol 17 (18) ◽  
pp. 4465-4469 ◽  
Author(s):  
Manickam Bakthadoss ◽  
Polu Vijay Kumar ◽  
Ravan Kumar ◽  
Vishal Agarwal
Keyword(s):  
Palladium Catalyst ◽  
Site Selectivity ◽  
Palladium Catalyzed ◽  
Site Selective

A new protocol for the acetoxylation and hydroxylation of oxobenzoxazine derivatives via an ortho-C–H functionalization strategy using a palladium catalyst has been developed with chemo- and site-selectivity.

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