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.

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

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.

scholarly journals Site-Selective Alkoxylation of Benzylic C–H Bonds via Photoredox Catalysis

2019 ◽  
Author(s):  
Byung Joo Lee ◽  
kimberly deglopper ◽  
Tehshik Yoon
Keyword(s):  
Late Stage ◽  
Functional Group ◽  
Bond Formation ◽  
Bioactive Molecules ◽  
Site Selectivity ◽  
Wide Range ◽  
High Site ◽  
Alkoxy Groups ◽  
Site Selective ◽  
Mediated Oxidation

<div> <div> <div> <p>There are relatively few methods that accom- plish the selective alkoxylation of sp3-hybridized C–H bonds, particularly in comparison to the numerous analogous strate- gies for C–N and C–C bond formation. We report a photo- catalytic protocol for the functionalization of benzylic C–H bonds with a wide range of readily available oxygen nucleo- philes. Our strategy merges the photoredox activation of arenes with copper(II)-mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C–O bonds with high site selectivity, chemoselectivity, and functional group tolerance. This method enables the late- stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential appli- cations in synthesis and medicinal chemistry. </p> </div> </div> </div>

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.

scholarly journals Site-Selective Alkoxylation of Benzylic C–H Bonds via Photoredox Catalysis

2019 ◽  
Author(s):  
Byung Joo Lee ◽  
kimberly deglopper ◽  
Tehshik Yoon
Keyword(s):  
Late Stage ◽  
Functional Group ◽  
Bond Formation ◽  
Bioactive Molecules ◽  
Site Selectivity ◽  
Wide Range ◽  
High Site ◽  
Alkoxy Groups ◽  
Site Selective ◽  
Mediated Oxidation

<div> <div> <div> <p>There are relatively few methods that accom- plish the selective alkoxylation of sp3-hybridized C–H bonds, particularly in comparison to the numerous analogous strate- gies for C–N and C–C bond formation. We report a photo- catalytic protocol for the functionalization of benzylic C–H bonds with a wide range of readily available oxygen nucleo- philes. Our strategy merges the photoredox activation of arenes with copper(II)-mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C–O bonds with high site selectivity, chemoselectivity, and functional group tolerance. This method enables the late- stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential appli- cations in synthesis and medicinal chemistry. </p> </div> </div> </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>

Palladium-catalyzed site-selective direct olefination of 6-electron-withdrawing group substituted 3-arylbenzo[d]isoxazoles

2017 ◽  
Vol 4 (10) ◽  
pp. 1962-1966 ◽  
Author(s):  
Ying Guo ◽  
Ling-Yan Shao ◽  
Kun-Kun Yu ◽  
Ya-Hua Hu ◽  
Hong-Wei Liu ◽  
...  
Keyword(s):  
Site Selectivity ◽  
Palladium Catalyzed ◽  
Electron Withdrawing Group ◽  
Site Selective

Palladium-catalyzed direct olefination of 6-electron-withdrawing group substituted 3-arylbenzo[d]isoxazoles has been developed with exclusive site-selectivity and excellent E-stereoselectivity.

scholarly journals Site-Selective Alkoxylation of Benzylic C–H Bonds via Photoredox Catalysis

2019 ◽  
Author(s):  
Byung Joo Lee ◽  
kimberly deglopper ◽  
Tehshik Yoon
Keyword(s):  
Late Stage ◽  
Functional Group ◽  
Bond Formation ◽  
Bioactive Molecules ◽  
Site Selectivity ◽  
Wide Range ◽  
High Site ◽  
Alkoxy Groups ◽  
Site Selective ◽  
Mediated Oxidation

<div> <div> <div> <p>There are relatively few methods that accom- plish the selective alkoxylation of sp3-hybridized C–H bonds, particularly in comparison to the numerous analogous strate- gies for C–N and C–C bond formation. We report a photo- catalytic protocol for the functionalization of benzylic C–H bonds with a wide range of readily available oxygen nucleo- philes. Our strategy merges the photoredox activation of arenes with copper(II)-mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C–O bonds with high site selectivity, chemoselectivity, and functional group tolerance. This method enables the late- stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential appli- cations in synthesis and medicinal chemistry. </p> </div> </div> </div>

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

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