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

Ying Guo; Ling-Yan Shao; Kun-Kun Yu; Ya-Hua Hu; Hong-Wei Liu; Dao-Hua Liao; Ya-Fei Ji

doi:10.1039/c7qo00435d

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

10.26434/chemrxiv.5717950 ◽

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 sp3 carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp3)–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(sp3)–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.

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

10.21203/rs.3.rs-1114441/v1 ◽

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.

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

Chemical Communications ◽

10.1039/c8cc00980e ◽

2018 ◽

Vol 54 (22) ◽

pp. 2759-2762 ◽

Cited By ~ 18

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.

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

Organic & Biomolecular Chemistry ◽

10.1039/c9ob00642g ◽

2019 ◽

Vol 17 (18) ◽

pp. 4465-4469 ◽

Cited By ~ 7

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

10.26434/chemrxiv.5717950.v1 ◽

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 sp3 carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp3)–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(sp3)–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.

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

10.26434/chemrxiv.11760519.v1 ◽

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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Remote C–H Functionalizations by Ruthenium Catalysis

Synthesis ◽

10.1055/a-1485-5156 ◽

2021 ◽

Author(s):

Korkit Korvorapun ◽

Ramesh C. Samanta ◽

Torben Rogge ◽

Lutz Ackermann

Keyword(s):

Steric Hindrance ◽

Late Stage ◽

Crop Protection ◽

Full Control ◽

Site Selectivity ◽

Important Approach ◽

Distinct Character ◽

Ruthenium Catalysis ◽

Material Sciences ◽

Site Selective

Synthetic transformations of otherwise inert C–H bonds have emerged as a powerful tool for molecular modifications during the last decades, with broad applications towards pharmaceuticals, material sciences and crop protection. Consistently, a key challenge in C–H activation chemistry is the full control of site-selectivity. In addition to substrate control through steric hindrance or kinetic acidity of C–H bonds, one important approach for the site-selective C–H transformation of arenes is the use of chelation-assistance through directing groups, therefore leading to proximity-induced ortho-C–H metalation. In contrast, more challenging remote C–H activations at the meta- or para-positions continue to be scarce. Within this review, we demonstrate the distinct character of ruthenium catalysis for remote C–H activations until March 2021, highlighting among others late-stage modifications of bio-relevant molecules. Moreover, we highlight important mechanistic insights by experiments and computation, highlighting the key importance of carboxylate-assisted C–H activation with ruthenium(II) complexes.

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Site-Selective [2+2+n] Cycloadditions for Rapid, Scalable Access to Alkynylated Polycyclic Aromatic Hydrocarbons

10.26434/chemrxiv.11309390 ◽

2019 ◽

Author(s):

Gavin R. Kiel ◽

Harrison Bergman ◽

T. Don Tilley

Keyword(s):

Polycyclic Aromatic Hydrocarbons ◽

Aromatic Hydrocarbons ◽

Structural Complexity ◽

Building Blocks ◽

Synthetic Methods ◽

Proof Of Concept ◽

Site Selectivity ◽

Polycyclic Aromatic ◽

Site Selective ◽

Nanometer Regime

Polycyclic aromatic hydrocarbons (PAHs) are attractive synthetic building blocks for more complex conjugated nanocarbons, but their use for this purpose requires appreciable quantities of a PAH with reactive functional groups. Despite tremendous recent advances, most synthetic methods cannot satisfy these demands. Here we present a general and scalable [2+2+n] (n = 1 or 2) cycloaddition strategy to access PAHs that are decorated with synthetically versatile alkynyl groups and its application to seven structurally diverse PAH ring systems (thirteen new alkynylated PAHs in total). The critical discovery is the site-selectivity of an Ir-catalyzed [2+2+2] cycloaddition, which preferentially cyclizes tethered diyne units with preservation of other (peripheral) alkynyl groups. The potential for generalization of the site-selectivity to other [2+2+n] reactions is demonstrated by identification of a Cp2Zr-mediated [2+2+1] / metallacycle transfer sequence for synthesis of an alkynylated, selenophene-annulated PAH. The new PAHs are excellent synthons for macrocyclic conjugated nanocarbons. As a proof of concept, four were subjected to Mo catalysis to afford large, PAH-containing arylene ethylene macrocycles, which possess a range of cavity sizes reaching well into the nanometer regime. More generally, this work is a demonstration of how site-selective reactions can be harnessed to rapidly build up structural complexity in a practical, scalable fashion.

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