Site-Selective C−H Bond Functionalization of Chromones and Coumarins

2018 ◽  
Vol 7 (7) ◽  
pp. 1136-1150 ◽  
Author(s):  
Dahye Kang ◽  
Kukcheol Ahn ◽  
Sungwoo Hong
Keyword(s):  
Bond Functionalization ◽  
Site Selective

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>

Highly Site-Selective Direct C−H Bond Functionalization of Unactivated Arenes with Propargyl α‑Aryl-α-diazoacetates via Scandium Catalysis

2021 ◽  
Author(s):  
Balu S. Navale ◽  
Debasish Laha ◽  
Subhrashis Banerjee ◽  
Kumar Vanka ◽  
Prof. Dr. Ramakrishna G. Bhat
Keyword(s):  
The Novel ◽  
Bond Functionalization ◽  
Site Selective

<p>Highly chemo- and regio-selective C–H bond functionalization of unactivated arenes with propargyl <i>α</i>-aryl-<i>α</i>-diazoacetates is developed using scandium catalysis. Variety of unactivated, mildly deactivated and electronically activated arenes are functionalized using this protocol. We have explored the novel combination of scandium triflate and propargyl <i>α</i>-aryl-<i>α</i>-diazoacetate as catalyst-reagent system for the effective C–H bond functionalization. The protocol avoids the use of expensive catalysts and practicality of the protocol has been demonstrated by the gram scale synthesis of very useful <i>α</i>-diarylacetates including antispasmodic drug-adephenine.</p>

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

scholarly journals Design principles for site-selective hydroxylation by a Rieske oxygenase

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianxin Liu ◽  
Jiayi Tian ◽  
Christopher Perry ◽  
April L. Lukowski ◽  
Tzanko I. Doukov ◽  
...  
Keyword(s):  
Structural Information ◽  
Diverse Range ◽  
Bond Functionalization ◽  
Site Selectivity ◽  
Site Selective ◽  
Common Architecture ◽  
Rieske Oxygenase ◽  
Rieske Oxygenases ◽  
Native Site ◽  
Selective Hydroxylation

AbstractRieske oxygenases exploit the reactivity of iron to perform chemically challenging C–H bond functionalization reactions. Thus far, only a handful of Rieske oxygenases have been structurally characterized and remarkably little information exists regarding how these enzymes use a common architecture and set of metallocenters to facilitate a diverse range of reactions. Herein, we detail how two Rieske oxygenases SxtT and GxtA use different protein regions to influence the site-selectivity of their catalyzed monohydroxylation reactions. We present high resolution crystal structures of SxtT and GxtA with the native β-saxitoxinol and saxitoxin substrates bound in addition to a Xenon-pressurized structure of GxtA that reveals the location of a substrate access tunnel to the active site. Ultimately, this structural information allowed for the identification of six residues distributed between three regions of SxtT that together control the selectivity of the C–H hydroxylation event. Substitution of these residues produces a SxtT variant that is fully adapted to exhibit the non-native site-selectivity and substrate scope of GxtA. Importantly, we also found that these selectivity regions are conserved in other structurally characterized Rieske oxygenases, providing a framework for predictively repurposing and manipulating Rieske oxygenases as biocatalysts.

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>

Asymmetric remote C–H borylation of aliphatic amides and esters with a modular iridium catalyst

Science ◽  
2020 ◽  
Vol 369 (6506) ◽  
pp. 970-974 ◽  
Author(s):  
Ronald L. Reyes ◽  
Miyu Sato ◽  
Tomohiro Iwai ◽  
Kimichi Suzuki ◽  
Satoshi Maeda ◽  
...  
Keyword(s):  
Quantum Chemical ◽  
Noncovalent Interactions ◽  
Saturated Hydrocarbon ◽  
Receptor Ligand ◽  
Bond Functionalization ◽  
Iridium Catalyst ◽  
Site Selectivity ◽  
Synthetic Utility ◽  
Tertiary Amides ◽  
Site Selective

Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

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