Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

2019 ◽  
Author(s):  
Yu Kawamata ◽  
Julien Vantourout ◽  
David P. Hickey ◽  
Peng Bai ◽  
Longrui Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Second Generation ◽  
Cross Coupling ◽  
Aryl Halides ◽  
Catalytic Systems ◽  
Full Disclosure ◽  
Aryl Amination ◽  
Mechanistic Understanding

<div> <div> <div> <p>C–N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles, including complex examples on oligopeptides, medicinally-relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations as well as procedures for both batch and flow scale-ups (100 gram) are also described. </p> </div> </div> </div>

Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

2019 ◽  
Author(s):  
Yu Kawamata ◽  
Julien Vantourout ◽  
David P. Hickey ◽  
Peng Bai ◽  
Longrui Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Second Generation ◽  
Cross Coupling ◽  
Aryl Halides ◽  
Catalytic Systems ◽  
Full Disclosure ◽  
Aryl Amination ◽  
Mechanistic Understanding

<div> <div> <div> <p>C–N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles, including complex examples on oligopeptides, medicinally-relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations as well as procedures for both batch and flow scale-ups (100 gram) are also described. </p> </div> </div> </div>

2-Nitropyrrole cross-coupling enables a second generation synthesis of the heronapyrrole antibiotic natural product family

2016 ◽  
Vol 52 (85) ◽  
pp. 12638-12641 ◽  
Author(s):  
Xiao-Bo Ding ◽  
Daniel P. Furkert ◽  
Margaret A. Brimble
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Second Generation ◽  
Product Family ◽  
Cross Coupling

The heronapyrroles are a family of antibiotic natural products containing the rare 2-nitropyrrole motif.

scholarly journals Electrochemical Organic Synthesis of Electron-Rich Biaryl Scaffolds: An Update

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6968
Author(s):  
Fabrizio Medici ◽  
Simonetta Resta ◽  
Alessandra Puglisi ◽  
Sergio Rossi ◽  
Laura Raimondi ◽  
...  
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Cross Coupling ◽  
Therapeutic Agents ◽  
The Other ◽  
Present Review ◽  
Single Class ◽  
Efficient Alternative ◽  
Privileged Class

Biaryl scaffolds are widely spread in biologically important natural products, in numerous therapeutic agents, but they are also considered a privileged class of ligands and (organo)catalysts; therefore, the development of efficient alternative methodologies to prepare such compounds is always attracting much attention. The present review discusses the organic electrosynthesis of biaryls starting from phenols, anilines, naphthols, and naphthylamines. The most significant examples of the works reported in the last decade are presented and classified according to the single class of molecules: after the introduction, the first three sections relate to the reactions of phenols, naphthols, and anilines, respectively; the other two sections refer to cross-coupling and miscellaneous reactions.

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

scholarly journals Mechanistic Studies of the Oxidative Addition of Aryl Halides to Ni(0) Centers Bearing Phosphine Ligands

2020 ◽  
Vol 74 (6) ◽  
pp. 495-498
Author(s):  
Pablo Marcelo Pérez-García ◽  
Marc-Etienne Moret
Keyword(s):  
Significant Influence ◽  
Oxidative Addition ◽  
Cross Coupling ◽  
Phosphine Ligands ◽  
Aryl Halides ◽  
Entry Point ◽  
Mechanistic Studies ◽  
Recent Advances ◽  
Mechanistic Understanding ◽  
Catalytic Cycles

The oxidative addition of aryl halides is a common entry point in catalytic cycles for cross-coupling and related reactions. In the case of phosphine-supported nickel(0) fragments, the formation of reactive Ni(ii)–aryl products often competes with the production of Ni(i) species. Here, recent advances in the mechanistic understanding of these reactions are highlighted. In particular, the denticity of the supporting ligand has a significant influence on the outcome of the reaction.

Carbon-Heteroatom Cross-Coupling via an Electronically Excited Nickel (II) Complex

2019 ◽  
Author(s):  
Randolph Escobar ◽  
Jeffrey Johannes
Keyword(s):  
Energy Transfer ◽  
Functional Groups ◽  
Cross Coupling ◽  
Reductive Elimination ◽  
Aryl Halides ◽  
Coupling Reactions ◽  
General Methodology ◽  
Cross Coupling Reactions ◽  
Electronically Excited ◽  
Energy Transfer Pathway

<div>While carbon-heteroatom cross coupling reactions have been extensively studied, many methods are specific and</div><div>limited to a set of substrates or functional groups. Reported here is a method that allows for C-O, C-N and C-S cross coupling reactions under one general methodology. We propose that an energy transfer pathway, in which an iridium photosensitizer produces an excited nickel (II) complex, is responsible for the key reductive elimination step that couples aryl halides to 1° and 2° alcohols, anilines, thiophenols, carbamates and sulfonamides.</div>

Microwave Assisted Organic Synthesis: Cross Coupling and Multicomponent Reactions

2013 ◽  
Vol 17 (5) ◽  
pp. 474-490 ◽  
Author(s):  
Amit Kumar Gupta ◽  
Neetu Singh ◽  
Krishna Nand Singh
Keyword(s):  
Organic Synthesis ◽  
Multicomponent Reactions ◽  
Cross Coupling ◽  
Microwave Assisted
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