Radical-clock α-halo-esters as mechanistic probes for bisphosphine iron-catalyzed cross-coupling reactions

Cross-coupling between substrates that can be easily derived from phenols is highly attractive due to the abundance and low cost of phenols. Here, we report a dual nickel/palladium-catalyzed reductive cross-coupling between aryl tosylates and aryl triflates; both substrates can be accessed in just one step from readily available phenols. The reaction has a broad functional group tolerance and substrate scope (>60 examples). Furthermore, it displays low sensitivity to steric effects demonstrated by the synthesis of a 2,2’disubstituted biaryl and a fully substituted aryl product. The widespread presence of phenols in natural products and pharmaceuticals allow for straightforward late-stage functionalization, illustrated with examples such as Ezetimibe and tyrosine. NMR spectroscopy and DFT calculations indicate that the nickel catalyst is responsible for activating the aryl triflate, while the palladium catalyst preferentially reacts with the aryl tosylate.

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An Iron-Based Catalyst Enables The Enantioconvergent Synthesis of Chiral 1,1-Diarylalkanes Through a Suzuki-Miyaura Cross-Coupling Reaction

10.26434/chemrxiv.12582284.v1 ◽

2020 ◽

Author(s):

Chet Tyrol ◽

Nang Yone ◽

Connor Gallin ◽

Jeffery Byers

Keyword(s):

Coupling Reaction ◽

Cross Coupling ◽

Coupling Reactions ◽

Radical Intermediates ◽

Cross Coupling Reactions ◽

Cross Coupling Reaction ◽

Boronic Esters ◽

Carbon Centered Radical ◽

Iron Based ◽

High Yields

By using an iron-based catalyst, access to enantioenriched 1,1-diarylakanes was enabled through an enantioselective Suzuki-Miyaura crosscoupling reaction. The combination of a chiral cyanobis(oxazoline) ligand framework and 1,3,5-trimethoxybenzene additive were essential to afford high yields and enantioselectivities in cross-coupling reactions between unactivated aryl boronic esters and a variety of benzylic chlorides, including challenging ortho-substituted benzylic chloride substrates. Mechanistic investigations implicate a stereoconvergent pathway involving carbon-centered radical intermediates.

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Phosphino-Triazole Ligands for Palladium-Catalysed Cross-Coupling

10.26434/chemrxiv.6823259 ◽

2018 ◽

Author(s):

Yiming Zhao ◽

Huy van Nguyen ◽

Louise Male ◽

Philip Craven ◽

Benjamin R. Buckley ◽

...

Keyword(s):

Drug Discovery ◽

Cross Coupling ◽

Product Formation ◽

Coupling Reactions ◽

Volume Determination ◽

Online Tool ◽

Triazole Derivatives ◽

Cross Coupling Reactions ◽

Modelling Approaches

<div>Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesised and used as ligands for palladium-catalysed Suzuki-Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca 2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD obtained data in a small number of cases proved to be informative. Two modelling approaches were compared for the determination of</div><div>the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki-Miyaura cross-coupling products, from which ten of the most lead-like were successfully synthesised. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimisation in drug discovery campaigns.</div>

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A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

10.26434/chemrxiv.7553444.v1 ◽

2019 ◽

Author(s):

Victor Bloemendal ◽

Floris P. J. T. Rutjes ◽

Thomas J. Boltje ◽

Daan Sondag ◽

Hidde Elferink ◽

...

Keyword(s):

Biological Activity ◽

Late Stage ◽

Medicinal Chemistry ◽

Cross Coupling ◽

Modular Approach ◽

Coupling Reactions ◽

One Pot ◽

Biologically Relevant ◽

Cross Coupling Reactions ◽

Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

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

10.26434/chemrxiv.9736049.v1 ◽

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>

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2,3-Dichloroquinoxaline in Cross-coupling Reactions: A Single Substrate, Many Possibilities

Current Organic Chemistry ◽

10.2174/1385272822666180806104824 ◽

2018 ◽

Vol 22 (16) ◽

pp. 1573-1588 ◽

Cited By ~ 3

Author(s):

Jannyely M. Neri ◽

Andre H. de Oliveira ◽

Renata M. Araujo ◽

Livia N. Cavalcanti ◽

Fabricio G. Menezes

Keyword(s):

Cross Coupling ◽

Coupling Reactions ◽

Cross Coupling Reactions ◽

Single Substrate

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Research Progress on Cross-coupling Reactions of Alkenylaluminum with Electrophilic Reagents

Current Organic Chemistry ◽

10.2174/1385272822666180704143509 ◽

2018 ◽

Vol 22 (15) ◽

pp. 1523-1535 ◽

Cited By ~ 2

Author(s):

Qing Han Li ◽

Xue Bei Shao ◽

Yong Ding ◽

Chang Wen ◽

Zhi Gang Zhao

Keyword(s):

Cross Coupling ◽

Research Progress ◽

Coupling Reactions ◽

Cross Coupling Reactions ◽

Electrophilic Reagents

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Monodentate Trialkylphosphines: Privileged Ligands in Metal-catalyzed Crosscoupling Reactions

Current Organic Chemistry ◽

10.2174/1385272824666200211114540 ◽

2020 ◽

Vol 24 (3) ◽

pp. 231-264 ◽

Cited By ~ 3

Author(s):

Kevin H. Shaughnessy

Keyword(s):

Transition Metal ◽

Cross Coupling ◽

Coupling Reactions ◽

Cross Coupling Reactions ◽

Aryl Bromides ◽

Wide Range ◽

Sterically Demanding ◽

Transition Metal Catalyzed ◽

Catalyzed Reactions ◽

Metal Catalyzed

Phosphines are widely used ligands in transition metal-catalyzed reactions. Arylphosphines, such as triphenylphosphine, were among the first phosphines to show broad utility in catalysis. Beginning in the late 1990s, sterically demanding and electronrich trialkylphosphines began to receive attention as supporting ligands. These ligands were found to be particularly effective at promoting oxidative addition in cross-coupling of aryl halides. With electron-rich, sterically demanding ligands, such as tri-tertbutylphosphine, coupling of aryl bromides could be achieved at room temperature. More importantly, the less reactive, but more broadly available, aryl chlorides became accessible substrates. Tri-tert-butylphosphine has become a privileged ligand that has found application in a wide range of late transition-metal catalyzed coupling reactions. This success has led to the use of numerous monodentate trialkylphosphines in cross-coupling reactions. This review will discuss the general properties and features of monodentate trialkylphosphines and their application in cross-coupling reactions of C–X and C–H bonds.

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