scholarly journals Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of -Aryl Nitriles – Role of a Chlorosilane Additive

2021 ◽  
Author(s):  
Nick Michel ◽  
Racquel Edjoc ◽  
Emmanuel Fagbola ◽  
Jonathan Hughes ◽  
Louis-Charles Campeau ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Pharmaceutical Sciences ◽  
Mechanistic Studies ◽  
Cyanoacetic Acid ◽  
Radical Intermediate ◽  
Reaction Conditions ◽  
Redox Active ◽  
Aryl Nitriles ◽  
Ester Substrate

<div><p>A nickel-catalyzed reductive cross-coupling of redox-active <i>N</i>-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted a-aryl nitriles, an important scaffold in pharmaceutical sciences. Mechanistic studies reveal that decarboxylation of the NHP ester to the reactive radical intermediate is accomplished by a combination of a chlorosilane additive and Zn dust. The reaction exhibits a broad scope as many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents.</p></div>

scholarly journals Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of α-Aryl Nitriles – Role of a Chlorosilane Additive

2021 ◽  
Author(s):  
Nick Michel ◽  
Racquel Edjoc ◽  
Emmanuel Fagbola ◽  
Jonathan Hughes ◽  
Louis-Charles Campeau ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Pharmaceutical Sciences ◽  
Mechanistic Studies ◽  
Cyanoacetic Acid ◽  
Radical Intermediate ◽  
Reaction Conditions ◽  
Redox Active ◽  
Aryl Nitriles ◽  
Ester Substrate

<p>A nickel-catalyzed reductive cross-coupling of redox-active <i>N</i>-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in pharmaceutical sciences. Mechanistic studies reveal that decarboxylation of the NHP ester to the reactive radical intermediate is accomplished by a combination of a chlorosilane additive and Zn dust. The reaction exhibits a broad scope as many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents.</p>

scholarly journals Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of α-Aryl Nitriles – Role of a Chlorosilane Additive

2021 ◽  
Author(s):  
Nick Michel ◽  
Racquel Edjoc ◽  
Emmanuel Fagbola ◽  
Jonathan Hughes ◽  
Louis-Charles Campeau ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Pharmaceutical Sciences ◽  
Mechanistic Studies ◽  
Cyanoacetic Acid ◽  
Radical Intermediate ◽  
Reaction Conditions ◽  
Redox Active ◽  
Aryl Nitriles ◽  
Ester Substrate

<p>A nickel-catalyzed reductive cross-coupling of redox-active <i>N</i>-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in pharmaceutical sciences. Mechanistic studies reveal that decarboxylation of the NHP ester to the reactive radical intermediate is accomplished by a combination of a chlorosilane additive and Zn dust. The reaction exhibits a broad scope as many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents.</p>

scholarly journals Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhan Li ◽  
Ke-Feng Wang ◽  
Xin Zhao ◽  
Huihui Ti ◽  
Xu-Ge Liu ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Late Stage ◽  
Materials Science ◽  
Reaction Pathway ◽  
Chemical Conversion ◽  
Primary Amines ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Aliphatic Acids ◽  
Redox Active

Abstract Alkyl carboxylic acids as well as primary amines are ubiquitous in all facets of biological science, pharmaceutical science, chemical science and materials science. By chemical conversion to redox-active esters (RAE) and Katritzky’s N-alkylpyridinium salts, respectively, alkyl carboxylic acids and primary amines serve as ideal starting materials to forge new connections. In this work, a Mn-mediated reductive decarboxylative/deaminative functionalization of activated aliphatic acids and primary amines is disclosed. A series of C-X (X = S, Se, Te, H, P) and C-C bonds are efficiently constructed under simple and mild reaction conditions. The protocol is applicable to the late-stage modification of some structurally complex natural products or drugs. Preliminary mechanistic studies suggest the involvement of radicals in the reaction pathway.

scholarly journals The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp3)–O Arylation

2020 ◽  
Author(s):  
Reginald Mills ◽  
John. J. Monteith ◽  
Sophie Rousseaux
Keyword(s):  
Cyclopropane Ring ◽  
Catalytic Cycle ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Design And Optimization ◽  
Redox Active ◽  
Leaving Group

<div><p>The ability to understand and predict reactivity is highly important for the development of new reactions. In the context of Ni-catalyzed C(sp<sup>3</sup>)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C(sp<sup>3</sup>)–O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active, and are consistent with a Ni(I)/Ni(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.</p></div>

scholarly journals Chemodivergent assembly of ortho-functionalized phenols with tunable selectivity via rhodium(III)-catalyzed and solvent-controlled C-H activation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Haiman Zhang ◽  
Shuang Lin ◽  
Hui Gao ◽  
Kaixin Zhang ◽  
Yi Wang ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Building Blocks ◽  
Allyl Ether ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Intramolecular Nucleophilic Substitution ◽  
Fixed Catalyst ◽  
Synthetic Approaches ◽  
Active Intermediates ◽  
Coupling Partner

AbstractOrtho-functionalized phenols and their derivatives represent prominent structural motifs and building blocks in medicinal and synthetic chemistry. While numerous synthetic approaches exist, the development of atom-/step-economic and practical methods for the chemodivergent assembly of diverse ortho-functionalized phenols based on fixed catalyst/substrates remains challenging. Here, by selectively controlling the reactivities of different sites in methylenecyclopropane core, Rh(III)-catalyzed redox-neutral and tunable C-H functionalizations of N-phenoxyacetamides are realized, providing access to both ortho-functionalized phenols bearing linear dienyl, cyclopropyl or allyl ether groups, and cyclic 3-ethylidene 2,3-dihydrobenzofuran frameworks under mild cross-coupling conditions. These divergent transformations feature broad substrate compatibility, synthetic applications and excellent site-/regio-/chemoselectivity. Experimental and computational mechanistic studies reveal that distinct catalytic modes involving selective β-C/β-H elimination, π-allylation, inter-/intramolecular nucleophilic substitution cascade and β-H’ elimination processes enabled by different solvent-mediated and coupling partner-controlled reaction conditions are crucial for achieving chemodivergence, among which a structurally distinct Rh(V) species derived from a five-membered rhodacycle is proposed as the corresponding active intermediates.

Transition-Metal-Free Synthesis of Thiosulfonates through Radical Coupling Reaction

Synlett ◽  
2018 ◽  
Vol 29 (15) ◽  
pp. 2076-2080 ◽  
Author(s):  
Wen-Ting Wei ◽  
Zhiyong Guo ◽  
Guodong Zhou ◽  
Xu-Dong Xu ◽  
Gan-Ping Chen
Keyword(s):  
Transition Metal ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Coupling Process ◽  
Metal Free ◽  
Radical Coupling ◽  
Radical Coupling Reaction ◽  
High Yields

An efficient and practical transition-metal-free radical ­coupling reaction of sulfonyl hydrazides mediated by NIS/K2S2O8 has been developed to afford a variety of biological activity thiosulfonates in moderate to excellent yields. Compared to a known approach for the synthesis of thiosulfonates from sulfonyl hydrazides, this strategy features high yields, mild reaction conditions, and broad substrate scope. The mechanistic studies revealed that the procedure undergoes via a radical cross-coupling process for the construction of S–S bonds.

scholarly journals The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp3)–O Arylation

2020 ◽  
Author(s):  
Reginald Mills ◽  
John. J. Monteith ◽  
Sophie Rousseaux
Keyword(s):  
Cyclopropane Ring ◽  
Catalytic Cycle ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Design And Optimization ◽  
Redox Active ◽  
Leaving Group

<div><p>The ability to understand and predict reactivity is highly important for the development of new reactions. In the context of Ni-catalyzed C(sp<sup>3</sup>)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C(sp<sup>3</sup>)–O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active, and are consistent with a Ni(I)/Ni(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.</p></div>

Suzuki–Miyaura cross-coupling for chemoproteomic applications

2020 ◽  
Author(s):  
Jian Cao ◽  
Ernest Armenta ◽  
Lisa Boatner ◽  
Heta Desai ◽  
Neil Chan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cross Coupling ◽  
Protein Profiling ◽  
Protein Labeling ◽  
Caspase 8 ◽  
Complex Cell ◽  
Bioorthogonal Chemistry ◽  
Reaction Conditions ◽  
Target Deconvolution ◽  
Palladium Catalyzed

Bioorthogonal chemistry is a mainstay of chemoproteomic sample preparation workflows. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper-catalyzed azide –alkyne cycloaddition (CuAAC) or 'click' chemistry. Here we demonstrate that gel-based activity-based protein profiling (ABPP) and mass-spectrometry-based chemoproteomic profiling can be conducted using Suzuki–Miyaura cross-coupling. We identify reaction conditions that proceed in complex cell lysates and find that Suzuki –Miyaura cross-coupling and CuAAC yield comparable chemoproteomic coverage. Importantly, Suzuki–Miyaura is also compatible with chemoproteomic target deconvolution, as demonstrated using structurally matched probes tailored to react with the cysteine protease caspase-8. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual protein labeling.

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