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 Doubly Decarboxylative Synthesis of 4-(Pyridylmethyl)chroman-2-ones and 2-(Pyridylmethyl)chroman-4-ones under Mild Reaction Conditions

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4689
Author(s):  
Jan Bojanowski ◽  
Anna Albrecht
Keyword(s):  
Carboxylic Acids ◽  
Reaction Pathway ◽  
Base Catalysis ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Michael Type Addition ◽  
Brønsted Base

The doubly decarboxylative Michael–type addition of pyridylacetic acid to chromone-3-carboxylic acids or coumarin-3-carboxylic acids has been developed. This protocol has been realized under Brønsted base catalysis, providing biologically interesting 4-(pyridylmethyl)chroman-2-ones and 2-(pyridylmethyl)chroman-4-ones in good or very good yields. The decarboxylative reaction pathway has been confirmed by mechanistic studies. Moreover, attempts to develop an enantioselective variant of the cascade are also described.

scholarly journals Rapid Access to Diverse Potassium Acyltrifluoroborates (KATs) Through Late-Stage Chemoselective Cross-Coupling Reactions

2020 ◽  
Author(s):  
Xingwang Deng ◽  
Guan Zhou ◽  
Xiao Han ◽  
Khadim Ullah ◽  
Rajavel Srinivasan
Keyword(s):  
Late Stage ◽  
Materials Science ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Library Synthesis ◽  
Reaction Conditions ◽  
Cross Coupling Reactions ◽  
Rapid Diversification ◽  
High Yields ◽  
Opening Up

Potassium acyltrifluoroborates (KATs) are opening up new avenues in chemical biology, materials science and synthetic organic chemistry due to their intriguing reactivities. However, the synthesis of these compounds remains mostly complicated and time-consuming. This lack of a rapid and facile synthetic route has hindered the widespread adoption of KAT-based chemistry, especially in the areas of compound library synthesis and drug discovery. Herein, we have developed chemoselective Pd-catalyzed approaches for the late-stage diversification of arenes bearing pre-functionalized KATs. These approaches feature chemoselective cross-coupling, rapid diversification, functional group tolerance, mild reaction conditions, and high yields.

scholarly journals Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leitao Huan ◽  
Xiaomin Shu ◽  
Weisai Zu ◽  
De Zhong ◽  
Haohua Huo
Keyword(s):  
Carboxylic Acids ◽  
Organic Synthesis ◽  
Late Stage ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Photoredox Catalysis ◽  
Mechanistic Studies ◽  
Cross Coupling Reaction ◽  
Aryl Ketones ◽  
Alkyl Benzenes

AbstractAsymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.

scholarly journals Rapid Access to Diverse Potassium Acyltrifluoroborates (KATs) Through Late-Stage Chemoselective Cross-Coupling Reactions

2020 ◽  
Author(s):  
Xingwang Deng ◽  
Guan Zhou ◽  
Xiao Han ◽  
Khadim Ullah ◽  
Rajavel Srinivasan
Keyword(s):  
Late Stage ◽  
Materials Science ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Library Synthesis ◽  
Reaction Conditions ◽  
Cross Coupling Reactions ◽  
Rapid Diversification ◽  
High Yields ◽  
Opening Up

Potassium acyltrifluoroborates (KATs) are opening up new avenues in chemical biology, materials science and synthetic organic chemistry due to their intriguing reactivities. However, the synthesis of these compounds remains mostly complicated and time-consuming. This lack of a rapid and facile synthetic route has hindered the widespread adoption of KAT-based chemistry, especially in the areas of compound library synthesis and drug discovery. Herein, we have developed chemoselective Pd-catalyzed approaches for the late-stage diversification of arenes bearing pre-functionalized KATs. These approaches feature chemoselective cross-coupling, rapid diversification, functional group tolerance, mild reaction conditions, and high yields.

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 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 Iron Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines

2020 ◽  
Author(s):  
Ozgur YIlmaz ◽  
Cagatay Dengiz ◽  
Marion Emmert
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Functional Groups ◽  
Late Stage ◽  
Functional Group ◽  
Reaction Pathway ◽  
Catalyst System ◽  
Tertiary Amines ◽  
Reaction Conditions ◽  
Catalyst Synthesis

This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines as well as its application in late stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates as well as complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles, as well as ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms, and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.

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>

Nitrate promoted mild and versatile Pd-catalysed C(sp2)–H oxidation with carboxylic acids

2020 ◽  
Vol 18 (34) ◽  
pp. 6732-6737
Author(s):  
Xue Xiong ◽  
Yang-Jie Mao ◽  
Hong-Yan Hao ◽  
Yu-Ting He ◽  
Zhen-Yuan Xu ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Reaction Conditions ◽  
Aliphatic Acids

A nitrate-promoted Pd-catalysed cross-dehydrogenative C(sp2)–H oxidation of oximes or azobenzenes with diverse aromatic and aliphatic acids was developed, allowing the versatile formation of O-aryl esters under mild reaction conditions.

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>

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