scholarly journals Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jia-Wang Wang ◽  
Yan Li ◽  
Wan Nie ◽  
Zhe Chang ◽  
Zi-An Yu ◽  
...  
Keyword(s):  
Catalytic Amount ◽  
Ester Group ◽  
Aliphatic Amines ◽  
Chiral Amines ◽  
Chiral Auxiliaries ◽  
Bioactive Natural Products ◽  
Chiral Carbon ◽  
Alkyl Electrophiles ◽  
Synthetic Intermediates ◽  
Pharmaceutical Agents

AbstractTo increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C–H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.

scholarly journals Catalytic Asymmetric Reductive Alkylation of Enamines to Chiral Aliphatic Amines

2020 ◽  
Author(s):  
Jia-Wang Wang ◽  
Yan Li ◽  
Wan Nie ◽  
Zhe Chang ◽  
Zi-An Yu ◽  
...  
Keyword(s):  
Bond Formation ◽  
Catalytic Amount ◽  
Aliphatic Amines ◽  
Chiral Amines ◽  
Reductive Alkylation ◽  
Alkyl Electrophiles ◽  
Catalytic Asymmetric

<p>Herein, we report a mild and general nickel-catalysed asymmetric reductive alkylation to effectively convert enamines—a class of important yet underexploited feedstock chemicals—into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamine to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.</p>

scholarly journals Catalytic Asymmetric Reductive Alkylation of Enamines to Chiral Aliphatic Amines

2020 ◽  
Author(s):  
Jia-Wang Wang ◽  
Yan Li ◽  
Wan Nie ◽  
Zhe Chang ◽  
Zi-An Yu ◽  
...  
Keyword(s):  
Bond Formation ◽  
Catalytic Amount ◽  
Aliphatic Amines ◽  
Chiral Amines ◽  
Reductive Alkylation ◽  
Alkyl Electrophiles ◽  
Catalytic Asymmetric

<p>Herein, we report a mild and general nickel-catalysed asymmetric reductive alkylation to effectively convert enamines—a class of important yet underexploited feedstock chemicals—into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamine to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.</p>

Copper Catalyzed sp3 C-H α-Acetylation

2019 ◽  
Author(s):  
Otome Okoromoba ◽  
Eun Sil Jang ◽  
Claire McMullin ◽  
Thomas Cundari ◽  
Timothy H. Warren
Keyword(s):  
Natural Products ◽  
Dft Studies ◽  
Alkyl Radicals ◽  
Important Chemical ◽  
Alkyl Electrophiles ◽  
Synthetic Intermediates ◽  
Alkylation Reactions

<p>α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp<sup>3</sup> C-H α-acetylation of sp<sup>3</sup> C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH<sub>2</sub>R at RT with <sup>t</sup>BuOO<sup>t</sup>Bu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [Cu<sup>II</sup>](CH<sub>2</sub>C(O)Ar) that capture alkyl radicals R• to give R-CH<sub>2</sub>C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH<sub>2</sub>CH<sub>2</sub>C(O)Ar.</p>

Copper Catalyzed sp3 C-H α-Acetylation

2019 ◽  
Author(s):  
Otome Okoromoba ◽  
Eun Sil Jang ◽  
Claire McMullin ◽  
Thomas Cundari ◽  
Timothy H. Warren
Keyword(s):  
Natural Products ◽  
Dft Studies ◽  
Alkyl Radicals ◽  
Important Chemical ◽  
Alkyl Electrophiles ◽  
Synthetic Intermediates ◽  
Alkylation Reactions

<p>α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp<sup>3</sup> C-H α-acetylation of sp<sup>3</sup> C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH<sub>2</sub>R at RT with <sup>t</sup>BuOO<sup>t</sup>Bu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [Cu<sup>II</sup>](CH<sub>2</sub>C(O)Ar) that capture alkyl radicals R• to give R-CH<sub>2</sub>C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH<sub>2</sub>CH<sub>2</sub>C(O)Ar.</p>

Glucose - and Allose-Derived Chiral Auxiliaries

2019 ◽  
Vol 800 ◽  
pp. 36-41
Author(s):  
Evija Rolava ◽  
Jevgeņija Lugiņina ◽  
Māris Turks
Keyword(s):  
Asymmetric Synthesis ◽  
Bioactive Compounds ◽  
Heterocyclic Compounds ◽  
Biologically Active ◽  
Important Class ◽  
Chiral Auxiliaries ◽  
Asymmetric Alkylation ◽  
Pharmaceutical Agents

Oxazolidinones are an important class of heterocyclic compounds that are used as chiral auxiliaries in asymmetric synthesis and as biologically active pharmaceutical agents. Moreover, carbohydrates are ideal scaffolds to generate libraries of bioactive compounds due the presence of defined configuration. We report here asymmetric alkylation studies on N-derivatized glucose-and allose-based spirooxazolidinones which do act as chiral auxiliaries.

Recent Advances in Photocatalytic C–N Bond Coupling Reactions

Synthesis ◽  
2020 ◽  
Author(s):  
Wing-Yiu Yu ◽  
Chun-Ming Chan ◽  
Yip-Chi Chow
Keyword(s):  
Carbonyl Compounds ◽  
Bond Formation ◽  
Coupling Reactions ◽  
Amino Groups ◽  
Cyclization Reactions ◽  
Radical Coupling ◽  
Synthetic Intermediates ◽  
Photocatalytic Reactions ◽  
Metal Catalyzed ◽  
Pharmaceutical Agents

Catalytic C–N bond formation is one of the major research topics in synthetic chemistry owing to the ubiquity of amino groups in natural products, synthetic intermediates and pharmaceutical agents. In parallel with well-established metal-catalyzed C–N bond coupling protocols, photocatalytic reactions have recently emerged as efficient and selective alternatives for the construction of C–N bonds. In this review, the progress made on photocatalytic C–N bond coupling reactions between 2012 and February 2020 is summarized.1 Introduction1.1 General Mechanisms for Photoredox Catalysis1.2 Pioneering Work2 C(sp2)–N Bond Formation2.1 Protocols Involving an External Oxidant2.2 Oxidant-Free Protocols3 C(sp3)–N Bond Formation3.1 Direct Radical–Radical Coupling3.2 Addition Reactions to Alkenes3.3 Reductive Amination of Carbonyl Compounds3.4 Decarboxylative Amination4 Cyclization Reactions4.1 C(sp2)–N Heterocycle Formation4.2 C(sp3)–N Heterocycle Formation5 Other Examples6 Conclusion and Outlook

Efficient Synthesis of Thieno [2,3-d] Pyrimidin-4(4H)-ones by the Aza-Wittig Methodology

2012 ◽  
Vol 455-456 ◽  
pp. 655-659
Author(s):  
Hong Chen ◽  
Kai Yan ◽  
Ming Guo Liu
Keyword(s):  
Wittig Reaction ◽  
Catalytic Amount ◽  
Aliphatic Amines ◽  
Efficient Synthesis ◽  
Sodium Alkoxide

The carbodiimides 4, obtained from the aza-Wittig reaction of iminophosphorane 3 with aromatic isocyanates, reacted with aliphatic amines or alcohols to give 2-substituted thieno [2,3-d] pyrimidin-4(4H)-ones 6 in the presence of catalytic amount of sodium alkoxide in good yields.

scholarly journals Alkynyl Triazenes Enable Divergent Syntheses of 2-Pyrones

2021 ◽  
Author(s):  
Jin-Fay Tan ◽  
Carl Thomas Bormann ◽  
Kay Severin ◽  
Nicolai Cramer
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Bioactive Natural Products ◽  
Synthetic Intermediates

The 2-pyrone motif occurs frequently in bioactive natural products and is appreciated as synthetic intermediates. However, only few methods allow for diversifying functional group modifications on this relevant heterocycle. The...

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