scholarly journals Active Ester Functionalized Azobenzenes as Versatile Building Blocks

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3916
Author(s):  
Sven Schultzke ◽  
Melanie Walther ◽  
Anne Staubitz
Keyword(s):  
Material Science ◽  
Biological Systems ◽  
Cross Coupling ◽  
Molecular Switches ◽  
Building Blocks ◽  
Coupling Method ◽  
Primary Amines ◽  
Mild Conditions ◽  
Active Ester

Azobenzenes are important molecular switches that can still be difficult to functionalize selectively. A high yielding Pd-catalyzed cross-coupling method under mild conditions for the introduction of NHS esters to azobenzenes and diazocines has been established. Yields were consistently high with very few exceptions. The NHS functionalized azobenzenes react with primary amines quantitatively. These amines are ubiquitous in biological systems and in material science.

Enantioselective C(sp3)–C(sp3) Cross-Coupling of Non-activated Alkyl Electrophiles via Nickel Hydride Catalysis

2020 ◽  
Author(s):  
Srikrishna Bera ◽  
Runze Mao ◽  
Xile Hu
Keyword(s):  
Organic Molecules ◽  
Functional Group ◽  
Cross Coupling ◽  
Building Blocks ◽  
Carbon Centers ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Nickel Hydride ◽  
Alkyl Electrophiles ◽  
Attractive Candidate

Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp<sup>3</sup>-hydridized carbon centers, which are attractive candidate compounds in drug discovery. Enantioselective C(sp<sup>3</sup>)-C(sp<sup>3</sup>) coupling, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl) is challenging. Here we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalyzed alkyl-alkyl coupling. This strategy enables enantioselective cross-coupling of non-activated alkyl iodides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional group tolerance. Applications in late-stage functionalization of natural products and drug molecules, synthesis of chiral building blocks, and enantioselective formal synthesis of (<i>S</i>)-(+)-Pregabalin are demonstrated.<br>

scholarly journals Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

2019 ◽  
Author(s):  
Van Tran ◽  
Zi-Qi Li ◽  
Timothy Gallagher ◽  
Joseph Derosa ◽  
Peng Liu ◽  
...  
Keyword(s):  
Organic Synthesis ◽  
Cross Coupling ◽  
Building Blocks ◽  
Reductive Elimination ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Wide Range ◽  
Directing Group ◽  
Weakly Coordinating ◽  
Analogous Method

Allylation and conjunctive cross-coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel-catalyzed conjunctive cross-coupling with a non-conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate azaheterocycle directing groups, that useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated in the facile reactivity of the β-γ alkene of the starting material, while the ε-ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of analogous method with alkyne substrates. Mechanistic studies reveal the importance of the weakly coordinating directing group in dissociating to allow binding of the allyl moiety to facilitate C(sp<sup>3</sup>)–C(sp<sup>3</sup>) reductive elimination.

scholarly journals Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

2019 ◽  
Author(s):  
Van Tran ◽  
Zi-Qi Li ◽  
Timothy Gallagher ◽  
Joseph Derosa ◽  
Peng Liu ◽  
...  
Keyword(s):  
Organic Synthesis ◽  
Cross Coupling ◽  
Building Blocks ◽  
Reductive Elimination ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Wide Range ◽  
Directing Group ◽  
Weakly Coordinating ◽  
Analogous Method

Allylation and conjunctive cross-coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel-catalyzed conjunctive cross-coupling with a non-conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate azaheterocycle directing groups, that useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated in the facile reactivity of the β-γ alkene of the starting material, while the ε-ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of analogous method with alkyne substrates. Mechanistic studies reveal the importance of the weakly coordinating directing group in dissociating to allow binding of the allyl moiety to facilitate C(sp<sup>3</sup>)–C(sp<sup>3</sup>) reductive elimination.

Enantioselective C(sp3)–C(sp3) Cross-Coupling of Non-activated Alkyl Electrophiles via Nickel Hydride Catalysis

2020 ◽  
Author(s):  
Srikrishna Bera ◽  
Runze Mao ◽  
Xile Hu
Keyword(s):  
Organic Molecules ◽  
Functional Group ◽  
Cross Coupling ◽  
Building Blocks ◽  
Carbon Centers ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Nickel Hydride ◽  
Alkyl Electrophiles ◽  
Attractive Candidate

Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp<sup>3</sup>-hydridized carbon centers, which are attractive candidate compounds in drug discovery. Enantioselective C(sp<sup>3</sup>)-C(sp<sup>3</sup>) coupling, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl) is challenging. Here we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalyzed alkyl-alkyl coupling. This strategy enables enantioselective cross-coupling of non-activated alkyl iodides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional group tolerance. Applications in late-stage functionalization of natural products and drug molecules, synthesis of chiral building blocks, and enantioselective formal synthesis of (<i>S</i>)-(+)-Pregabalin are demonstrated.<br>

scholarly journals Nickel-Catalyzed Asymmetric Reductive Cross-Coupling of a-Chloroesters with (Hetero)Aryl Iodides

2021 ◽  
Author(s):  
Travis DeLano ◽  
Sara Dibrell ◽  
Caitlin Lacker ◽  
Adam Pancoast ◽  
kelsey poremba ◽  
...  
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Functional Groups ◽  
Linear Regression Model ◽  
Cross Coupling ◽  
Building Blocks ◽  
Multivariate Linear Regression Model ◽  
Mild Conditions ◽  
Aryl Iodides ◽  
Reaction Proceeds

<a></a><a>An asymmetric reductive cross-coupling of alpha-chloroesters and (hetero)aryl iodides is reported. This nickel-catalyzed reaction proceeds with a chiral BiOX ligand under mild conditions, affording alpha-arylesters in good yields and enantioselectivities. The reaction is tolerant of a variety of functional groups, and the resulting products can be converted to pharmaceutically-relevant chiral building blocks</a>. A multivariate linear regression model was developed to quantitatively relate the influence of the alpha-chloroester substrate and ligand on enantioselectivity

C–O Bond Activation as a Strategy in Palladium-Catalyzed Cross-Coupling

Synlett ◽  
2020 ◽  
Author(s):  
David C. Leitch ◽  
Joseph Becica
Keyword(s):  
Bond Activation ◽  
Complex Molecule ◽  
Cross Coupling ◽  
Building Blocks ◽  
Alternative Mechanism ◽  
Major Focus ◽  
Reaction Conditions ◽  
Mild Conditions ◽  
Oxidative Additions ◽  
Palladium Catalyzed

AbstractThe activation of strong C–O bonds in cross-coupling catalysis can open up new oxygenate-based feedstocks and building blocks for complex-molecule synthesis. Although Ni catalysis has been the major focus for cross-coupling of carboxylate-based electrophiles, we recently demonstrated that palladium catalyzes not only difficult C–O oxidative additions but also Suzuki-type cross-couplings of alkenyl carboxylates under mild conditions. We propose that, depending on the reaction conditions, either a typical Pd(0)/(II) mechanism or a redox-neutral Pd(II)-only mechanism can operate. In the latter pathway, C–C bond formation occurs through carbopalladation of the alkene, and C–O cleavage by β-carboxyl elimination.1 Introduction2 A Mechanistic Challenge: Activating Strong C–O Bonds3 Exploiting Vinylogy for C–Cl and C–O Oxidative Additions4 An Alternative Mechanism for Efficient Cross-Coupling Catalysis5 Conclusions and Outlook

scholarly journals Nickel-Catalyzed Asymmetric Reductive Cross-Coupling of a-Chloroesters with (Hetero)Aryl Iodides

2021 ◽  
Author(s):  
Travis DeLano ◽  
Sara Dibrell ◽  
Caitlin Lacker ◽  
Adam Pancoast ◽  
kelsey poremba ◽  
...  
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Functional Groups ◽  
Linear Regression Model ◽  
Cross Coupling ◽  
Building Blocks ◽  
Multivariate Linear Regression Model ◽  
Mild Conditions ◽  
Aryl Iodides ◽  
Reaction Proceeds

<a></a><a>An asymmetric reductive cross-coupling of alpha-chloroesters and (hetero)aryl iodides is reported. This nickel-catalyzed reaction proceeds with a chiral BiOX ligand under mild conditions, affording alpha-arylesters in good yields and enantioselectivities. The reaction is tolerant of a variety of functional groups, and the resulting products can be converted to pharmaceutically-relevant chiral building blocks</a>. A multivariate linear regression model was developed to quantitatively relate the influence of the alpha-chloroester substrate and ligand on enantioselectivity

Concise Synthesis of GB22 by Endo-Selective Siloxycyclopropane Arylation

2019 ◽  
Author(s):  
Hannah E. Burdge ◽  
Takuya Oguma ◽  
Takahiro Kawajiri ◽  
Ryan Shenvi
Keyword(s):  
Intramolecular Cyclization ◽  
Cross Coupling ◽  
Building Blocks ◽  
Ring Expansion ◽  
Dual Catalysis ◽  
Acid Labile

<div><div><div><p>The first synthesis of GB22 was accomplished by a con- cise, modular route. Two building blocks converged in a novel sp3-sp2 attached-ring coupling that used Ir/Ni dual-catalysis to reverse the regioselectivity of siloxycy- clopropane arylation. This cross-coupling proved general to access β-substituted tetralones via ring-expansion of indanone-derived siloxycyclopropanes. The congested, bridging rings of the GB alkaloids were completed using an aluminum-HFIP complex that effected intramolecular cyclization of an acid-labile substrate.</p></div></div></div>

Concise Synthesis of GB22 by Endo-Selective Siloxycyclopropane Arylation

2019 ◽  
Author(s):  
Hannah E. Burdge ◽  
Takuya Oguma ◽  
Takahiro Kawajiri ◽  
Ryan Shenvi
Keyword(s):  
Intramolecular Cyclization ◽  
Cross Coupling ◽  
Building Blocks ◽  
Ring Expansion ◽  
Dual Catalysis ◽  
Acid Labile

<div><div><div><p>The first synthesis of GB22 was accomplished by a con- cise, modular route. Two building blocks converged in a novel sp3-sp2 attached-ring coupling that used Ir/Ni dual-catalysis to reverse the regioselectivity of siloxycy- clopropane arylation. This cross-coupling proved general to access β-substituted tetralones via ring-expansion of indanone-derived siloxycyclopropanes. The congested, bridging rings of the GB alkaloids were completed using an aluminum-HFIP complex that effected intramolecular cyclization of an acid-labile substrate.</p></div></div></div>

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

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