scholarly journals General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

2021 ◽  
Author(s):  
Daniel Matheau-Raven ◽  
Darren J. Dixon
Keyword(s):  
Carboxylic Acid ◽  
Late Stage ◽  
Coupling Reaction ◽  
Reductive Activation ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Drug Conjugates ◽  
Iminium Ion ◽  
Tertiary Amides ◽  
Coupling Partner

An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol%) Vaska’s complex (IrCl(CO)(PPh<sub>3</sub>)<sub>2</sub>) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of structurally complex α-amino 1,3,4-oxadiazole architectures were efficiently accessed from diverse carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles. Furthermore, the high chemoselectivity of the catalytic reductive activation step allowed the late-stage functionalization of 10 drug molecules, including the synthesis of novel heterodiazole-fused drug-drug conjugates.<br>

scholarly journals General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

2021 ◽  
Author(s):  
Daniel Matheau-Raven ◽  
Darren J. Dixon
Keyword(s):  
Carboxylic Acid ◽  
Late Stage ◽  
Coupling Reaction ◽  
Reductive Activation ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Drug Conjugates ◽  
Iminium Ion ◽  
Tertiary Amides ◽  
Coupling Partner

An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol%) Vaska’s complex (IrCl(CO)(PPh<sub>3</sub>)<sub>2</sub>) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of structurally complex α-amino 1,3,4-oxadiazole architectures were efficiently accessed from diverse carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles. Furthermore, the high chemoselectivity of the catalytic reductive activation step allowed the late-stage functionalization of 10 drug molecules, including the synthesis of novel heterodiazole-fused drug-drug conjugates.<br>

Carbene and Photocatalyst-Catalyzed Decarboxylative Radical Coupling of Carboxylic Acids and Acyl Imidazoles to Form Ketones

2021 ◽  
Author(s):  
Shi-Chao Ren ◽  
Xing Yang ◽  
Bivas Mondal ◽  
Chengli Mou ◽  
Weiyi Tian ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Radical Coupling ◽  
Mild Conditions ◽  
Two Component ◽  
Decarboxylative Coupling ◽  
Coupling Partner ◽  
Powerful Strategy ◽  
Operational Simplicity

Abstract The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids were directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction was successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Aliphatic Carboxylic Acid as Hydrogen-Bond Donor for Converting CO2 and Epoxide into Cyclic Carbonate under Mild Conditions

2021 ◽  
Author(s):  
Zheng Wang ◽  
Yajun Wang ◽  
Qianjie Xie ◽  
Zhiying Fan ◽  
Yehua Shen
Keyword(s):  
Hydrogen Bond ◽  
Carboxylic Acid ◽  
Value Added ◽  
Cyclic Carbonate ◽  
Hydrogen Bond Donor ◽  
Title Reaction ◽  
Aliphatic Carboxylic Acid ◽  
Mild Conditions ◽  
Atmospheric Carbon

The coupling of CO2 and epoxide is promising way to reduce atmospheric carbon by converting it into value-added cyclic carbonate. Pursuing efficient catalysts is highly attractive for the title reaction....

scholarly journals Mechanically induced solvent-free esterification method at room temperature

RSC Advances ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 5080-5085
Author(s):  
Lei Zheng ◽  
Chen Sun ◽  
Wenhao Xu ◽  
Alexandr V. Dushkin ◽  
Nikolay Polyakov ◽  
...  
Keyword(s):  
Natural Products ◽  
Carboxylic Acids ◽  
Late Stage ◽  
Reaction Mechanisms ◽  
Room Temperature ◽  
Solvent Free ◽  
Mild Conditions

We have developed I2/KH2PO2 and KI/P(OEt)3 strategy syntheses of esters from carboxylic acids and alcohols through different reaction mechanisms. The advantages of present protocol: mild conditions and late-stage diversification of natural products.

scholarly journals Pd Nanoparticles Stabilized by Hypercrosslinked Polystyrene Catalyze Selective Triple C-C Bond Hydrogenation and Suzuki Cross-Coupling

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Linda Zh. Nikoshvili ◽  
Nadezhda A. Nemygina ◽  
Tatiana E. Khudyakova ◽  
Irina Yu. Tiamina ◽  
Alexey V. Bykov ◽  
...  
Keyword(s):  
Phase Transfer ◽  
Aryl Halide ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Pd Nanoparticles ◽  
Hypercrosslinked Polystyrene ◽  
Reductive Activation ◽  
Pd Nanoparticle ◽  
Cross Coupling Reaction ◽  
Precursor Decomposition

This paper describes the synthesis of Pd-containing catalysts based on nonfunctionalized hypercrosslinked polystyrene via impregnation with Pd acetate. Developed Pd nanoparticulate catalyst allowed achieving conversion of aryl halide up to 90% in Suzuki cross-coupling reaction under mild conditions and at the absence of phase-transfer agents. During the selective hydrogenation of triple C-C bond of 2-methyl-3-butyn-2-ol, up to 96% selectivity with respect to corresponding olefinic alcohol was found at 95% conversion. The influences of the procedure of catalyst synthesis like precursor decomposition and reductive activation method on Pd nanoparticle formation are discussed.

scholarly journals Phosphite-Mediated Reductive Cross-Coupling of Isatins and Nitro­styrenes

Synthesis ◽  
2017 ◽  
Vol 49 (12) ◽  
pp. 2663-2676 ◽  
Author(s):  
Somayeh Motevalli ◽  
Jeffrey Johnson
Keyword(s):  
Coupling Reaction ◽  
Cross Coupling ◽  
Reductive Coupling ◽  
Title Reaction ◽  
Dimethyl Phosphite ◽  
Mild Conditions ◽  
Michael Type Addition

A new reductive coupling reaction between N-alkylisatins, dimethyl phosphite, and nitrostyrenes has been developed. The reaction relies on Pudovik addition, subsequent phosphonate–phosphate rearrangement, and Michael-type addition of a transient carbanion on the indolinone with β-nitrostyrenes. This protocol introduces a convenient and versatile method for the construction of polyfunctionalized tertiary phosphates under mild conditions. Chiral general bases catalyze the title reaction with promising levels of enantioselectivity.

scholarly journals Late-Stage β-C(sp3)–H Deuteration of Carboxylic Acids

2021 ◽  
Author(s):  
Alexander Uttry ◽  
Sourjya Mal ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Late Stage ◽  
Bioactive Molecules ◽  
Wide Range ◽  
Catalyst Systems ◽  
First Time

Carboxylic acid moieties are highly abundant in bioactive molecules. In this study we describe the late-stage β-C(sp<sup>3</sup>)–H deuteration of free carboxylic acids. Based on our finding that the C–H activation with our catalyst systems is reversible, the de-deuteration process was first optimized. The resulting conditions involve ethylenediamine-based ligands, which, amongst other positions, for the first time enables the functionalization of non-activated methylene β-C(sp<sup>3</sup>)–H bonds and can be used to achieve the desired deuteration when using a deuterated solvent. The reported method allows for the functionalization of a wide range of free carboxylic acids with diverse substitution patterns, as well as the late-stage deuteration of bioactive molecules and related frameworks.

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