scholarly journals Direct β- and γ-C(sp3)–H Alkynylation of Free Carboxylic Acids

2020 ◽  
Author(s):  
Francesca Ghiringhelli ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Synthetic Methods ◽  
Broad Scope ◽  
Palladium Catalyzed ◽  
Directing Group

In this study we report the identification of a novel class of ligands for palladium-catalyzed C(sp3)–H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α-quaternary and challenging α-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal γ-position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

scholarly journals Direct β- and γ-C(sp3)–H Alkynylation of Free Carboxylic Acids

2020 ◽  
Author(s):  
Francesca Ghiringhelli ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Synthetic Methods ◽  
Broad Scope ◽  
Palladium Catalyzed ◽  
Directing Group

In this study we report the identification of a novel class of ligands for palladium-catalyzed C(sp3)–H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α-quaternary and challenging α-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal γ-position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

scholarly journals Stereoselective Palladium-Catalyzed C(sp3)–H Mono-Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group

2021 ◽  
Author(s):  
Amalia-Sofia Piticari ◽  
Daniele Antermite ◽  
Joe I. Higham ◽  
J. Harry Moore ◽  
Matthew P. Webster ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Functional Groups ◽  
One Pot ◽  
Palladium Catalyzed ◽  
Directing Group

A selective Pd-catalyzed C(3)–H cis-functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)–H functionalization reactions, which is facilitated by a DoE optimization. A one-pot C–H functionalization-epimerization procedure provides the trans-3,4-disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall fragment compounds suitable for screening are generated in 3–4 steps from readily-available heterocyclic carboxylic acids.

The Direct Pd-Catalyzed β-C(sp3)–H Activation of Carboxylic Acids

Synlett ◽  
2018 ◽  
Vol 29 (15) ◽  
pp. 1937-1943 ◽  
Author(s):  
Manuel van Gemmeren ◽  
Alexander Uttry
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Bond Activation ◽  
State Of The Art ◽  
Acid Moiety ◽  
Straightforward Manner ◽  
Aliphatic Acids ◽  
Tremendous Progress ◽  
Palladium Catalyzed ◽  
Directing Group

The carboxylic acid moiety is one of the most versatile and abundant functional groups. However, despite of tremendous progress in the field of C–H functionalization reactions its use as a directing group for C(sp3)–H activation has remained limited. In this Synpact article we present the challenges associated with the carboxylic acid moiety as a native directing group and report on the newest developments in this field, including our recent study in which we developed a generally applicable protocol for the direct palladium catalyzed β-C(sp3)–H arylation of propionic acid and related α-branched aliphatic acids giving access to hydrocinnamic acids derivatives in a highly straightforward manner.1 Introduction2 Challenges in the C(sp3)–H Bond Activation of Carboxylic Acids3 History/State of the Art4 Studies towards a General β-C(sp3)–H Functionalization of ­Aliphatic Acids5 Conclusion

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

2020 ◽  
Author(s):  
Aleksandra Balliu ◽  
Aaltje Roelofje Femmigje Strijker ◽  
Michael Oschmann ◽  
Monireh Pourghasemi Lati ◽  
Oscar Verho
Keyword(s):  
Carboxylic Acid ◽  
Building Blocks ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
High Yields ◽  
Vinyl Iodides ◽  
Initial Results

<p>In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both <i>cis</i>- and <i>trans</i>-configured carboxylic acid building blocks from the C–H alkenylation products.</p>

Direct C(sp3)–H Activation of Carboxylic Acids

Synthesis ◽  
2019 ◽  
Vol 52 (04) ◽  
pp. 479-488 ◽  
Author(s):  
Alexander Uttry ◽  
Manuel van Gemmeren
Keyword(s):  
Carboxylic Acid ◽  
General Solution ◽  
Carboxylic Acids ◽  
Bond Activation ◽  
Acid Moiety ◽  
Group Approach ◽  
Research Fields ◽  
Directing Group ◽  
Aliphatic Carboxylic Acids

Carboxylic acids are important in a variety of research fields and applications. As a result, substantial efforts have been directed towards the C–H functionalization of such compounds. While the use of the carboxylic acid moiety as a native directing group for C(sp2)–H functionalization reactions is well established, as yet there is no general solution for the C(sp3)–H activation of aliphatic carboxylic acids and most endeavors have instead relied on the introduction of stronger directing groups. Recently however, novel ligands, tools, and strategies have emerged, which enable the use of free aliphatic carboxylic acids in C–H-activation-based transformations.1 Introduction2 Challenges in the C(sp3)–H Bond Activation of Carboxylic Acids3 The Lactonization of Aliphatic Carboxylic Acids4 The Directing Group Approach5 The Direct C–H Arylation of Aliphatic Carboxylic Acids6 The Direct C–H Olefination of Aliphatic Carboxylic Acids7 The Direct C–H Acetoxylation of Aliphatic Carboxylic Acids8 Summary

Rh(III)-Catalyzed Decarboxylativeortho-Heteroarylation of Aromatic Carboxylic Acids by Using the Carboxylic Acid as a Traceless Directing Group

2015 ◽  
Vol 17 (7) ◽  
pp. 1762-1765 ◽  
Author(s):  
Xurong Qin ◽  
Denan Sun ◽  
Qiulin You ◽  
Yangyang Cheng ◽  
Jingbo Lan ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Aromatic Carboxylic Acids ◽  
Directing Group

Transient- and Native-Directing-Group-Enabled Enantioselective C–H Functionalization

Synthesis ◽  
2021 ◽  
Author(s):  
Chuan He ◽  
Bing Zu ◽  
Yonghong Guo ◽  
Jie Ke
Keyword(s):  
Carboxylic Acid ◽  
Transition Metal ◽  
Carboxylic Acids ◽  
Short Review ◽  
Synthetic Approach ◽  
Bond Functionalization ◽  
Axial Chirality ◽  
Planar Chirality ◽  
Directing Group ◽  
Metal Catalyzed

AbstractIn recent years, transition-metal-catalyzed enantioselective C–H bond functionalization using chiral transient directing groups (cTDGs) or native directing groups (NDGs) has emerged as a powerful and attractive­ synthetic approach to streamline the synthesis of chiral molecules­. This short review focuses on recent advances on imine-based cTDGs strategies and native amine and carboxylic acid directed strategies for the asymmetric functionalization of various C–H bonds. We have endeavored to highlight the great potential of this methodology and hope that this review will inspire further research in this area.1 Introduction2 Transient-Directing-Group-Enabled Enantioselective C–H Functionalization2.1 Generation of Central Chirality2.2 Generation of Axial Chirality2.3 Generation of Planar Chirality3 Native-Directing-Group-Enabled Enantioselective C–H Functionalization3.1 Native Amines as Directing Groups3.2 Native Carboxylic Acids as Directing Groups4 Conclusions and Outlook

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

2020 ◽  
Author(s):  
Aleksandra Balliu ◽  
Aaltje Roelofje Femmigje Strijker ◽  
Michael Oschmann ◽  
Monireh Pourghasemi Lati ◽  
Oscar Verho
Keyword(s):  
Carboxylic Acid ◽  
Building Blocks ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
High Yields ◽  
Vinyl Iodides ◽  
Initial Results

<p>In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both <i>cis</i>- and <i>trans</i>-configured carboxylic acid building blocks from the C–H alkenylation products.</p>

Synthesis of pregnane 3-carboxylic acids via Pd-catalyzed alkoxycarbonylation and their effect on NMDA receptor activity

2011 ◽  
Vol 76 (9) ◽  
pp. 1141-1161 ◽  
Author(s):  
Eva Šťastná ◽  
Hana Chodounská ◽  
Vladimír Pouzar ◽  
Jiřina Borovská ◽  
Ladislav Vyklický
Keyword(s):  
Nmda Receptor ◽  
Carboxylic Acid ◽  
Voltage Clamp ◽  
Carboxylic Acids ◽  
Substitution Reaction ◽  
Hippocampal Neurons ◽  
Receptor Activity ◽  
Induced Responses ◽  
Palladium Catalyzed ◽  
Leaving Groups

We have prepared 20-oxo-5α- and 20-oxo-5β-pregnane-3-carboxylic acids by palladium catalyzed alkoxycarbonylation using triflate and nonaflate as the leaving groups in this substitution reaction. The activity of the synthesized compounds was studied in cultured rat hippocampal neurons under voltage-clamp conditions. The 5β-carboxylic acid derivatives were found to diminish NMDA-induced responses, whereas the 5α-derivative potentiated the response.

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