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.

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.

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>

Synthesis of 3-(Cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8- carboxylic Acids Via an Efficient Three-component Condensation Reaction between Cyclohexylisocyanide and 2-Aminopyridine-3-carboxylic Acid in the Presence of Aromatic Aldehyde

2018 ◽  
Vol 21 (4) ◽  
pp. 298-301 ◽  
Author(s):  
Ghasem Marandi
Keyword(s):  
Biological Sciences ◽  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
High Performance ◽  
Condensation Reaction ◽  
Aromatic Aldehydes ◽  
New Materials ◽  
One Pot ◽  
High Yields ◽  
Benzaldehyde Derivatives

Aim and Objective: The reaction of cyclohexylisocyanide and 2-aminopyridine-3- carboxylic acid in the presence of benzaldehyde derivatives in ethanol led to 3-(cyclohexylamino)-2- arylimidazo[1,2-a]pyridine-8-carboxylic acids in high yields. In a three component condensation reaction, isocyanide reacts with 2-aminopyridine-3-carboxylic acid and aromatic aldehydes without any prior activation. Material and Methods: The synthesized products have stable structures which have been characterized by IR, 1H, 13C and Mass spectroscopy as well as CHN-O analysis. Results: In continuation of our attempts to develop simple one-pot routes for the synthesis of 3- (cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8-carboxylic acids, aromatic aldehydes with divers substituted show a high performance. Conclusion: In conclusion, this study introduces the art of combinatorial chemistry using a simple one-pot procedure for the synthesis of new materials which are interesting compounds in medicinal and biological sciences.

scholarly journals Unsymmetrical Difunctionalization of Two Different C–H Bonds in One Pot Under Transition-Metal Catalysis

Synthesis ◽  
2018 ◽  
Vol 51 (01) ◽  
pp. 40-54 ◽  
Author(s):  
Masahito Murai ◽  
Kazuhiko Takai
Keyword(s):  
Transition Metal ◽  
Functional Groups ◽  
Aromatic Compounds ◽  
Transition Metal Catalysis ◽  
One Pot ◽  
Metal Catalysis ◽  
Selective Functionalization ◽  
Sequential Addition ◽  
Target Molecules ◽  
Directing Group

Recent advancements in unsymmetrical difunctionalization based on the substitution of two different C–H bonds in one-pot are described. Due to the difficulty of controlling reactivity and selectivity, multi-functionalization via substitution of several C–H bonds to install different functional groups has been limited until recently, in comparison with well-studied functionalization via sequential addition to unsaturated π-bonds. This difunctionalization protocol provides an efficient and rapid approach to a library of structurally complicated target molecules through the formation of multiple C–X bonds with high atom- and step-economy.1 Introduction2 ortho-Selective Functionalization of Two Different C–H Bonds Relative to the Directing Group2.1 Unsymmetrical Difunctionalization with the Introduction of Similar Functional Groups2.2 Unsymmetrical Difunctionalization with the Introduction of Different Functional Groups2.3 ortho-Selective Unsymmetrical Difunctionalization Promoted by Two Different Directing Groups Appearing During the Progress of the Reaction3 ortho/meta-Selective C–H Bond Difunctionalization Relative to the Directing Group4 Sequential Difunctionalization of Fused Aromatic Compounds and Heterocycles5 Summary and Outlook

scholarly journals Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C-H Acetoxylation and Alkenylation of the Arylacetamides

2019 ◽  
Author(s):  
Maryia V. Barysevich ◽  
Marharyta V. Laktsevich-Iskryk ◽  
Anastasiya V. Krech ◽  
Vladimir N. Zhabinskii ◽  
Vladimir A. Khripach ◽  
...  
Keyword(s):  
One Pot ◽  
Palladium Catalyzed ◽  
Directing Group

A directing group that promotes very fast diacetoxylation of the arylacetamides is reported. The auxiliary also promotes alkenylation with vinyl ketones, which were generated in one-pot from the cyclopropanols.

scholarly journals Palladium-Catalyzed [3+2] Cycloaddition via Two-Fold 1,3-C(sp3)−H Activation

2020 ◽  
Author(s):  
Hojoon Park ◽  
jin-quan yu
Keyword(s):  
Functional Groups ◽  
Sulfonic Acid ◽  
Cycloaddition Reaction ◽  
Wide Range ◽  
Leaving Group ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
Overall Efficiency ◽  
Weak Coordination ◽  
Single Reaction

<div>Cycloaddition reactions provide an expeditious route to construct ring systems in a highly convergent and stereoselective manner. For a typical cycloaddition reaction to occur, however, the installation of multiple reactive functional groups (π-bonds, leaving group, etc.) are required within the substrates, compromising the overall efficiency or scope of the cycloaddition reaction. Here, we report a palladium-catalyzed [3+2] reaction that utilizes C(sp<sup>3</sup>)–H activation to generate the three-carbon unit for formal cycloaddition with maleimides. We implemented a strategy where the initial C(sp<sup>3</sup>)–H activation/olefin insertion would trigger a relayed, second remote C(sp<sup>3</sup>)–H activation to complete a formal [3+2] cycloaddition. The diastereoselectivity profile of this reaction resembles that of a typical pericyclic cycloaddition reaction in that the relationships between multiple stereocenters are exquisitely controlled in a single reaction. The key to success was the use of weakly coordinating amides as the directing group, as undesired Heck or alkylation pathways were preferred with other types of directing groups. The use of the pyridine-3-sulfonic acid ligands is critical to enable C(sp<sup>3</sup>)–H activation directed by this weak coordination. The method is compatible with a wide range of amide substrates, including lactams, which lead to novel spiro-bicyclic products. The [3+2] product is also shown to undergo a reductive desymmetrization process to access chiral cyclopentane bearing multiple stereocenters with excellent enantioselectivity.</div>

scholarly journals Palladium(II)-Catalyzed C(sp3)–H Activation of N,O-Ketals towards a Method for the β-Functionalization of Ketones

Synlett ◽  
2019 ◽  
Vol 30 (04) ◽  
pp. 454-458 ◽  
Author(s):  
Danny Ho ◽  
Jonas Calleja ◽  
Matthew Gaunt
Keyword(s):  
Carboxylic Acids ◽  
Functional Groups ◽  
Building Blocks ◽  
Activation Pathway ◽  
Bond Forming ◽  
Aliphatic Ketones ◽  
Palladium Catalyzed

A method for the formal β-functionalization of aliphatic ketones via a palladium-catalyzed sp3 C–H activation pathway is reported. An N,O-ketal directs an aliphatic C–H carbonylation to form γ-lactams which upon hydrolysis generate γ-keto carboxylic acids. This C–C bond-forming reaction is tolerant of a range of functional groups, enabling the synthesis of a range of synthetically important building blocks. Furthermore, the concepts underlying this transformation have also enabled the development of a related C–H alkenylation process to highly functionalised heterocycles.

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

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