Synthesis Of Enamides Research Articles

Synthesis of Enamides through Hydro‐Functionalization of Ynamides

Most of the methods for the synthesis of functionalized enamides from ynamides were developed in the last two decades showing the contemporary interest in the exploration of ynamide chemistry. The utilization of the intrinsic reactivity of the ynamide triple bond through keteniminium intermediacy, coordination with metals, and as a radical acceptor toward the development of strategies for the synthesis of functionalized enamides reflect the constant strive and creativity in the design and execution of synthetic methods. The present review summarizes the synthetic strategies developed during the last two decades and is divided into the sections depending on the type of hydrofunctionalization reaction. It may be predicted that this field of chemistry will continue to grow exponentially in the coming years and the ready availability of a wide range of ynamides now provides an excellent opportunity to further enrich mainstream synthetic methodologies.

Unlock the C-N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation.

The C-N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence of trifluoromethanesulfonic acid (TfOH). The method enables the practical synthesis of valuable enamides without the use of any metal reagent. In addition, this transamidation protocol can also be expanded to the reactions of sulfonamides, and the late-stage functionalization on sulfonamide drugs such as Celecoxib and Valdecoxib has been verified. Moreover, the participation of water in assisting the transamidation process has been identified by the isotope labeling experiments using D2O, disclosing a new possibility in designing catalytic tactic to other transamidation reactions.

Decarboxylative Enamide Synthesis from Carboxylic Acid and Alkenyl Isocyanate.

Herein, we reported a protocol to access the enamide via employing carboxylic acid and alkenyl isocyanate as the precursors promoted by DMAP without involving any metal catalysts and dehydration reagents. This protocol is simple and practical and tolerates numerous functional groups. Considering the simplicity, the ready availability of both starting materials, and the significance of the enamides, we expect that this reaction will find broad application.

Synthesis of Polysubstituted Enamides by Hydrogen Atom Transfer Alkene Isomerization Using Dual Cobalt/Photoredox Catalysis.

M-HAT isomerization is a highly reliable method to access thermodynamically stable alkenes with high functional group tolerance. However, synthesis of heteroatom-substituted alkenes by M-HAT isomerization reaction is still underdeveloped. Herein, we report an enamide synthesis using M-HAT via a combination of cobalt and photoredox catalysis. This method tolerates a variety of functional groups including haloarenes, heteroarenes, free hydroxy groups, non-protected indoles, and drug derivatives. Furthermore, this method can isomerize styrene derivatives in good yield and E/Z selectivity.

Stereoselective Synthesis of Enamides through Palladium‐Catalyzed Oxidative Amidation of Conjugated Olefins with 2‐Pyridones

AbstractA palladium‐catalyzed oxidative amidation of conjugated olefin with 2‐pyridone is described. A series of E‐Enamides were synthesized in a highly stereocontrolled manner. The reaction also accommodates other cyclic and acyclic amides. Z‐Enamides were predominantly prepared for primary amides probably due to the presence of an intramolecular hydrogen bond. Gram‐scale synthesis of enamide and the following oxidative annulation with diphenylacetylene demonstrates the synthetic utility of this reaction.

Enamide Synthesis from Amides Using Tf2O for Electrophilic Activation

Key words electrophilic activation - enamides - lithium bis(trimethylsilyl)amide

Direct Synthesis of Enamides via Electrophilic Activation of Amides.

A novel, one-step N-dehydrogenation of amides to enamides is reported. This reaction employs the unlikely combination of LiHMDS and triflic anhydride, which serves as both the electrophilic activator and the oxidant, and is characterized by its simple setup and broad substrate scope. The synthetic utility of the formed enamides was readily demonstrated in a range of downstream transformations.

Photoredox/Cobalt Dual-Catalyzed Decarboxylative Elimination of Carboxylic Acids: Development and Mechanistic Insight.

Recently, dual-catalytic strategies towards the decarboxylative elimination of carboxylic acids have gained attention. Our lab previously reported a photoredox/cobaloxime dual catalytic method that allows the synthesis of enamides and enecarbamates directly from N-acyl amino acids and avoids the use of any stoichiometric reagents. Further development, detailed herein, has improved upon this transformation's utility and further experimentation has provided new insights into the reaction mechanism. These new developments and insights are anticipated to aid in the expansion of photoredox/cobalt dual-catalytic systems.

Acid mediated synthesis of thiazolines, thiazoles and enamide derivatives from methyl enol ethers: Application towards synthesis of wilsoniamine B

An efficient metal-free synthesis of thiazolines, dihydrothiazole and enureas or thioureas from methyl enol ether with urea or thiourea derivatives in the presence of TFA (trifluoroacetic acid) are reported here. This synthetic protocol involves the formation of two bonds, C–N as well as C–S, in one step for the synthesis of thiazoline derivatives, dihydrothiazoles and a direct C–N bond for the synthesis of enamides with good to excellent yields. Further, this method was employed for the synthesis of wilsoniamine B alkaloid.

Rhodium-catalyzed Sommelet-Hauser type rearrangement of α-diazoimines: synthesis of functionalized enamides.

An efficient rhodium catalyzed Sommelet-Hauser type rearrangement of sulfur ylides derived from α-thioesters and N-sulfonyl-1,2,3-triazoles has been successfully accomplished for the synthesis of various functionalized enamides. The developed reaction involves the unprecedented [2,3]-sigmatropic rearrangement of sulfur ylides with the imine motif. Importantly, the method works well with various substituted α-thioesters/-amides/-ketones and substituted N-sulfonyl-1,2,3-triazoles and allows the synthesis of diverse enamide derivatives in good to excellent yields. The reaction was also successfully extended to the one-pot synthesis of enamides from terminal alkynes.

Efficient and practical synthesis of N-acetyl enamides from ketoximes by unique iron catalytic system

A new procedure for the iron-catalyzed synthesis of enamides from ketoximes was developed, and its mechanism was proposed. A unique reduction system, with the concerted use of KI and Na2S2O4, was involved. The reaction exhibited a wide substrate scope and gave good yields in a short reaction time. The procedure is operationally simple and also applicable for the large-scale synthesis.

Copper-Catalyzed Electrophilic Amidation of Organotrifluoroborates with Use of N-Methoxyamides.

A copper-catalyzed electrophilic amidation of aryltrifluoroborates with use of N-methoxyamides is reported. The reaction shows high functional group compatibility derived from two distinct features: 1) the high stability of the N-methoxyamides and 2) the nonbasic mild conditions in the presence of LiCl. The developed method can also be applied to the synthesis of enamides, which are widely distributed in natural products. Preliminary mechanistic studies suggest that the initial step is the transmetalation of the aryltrifluoroborate by the assistance of LiCl, and the resulting aryl copper intermediate provides the anilide through non-SN 2 oxidative addition to the N-methoxyamide and subsequent reductive elimination.

Chemo- and Regioselective Asymmetric Synthesis of Cyclic Enamides through the Catalytic Umpolung Organocascade Reaction of α-Imino Amides.

The efficient chemo- and regioselective catalytic asymmetric syntheses of enamides, which are important core structures of bioactive natural products, have been achieved through the first umpolung organocascade reaction of α-imino amides. A variety of enamides have been synthesized enantioselectively in high yields with up to 99% ee. Notably, both enantiomers of the products can be selectively prepared by the simple pretreatment of the substrate. Mechanistic studies reveal that E/ Z-geometry information from the substrate is transferred to the product. The present method can be applied to a wide range of α-imino amides, irrespective of the electronic nature of the substituents.

Photoinduced Kochi Decarboxylative Elimination for the Synthesis of Enamides and Enecarbamates from N-Acyl Amino Acids.

Decarboxylative elimination of easily accessible N-acyl amino acids to provide enamide and enecarbamate building blocks has been realized through the combination of an organophotoredox catalyst and copper acetate as the terminal oxidant. This operationally simple process utilizes inexpensive and readily available reagents without preactivation of the carboxylic acid. Enamides and enecarbamates are now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi's oxidative decarboxylation of carboxylic acids.

Iron-catalysed 1,2-acyl migration of tertiary α-azido ketones and 2-azido-1,3-dicarbonyl compounds

Synthesis of enamides via 1,2-acyl migration of tertiary α-azido ketones was accomplished efficiently by the catalysis of FeBr2 and Et3N.

Decarboxylative Elimination of N-Acyl Amino Acids via Photoredox/Cobalt Dual Catalysis

A dual-catalytic strategy for the synthesis of enamides and enecarbamates directly from easily accessible and inexpensive amino acids has been realized. This mild and efficient protocol makes use of an organic photoredox catalyst and a cobaloxime catalyst to achieve decarboxylative elimination using hydrogen evolution to drive the oxidation. Thus, the reaction occurs without a stoichiometric oxidant or the forcing conditions previously employed in attempts to achieve similar eliminations.

Cp*Co(iii)-catalyzed amidation of olefinic and aryl C-H bonds: highly selective synthesis of enamides and pyrimidones.

A highly efficient and selective synthesis of enamides via C-H amidation of N-methoxy acrylamides with dioxazolones is realized under [Cp*CoIII] catalysis. The resulting enamide can further selectively cyclize to form pyrimidones, which can also act as a directing group for a second C-H amidation. All these three classes of products were selectively delivered under controlled conditions.

Extension of the Modified Julia Olefination on Carboxylic Acid Derivatives: Scope and Applications

This account relates our work in the field of modified Julia olefination to extend this very useful olefination method to carboxylic acid derivatives. Since our preliminary results on lactones in 2005, the reaction has been extended to a large range of derivatives (lactams, imides and anhydrides) through an intra- or intermolecular process leading to a great variety of structures (enol ethers, enamides and exo enol esters). This article will also focus on the application of this methodology for the preparation of biologically interesting compounds and/or total syntheses of natural products such as C-disaccharide, bistramide A, jaspine B and maculalactone B.1 Introduction2 Modified Julia Olefination on Lactones2.1 Methylene Enol Ether Synthesis2.2 Substituted Enol Ether Synthesis2.3 Monofluorinated Enol Ether Synthesis2.4 Difluorinated Enol Ether Synthesis3 Applications3.1 Spiroketal Synthesis3.2 Spirocompound Synthesis3.3 Pseudodisaccharide Synthesis3.4 Total Synthesis of Jaspine B4 Modified Julia Olefination on Other Carboxylic Acid Derivatives4.1 Lactam Olefination and Spiroaminal Synthesis4.2 Bicyclic Enamide Synthesis by Intramolecular Modified Julia Olefination on Imides4.3 Modified Julia Olefination on Anhydrides5 Conclusion

ChemInform Abstract: Synthesis of Enamides by Ruthenium‐Catalyzed Reaction of Alkyl Azides with Acid Anhydrides in Ionic Liquid

Abstract50 examples

ChemInform Abstract: Nickel‐Catalyzed Synthesis of Enamides and Enecarbamates via Isomerization of Allylamides and Allylcarbamates.

A single-component, air-stable nickel precatalyst can catalyze the isomerization of allylamides for the synthesis of enamides. The scope of the reaction encompasses various substituted allylamides and allylcarbamates as well as homoallylamides. The reaction can be performed on a multigram-scale without specialized glove-box equipment or Schlenk techniques.