The concept of using amide bond distortion to modulate amidic resonance has been known for more than 75 years. Two classic twisted amides (bridged lactams) ingeniously designed and synthesized by ...Kirby and Stoltz to feature fully perpendicular amide bonds, and as a consequence emanate amino‐ketone‐like reactivity, are now routinely recognized in all organic chemistry textbooks. However, only recently the use of amide bond twist (distortion) has advanced to the general organic chemistry mainstream enabling a host of highly attractive N−C amide bond cross‐coupling reactions of broad synthetic relevance. In this Minireview, we discuss recent progress in this area and present a detailed overview of the prominent role of amide bond destabilization as a driving force in the development of transition‐metal‐catalyzed cross‐coupling reactions by N−C bond activation.
Twist of faith! Recently the use of amide bond twist (distortion) has advanced to the general organic chemistry mainstream enabling a host of highly attractive N−C amide bond cross‐coupling reactions of broad synthetic relevance. In this Minireview, recent progress in this area is discussed and a detailed overview of the prominent role of amide bond destabilization as a driving force in the development of transition‐metal‐catalyzed cross‐coupling reactions by N−C amide bond activation is presented.
Amide chemistry has an essential role in the synthesis of high value molecules, such as pharmaceuticals, natural products, and fine chemicals. Over the past years, several examples of transamidation ...reactions have been reported. In general, transition-metal-based catalysts or harsh conditions are employed for these transformations due to unfavorable kinetics and thermodynamics of the process. Herein, we report a significant advance in this area and present the general method for transition-metal-free transamidation of amides and amidation of esters by highly selective acyl cleavage with non-nucleophilic amines at room temperature. In contrast to metal-catalyzed protocols, the method is operationally-simple, environmentally-friendly, and operates under exceedingly mild conditions. The practical value is highlighted by the synthesis of valuable amides in high yields. Considering the key role of amides in various branches of chemical science, we envision that this broadly applicable method will be of great interest in organic synthesis, drug discovery, and biochemistry.
Metal‐catalyzed reactions of amides proceeding via metal insertion into the NCO bond are severely underdeveloped due to resonance stabilization of the amide bond. Herein we report the first Heck ...reaction of amides proceeding via highly chemoselective NCO cleavage catalyzed by Pd0 utilizing amide bond ground‐state destabilization. Conceptually, this transformation provides access to a myriad of metal‐catalyzed transformations of amides via metal insertion/decarbonylation.
Welcome disturbance: The first Pd0‐catalyzed Heck reaction of amides proceeding through highly chemoselective NC activation utilizing amide bond ground‐state distortion is reported. The reaction shows excellent functional group tolerance and avoids the formation of corrosive halide waste (base‐free Heck). It provides access to a myriad of metal‐catalyzed transformations of amides through metal insertion/decarbonylation.
Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold ...particular significance. A conventional method for the synthesis of C−P bonds involves cross‐coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The present method tolerates a wide range of functional groups. The reaction constitutes the first example of a transition‐metal‐catalyzed generation of C−P bonds from amides. This redox‐neutral protocol can be combined with site‐selective conventional cross‐coupling for the regioselective synthesis of potential pharmacophores. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni‐catalyzed C−P bond forming method will find broad application.
C−P coupling: A general method for catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst provides access to aryl phosphonates in good to excellent yields. The reaction constitutes the first example of a transition‐metal‐catalyzed generation of C−P bonds from amides.
Highly chemoselective, palladium(0)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides is reported. The reaction proceeds via selective activation of the ...N–C(O) bond, shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. The observed reactivity is consistent with a decrease of nN → π*CO conjugation resulting from destabilization of the amide ground state. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions.
Isoxazoles are important five‐membered aromatic heterocycles in organic chemistry. Recently, many exciting advances in the synthesis and functionalization of isoxazoles have been reported. New ...transition metal‐catalyzed reactions have resulted in the development of attractive and highly efficient synthetic approaches to densely functionalized isoxazoles. Complete control of regioselectivity can be achieved on the basis of a judicious choice of metal catalyst and reaction partners using dipolar cycloaddition and cycloisomerization reactions, while more recent studies have focused on the site‐selective functionalization of isoxazoles via CH functionalization. New strategies for the use of isoxazoles as scaffolding templates in asymmetric synthesis have emerged, thus opening new prospects for the synthesis of enantioenriched motifs under the conditions that are orthogonal to other transformations. In this review, recent advances involving the synthesis and reactivity of isoxazoles are summarized. The review covers the period from January 2005 to June 2015.
In this Microreview, we describe the recent exciting developments in the burgeoning area of amide N–C cross‐coupling enabled by amide bond twist of N‐acyl‐glutarimides. Since the initial reports in ...2015, these amides have been demonstrated to be by far the most reactive amide derivatives in the biologically‐relevant manifold of N–C activation/cross‐coupling, thus stimulating the development of more than 10 previously unknown catalytic modes of reactivity of the amide bond. The capacity of N‐acyl‐glutarimides as privileged scaffolds to expedite acyl and decarbonylative cross‐couplings by amide N–C cleavage is discussed.
In this Microreview, we describe the recent exciting developments in the burgeoning area of amide N–C cross‐coupling enabled by amide bond twist of N‐acyl‐glutarimides. The capacity of N‐acyl‐glutarimides as privileged scaffolds to expedite acyl and decarbonylative cross‐couplings by amide N–C cleavage is discussed.
The scarcity of precious metals has led to the development of sustainable strategies for metal‐catalyzed cross‐coupling reactions. The establishment of new catalytic methods using iron is attractive ...owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron‐catalyzed cross‐couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field‐tested as highly effective base‐metal catalysts in practical, kilogram‐scale industrial cross‐couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross‐coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.
With an iron hand: Iron is one of the very few metals that have been successfully used as highly effective base‐metal catalysts in practical, kilogram‐scale industrial cross‐couplings. The Minireview provides an introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.
The first Negishi cross‐coupling of amides for the synthesis of versatile diaryl ketones by selective C−N bond activation under exceedingly mild conditions is reported. The cross‐coupling was ...accomplished with bench‐stable, inexpensive precatalyst Ni(PPh3)2Cl2 that shows high functional‐group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs. The coupling occurred with excellent chemoselectivity favoring the ketone (cf. biaryl) products. Notably, this process represents the mildest conditions for amide N−C bond activation accomplished to date (room temperature, <10 min). Considering the versatile role of polyfunctional biaryl ketone linchpins in modern organic synthesis, availability, and excellent functional‐group tolerance of organozinc reagents, this strategy provides a new platform for amide N−C bond/organozinc cross‐coupling under mild conditions.
Easy crossing: The first Negishi cross‐coupling of amides for the synthesis of versatile diaryl ketones by selective C−N bond activation under exceedingly mild conditions is reported (see scheme). The cross‐coupling was accomplished with bench‐stable, inexpensive NiII(PPh3)2Cl2 precatalyst that shows high functional‐group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs.
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