Aryldiazonium tetrafluoroborate salts are highly accessible from readily available and inexpensive amines, and by realizing these advantages, an efficient protocol is developed that employs aryldiazonium tetrafluoroborate salts as an effective electrophile for oxidative aminocarbonylation with unreactive tertiary amines. In this, molecular oxygen has been used as an ideal and green oxidant, which activates the inert CN bond. Various derivatives of aryldiazonium tetrafluoroborate salts are prepared, which include different electron-withdrawing and electron-donating group substituents. This protocol utilizes Pd/C as a heterogeneous catalyst, which is smoothly recyclable. Moreover, this developed method is ligand and cocatalyst free, and it does not require any base to activate the amines as nucleophile, and the new process effectively provides a mild pathway toward a variety of tertiary amide moieties with significant yield. This way, the potent protocol is economical, simple, recyclable, and operates at milder conditions and contributes toward valuable products that are vital in an industrial domain.

β,γ-Unsaturated amides are valuable substrates for downstream functionalization reactions but can be challenging to prepare. Herein, we introduce an approach featuring the regioselective addition of carbamoyl chlorides to unactivated alkenes, present its scope and limitations, and exemplify its synthetic utility.

The transesterification of unactivated carboxylic esters with alcohols was achieved in one pot through acid/halide cooperative catalysis. By this strategy, various weakly nucleophilic phenols could react with unactivated methyl esters to produce the corresponding phenolic esters in good to high yields. Aliphatic alcohols could also be used as the nucleophiles and showed higher reactivity. Moreover, high functional group tolerance has been demonstrated. This reaction is also applicable to the late-stage modification of clinical drug derivatives. These results clearly show the potential synthetic value of this new reaction in organic synthesis.

The transformation and utilization of amides are significant in organic synthesis and drug discovery. Here we demonstrate a divergent alkynylative difunctionalization of amides in a single transformation. In this reaction, amides react with an organometallic nucleophile to form a tetrahedral intermediate. By altering the N-substitution or the acyl group, the tetrahedral intermediate species selectively undergoes C-O or C-N cleavage with a concomitant capture by an alkynyl nucleophile generated in situ. This process enables the selective introduction of two different functional groups into the amide molecular architecture, producing valuable propargyl amine and propargyl alcohol products. The selectivity between deoxygenation and deamination process has been further elucidated by DFT calculations. Overall, this reaction successfully transforms the traditional mode of nucleophilic acyl addition to amides to a divergent C-O/C-N cleavage. The particularly wide substrate scope, including late-stage modification of bioactive molecules, demonstrates its potential broad applications in organic synthesis.

A metal-free and mild cleavage of tertiary p-methoxybenzyl amides (PMB tert-amide) under photoredox conditions is developed using Mes-Acr-Ph+BF4- and Selectfluor to activate the electron-rich benzylic C-H bond of the PMB moiety. The resulting acyl fluoride intermediate is versatile and facilitates a one-pot transamidation of the PMB tert-amide. The value of this protocol is highlighted by performing the chemoselective activation of the PMB tert-amide in bifunctional molecules containing more reactive functionalities than the amide.

A BF3·OEt2-mediated transamidation between unactivated amides and amines is reported, enabling access to diverse secondary and tertiary amides under transition-metal-free and solvent-free conditions. The operationally simple procedure provides a novel manifold for converting amide-amide bonds with excellent chemoselectivity. In particular, a series of amides including challenging thioamides enable direct transamidation to products with modest to excellent yields. Meanwhile, additional experiments were conducted to elucidate the mechanism of this transformation, and a plausible mechanism was proposed based on the results and related literature.

The esterification of carboxylic acids is an important reaction for preparing esters which find wide applications in various research fields. In this manuscript, we report an acid/iodide cooperative catalytic method which enables highly efficient esterification of carboxylic acids with a wide range of equivalent O-H nucleophiles including both alcohols and weak nucleophilic phenols. Under the reaction conditions, both aromatic and aliphatic carboxylic acids including those bearing functional groups work well, furnishing the corresponding esters in good to high yields. Moreover, this reaction is scalable and applicable to the modification of bioactive molecules. These results demonstrate the synthetic value of this new reaction in organic synthesis.

Organoalkali compounds have undergone a far-reaching transformation being a coupling partner to a mediator in unusual organic conversions which finds its spot in the field of sustainable synthesis. Transition-metal catalysis has always been the priority in C(sp3)-H bond functionalization, however alternatively, in recent times this has been seriously challenged by earth-abundant alkali metals and their complexes arriving at new sustainable organometallic reagents. In this line, the importance of MN(SiMe3)2 (M=Li, Na, K & Cs) reagent revived in C(sp3)-H bond functionalization over recent years in organic synthesis is showcased in this minireview. MN(SiMe3)2 reagent with higher reactivity, enhanced stability, and bespoke cation-π interaction have shown eye-opening mediated processes such as C(sp3)-C(sp3) cross-coupling, radical-radical cross-coupling, aminobenzylation, annulation, aroylation, and other transformations to utilize readily available petrochemical feedstocks. This article also emphasizes the unusual reactivity of MN(SiMe3)2 reagent in unreactive and robust C-X (X=O, N, F, C) bond cleavage reactions that occurred alongside the C(sp3)-H bond functionalization. Overall, this review encourages the community to exploit the untapped potential of MN(SiMe3)2 reagent and also inspires them to take up this subject to even greater heights.

We report a Pd-catalyzed ortho-C-H arylation of free anilines with arylboric acids. Under the reaction conditions, a wide range of arylboric acids can couple with free anilines to produce the corresponding o-amino biaryls in moderate to good yields with good functional group tolerance. This reaction can be conducted on the gram scale. The products can be easily further functionalized via transformation of the free amino group. These results indicate the potential synthetic value of this new reaction in organic synthesis.

We successfully developed a nickel-catalyzed transamidation method for the ring opening of N-acyl lactams. The method involves a reaction between N-benzoylpyrrolidin-2-one derivatives and aniline derivatives, with Ni(PPh3)2Cl2 serving as the catalyst, 2,2'-bipyridine as the ligand, and manganese as the reducing agent. This reaction led to the formation of ring-opening-amidated products in good yields. Notably, the method exhibited excellent efficiency for producing the corresponding ring-opening transamidation products for various ring sizes, including four-, five-, six-, seven-, and eight-membered ring lactams.

A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.

We report on a new method for the synthesis of amides using acyl pyrazoles and nitroarenes under reducing conditions. It was found that acyl pyrazoles react with organo-nitro compounds in the presence of B2(OH)4, giving the corresponding amides in good yields. We demonstrated that benzoyl pyrazoles having various substituents and nitroarenes with different substituents can be used to produce a range of N-substituted benzamides. The method shows good functional group tolerance and has potential application in the synthesis of a variety of organic molecules.

Ground-state destabilization of the N-C(O) linkage represents a powerful tool to functionalize the historically inert amide bond. This burgeoning reaction manifold relies on the availability of amide bond precursors that participate in weakening of the nN → π*C=O conjugation through N-C twisting, N pyramidalization, and nN electronic delocalization. Since 2015, acyl N-C amide bond activation through ground-state destabilization of the amide bond has been achieved by transition-metal-catalyzed oxidative addition of the N-C(O) bond, generation of acyl radicals, and transition-metal-free acyl addition. This Perspective summarizes contributions of our laboratory in the development of new ground-state-destabilized amide precursors enabled by twist and electronic activation of the amide bond and synthetic utility of ground-state-destabilized amides in cross-coupling reactions and acyl addition reactions. The use of ground-state-destabilized amides as electrophiles enables a plethora of previously unknown transformations of the amide bond, such as acyl coupling, decarbonylative coupling, radical coupling, and transition-metal-free coupling to forge new C-C, C-N, C-O, C-S, C-P, and C-B bonds. Structural studies of activated amides and catalytic systems developed in the past decade enable the view of the amide bond to change from the "traditionally inert" to "readily modifiable" functional group with a continuum of reactivity dictated by ground-state destabilization.

Here, we demonstrate that α-C-H and C-N bonds of unactivated secondary amides can be activated simultaneously by the copper catalyst to synthesize α-ketoamides or α-ketoesters in one step, which is a challenging and underdeveloped transformation. Using copper as a catalyst and air as an oxidant, the reaction is compatible with a broad range of acetoamides, amines, and alcohols. The preliminary mechanism studies and density functional theory calculation indicated that the reaction process may undergo first radical α-oxygenation and then transamidation with the help of the resonant six-membered N,O-chelation and molecular oxygen plays a role as an initiator to trigger the transamidation process. The combination of chelation assistance and dioxygen selective oxygenation strategy would substantially extend the modern mild synthetic amide cleavage toolbox, and we envision that this broadly applicable method will be of great interest in the biopharmaceutical industry, synthetic chemistry, and agrochemical industry.

This Graphical Review provides an overview of amide bond activation achieved by selective oxidative addition of the N-C(O) acyl bond to transition metals and nucleophilic acyl addition, resulting in acyl and decarbonylative coupling together with key mechanistic details pertaining to amide bond distortion underlying this reactivity manifold.

Amides reacted with NaN₃ to give the acyl azides in DMF at 25 °C and produce the symmetrical ureas in THF/H₂O at 80 °C via the sequential reaction of acyl substitution and Curtius rearrangement. All acyl azides were also obtained from the secondary amides via sequential reaction of p-toluenesulfonyl chloride and NaN₃. In addition, keto-stabilized iminophosphoranes were prepared from a one-pot reaction of amides, NaN₃, and phosphines.

A transition-metal-free catalytic system was designed to address the dehydrative cross-coupling of unactivated primary/secondary alcohols with amines/amides under environmentally benign conditions. Mg²⁺ and counteranion (PF₆^-) worked synergistically to realize C-OH bond cleavage and concomitant C-N bond formation. A wide range of allylic alcohols and amines/amides were tolerated well in this transformation, which allowed C-N bond construction with high efficiency.