Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Language: Английский

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Classes of Amides that Undergo Selective N–C Amide Bond Activation: The Emergence of Ground-State Destabilization

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 88(19), P. 13371 - 13391

Published: Sept. 2, 2022

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

Language: Английский

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Applications of palladium-catalyzed C–N cross-coupling reactions in pharmaceutical compounds

RSC Advances, Journal Year: 2023, Volume and Issue: 13(27), P. 18715 - 18733

Published: Jan. 1, 2023

C–N cross-coupling bond formation reactions have become valuable approaches to synthesizing anilines and their derivatives which are known as important chemical compounds.

Language: Английский

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Photomediated reductive coupling of nitroarenes with aldehydes for amide synthesis

Chemical Science, Journal Year: 2022, Volume and Issue: 13(32), P. 9361 - 9365

Published: Jan. 1, 2022

In view of the widespread significance amide functional groups in organic synthesis and pharmaceutical studies, an efficient practical synthetic protocol that avoids use stoichiometric activating reagents or metallic reductants is highly desirable. A straight-forward pathway to access amides from abundant chemical feedstock would offer a strategic advantage complex amides. We herein disclose direct reductive amidation reaction using readily available aldehydes nitroarenes enabled by photo-mediated hydrogen atom transfer catalysis. It production toxic waste. While represent classic class electrophilic synthons, corresponding nucleophilic acyl radicals could be directly accessed photo catalysis, enabling polarity inversion. Our method provides orthogonal strategy conventional couplings, tolerating substituents such as free alcohols sensitive amines carbonyl formyl groups. The utilization this demonstrated late-stage modification biologically active molecules drug leflunomide lidocaine.

Language: Английский

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Titanium‐Catalyzed Exhaustive Reduction of Oxo‐Chemicals

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 20, 2022

Catalytic reduction of carboxylic acids and derivatives all the way to their corresponding methyl-compounds is very rare still challenging for homogeneous transition-metal catalysis. Herein, we report an unprecedented general catalytic exhaustive functional group straightforwardly a methyl group. This reaction was achieved using earth-abundant readily available titanium as catalyst. Our system has broad tolerance works various other types oxo-chemicals such alcohols, aldehydes, ketones, lactones, carboxylates (>100 examples). Preliminary mechanistic studies revealed that in situ-generated TiIII -H species vital this transformation.

Language: Английский

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Copper-Catalyzed Transamidation of Unactivated Secondary Amides via C–H and C–N Bond Simultaneous Activations

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(4), P. 2140 - 2157

Published: Jan. 26, 2023

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 underdeveloped transformation. Using as air an oxidant, reaction compatible with broad range acetoamides, amines, alcohols. The preliminary mechanism studies density functional theory calculation indicated process may undergo first radical α-oxygenation then transamidation help resonant six-membered N,O-chelation molecular oxygen plays role initiator trigger process. combination chelation assistance dioxygen selective oxygenation strategy would substantially extend modern mild synthetic amide cleavage toolbox, envision this broadly applicable method will great interest biopharmaceutical industry, chemistry, agrochemical industry.

Language: Английский

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Masters of Mediation: MN(SiMe₃)₂ in Functionalization of C(sp³)−H Latent Nucleophiles

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(29)

Published: March 18, 2024

Abstract Organoalkali compounds have undergone a far‐reaching transformation being coupling partner to mediator in unusual organic conversions which finds its spot the field of sustainable synthesis. Transition‐metal catalysis has always been priority C( sp 3 )−H bond functionalization, however alternatively, recent times this seriously challenged by earth‐abundant alkali metals and their complexes arriving at new organometallic reagents. In line, importance MN(SiMe ) 2 (M=Li, Na, K & Cs) reagent revived functionalization over years synthesis is showcased minireview. with higher reactivity, enhanced stability, bespoke cation‐π interaction shown eye‐opening mediated processes such as )−C( cross‐coupling, radical‐radical aminobenzylation, annulation, aroylation, other transformations utilize readily available petrochemical feedstocks. This article also emphasizes reactivity unreactive robust C−X (X=O, N, F, C) cleavage reactions that occurred alongside functionalization. Overall, review encourages community exploit untapped potential inspires them take up subject even greater heights.

Language: Английский

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Reaction of Amide and Sodium Azide for the Synthesis of Acyl Azide, Urea, and Iminophosphorane

Organic Letters, Journal Year: 2022, Volume and Issue: 24(33), P. 6186 - 6191

Published: Aug. 12, 2022

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

Language: Английский

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Visible-light induced FeCl₃-catalyzed reductive transamidation of N-acyl benzotriazoles with nitro compounds

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(7), P. 2095 - 2101

Published: Jan. 1, 2024

A mild and efficient visible-light promoted FeCl 3 -catalyzed reductive transamidation of N -acyl benzotriazoles with nitro compounds by PhSiH was developed.

Language: Английский

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Ring Opening of N-Acyl Lactams Using Nickel-Catalyzed Transamidation

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(2), P. 1336 - 1344

Published: Jan. 4, 2024

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

Language: Английский

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