Bonds Of Aliphatic Amides Research Articles

Pd(II)‐Catalyzed Selective Amination of Inert γ‐C(sp3)−O Bonds of Aliphatic Amides with Hydrazines

AbstractThe first palladium‐catalyzed selective amination of inert methyl and methylene γ‐C(sp3)−O bonds of aliphatic amides with hydrazines by using the strategy of 8‐aminoquinoline‐directed C(sp3)−H activation/β‐O elimination/hydrofunctionalization is reported. This method features a broad scope of hydrazines, affording an efficient and simple method for the synthesis of corresponding γ‐hydrazine substituted carboxylic acid derivatives that are commonly seen in drug molecules and other bioactive compounds.

Palladium‐Catalyzed Selective Carbofunctionalization of Inert γ‐C(sp3)−O Bonds with 4‐Hydroxypyridin‐2(1H)‐ones and 4‐Hydroxy‐2H‐pyran‐2‐ones

AbstractThe palladium‐catalyzed selective carbofunctionalization of inert γ‐C(sp3)−O bonds of aliphatic amides by using the strategy of sp3 C−H activation/β‐O elimination/hydrocarbofunctionalization with the assistance of 8‐aminoquinolyl directing group is presented here. This method features a broad scope of both 4‐hydroxypyridin‐2(1H)‐ones and 4‐hydroxy‐2H‐pyran‐2‐ones, providing a versatile method for the synthesis of corresponding γ‐substituted amide derivatives.magnified image

Nickel-Catalyzed Annulation of Aliphatic Amides with Alkynyl­silanes: An Expeditious Approach to Five-Membered Lactams

An expeditious approach for the synthesis of diverse five-membered lactams through nickel-catalyzed annulation of the C(sp3)–H bonds of aliphatic amides with alkynylsilanes assisted by an 8-aminoquinolinyl directing group is reported, delivering the corresponding lactam derivatives in moderate to high yields. It is worth noting that alkynylsilanes are employed for the first time as coupling partners in the transition-metal-catalyzed functionalization of C(sp3)–H bonds of aliphatic amides. Equimolar amounts of alkynylsilanes and aliphatic amides are utilized, which greatly increases the efficiency of this protocol.

Facile synthesis of unnatural β-germyl-α-amino amides via Pd(ii)-catalyzed primary and secondary C(sp3)-H bond germylation.

Pd(ii)-Catalyzed direct C(sp3)-H germylation of α-AA derivatives with the assistance of a bidentate auxiliary for the efficient synthesis of β-germyl-α-amino amides is reported. This protocol features good generality for primary and secondary C-H bonds of aliphatic amides. Mechanistic studies show that a crucial five-membered palladacycle intermediate may play a key role in this process.

Cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds.

A general efficient regioselective cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was demonstrated using atmospheric (1-2 atm) carbon monoxide as a C1 source. This straightforward approach provides access to α-spiral succinimide regioselectively in a good yield. Cobalt catalyzed sp3 C-H bond carbonylation is reported for the first time including the functionalization of (β)-C-H bonds of α-1°, 2°, 3° carbons and even internal (β)-C-H bonds. Our initial mechanistic investigation reveals that the C-H activation step is irreversible and will possibly be the rate determining step.

Copper‐Catalyzed Bromination of C(sp3)−H Bonds Distal to Functional Groups

AbstractSelective bromination of γ‐methylene C(sp3)−H bonds of aliphatic amides and δ‐methylene C(sp3)−H bonds of nosyl‐protected alkyl amines are developed using NBS as the brominating reagent and catalytic amount of CuII/phenanthroline complexes as the catalyst. Aryl and benzylic C−H bonds at other locations remain intact during this directed radical abstraction reaction.

Copper-Catalyzed Bromination of C(sp3 )-H Bonds Distal to Functional Groups.

Selective bromination of γ-methylene C(sp3 )-H bonds of aliphatic amides and δ-methylene C(sp3 )-H bonds of nosyl-protected alkyl amines are developed using NBS as the brominating reagent and catalytic amount of CuII /phenanthroline complexes as the catalyst. Aryl and benzylic C-H bonds at other locations remain intact during this directed radical abstraction reaction.

Nickel-Catalyzed Oxidative Coupling of Unactivated C(sp3)–H Bonds in Aliphatic Amides with Terminal Alkynes

In this work, we demonstrated Ni-catalyzed oxidative coupling of unactivated C(sp3)–H bonds with terminal alkynes for construction of C(sp3)–C(sp) bonds to synthesize alkyl-substituted internal alkynes. Different amides exhibited good compatibility. Preliminary mechanistic studies were conducted to account for this alkynylation.

Ligand-accelerated enantioselective methylene C(sp3)-H bond activation.

Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C-H bonds in aliphatic amides. Using bidentate ligands to accelerate C-H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C-H activation is also demonstrated by enantioselective β-C-H arylation of simple carboxylic acids without installing directing groups.

ChemInform Abstract: Phenyltrimethylammonium Salts as Methylation Reagents in the Nickel‐Catalyzed Methylation of C—H Bonds.

AbstractA surprising methylation of C(sp3)—H bonds in aliphatic amides and of C(sp2)—H bonds in benzamides with phenyltrimethylammonium iodide as methyl source is reported.

Phenyltrimethylammonium Salts as Methylation Reagents in the Nickel‐Catalyzed Methylation of C−H Bonds

AbstractMethylation of C(sp2)−H bonds was achieved through the NiII‐catalyzed reaction of benzamides with phenyltrimethylammonium bromide or iodide as the source of the methyl group. The reaction has a broad scope and shows high functional‐group compatibility. The reaction is also applicable to the methylation of C(sp3)−H bonds in aliphatic amides.

Phenyltrimethylammonium Salts as Methylation Reagents in the Nickel-Catalyzed Methylation of C-H Bonds.

Methylation of C(sp(2))-H bonds was achieved through the Ni(II)-catalyzed reaction of benzamides with phenyltrimethylammonium bromide or iodide as the source of the methyl group. The reaction has a broad scope and shows high functional-group compatibility. The reaction is also applicable to the methylation of C(sp(3))-H bonds in aliphatic amides.

Palladium-catalyzed ligand-promoted site-selective cyanomethylation of unactivated C(sp3)-H bonds with acetonitrile.

The direct cyanomethylation of unactivated sp3 C-H bonds of aliphatic amides was achieved via palladium catalysis assisted by a bidentate directing group with good functional group compatibility. This process represents the first example of the direct cross-coupling of sp3 C-H bonds with acetonitrile. Considering the importance of the cyano group in medicinal and synthetic organic chemistry, this reaction will find broad application in chemical research.

Pd(II)-catalyzed Chelation-assisted Cross Dehydrogenative Coupling between Unactivated C(sp3)–H Bonds in Aliphatic Amides and Benzylic C–H Bonds in Toluene Derivatives

The chelation-assisted cross dehydrogenative coupling of C(sp3)–H bonds is achieved by the Pd(II)-catalyzed reaction of aliphatic amides that contain a 5-chloro-8-aminoquinoline moiety as the direc...

ChemInform Abstract: Nickel‐Catalyzed Addition‐Type Alkenylation of Unactivated, Aliphatic C—H Bonds with Alkynes: A Concise Route to Polysubstituted γ‐Butyrolactones.

AbstractThe β‐C(sp3)—H bonds of aliphatic amides containing a quinolinyl group [e.g. (I)] are activated by nickel through a chelation.

ChemInform Abstract: Palladium‐Catalyzed Asymmetric Arylation of C(sp3)—H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids.

AbstractAmong various chiral ligands tested, BPA is found to be the most efficient one.

ChemInform Abstract: Pd(II)‐Catalyzed Pyridine N‐Oxides Directed Arylation of Unactivated C(sp3)—H Bonds.

AbstractThe novel Pd(II)‐catalyzed pyridine N‐oxide directed arylation of unactivated C(sp3)—H bonds in aliphatic amides with aryl iodides allows to install various aryl groups at the β‐ or γ‐C(sp3) atom of alkyl carboxylic acid amides.

Palladium-Catalyzed Asymmetric Arylation of C(sp(3))-H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids.

Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

ChemInform Abstract: Direct Arylation of C(sp3)—H Bonds in Aliphatic Amides with Diaryliodonium Salts in the Presence of a Nickel Catalyst.

The Ni(II)-catalyzed direct arylation of C(sp3)–H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as the directing group with diaryliodonium salts as coupling electrophiles is described. A wide variety of functional groups are tolerated in the reaction. The reaction represents the first example of the Ni-catalyzed direct arylation of C(sp3)–H bonds with diaryliodonium salts.

Nickel-Catalyzed Addition-Type Alkenylation of Unactivated, Aliphatic C-H Bonds with Alkynes: A Concise Route to Polysubstituted γ-Butyrolactones.

Through the nickel-catalyzed chelation-assisted C-H bond activation strategy, the addition-type alkenylation of unreactive β-C(sp(3))-H bonds of aliphatic amides with internal alkynes is developed for the first time to produce γ,δ-unsaturated carboxylic amide derivatives. The resulting alkenylated products can further be transformed into polysubstituted γ-butyrolactones with pyridinium chlorochromate (PCC).