Copper-catalyzed Cross-dehydrogenative Coupling Research Articles

Modular Synthesis of α-Aryl-α-Heteroaryl α-Amino Acid Derivatives via a Copper-Catalyzed Cross-Dehydrogenative-Coupling Reaction Using Air as the Sole Oxidant.

A novel copper-catalyzed cross-dehydrogenative-coupling (CDC) process of arylglycine derivatives with N-heteroarenes for the straightforward synthesis of α-aryl-α-heteroaryl α-amino acid scaffolds has been successfully developed. This protocol exhibits a broad substrate scope with good functional group compatibility by utilizing air as the sole oxidant. The use of the reaction is also displayed through the late-stage functionalization of arylglycines bearing natural compounds or drug motifs.

Copper-catalyzed cross-dehydrogenative coupling of P(O)−H compounds with O-/S-nucleophiles

The copper-catalyzed cross-dehydrogenative coupling of P(O)−H compounds with O-/S-nucleophiles to construct P−O bonds and P−S bonds for the synthesis of phosphinates and phosphinothioates was developed. A broad range of O- and S-nucleophiles are well tolerated in this transformation, affording the target products with good to excellent yields. This protocol is effective and convenient, which not only employed inexpensive copper iodide as the catalyst, but also avoided the use of hazadous and toxic reagents. Through the step-by-step control experiments and competitive experiments, we proposed a plausible reaction mechanism, and further confirmed that the reaction may follow a radical process.

Synthesis of N-methoxy-1‑phosphoryloxy imidates through a copper-catalyzed cross-dehydrogenative coupling of N-methoxylamides with phosphites

Phosphonates are important organic compounds, which are widely used in medicine, materials, agriculture and catalysis. In this paper, we report a copper-catalyzed cross-dehydrogenative coupling of N-methoxamides with various phosphites to synthesize a series of N-methoxy-1‑phosphoryloxy imidates. O-Functionalization of N-methoxamides has been achieved, and N-functionalization was avoided by employing this methodology. Studies show that the N-methoxy group is essential for the selectivity and activity of the reaction.

Copper-Catalyzed Cross-Dehydrogenative Coupling for Amino Acid and Peptide Synthesis

Key words copper catalysis - cross-dehydrogenative coupling - tetrasubstituted amino acids - photocatalysis

Synthesis of β‐Keto Sulfoxides via Copper(II)‐Catalyzed Aerobic Oxidation

AbstractA copper‐catalyzed cross‐dehydrogenative coupling (CDC) reaction between aromatic aldehydes and DMSO was developed, which afforded β‐keto sulfoxides in 73–92% yields. The reaction process involved base‐promoted DMSO addition to aldehydes, and copper‐catalyzed aerobic oxidation. Furthermore, the aromatic alcohols which could be oxidized to aldehydes are also suitable substrates for this catalytic system.magnified image

Synthesis of N-Methoxy-1-Phosphoryloxy Imidates Through a Copper-Catalyzed Cross-Dehydrogenative Coupling of N-Methoxylamides with Phosphites

Synthesis of N-Methoxy-1-Phosphoryloxy Imidates Through a Copper-Catalyzed Cross-Dehydrogenative Coupling of N-Methoxylamides with Phosphites

Copper-Catalyzed Cross-Dehydrogenative Coupling of α-Hydroxy Esters with Nitromethane

AbstractAn efficient copper-catalyzed tandem oxidation/nitroaldol reaction of hydroxyl compounds with nucleophiles is developed. In this work, β-nitro-α-hydroxy esters were prepared via cross-dehydrogenative coupling reaction using α-hydroxy esters as hydroxy compounds and nitromethane as a nucleophile. The reaction is believed to undergo an oxidation of the hydroxy group and then an addition of the generated carbonyl group. It is an example of CDC reactions related to hydroxy compounds via carbonyl intermediates.

Copper catalyzed cyanomethylation reaction of 4-thiazolidinone

An effective copper catalyzed Cross Dehydrogenative Coupling (CDC) reaction of 4-thiazolidinones with acetonitrile has been developed. The described strategy undergoes radical pathway by employing copper, oxidant and easily available acetonitrile as a cyanomethyl source. Various cyanomethylated 4-thiazolidinone derivatives were obtained easily and conveniently in moderate to good yield by employing this method. Substrate scope and optimization have been carried out appropriately. Optimization was carried out through different oxidants, catalyst and various additives.

Copper-Catalyzed Direct C-H Alkylation of Polyfluoroarenes by Using Hydrocarbons as an Alkylating Source.

Construction of carbon-carbon bonds is one of the most important tools in chemical synthesis. In the previously established cross-coupling reactions, prefunctionalized starting materials were usually employed in the form of aryl or alkyl (pseudo)halides or their metalated derivatives. However, the direct use of arenes and alkanes via a 2-fold oxidative C-H bond activation strategy to access chemoselective C(sp2)-C(sp3) cross-couplings is highly challenging due to the low reactivity of carbon-hydrogen (C-H) bonds and the difficulty in suppressing side reactions such as homocouplings. Herein, we present the new development of a copper-catalyzed cross-dehydrogenative coupling of polyfluoroarenes with alkanes under mild conditions. Relatively weak sp3 C-H bonds at the benzylic or allylic positions, and nonactivated hydrocarbons could be alkylated by the newly developed catalyst system. A moderate-to-high site selectivity was observed among various C-H bonds present in hydrocarbon reactants, including gaseous feedstocks and complex molecules. Mechanistic information was obtained by performing combined experimental and computational studies to reveal that the copper catalyst plays a dual role in activating both alkane sp3 C-H bonds and sp2 polyfluoroarene C-H bonds. It was also suggested that the noncovalent π-π interaction and weak hydrogen bonds formed in situ between the optimal ligand and arene substrates are key to facilitating the current coupling reactions.

Suzuki cross coupling followed by cross dehydrogenative coupling: An efficient one pot synthesis of Phenanthrenequinones and analogues

An efficient one pot protocol has been developed towards the synthesis of substituted phenanthrenequinone and analogous derivatives via Suzuki cross coupling followed by copper catalyzed cross dehydrogenative coupling.

Copper-catalyzed cross-dehydrogenative coupling between quinazoline-3-oxides and indoles.

A novel and simple protocol for the synthesis of 4-(indole-3-yl)quinazolines via cross-dehydrogenative coupling of quinazoline-3-oxides and indoles under an air atmosphere has been developed. A series of biheteroaryl products were obtained in moderate to good yields.

Synthesis of α-Substituted Primary Benzylamines through Copper-Catalyzed Cross-Dehydrogenative Coupling.

A copper-catalyzed route to α-substituted, primary benzylamines by C-H functionalization of alkylarenes is described. The method directly affords the amine hydrochloride salt. Catalyst loadings down to 0.1 mol % in combination with scalability, insensitivity to air and moisture, and no need for column chromatography makes the procedure highly practical. The facile synthesis of the racemate of a blockbuster drug highlights the relevance for the development of pharmaceuticals. Preliminary mechanistic data are also included.

Copper(II)-catalyzed-α-C(sp3)-H activation of cyclic amines: A simple and efficient strategy for the synthesis of fused pyrazole derivatives

In this paper, we have described a simple and efficient strategy for the synthesis of fused pyrazole derivatives. The key steps of our strategy involves hydroamination, copper-catalyzed cross dehydrogenative coupling (CDC) followed by aromatization (aerial oxidation) in one-pot. Our strategy offers a valuable alternative to known methods for synthesis of fused pyrazole derivatives. Overall, we have synthesized 13 diverse fused pyrazole derivatives in moderate to excellent yields.

Synthesis of (Z)-nitroalkene derivatives through oxidative dehydrogenation coupling of α-aminocarbonyl compounds with nitromethane by copper catalysis

A novel copper-catalyzed cross-dehydrogenative coupling reaction of α-amino carbonyl compounds with nitromethane to synthesis of (Z)-nitroalkene derivatives has been established. (Z)-Nitroalkene derivatives are achieved through the cleavage of sp3 CsbndH bonds and formation of CsbndC double bond, with mild reaction conditions and excellent stereoselectivity.

Copper-Catalyzed Highly Efficient Esterification of Aldehydes with N-Hydroxyphthalimide via Cross-Dehydrogenative Coupling in Water at Room Temperature

A copper-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide and aldehydes using PhI(OAc)2 as an oxidant is described. It is reported for the first time to synthesize NHPI esters in water, providing the corresponding NHPI esters in moderate to good yields. This facile and efficient method is eco-friendly and possesses the advantages of mild conditions, short reaction time, and broad substrate scope.

ChemInform Abstract: Copper‐Catalyzed Cross‐Dehydrogenative‐Coupling (CDC) of Coumarins with Cyclic Ethers and Cycloalkane.

Abstract4‐Methylcoumarins yield only trace amounts of product due to steric hindrance.

Copper-catalyzed cross-dehydrogenative coupling of pyridine N-oxides with cyclic ethers

Highly chemo- and regioselective synthesis of 2-alkylpyridine N-oxides from pyridine N-oxides and cyclic ethers has been developed through copper-catalyzed CDC reactions using CuO as the catalyst under mild reaction conditions. Optimization study showed that, K2S2O8 is the best oxidant for the reaction and the mechanistic study proved the radical pathway for this transformation. It was found that the substrates with electron donating or electron withdrawing groups could react smoothly to afford the desired products.

ChemInform Abstract: Copper‐Catalyzed Cross Dehydrogenative Coupling of N,N‐Disubstituted Formamides and Phenols: A Direct Access to Carbamates.

AbstractAn efficient process for the oxidative coupling of a variety of phenols having an ortho‐benzothiazole substituent, 8‐hydroxyquinoline and ortho‐formyl phenols with N,N‐dialkylformamides using tBuOOH as the oxidant in the presence of a Cu(II)‐catalyst is presented.

Copper-catalyzed cross-dehydrogenative coupling of N-arylacrylamides with chloroform using tert-butyl peroxybenzoate as oxidant for the synthesis of trichloromethylated 2-oxindoles

A Cu-catalyzed cross-dehydrogenative coupling of N-arylacrylamides with chloroform is achieved using tert-butyl peroxybenzoate as oxidant, and trichloromethylated oxindoles were obtained in excellent yield and regioselectivity. This reaction should proceed by cascade CCl3 radical CC addition and aryl cyclization.

ChemInform Abstract: Thioesterification of Alkylbenzenes with Thiols via Copper‐Catalyzed Cross‐Dehydrogenative Coupling Without a Directing Group.

A unique copper-catalyzed cross-dehydro- genative coupling (CDC) of thiols and alkylbenzenes has been developed for the synthesis of thioesters without the assistance of any directing group. A thio- ester moiety is created via successive CS and CO bond formation at the expense of three sp 3 CH bonds of the alkylbenzene and one sp 3 SH bond of the thiol.