CDC Reaction Research Articles

Ag-Catalyzed cross-dehydrogenative-coupling for the synthesis of 1,4-dioxan-2-yl substituted quinazoline hybrids in an aqueous medium.

We herein developed an effective approach for the construction of 2- or 4-(1,4-dioxan-2-yl) substituted quinazolines under mild conditions. A silver-K2S2O8 catalyzed direct CDC reaction between quinazolines and 1,4-dioxane for the synthesis of a series of 2- or 4-(1,4-dioxan-2-yl) substituted quinazoline hybrids is reported. The reaction proceeded well in water under mild conditions and showed a broad substrate scope and good functional group compatibility.

Cross Dehydrogenative Coupling of Chloro‐ and Fluoroalkanes with Methylarenes

Cross dehydrogenative coupling reactions (CDCs) are considerably more step- and atom efficient compared to classical cross coupling methods. In this context, the photochemical CDCs of hydrochlorocarbons and hydrofluorocarbons with methylarenes are herein described. This unprecedented CDC reaction concept enables a new retrosynthetic cut for the selective construction of valuable chlorinated and fluorinated organic skeletons, from industrially important dichloromethane, dichloroethane, difluoromethane (HFC-32), and 1,1,1,2-tetrafluoroethane (HFC-134a).

Visible-light-induced direct C–N coupling of benzofurans and thiophenes with diarylsulfonimides promoted by DDQ and TBN

A visible-light-induced direct imidation of five-membered heteroaromatics with diarylsulfonimides via CDC reaction in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)/tert-butyl nitrite (TBN)/O2 is reported. Under the optimized conditions, various benzofurans/thiophenes can be coupled with a range of diarylsulfonimides to give their corresponding imidation products in moderate to excellent yields. This method is characterized by mild reaction conditions, metal-free catalysis and the use of a green oxidant.

Separated redox site strategies for engineering highly efficient photocatalysts: a pagoda-like In2O3/CuO heteroepitaxial structure coated with a N-doped C layer

Novel In2O3/CuO@N-C micro-rods with effective separation of redox sites have been synthesized and they exhibited excellent photocatalytic activity for the CDC reaction.

Rh(III)-catalyzed direct cross-dehydrogenative coupling of aromatic nitriles with heteroarenes: Rapid access to biheteroaryl-2-carbonitriles

Transition-metal-catalyzed direct C–H/C–H cross-coupling reactions as efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds. However, the strategy for preparation of biphenyl-2-carbonitriles has not been well established. Herein, we described the first cyanogen directed Rh(III)-catalyzed CDC reaction of aromatic nitriles with heteroarenes. Various biphenyl-2-carbonitrilederivatives were obtained with broad functional group compatibility.

CuMgAl hydrotalcite as an efficient bifunctional catalyst for the cross-dehydrogenative C–C coupling reactions under mild conditions

CuMgAl layered double hydroxide compounds (CuMgAl-LDHs) have been synthesized, characterized and investigated in the aerobic CDC reactions. The results indicated that NH3·H2O coprecipitated CuMgAl LDH (N-CuMgAl-LDH) was able to efficiently accelerate the CDC reactions between the α-Csp3–H of N-aryltetrahydroisoquinolines and nucleophiles. A wide scope of N-aryltetrahydroisoquinoline analogues and nucleophiles with different CH bonds (Csp3–H, Csp2–H and Csp–H) could be tolerated by the N-CuMgAl-LDH system. Compared with the sample using Na2CO3 as the precipitant (C-CuMgAl-LDH), N-CuMgAl-LDH showed higher catalytic activity, which probably was due to its higher surface acidity. Dual function of redox and acidity for the N-CuMgAl-LDH catalyst has been observed in the CDC reaction. According to the obtained catalytic results, kinetic isotope effect experiment and XPS analysis, iminium ion was proposed as the key intermediate, made possible by the cycle of Cu2+ and Cu+ under the aerobic conditions.

Selective C(sp3)−H Functionalization of Alkyl Esters with N‐/S‐/O‐Nucleophiles Using Perfluoroalkyl Iodide as Oxidant

AbstractAn efficient transition metal‐free approach to achieve the selective cleavage of the α‐carbonyl C(sp3)−H bond in alkyl esters by using inexpensive, low‐toxic, and insensitive perfluoroalkyl iodide as the radical initiator has been developed. A variety of enamides, N‐heterocycles, amides, thiophenols, and phenols could be successfully incorporated into functionalized alkyl groups by intermolecular amination, thioetherification, and etherification. The distinguishing features of this CDC reaction are its broad substrate scope, synthetic simplicity, and mild reaction conditions.magnified image

Transition-Metal-Controlled Synthesis of 11H-Benzo[a]carbazoles and 6-Alkylidene-6H-isoindo[2,1-a]indoles via Sequential Intermolecular/Intramolecular Cross-Dehydrogenative Coupling from 2-Phenylindoles.

A catalyst-controlled synthesis of 11H-benzo[a]carbazoles and 6-alkylidene-6H-isoindo[2,1-a]indoles is described. Pd(OAc)2 favored 6-alkylidene-6H-isoindo[2,1-a]indoles via intramolecular C-H/N-H CDC reaction, while [Cp*RhCl2]2 led to 11H-benzo[a]carbazoles through intramolecular C-H/C-H CDC reaction. Moreover, the synthesis of 11H-benzo[a]carbazoles via sequential intermolecular ortho C-H/olefin coupling and intramolecular C3-H/olefin coupling from 2-phenylindoles and alkenes can be operated in one pot.

Dehydrogenative C(sp3)-H bond functionalization of tetrahydroisoquinolines mediated by organic oxidants under mild conditions.

The organocatalyzed Mannich reaction of unsubstituted and N-aryl-substituted tetrahydroisoquinolines (THIQs) and the Strecker reaction of several N-aryl-substituted THIQs through dehydrogenative C(sp3)-H bond functionalization (cross-dehydrogenative coupling) promoted by organic single electron oxidants DDQ and IBX are presented. The C-H oxidation/Mannich reaction of less reactive N-aryl substituted pyrrolidines is achieved via metal catalyzed photoredox catalysis. Operationally simple procedures provide desired products in an effective and time preserving manner.

Direct intramolecular double cross-dehydrogentive-coupling (CDC) cyclization of N-(2-pyridyl)amidines under metal-free conditions.

A facile transition-metal-free protocol to form 2-iminoimidazo[1, 2-a]-pyridines bearing a –CHBr2 group and an aza-quaternary carbon center at the 3 position from N-(2-pyridyl)amidines substrates, in which the new heterocyclic skeletons constructed from amidines via radical reactions or nucleophilic substitution reactions are promoted only by CBr4 under mild conditions, is demonstrated. The reactions were realized by intramolecular CDC reaction involving C–N and C–C bond formation via the sequential C(sp3)–H bifunctionalization mode on the same carbon atom under mild conditions. Moreover, this work also provides an excellent and representative example for CBr4 as an efficient reagent to initiate radical reactions under initiator-free conditions or to give rise to nucleophilic substitution reactions only by base.

Synthesis of rutaecarpine alkaloids via an electrochemical cross dehydrogenation coupling reaction

We have developed a metal- and oxidant-free method for the synthesis of rutaecarpine alkaloids via an electrochemical CDC reaction.

Copper‐Catalyzed Direct Oxidative α‐Functionalization of Tetrahydroquinoline in Water under Mild Conditions

AbstractAn efficient one‐step α‐functionalization of tetrahydroquinoline under mild conditions is achieved. The direct oxidative copper‐catalyzed dehydrogenative cross C(sp3)−C(sp2) couplings of tetrahydroquinolines and indoles produced the products in aqueous and open air medium. The use of inexpensive copper catalyst, water solvent, easy to operate open air condition combined with the most step and atom economic features qualify the CDC reaction for a green process.magnified image

A visible-light-promoted cross-dehydrogenative-coupling reaction of N-arylglycine esters with imidazo[1,2-a]pyridines

A mild and convenient visible-light-promoted cross-dehydrogenative-coupling reaction between N-arylglycine esters and imidazo[1,2-a]pyridines for the construction of CC bond was developed. A range of N-arylglycine esters and imidazo[1,2-a]pyridines were able to undergo the CDC reaction readily to afford α-heteroaryl substituted α-amino acid derivatives in good to excellent yields. A tentative mechanism for the photoredox reaction was also proposed. Importantly, the use of copper(II) salt as the sole catalyst in this visible-light-promoted transformation makes this reaction sustainable and practical.

A copper/O2-mediated direct sp3 C-H/N-H cross-dehydrogen coupling reaction of acylated amines and N-aryl glycine esters.

A copper salt-catalyzed cross-dehydrogenative coupling reaction between N-aryl glycine esters and acylated amines has been developed. The reaction proceeded effectively under an oxygen atmosphere without the use of peroxide agents. This simple protocol allows for the preparation of a series of new compounds in a moderate to excellent yield via the CDC reaction of a wide range of N-aryl glycine derivatives with acylated amines, which are of great interest in the field of medicinal chemistry. A plausible mechanism involving the formation of an iminium ion intermediate, followed by coupling with acylated amines was proposed after some control experiments were conducted.

A new route to π-extended polycyclic aromatic hydrocarbons via cross-dehydrogenative coupling

A rare example of fruitful construction of highly π-extended PAHs expressly via palladium-catalyzed CDC reaction is demonstrated.

Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement.

A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross-dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant).

A Highly Effective Ruthenium System for the Catalyzed Dehydrogenative Cyclization of Amine-Boranes to Cyclic Boranes under Mild Conditions.

We recently disclosed a new ruthenium-catalyzed dehydrogenative cyclization process (CDC) of diamine-monoboranes leading to cyclic diaminoboranes. In the present study, the CDC reaction has been successfully extended to a larger number of diamine-monoboranes (4-7) and to one amine-borane alcohol precursor (8). The corresponding NB(H)N- and NB(H)O-containing cyclic diaminoboranes (12-15) and oxazaborolidine (16) were obtained in good to high yields. Multiple substitution patterns on the starting amine-borane substrates were evaluated and the reaction was also performed with chiral substrates. Efforts have been spent to understand the mechanism of the ruthenium CDC process. In addition to a computational approach, a strategy enabling the kinetic discrimination on successive events of the catalytic process leading to the formation of the NB(H)N linkage was performed on the six-carbon chain diamine-monoborane 21 and completed with a (15) N NMR study. The long-life bis-σ-borane ruthenium intermediate 23 possessing a reactive NHMe ending was characterized in situ and proved to catalyze the dehydrogenative cyclization of 1, ascertaining that bis σ-borane ruthenium complexes are key intermediates in the CDC process.

ChemInform Abstract: Sulfuryl Chloride as an Efficient Initiator for the Metal‐Free Aerobic Cross‐Dehydrogenative Coupling Reaction of Tertiary Amines.

A metal-free cross-dehydrogenative (CDC) reaction of tertiary amines was developed using a catalytic amount of sulfuryl chloride (SO2Cl2) under mild aerobic conditions. On the basis of the nature of SO2Cl2, it was assumed that the reagent acts as a radical initiator to induce the metal-free CDC reaction via a radical-initiated autoxidation mechanism.

ChemInform Abstract: Palladium‐Catalyzed Oxidative C—H/C—H Cross‐Coupling of Benzothiazoles with Thiophenes and Thiazoles

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Sulfuryl chloride as an efficient initiator for the metal-free aerobic cross-dehydrogenative coupling reaction of tertiary amines.

A metal-free cross-dehydrogenative (CDC) reaction of tertiary amines was developed using a catalytic amount of sulfuryl chloride (SO2Cl2) under mild aerobic conditions. On the basis of the nature of SO2Cl2, it was assumed that the reagent acts as a radical initiator to induce the metal-free CDC reaction via a radical-initiated autoxidation mechanism.