Highly Efficient Four‐Component Synthesis of 4(3H)‐Quinazolinones: Palladium‐Catalyzed Carbonylative Coupling Reactions

Given the importance of quinazolinones and carbonylative transformations, a palladium‐catalyzed four‐component carbonylative coupling system for the synthesis of diverse 4(3H)‐quinazolinone in a concise and convergent fashion has been developed. Starting from 2‐bromoanilines (1 mmol), trimethyl orthoformate (2 mmol), and amines (1.1 mmol), under 10 bar of CO, the desired products were isolated in good yields in the presence of Pd(OAc)₂ (2 mol %), BuPAd₂ (6 mol %) in 1,4‐dioxane (2 mL) at 100 °C, using N,N‐diisopropylethylamine (2 mmol) as the base. Notably, the process tolerates the presence of various reactive functional groups and is very selective for quinazolinones, and was used in the synthesis of the precursor to the bioactive dihydrorutaempine.     

Copper‐Catalyzed Aerobic Oxidative CC Bond Cleavage for CN Bond Formation: From Ketones to Amides

A novel copper‐catalyzed aerobic oxidative C(CO)? C(alkyl) bond cleavage reaction of aryl alkyl ketones for C? N bond formation is described. A series of acetophenone derivatives as well as more challenging aryl ketones with long‐chain alkyl substituents could be selectively cleaved and converted into the corresponding amides, which are frequently found in biologically active compounds and pharmaceuticals.     

Nickel‐Catalyzed Enantioselective CC Bond Formation through CO Cleavage in Aryl Esters

We report the first enantioselective C? C bond formation through C? O bond cleavage using aryl ester counterparts. This method is characterized by its wide substrate scope and results in the formation of quaternary stereogenic centers with high yields and asymmetric induction.     

Ruthenium‐Catalyzed CC Bond Cleavage in Lignin Model Substrates

Ruthenium–triphos complexes exhibited unprecedented catalytic activity and selectivity in the redox‐neutral C? C bond cleavage of the β‐O‐4 lignin linkage of 1,3‐dilignol model compounds. A mechanistic pathway involving a dehydrogenation‐initiated retro‐aldol reaction for the C? C bond cleavage was proposed in line with experimental data and DFT calculations.     

Palladium‐Catalyzed Dearomative Cyclocarbonylation by CN Bond Activation

A fundamentally novel approach to bioactive quinolizinones is based on the palladium‐catalyzed intramolecular cyclocarbonylation of allylamines. [Pd(Xantphos)I₂], which features a very large bite angle, has been found to facilitate the rapid carbonylation of azaarene‐substituted allylamines into bioactive quinolizinones in good to excellent yields. This transformation represents the first dearomative carbonylation and is proposed to proceed by palladium‐catalyzed C? N bond activation, dearomatization, CO insertion, and a Heck reaction.     

Rhodium(III)‐Catalyzed Three‐Component Reaction of Imines,Alkynes, and Aldehydes through CH Activation

An efficient rhodium(III)‐catalyzed tandem three‐component reaction of imines, alkynes and aldehydes through C?H activation has been developed. High stereo‐ and regioselectivity, as well as good yields were obtained in most cases. The simple and atom‐economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.     

Palladium‐Catalyzed Direct CH Functionalization of Benzoquinone

A direct Pd‐catalyzed C? H functionalization of benzoquinone (BQ) can be controlled to give either mono‐ or disubstituted BQ, including the installation of two different groups in a one‐pot procedure. BQ can now be directly functionalized with aryl, heteroaryl, cycloalkyl, and cycloalkene groups and, moreover, the reaction is conducted in environmentally benign water or acetone as solvents.     

One‐Pot Palladium‐Catalyzed Borrowing Hydrogen Synthesis of Thioethers

Palladium on magnesium oxide is able to allow a one‐pot reaction to synthesize thioethers from thiols and aldehydes formed in situ from the respective alcohol by means of a borrowing hydrogen method. The reaction is initiated by dehydrogenation of the alcohol to give a palladium hydride intermediate and an aldehyde. The latter reacts with a thiol involving most probably the intermediacy of a thionium ion RCH?S⁺R, which can be reduced in situ by the metal hydride to afford thioethers.     

Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Palladium‐Catalyzed Cascade CH Trifluoroethylation of Aryl Iodides and Heck Reaction: Efficient Synthesis of ortho‐Trifluoroethylstyrenes

A palladium‐catalyzed selective C? H bond trifluoroethylation of aryl iodides has been explored. The reaction allows for the efficient synthesis of a variety of ortho‐trifluoroethyl‐substituted styrenes. Preliminary mechanistic studies indicate that the reaction might involve a key Pd^IV intermediate, which is generated through the rate‐determining oxidative addition of CF₃CH₂I to a palladacycle; the bulky nature of CF₃CH₂I influences the reactivity. Reductive elimination from the Pd^IV complex then leads to the formation of the aryl–CH₂CF₃ bond.     

Palladium‐Catalyzed Carbonylative Four‐Component Synthesis of Thiochromenones: The Advantages of a Reagent Capsule

Multicomponent reactions, especially those involving four or even more reagents, have been a long‐standing challenge because of the issues associated with balancing reactivity, selectivity, and compatibility. Herein, we demonstrate how the use of a reagent capsule provides straightforward access to synthetically valuable thiochromenone derivatives by a palladium‐catalyzed carbonylative four‐component reaction. To the best of our knowledge, this is the first example of applying a capsule to prevent catalyst poisoning and undesired side reactions of the multicomponent reaction.     

Highly Efficient CSeCF3 Coupling of Aryl Iodides Enabled by an Air‐Stable Dinuclear PdI Catalyst

Building on our recent disclosure of catalysis at dinuclear Pd^I sites, we herein report the application of this concept to the realization of the first catalytic method to convert aryl iodides into the corresponding ArSeCF₃ compounds. Highly efficient C? SeCF₃ coupling of a range of aryl iodides was achieved, enabled by an air‐, moisture‐, and thermally stable dinuclear Pd^I catalyst. The novel SeCF₃‐bridged dinuclear Pd^I complex 3 was isolated, studied for its catalytic competence and shown to be recoverable. Experimental and computational data are presented in support of dinuclear Pd^I catalysis.     

Modular Synthesis of Multisubstituted Furans through Palladium‐Catalyzed Three‐Component Condensation of Alkynylbenziodoxoles,Carboxylic Acids,and Imines

Mild and regiocontrolled synthesis of a multisubstituted furan is achieved through Pd(OAc)₂‐catalyzed room‐temperature condensation of an alkynylbenziodoxole, a carboxylic acid, and an enolizable ketimine, which contribute to C1, CO, and C2 fragments, respectively, to the furan skeleton. The reaction tolerates a broad range of functional groups in each of the reaction components, and enables highly modular and flexible synthesis of variously substituted furans. The reaction is particularly effective for the rapid generation of tri‐ and tetraarylfurans and furan‐containing oligoarylenes without relying on conventional cross‐coupling chemistry.     

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal‐catalyzed C?H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N‐oxide is used as an arene source in C?H activation studies, the N?O bond can act as a directing group as well as an O‐atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N?O bond and alkynes, which results in C?H activation and O‐atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh?C bond, a reductive elimination to form an oxazinoquinolinium‐coordinated Rh^I intermediate, an oxidative addition to break the N?O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop‐1‐yn‐1‐ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1‐phenyl‐2‐quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity‐determining step. These calculated data are consistent with the experimental observations.