Intermolecular C-H silylation through cascade carbopalladation and vinylic to aryl 1,4-palladium migration.

A palladium-catalyzed remote C-H silylation reaction has been developed through vinylic to aryl 1,4-palladium migration. By using alkyne-tethered aryl iodides as the starting materials and hexamethyldisilane as the silylating reagent, the reaction involves cascade intramolecular carbopalladation, 1,4-palladium migration, and silylation with hexamethyldisilane, and leads to the formation of exocyclic alkene-containing 5-silylisoquinolines as the final products.

Palladium-Catalyzed -Carbosilylation of Alkynes to Access Isoquinolinone-Containing Exocyclic Vinylsilanes.

A Pd-catalyzed -selective carbosilylation reaction of alkynes has been developed. The -vinylpalladium species, generated through intramolecular -carbopalladation of alkynes and subsequent - isomerization, were captured by hexamethyldisilane to form multisubstituted vinylsilanes. This reaction provides a useful strategy for the stereoselective synthesis of isoquinolinone-containing exocyclic tetrasubstituted vinylsilanes.

Palladium-catalyzed diastereoselective cross-coupling of two aryl halides C-H activation: synthesis of chiral eight-membered nitrogen heterocycles.

A method for the synthesis of enantiopure eight-membered nitrogen heterocycles has been developed through diastereoselective cross-coupling of 2-iodobiphenyls with 2-bromobenzylamines. The products represent a novel type of chiral scaffold, which feature easy modification and high configurative stability and have the potential to be applied in asymmetric synthesis. Palladacycles that were formed via the C-H activation of 2-iodobiphenyls should act as the intermediates.

Diastereoselective Construction of Eight-Membered Carbocycles through Palladium-Catalyzed C(sp)-H Functionalization.

A palladium-catalyzed cross-coupling reaction of 2-alkylphenyl bromides with biphenylene has been developed. The reactions formed eight-membered carbocycles through C(sp)-H activation and the formation of two C-C bonds, and the chiral products were obtained with excellent diastereoselectivity. The reaction provides a new strategy for the construction of eight-membered carbocycles, and the products represent a novel type of chiral scaffold.

Palladium-Catalyzed Dual Coupling Reaction of 2-Iodobiphenyls with -Bromoanilines through C-H Activation: An Approach for the Synthesis of Tribenzo[,,]azepines.

A novel and straightforward approach for the synthesis of tribenzo[,,]azepines starting from 2-iodobiphenyls and 2-bromoanilines has been developed. A wide range of tribenzo[,,]azepines were obtained in good to excellent yields via a cascade intermolecular palladium-catalyzed C-H activation/dual coupling reaction. ,-palladacycles, which are generated by C-H activation of 2-iodobiphenyls, should be the reaction intermediates.

Synthesis of 3,4-Fused Tricyclic Indoles through Cascade Carbopalladation and C-H Amination: Development and Total Synthesis of Rucaparib.

3,4-Fused tricyclic indole scaffolds are ubiquitous in bioactive natural products and pharmaceuticals. A new protocol for the synthesis of 3,4-fused tricyclic indoles has been developed through cascade carbopalladation and C-H amination with ,-di--butyldiaziridinone. The protocol allows access to a range of 3,4-fused tricyclic indoles, including those containing various linkers and fused with medium-sized rings.

Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation.

A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.

Enantioselective synthesis of quaternary 3,4-dihydroisoquinolinones Heck carbonylation reactions: development and application to the synthesis of Minalrestat analogues.

Minalrestat and its analogues represent structurally novel aldose reductase inhibitors, and the asymmetric synthesis of such pharmaceutically privileged molecules has not been reported yet. We have developed a palladium-catalyzed enantioselective intramolecular carbonylative Heck reaction by using formate esters as the source of CO, which represents the first enantioselective synthesis of quaternary 3,4-dihydroisoquinolines. The reaction provides a facile and efficient method for the synthesis of enantiopure nitrogen-containing heterocyclic compounds bearing an all-carbon quaternary stereocenter.

Synthesis of Indolines by Palladium-Catalyzed Intermolecular Amination of Unactivated C(sp)-H Bonds.

A new palladium-catalyzed C(sp)-H amination reaction has been developed. 1-(-Butyl)-2-iodobenzene and its derivatives undergo palladium-catalyzed C-H activation to form palladacycles. The palladacycles are aminated with diaziridinone to form indolines as the final products.

Enantioselective Cascade Reaction for Synthesis of Quinolinones through Synergistic Catalysis Using Cu-Pybox and Chiral Benzotetramisole as Catalysts.

In contrast to the well-studied asymmetric catalyzed synthesis of tetrahydroquinolines, the asymmetric methodologies toward 3,4-dihydroquinolin-2-ones are quite rare. Herein, the first asymmetric cascade reaction is reported between ethynyl benzoxazinanones and mixed-anhydrides generated from aryl acetic acids and pivaloyl chloride, based on synergistic catalysis. This allowed the formation of attractive 3,4-dihydroquinolin-2-ones bearing two vicinal chiral centers at C3 and C4 in high yields with excellent diastereo- and enantioselectivities.

Amide-Phosphonium Salt as Bifunctional Phase Transfer Catalyst for Asymmetric 1,6-Addition of Malonate Esters to para-Quinone Methides.

Asymmetric 1,6-addition of malonates to para-quinone methides has been developed by using amide-phosphonium salts derived from easily available chiral α-amino acids as bifunctional phase transfer catalysts. Stabilized para-quinone methides with various substituents on the phenyl ring were reacted with diphenyl malonates to give functionalized diaryl methines in excellent yields and high to excellent ee's. Furthermore, to show the utility of this methodology, a gram scale synthesis of an 1,6-addition adduct and its further elaboration into the key intermediate for synthesis of GPR40 agonists were also described.

Trialkyl Methanetricarboxylate as Dialkyl Malonate Surrogate in Copper-Catalyzed Enantioselective Propargylic Substitution.

The first copper-catalyzed enantioselective propargylation of trialkyl methantricarboxylate with propargylic alcohol derivatives was developed. The tricarboxylate unit in the obtained adducts could be easily transformed into a malonate moiety by treating with in situ generated NaOEt in excellent yield without racemization.