Enantioselective synthesis of polycyclic pyrrole derivatives by iridium-catalyzed asymmetric allylic dearomatization and ring-expansive migration reactions.

Herein, we report an N-alkylation of pyrroles triggered by an unprecedented selective ring-expansive migration of the spiro-2H-pyrrole intermediates obtained via Ir-catalyzed asymmetric allylic dearomatization. The reaction affords a series of tetrahydropyrrolo[1,2-c]pyrimidine derivatives in good yields (up to 88%) with excellent enantioselectivity (up to >99% ee). The proposed reaction mechanism is supported by DFT calculations and the characterization of the key intermediate.

Palladium(0)-Catalyzed Intermolecular Asymmetric Allylic Dearomatization of Polycyclic Indoles.

An intermolecular Pd-catalyzed allylic dearomatization reaction of polycyclic indoles with substituted allylic carbonates was realized in the presence of a newly synthesized chiral phosphoramidite ligand. Various polycyclic indoline and indolenine derivatives were successfully synthesized in excellent yields (up to 99%) with excellent enantioselectivity (up to 98% ee). The obtained products could undergo versatile transformations, increasing the application potential of the method in organic synthesis.

Synthesis of C3-Methyl-Substituted Pyrroloindolines and Furoindolines via Cascade Dearomatization of Indole Derivatives with Methyl Iodide.

A highly efficient method for constructing C3-methyl-substituted pyrroloindolines and furoindolines via cascade dearomatization reaction of indole derivatives with methyl iodide was developed. This protocol offers a direct approach to a wide range of C3 methyl substituted pyrroloindolines under mild conditions. The utility of this method was further demonstrated in the concise synthesis of (±)-esermethol.

Iridium-Catalyzed Enantioselective Synthesis of Pyrrole-Annulated Medium-Sized-Ring Compounds.

Enantioselective synthesis of pyrrole-annulated medium-sized-ring compounds by an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis sequence is presented. Various substituted pyrrole-annulated seven- and eight-membered-ring products were obtained under mild reaction conditions with moderate to good yields and excellent enantioselectivity. Additionally, these products contain a scaffold widely distributed in natural products and biologically active compounds. The current method provides a convenient way for accessing such pyrrole-anuulated medium-sized-ring compounds.

Pd-catalyzed cascade allylic alkylation and dearomatization reactions of indoles with vinyloxirane.

We have developed Pd-catalyzed intermolecular Friedel-Crafts-type allylic alkylation and allylic dearomatization reactions of substituted indoles bearing a nucleophilic group with vinyloxirane, providing an efficient method to synthesize structurally diverse tetrahydrocarboline and spiroindolenine derivatives under mild conditions.

Palladium(0)-Catalyzed Intermolecular Allylic Dearomatization of Indoles by a Formal [4+2] Cycloaddition Reaction.

Bridged indoline derivatives were synthesized by an intermolecular Pd-catalyzed allylic dearomatization reaction of substituted indoles. The reaction between indoles and allyl carbonates bearing a nucleophilic alcohol side-chain proceeds in a cascade fashion, providing bridged indolines in excellent enantioselectivity.

An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand.

Copper(I)-Catalyzed Asymmetric Dearomatization of Indole Acetamides with 3-Indolylphenyliodonium Salts.

The rapid and direct asymmetric synthesis of 3-(3a-indolyl)hexahydropyrroloindoline motifs is an extremely important part of the total synthesis of several alkaloid structures. Herein, an intermolecular, asymmetric cascade dearomatization reaction of indole acetamides with 3-indolylphenyliodonium salts has been developed. This protocol provides a straightforward access to 3-(3a-indolyl)hexahydropyrroloindolines bearing an all-carbon quaternary stereocenter at the C3 position of the indoline ring with high enantioselectivities. The utility of the protocol has been demonstrated by the formal asymmetric synthesis of folicanthine.

Enantioselective Synthesis of Indole-Annulated Medium-Sized Rings.

Asymmetric synthesis of indole-annulated medium-sized-ring compounds is developed through an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis cascade reaction. The reaction features mild conditions and a broad substrate scope. Under the optimal conditions, various seven-, eight-, or nine-membered-ring compounds can be afforded in good to excellent yields and excellent enantioselectivity. The proposed mechanism is supported by capturing the dearomatized intermediate through in situ reduction.

Enantioselective Synthesis of 3a-Amino-Pyrroloindolines by Copper-Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines.

A direct asymmetric dearomative amination of tryptamines with O-(2,4-dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr-bisoxazoline complex as a catalyst, affording 3a-amino-pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (-)-psychotriasine in a highly concise manner.

Synthesis of pyrroloindolines and furoindolines via cascade dearomatization of indole derivatives with carbenium ion.

A highly efficient intermolecular cascade dearomatization of substituted indoles with benzodithiolylium tetrafluoroborate has been developed. This reaction provides a novel strategy to synthesise C3 methyl-substituted pyrroloindolines and furoindolines under mild reaction conditions, the utility of which has been demonstrated by the synthesis of esermethol and physovenine in a highly concise manner.

Ruthenium-catalyzed regioselective allylic trifluoromethylthiolation reaction.

An efficient Ru-catalyzed regioselective allylic trifluoromethylthiolation reaction of allylic carbonates was developed. The linear allylic trifluoromethyl thioethers were obtained in 52-91% yields. Mechanistic investigation revealed that this reaction proceeds via a double allylic trifluoromethylthiolation sequence.

Pd(0)-catalyzed alkenylation and allylic dearomatization reactions between nucleophile-bearing indoles and propargyl carbonate.

Spiroindolenine derivatives were synthesized by intermolecular Pd-catalyzed dearomatization of indoles. The reaction between nucleophile bearing indoles and propargyl carbonate proceeds in a cascade fashion providing spiroindolenines or spiroindolines in good to excellent yields.

Copper-catalyzed C-2 arylation or vinylation of indole derivatives with iodonium salts.

Copper-catalyzed C-2 arylation and vinylation of indole derivatives with iodonium salts have been realized. This method, featuring a simple operational procedure, mild reaction conditions, and a wide substrate scope, provided versatile indole derivatives with direct and selective functionalization at the C-2 position of the indole core. In the presence of excess amounts of iodonium salts, cascade C-2 arylation and dearomatization through the C-3 arylation reaction also proceeded smoothly.

Regio- and enantioselective synthesis of N-allylindoles by iridium-catalyzed allylic amination/transition-metal-catalyzed cyclization reactions.

Regio- and enantioselective synthesis of N-allylindoles was realized through an iridium-catalyzed asymmetric allylic amination reaction with 2-alkynylanilines and subsequent transition-metal-catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir-catalysis were treated with catalytic amount of NaAuCl4⋅2 H2O or PdCl2 providing various substituted N-allylindoles in excellent yields and enantioselectivities.

A new strategy to construct a C=C-CF3 subunit via CuBr-catalyzed domino reaction of homopropargyl amines: an efficient synthesis of trifluoromethyl containing building blocks 4-trifluoromethyl-2,3-dihydro-pyrroliums.

A new strategy for the construction of a C=C-CF3 subunit has been developed via CuBr-catalyzed domino cyclization-trifluoromethylation of homopropargyl amines with Umemoto's reagent. 4-Trifluoromethyl-2,3-dihydro-pyrroliums were produced in high yields. The usefulness of these products has been demonstrated by the transformation of them into various other trifluoromethylated molecules.

Pd-catalyzed allylic alkylation of dienyl carbonates with nitromethane with high C-5 regioselectivity.

A highly regioselective palladium-catalyzed allylic alkylation of dienyl esters with nitromethane has been developed, providing selective access to the C-5 attacked products. The structures of the ligands as well as the steric effect of the substrates are important factors in determining the regiochemical outcome of the reaction.

Highly enantioselective synthesis of tetrahydrocarbolines via iridium-catalyzed intramolecular Friedel-Crafts type allylic alkylation reactions.

A highly enantioselective synthesis of substituted tetrahydrocarbolines via Ir-catalyzed Friedel-Crafts type intramolecular asymmetric allylic alkylation of 2-indolyl allyl carbonates has been developed. This strategy features excellent chemoselectivity and enantioselectivity, mild reaction conditions, and an easily accessed chiral ligand.

Palladacycle-catalyzed methylenecyclopropanation of bicyclic alkenes with propiolates.

An efficient way to access functionalized methylenecyclopropanes has been developed by palladacycle-catalyzed cyclopropanation of bicyclic alkenes with propiolates in high yields. The structure of the palladacycle was kept intact in the reaction, shown by (31)P NMR spectrum studies. A rational mechanism has been proposed with a deuterium-labeled experiment. The usefulness of the functionalized methylenecyclopropanes has also been demonstrated.

Palladium(0)-catalyzed intramolecular dearomative arylation of pyrroles.

The palladium(0)-catalyzed dearomative arylation of pyrroles has been accomplished to afford the spironaphthalenepyrrole derivatives in good to excellent yields.