Hsuan-Hung Liao

Enantio‐ and Diastereoselective Access to Distant Stereocenters Embedded within Tetrahydroxanthenes: Utilizing ortho‐Quinone Methides as Reactive Intermediates in Asymmetric Brønsted Acid Catalysis

A protocol for the highly enantioselective synthesis of 9-substituted tetrahydroxanthenones by means of asymmetric Brønsted acid catalysis has been developed. A chiral binol-based N-triflyphosphoramide was found to promote the in situ generation of ortho-quinone methides and their subsequent reaction with 1,3-cyclohexanedione to provide the desired products with excellent enantioselectivities. In addition, a highly enantio- and diastereoselective Brønsted acid catalyzed desymmetrization of 5-monosubstituted 1,3-dicarbonyl substrates with ortho-quinone methides gives rise to valuable tetrahydroxanthenes containing two distant stereocenters.

Ortho‐Quinone Methides as Reactive Intermediates in Asymmetric Brønsted Acid Catalyzed Cycloadditions with Unactivated Alkenes by Exclusive Activation of the Electrophile

An efficient method for the highly enantioselective synthesis of chiral chromanes bearing multiple stereogenic centers was developed. A chiral BINOL-based N-triflylphosphoramide proved to be an effective catalyst for the in situ generation of ortho-quinone methides (o-QMs) and their subsequent cycloaddition reaction with unactivated alkenes provided chromanes with excellent diastereo- and enantioselectivity.

Shedding light on organocatalysis-light-assisted asymmetric ion-pair catalysis for the enantioselective hydrogenation of pyrylium ions.

A new light-driven asymmetric ion-pair catalysis procedure for the metal-free enantioselective hydrogenation of in situ generated pyrylium ions from readily available chalcones was developed (see scheme). The photo-assisted Brønsted acid catalyzed procedure has broad scope and allows, for the first time, access to valuable 4H-chromenes in good yields and with excellent enantioselectivities.

Catalytic Ester and Amide to Amine Interconversion: Nickel-Catalyzed Decarbonylative Amination of Esters and Amides by C-O and C-C Bond Activation

An efficient nickel-catalyzed decarbonylative amination reaction of aryl and heteroaryl esters has been achieved for the first time. The new amination protocol allows the direct interconversion of esters and amides into the corresponding amines and represents a good alternative to classical rearrangements as well as cross coupling reactions.

Asymmetric Brønsted Acid Catalyzed Synthesis of Triarylmethanes—Construction of Communesin and Spiroindoline Scaffolds

Aza-ortho-quinone methides allow the straightforward asymmetric synthesis of natural-product-inspired indole scaffolds possessing a quaternary stereocenter. Our approach provides access to diverse communesin and spiroindoline derivatives with high enantioselectivity under mild reaction conditions. Predictable substitution patterns are found to be the key to our regiodivergent protocols.

Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers.

An enantioselective addition of thiols and alcohols to aza-ortho-quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.

Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides

A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.

Ligand-Controlled Chemoselective C(acyl)–O Bond vs C(aryl)–C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)–C(sp3) Cross-Couplings

A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp2)-C(sp3) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)-O bond, which later generates the ketone product.

Nickel-Catalyzed C–CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides

An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.

Nickel-Catalyzed C−S Bond Formation via Decarbonylative Thioetherification of Esters, Amides and Intramolecular Recombination Fragment Coupling of Thioesters

A nickel catalyzed cross-coupling protocol for the straightforward C-S bond formation has been developed. Various mercaptans and a wide range of ester and amide substrates bearing various substituents were tolerated in this process which afforded products in good to excellent yields. Furthermore, an intramolecular protocol for the synthesis of thioethers starting from thioesters has been developed. The utility of this protocol has been demonstrated in a new synthetic protocol of benzothiophene.