Jen-Chieh Hsieh

Structure/Activity Relationship Studies of Small-Molecule Inhibitors of Wnt Response

Suppression of oncogenic Wnt-mediated signaling holds promise as an anti-cancer therapeutic strategy. We previously reported a novel class of small molecules (IWR-1/2, inhibitors of Wnt response) that antagonize Wnt signaling by stabilizing the Axin destruction complex. Herein, we present the results of structure-activity relationship studies of these compounds.

Novel Syntheses of Fluorenones via Nitrile-Directed Palladium-Catalyzed C–H and Dual C–H Bond Activation

Novel procedures for the [Pd]/[Ag]/TFA system catalyzed cascade reactions of nitrile directed remote C-H and dual C-H bond activation with insertion of nitrile were developed, which afforded variously polysubstituted fluorenones in moderate to good yields with tolerance of a wide variety of substrates.

Nickel-Catalyzed Intermolecular Insertion of Aryl Iodides to Nitriles: A Novel Method to Synthesize Arylketones

A novel procedure for the NiCl(2)(DME)/dppp/Zn system catalyzed intermolecular insertion of aryl iodides to nitriles was developed, which afforded variously substituted arylketone derivatives in moderate to good yields with tolerance of a wide variety of functional groups.

Nickel-catalyzed highly chemoselective cocyclotrimerization of arynes with allenes: a novel method for 10-methylene-9,10-dihydrophenanthrenesElectronic supplementary information (ESI) available: synthesis and characterization data of compounds 3. See http://www.rsc.org/suppdata/cc/b3/b315795d/

The NiBr(2)(dppe)-Zn system effectively catalyzes the [2+2+2] cocyclotrimerization of arynes with allenes, leading to 10-methylene-9,10-dihydrophenanthrenes in moderate to good yields. The cocyclotrimerization is highly selective with only the internal double bond of the allenes being involved in the reaction.

Hydride-Induced Anionic Cyclization: An Efficient Method for the Synthesis of 6-H-Phenanthridines via a Transition-Metal-Free Process

A novel procedure for hydride-induced anionic cyclization has been developed. It includes the reduction of a biaryl bromo-nitrile with a nucleophilic aromatic substitution (S(N)Ar). A range of polysubstituted 6-H-phenanthridines were so obtained in moderate to good yield with good substrate tolerance. This method involves a concise transition-metal-free process and was applied to synthesize natural alkaloids.

Synthesis of polysubstituted phenanthridines via ligand-free copper-catalyzed annulation.

A novel procedure for the cascade reaction of the addition of a Grignard reagent to a nitrile with a copper-catalyzed C-N bond coupling was developed, which afforded various polysubstituted phenanthridines in moderate to good yields with tolerance for a wide variety of substrates. Experimental data demonstrated that the reaction proceeded more likely through a Cu(I/III) catalytic cycle.

An efficient synthesis of (NH)-phenanthridinones via ligand-free copper-catalyzed annulation

An efficient and concise procedure for the ligand-free copper-catalyzed cascade reaction of C–O and C–N bond coupling was developed, which afforded various (NH)-phenanthridinones in moderate to good yields with tolerance of a wide variety of substrates. This method could be useful for the syntheses of natural alkaloids.

Nickel-catalyzed cocyclotrimerization of arynes with diynes; a novel method for synthesis of naphthalene derivatives

The NiBr2(dppe)-Zn system effectively catalyzes the [2 + 2 + 2] cocyclotrimerization of arynes with diynes, leading to substituted naphthalene derivatives in moderate to good yields. This cocyclotrimerization reaction shows excellent tolerance of functional groups and leads to products of 5- to 7-membered fused-ring sizes.

Direct synthesis of chiral 3-arylsuccinimides by rhodium-catalyzed enantioselective conjugate addition of arylboronic acids to maleimides.

Chiral rhodium catalysts comprising 2,5-diaryl- substituted bicyclo[2.2.1]diene ligands L1-L10 were utilized in the enantioselective 1,4-addition reaction of arylboronic acids to N-substituted maleimides. In the presence of 2.5 mol % of Rh(I) /L2, enantioenriched conjugate addition adducts were isolated in 72-99 % yields with 86-98 % ee. This protocol offers a convenient method to access a variety of 3-arylsuccinimides in a highly enantioselective manner. Maleimides with readily cleavable N-protecting groups were tolerated enabling the synthesis of useful synthetic intermediates. Pyrrolidine 4, a biologically active compound, and pyrrolidine 5, an ent-precursor to an HSD-1 inhibitor, were synthesized to demonstrate the utility of this method.

Copper-Catalyzed Annulation: A Method for the Systematic Synthesis of Phenanthridinium Bromide.

A novel procedure for the Cu-catalyzed systematic synthesis of phenanthridinium bromide is reported. This transformation was achieved with direct construction of central pyridinium core by using an in situ formed biaryl imine as a substrate. Tolerance of a very wide variety of N-substituents is indicated; this has never previously been disclosed by other reports. Application of this method to synthesis of the natural alkaloid bicolorine, and its derivatives, was also carried out in only three synthetic steps from commercially available compounds.