Direct Catalytic Asymmetric Aldol Reaction of Thioamide with an α-Vinyl Appendage.

The direct catalytic asymmetric aldol reaction is an emerging catalytic methodology that provides atom-economical access to functionalized chiral building blocks. Thioamides are useful aldol donors due to their high-fidelity chemoselective enolization and divergent post-aldol transformations. Herein we describe the incorporation of an α-vinyl appendage on a thioamide, which expands the utility of aldol adducts for natural product synthesis.

Combined Theoretical and Experimental Studies of Nickel-Catalyzed Cross-Coupling of Methoxyarenes with Arylboronic Esters via C-O Bond Cleavage.

Nickel(0)-catalyzed cross-coupling of methoxyarenes through C-O bond activation has been the subject of considerable research because of their favorable features compared with those of the cross-coupling of aryl halides, such as atom economy and efficiency. In 2008, we have reported nickel/PCy-catalyzed cross-coupling of methoxyarenes with arylboronic esters in which the addition of a stoichiometric base such as CsF is essential for the reaction to proceed. Recently, we have also found that the scope of the substrate in the Suzuki-Miyaura-type cross-coupling of methoxyarenes can be greatly expanded by using 1,3-dicyclohexylimidazol-2-ylidene (ICy) as the ligand.

Nickel/N-Heterocyclic Carbene-Catalyzed Suzuki-Miyaura Type Cross-Coupling of Aryl Carbamates.

The utility of N-heterocyclic carbene ligands in nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl esters and carbamates is investigated. Imidazol-2-ylidene bearing 2-adamantyl groups at its nitrogen atoms generates the most active nickel species among the ligands examined, allowing cross-coupling of a range of aryl carbamates and pivalates. Unlike the previously reported system using tricyclohexylphosphine, this protocol is suitable for the cross-coupling using arylboronic esters in addition to arylboronic acids.

Nickel-catalyzed reductive cleavage of aryl alkyl ethers to arenes in absence of external reductant.

The reductive cleavage of the C-O bonds of aryl ethers has great potential in organic synthesis. Although several catalysts that can promote the reductive cleavage of aryl ethers have been reported, all such systems require the use of an external reductant, , hydrosilane or hydrogen. Here, we report the development of a new nickel-based catalytic system that can cleave the C-O bonds of ethers in the absence of an external reductant.

Photocontrolled Organocatalyzed Living Radical Polymerization Feasible over a Wide Range of Wavelengths.

Photocontrolled organocatalyzed living radical polymerization was conducted over a wide range of irradiation wavelengths (350-750 nm). The polymerization was induced and controlled at the desired wavelengths by exploiting suitable organic catalysts. This system was finely responsive to the irradiation wavelength; the polymerization was instantly switched on and off, and the polymerization rate was sensitively modulated by altering the irradiation wavelength.

Nickel-catalyzed alkynylation of anisoles via C-O bond cleavage.

A new cross-coupling reaction has been developed for the introduction of an alkyne moiety to an anisole derivative through C-O bond activation using an NHC ligand. This method has been used for direct alkynylation of a broad range of anisole derivatives and provided rapid access to compounds with potential applications in biological and materials science.

Reversible generation of a carbon-centered radical from alkyl iodide using organic salts and their application as organic catalysts in living radical polymerization.

A new method of producing carbon-centered radicals was discovered through the reaction of an alkyl iodide (R-I) with organic salts to reversibly generate the corresponding alkyl radical (R(•)). Via this new reaction, the organic salts were used as new and highly efficient organic catalysts in living radical polymerization. The catalysts included common and inexpensive compounds such as tetrabutylammonium iodide and methyltributylphosphonium iodide.

Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes.

Epigenetic modifications that govern the gene expression are often overlooked with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole (PI) hairpin polyamides are programmable small DNA binding molecules that have been studied in the context of gene regulation. Recently, we synthesized a library of compounds by conjugating PI polyamides with SAHA, a chromatin-modifier.

Synthetic small molecules for epigenetic activation of pluripotency genes in mouse embryonic fibroblasts.

Considering the essential role of chromatin remodeling in gene regulation, their directed modulation is of increasing importance. To achieve gene activation by epigenetic modification, we synthesized a series of pyrrole-imidazole polyamide conjugates (PIPs) that can bind to predetermined DNA sequences, and attached them with suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor. As histone modification is associated with pluripotency, these new types of conjugates, termed SAHA-PIPs, were screened for their effect on the expression of induced pluripotent stem cell (iPSC) factors.

The distance between donor and acceptor affects the proportion of C1' and C2' oxidation products of DNA in a BrU-containing excess electron transfer system.

We have investigated the products of (Br)U in excess electron transfer and have demonstrated that in DNA the proportion of products changes with the distance between the donor and acceptor. On the basis of a labeling experiment using H(2)(18)O, we have shown that hole migration from Py(•+) formed after charge separation is involved in the reaction.

Requirement of beta-alanine components in sequence-specific DNA alkylation by pyrrole-imidazole conjugates with seven-base pair recognition.

To investigate the effect of incorporation of beta-alanine in alkylating N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide, seco-CBI conjugates 2-8 were synthesized by an Fmoc solid-phase method and subsequent coupling with an alkylating moiety. DNA-alkylating activities of conjugates 2-8 were evaluated by high-resolution denaturing gel electrophoresis with 202-base pair (bp) DNA fragments. Alkylation by conjugates 2 and 3, which have antiparallel pairings of beta-alanine (beta) opposite beta (beta/beta) and Py/beta, occurred mainly at the adenine (A) of the matching sequences, 5'-AGCTCCA-3' (site 1) and 5'-AGCACCA-3' (site 3).