Chiral N-heterocyclic carbene ligands with a phenol or naphthol N-substituent (phenol-NHC chiral ligands) enabled various copper-catalyzed enenatioselective reactions such as allylic alkylation of terminal alkynes and electron-deficient (hetero)arenes, allyl-allyl coupling between allyboronates and substituted allyl phosphates, 1,6-conjugate addition of allylboronates, three-component coupling with hydrosilanes, isocyanides, and allylic phosphates (umpolung allylic formimidoylation), conjugate reduction of α,β-unsaturated esters with a hydrosilane, and cyclopropanol ring-opening allylic allylation (homoenolate allylic alkylation). DFT calculations for the cyclopropanol ring-opening allylic alkylation gave insights into the mechanism of enantiocontrol by the phenol-NHC-Cu chiral catalysts, showing that C-H…O interactions provided by the naphtholate oxygen atom orient the aromatic substituents of the NHC framework toward creating a well-organized chiral catalytic environment.

Cationic iodine(I)-mediated electrophilic cyclization, termed iodocyclization, allows ring formation and iodination at the same time. In particular, iodocyclization of alkynes as substrates gives cyclic products containing C(sp²)-I bond, that would be able to introduce various substituents by performing well-established cross-coupling reactions afterwards. Thus, the iodocyclization of alkynes is suitable for diversity-oriented synthesis of cyclic compounds, and has been extensively studied over the past few decades. On the other hand, there are many problems such as 1) overreaction caused by iodine reagents, 2) poor selectivity of cyclic mode (endo/exo), and 3) difficulty of cyclization itself. The author has solved these problems and systematically developed practical methods for synthesizing heterocyclic and carbocyclic rings using the iodocyclization. This article also describes dearomative spirocyclization of phenol derivatives leading to three-dimensional polycyclic compounds.

An ester group is one of ubiquitous and important functional groups in the field of organic chemistry. Stereoselective transformations of substrates having ester groups using artificial catalysts such as metal complexes and organocatalysts have been developed such as 1,4-addition of α,β-unsaturated esters and functionalizations at α-carbon of esters. However, stereoselective transformations of the ester group itself have been still highly limited.

Hydrolase-catalyzed asymmetric hydrolysis of esters, which is a basic and important reaction categorized as the latter reaction type, has long been studied, and widely used from the lab scale to the industrial scale synthesis. However, enzymatic reactions generally have several issues such as their low specific activity and high cost. Under these circumstances, we hypothesized that stereoselective base hydrolysis of esters would be achieved by using liquid-liquid biphasic system with chiral onium salt catalysts. Herein, we describe the asymmetric base hydrolysis of esters using chiral onium salt catalysts derived from Cinchona alkaloids and chiral amino acids as well as the related dynamic kinetic resolution of azlactones via phase-transfer catalytic base alcoholysis. In addition, we also demonstrated the computational investigations using ConFinder program with pseudo-transition state conformational search (PTSCS) method.

The unique nucleic acid structures such as threaded structures and interstrand crosslinking have high potential in chemical biology, nanotechnology and oligonucleotide therapeutics. For example, the noncovalent labeling and modification by the threaded structures are useful as new chemical biology and nanotechnology tools. The properly designed crosslinking structures provide high activity and nuclease resistance for anti-miRNA and siRNA. This paper introduces the creation of threaded structures, such as rotaxane-like structures and catenanes, and interstrand crosslinking with flip-out bases based on our hybridization-specific template reactions. In the hybridization-specific reaction fields, the reactions are accelerated by the proximity effect achieving efficient and selective creations. Regarding the creation of threaded structures, we designed pseudorotaxane-forming oligo DNAs (prfODNs) with reactive moieties and achieved automatic pseudorotaxane formation toward the target DNA and RNA by taking advantage of hybridization-specific reaction fields. The pseudorotaxane structures were also obtained using cyclized ODNs via the slipping process. The catenane structure was formed by the combination of pseudorotaxane formation with a 5’-end-phosphorylated RNA and enzymatic ligation. For crosslinking, we created the crosslinked DNA with flip-out bases using the base flipping-induced artificial bases and photoinduced [2+2+2] cycloaddition reaction among alkynes and molecular oxygen. From the viewpoint of organic chemistry, it is hoped that further creation of unique functional nucleic acids and structures will lead to the development of new concepts for oligonucleotide therapeutics, new tools for RNA research and DNA nanotechnology.

Chiral photoswitchable catalysts can modulate reactivity and selectivity of enantioselective reaction by photoisomerization. While a variety of the catalysts have been developed due to their utility in the field of asymmetric synthesis, azobenzene, which is readily available and well-known photoresponsive unit, has rarely been applied to chiral photoswitchable catalysts. We have developed a variety of azobenzene-based chiral photoswitchable organocatalysts and ligand such as azobenzene BINOL crown ether (ABCE), azobenzene BINOL hybrid oligoethylene glycol (ABOEG), and azopyridine-oxazoline (AZOX). The (Z)-ABCE accelerated enantioselective alkylation of glycine Schiff base in comparison with the (E)-ABCE. The ABOEG changed reactivity and enantioselectivity in asymmetric amination of imines through photoisomerization. The AZOX also controlled enantioselectivity in asymmetric intermolecular cyclization of sulfonamide through the photomodulation of the coordination mode.

Deracemization reactions are a simple and attractive strategy to obtain a single enantiomer from a racemic mixture without structural change. However, two challenges to the reactions exist. One is the thermodynamically disfavored process due to the negative entropy change. The other is the racemization pathway based on the principle of microscopic reversibility. This review focuses on the recent catalytic deracemization reactions under photochemical conditions, which have allowed the accumulation of a single enantiomer.