University of Osaka SANKEN synthesizes NOBIN molecules using vanadium catalysts and light

A research group led by Professor Shinobu Takizawa, Specially Appointed Assistant Professor Mohamed S. H. Salem, and Visiting Researcher Muthu Karuppasamy (JSPS Postdoctoral Fellowship for Research in Japan) from SANKEN, at the University of Osaka has developed a new reaction in which only the oxidative asymmetric heterocoupling reaction of 2-naphthol and 2-naphthylamine proceeds by combining vanadium catalysts with light (LED irradiation). This method enables the efficient production of NOBIN, a group of organic molecular compounds useful for supplying pharmaceutical resources. The yield reaches up to 95%, and the enantiomeric ratio also shows a high level of 90:10, attracting attention as a synthesis method with low environmental impact. Organic synthesis that activates molecules using light combines energy savings with high safety, and the discovery of this method will further accelerate next-generation catalytic asymmetric synthesis research. The work was published in ACS Catalysis and selected for the supplementary cover.

Chiral organic compounds (organic molecules that exist in mirror-image relationships like right and left hands) play important roles in many industries, from pharmaceuticals to agrochemicals, fragrances, and foods. Among these, NOBIN, which possesses axial chirality, is an indispensable compound in the fields of organic synthetic chemistry and asymmetric synthesis, similar to BINOL, which is the raw material for BINAP ligands, and BINAM, which is applied to chiral organocatalysts and polymer materials.

Oxidative asymmetric heterocoupling using metal catalysts is one of the most promising methods to directly synthesize NOBIN molecules. However, there have been problems such as the progression of side reactions (such as homocoupling), which is not environmentally friendly due to large amounts of waste generated, and poor production efficiency due to the need to add excess raw materials because of the influence of side reactions.

Researchers around the world have been working since the 1990s on methods to synthesize NOBIN with high enantiomeric ratios while overcoming these challenges. However, simultaneously achieving productivity, environmental compatibility, and high asymmetric catalytic activity remained unrealized for a long time.

In this research, two elements-vanadium catalysts and light-were skillfully combined. The vanadium catalyst converts only 2-naphthol into radical species, while irradiation of 2-naphthylamine with LED light in an oxygen atmosphere generates a charge-transfer complex, which is then efficiently converted into cation radical species. Through the cooperative coupling of these two types of radicals, only NOBIN derivatives are obtained.

A major feature, different from conventional methods, is that raw materials can be added in a 1:1 ratio. Additionally, because this method uses low-energy LED light, the environmental impact is small, and it is evaluated as a sustainable synthesis method. The research group verified the reaction under various conditions and identified the optimal solvent and detailed LED light conditions. As a result, side reactions were significantly suppressed compared with conventional methods, and they succeeded in synthesizing only the target molecules with high yields.

Takizawa commented: "This achievement opens a new path in chemical synthesis. In the future, applications to more complex molecules and drug candidate substances are expected. Furthermore, the concept of 'cooperative catalysis' combining light and metal catalysts will continue to be widely developed as a chemical process suitable for a sustainable society. This research, originating from SANKEN (the University of Osaka), goes beyond the framework of basic chemistry and represents a major step toward contributing to the creation of an environmentally harmonious future society."

Journal Information
Publication: ACS Catalysis
Title: Enantioselective Heterocoupling of 2-Naphthylamines with 2-Naphthol Derivatives via Cooperative Photoactivation and Chiral Vanadium(V) Catalysis
DOI: 10.1021/acscatal.5c05038