Prof. Kobayashi has made significant contributions to the development of green sustainable chemistry by focusing on designing and discovering new synthetic methodologies that are less wasteful, energy-saving, and more practical than traditional synthetic methods. His research topics are summarized below.
1. Development new catalysts and reaction systems for organic reactions in aqueous media
Based on the rule of "like dissolves like", organic reactions are conducted in organic solvents since good solubility of organic starting materials to the reaction media is very important for efficient reaction progress. However, most organic solvents are highly flammable and toxic, which has led to the search for environmentally benign and safe solvents. Water is a ubiquitous, non-toxic, safe, and inexpensive solvent. However, poor solubility of organic compounds and instability of many commonly used metal catalysts and reagents in water has prevented its widespread use as a solvent in organic synthesis. Prof. Kobayashi has been focused on overcoming these limitations and discovered that rare earth metal triflates functions as water-stable Lewis acid catalysts, and later designed Lewis acid-surfactant-combined catalysts (LASC), that efficiently promoted various Lewis acid-catalyzed reactions in water. During these studies, new reactivities and selectivities, compared to the same reactions in organic solvents, were observed. These results has led to moving organic synthesis into a new direction in water.
2. Development of new heterogeneous metal catalysts based on microencapsulation and polymer-incarceration methods
Heterogeneous catalysts are the ideal green catalysts in organic synthesis since these can be recovered and reuse. However, they are often less reactive compared to homogeneous catalysts and/or decompose after several reuse. Prof. Kobayashi sought to overcome these limitations by developing new methods to immobilize metal catalysts. Microencapsulation, which is a common technique used in the food and pharmaceutical industries, was found to be an effective process to immobilize metal catalysts to polystyrene, and these microencapsulated metal catalysts were found to be highly active heterogeneous catalysts for various organic transformation. However, due to stability issues, an evolved strategy, polymer-incarceration (PI) method, that combined microencapsulation with a cross-linking process using a designed polystyrene-based co-polymer, was developed. PI Catalysts were found to be highly active and robust heterogeneous catalyst that enable a wide range of organic transformations, and could be recovered easily by simple filtration and reused several times. Moreover, he found that the PI technique could be applied for the immobilization of metal nanoparticles (NPs), and chiral ligand-modified metal NPs could be employed for highly enantioselective C-C bond formation reactions.
3. Development of highly efficient catalytic addition reactions
Addition reactions are highly atom-economical processes and represents the ideal green organic transformations. Prof. Kobayashi has made significant contributions in the development of highly selective catalytic addition reactions that are based on the use of sustainable and abundant metals as catalysts and that can be employed for challenging substrates to prepare fine chemicals, such as active pharmaceutical ingredients (APIs). His early contributions were focused on enantioselective carbon-carbon bond forming reactions using chiral transition and rare-earth metal complexes. However, due to the scarcity and toxicity of many of these metal catalysts, Prof. Kobayashi focused on alkaline earth metals, which are ubiquitous and safe metals, and demonstrated that these rarely studied metals could be employed as highly active and selective Lewis catalysts for various addition reactions. Addition reactions of C-H pronucleophiles are 100% atom-economical but are limited to activated (acidic) substrates. To overcome this limitation, Prof. Kobayashi proposed an original mechanistic framework that employs a strong Brønsted base, as a catalyst or initiator, and a well-designed highly basic reaction intermediate to enable catalytic addition reactions of weakly acidic compounds (alkylesters, alkylamides, alkylarenes, etc.) as pronucleophiles. Moreover, catalytic asymmetric additions reactions of weakly acidic compounds were achieved with chiral Brønsted bases.
4. Development of flow fine organic synthesis
In order to meet or exceed current environmental regulations and to reduce the overall cost of producing fine chemicals, new synthetic routes and chemical manufacturing techniques are needed. In industry, fine chemicals are typically prepared in batch using large reaction vessels. However, there is growing interest in conducting multi-step organic synthesis in continuous-flow since flow processes allows organic reactions to be more efficient and safer. The major drawback of conducting continuous-flow reactions is that the carryover of contaminants (waste co-products, catalyst) from one flow reactor to the next can have an adverse effect. To overcome this issue, Prof. Kobayashi has developed various continuous-flow addition and condensation reactions through columns packed with heterogeneous catalysts. Moreover, he was able to demonstrate that fine chemicals, such as APIs and their intermediates, could be prepared in multi-step continuous-flow conditions by redesigning synthetic routes based mainly on addition and condensation reactions catalyzed by heterogeneous catalysts.
Prof. Kobayashi's research over the past several years has made significant scientific contributions to the development of green sustainable chemistry in organic synthesis. Therefore, his contribution to chemistry is worthy of the CSJ Award.