Foreword

Since the mid-20th century, transition metal-catalyzed organic synthesis has rapidly progressed, contributing to the development of innovative chemical bond formations and selective chemical transformations. Classical organic synthesis methodologies based on the basic principle of “anions attacking cations” cannot achieve many of these transformations. Transition metal catalysis has also been a powerful tool in drug discovery research, which requires efficient synthesis of molecules with complex carbon skeletons and many heteroatoms. Such catalytic synthetic methods have greatly expanded the chemical space available for drug discovery research. In addition, recent dramatic advances in photochemistry and computational chemistry have revolutionized research strategies for developing transition metal catalysis. There is no doubt that the importance of transition metal catalysis technologies in the field of pharmaceutical organic chemistry will continue to grow in the future. This Current Topics of Chemical and Pharmaceutical Bulletin contains one communication and four regular articles describing the latest research on transition metal catalysis research in pharmaceutical organic chemistry. Topics include transition metal-catalyzed radical-mediated allylic substitution, oxidation reactions, heterocyclic compound synthesis, direct alkylation using allylic alcohols and amines, and theoretical analysis of transition metal catalysis.

The first communication entitled “Noble-Metal-Free C–H Allylation of Tetrahydroisoquinolines Using a Cobalt-Organophotoredox Dual Catalyst System” is reported by Dr. Kojima and Prof. Matsunaga and colleagues. Metallaphotoredox-catalyzed allylation is a state-of-the-art technology that enables nucleophilic radical-mediated allylic substitution. Previous methods, however, have required the use of noble metal catalysts. To address this issue, the authors succeeded in the radical-mediated C–H allylation of tetrahydroisoquinoline derivatives without the use of noble metals by using a cobalt/organophotoredox dual catalyst system.

The first regular article entitled “Copper-Catalyzed Aerobic C(sp³)–H Oxidation of β-(Alkoxy)imino Carbonyl Compounds” is reported by Prof. Ueda et al. Direct C(sp³)–H oxidation of readily accessible substrates is an important technology in organic synthesis. The authors succeeded in the direct synthesis of 1-imino-2,3-dicarbonyl compounds based on the Cu(II)-catalyzed C–H aerobic oxidation β-(alkoxy)imino carbonyl compounds. The developed method is featured by the simple operation, atom economy, environmental benignity, and broad substrate scope.

The second regular article entitled “Palladium-Catalyzed Intramolecular Migratory Cycloisomerization of 3-Phenoxy Acrylic Acid Ester via C–O Bond Cleavage and C–O/C–C Bonds Formation for 2,3-Disubstituted Benzofurans Synthesis” is reported by Prof. Arisawa and colleagues. Because of the ubiquity of benzofuran structural motif in agrochemical and pharmaceutical compounds, its synthetic methods are recognized as an important topic in organic synthesis. The authors achieved Pd-catalyzed migratory cycloisomerization of 3-o-alkenylphenoxy acrylic acid esters to give 2,3-disubstituted benzofuran derivatives. The mechanistic novelty features the developed method in the Pd-catalyzed cycloisomerization of C(sp²)–O bond cleavage.

The third regular article entitled “O- and N-Selective Electrophilic Activation of Allylic Alcohols and Amines in Pd-Catalyzed Direct Alkylation” is reported by Prof. Ohshima and colleagues. Control of chemoselectivity is one of the most important research topics in organic synthesis. In this article, the authors achieved the O- and N-selective electrophilic activation of allylic alcohols and amines in Pd-catalyzed direct allylic alkylation. The additive effect was discussed using density functional theory (DFT) calculation, revealing the mode of selective activation of allylic amines and allylic alcohols.

The final regular article entitled “Theoretical Investigation of Chemoselectivity between C–H Insertion and Amide Insertion in Intramolecular Rhodium-Carbene Reactions” is reported by Dr. Harada and Prof. Nemoto and colleagues. The rapid progress and widespread use of theoretical studies of reaction mechanisms using DFT calculations have revolutionized the strategy of synthetic chemistry research. The authors previously reported an amide insertion reaction of Rh-carbene, which is mechanistically characteristic compared with conventional Rh-carbene-mediated C–H insertion reactions. Theoretical discussions of the origin of chemoselectivity are described in this report.

I am sure that the research articles in this Current Topics provide you the latest development in transition metal catalysis research in pharmaceutical organic chemistry. I thank all the authors for their great contribution to this Current Topics.