The study of Prof. Masahiro Miura has focused on the development of effective methods for molecular construction applicable to producing various organic fine chemicals including medicines and organic functional materials which are significantly supporting affluent human society. In particular, he has extensively studied aromatic cross-coupling reactions through C-H bond cleavage leading to new C-C and C-heteroatom bonds. The research strategies involve directing functional group control and utilization of unique properties of reaction substrates and catalysts, which enable efficient regioselective coupling reactions. Thus, he has tremendously contributed to the progress of chemistry of direct C-H functionalization for the short step and atom-economic construction of given target molecules. The outline of his recent research achievements is as follows.
1. Reactions utilizing nitrogen-containing functionalities
In the early stage of his research work, Prof. Miura developed the direct regioselective C-H arylation and alkenylation of aromatic substrates bearing hydroxy and amide functions as directing groups using Pd(0) and Pd(II) catalysts. Thereafter, he also undertook to utilize less expensive first row transition metals for such reactions, and found that amides with an N-N bidentate group can acid-mediated undergo dehydrogenative aryl-heteroaryl coupling in the presence of a Cu(II) salt. It was also demonstrated that similar amide substrates react with epoxides and oxetanes accompanied by elimination of the nitrogen functionality to provide the corresponding benzolactones in good yields. Furthermore, the Cu(II)-catalyzed syntheses of carbazole derivatives by the dehydrogenative cyclization of amides of 2-aminobiphenyls and of triphenylamine derivatives by the direct ortho-amination of phenols capped by a removable and recoverable phenanthroline-bidentate auxiliary.
2. Reactions utilizing sulfur-containing functionalities
The C-H bond transformation with the aid of sulfur-containing directing group was far less explored until recently, probably because the impediment effect of sulfur was a matter of concern. Prof. Miura tried to utilize sulfur-containing directing groups by employing Rh(III) catalyst systems developed by his own research group and achieved the regioselective alkenylation and arylation of aromatic thioeters, dithianes, sulfoxides, and sulfones. In particular, the thiomethyl function is useful, as it can be removed or transformed to the other substituents, after the coupling event, by either reduction or conventional cross-coupling reactions. Furthermore, by treatment with an acid after the oxidation to the sulfoxides, selective cyclization occurs to furnish benzothiophene and thiophenarene derivatives. Based on this method, a number of sulfur-containing polycyclic aromatic compounds that exhibit semiconducting property were prepared.
3. Reactions utilizing phosphorous-containing functionalities
The C-H bond transformation with the aid of phosphorous-containing directing groups was also very little explored until recently. Prof. Miura first reported a synthetic method of benzoxaphosphorine derivatives through the dehydrogenative cycloaddition reaction of phenylphosphinic acids with alkynes with use of Rh(III) catalysts. In the reaction of phenylphosphine oxides with alkynes, Ag(I) and Mn(III) salats were found to act as effective oxidants to give benzophosphole derivatives. The phosphorous heterocycle products may act as fluorescent and electron-transporting materials. The latter cyclization is highly efficient, but a regioisomeric mixture of the product is formed when a para-substituted phenylphosphine oxide is used as substrate. To overcome this problem, a two-step method involving ortho-C-H alkenylation of phenylthiophosphinamides by Rh(III) catalysis followed by the ring formation through acid-mediated cyclization as the key step. In addition, based on the information about the cyclization, a convenient benzophosphole synthesis by the reaction phenylphophine oxides with alkynes only with triflic anhydride as promotor was attained.
4. Reactions on aromatic and heteroaromatic rings through direct metalation
Direct metalation of arenes has been known to be possible by transition metals with electrophilic nature, and thus, direct C-H functionalization without using any directing group may be performed, while regioselectivity is always a matter of concern. As part of his work employing Pd(II) and Rh(III) catalysts, he undertook to develop the direct alkenylation of polycyclic aromatics and heteroaromatics such as naphthalene, pyrene, and benzo-fused thiophenes, directed toward the synthesis of p-electron-conjugated compounds. It was found that the thiophenes can be selectively alkenylated at the a-positions by using a Pd(II) catalyst, while a Rh(III) catalyst is suitable for the reactions of naphthalene and pyrene to provide the products selectively alkenylated at the b-positions. The unique regioselectivities are attributable to electronic and steric controls, respectively. Meanwhile, the dehydrogenative annulation of arylated thiophenes with alkynes to furnish sulfur-containing polycyclic heteroaromatics and double dehydrogenative coupling of biheteroaryls to construct cyclic tetramers of heteroarenes were successfully attained. These products exhibit unique redox properties.
In summary, the research work of Prof. Miura has been aiming at contributing to an innovative area in organic synthesis, especially direct C-H transformation chemistry. As a pioneer of this area, he has developed a variety of catalytic direct C-C and C-heteroatom bond formation reactions and many effective methods for constructing valuable molecules by ingeniously using transition metal catalysts and reagents. His work has given a highly influential impact to synthetic chemistry. Therefore, his achievement is worthy of the Chemical Society of Japan Award.