Foreword

One of the most important issues in organic synthesis is to synthesize the end objective product in an efficient way. For that purpose, organic chemists are attempting to develop novel reactions to synthesize their objective products more efficiently. This Current Topics section in this issue of the Chemical and Pharmaceutical Bulletin contains two reviews, two communications, and one full paper, all focusing on the reversal or control of the reactivity of functional groups.

In the first review, Professor Hironao Sajiki and his colleagues describe their study on the “Recent Development of Palladium-supported Catalysts for Chemoselective Hydrogenation.” Although palladium catalysts are good catalysts for the hydrogenation of many functional groups, their high catalyst activity often causes problems for chemoselectivity. Professor Sajiki is engaging in chemoselective hydrogenation using heterogeneous metal catalysts. This review provides practical and selective hydrogenation methodologies using heterogeneous palladium catalysts supported on the chelate resine, ceramic, and spherically-shaped activated carbon. The chemoselective hydrogenation applicable to flow technology is also described using immobilized palladium catalysts.

The second review, entitled “Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an in Situ Protecting Group,” is described by Professor Hiromichi Fujioka and his colleague. The order of the innate reactivity of carbonyl groups toward nucleophiles is generally aldehyde>ketone≈α,β-unsaturated ketone>ester>amide and nitrile. Chemoselective transformations of less reactive carbonyl groups in the presence of more reactive ones, or of one carbonyl group of two carbonyl groups having similar reactivity, are quite difficult to achieve. They developed new methodologies using phosphonium salts as an in situ protecting group. Thus, the reversal or control of the reactivity of carbonyl functions in reduction and alkylation was achieved. The application of these newly developed methods to the concise syntheses of bioactive natural products is also described.

The third article, “Catalytic Chemoselective Conjugate Addition of Amino Alcohols to α,β-Unsaturated Ester: Hydroxy Group over Amino Group and Conjugate Addition over Transesterification,” communicated by Professor Takashi Ohshima and his colleagues, presents a highly chemoselective conjugate addition of amino alcohols to α,β-unsaturated esters and acrylamide. Although the nucleophilicity of amine is much stronger than alcohol, Oshima and colleagues succeeded in reversing their intimate reactivity using a soft Lewis acid/hard Brønsted base cooperative catalyst, and succeeded in the oxa-Michael reaction of amino alcohols. They also described controlling the chemoselectivity of conjugate addition (1,4-addition) and transesterification (1,2-addition).

A communication entitled “Concise, Protecting-Group-Free Synthesis of (+)-Nemonapride via Eu(OTf)₃-Catalyzed Aminolysis of 3,4-Epoxy Alcohol,” by Professor Yoshiharu Iwabuchi and his colleagues, offers a solution for chemoselectivity in the mesylation of amino groups and hydroxyl groups. The nucleophilic ring opening of a chiral epoxide serves as a valuable chiral synthon with contiguous stereogenic centers. They first found that the C4 selective aminolysis of chiral 3,4-epoxy alcohol with benzylamine is catalyzed by Eu(OTf)₃. They also succeeded in the selective mesylation of a hydroxyl group in the presence of an amino group, owing to their steric factors. Concise, protecting-group-free synthesis of (+)-nemonapride has thus been achieved.

The last one is a regular article, entitled “Total Synthesis of Ellagitannins via Sequential Site-Selective Functionalization of Unprotected D-Glucose,” from professor Takeo Kawabata and his colleagues. Sequential one-point functionalization among the same several functional groups usually requires several steps, such as protection and deprotection. Professor Kawabata developed a C₂-symmetric, chiral organocatalyst, and realized catalyst-controlled and substrate-controlled site-selective introductions of a galloyl group into inherently less reactive hydroxyl groups of the glucoside. Thus, extremely short-step total synthesis of tellimagrandin II and pterocarinin C was accomplished.

Methods for the reversal or control of the innate reactivity of functional groups don’t necessarily require tedious processes such as protection–deprotection; the objective substance can be synthesized in relatively few steps. Studies such as those above will assume more importance in synthetic organic chemistry.

We sincerely thank Professors Sajiki, Iwabuchi, Kawabata and their colleagues for their significant contributions.