The design of highly functionalized artificial catalysts is very important for practical organic synthesis. We have succeeded in the rational design of high-performance catalysts based on acid-base combined salts. Acid-base combined salt catalysts can be classified into three types: (1) Metal oxide-Lewis base combined salts, (2) Bronsted acid-Bronsted base combined salts, and (3) Lewis acid-Lewis base combined salts. Here we report our recent studies on development of highly selective cyclization reactions for the synthesis of key intermediates of bioactive natural products. Molybdenum(VI) oxide-bis(quinolinolato) complexes (class 1) efficiently catalyze biomimetic dehydrative cyclization of serine, threonine and cysteine derivatives to give oxazolines and thiazolines. Chiral 1, 1'-binaphthyl-2, 2'-diammonium salts (class 2) are useful catalysts for enantioselective Diels-Alder reaction of α-acyloxyacroleins. We also have developed the first enantioselective biomimetic iodocyclization of isoprenoids using a chiral nucleophilic promoter (class 3).
Axially chiral biaryls and N-aryl indoles are stereoselectively prepared by utilizing planar chiral transition metal complexes. Both enantiomers of axial biaryls and N-aryl indoles could be synthesized starting from an identical enantiomerically pure arene chromium complex. We applied this method to the synthesis of vancomycin A-B ring system and korupensamines. Kinetically controlled biaryl and N-aryl indole transition metal complexes with sp3 heteroatom at the side chain could be converted to thermodynamically stable complexes involving the inversion or transfer of planar chirality. These results indicate that transition metal fragment in planar chiral η6-transition metal complexes can be utilized as dynamic complexes with mobile chiral auxiliary.
A transition metal-catalyzed aryl carbon-chalcogen bond formation has been well performed by a combination of aryl halides and thiol or selenol under basic conditions. However, a catalytic process using dichalcogenides has been rarely explored to date . We have developed copper or nickel-catalyzed procedures, which realize preparation of unsymmetrical mono-chalcogenides from dichalcogenides with aryl halides under reductive conditions or with organoboronic acids under oxidative conditions. Furthermore, these reactions can utilize both organochalcogenide-groups on dichalcogenide.
We developed new synthetic methods for seven-membered carbocycles by the nickel-catalyzed cycloaddition of electron-deficient alkylidenecyclopropanes with unsaturated hydrocarbons. The selective cycloaddition proceeded in good yields, and the three-component cocyclization was also realized. The chemo- and regioselectivity is controlled by steric and electronic effect of the sub-strates. Electron-deficient alkylidenecyclopropanes are good substrates as three-carbon units, and a variety of unsaturated hydrocarbons such as alkynes, α, w-diynes, 1, 3-diynes, 1, 3-enynes and 1, 3-dienes was applicable to give cycloheptadienes, cycloheptenes and bicyclic compounds.
Half-esters are very important synthetic building blocks. They are commonly prepared by monohydrolysis of symmetric diesters. However, successful distinction of the two identical ester groups has been a challenging task. Enzyme reactions do not provide any basis for prediction of the reactivities. Classical saponification reactions typically produce a slurry mixture of the starting diester, dicarboxylic acid and a small amount of the half-ester, and the separation is very difficult. However, earlier, we reported a highly efficient and practical selective monohydrolysis of symmetric diesters with the use of THE and aqueous NaOH or KOH at 0°c. The reaction mixtures are quite clean, and therefore even when the yields are less than quantitative, the isolation and purification of the resultant half-esters is straightforward. The procedure is simple, and reaction conditions are mild and environmentally friendly, and therefore synthetic versatility of this selective monohydrolysis is anticipated. This review article describes the current progress and the scope of this selective monohydrolysis reaction.
Stereoisograms proposed for reexamining the relationships between stereoisomers (RS-stereoisomers) contain three relationships (enantiomeric, RS-diastereomeric, and holantimeric relationships), which correspond to three attributes (chirality, RS-stereogenicity, and sclerality). The three relationships are correlated to three relationships for describing internal structures: Enantiotopic, RS-diastereotopic, and holantitopic relationships. Among them, the term enantiotopic is used to specify the term prochirality, while the term RS-diastereotopic is used to specify the term pro-RS-stereogenicity. The term pro-RS-stereogenicity is clarified to correspond to the pro-R/pro-S-nomenclature, just as the term RS-stereogenicity corresponds to the RS-nomenclature. Substitution criteria based on stereoisograms are introduced to determine pro-RS-stereogenicity as well as prochirality.
Oxidation of hemiaminal prepared from aldehydes and amines is an alternative method for creating amide bond. In this mini review, recent developments of versatile amide bond formation reactions via oxidation process from aldehydes (or alcohols) and amines are described.
A nostalgic memoir of the author-then a young organic chemist-is disclosed. He describes his experience in colleges, in Canadian and American post-doctoral life, and in the earlier days thereafter of his long career in Sendai and Tokushima. He tries to emphasize the importance of determination, taking chance, diligence, patience, and gratitude in chemistry as well as in one's life.