Here, the preparative reactions, chemical reactivities, and synthetic utilization of MT-sulfone, a typical dithioacetal S, S-dioxide, are described. MT-sulfone, which is the abbreviation name of (methylthio) methyl p-tolyl sulfone, is conveniently prepared from DMSO in the so-called “one-pot” manner. The combination of methylthio group and p-tolylsulfonyl (tosyl) group contributes to the easy formation of a carbanion and a radical on the central carbon of dithioacetal S, S-dioxide functionality and realizes many types of reaction that transform the dithioacetal S, S-dioxide group into the desired functionalities. The C-C bond formation of MT-sulfone with a wide range of functional groups such as alkyl halides, aldehydes, and carboxylic esters makes synthetic intermediates, which are finally converted to the desired target molecules. Thus, MT-sulfone has proven to be a versatile reagent in organic synthesis. In this review, the synthetic methods using the ketene dithioacetal S, S-dioxides that can be easily derived from MT-sulfone are also surveyed.
An indium-catalyzed reductive Friedel-Crafts reaction using chlorohydrosilane with carbonyls in aromatic solvents gave alkylated aromatics. When allylsilane was used instead of aromatics, hydro-allylation of carbonyls proceeded in high yield. A direct substitution of OH group in alcohols was also catalyzed by indium compounds in the reaction with silyl nucleophiles. The system provides the direct reduction, chlorination, allylation, or alkynylation pathways for substitution of alcohols in a catalytic manner. The direct reaction of alcohols with active methylene compounds instead of silyl nucleophiles catalyzed by InCl3 was accomplished without any activator or promoter. Allylic alcohols and benzylic alcohols served as electrophiles. α-Methoxyketone and indoles as nucleophiles were applicable to this system. Since H2O is the only side product of this system, the alkylated products were easily isolated in pure form. Indium compounds that have moderate (not strong) Lewis acidity and oxophilicity enables the catalytic reactions effectively.
Catalytic asymmetric hydrogenation of olefins, ketones, and imines has widely been used to prepare various optically active compounds. Meanwhile, few asymmetric hydrogenations of aromatic groups had been reported until recently. We found hydrogenation of indoles to proceed with high enantioselectivity in the presence of a rhodium catalyst modified with a trans-chelating chiral ligand PhTRAP. The rhodium catalyst transformed N-acetylindoles bearing a substituent at 2-position into the corresponding indolines with up to 95% ee. 3-Substituted indoles were hydrogenated with high enantioselectivity (up to 98% ee) when their nitrogen was protected with a sulfonyl group. A PhTRAP-ruthenium catalyst exhibited high enantioselectivity (up to 95% ee) for the hydrogenation of N-Boc-indoles. The ruthenium complex catalyzed the hydrogenation of 2, 3-disubstituted indoles as well as 2- or 3-monosubstituted indoles. Furthermore, the recent progress of asymmetric hydrogenation of aromatic compounds was surveyed in this paper.
Three total syntheses of potent anticancer natural product FR901464 are described. The first total synthesis by the Jacobsen group used transition metal-catalyzed reactions to prepare their chiral fragments. Subsequently, the Kitahara group described their synthesis using the chiral pool to construct their building blocks. Finally, the Koide group published the most recent synthesis of FR901464 using both asymmetric reactions and the chiral pool for their chiral fragment syntheses. It is envisioned that these total syntheses will assist biological studies of FR901464 and its unique mode of action.
Chiral compounds containing a pyridine unit have been used widely for many functional molecules including ligands for molecular recognition chemistry and catalytic asymmetric reactions and medicines. In this review, the synthesis of chiral non-racemic pyridinylethyl units and some functional molecules that have the units are described. Our synthetic approach involves a lipase catalyzed acetylation of pyridinyl alcohols and a stereospecific subsitution of their methane-sulfonates with N-, S-, O-, and C-nucleophiles. Although a nucleophilic substitution reaction on the benzylic position has been extensively investigated, there have been few studies of that on the pyridinylmethyl position. We have revealed that perfect stereospecific substitutions occur in the reaction of non-racemic 1- (2-pyridinyl) ethyl methanesulfonates with various nucleophiles through a SN2 process. A number of optically pure chiral non-racemic 1- (2-pyridinyl) ethyl derivatives were synthesized.
Aromatic chain imides possessing chromophores connected by iminodicarbonyl linkers were synthesized as novel aromatic foldamers. In these molecules chromophores face each other and form the helical folding structures both in solution and in solid state. Their folding structures were investigated by single crystal X-ray analysis and 1H NMR spectroscopy. A circular dichroism (CD) spectral study on the chiral aromatic chain imides with bulky N-substituents showed that their helically chiral conformation based on folding remained for a reasonably long time without racemization in solution. As the number of folded chromophores increased, their absorption and fluorescence spectra were red-shifted, and induced CD signals were increased. This remarkable change is based on the intramolecular interaction between folded chromophores. As an application of these aromatic chain imides, a chiral photochromic system was investigated by utilizing the intramolecular photo [4+4] cycloaddition and thermal cycloreversion of anthracene and naphthalene chromophores connected by iminodicarbonyl linkers.
Oseltamivir phosphate (Tamiflu®) 1 is the only orally active anti-influenza drug. Although constant supply of 1 has been required to avert a possible lethal influenza outbreak, the current commercial synthetic route depends on (-) -shikimic acid 2 of limited availability. New and advantageous synthetic routes to 1 via the catalytic asymmetric reaction have been developed recently, revealing the evolution of synthetic methodology.