Chemical synthesis in microreactors has received significant research interests both from academia and industry. Herein we report that organolithium reactions that are difficult to be done in batch can be achieved in flow microreactors. Characteristic features of flow microreactors such as precise residence time control are responsible for the control of unstable organolithiums. Protecting-group free synthesis and stereoselective synthesis using unstable organolithiums using flow microreactors serve as powerful tools in organic synthesis. Integration of such organolithium reactions also enhances the power and speed of organic synthesis and polymer synthesis.
The use of carbon dioxide as a low-cost and inherently renewable C1 building block for the synthesis of value-added fine chemicals is of great importance and has been attracted increasing interest. Especially, development of efficient methods to incorporate carbon dioxide into organic compounds forming robust carbon-carbon bonds is challenging issue. For such reactions, various carboxylation reactions using carbon dioxide as a “carboxyl unit” to synthesize carboxylic acids have been realized recently by using transition-metal complexes to activate carbon dioxide. In those examples, specifically, unsaturated compounds having carbon-carbon multiple bonds, such as alkynes, dienes, allenes, and aromatic compounds, have been used as good substrates. In this review article, transition-metal-promoted or -catalyzed carboxylation reactions of unsaturated compounds using carbon dioxide as the building block of carboxyl group are introduced in a comprehensive manner.
This account deals with recent advances in the chemistry of magnesium carbenoids, especially new synthetic application, by using the electrophilic nature of magnesium carbenoids mainly reported from 2009 to present from our laboratory. Magnesium carbenoids, magnesium alkylidene carbenoids, cyclopropylmagnesium carbenoids, and cyclobutylmagnesium carbenoids were generated from aryl 1-chloroalkyl sulfoxides, aryl 1-chlorovinyl sulfoxides, 1-chlorocyclopropyl p-tolyl sulfoxides, and 1-chlorocyclobutyl p-tolyl sulfoxides, respectively, with a Grignard reagent at low temperature. The generated magnesium carbenoids were found to be stable at around −78 °C or higher at least 30 min. The reactions of the generated magnesium carbenoids with carbon- and heteroatom-nucleophiles resulted in the formation of many interesting products. These results offer new synthetic methods that are unprecedented and also lacking common sense. The essence of the reactivity and the structure of the magnesium carbenoids were investigated by DFT calculations.
Multiblock amphiphiles adopting a multipass transmembrane (MTM) structure on a bilayer membrane have been developed by mimicking the molecular structures of MTM proteins. The amphiphiles are composed of alternative hydrophobic and hydrophilic parts. The hydrophobic parts that penetrate the membrane consist of a fluorescent aromatic group, so that absorption and fluorescent spectroscopy allows the characterization of the assembling/disassembling states of the hydrophobic parts. The spectroscopic analyses revealed that the tetra block amphiphile, bearing four hydrophobic parts, forms intramolecular stacking of the aromatic portions within the membrane, indicating the formation of an MTM structure. Moreover, the tetra block amphiphile shows ion transportation through the membrane following Eisenman sequence XI, where the four molecules self-assemble into a dynamic ion channel with a milli second scale opening-closing motion. The hierarchical construction of a higher-order structure by self-assembly of foldamers can be a rational design of programmable functional molecular organisms.
Ellagitannins are a biologically and structurally diverse class of natural products. The structure typically consists of galloyl and hexahydroxydiphenoyl (HHDP) group(s) esterified to glucose. The pyranose ring of the glucose moiety can even be in the axial-rich conformation when the HHDP group bridges the discontiguous hydroxy groups. We here described first total syntheses of two “axial-rich ellagitannins,”(−)-corilagin and (+)-davidiin, which have the HHDP bridge between 3- and 6-oxygens and between 1- and 6-oxygnens, respectively. In the synthesis of corilagin, the 3,6-bridge was constructed through a temporary ring-opening strategy. With this strategy, three synthetic method of the HHDP group were investigated. The total synthesis was achieved using originally developed method that is the CuCl2-n-BuNH2 mediated coupling of 4-O-benzylated gallates. The 1,6-bridge in davidiin was also constructed by this method with conformational locked strategy relying on the steric repulsion of bulky silyl groups.
After a brief introduction of photochromism, the results of the following research subjects elaborating extremely high-performance photochromic systems are described: (1)A photochromic bisthiazolylcoumarin with a phenolic hydroxy group was synthesized and it showed dual-mode luminescence control, i.e. photochromism and pH change, in a methanolic aqueous media; (2)Bisthiazolylindenone ethylene acetal was synthesized and it showed a large cyclization quantum yield caused by fixation of the conformation by intramolecular hydrogen bonds between the hydrogen atom on the acetal and the nitrogen atom of a thiazole as well as the hydrogen atom on the phenyl group of the indene moiety and the nitrogen atom of the other thiazole group; (3)Bisthiazolylindenols were synthesized, in which the hydrogen bond between the hydroxy group and the nitrogen atom of a thiazole played a crucial role in fixing the conformation in favor of photocyclization in a diastereoselective manner; (4)Complete diastereoselectivity of a facially chiral bisthienylethene having intramolecular bridging with a triethyleneglycol tether across the surface of one of the thiophene rings was achieved and, in this compound, the approach of the other thiophene ring was rigorously restricted only from the opposite side of the bridge; (5)Enantioselective photochromic ring closure of a bishydroxymethyl-substituted diarylethene was carried out in the presence of human serum albumin (HSA) in a buffered aqueous solution; and (6)The curious temperature dependence phenomenon for the diastereoselectivity of C2-symmetric bisbenzothienylethene with two chiral substituents was clarified.
Gold catalyst has attracted much attention in terms of its remarkable π-activation ability toward C-C multiple bonds. Recently, oxidative cross-coupling reactions, which are uncommon in gold catalysis, have been achieved using gold catalyst and Selectfluor®. In this review, the discovery and recent progress of oxidative cross-coupling reaction through the gold/Selectfluor® catalytic system are described.
Heterodendralenes have received increasing attention as building blocks for multiple cycloaddition reactions, namely diene-transmissive hetero-Diels-Alder (DTHDA) reactions, which lead to the rapid generation of molecular complexity. Therefore, the DTHDA protocol is an efficient and attractive method for stereoselective synthesis of a variety of heterocycles. In this review, DTHDA reactions of four different heterodendralenes are described.