The development of chelation-assisted C-H functionalization reactions has long been driven by noble transition metal catalysts, despite the obvious economic benefits of using earth-abundant transition metals. In this context, seminal reports in the literature suggest the potential of cobalt complexes as catalysts for C-H functionalization. This account summarizes our studies on the development of a series of cobalt-based catalysts for chelation-assisted C-H functionalization reactions such as addition of C-H bonds across carbon-carbon multiple bonds (hydroarylation), and coupling between C-H bonds and organic electrophiles. These studies have demonstrated that cobalt catalysts not only serve as mild and cost-effective alternatives to noble metal catalysts for existing C-H functionalizations, but also enable hitherto unknown or difficult transformations, including branched-selective hydroarylation of styrenes and ortho-alkylation using unactivated secondary alkyl halides.
This account describes our studies on the use of alkylboranes for copper-catalyzed allylic substitution and conjugate addition reactions. The wide availability of alkylboranes via the established alkene hydroboration reaction is an attractive feature of these transformations. Various functional groups are tolerated in the substrates. Catalytic mechanisms involving the formation of alkylcopper(I) species from alkylboranes through B/Cu transmetalation are proposed.
The development of cascade reactions is an area of considerable interest in modern organic chemistry. Recent advances in homogeneous gold catalysis have opened up further possibilities for atom-economical cascade reactions for efficient synthesis of complex target molecules. We have been involved in the development of cascade reactions based on the activation of carbon-carbon triple bonds by a gold catalyst to facilitate intra- and intermolecular nucleophilic attack. Quite recently, we succeeded in forming gold carbenoids, which are useful intermediates for further elaborations, from ynamides. This account describes our efforts towards the development of gold-catalyzed cascade reactions for atom-economical synthesis of fused carbazoles, naphthalenes, dihydropyrazoles/indazoles, and indoloquinolines.
The Mannich reaction is a synthetically useful method for the construction of nitrogen-containing molecules. Organocatalysts have been successfully applied to the Mannich reaction. Our group has been engaged in research on the organocatalyst-mediated Mannich reaction since the early days of its development in 2002. We have developed a proline-mediated three-component Mannich reaction of aldehyde, ketone and p-anisidine under the high pressure induced by water-freezing. Proline was found to effectively promote the cross Mannich reaction of two different aldehydes to afford the Mannich product with syn-selectivity and excellent enantioselectivity, conditions successfully employed as a key reaction for the stereoselective synthesis of the N-terminal amino acid moiety of Nikkomycin B and Bx. A trifluoromethyl-substituted diarylprolinol silyl ether is an effective organocatalyst of the Mannich reaction with acetaldehyde as nucleophile. It is also effective in the desulfonylative Mannich reaction of aliphatic aldehyde, α-chloroacetaldehyde and α-keto aldehyde which are employed as a precursor of the imine, affording the desired Mannich products with anti-selectivity and excellent enantioselectivity. As the obtained Mannich products are useful chiral building blocks which can be prepared by this simple procedure, the present methods are important for the synthesis of nitrogen-containing molecules.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) continues to be a serious major global health risk. More than one-third of the world’s human population is infected, resulting in 1.4-2.0 million deaths per year. The first-line therapy using a multidrug regimen has existed since the 1970s, however, there has been an alarming increase in the number of patients with multi (MDR)- and extensive (XDR)-drug-resistant TB in recent years. Hence, there is an urgent need to develop novel drugs with new mechanisms of action and new chemotypes in order to combat drug-resistant TB. A target-based approach to finding new anti-TB agents has been widely used, however this approach has not led to the identification of clinical candidates. The recent trend has been to go back to whole-cell screens, in which compounds are identified based on their anti-TB activity. Consequently, various groups have reported structurally diverse active compounds against Mtb, which were originally identified from phenotypic screens. This review will cover recent scientific accounts published from these groups that have described medicinal chemistry optimization studies from whole-cell screening hits. In vivo pharmacokinetics and efficacy of optimized compounds as well as their potential molecular targets will be also discussed.
Minireview describes most recent mechanistic studies of the synthetically or theoretically important catalytic asymmetric reactions. Contrary to the commonly accepted view of competition between two almost identical catalytic pathways leading to the opposite enantiomers of the product, in most cases it was essential to analyze numerous mechanistic possibilities and competition of structurally dissimilar catalytic pathways.
Room temperature liquid formulation of intrinsically stiff, optically or optoelectronically active, π-conjugated molecules, such as anthracenes, oligo(p-phenylenevinylenes), and fullerenes, by attaching soft branched long-alkyl chains is demonstrated. Multiple modification with the branched long-alkyl chains on the periphery of an emissive π-conjugated moiety results in isolation of the π-unit core, thus generating a room temperature liquid state with almost no π-π interaction among the adjacent π-units and which shows considerably good luminescence. When only partially wrapping a π-unit core, e.g. C60, attached by branched alkyl chains, those alkyl-π compounds are liquid/amorphous at room temperature, which however, can be directed into assembly by adding either of their own molecular segments, the π-unit or the alkyl-unit (alkane solvents). These ordered materials change from non-photoconductive monomer species to photoconductive assemblies.
Recent progress in direct arylation polycondensation made by our group is summarized herein. Polycondensation via direct arylation of C-H bonds in fluorinated benzenes or thiophene analogs afforded the corresponding conjugated polymers with high molecular weight in good yield. These protocols enable synthesis of conjugated polymers without prior preparation of organometallic monomers. Optimization of the reaction conditions led to the establishment of a simple catalytic system employing reduced Pd catalyst loading in the absence of a phosphine ligand. Elemental analysis and microanalysis revealed the high purity of the obtained polymer, which is derived from the simple catalytic system. The pure polymer exhibited excellent performance as a material for organic field effect transistors and organic photovoltaics.
Relative to π-electron systems between elements from the second row of the periodic table, those between heavier main group elements should exhibit higher HOMO and lower LUMO levels. Moreover, such π-electron systems between heavier main group elements are expected to be good electron acceptors and donors, and they should also exhibit good electron transporting properties. With the ultimate goal to create unprecedented π-electron systems between heavier main group elements in mind, we designed d-π electron systems containing heavier main group elements in the π-electron moiety and transition metals in the d-electron moiety. In this account article, we present our recent progress on the generation of bimetallic ferrocenyl- and ruthenocenyl-based d-π electron systems containing π-bond spacers of heavier main group elements from group 14 or 15.
The degree of oligomerization in the Wurtz-type coupling of 1,1,2,2-tetrachlorocyclooligosilanes was found to be controlled by the ring sizes of the cyclooligosilanes. The Wurtz-type coupling of 1,1,2,2-tetrachlorocyclotetrasilane, -cyclopentasilane, and -cyclohexasilane gave a tetramer, a trimer, and a dimer, respectively. These oligomers are the first examples of octasilacuneane, hexasilabenzvalene, and bicyclo[4.1.0]heptasil-1(6)-ene derivatives.