Aldol condensation is one of the most fundamental reactions. However, the conventional basic or acidic conditions limit the range of substrates and often lead to undesirable side reactions such as self-condensation. We have found a new one-pot aldol condensation method that consists of TiCl₄-promoted aldol reaction followed by base-promoted elimination of oxytitanium species. This method is applicable to the hitherto difficult condensations between two ketones, between thioester and ketone or aldehyde, or between selenoester and aldehyde, furnishing β,β-disubstituted α,β-unsaturated ketones, multiunsaturated thioesters, and α,β-unsaturated selenoesters. Synthetic utilities of unsaturated products in Lewis base-catalyzed conjugate reduction with HSiCl₃ and in preparation of synthetic intermediates of polyene natural products have been demonstrated. Neuroprotective activity of ar-atlantone and ar-turmrone as well as antiviral activity of α,β-unsaturated selenoesters toward HIV-1, SARS-CoV-2, and HBV have also been revealed.

Organofluorine compound is one of the most important classes of organic compounds in medicinal chemistry, because fluorine has several effects for improving biological activity. In order to express these effects of fluorine as expected, fluorine has to be installed at a specific location in molecules with well-controlled stereoconfiguration; in the case of sp³ fluorinated carbon in a structure, an enantioselective fluorination is highly demanded. In this context, we have developed β,β-diaryl serine as a new primary amine catalyst, which has been found to be an efficient catalyst for enantioselective α-fluorination of α-branched β-dicarbonyl compounds, such as β-diketone, β-ketoester, and β-ketoamide with high enantioselectivity (≥90% ee). Moreover, the cinchona-alkaloid based primary amine was found as the effective catalyst for enantioselective α-fluorination of γ-enolizable α,β-unsaturated aldehydes (≥90% ee). On the other hand, α-regioselective difluorination of γ-enolizable α,β-unsaturated aldehydes was successfully carried out by L-proline as a catalyst with high stereoselectivity (E/Z=≥20/1).

Carbon dioxide (CO₂) is a renewable chemical feedstock. However, the thermodynamic considerations of CO₂ limit its widespread use in chemical transformation. This paper summarizes the transition metal-catalyzed transformation of CO₂ via carbon-carbon bond-forming event. Cu complexes can catalyze the hydrocarboxylation of unsaturated hydrocarbons such as alkynes and 1,2-dienes using hydrosilanes as hydride sources. Similarly, the silacarboxylation of alkynes as well as 1,2-dienes proceeds using Cu catalysts and silylboranes as silicon sources. Ni complexes catalyze the carboxylation of less reactive aryl chlorides using Mn powder as the reducing agent. Ni complexes also work as catalysts for the double carboxylation of alkynes in the presence of Zn powder. The carboxyzincation reaction of internal alkynes proceeds using Co complexes as the catalysts and Zn powder as the reagent.

Functional organic materials play an important role in the innovation of science and technology as well as in updating our daily lives. Therefore, developing new synthetic methods that enable to create new functional materials is attracting increasing attention. This article describes the synthesis of dibromoindenes and tetrabromoindacenes, which are important synthetic modules in synthetic organic chemistry, based on the Friedel-Crafts type cyclization reaction using Lewis acid or Brønsted acid. Our protocol features the absence of special care for air and moisture and facile derivatization from commercially available starting materials. These dibromoindenes and tetrabromoindacenes have served as precursors to obtain a new family of carbon-bridged oligo(phenylenevinylene)s (COPVs) which have broad scope of substituents on the bridging carbon atoms and were impossible to obtain using the previous methods. Developments on the creation of novel photofunctional materials based on COPV, such as near infrared light emitting materials and photonic crystals, will also be introduced.

Cyclic peptides are attracting more and more attention as drug modalities targeting intracellular protein-protein interactions (PPIs). To realize cyclic peptides that can inhibit intracellular proteins, establishing design principles for highly membrane-permeable peptides is demanded. Here, we describe our recent investigations of the structure-permeability relationship of cyclic peptides. We first introduce standard permeability assays used for cyclic peptides. We next describe our recent studies on the membrane permeability of cyclic peptides. Using parallel artificial membrane permeability assay (PAMPA), we studied the influence of backbone stereochemistry and side chain structures on the membrane permeability of a cyclic hexapeptide. Finally, we describe a novel permeability assay using lipid bilayers. The assay enables measuring pure passive membrane permeability of cyclic peptides across lipid bilayers. We determined the lipid bilayer permeability coefficient of an important natural cyclic peptide cyclosporin A (CsA) and investigated the structure-permeability relationship of CsA.

Carvone, which has a chiral isopropenyl group, is sometimes used for total synthesis of natural product as the starting material. Recently, removal of isopropenyl group using hydrodealkenylation reaction was reported. Formal and total syntheses of natural products were achieved by using this reaction. In this short review, the reaction mechanism of hydrodealkenylation reaction and its application in the formal and total syntheses of natural products were described.