Seiji Shirakawa

Human breath can be utilized as a source of carbon dioxide for organic synthesis.

Cysteine‐containing peptides are important building blocks for the preparation of artificially designed peptides. Therefore, the development of efficient methods for the synthesis of cysteine‐containing peptides is recognized as an important area of research. To achieve an efficient preparation method for cysteine‐containing peptides, we became interested in developing a mechanochemical native chemical ligation approach. First, amino acid thioesters, which are key reagents for native chemical ligation, were prepared in a ball‐mill reactor using a user‐friendly, odorless thiol reagent. Next, mechanochemical native chemical ligation between amino acid thioesters and cysteine derivatives was performed. As a result of these mechanochemical processes, cysteine‐containing peptides, including C ‐terminal unprotected peptides, were efficiently prepared.

A concise method for the preparation of dehydroselenocysteine-containing peptides has been developed via the direct transformation of cysteine derivatives.

An efficient method for the enantio- and diastereoselective synthesis of tricyclic γ-butyrolactones bearing three quaternary stereocenters has been developed through transformations of achiral alkenoic acid substrates. The target optically active tricyclic lactones were obtained as single diastereomers with good enantioselectivities through a sequence of catalytic asymmetric bromolactonization, azidation, and subsequent 1,3-dipolar cycloaddition. The origin of the complete diastereoselectivity observed in the formation of the tricyclic γ-butyrolactone products was elucidated in this study.

A BINOL‐derived sulfide catalyst bearing a diphenylmethanol unit was prepared. The catalytic ability of the chiral sulfide with a diphenylmethanol unit was investigated in the desymmetrizing bromolactonization for the asymmetric synthesis of functionalized chiral γ‐butyrolactones. Excellent catalytic performance was observed in the catalytic desymmetrizing bromolactonization. Furthermore, the role of each functional group in the BINOL‐derived sulfide catalyst was clarified in this study.

The structure of highly substituted chiral γ‐lactones is found in many important natural products. Therefore, the development of methods for the catalytic asymmetric synthesis of highly substituted γ‐lactones is recognized as an important area of research. Catalytic asymmetric halolactonizations are known to be reliable methods for the stereoselective preparation of optically active γ‐lactones. However, catalytic asymmetric halolactonizations for the synthesis of highly substituted γ‐lactones, such as α,γ‐bis‐quaternary γ‐lactones with four different carbon substituents on the lactone backbone, remain underdeveloped. To address this limitation, we report here the diastereo‐ and enantioselective synthesis of α,γ‐bis‐quaternary γ‐lactones possessing four carbon substituents at the α‐ and γ‐positions, achieved through chiral bifunctional sulfide‐catalyzed desymmetrizing bromolactonization.

An efficient method for preparing peptides containing a dehydroalanine residue was developed through the direct and chemoselective transformation of a cysteine residue.

Catalytic kinetic resolutions of racemic carboxylic acids are important methods for preparing chiral carboxylic acids in their optically active forms. While several effective methods for the catalytic kinetic resolution of chiral α‐tertiary carboxylic acids have been reported, the efficient kinetic resolution of α‐quaternary carboxylic acids remains a significant challenge. In this context, we aimed to develop methods for the kinetic resolution of α‐quaternary carboxylic acids. Our approach involves a BINOL‐derived chiral bifunctional sulfide‐catalyzed bromolactonization technique, which was developed by our research group. In this work, we report the kinetic resolution of α‐allyl‐α‐cinnamyl carboxylic acids bearing an α‐quaternary stereocenter via chemo‐ and stereoselective bromolactonizations. The use of a BINOL‐derived chiral bifunctional sulfide catalyst with a hydroxy group was key for the efficient kinetic resolution of racemic α‐allyl‐α‐cinnamyl carboxylic acids.

Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates without substituents on the carbon–carbon double bond have remained a formidable challenge. To address this limitation, we report herein the asymmetric bromolactonization of 5-hexenoic acid derivatives catalyzed by a BINOL-derived chiral bifunctional sulfide.