Hydrosilanes are versatile reagents in organic synthetic chemistry as well as oraganosilicon chemistry. Since the Si-H bond is rather inert, its activation is generally required. Recently electrophilic activation of the Si-H bond by a strong Lewis acid such as triarylboranes has received much attention. The highly electrophilic boron center interacts with the hydrogen on the silicon, which renders the Si-H bond polarized. We report here the intramolecular electrophilic activation of a Si-H bond by an ortho boryl group in o-(hydrosilyl)(dimesitylboryl)benzenes, which leads to (i) dehydrogenative condensation with alcohols and amines and (ii) mesityl-H ligand exchange between the silicon atom and the boron atom to form the o-(silyl)(hydroboryl)benzene intermediates. The o-(silyl)(hydroboryl)benzene intermediates undergo (i) hydroboration to carbonyl compounds and (ii) intramolecular B-H/C-H dehydrogenative cyclization to form the dibenzosilaborins.

Organoaluminum compounds have been widely utilized in synthetic organic chemistry as nucleophiles, reducing reagents, and Lewis acids. Most of the organoaluminum compounds contain trivalent aluminum atoms with the formula of AlR₃. In contrast, the properties of low-oxidation state aluminum species, Al(II) and Al(I), have not been investigated thoroughly to date. The low-oxidation state aluminum species are generally highly reactive and thus have been proposed only as short-lived, elusive intermediates in several organic reactions. Recent development in main group element chemistry, however, have made its possible to isolate highly reactive low-valent organoaluminum species as bottlable compounds and investigate their reactivity in detail. We report here the reactivity of organoaluminum species bearing Al-Al bonding towards various unsaturated compounds and dihydrogen. Structure and reactivity of formally anti-aromatic aluminacyclopentadienes (alumoles) are also described.

Developing clinically relevant synthetic agents that are capable of modulating protein-protein interactions (PPIs) has been recognized as a central goal in the Post-Genomic era. Specific control of the large and flexible PPI interfaces requires multivalent large agents. Mid-sized molecules provide a promising scaffold for designing PPI inhibitors, however, their large size often limits cell permeation, and the requirement of appropriate spatial distribution of many functional groups leads the issue of chemical tractability. In an effort to explore a new methodology of designing mid-sized PPI inhibitors to target intracellular targets, we have studied the strategy based on assembling small module compounds to create multivalent mid-sized agents. Herein, I describe three particular approaches based on the module assembly; metal-coordination-based ligand assembly, assembly of two modules for a pocket and a local surface, and intracellular assembly to generate an inhibitor in cells. These agents were shown to possess abilities to recognize targeted protein surfaces selectively and inhibit their PPIs in cells. This strategy may open a general approach that are applicable for regulation of intracellular PPIs by synthetic molecules.

In 1872, Wilhelm Lossen discovered the rearrangement bearing his name when he observed that pyrolysis of O-benzoylbenzohydroxamic acid affords phenyl isocyanate. Since that report, it has been believed over the years that this rearrangement requires the preliminary activation of primary hydroxamic acids (RCO-NHOH) by using an equivalent or more amount of activating agents except harsh reaction conditions. In this account, our recent research on base-mediated self-propagative Lossen rearrangement of primary hydroxamic acids for the efficient and facile synthesis of primary aromatic and aliphatic amines is described. This rearrangement has several features including no external activating agents to be needed for promoting the rearrangement, less than one equivalent of base to be used, and a clean reaction in which only carbon dioxide is produced as a by-product. A self-propagating mechanism through activation of a hydroxamic acid by an isocyanate intermediate is proposed and elementary reaction steps, namely, chain propagation reactions are supported by experiments.

Synthesis of nitrogen heterocycles using isocyanates was achieved by organotin reagents and catalysts. The reactions proceeded via intramolecular alkylation through terminally functionalized tin species. Thus terminally halogenated, enone-substituted and carbonyl substituted tin alkoxides have been provided as key intermediates. Such tin species could be generated by tin-mediated selective reactions, the ring cleavage of halo lactones and the addition to functionalized carbonyl compounds. These equimolar reactions induced to tin alkoxide-catalyzed reactions, that is, catalytic annulation of isocyanates with α-hydroxyl carbonyls, glycolide, lactide. In particular, optically pure nitrogen heterocycles were obtained directly from easily available plant-derived chiral sources, lactides. Further, tin halide-catalyzed reactions could be developed, that is, catalytic annulation of isocyanates with epoxides, 2-methyleneaziridines and cyclopropanes. This article includes author’s development of tin promoted synthesis of nitrogen heterocycles using isocyanates.

Native chemical ligation (NCL), featuring the use of N-terminal cysteinyl peptides and peptide thioesters, is among the most widely used methods to chemoselectively assemble unprotected peptides. To expand the applicability of the NCL-based assembly, ligation techniques using N-terminal selenocysteinyl peptides and/or peptide selenoesters have been developed. This review describes the recent applications of the selenium-driven peptide ligations.

Ryanodine is a ryanodane diterpene isolated from Ryania speciosa in 1948. This compound has an agonist activity for ryanodine receptor (RyR) as the calcium channel. Moreover, ryanodol is known as the hydrolysis analogue of ryanodine. The structural features of these compounds are a unique complex ring system with highly oxygenated carbon skeleton. Thus, it is important to construct pentacyclic rings and introduce oxygen functions efficiently for the synthesis. In this review, the total syntheses of ryanodol reported by three groups are described.