A metal-catalyzed introduction of sulfur substituents to unsaturated carbon-carbon bonds is important methodology in organic synthesis. In particular, an addition of thiols is well used as a convenient procedure. As a general rule, the reaction affords anti-Markovnikov type products via a radical process. On the contrary, a report of Markovnikov-type reaction is very restricted. A catalytic procedure has not been extremely exploited. However, we found that a zinc-catalyzed hydrothiolation of alkenes proceeds smoothly in the presence of Brøntsted acid.

A reaction of alkynes with thiols usually affords β-vinyl sulfides via a radical process. The procedure is well researched using various metal catalysts. The reaction can perform region- and stereoselectively. Regrettably, a double hydrosulfenylation of alkynes hardly proceeds. We found that a dihydrosulfenylation of alkyne was promoted by using zinc or nickel catalyst in air, and the desired β-dithioacetals were obtained regioselectively in good yields.

This article describes about a metal-catalyzed convenient regioselective introduction of sulfide-groups to alkenes or alkynes.

Dehydroamino acids are often found in nitrogen-containing natural products and widely utilized as a useful intermediate for the synthesis of nitrogen-containing organic molecules. In this article, we would like to report our recent efforts toward development of the stereoselective syntheses of α,β-dehydroamino acids and its application to the synthesis of nitrogen containing natural products and biologically active molecules. We developed a new olefination reagent, (diphenylphosphono)glycine esters, which allowed smooth condensation with aldehydes to provide E-dehydroamino acids in a stereoselective manner. The new method was successfully applied to the stereoselective synthesis of dehydroisoleucine and the tripeptide side chain of phomopsin A. Stereo-selective synthesis of (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid, 2,6-diaminosuberic acid, and kaitocephalin via hydrogenation of dehydroamino acid moieties are also described.

A skipped diene (1,4-diene) is an important structural motif found in a variety of biologically active natural products. We report the stereodivergent method, consisting of hydroboration of allenes and the Migita-Kosugi-Stille coupling, which allows for access to all four possible stereoisomers of the skipped dienes. The hydroboration of allenes is especially useful because both E-allylic and Z-allylic alcohols are obtained by simply changing the organoborane reagent. While use of 9-BBN provides E-allylic alcohols as thermodynamic products, the reaction with HB(Sia)₂ gives Z-allylic alcohols as kinetic products. The developed method was successfully applied to the unified total synthesis of madangamine alkaloids.

Over the past decade, C-H activation reaction in which a bond formation is accomplished by breaking otherwise inert C-H bonds, has emerged as an ideal tool for constructing molecular framework of valuable compounds such as drugs and natural products. While considerable efforts have been made to expand scope of the methodology particularly on the type of accessible C-H bonds, there are still formidable challenges that should be addressed to be involved in cost effective manufacturing process of the organic molecules. This article describes our recent accomplishments to develop efficient catalytic systems for the C-H activation and their application to practical synthesis of pharmaceuticals.

In recent years, the modality of pharmaceuticals has diversified but small molecule drugs are still important because they are easy to produce and can target intracellular molecules. Heterocycles have long been used as the main scaffold of drugs and often control the properties of the molecule such as three dimensionality, lipophilicity, metabolic stability, and toxicity. Transition metal-catalyzed cross-coupling reactions have enabled the introduction of various substituents on aromatic rings. On the other hand, establishment of efficient synthetic methods for the construction of various non-planar heterocycles remains an important pursuit. Herein, we report the development of efficient synthetic methods for sp³ atom-containing benzo-aza/oxacycles and peptide mimetics based on skeletal diversity-oriented synthesis.

Direct oxygenation of arene C-H bond is an attractive chemical transformation in terms of both the most fundamental metabolism of aromatic compounds in organism and the most straightforward way to obtain phenolic compounds from abundant aromatic materials. This transformation has been studied for a long time and recent efforts have overcome long-standing drawbacks such as low efficiency and narrow substrate scope. This review highlights such the outstanding examples of direct aromatic C-H oxygenation aspiring to “late-stage functionalization” of complex molecules.