Trivalent arsenic compounds have lone pairs, which can coordinate with many kinds of transition metals. Several studies of organoarsine-transition metal complexes have been reported to show attractive properties. However, most synthesis of the organoarsenic compounds used for complexations are prepared from arsenic chlorides or arsenic hydrides. Ultimate care should be given for handling of these arsenic intermediates due to their volatility. To stimulate the field of organoarsenic chemistry, practical synthetic methods should be discovered. We have synthesized cis-1,4-dihydro-1,4-diarsinines, 1,4-diarsa-1,4-cyclohexadienes, as cyclic organoarsenic compounds by radical reaction of pentamethylcyclopentaarsine and acetylene derivatives. The cis-1,4-dihydro-1,4-diarsinines have unique structures, two arsenic atoms are connected with two rigid ethylene bridges and have divergent syn conformations of the two lone pairs on the arsenic atoms. Their stability toward air and moisture was great enough to allow their handling in air. The present report describes unique reactivity and coordination behaviors of the cis-1,4-dihydro-1,4-diarsinines. The experimental results suggest that the flexibility of the bond angles around the arsenic center is an inherent property in the present organiarsenic compounds, and the flexibility might be a main reason for the stabilization of the strained conformations, enable synthesis of unusual complexes, and showing unique properties.
Chronic obstructive pulmonary disease (COPD) is a respiratory disorder and is the fourth leading cause of death worldwide. Presently, there is a lack of effective medicines that can prevent progression of the disease, and thus survival rates cannot be improved. The development of biomarkers that can act as indicators of the severity of COPD and the level of patients’ response to therapy would thus aid the drug discovery activities. Elastin fibers are a part of the extracellular matrix and are an essential structural component of the lungs, ligaments, skin, blood vessels, etc. Desmosine (1) and isodesmosine (2) are crosslinking amino acids of elastin. The irreversible degradation of lung elastin that occurs in COPD is known to give rise to these two amino acids, which can be measured in clinical samples by LC-MS. Therefore, 1 and 2 are useful as attractive biomarkers for both drug discovery and rapid diagnosis of COPD. In this study, total synthesis of COPD biomarkers 1 and 2 and the related amino acids are reported utilizing palladium-catalyzed cross-coupling reactions.
Fluorovinyl compounds like fluorostyrenes and fluoroacrylates have been drawing enormous interests as building blocks for various types of organofluorine compounds as well as monomers for high performance fluoropolymers. Although synthetic methods of fluorovinyl compounds have been developed since several decades, more effective and practical methods are still highly desirable. Reactions of organometallic species with electrophiles are recognized as one of the most effective and selective C-C bond forming reactions. The strategy could be adapted as the synthetic methods for various organofluorine compounds. Herein are described effective, selective and practical synthetic approaches to fluorovinyl compounds by employing fluorinated vinylmetal species, such as α,β,β-trifluorovinylmetal, α,β- and β,β-difluorovinylmetal, α- and β-fluorovinylmetal species.
Oxypalladation is an attractive reaction to introduce an oxygen functionality to alkene. This review focuses on the recent development of stereocontrolled THP and THF ring formations by intramolecular oxypalladation reaction. Chiral THP and THF rings are constructed by PdII-catalyzed O-C bond forming reaction with 1,3-chirality transfer of chiral allylic alcohol. Examples of the stereoselective synthesis of these rings from chiral allylic alcohols are described. The origin of stereoselectivity of the chirality transfer is discussed and we propose that the reaction proceeds in the following sequences, i) formation of PdII-π-complex by syn-coordination of PdII-catalyst directed by chiral hydroxy group, ii) hydroxyl ligand exchange with nucleophilic hydroxyl group, iii) syn-oxypalladation, and iv) syn-elimination of the resulted σ-Pd-complex with the adjacent hydroxyl group. THP and THF rings are often found in the core structure of many natural products and these natural products exhibit often a diverse range of biological activities. Some examples for the total synthesis of natural products achieved in our laboratory are described, in which PdII-catalyzed THP and DHP ring formations are demonstrated for the synthesis of (−)-diospongins, (−)-aspergillide B, (−)-laulimalide, and (−)-apicularen A.
This review focuses on synthetic studies on mersicarpine that has a characteristic skeleton including seven-membered cyclic imine fused with indoline and δ-lactam. After a brief discussion of structural features and proposed biogenesis of this compound, several synthetic efforts toward construction of mersicarpine core are described. Total syntheses of mersicarpine are described including Kerr’s racemic synthesis utilizing a formation of seven-membered cyclic imine from α-hydroxyketone prepared by oxidation of indole, racemic syntheses of the Kerr’s synthetic intermediate by Zard and Han, the first enantiocontrolled total synthesis by Fukuyama based on the construction of seven-membered α-hydroxyimine by autoxidation of azepinoindole, and the second enantiocontrolled synthesis by Tokuyama employing a DIBALH-mediated ring-expansion reaction of cyclic ketoxime fused with indole.
Decarboxylative reaction of aliphatic carboxylic acids is a powerful tool for formation of aliphatic compounds in organic synthesis, because carboxylic acids occur widely in nature and are readily commercially available. Thus, a general method for the decarboxylative reaction of carboxylic acids under mild conditions is desired. In this paper, the author reports that alkyl radicals are generated in the decarboxylation of free aliphatic carboxylic acids by a radical cation of arene via photoinduced electron transfer. The generated alkyl radicals react with a variety of reagents such as thiols, alkenes, oxime ethers to yield the respective reduction and adduct products in high yields. This photochemical method represents a less toxic and milder process for formation of aliphatic compounds from aliphatic carboxylic acids via decarboxylation than conventional methods, because light is a clean and selective reagent.
The metal-catalyzed aminohydroxylation is a powerful method for the stereo-controlled construction of β-amino alcohols. However, very few intermolecular aminohydroxylations have been reported to date. This short review provides a recent development of the intermolecular copper- or iron-catalyzed oxaziridine-mediated aminohydroxylation of styrenes with high regio- and enantioselectivity.
Total syntheses of dimeric alkaloids, P-(+)-dispegatrine, (−)-neothiobinupharidine and (+)-dideepoxy-tabernaebovine, inspired by biogenesis were described. The stereoselective dimerization provided new biosynthetic aspects of these natural products.
Direct C-H (carbon-hydrogen) bond functionalization on heteroaromatic ring is desired in many chemical areas such as medicinal chemistry and material science, because it requires multi-step process with traditional methods. Herein we describe C-H arylation of electron-deficient heterocycles and quinones, and C-H alkylation of various heterocycles. These mild, cheap, operationally simple, chemoselective, and scalable reactions are applicable for functionalization of various heterocycles and quinones. These advantages allow for rapid access to functionalized heterocycles or natural products such as meroterpenoids that would be difficult to access with traditional methods. Mechanistic studies suggest that aromatic/aliphatic boronic acid or sodium/zinc alkyl sulfinate salts work as carbon-centered radical precursor under oxidative conditions.