鈴木 教之

Cynaropicrin is found in artichoke (Cynara scolymus) and is the source of its bitter taste and it is a sesquiterpene lactone with a 5-7-5 tricyclic skeleton, six chiral centers, and four exo-olefins. This natural product has numerous attractive biological activities including the inhibition of NF-kappa B activation, antihepatitis C activity, and antitrypanosomal activity. In this study, the first total synthesis of cynaropicrin was achieved starting from (S)-alpha-pinene. The synthesis involved a stereoselective Favorskii rearrangement and an indium-promoted diastereoselective Barbier reaction.

Five-membered metallacycloallene compounds, 2,5-disubstituted 1-zirconacylopenta-2,3-dienes were prepared from (E)-1,4-trialkylsilylbut-1-en-3-ynes in good yields. The structures of these compounds were determined by X-ray diffraction study. Contrary to our previous study on 2,4-disubstituted 1-zirconacylopenta-2,3-dienes, which gave alkynyl alcohols by the reaction with ketones after hydrolysis, the 2,5-bis(trialkylsilyl) complexes reacted with ketones to afford allenyl alcohols. Reactions with a nitrile gave a pyrolle compound probably via the formation of seven-membered 1-aza-2-zirconacylcohepta-3,4,7-triene compounds. When the (E)-1,4-bis(trialkylsilyl)but-1-en-3-ynes were treated with titanium isopropoxide/n-butyllithium followed by reaction with nitriles, the corresponding alkynyl ketones were obtained.

A Ph3PAuCl–SnCl2 composite, prepared in situ from Ph3PAuCl and SnCl2, catalyzed the formation of 1-benzopyrans from phenols and phenylacetylene. The Ph3PAuCl–SnCl2 composite catalyzed reaction was presumed to proceed through the successive ortho-alkenylation and O-alkenylation of phenols with phenylacetylene followed by cyclization of the prepared ortho- and O-dialkenylated phenol derivatives. Conveniently, all reactions with Ph3PAuCl–SnCl2 composite were established without rigorous exclusion of air and water.

The aldol reaction of 4-nitrobenzylaldehyde and cyclohexanone was catalyzed with the copolymer micelles, and the product was obtained in good yield with excellent diastereo- and enantioselectivity. Both the yield and stereoselectivity were superior to those obtained by using our previously developed proline-immobilized “broom”-type PNIPAAm-b- PEG copolymer catalysts. The Michael reaction was also catalyzed by the “linear”-type PNIPAAm-b-PEG catalyst and resulted in moderate yields with good stereoselectivity.

Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring. The total synthesis of isodesmosine, a crosslinking amino acid of elastin and an attractive biomarker of COPD, has been achieved by stepwise and regioselective Negishi and Sonogashira cross-coupling reactions.

Stable five-membered sulfur-containing metallacyclic allenes, 1-thia-2-metallacyclopenta-3,4-diene, were synthesized from the reactions of low-valent zirconocene or titanocene with alkynylthioamides.

The Negishi cross-coupling reaction of an organozinc derivative prepared from protected l-aspartic acid with monohalopyridines was improved by employing a combination catalyst of Pd2(dba)3 and P(2-furyl) 3 and removing an extra Zn from the organozinc reagent via centrifugation. The reactivity of halogenated pyridines (Cl, Br, I) with substituents at the C2, C3, and C4 positions of the pyridine ring was investigated, and it was found that the use of 4-iodopyridine as a substrate gave the best yield (90%) for the cross-coupling reaction. © 2013 HeteroCorporation.

Tin(II) chloride, which is insensitive to water and air, mediated the coupling reaction between alkynes and aldehydes as a Lewis acid in nitromethane to produce (E)-α,β-unsaturated ketones by a skeletal transformation in which one alkynic carbon atom changed into an oxo carbon atom accompanied by the cleavage of a C=O bond in the starting aldehydes. This coupling reaction was promoted by a catalytic amount of a primary or secondary alkanol. The coupling reaction between 1-deuterio-2-phenylethyne and benzaldehyde with BuOH afforded 1,3-diphenyl-2-deuterio-2-propenone (2-deuteriation: 94 % D), whereas the coupling reaction between phenylethyne and benzaldehyde with BuOD afforded 1,3-diphenyl-2-propenone (2-deuteriation: 0 % D). Because almost no exchange between hydrogen and deuterium at the 2-position of 1,3-diphenyl-2-propenone occurs in either of the reactions, the coupling reaction between alkynes and aldehydes with tin(II) chloride is presumed to proceed by nucleophilic addition of alkynes to aldehydes. The cleavage of the C-O single bond generated by the nucleophilic addition might be induced by the strong oxophilicity of tin. Coupling reactions occur between alkynes and aldehydes mediated by tin(II) chloride as a Lewis acid to produce (E)-α,β-unsaturated ketones by a skeletal transformation in which an alkynic carbon atom changes into an oxo carbon atom accompanied by cleavage of the C=O bond in the starting aldehydes. This coupling reaction is promoted by a catalytic amount of a primary or secondary alkanol. Copyright © 2013 WILEY-VCH Verlag GmbH &amp Co. KGaA, Weinheim.

Seven-membered metallacyclic allene compounds, 1-zirconacyclohepta-2,3,6-trienes, were synthesized by intermolecular coupling between alkynes and 1-en-3-ynes on a zirconium atom. X-ray diffraction studies and NMR spectroscopic observation indicated their seven-membered structures, although the contribution from 2-alkynyl-1-zirconacyclopent-4-ene might be considered. Benzyne, an unstable alkyne, also coupled with 1-en-3-ynes on zirconium and titanium.

The cyclotrimerization of terminal alkynes, such as ethyl propynoate, arylacetylenes, and alkylacetylenes, catalyzed by phosphine-free [IrCl(cod)]2 is induced by a catalytic amount of tin(II) chloride in 1,4-dioxane to afford 1,2,4- and/or 1,3,5-trisubstituted benzenes. Terminal α,ω-diynes also undergo the cyclotrimerization with monoynes to form bicyclic benzene derivatives. cod=1,5-cyclooctadiene.

ビス（トリメチルシリル）[3]クムレンと共役エノンが、ルイス酸存在下でエン反応し1,3-エンイン構造を持つカルボニル化合物を与えた。このとき出発物質のトリメチルシリル基は生成物中に保たれており、続く合成反応に供することが出来た。

Seven-membered metallacycloalkyne compounds were synthesized. The reaction of the zirconocene-ethylene complex and (Z)-1,4-bis(trimethylsilyl)buta-1,2,3- triene gave a mixture of 1-zirconacyclopent-3-yne and 1-zirconacyclohept-3-yne. In contrast, zirconocene-alkyne complexes, such as those of 1-(trimethylsilyl) prop-1-yne and diphenylacetylene, gave 1-zirconacyclohept-2-en-5-yne in good yields. Consideration of structural parameters suggests that both a seven-membered cyclic alkyne and a five-membered structure contribute to generation of this complex. Coupling of benzyne and [3]cumulenes on a metal was also found to afford the corresponding metallacycles. Seven-membered metallacycloalkyne compounds were synthesized and structurally characterized. Zirconocene-alkyne complexes, such as those of 1-(trimethylsilyl)prop-1-yne and diphenylacetylene reacted with [3]cumulene to give 1-zirconacyclohept-2-en-5-yne in good yields. Coupling of benzyne and [3]cumulenes on the metal also gave the corresponding metallacycles. Copyright © 2013 WILEY-VCH Verlag GmbH &amp Co. KGaA, Weinheim.

L-Proline moieties, which serve as organocatalysts, were tethered on block copolymers that consisted of thermoresponsive poly(N-isopropylacrylamide) and PEG-grafted polyacrylate blocks. The copolymer dissolved in water under the LCST (25 °C), while they formed micelle above the LCST (50 °C). Aldol reactions between an aryl aldehyde and a ketone were conducted in this aqueous solution. The aldol products were obtained in high yield with high diastereo- and enantioselectivity (96% ee). The catalyst solution could be reused up to three times.

O,N,O-tridentate ligands 2-H-2 based on a 2,6-substituted pyridine structure and their dichlorotitanium complexes 3 were synthesized and structurally characterized. The complexes have five-coordinated, trigonal bipyramidal structure, in which one chlorine atom was located at trans-position to the nitrogen atom of the pyridine ring and the other was at cis-position. NMR spectroscopy indicated their fluxional structure in solution. The complexes showed low to modest catalytic activity for ethylene polymerization in the presence of methylaluminoxane (MAO) as a co-catalyst. (C) 2012 Elsevier B.V. All rights reserved.

Reaction of η2-iminozirconocene chloride complexes with trimethylsilylethynyl lithium yields the corresponding five-membered aza-zirconacycloallenoids, which were also obtained from in situ generated zirconocene with alkynyl imines.

The stereoisomerization of 2,5-disubstituted 1-zirconacyclopent-3-yne compounds, stable five-membered cycloalkynes, has been studied with regard to the mechanism. The bimetallic complex of 1,4-bis(trimethylsilyl)butatriene was synthesized and structurally characterized, although it seems unimportant for the stereoisomerization reactions. The isomerization of trans-1,1-bis(eta(5)-cyclopentadienyl)-2,5-bis(trimethylsilyl)-1-zirconacyclopent-3-yne 2a into the cis-form in benzene-d(6) solution were observed using H-1 NMR spectroscopy at 50 degrees C in various concentrations. The reaction was first order with respect to trans-2a. This ruled out the possibility that a bimetallic complex was responsible for the isomerization. A kinetic isotope effect was observed (k(H)/k(D) 1.8), suggesting that C-H activation is involved in the rate-determining step. A mechanism via hydrogen elimination from the complex of eta(4)-pi,pi-coordination mode is proposed. (C) 2011 Elsevier B.V. All rights reserved.

Palladium(II)-exchanged hydroxyapatite (PdHAP; Pd/Ca ratio = ca. 1/200) was prepared by ion-exchanging with Ca2+ from calcined hydroxyapatite and Pd(NO3)2 in water at 70 °C for 24 h. The PdHAP functioned as a catalyst for the Suzuki–Miyaura-type cross-coupling reaction of aryl bromides and potassium aryltrifluoroborates with triphenylphosphine (1 mol%) and excess potassium carbonate at 50 °C in methanol under air. The heterogeneous PdHAP catalyst was used ten times repeatedly at 50 °C in methanol under air, though its catalytic activity gradually declined. XRD and XRF analyses and TEM images revealed that most of palladium species would still be supported as isolated ions on the repeatedly used PdHAP, in spite of the changes of the structure and composition of PdHAP surface at the late stages in the repetitive uses and the partial leaching of Pd species at the initial stages in the repetitive uses.

Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total synthesis of (+)-desmosine was achieved in 11% overall yield in 13 steps utilizing stepwise and regioselective Sonogashira cross-coupling reactions.

Copper(II)-exchanged hydroxyapatite, prepared by ion-exchanging of Ca(II) in calcium hydroxyapatite [Ca-10(PO4)(6)(OH)(2)] with Cu(NO3)(2) at 70 degrees C in water, functions as a reusable heterogeneous catalyst with neither reducing agents nor bases for azide-alkyne [3+2] cycloaddition at 50 degrees C in water under air. (C) 2011 Elsevier Ltd. All rights reserved.

The E isomer of a [5]cumulene derivative, 2,2, 9,9-tetramethyl-3,8-diphenyldeca-3,4,5,6,7-pentaene (1), which was previously believed to be unisolable owing to very fast E/Z isomerization, was isolated and structurally characterized. The Z isomer was trapped as the transition-metal complex 5, and the molecular structure was determined. DFT calculations and an electrochemical study on 1 are also described.

Ruthenium complexes bearing ethylbis(2-pyridylethyl)amine (ebpea), which has flexible -C2H4- arms between the amine and the pyridyl groups and coordinates to a metal center in facial and meridional modes, have been synthesized and characterized. Three trichloro complexes, fac-[(RuCl3)-Cl-III-(ebpea)] (fac-[1]), mer-[(RuCl3)-Cl-III(ebpea)] (mer-[1]), and mer-[(RuCl3-)-Cl-II{eta(2)-N(C2H5)(C(2)H(4)py)=CH-CH(2)py}] (mer-[2]), were synthesized using the Ru blue solution. Formation of mer-[2] proceeded via a C-H activation of the CH2 group next to the amine nitrogen atom of the ethylene arm. Reduction reactions of fac- and mer-[1] afforded a triacetonitrile complex mer- [Ru-II((CHCN)-C-3)(3)(ebpea)(PF6)(2) (mer-[3](PF6)(2)). Five nitrosyl complexes fac-[RuX2(NO) (ebpea)]PF6 (X = Cl for fac-[4]PF6; X = ONO2 for fac-[5]PF6) and mer-[RuXY(NO)(ebpea)]PF6 (X = Cl, Y = Cl for mer-[4]PF6; X = Cl, Y = CH3O for mer-[6]PF6; X = Cl, Y = OH for mer-[7]PF6) were synthesized and characterized by X-ray crystallography. A reaction of mer-[2] in H2O-C2H5OH at room temperature afforded mer-[1]. Oxidation of C2H5OH in H2O-C2H5OH and i-C3H7OH in H2O-i-C3H7OH to acetaldehyde and acetone by mer-[2] under stirring at room temperature occurred with formation of mer-[1]. Alternative C-H activation of the CH2 group occurred next to the pyridyl group, and formation of a C-N bond between the CH moiety and the nitrosyl ligand afforded a nitroso complex [Ru-II(N-3)(2){N(O)CH(py)CH2N(C2H5)C(2)H(4)py}] ([8]) in reactions of nitrosyl complexes with sodium azide in methanol, and reaction of [8] with hydrochloric acid afforded a corresponding chloronitroso complex [(RuCl2)-Cl-II{N(O)CH(py)CH2N(C2H5)C(2)H(4)py}] ([9]).

A five-membered metallacycloallene complex, 1-zirconacyclopenta-2,3-diene, was prepared from low-valent zirconocene and 2,4-bis(trimethylsilyl)but-1-en-3-yne. The complex reacted with carbonyl compounds to afford alkynyl alcohols after hydrolysis via C=O insertion into Zr-C bond. Similarly, nitriles inserted into the Zr-C bond to give the corresponding ketones after hydrolysis. The insertion of C=O and CN selectively took place at zirconium-sp(3) carbon of the metallacycle.

In this account [3]- and [5]cumulene complexes of group 4 metallocenes that form five-membered metallacycles are described. These complexes have a "triple bond" despite their five-membered ring structure, showing that they are regarded as 1-metallacyclopent-3-ynes. The molecular structures show their strained alkyne character. These complexes react with transition metals to form alkyne-coordinated bimetallic complexes. They also receive electrophilic attack by protons and boranes resulting in M-C bond cleavage. When a [3]cumulene couples with an alkyne on the metal, the reaction produces seven-membered metallacycloalkynes that have a strained structure showing an interaction between the "triple bond" and the metal center. Hexapentaenes. [5]cumulenes, form conjugated 1-metallacyclopent-3-ynes. The aryl-substituted [5]cumulene complex was reduced by alkali metal to give dianionic species that reacted with protons to give 1-metallacyclopent-3-ene, a cycloalkene, and with iodomethane to give 1-metallacyclopenta-2,3-diene, a cycloallene. The hexapentaene with tert-butyl groups reacts with zirconocene to form an eta(2)-pi-coordinated complex in the presence of trimethylphosphine, although it gave a 1-metallacyclopent-3-yne in the absence of the phosphine. The former was transformed into the latter by addition of a phosphine, and vice versa by removing the phosphine, showing a "haptotropic" shift. (C) 2009 Elsevier B.V. All rights reserved.

The (iminium ion)ruthenium(II) complex mer(Cl, Cl,Cl)-[RuCl(3){eta(2)-NCHCH(2)py(C(2)H(4)py)C(2)H(5)}] was synthesized via a C-H activation of the bridging ethyl group of an ethylbis(2-pyridylethyl)amine ligand and characterized by X-ray structural analysis. Oxidations of alcohols by the (iminium ion)ruthenium(11) complex occurred with generation of mer-[Ru(III)Cl(3)(ebpea)].

The first highly selective 1:2 cross-trimerization between triisopropylsilytacetylene and 2 equiv of internal alkynes, leading to 1,3-diene-5-yne compounds, was achieved using the Ni(cod)(2)/P(n)Pr(3) catalyst. Various symmetrical and asymmetrical internal alkynes could be used for the cross-trimerization reaction with high regio- and stereoselectivity.

Low-valent zirconocene species reacted with 1,1,6,6-tetraalkyl-1,2,3,4,5-hexapentaenes to form both 1-zirconacyclopent-3-ynes and n(2)-pi-coordinated complexes according to the alkyl groups (R) and the existence of the neutral ligand (L). Haptotropic interconvertion between these two complexes was observed. It was proposed that double insertion of isocyanide into the Zr-C bond of 1-zirconacyclopent-3-ynes takes place via the isocyanide adduct of the eta(2)-pi-complex as an intermediate.

We measured steady-state fluorescence of cis-stilbene in solution, by carefully separating the contribution of coexisting trace amount of trans isomer. The obtained 'pure' fluorescence spectrum of cis-stilbene shows a broad structureless band (peaked around 420 nm) extending to the wavelength region as long as 700 nm. Compared to the fluorescence intensity from the coexisting trans isomer, the oscillator strength of the cis fluorescence was evaluated as 0.17, which indicated that the S(1) state of cis-stilbene is an optically allowed state. (C) 2008 Elsevier B.V. All rights reserved.

The new iridium(I)-guanidinate complex served as an efficient catalyst for phosphine-dependent selective cross-dimerization between silylacetylene and terminal alkyl- or arylacetylene. Especially, in case of cross-dimerization between silylacetylene and alkylacetylene, E/Z selectivity of resulting enynes could be controlled by changing phosphine.