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The catalytic asymmetric Friedel-Crafts/protonation of indoles and pyrroles with α-substituted nitroalkenes to give the corresponding adducts in a highly anti-selective manner was achieved by an imidazoline-aminophenol (L2)-Cu complex. The anti-adducts could be successfully transformed to biochemically important α-substituted β-heteroarylalkylamines.

The [6 + 2] cycloaddition reaction of 2-vinylazetidines with electron-deficient isocyanates such as tosyl isocyanate proceeded smoothly in the absence of the catalyst at room temperature, and various cyclic ureas were isolated in good to high yields. Electron-deficient allenes also reacted with the 2-vinylazetidine, and the corresponding azocine derivatives were isolated.

Intramolecular [2+2] photocycloaddition of aromatic chain imides possessing bis-phenanthrene moieties afforded straight and cross ring closure products. The ratio of cycloadducts was dependent on reaction time and temperature, which resulted in a reversal of regioselectivity. The reaction was proved to involve a retro cycloaddition. The cross ring closure products were formed predominantly in the early stage of the reaction at lower reaction temperature. In contrast, the straight ring closure products were predominant at higher reaction temperature with prolonged irradiation.

The total syntheses of tetrapeptides tubulysins D (1 b), U (1 c), and V (1 d), which are potent tubulin polymerization inhibitors, are described. The synthesis of Tuv (2), an unusual amino acid constituent of tubulysins, includes an 1,3-dipolar cycloaddition reaction of chiral nitrone D-6 derived from D-gulose with N-acryloyl camphor sultam (-)-9 employing the double asymmetric induction, whereas the synthesis of Tup (20), another unusual amino acid, involves a stereoselective Evans aldol reaction of (Z)-boron enolate generated from (S)-4-isopropyl-3-propionyl-2-oxazolidinone with N-protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins U (1 c) and V (1 d) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for γ-amido alcohol functionality. Furthermore, to understand the structure-activity relationship of tubulysins, we synthesized tubulysin D (1 b) and cyclo-tubulysin D (1 e) from 2-Me and 20, and ent-tubulysin D (ent-1 d) from ent-2-Me and ent-20, respectively. The preliminary results regarding their biological activities are also reported.

We synthesized various block-like molecules based on stereochemistry of tertiary aromatic amide which prefers cis (folded) conformation and weak intramolecular interactions such as aromatic-aromatic interactions. Their crystal structures and dynamic behaviors in solution were revealed by X-ray crystallographic analysis and dynamic 1H NMR measurement. The block-like molecules were triangular, rhombic, twisted, spherical or pinched circle in shape. Some of them aggregated into a channel-shaped network via weak intermolecular interactions.

The [6 + 2] cycloaddition reaction of 2-vinylazetidines with electron-deficient isocyanates such as tosyl isocyanate proceeded smoothly in the absence of the catalyst at room temperature, and various cyclic ureas were isolated in good to high yields. Electron-deficient allenes also reacted with the 2-vinylazetidine, and the corresponding azocine derivatives were isolated.

Adamantane-based macrocycles and a cage with aromatic ring moieties have been developed and structurally revealed by X-ray crystallographic analysis. The dimerized (1) and trimerized (2) macrocycles of binary molecules based on adamantane with acetylenic aromatic ring moieties were designed and effectively synthesized. Similarly, a cryptand-like macrobicyclic cage (3) was constructed from a trisubstituted adamantane derivative. Single-crystal X-ray analysis revealed that both cyclic compounds have nearly a rectangular shape with or without a solvent molecule in the cavity. The macrobicyclic cage has an inner space and accommodates a chloroform molecule via C-H...pi interactions. Macrocycles and cage encapsulate 1,3,5-trinitrobenzene (4) as an electron-poor guest in a one-to-one complex via charge-transfer interactions in a parallel fashion, and showed the formation of molecular networks such as columns, tubes, 2D layers, and 3D networks composed of two different types through noncovalent interactions in the solid state.

The Ni-catalyzed [3+2+2] cocyclization between ethyl cyclopropylideneacetate (1) and 1,3-diynes afforded cycloheptadiene derivatives. The three-component reaction of 1, 1,3-diynes, and alkynes proceeded with good yield and high selectivity. Scope of the substrates was studied, and the origin of chemo- and regioselectivity of the reaction is discussed.

Four-component synthesis of nitroimine derivatives (3) via double nitro-Mannich reaction was carried out in which nitroalkane, two moles of aldehyde, and lithium hexamethyldisilazide (LHMDS) were coupled in one-pot. In situ generated N-trimethylsilylaldimine was reacted with nitroalkane dianion followed by the second addition of the resulting nitrogen anion to the aldimine and the subsequent elimination of bistrimethylsilylamine furnished nitoroimine. The reaction was proceeded with erythro selectivity.

Base-promoted self-condensation reactions of trans-stilbene and diphenylacetylene monomers bearing 4-alkylamino and 4'-methoxycarbonyl groups were investigated. Reactions of N-propyl monomers under pseudohigh-dilution conditions (a THF solution of monomer was added dropwise to a THF solution of LiHMDS) afforded the corresponding cyclic triamides in good yields. X-ray crystallographic analysis showed that these cyclic triamides possessed an almost equilateral triangle structure with a cavity surrounded by tilted benzene rings.

We constructed a novel molecular conformational alteration system with an N-aryl-N-phenylacetamide structure, in which the N-aryl group consists of a hydroquinone-p-quinone system as a redox-dependent aromatic trigger. The amide conformation depended on the oxidation state of the aryl group, and the two states (compounds 2 and 3) were reversibly converted to each other by redox reactions. Such compounds would be applied as useful structural units for external stimulus-responsive control on the shape and function of large molecules or supramolecules.

The structural features and conformational conversion of the N-methyl pyridyl amide oligomer bearing 2,6-disubstituted pyridines were investigated. 1H NMR and X-ray crystallography revealed that the environment-responsive type of conformational control can be performed. The amide bond switching together with intramolecular hydrogen-bonding effects caused dynamic protonation-associated conformational conversion from layered to spiral and then flat.

Octahomotetraoxacalix[4]arenes bearing long alkyl chains on their lower rim were prepared. Ester 4a existed in a 1,2-alternate conformation in its crystal structure, which was examined by single-crystal X-ray diffraction analysis. To prepare liquid crystalline materials possessing calixarene moieties by self-assembling, carboxylic acid derivatives 5 were synthesized. Among them, 5c, the octadecyloxy derivative, showed smectic liquid crystal phase. Homooxacalixarenes 5 also formed liquid crystal phases with longer layer distances when two equivalent moles of 1,2-ethylenediamine were added as a linker. These phases were investigated with X-ray diffraction, differential scanning calorimetry, and polarized optical microscopy.

[reaction: see text]. Cycloaddition of aziridines with isocyanates proceeded smoothly in the presence of a nickel catalyst, and five iminooxazolidine derivatives were isolated in good yields. The best result was obtained when the reaction was carried out in the presence of NiI2, and a longer reaction time allowed the isomerization of the iminooxazolidine to the corresponding imidazolidinone derivatives.

[reaction: see text] The enantioselective [2,3]-Wittig rearrangement of 1-allyloxy-1-(naphthalen-2-yl)-4-siloxy-2,4-pentadienyl anion, derived from optically enriched 4,5-epoxy-1-(naphthalen-2-yl)-5-silyl-2-pentenyl allyl ether via a base-induced ring opening of the epoxide followed by Brook rearrangement, has been studied. The chirality of the epoxide was transferred to the alcohols in up to 97% ee, depending on the solvent used. The best result was obtained in 1,4-dioxane at a temperature above room temperature.

[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.

Single-crystal X-ray structures of 6 carboxamides possessing two units of 2-pyridone moieties connected with an iminodicarbonyl linker were examined to show the usefulness of this linker for the cr...

The development of a direct catalytic asymmetric aldol-Tishchenko reaction and the nature of its catalyst are described. An aldol-Tishchenko reaction of various propiophenone derivatives with aromatic aldehydes was promoted by [LaLi 3 (binol) 3 ] (LLB), and reactivity and enantioselectivity were dramatically enhanced by the addition of lithium trifluoromethanesulfonate (LiOTf). First, we observed a dynamic structural change of LLB by the addition of LiOTf using 1 3 C NMR spectroscopy, electronspray ionization mass spectrometry (ESI-MS), and cold-spray ionization mass spectrometry (CSI-MS). X-ray crystallography revealed that the structure of the newly generated self-assembled complex was a binuclear [La 2 Li 4 (binaphthoxide) 5 ] complex 6. A reverse structural change of complex 6 to LLB by the addition of one equivalent of Li 2 (binol) was also confirmed by ESI-MS and experimental results. The drastic concentration effects on the direct catalytic asymmetric aldol-Tishchenko reaction suggested that the addition of LiOTf to LLB generated an active oligomeric catalyst species.

Reaction of γ-silyl-β,γ-epoxybutanenitrile with a base generates an α-nitrile carbanion derivative of 4-siloxybut-3-enenitrile, which undergoes reaction with bis-electrophiles such as 1,ω-dihaloalkanes, ω-bromo-α,β-unsaturated esters, and bisenoates to provide highly functionalized carbocycles.

Phase-selective photochemical reaction of 2-pyridone derivatives was examined. Irradiation of 1 in benzene mainly gave rearrangement products 2. However, intermolecular [4 + 4] photocycloaddition proceeded quantitatively in the solid state, affording photodimers 3. An effective pi-pi stacking and dipole-dipole interaction between two pyridone moieties might play important roles in an effective arrangement of 1 for photodimerization in their crystal structures. [reaction: see text]

Photoreactivity of seven 9-anthryl-N-(naphthylcarbonyl)carboxamide derivatives, 1a-g, in their intramolecular [4 + 4] photocycloadditions in solid state is discussed on the basis of their single-crystal X-ray analyses. The distances (d(1) and d(2)) between the two carbon atoms to be reacted, the angles (theta(1) and theta(2)), and the torsion angle (theta(3)) between the anthracene and naphthalene rings were chosen as structural parameters for reactivity. For 1a and 1e, the first example of absolute asymmetric synthesis in [4 + 4] photocycloaddition was attained. [reaction: see text]

Novel cyclic aromatic amide oligomers containing highly fluorescent 9,10-diphenylanthracene units were prepared by condensation of a monomer with amino and ester functional groups using lithium bis(trimethylsilyl)amide. The cyclic trimer (C3A, 40%) and tetramer (C4A, 8%) were isolated using preparative gel permeation chromatography. Some of the aromatic proton signals derived from anthracene were observed in the upfield region (6.96–6.87 ppm) in the 1H nuclear magnetic resonance spectrum of C3A. X-ray crystallographic analysis indicated that three anthracene moieties are inclined with respect to the cyclic skeleton and partly overlap each other. The fluorescence peak maximum of C3A (438 nm) showed a small red-shift compared with that of an acyclic model compound (425 nm). Reduction of the amide carbonyl group in C3A gave the cyclic trimer HC3A, which has a tertiary amine unit. The fluorescence peak maximum of HC3A (489 nm) was largely red-shifted from that of C3A and exhibited strong solvent dependence. A linear correlation was observed between the Stokes shift (Δν), ranging from 2981 to 6646 cm−1, and the Reichardt's solvent polarity parameter [ET(30)].

Perchlorate-doped 3-methoxythiophene oligomer was chemically synthesized, and its solutions were applied to produce films characterized by their gold-like luster which showed no degradation in the ambient atmosphere for at least one year. The oligomer is characterized by its good solvent-soluble, good film-forming, and moderate electrical conducting properties. More importantly, wide-angle and grazing incidence X-ray diffraction measurements revealed that the gold-like films have a compact periodic layered structure with a lamellar interlayer spacing of 1.10 nm and an intralayer spacing of 0.34 nm, though the oligomer involves no long alkyl chains. It was proposed that the strong gold-like luster could be related to the highly regular and compact nature of the lamellae in the oligomer films.

Intramolecular diastereoselective [4 + 4] photocycloadditions of acyclic imides 1a and 1b possessing anthracene and naphthalene moieties were carried out in the solid state and in solution. For 1a, novel reversal of diastereoselectivity was observed on changing the reaction phase. The diastereomeric excess was changed from −60% de in the solid state at 60 °C to 70% de in acetone at −78 °C. Almost 100% de was observed for the solid-state photocycloaddition of 1b. The reactivity of 1a in the solid state was discussed based on its single crystal X-ray analysis.

A triple helicate, a macrocyclic aromatic amide with a helical structure, is complexed with La(III) ion leading to the self-assembly of a helical coordination polymer. Each La(III) atom is coordina...

The crystal structures of two aromatic chain imides, N-(naphthyl)-N-benzyl-9-phenanthylcarboxamide (1) and N-(9-anthrylcarbonyl)-N-{12-[9-anthryl-N-(phenylcarbonyl)carbonylamino]dodecyl}benzamide (2), were examined. In both imides, two aromatic moieties face each other, creating concave-shaped conformations.

Optically active materials could be generated by simple solidification of achiral materials without an external chiral source. When achiral cis-3,4-diphenylsuccinimides were solidified in the presence of a catalytic amount of DBU by evaporating the solvent with stirring, optically active trans-3,4-diphenylsuccinimides were obtained quantitatively with high enantiomeric excesses.

A low-molecular-mass molecule with no long alkyl chain, a mixed-valence 9,9′-dimethyl-3,3′-bicarbazyl, is self-assembled into highly-regular straight micro/nanotubes by the one-step electro-oxidation of its precursor, 9-methylcarbazole, in methanol without templates. The driving force of the tube formation is investigated.

An adamantane-based bisphenol (1) assembled into three types of 2D layers with or without channels or a doubly interpenetrated 3D network bearing clathrate hydratesviahydrogen bonds. The different stoichiometries of 1 and water facilitated the formation of the diverse molecular packing structures. Infinite chains and finite triangle clusters of water were formed within the channels and cavities.

Molecules of macrocyclic aromatic hydrocarbon 1 assembled to form various three-dimensional (3D) structures via weak intermolecular interactions, including aromatic–aromatic interactions (1a–d). In the crystal obtained from a chloroform and acetonitrile mixture (1a), the molecules arranged in a columnar stack with a progressive helical twist between adjacent molecules due to intermolecular aromatic–aromatic interactions. The chirality of the helices was spontaneously resolved within individual single crystals. In the crystal obtained from a chloroform and nonane mixture (1b), the molecules formed a columnar stack through tilted T-shaped aromatic–aromatic interactions. Furthermore, in the crystal obtained by vapour diffusion of n-hexane or ethyl acetate into a chloroform solution, inclusion compounds (1c and 1d) were formed via van der Waals interactions between the guest molecule and the benzene ring of the biphenyl unit. The n-hexane penetrated 1 to construct [3]pseudorotaxane and an ethyl acetate molecule was trapped by 1.

The nickel-catalyzed [3 + 2 + 2] cycloaddition of ethyl cyclopropylideneacetate and conjugated enynes proceeded smoothly and divinylcycloheptadienes were isolated in high yields. The three-component cocyclization of ethyl cyclopropylideneacetate, conjugated enynes, and (trimethylsilyl)acetylene also proceeded in a highly selective manner to afford vinylcycloheptadienes, which were reacted with various dienophiles. This study provided a new, short-step synthesis of polycyclic compounds with cycloheptane skeleton.

Novel complexes of a cyclic amide with lanthanide metal cations form 2-D coordination networks; different metal cations give different chiral properties in the crystal structure.