Hidetoshi Kawai

Entropy- and Hydrolytic-Driven Positional Switching of Macrocycle between Imine- and Hydrogen-Bonding Stations in Rotaxane-Based Molecular Shuttles

The construction and switching properties of a novel class of molecular shuttles 1 with imine-bonding stations for macrocyclic diamine parts are reported. Studies on dithioacetalized [2]rotaxane 4 with two hydrogen-bonding stations and a masked imine-bonding station showed that protonation of a macrocycle increases the shuttling barrier due to hydrogen-bond formation between NH 3 (+) groups and the TEG-stations. Hydrolysis of the imine-bonds of the imine-bridged molecular shuttles 1b, c with TEG-stations could exclusively give the [2]rotaxane 2b, c.2H (2+), with the macrocycle hydrogen-bonded with the TEG-station. In contrast, 1a without TEG-stations gave an equilibrated mixture of 1a, monoimine 3a.H (+), and 2a.2H (2+) under similar acidic hydrolytic conditions. The equilibrium between 1b, c and 2b, c.2H (2+) to control the position of the macrocycle could be successfully switched to either side by applying acidic hydrolytic or dehydrating conditions. Furthermore, the equilibrium was largely biased to [2]rotaxane 2b, c.2H (2+) under acidic hydrolytic conditions and could be reversed in favor of bis-imine 1b, c just by heating. This is a successful example of a molecular shuttle exhibiting entropy-driven translational isomerism with remarkable positional discrimination. An examination of thermodynamic parameters showed that imine-bond hydrolyses and the formation of hydrogen bonds between the macrocycle and the station are thermodynamically matched processes, because both processes are enthalpically favored and accompanied by a loss of entropy. The combination of imine-bonding and hydrogen-bonding station in a rotaxane system is the key to realizing the clear entropy-driven positional switching of the macrocycle observed.

A novel redox switch for fluorescence: drastic UV–vis and fluorescence spectral changes upon electrolysis of a hexaphenylethane derivative of 10,10′-dimethylbiacridan

The newly prepared title donor 1 has a very long CC bond [1.635(2) A], which was readily cleaved upon oxidation to give dication 2 2+ containing two 10-methylacridinium chromophores. Colorless donor 1 ( E ox +0.18 V) is non-fluorescent whereas orange dication 2 2+ ( E red −0.27 V) emits strong green fluorescence, so that, this pair can be considered as a novel redox switch for fluorescence with high electrochemical bistability.

Dynamic Molecular Propeller: Supramolecular Chirality Sensing by Enhanced Chiroptical Response through the Transmission of Point Chirality to Mobile Helicity

The secondary terephthalamide host 1a-H attached to four aryl blades was prepared from tetrabromide 2a by Suzuki-Miyaura coupling and undergoes a conformational change from a nonpropeller anti-form to a propeller-shaped syn-form upon complexation with ditopic guests such as p-xylylenediammonium derivatives (R,R)/(S,S)-3 (chirality generation). Through transmission of the point chiralities attached on the nitrogens in the chiral guests to the mobile helicity in 1a-H, the propeller-shaped host in the complex is biased to prefer a particular handedness (chirality biasing). While chiral guests with simple point chiralities such as (R,R)/(S,S)-3 exhibit only very weak CD activity, complexation with the dynamic propeller host 1a-H results in much stronger chiroptical signals (chiroptical enhancement). The chirality generation-chirality biasing protocol was successfully applied to a neurotransmitter, (-)-phenylephrine 4, acting as a chiral ditopic guest. When the chiral auxiliaries are attached to the host as in (R,R)-1b-H, complexation with (S,S)-3 causes CD enhancement but not with (R,R)-3, due to chiral recognition.

Facile Two-Step Synthesis of 1,10-Phenanthroline-Derived Polyaza[7]helicenes with High Fluorescence and CPL Efficiency

A facile two-step synthesis of aza[7]helicenes possessing a 6-5-6-6-6-5-6 skeleton from commercially available 2,9-dichloro-1,10-phenanthroline via double amination with aniline derivatives followed by hypervalent iodine reagent-mediated intramolecular double-NH/CH couplings was developed. Single-crystal X-ray analyses of the helicenes revealed unique structures, including both a significantly twisted center and planar terminals of the skeleton. The azahelicenes show high fluorescent quantum yields (Φs) under both neutral (Φ: 0.25-0.55) and acidic conditions (Φ: up to 0.80). An enantiomerically pure aza[7]helicene showed high circularly polarized luminescence (CPL) activity under both neutral and acidic conditions (glum : up to 0.009).

Butane-1,4-diyl dications stabilized by steric factors: electrochiroptical response systems based on reversible interconversion between dihydro[5]helicene-type electron acceptors and electron-donating 1,1′-binaphthyls

Incorporation in the dihydro[5]helicene framework prevents deprotonation of the title dications by steric factors, thus allowing their isolation as deeply colored stable salts. Based on the reversible interconversion with the electron-donating binaphthylic diolefins, they constitute a new class of electrochromic systems, in which C-C bond making/breaking is accompanied by two-electron transfer. Optically pure (R)-binaphthylic donors are interconvertible with the 1,4-dications with the R,R-configuration. The very large molar ellipticity makes it possible for them to be used as electrochiroptical response systems, by which the electrochemical input is transduced into two spectral outputs, i.e. UV-Vis and circular dichroism. Structurally related push-pull-type bis(quinonemethide)s also exhibit a similar multi-output electrochemical response.

7,7,8,8-Tetraaryl-o-quinodimethane Stabilized by Dibenzo Annulation: A Helical π-Electron System That Exhibits Electrochromic and Unique Chiroptical Properties

When two benzene rings are fused to a tetraaryl-o-quinodimethane skeleton, sterically hindered helical molecules 1 acquire a high thermodynamic stability. Because the tetraarylbutadiene subunit contains electron-donating alkoxy groups, 1 undergo reversible two-electron oxidation to 2(2+), which can be isolated as deeply colored stable salts. Intramolecular transfer of the point chirality (e.g., sec-butyl) on the aryl groups to helicity induces a diastereomeric preference in dications 2 b(2+) and 2 c(2+), which represents an efficient method for enhancing circular-dichroism signals. Thus, those redox pairs can serve as new electrochiroptical response systems. X-ray analysis of dication 2(2+) revealed π-π stacking interaction of the diarylmethylium moieties, which is also present in solution. The stacking geometry is the key contributor to the chirosolvatochromic response.

A Kinetically Stabilized [1.1]Paracyclophane: Isolation and X-Ray Structural Analysis

Benzene rings severely bent and closely stacked face-to-face are revealed in the crystal structure of the [1.1]paracyclophane derivative 1, which could be isolated thanks to the kinetic stabilization provided by the steric shielding of the bridgehead sites by the substituents.

Total Synthesis of Pectenotoxin‐2

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

Formation of keto-carbeniums from 1,2,2-triarylacenaphthen-1-ols by breaking a long CC bond: unusual alcohol protonolysis accompanied by formal hydride abstraction

Abstract Oxidation of 1,2,2-tris(4-dimethylaminophenyl)- and 2,2-bis(4-dimethylaminophenyl)-1-phenylacenaphthen-1-ols 1a , b with I 2 induced the C 1 C 2 bond fission to give 8-aroylnaphthalen-1-yl-bis(4-dimethylaminophenyl)carbenium derivatives 2a , b + , the intramolecular Lewis acid–base pairs. Treatment of 1 with HBF 4 did not induce the expected COH bond heterolysis but caused fission of COH and C 1 C 2 bonds to give exactly the same carbenium 2 + .

Encapsulation-induced remarkable stability of a hydrogen-bonded heterocapsule.

Remarkably enhanced stability of the self-assembled hydrogen-bonded heterocapsule 1⋅2 by the encapsulation of 1,4-bis(1-propynyl)benzene 3 a was found with Ka =1.14×10(9)  M(-1) in CDCl3 and Ka2 =1.59×10(8)  M(-2) in CD3 OD/CDCl3 (10 % v/v) at 298 K. The formation of 3 a@(1⋅2) was enthalpically driven (ΔH°<0 and ΔS°<0) and there was a unique inflection point in the correlation between ΔH° versus ΔS° as a function of polar solvent content. The ab initio calculations revealed that favorable guest-capsule dispersion and electrostatic interactions between the acetylenic parts (triple bonds) of 3 a and the aromatic inner space of 1⋅2, as well as less structural deformation of 1⋅2 upon encapsulation of 3 a, play important roles in the remarkable stability of 3 a@(1⋅2).