The first supramolecular photosensitization of enantiodifferentiating bimolecular reaction: anti-Markovnikov photoaddition of methanol to 1,1-diphenylpropene sensitized by modified beta-cyclodextrin

Enantiodifferentiating polar photoaddition of methanol to 1,1-diphenylpropene included and sensitized by cyanonaphthalene-modified beta-cyclodextrin was examined for the first time to give optically active anti-Markovnikov adduct with accompanying inversion of the chiral sense of the photoproduct by temperature, which is entropic in origin.     

Unusual temperature dependence of enantioselectivity in asymmetric reductions by chiral NADH models

[reaction: see text] Unusual stereoselectivity changes, i.e., enhancement and inversion of enantioselectivity with increasing temperature, were observed in the asymmetric reduction of methyl benzoylformate with chiral 1,4-dihydropyridines possessing amino acid residues as ligating chiral auxiliaries. The differential activation parameters, DeltaDeltaH(S-R) and DeltaDeltaS(S-R), obtained from the Eyring plots demonstrate that the entropy term controls the enantiodifferentiating step, accounting for the observed unique temperature dependencies.     

Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E photoisomerization of cyclooctene included and sensitized by permethylated 6-O-modified beta-cyclodextrins

Permethylated 6-O-modified beta-cyclodextrins 2a-2d were synthesized as novel photosensitizing hosts with a flexible skeleton. Circular dichroism (CD) and 2D NMR spectral examinations of benzoate 2a revealed that the benzoate moiety is deeply included into its own cavity in aqueous solution. Upon addition of (Z)-cyclooctene (1Z) to a 50% aqueous methanol solution of 2a at 25 degrees C, the benzoate moiety of 2a was gradually excluded from the cavity as indicated by the CD spectral changes; the Job's plot revealed the formation of a 1:1 complex of 2a with 1Z. The binding constants for the complexation of 1Z by 2a were determined by CD spectral titration in 50% aqueous methanol at various temperatures. The van't Hoff analysis of the obtained data afforded the thermodynamic parameters (DeltaH degrees = -3.1 kJ mol(-1), DeltaS degrees = 48.5 J mol(-1) K(-1)), demonstrating the entropy-driven complexation by the permethylated cyclodextrin. This is in sharp contrast to the complexation of 1Z by nonmethylated beta-cyclodextrin benzoate that is driven by enthalpy (DeltaH degrees = -31.8 kJ mol(-1) and DeltaS degrees = -51.1 J mol(-1) K(-1)). Upon supramolecular photosensitization with 2a-2d, 1Z isomerized to the (E)-isomer (1E) in moderate enantiomeric excesses (ee's), which however displayed significant temperature dependence with accompanying switching of the product's chirality in an extreme case. Such dynamic behavior of ee is very different from that reported for the photosensitization with nonmethylated cyclodextrin benzoate, where the product's ee is controlled by host occupancy. Eyring treatment of the ee obtained at various temperatures (<0 degrees C) gave the differential activation parameters for the enantiodifferentiation process occurring in the supramolecular exciplex, revealing the crucial role of entropy, as indicated by the DeltaDeltaS(++) value changing dynamically from +4 to -24 J K(-1) mol(-1). The origin of the contrasting behavior of permethylated versus nonmethylated cyclodextrin hosts is inferred to be the conformational flexibility of the former host, which enables the entropy-driven guest complexation in the ground state and the entropy-controlled enantiodifferentiation in the excited state.     

Pressure and temperature-controlled enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylate mediated by secondary face- and skeleton-modified gamma-cyclodextrins

A series of secondary-face-substituted and skeleton-modified gamma-cyclodextrins (gamma-CDs) were prepared as chiral hosts for enantiodifferentiating [4+4] photocyclodimerization reactions of 2-anthracenecarboxylic acid (AC). These gamma-CD derivatives form stable ternary complexes with ACs, with altroside-bearing gamma-CDs undergoing induced-fit conformational changes upon complexation, and the photocyclodimerization of AC was, thus, dramatically accelerated. The enantiomeric excess (ee) of anti-head-to-head cyclodimer 3 was greatly enhanced in general with altroside-bearing gamma-CDs 7-9. Although mono-altro-gamma-CD 9 and 3A-azido-3A-deoxy-altro-gamma-CD 7 gave 2 in ee's smaller than those obtained with native gamma-CD, 3A-amino-3A-deoxy-altro-gamma-CD 8 yielded 2 in much higher ee's, which is likely to be ascribed to the combined effects of the less-symmetric cavity and the electrostatic interactions. The influence of temperature and high pressure on the supramolecular photochirogenic reaction has been investigated in depth. An ee as high as 71% was obtained for cyclodimer 2 in the photocyclodimerization of AC mediated by 8 at 210 MPa and -21.5 degrees C.     

Monte Carlo simulation of crystal-fluid coexistence states in the hard-sphere system under gravity with stepwise control

Monte Carlo (MC) simulations were performed for hard spheres (with diameter sigma and mass m) placed between well-separated upper and lower hard walls. A periodic boundary condition was imposed in the horizontal direction. The system was exposed to the gravitational field with the acceleration due to gravity g. After preparing a melt as the initial state, g was increased stepwise up to mgsigma/k(B)T(identical with g(*))=1.5 or 2.0 with an increment Deltag(*) = 0.1; k(B)T is the temperature multiplied by Boltzmann's constant. We maintained g(*) at each value for 2.0 x 10(5) MC cycles. The transition of the system into a metastable state such as a polycrystalline state due to trapping phenomena was successfully avoided. A monotonic increase and subsequent saturation were observed for the development of the crystalline region formed at the bottom of the system. The development of this region accompanied a shrinkage of the defective (or less ordered) crystalline region that was formed between the bottom region and the fluid phase. As the development of the bottom region almost saturated, the defective region grew upward again.     

Quinolone analogs 11: Synthesis of novel 4‐quinolone‐3‐carbohydrazide derivatives with antimalarial activity

The reaction of the 6‐substituted 1‐methyl‐4‐quinolone‐3‐carboxylates 10a , 10b with hydrazine hydrate gave the 3‐carbohydrazides 7a , 7b , respectively, whose reaction with 2‐, 3‐, and 4‐pyridinecarbaldehydes afforded the 3‐(N²‐pyridylmethylene)carbohydrazides 8a , 8b , 8c and 9a , 9b , 9c . The Curtius rearrangement of compound 7b provided the N,N′‐bis(4‐quinolon‐3‐yl)urea 14 presumably via the 3‐carboazide 11 and then 3‐isocyanate 12 . Compounds 7a , 8a , and 9a were found to possess antimalarial activity from the in vitro screening data. J. Heterocyclic Chem.,(2011).     

Entrainer effects on enantiodifferentiating photocyclization of 5-hydroxy-1,1-diphenylpentene in near-critical and supercritical carbon dioxide

Enantiodifferentiating photocyclization of 5-hydroxy-1,1-diphenyl-1-pentene (1) sensitized by bis(1,2;4,5-di-O-isopropylidene-α-fructopyranosyl) 1,4-naphthalenedicarboxylate (2) was performed in near-critical and supercritical carbon dioxide media containing organic entrainers to obtain a chiral tetrahydrofuran derivative (3) in enantiomeric excess (ee) higher than those obtained in conventional organic solvents. Interestingly, the entrainer-driven ee enhancement did not depend on the entrainer polarity, which is in contrast to the behavior of the ee observed upon selective solvation in nonpolar organic solvents. This indicates that entrainer clustering around the intervening exciplex is essential in order to keep the intimate sensitizer-substrate contact within the exciplex. Therefore, the clustering itself, rather than its property, is more crucial to prevent the dissociative diffusion to gaseous CO(2). The wider allowance in choosing the entrainer enables us to use more "green" solvents for achieving the ee enhancement, while reducing the environmental risk.     

Theoretical and experimental investigations of circular dichroism and absolute configuration determination of chiral anthracene photodimers

Substituted anthracenes photodimerize to stereoisomeric [4 + 4] cyclodimers, some of which are inherently chiral. Recent supramolecular photochirogenic studies enabled the efficient preparation of specific stereoisomers, the absolute configurations of which should reflect the chiral environment of supramolecular host or scaffold employed but have not been determined, hindering detailed mechanistic elucidation and further host/scaffold design. In this study, we performed the combined experimental and state-of-the-art theoretical analyses of the circular dichroism spectra of chiral cyclodimers of 2-anthracenecarboxylic and 2,6-anthracenedicarboxylic acids to reveal the configurational and molecular orbital origin of the Cotton effects observed, and unambiguously determined the absolute configurations of these chiral cyclodimers. The present results allow us to directly correlate the enantiotopic face-selectivity upon photocyclodimerization with the absolute configuration of the cyclodimer derived therefrom and also to precisely elucidate the chiral arrangement of two cyclodimerizing anthracenes.     

Control of conformer population and product selectivity and stereoselectivity in competitive photocyclization/rearrangement of chiral donor-acceptor dyad

The conformer population and the relative excitation efficiency of each conformer, assessed by theoretical and experimental examinations, enabled us to precisely control the chemo- and diastereoselectivities of the competitive photocyclization/rearrangement reaction of a chiral donor-acceptor (D/A) dyad by irradiation wavelength, solvent polarity, and reaction temperature. Manipulating the ground- and excited-state conformer equilibria is essential for critically controlling the intramolecular D/A system, in sharp contrast to the rather divergent excited species involved in relevant intermolecular systems.