Supramolecular Photochirogenesis Research Articles

Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate.

Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of β-CD derivatives; (ii) methods for investigating the host-guest inclusion behavior between AC and β-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of β-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of β-CD derivatives require 3-5 d of work. The photoirradiation of AC with β-CD derivatives can be done within 1 h. The product analysis requires 5 h.

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylic Acid Mediated by Bridged β-Cyclodextrins: Critical Effects of the Host Structure, pH and Co-Solvents.

Several sulfoxide- and sulfone-bridged β-cyclodextrin (CD) dimers were synthesized for mediating the enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these chiral hosts with AC was investigated by UV-vis, circular dichroism, fluorescence, and NMR spectroscopies and certified the formation of 1 : 1 and 1 : 2 host-guest complexes. The product distribution and enantioselectivity of the photoreaction turned out to be a critical function of the chemical structure of bridged CDs. Comparing to the sulfur-bridged 2AX -3GX β-CD dimer 7, the conversion of the photolyzes with sulfoxide-bridged was significantly improved, and the ee of cyclodimer 2 was remarkably increased from -82.8% with 7 to -96.7% with the sulfoxide-bridged 2AX -3GX β-CD dimer 8. The relative yields and ee values of the slipped cyclodimers 5 and 6 were greatly enhanced in the presence of 6 M CsCl. The reaction selectivity is susceptible to the pH variation of the aqueous buffer solution, demonstrating that the supramolecular photochirogenesis is controlled by multidimensional factors, including the chemical structure of the chiral host, solvent, and pH conditions.

Supramolecular Photochirogenesis Driven by Higher-Order Complexation: Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate to Slipped Cyclodimers via a 2:2 Complex with β-Cyclodextrin.

Chiral slipped 5,8:9',10'-cyclodimers were preferentially produced over classical 9,10:9',10'-cyclodimers upon supramolecular photocyclodimerization of 2-anthracenecarboxylate (AC) mediated by β-cyclodextrin (β-CD). This photochirogenic route to the slipped cyclodimers, exclusively head-to-tail (HT) and highly enantioselective, has long been overlooked in foregoing studies but is dominant in reality and is absolutely supramolecularly activated by 2:2 complexation of AC with β-CD. The intricate structural and photophysical aspects of this higher-order complexation-triggered process have been comprehensively elucidated, while the absolute configurations of the slipped cyclodimers have been unambiguously assigned by comparing the experimental and theoretical circular dichroism spectra. In the 2:2 complex, two ACs packed in a dual β-CD capsule are not fully overlapped with each other but are only partially stacked in a slipped anti- or syn-HT manner. Hence, they do not spontaneously cyclodimerize upon photoexcitation but instead emit long-lived excimer fluorescence at wavelengths slightly longer than the monomer fluorescence, indicating that the slipped excimer is neither extremely reactive nor completely relaxed in conformation and energy. Because of the slipped conformation of the AC pair in the soft capsule, the subsequent photocyclodimerization becomes manipulable by various internal or external factors, such as temperature, pressure, added salt, and host modification, enabling us to exclusively obtain the slipped cyclodimers with high regio- and enantioselectivities. In this supramolecularly driven photochirogenesis, the dual β-CD capsule functions as a chiral organophotocatalyst to trigger and accelerate the nonclassical photochirogenic route to slipped cyclodimers by preorganizing the conformation of the encapsulated AC pair, formally mimicking a catalytic antibody.

Enantiodifferentiation in the Photoisomerization of (Z,Z)-1,3-Cyclooctadiene in the Cavity of γ-Cyclodextrin-Curcubit[6]uril-Wheeled [4]Rotaxanes with an Encapsulated Photosensitizer.

A biphenyl photosensitizer axle was implanted into the cavities of native and capped γ-cyclodextrins through rotaxanation using a cucubit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition, resulting in the construction of highly defined chiral binding/sensitizing sites. The orientation and interaction of the axle and capping moieties at the ground and excited states were interrogated by NMR, UV-vis, circular dichroism, and fluorescence spectroscopic studies. In situ photoisomerization of (Z,Z)-1,3-cyclooctadiene sensitized in the cavity of these [4]rotaxanes afforded (Z,E)-1,3-cyclooctadiene in up to 15.3% ee, which represents the highest level of enantiodifferentiation obtained to date for this supramolecular photochirogenesis.

Enantiodifferentiating [4 + 4] photocyclodimerization of 2-anthracenecarboxylate mediated by a self-assembled iron tetrahedral coordination cage

Abstract Photochirogenesis through supramolecular assembly provides an intriguing approach to the highly challenging research field of chiral photochemistry. In the present paper, an enantiopure coordination self-assembly cage (cage T) has been employed for mediating the enantiodifferentiating [4 + 4] photocyclodimerization of 2-anthracenecarboxylate (AC) in aqueous medium. The complexing behavior of AC with the cage T has been investigated by UV–vis, circular dichroism and NMR spectral studies. It was found that in aqueous solution, cage T could form both 1:1 and 1:2 host–guest complexes with AC. Photocyclodimerization of AC mediated by cage T were studied at different temperatures and different host/guest ratios. The anti-HT photodimer dominate the photocyclodimerization of AC with cage T. In the presence of an enantiopure cage T, the chiral syn-HT and anti-HH photodimers were produced in moderate enantioselectivity. The enantiodifferentiating mechanism of this supramolecular photochirogenesis system and the effects of external factors are discussed.

Catalytic Supramolecular Photochirogenesis

AbstractSupramolecular photochirogenesis is a new strategy for circumventing the inherent difficulties encountered in conventional photochirogenesis, i.e. the interactions associated with geometrically less-defined, short-lived excited states, by confining a prochiral substrate(s) in a chiral supramolecular environment(s) prior to photoexcitation. This rather simple, but very successful, strategy has been applied to a variety of chiral photoreactions. However, a stoichiometric, or even excess amount of supramolecular host is often needed to ensure full complexation of the substrate, and achieve the optimum stereochemical outcome. This apparent drawback has recently been removed by introducing a sensitizing moiety to the supramolecular host, or by bathochromically shifting the absorption band of substrate through Lewis acid, or charge-transfer complexation. Recent progress in catalytic supramolecular photochirogenesis will be reviewed.

Supramolecular photochirogenesis

Supramolecular photochirogenesis is a rapidly growing interdisciplinary area of science at the boundary of photochemistry, asymmetric synthesis and supramolecular chemistry. The major advantage of supramolecular photochirogenesis over the conventional molecular one is entropic in origin, being achieved by preorganizing substrate(s) in the ground state and manipulating subsequent photochemical transformation by weak but non-transient interactions in chiral supramolecular media. The chirality transfer often becomes more efficient through the cooperative non-covalent interactions and the confinement by host in both ground and excited states. Thus, all of the ground- and excited-state events, including complexation stoichiometry and affinity, chiroptical properties, photophysical behaviour and photochemical reactivity, jointly play pivotal roles in supramolecular photochirogenesis. This may appear to cause complication but in reality expands the range of manipulable factors and available experimental/theoretical tools for elucidating the mechanism and controlling photochirogenic processes both thermodynamically and kinetically, from which some new concepts/methodologies unique to supramolecular photochemistry, such as non-sensitizing catalytic photochirogenesis and wavelength-controlled photochirogenesis, have already been developed. In this review, we will discuss the recent progress and future perspective of supramolecular photochirogenesis.

Supramolecular Photochirogenesis with Novel Cyclic Tetrasaccharide: Enantiodifferentiating Photoisomerization of (Z)‐Cyclooctene with Cyclic Nigerosylnigerose‐Based Sensitizers

Isophthalic and terephthalic acid monoesters of cyclic nigerosyl-(1→6)-nigerose (CNN), a cyclic tetrasaccharide composed of four d-glucopyranosyl residues connected by alternating α-1,3- and α-1,6-linkages, were synthesized as novel chiral supramolecular sensitizers for enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to planar chiral (E)-isomer (1E). Despite the saucer-shaped shallow cavity of CNN that does not immediately guarantee strong ground-state interactions with 1Z, the sensitizer-appended CNNs afforded optically active 1E in such enantiomeric excesses that are much improved than those obtained with an α-cyclodextrin analog and comparable with those obtained with a β-cyclodextrin analog. Interestingly, the enantiomeric excess values obtained were a critical function of temperature and solvent to show an inversion of the product chirality by changing the environmental variants. Nevertheless, all of the differential activation parameters calculated from the temperature-dependent enantiomeric excesses gave an excellent compensatory enthalpy-entropy relationship, indicating an operation of a single enantiodifferentiating mechanism in the present chiral photosensitization with modified CNNs.

New Paradigm of Biomolecular Soft-interfaces as Chiral Reaction Fields for Supramolecular Asymmetric Photochirogenesis

Asymmetric photochemistry provides us with new versatile routes to novel/strained chiral compounds. Recently, much effort has been devoted to the supramolecular photochirogenesis, exploiting the chiral environment of natural and synthetic hosts, such as cyclodextrin, modified zeolite, ds-DNA and protein. Photochirogenesis with biomolecule is particularly attractive and advantageous in view of the inherently chiral, finely-defined 3D structures. Serum albumins are the most abundant and well characterized water-soluble plasma proteins, which transport hydrophobic compounds. However, little is known about the supramolecular photochirogenesis with the protein used as chiral environment for reaction. We employed Bovine and Human Serum Albumin (BSA and HSA) as a chiral supramolecular host and 2-anthracenecarboxylate (AC) as a substrate. The photocyclodimerization of AC was performed in aqueous buffer solutions in the presence of BSA and HSA to give the [4+4] cyclodimers with high enantioselectivities of up to 90% ee.

Strictly diastereocontrolled photocyclodimerization of 2-anthracenecarboxylates tethered to cyclic tetrasaccharides

Photocyclodimerization of 2-anthracenecarboxylate tethered to a cyclic nigerosylnigerose scaffold gave a single chiral cyclodimer (out of two achiral and two chiral stereoisomers) in 99% optical and 96% chemical yields, achieving the ultimate stereocontrol of the supramolecular photochirogenesis in aqueous solution at 25 °C.

Role of entropy in supramolecular photochirogenesis: enantiodifferentiating photoisomerization of cyclooctenes in chiral sensitizer-immobilized MCM-41 cavities

To examine the effects of confinement, or low-entropy environments, we employed the mesoporous silicate MCM-41 modified with optically active benzenetetracarboxylates as chiral reaction media to effect the enantiodifferentiating photoisomerization of (Z)-cyclooctene and (Z,Z)-1,5-cyclooctadiene. The ee of the (E)-isomer produced and its temperature dependence behavior in MCM-41 were completely different from those observed in homogeneous solutions. Immobilizing the sensitizer in MCM-41 reduced the contribution of the entropy factor.

Dual Supramolecular Photochirogenesis: Ultimate Stereocontrol of Photocyclodimerization by a Chiral Scaffold and Confining Host

In contrast to the brilliant success in thermal asymmetric synthesis, precise stereocontrol remains a great challenge in chiral photochemistry because of the lack of effective tools and methodologies for controlling the short-lived, weakly interacting, and highly reactive electronically excited species. In this work, we achieved this goal through the "dual-chiral, dual-supramolecular" photochirogenesis approach, which enabled us to realized dramatic acceleration and perfect stereocontrol in one of the most representative photoreactions. Thus, the [4 + 4] photocyclodimerization of 2-anthracenecarboxylate tethered to an α-cyclodextrin scaffold was accelerated by a γ-cyclodextrin or cucurbit[8]uril host and gave a single enantiomeric cyclodimer (out of four possible chiral and achiral stereoisomers) in up to 98% chemical and 99% optical yield.

Enantiodifferentiating Photoisomerization of (Z,Z)-1,3-Cyclooctadiene Included and Sensitized by Naphthoyl-Curdlan

6-O-(2-naphthoyl)curdlan was newly synthesized as a sensitizing polysaccharide host to examine the chiroptical properties, supramolecular complexation, and photochirogenic behavior with (Z,Z)-1,3-cyclooctadiene (1ZZ). The enantiodifferentiating photoisomerization of 1ZZ included and sensitized by this polysaccharide host gave a highly strained chiral (E,Z)-isomer in up to 8.7% enantiomeric excess (ee) in solution and 11.7% ee in the solid state, which are the highest values ever reported for a supramolecular photochirogenesis of 1EZ.

Critical stereocontrol by inter-amino distance of supramolecular photocyclodimerization of 2-anthracenecarboxylate mediated by 6-(ω-aminoalkylamino)-γ-cyclodextrins

A series of 6-(ω-aminoalkylamino)-6-deoxy-γ-cyclodextrins (CDs) 5–8 with varying inter-amino distances were synthesized to control the stereoselectivity of [4+4] photocyclodimerization of 2-anthracenecarboxylate (AC). Complexation behavior of these CD hosts with AC was studied in aqueous solutions by UV-vis and circular dichroism spectral titration. Supramolecular photocyclodimerization of AC mediated by the CDs was performed in water as well as in water–methanol mixture to reveal that aminopropylamino-CD 6 leads to the formation of head-to-head photodimers 3 and 4 in highest yields, while aminobutylamino-CD 7 affords chiral syn-head-to-tail and anti-head-to-head photodimers 2 and 3 in highest enantioselectivities. These results indicate that the inter-amino distance critically control the product's stereo- and enantioselectivities through the electrostatic interactions of two anionic AC guests with the dicationic sidechain attached to the γ-CD rim and can be used as a convenient, yet effective, tool for manipulating the stereochemical outcomes of supramolecular photochirogenesis.

Supramolecular Photochirogenesis with Carbenes Entrapped in Cyclodextrins

AbstractTwo achiral diazirines 1a and 1b have been encapsulated in the inherently chiral cavity of α‐cyclodextrin (6‐Cy), β‐cyclodextrin (7‐Cy) and permethylated β‐cyclodextrin (TRIMEB) and photolyzed. Because of supramolecular photochirogenesis the generated carbenes afford intramolecular C–H insertion products not as a racemate but one enantiomer is slightly favored. With 1a@(6‐Cy)2 the ee of product 7a is doubled. To the best of our knowledge for the first time for carbene reactions, products are imprinted, though modestly, with handedness derived from Cys. The reaction of 1b is highly dependent on the molecular reactor used for inclusion. Whereas 7‐Cy is very efficient for favoring dimerization through azine formation, the use of TRIMEB permits exclusive formation of intramolecular insertion product 7b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Catalytic Enantiodifferentiating Photocyclodimerization of 2‐Anthracenecarboxylic Acid Mediated by a Non‐Sensitizing Chiral Metallosupramolecular Host

Cap in hand: Combined use of diamino-γ-cyclodextrin (CD) and Cu(ClO4)2 resulted in the first catalytic supramolecular photochirogenesis in the photocyclodimerization of 2-anthracenecarboxylic acid. The anti-head-to-head cyclodimer formed in 64–70 % enantiomeric excess and about 50 % yield; these values are the highest ever reported for CD-mediated photochirogenesis. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Supramolecular enantiodifferentiating photoisomerization of (Z)‐cyclooctene in lyotropic and thermotropic liquid crystals

In order to understand the roles of moderately organized media and the factors controlling the chirality transfer in supramolecular photochirogenesis, enantiodifferentiating photoisomerization of (Z)-cyclooctene to the chiral (E)-isomer (1E) has been performed for the first time in liquid crystal (LC) systems such as lyotropic LCs of poly(gamma-benzyl-L-glutamate) (PBLG), difluorobenzene derivatives mixture, and thermotropic cholesteryl oleyl carbonate LCs. Basically, the as-employed LCs provided small enantiomer excess (<5%). It is interesting that lyotropic PBLG LCs give contrasting results in cholesteric and nematic mesophases, revealing the importance of the relevant mesophase structure of LC. Selective excitation in achiral difluorobenzene LC doped with a chiral sensitizer facilitates us to conclude that the LC's chiral spatial arrangement is not sufficient or suitable to induce appreciable enantiomeric excess (ee) in the product, but the existence of molecular chirality (of a chiral sensitizer) is essential to afford an optically active (nonracemic) product at least in the present photosensitization system. The photosensitizations in thermotropic LCs further reveal that the product's ee can be manipulated by the LC mesophase not directly but through the sensitizer's conformational changes induced by the supramolecular interactions with the surrounding LC structure.

Supramolecular enantiodifferentiating photoisomerization of cyclooctene with modified β-cyclodextrins: critical control by a host structure

Enantiodifferentiating photoisomerization of (Z)-cyclooctene included and sensitized by m-methoxybenzoyl-beta-cyclodextrin gave chiral (E)-isomers in up to 46% enantiomeric excess, which is the highest value ever reported for supramolecular photochirogenesis with analogous hosts, thus demonstrating the crucial role of the sensitizer-spacer moiety in supramolecular photochirogenic systems.

Supramolecular Photochirogenesis with Biomolecules. Mechanistic Studies on the Enantiodifferentiation for the Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Bovine Serum Albumin

Photophysics and photochemistry of 2-anthracenecarboxylate (AC) bound to bovine serum albumin (BSA) were investigated in detail for the first time by electronic absorption, circular dichroism (CD), steady-state and time-resolved fluorescence, fluorescence quenching, and product analysis studies. Through the spectroscopic investigations, it was revealed that the four independent binding pockets of BSA, which are known to accommodate 1, 3, 2, and 3 AC molecules in the order of decreasing affinity, are distinctly different in hydrophobicity, chiral environment, and accessibility. Interestingly, AC bound to site 1 gave highly structured fluorescence with dual lifetimes of 4.8 and 2.1 ns in an intensity ratio of 3:2, which may be assigned to the existence of two positional or orientational isomers within the very hydrophobic site 1. In contrast, the lifetime of AC in site 2 was much longer (13.3 ns), and ACs in sites 3 and 4 have broader fluorescence spectra with lifetimes that were practically indistinguishable from that in bulk water (15.8 ns). Although each of sites 2-4 simultaneously binds multiple AC molecules, no CD exciton coupling or static fluorescence quenching was detected, indicating that ACs bound to each site are not in close proximity to each other. Quenching studies with nitromethane further confirmed the significant difference in accessibility among the binding sites; thus, ACs bound to sites 1 and 2 are highly protected from the attack of the quencher, affording 32 and 10 times smaller rate constants than that for free AC in water. Product studies in the presence and absence of nitromethane more clearly revealed the photochirogenic performance of each binding site. Although the addition of nitromethane did not greatly alter the product distribution, the enantiomeric excesses (ee's) of chiral cycloadducts 2 and 3 were critically manipulated by selectively retarding the photoreaction occurring at the more accessible binding sites. Thus, the highest ee of 38% was obtained for 2 in the presence of 18 mM nitromethane, while the highest ee of 58% was attained for 3 in the absence of nitromethane, both at [AC]/[BSA]=3.6.

Entropy‐Controlled Supramolecular Photochirogenesis: Enantiodifferentiating Z—E Photoisomerization of Cyclooctene Included and Sensitized by Permethylated 6‐O‐Modified β‐Cyclodextrins.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.