Supramolecular photochirogenesis.

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Supramolecular photochirogenesis† Cite this: Chem. Soc. Rev., 2014, 43, 4123

Cheng Yang*a and Yoshihisa Inoue*b 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

Received 25th September 2013

processes both thermodynamically and kinetically, from which some new concepts/methodologies

DOI: 10.1039/c3cs60339c

unique to supramolecular photochemistry, such as non-sensitizing catalytic photochirogenesis and wavelength-controlled photochirogenesis, have already been developed. In this review, we will discuss

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the recent progress and future perspective of supramolecular photochirogenesis.

a

Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China. E-mail: [email protected]; Tel: +86-28-85416298 b Department of Applied Chemistry, Osaka University, Yamada-oka 2-1, Suita. 565-0871, Japan. E-mail: [email protected]; Fax: +81-6-68797923; Tel: +81-6-68797920 † This paper is dedicated to the warm memory of Professor Nicholas John Turro.

Cheng Yang

Cheng Yang received his PhD in supramolecular chemistry from Nagasaki University in 2004, working with Prof. Kahee Fujita and Prof. Deqi Yuan. After postdoctoral work with Prof. Yoshihisa Inoue in the Entropy Control Project of JST, he became an Assistant Professor in the Inoue group at Osaka University in 2007. He has been a PRESTO researcher during 2008–2012. Since September 2012, he has been a Professor of College of Chemistry, Sichuan University, China.

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1. Introduction Photochirogenesis is a rather new term,1,2 which is synonymous with asymmetric or chiral photochemistry but lays more emphasis on the photochemical creation of new stereogenic centres or chiral compounds. Photochirogenesis is attained under the influence of physical and/or chemical sources of chirality, such

Yoshihisa Inoue got his PhD from Osaka University in 1977. He became an assistant professor of the Faculty of Engineering, Himeji Institute of Technology (HIT), in 1977, was promoted to associate professor at the Basic Research Institute, HIT, in 1985 and then returned to Osaka University as a full professor in 1994. On leave from HIT, he spent a year as a research associate in Nick Turro’s group Yoshihisa Inoue at Columbia University in 1978– 1979. He has been a PRESTO researcher in 1992–1994, Director of the ERATO Photochirogenesis Project in 1996–2002 and Director of the ICORP Entropy Control Project in 2002–2008, all supported by the Japan Science and Technology Agency (JST).

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as circularly polarized light (CPL), chiral auxiliaries, templates, photosensitizers, solvents and supramolecular hosts/assemblies.3 Since the first photochirogenic study of Kuhn and Braun on the enantioselective photodecomposition by CPL reported in 1929,4 a variety of chirality sources and photochirogenic strategies have hitherto been proposed and examined experimentally.3,5–7 In 1965, Hammond and Cole reported the first enantiodifferentiating photosensitization to demonstrate that the geometrical photoisomerization of 1,2-diphenylcyclopropane sensitized by (R)-Nacetyl-1-naphthylethylamine affords the chiral trans-isomer in 6.8% enantiomeric excess (ee),8 while Martin et al. reported the first diastereodifferentiating photocyclization of a chiral auxiliary-appended diarylethene to the corresponding helicene in 28% diastereomeric excess (de) in 1975.9 The modest optical yields obtained in these and many subsequent studies were thought to be inherent to the asymmetric induction in the excited state, which would have discouraged the photochirogenic studies. In particular, less effort appears to have been devoted to the research of enantiodifferentiating photosensitization, which is however more chirality source-efficient (requiring only a catalytic amount of the chiral sensitizer) but harder to achieve than a diastereodifferentiating photoreaction. After 60 years of rather slow progress, photochirogenesis has started to attract broader interest at the end of 1980s, when an unprecedentedly high 40% ee was achieved with accompanying inversion of the chiral sense of the photoproduct by temperature upon enantiodifferentiating photoisomerization of cyclooctene sensitized by chiral benzene(poly)carboxylates.10,11 Since then, the photochirogenesis research has made great progress in both quantity and quality particularly in the last decade, due to the new methodologies developed for controlling the photochirogenic processes involved. Nevertheless, the intrinsic difficulty in critically controlling the stereochemistry of an excitedstate reaction has not completely been solved yet. The biggest challenge in photochirogenesis relates to the inherent nature of the electronically excited state, i.e., high reactivity, short lifetime, and weak intra/intermolecular interactions, all of which make the chirality delivery in the excited state less efficient. Thus, the much smaller activation parameters for excited-state, rather than ground-state, reactions leave us little space for energetically differentiating the diastereomeric transition states leading to a pair of enantiomers. Apart from the Tamaki’s pioneering work in the mid1980s,12,13 using cyclodextrins (CDs) as chiral hosts, supramolecular photochirogenesis became a target of active research in the mid-1990s by using CDs14 and chirally modified zeolites15 as chiral hosts, and now covers a variety of chiral photoreactions and supramolecular systems. The key idea of supramolecular photochirogenesis is to exploit the relatively strong, longlasting non-covalent interactions between the host and the guest in the ground state to complement the weak, shortlived excited-state interactions. The supramolecular confinement upon complexation and subsequent photoreaction is expected to synergetically augment the efficiency and selectivity of chirality transfer in the excited state. Crucially, the guest conformation and/or configuration attained in the host cavity

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are directly transferred to the product chirality upon irradiation in most cases, as the excited-state lifetime is much shorter than the residence and conformational relaxation times of a guest in the complex. Also, the confinement often increases the difference in activation free energy to facilitate the discrimination of two diastereomeric transition states, boosting the enantioselectivity. In this review, we mostly focus on recent advances in supramolecular photochirogenesis in solution. Readers may find a complete list and comprehensive explanations of earlier works in previous reviews.6,7 Supramolecular photochirogenesis with cyclodextrins Among the supramolecular hosts for mediating photochirogenic reactions, CD is most widely employed. The naturally occurring cyclic oligosaccharides with a truncated cone shape are watersoluble, biodegradable, chemically modifiable and capable of accommodating organic guests in the hydrophobic cavity. Nowadays, not only native a-, b- and g-CDs (which are composed of 6–8 glucose units, respectively) but also a vast variety of derivatives are commercially available. For these reasons, CDs have been playing a prominent role in the field of supramolecular chemistry. In addition to the above-mentioned features, CDs are inherently chiral, optically transparent over the whole UV-vis region and compatible with most electronically excited species, all of which facilitate their use in chiral photochemistry. Native and sensitizer-modified CDs have been employed for the enantiodifferentiating geometrical photoisomerization of (Z)-cyclooctene 1Z to planar-chiral (E)-isomer 1E (Scheme 1). This is one of the benchmark photoreactions that has been widely investigated with various chiral sensitizers and hosts. Native b-CD forms a 1 : 1 complex with 1Z to give precipitates in aqueous solution. Direct excitation at 185 nm of the solid-state complex affords nearly racemic 1E (0.5–1.5% ee), indicating the poor photochirogenic ability of native b-CD at least for 1Z.16 For better enantiodifferentiation, the supramolecular photoisomerization of 1Z included and sensitized by benzoate-modified CDs 3 (Scheme 2) was examined in aqueous solution.14,17–23 In this supramolecular photosensitizing system, the sensitizer-modified CD host and the guest substrate are in equilibrium with the host–guest complex in aqueous solution, as illustrated in Scheme 3. When the host cavity is vacant (left), the sensitizing moiety appended to CD is embedded in the cavity and not accessible to the substrate located in the bulk

Scheme 1

Enantiodifferentiating photoisomerization of cyclooctene.


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Fig. 1 Cyclodextrin nanosponges prepared by cross-linking CDs with pyromellitic dianhydride. Scheme 2

Benzoate-modified CDs 3 used as supramolecular sensitizers.

solution due to the CD walls, while in the complex (right) the energy transfer to the included substrate becomes highly efficient, thus permitting the photosensitization to occur only when the guest substrate is placed in the chiral environment to facilitate its enantiodifferentiating transformation in the excited state. This strategy works fairly well in the enantiodifferentiating photoisomerization of 1Z with sensitizer-appended CDs 3. Thus, the ee of 1E produced increases from 0.5–1.5% for native b-CD16 to 11% for 6-O-benzoyl-b-CD 3a14 and then to 24% for 6-O-(methyl phthaloyl)-b-CD 3b.24 Interestingly, the use of 6-O-(m-methoxybenzoyl)-b-CD 3g further enhances the ee of 1E up to 46%, while the ortho- and para-isomers (3f and 3h) afford much lower enantioselectivities (4–13% ee).17,21 This reveals the importance of host modification as well as the critical role of the substituent (and its position) introduced to the sensitizer moiety in fine-tuning the chiral environment of the host cavity, and further provides guiding principles to optimize the stereochemical outcomes in supramolecular photochirogenesis (Fig. 1).21 From the point of view of the activation parameters governing the photochirogenic process, the supramolecular photochirogenesis by sensitizing hosts essentially differs from the conventional one by

molecular sensitizers. The product’s ee obtained in the enantiodifferentiating photoisomerization of 1Z by conventional chiral sensitizers is critically affected by the entropy-related factors, such as temperature, solvent and pressure, for which the conformational flexibility of the exciplex intermediate is responsible.25–29 In contrast, the enantioselectivity obtained in the supramolecular photochirogenesis of 1Z with CD-based sensitizers is independent of temperature, indicating insignificant contribution of the entropy term in the enantiodifferentiation process, which is rationalized by the reduced conformational flexibility of the sensitizer moiety and the substrate tightly packed in the rigid host cavity. Indeed, the enantioselectivity becomes highly temperature-dependent when more flexible permethylated 6-O-benzoyl-b-CD 3i is used as a sensitizing host, demonstrating the crucial role of host flexibility.18,20 Controlling enantioselectivity seems more challenging for the photoisomerization of (Z,Z)-1,3-cyclooctadiene 2ZZ to planar chiral (E,Z)-isomer 2EZ (Scheme 1). Despite the formal similarity to the photoisomerization of monoene analogue 1Z to 1E, the highest enantioselectivity ever obtained with conventional chiral sensitizers is only 17% ee.30 The supramolecular photoisomerization of 2ZZ sensitized by naphthalene-appended a-, b- and g-CDs 3k–m (Scheme 2) also affords 2EZ in low ee’s

Scheme 3 Principle of supramolecular photochirogenesis based on the host–guest complexation equilibrium and the subsequent photosensitization occurring only in the chiral cavity; ‘‘Sens’’ for sensitizing moiety.


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o5%, revealing that the simple supramolecular approach is not always effective.31 Recently, the enantiodifferentiating photoisomerizations of 1Z and 2ZZ were investigated by using a series of CD-based supramolecular architectures called cyclodextrin nanosponges (CDNSs).32,33 CDNSs 4–6 (Fig. 1) prepared by reacting 2 or 4 equivalents of pyromellitic dianhydride with b- or g-CD were used as sensitizing hosts. Increasing CDNS concentration in water from 0.2 to 2000 mg mL1 leads to a stepwise phase evolution from solution to suspension, flowing gel and eventually rigid gel for all nanosponges examined but at different transition concentrations. The supramolecular photosensitizations of 1Z and 2ZZ by CDNSs are critically affected by the phase of CDNS. For example, the ee of 2EZ obtained upon photosensitization of 2ZZ by b-CDNS 4 decreases from 4.7% in the sol phase to nearly zero in suspension, but revives to 6.1% in the rigid gel. Upon sensitization with g-CDNS 6, almost racemic 2EZ is produced in the sol and flowing gel phases, but the ee increases up to 13.3% in the rigid gel, the highest value ever reported for the supramolecular photosensitization of 2ZZ. It is interesting that the ee value consistently maximizes at the border of flowing and rigid gel in all the examined cases. The unprecedented phasedependent photochirogenic behaviour may be attributed to the alternation of the chiral recognition site and environment caused by the phase transition of CDNS. The enantiodifferentiating meta-photocycloaddition of alkenoxybenzene, in which five or more stereogenic centres are created in a single step, has been examined in the solid state by using b-CD as a chiral host.34 Gradual addition of 4-phenoxybutene derivatives (7a–d) to a hot aqueous solution of b-CD leads to the formation of a 1 : 1 complex with 7b or a 2 : 1 complex with 7a, 7c and 7d as precipitates, which afford polycyclic compounds 8 and/or 9 in modest ee’s (of up to 17% ee for 8c) (Scheme 4). In this supramolecular photochirogenic meta-cycloaddition, the enantiodifferentiation is realized by preferentially shielding one of the enantiotopic faces of the benzene ring by the CD wall and facilitating the attack of the vinyl sidearm from the opposite side. Enantio- and diastereodifferentiating photoisomerizations of cis-1,2-diphenylcyclopropane derivatives 10a–d (Scheme 5)

Scheme 4

Photocyclization of phenoxyalkenes 7.

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complexed with native b-CD were examined comparatively in solid and solution phases.35 The solid-phase irradiation of b-CD complexes of 10a (with 4-methoxyacetophenone added as a triplet sensitizer (Sens)) and 10b affords trans-isomers 11a and 11b, respectively, in the same 13% ee in both cases. The diastereodifferentiating photoisomerization of chiral 10c and 10d in the b-CD cavity gives trans-isomers 11c and 11d in 28% and 30% de, respectively, in the solid state, but in o2% de in solution, probably due to the different guest conformation in the solid and solution phase. Photocyclization of tropolone ethers 12a–g (Scheme 6, left) mediated by CD in aqueous solution affords 13a–g in low enantioselectivities, while the photolysis of their b-CD complexes in the solid state leads to moderate ee’s of up to 33%. The size matching between the substrate and the chiral host appears to be a key factor determining the enantioselectivity, as indicated by the fact that b-CD which is best size-fitted to 11a affords 13a in 28%, while smaller a- and larger g-CDs give much lower 5% and 0% ee, respectively.36 Photocyclization of pyridone derivatives 14a–f (Scheme 6, right) mediated by CD shows similar behaviours, affording better enantioselectivity in the solid state than in solution. In contrast to nearly racemic products obtained upon irradiation of 14a or 14b with an excess amount of b-CD in aqueous solution, the solid-state complexes prepared by grinding 14 with b-CD give cyclization product 15 in up to 60% ee (for 15b) upon photoirradiation.37 Interestingly, the water content of the solid-state complexes significantly influences the stereochemical outcomes. Thus, the ee of 15b decreases from 60% to 26% with accompanying inversion of the chiral sense of the product by reducing the water content of the precursor complex from 9% to 2% by vacuum drying, and the original absolute configuration and ee are recovered by adding a small amount of water or methanol to the precursor complex, indicating the vital role of hydrogen-bonding interactions in the photochirogenic process.37 Photolysis of chiral aryl ester 16 (Scheme 7) affords decarboxylation product 17 through concerted elimination of carbon dioxide via a spiro-lactonic transition state.38–42 In accordance with this concerted mechanism, the photodecarboxylation of enantiopure 16 gives 17 in 499% ee in the solution phase. However, the photoirradiation of racemic 16 in the presence of b-CD yields (R)-17 in 14.1% ee, suggesting preferential complexation and/or faster photodecomposition of one of the enantiomers of 16 when mediated by b-CD. Photolysis of benzaldehyde 18 gives a complex mixture of photoproducts including radical-coupling products 19a–c (Scheme 8). Rao and Turro revealed that a b-CD complex of 18 (presumably in 2 : 2 stoichiometry) affords (R)-()-benzoin 19a of 15% ee in 56% yield and 4-benzoylbenzophenone 19b in 24% yield upon irradiation in the solid state, while the photolysis of an aqueous suspension of a sonicated mixture of 18 and a- or b-CD gives meso- and d,l-hydrobenzoin 19c in 60–70% yield, along with trace amounts of 19a (3%) and 19b (o1%); no ee values were determined for 19a or d,l-19c.43 Enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylate (AC) is one of the most comprehensively


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Scheme 5 (Sens).

Enantio- and diastereodifferentiating photoisomerization of cis-1,2-diphenylcyclopropane derivatives 10a–d with and without a sensitizer

Scheme 6

Enantiodifferentiating photocyclization of tropolone and pyridone derivatives.

Scheme 7

Photodecarboxylation of chiral aryl ester.

investigated photochirogenic reactions. This is partly because the photoreaction of AC is inherently clean to quantitatively afford stereoisomeric 9,10-bridged cyclodimers 20–23 (Scheme 9), of which syn-head-to-tail (syn-HT) dimer 21 and anti-head-to-head (anti-HH) dimer 22 are chiral. Perfectly controlling the anti/syn-, HT/HH- and enantio-selectivities is a highly challenging task that demands comprehensive mechanistic elucidation and development of new theoretical and experimental tools. Tamaki et al. investigated the supramolecular photocyclodimerization of AC mediated by native g-CD for the first time to reveal significant enhancement of the photocyclodimerization quantum yield from 0.05 to 0.4 upon addition of g-CD.12,13

Scheme 8

However, further photochirogenic studies seem to have been hindered by the lack of tools for separating and quantifying all the stereoisomeric products. After two decades since Tamaki’s work, the complete chiral HPLC separation of stereoisomeric AC dimers was achieved44 and the enantiodifferentiating photocyclodimerization of AC became a major target of supramolecular photochirogenic studies. Recently, the absolute configurations of chiral cyclodimers 21 and 22 were determined by comparing the theoretical versus experimental circular dichroism spectra45 and correlated with the elution order of each enantiomer on chiral HPLC. Knowing the absolute configuration of the preferred enantiomer is essential for elucidating the stereochemical aspects of supramolecular photochirogenesis. More detailed and quantitative studies on the CD-mediated photocyclodimerization of AC have flourished in the last decade. Native g-CD forms a stable 1 : 2 host–guest complex with stepwise association constants of K1 = 161 M1 and K2 = 38 500 M1 in aqueous buffer solution at 25 1C,44 facilitating the subsequent photocyclodimerization. The photocyclodimerization of AC mediated by native g-CD affords HT dimer 21 in 41% ee and HH dimer 22 in o5% ee at 0 1C.44 This result reported in 2003

Photolysis of the benzaldehyde–CD complex.


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Scheme 9

Photocyclodimerization of 2-anthracenecarboxylate (AC) mediated by chiral hosts.

stimulated the endeavors to improve the anti/syn-, HT/HH- and enantio-selectivities of AC photocyclodimerization through modification of g-CD.46–53 The influence of altering the CD skeleton and/or introducing substituents on the photocyclodimerization stereoselectivity has been assessed by using secondary rim-modified g-CDs 24a–e (Fig. 2). Although most of the modified CDs give syn-HT dimer 21 in comparable or lower ee’s than that obtained with native g-CD (45% ee), 3A-amino-3A-deoxy-altro-g-CD 24e considerably enhances the ee of 21, probably as a result of the combined effect of the electrostatic ammonium-carboxylate interaction and the flexible cavity of altro-g-CD.54 In aqueous solution at 21 1C under a pressure of 210 MPa, the photocyclodimerization of AC mediated by 24e gives HH dimer 21 in up to 71% ee. Photocyclodimerization of AC in aqueous solution consistently affords HH dimers 22 and 23 as minor products, due to the steric and electrostatic repulsions, and the ee of 22 rarely exceeds 5%. For better chemical and optical yields of HH dimers, dicationic g-CD derivatives, 24g, 25a–d and 26a–d (Fig. 2), were designed and synthesized as photochirogenesis mediators that preorganize two AC molecules in HH fashion in the g-CD cavity through electrostatic interactions.46,55 Upon photocyclodimerization with

Fig. 2

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Skeleton modified and transannularly disubstituted g-CDs.

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25b and 26c, the HH dimers are obtained in higher chemical yields and the ee of HH-dimer 22 is enhanced to 35% and 15%, respectively. Furthermore, the anti/syn ratio of the HH dimers increased with the increasing inter-amino distance in diamino-gCDs 25a–d.22 The highest ee of 41% was attained by using 24g (with one dicationic sidearm) rather than 25a–d (with two monocationic substituents), suggesting that the flexible side arm is advantageous in diastereomerically preorganizing two AC molecules in a g-CD cavity. Effects of capping modification have also been examined by using aryl-capped g-CDs 27–31 (Fig. 3). g-CDs 28 and 29 with a flexible diphenyl ether cap bridging the A and D or the A and E glucose rings afford chiral HH-dimer 22 in low enantioselectivities, while 27 with a more rigid biphenyl cap bridging the A and D ring gives antipodal 22 in much higher ee of 56%. The apparently trivial difference in the structure of 27 versus 28, lacking one oxygen atom in the capping moiety, causes the dramatic enhancement of ee, indicating the crucial role of rigidity in preorganizing the guests in the cavity.54,56 g-CDs 30 and 31, capped by a p-cresolbisbenzimidazole unit (Fig. 3), show not only pH-dependent UV-vis, circular dichroism and fluorescence spectral changes but also pH-controlled enantiodifferentiating photocyclodimerization behaviour, including the switching of chiral sense of 22 due to the pH-responsive conformational changes of the capping moiety.57 The photocyclodimerization of AC is greatly accelerated by adding g-CD and the cyclodimers produced do not appear to block the cavity but are readily replaced by AC in the bulk solution. Nevertheless, the catalytic photocyclodimerization with a trace amount of g-CD is difficult to achieve, simply because there is an equilibrium between complexed and free AC and the latter in the bulk solution also photocyclodimerizes to give racemic cyclodimers in appreciable yields. Recently, a

Fig. 3

Aryl-capped g-CDs.


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Fig. 4 Modified g-CDs with a diamino sidearm.

smart trick has been invented to avoid this problem. The catalytic photocyclodimerization of AC was achieved by merely adding Cu2+ (in excess against the host) to the sample solution containing diamino-g-CDs 32–34 (Fig. 4) and AC.58 Cu2+ added forms a chelate complex with the diamino sidearm of 32–34 and attracts two AC anions to form HH-oriented 1 : 2 complexes in the g-CD cavity, while excess Cu2+ is coordinated by ACs in the bulk solution. The trick relies on the phenomena that chelated Cu2+ does not quench the excited state of AC, but Cu2+ in the bulk solution strongly quenches the coordinating ACs, permitting photocyclodimerization exclusively in the chiral cavity. By employing this strategy, HH dimer 22 of 70% ee was obtained in 52% yield upon photocyclodimerization of AC catalyzed by 0.1 equivalent of the diamino-g-CD-Cu2+ complex in aqueous methanol solution at 50 1C.58 Dual supramolecular photochirogeneses have been examined by using a-CD as a chiral auxiliary or scaffold and g-CD or cucurbit[8]uril as a confining host. In these systems, one or two AC moiety/ies are introduced to the primary rim of a-CD with an ester linkage to assess the influence of multiple supramolecular interactions on the stereochemical outcomes of diastereodifferentiating photocyclodimerization of AC. The photolyses of a-CD esters of AC (35 and 36) (Fig. 5) in the presence of g-CD or cucurbit[8]uril (CB[8]), followed by saponification, afford cyclodimers 20–23 (see Scheme 9) in varying chemical and optical yields. In the photocyclodimerization of 35 via a 2 : 1 complex with g-CD, chiral HT dimer 21 of 91% ee is obtained in 68% yield in aqueous solution at 20 1C under a pressure of

Fig. 5

6-Mono- and 6A,6B-, 6A,6C- and 6A,6D-dianthroyl-a-CDs.


210 MPa. Interestingly, when CB[8] was used instead of g-CD, HH dimers 22 and 23 are formed almost exclusively in 99% combined yield. Probably, the steric bulk of a-CD attached to AC and the narrow portal and long, rigid cavity of CB[8] allow only the shallow penetration of two AC moieties into the CB cavity, preventing the HT-oriented precursor complex from undergoing photocyclodimerization. In the case of regioisomeric 6A,6X-dianthroyl-a-CDs (36a–c), the stereochemical course of the photocyclodimerization of two AC moieties on the scaffold is strictly controlled by the inter-AC distance on the rim of a-CD. Thus, the photolyses of 6A,6Band 6A,6C-isomers 36a,b exclusively afford the HH dimers, while the HT dimers are highly favored upon irradiation of 6A,6D-dianthroyl-a-CD 36c. Even in the absence of a confining host, the photolyses of 36b and 36c afford 22 in up to 92% ee and 21 in 63% ee. Upon addition of g-CD or CB[8], the photocyclodimerization of 36b becomes nearly quantitative in chemical and optical yields, affording HH-dimer 22 in up to 98% yield and 99% ee under optimized conditions. Irradiation wavelength can be used as a convenient, yet powerful tool for manipulating the stereochemical outcome of a photochirogenic reaction. The concept of the wavelength control in supramolecular photochirogenesis was first proposed and experimentally proven by using the photocyclodimerization of AC mediated by CD.59 As illustrated in Scheme 10, there are three key steps that may affect the stereoselectivity of photocyclodimerization of AC: (1) complexation, (2) excitation and (3) photoreaction. Under a given temperature, pressure and solvent condition, the equilibrium and rate of the first and last steps are determined a priori by the ground-state thermodynamics and excited-state kinetics, respectively. However, the excitation step is totally free from these parameters, but depends solely on the spectral profile of the relevant precursor complex, which is a function of wavelength and in principle varies with the stacking geometry of the stereoisomeric precursor complex. Indeed, the anti/syn preference is switched by irradiation wavelength in the photocyclodimerization of AC with g-CD, affording 20 and 21 in 55% and 33% yield at 300 nm, but in 31% and 61% at 440 nm.59 The enantioselectivity also depends significantly on irradiation wavelength, varying from 24% to 41% ee for 21 and from 9% to 12% ee for 22. Naturally, the magnitude of wavelength effect is a function of the chiral host, reaction temperature and solvent,

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Scheme 12

Scheme 10 Stereodifferentiation mechanism upon complexation and subsequent photocyclodimerization of AC with g-CD.

indicating that this extra tool unique to photochemistry is widely applicable to various photochirogenic systems and even manipulable by environmental variants.59 Recently, supramolecular photocyclodimerization of 2-hydroxyanthracene (HA) to four stereoisomeric cyclodimers 37–40 has been examined by using g-CD and other hosts (Scheme 11).60 In sharp contrast to AC, anionic HA mainly forms a 1 : 1 complex with g-CD with an association constant of 4100 M1, probably because the negative charge delocalized to the aromatic ring discourages the inclusion of a second HA anion. This is supported by the fact that neutral HA forms a stable 1 : 2 host–guest complex with g-CD. Photolysis of HA with g-CD in aqueous solution affords syn-HT dimer 38 in 12–14% ee and anti-HH dimer 39 in 5–6% ee. Photocyclodimerization of the solid-state complex prepared by grinding HA with 0.5 equivalent of g-CD gives anti-HH dimer 39 as a major product (48% yield) but in nearly zero ee, but syn-HT dimer 38 in 17% ee.60 Tung, Wu et al. investigated the enantiodifferentiating photocyclodimerization of methyl 3-methoxyl-2-naphthoate 41 mediated by g-CD to reveal that the photocyclodimerization of 41 to cage compound 43 is not a concerted but a stepwise twophoton process via [4+4] cyclodimer 42 (Scheme 12).61,62 Native g-CD forms a 1 : 2 complex with 41 to greatly accelerate the photocyclodimerization of 41 that is almost unreactive in aqueous solution in the absence of g-CD. The enantioselectivity is appreciably higher for the final product 43 (48% ee) than for

Photocyclodimerization of methyl 3-methoxyl-2-naphthoate.

the intermediate 42 (39% ee), suggesting that the second [2+2] photocyclodimerization occurs inside the g-CD cavity and hence is enantiodifferentiating. Secondary rim-modified g-CDs, such as 24b–e, lead to slightly reduced enantioselectivities.63 Competitive polar photoadditions of methanol and water to 1,1-diphenylpropene 44 included and sensitized by 6-(5-cyanonaphthyl-1-carboamido)-6-deoxy-b-CD 47 give antiMarkovnikov adducts 45 and 46 via the nucleophilic attack of methanol/water to radical cationic 44 (Scheme 13).64,65 Methanol-adduct 45 is favored by a factor of 2.5 over wateradduct 46 due to the higher nucleophilicity of methanolic oxygen. Up to 13% ee is achieved for 45 and 18% ee for 46 in 10% aqueous methanol solution at 10 1C. However, the ee and chiral sense of the adducts are critical functions of the environmental variants; thus, the ee of 45 varies from 2.1% to 5.8% by lowering the temperature from 45 1C to 40 1C, while the ee of 46 is improved to 24–26% by lowering the temperature and/or applying high pressure. Supramolecular photochirogenesis with biomolecular hosts Possessing well organized binding site(s) of high affinity and specificity, some biomolecules, such as proteins, antibodies and DNA, can be used as chiral supramolecular hosts for photochirogenesis. Bio-supramolecular hosts accommodate various organic substrates in their inherently chiral 3D cavity/ies, while photochemistry provokes chemical transformations under mild conditions in aqueous solution at ambient temperature without damaging the structure and function of biomolecules by

Scheme 13 Photosensitized anti-Markovnikov addition of methanol and water to 1,1-diphenylpropene.

Scheme 11 Photocyclodimerization of 9-hydroxylanthracene.

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choosing appropriate irradiation wavelengths. It is thus crucial to carefully examine the UV-vis spectra of substrates and biomolecules and avoid the absorption range of biomolecular hosts. Most proteins absorb UV light up to 320 nm due to the tryptophan and tyrosine residues, while common nucleosides have absorption up to 300 nm due to the purine moieties. Protein hosts, such as serum albumin, often possess several binding sites that differ in shape, affinity, selectivity and reactivity. Therefore, preliminary spectroscopic and photophysical studies are often indispensable to understand their binding and photochirogenic behaviours. Serum albumin, the most abundant plasma protein in mammalian blood, has been employed as a biomolecular host in supramolecular photochirogenesis. Zandomeneghi et al. used bovine serum albumin (BSA) as a chiral host for the photochemical kinetic resolution of racemic 1,1 0 -binaphthol 48 in water (Scheme 14). BSA preferentially binds (S)-48 to cause a bathochromic shift of the UV-vis spectrum of bound 48, which enables selective photochemical decomposition and enantiomeric isomerization of the bound enantiomer, leaving (R)-48 in 99.5% ee at 77% conversion.66–68 Recently, this reaction was reinvestigated by using BSA and human serum albumin (HSA) not in water but in phosphate buffer at pH 7 to reveal that both BSA and HSA preferentially bind (S)-48 at affinity ratios (KS/KR) of 8.9 and 160, respectively, and also that the kinetic resolution of rac-48 is much less efficient, affording (R)-48 in 98% ee only at 99% decomposition with BSA and in 46% ee at 65% decomposition with HSA.69 The enantiodifferentiating photoisomerization of 1Z to 1E (see Scheme 1) can be sensitized by nucleosides and nucleotides.70 Pyrimidine and purine nucleosides used as chiral sensitizers afford 1E in up to 5.2% ee in the photostationary state, while the use of calf thymus DNA enhances the ee up to 15.2%. This is probably due to the binding of 1Z to the hydrophobic minor grove of double stranded DNA prior to photosensitization, since the ee of 1E dramatically decreases to nearly zero upon irradiation at higher temperatures or in 50% aqueous methanol, indicating the crucial role of supramolecular interaction in the enantiodifferentiating process. Bio-supramolecular photocyclodimerization of AC (see Scheme 9) mediated by serum albumins of different origin has been investigated in considerable detail.71–74 UV-vis, fluorescence and circular dichroism spectral examinations revealed the existence of four independent binding sites in BSA, which accommodate 1, 3, 2, and 3 AC molecules in the order of binding affinity. In the first unimolecular binding site, two binding modes are available for AC to give two distinct fluorescence lifetimes of 4.8 and 2.1 ns. ACs in the second site show a much longer fluorescence lifetime of 13.2 ns, while those of

Scheme 14

Photochemical kinetic resolution of racemic 1,1 0 -binaphthol.


Review Article

ACs bound to sites 3 and 4 are indistinguishable from that of free AC in the bulk water (15.8 ns), indicating that these sites are highly hydrophilic and probably exposed to bulk water in view of the effective quenching of AC fluorescence by nitromethane added to the solution. In the photocyclodimerization of AC mediated by BSA, the sterically and electrostatically hindered HH dimers become dominant in sharp contrast to the predominant formation of the HT dimers in solution, and anti-HH dimer 22 is produced in 40% yield and 58% ee at AC/BSA = 3.8, while the ee of syn-HT dimer 21 is enhanced to 38% upon addition of 18 mM nitromethane.71 HSA differs from BSA by only 26 (out of ca. 600) amino acid residues but behaves very differently upon complexation and photocyclodimerization of AC. HSA has at least four independent binding sites to accommodate 1, 1, 3 and 5 AC molecules. The unimolecular binding sites 1 and 2, assignable to the Sudlow’s drug sites II and I, respectively, exhibit the highest affinities to AC of up to 107–8 M1 but are totally non-productive for the photocyclodimerization. The AC molecules residing in sites 3 and 4 are photoreactive to afford cyclodimers 20–23 (see Scheme 9) in such ratios that are similar to those obtained for free AC in the bulk solution but very different from those obtained with BSA.75 HSA affords syn-HT dimer 21 and antiHH dimer 22 in 82% and 90% ee, respectively,73 which are much higher than those obtained with BSA. Further photophysical studies revealed that the excited states of the ACs bound to the third site have a long rotational correlation time of 36 ns, proving the restricted mobility of AC in this site and accounting for the high ee observed with HSA.76 Although serum albumins strongly bind substrates and often afford photoproducts in good to high enantioselectivities, usually a comparable amount of albumin is needed to prevent possible photoreaction of free substrates in bulk solution, which is not desirable in view of the chirality source economy. Recently, a batch-operated catalytic photochirogenesis by recycling HSA has been reported. In this strategy, the AC/HSA ratio is consistently kept low at ca. 3 to hold ACs only in the highly enantiodifferentiating site 3 by incremental additions of extra AC upon consumption by photoirradiation.77 By this method, a turnover number of 3.4 is achieved after three incremental additions without serious reduction of the original high ee values. Very recently, Yokoyama et al. have reported the enantiodifferentiating 6p-photocyclization of photochromic diarylethenes (M)- and (P)-49a–c to (S,S)- and (R,R)-50a–c mediated by HSA (Scheme 15).78 The diarylethenes are weakly bound to HSA (in the Sudlow’s drug site I at K = 8200 M1 for 49b) to show induced circular dichroism spectra. Photoirradiation of 49a–c at 313 nm in the presence of 0.2–10 equivalents of HSA gives ring-closed 50a–c in 8–42%, 18–63% and 3–27% ee, respectively, at room temperature and the highest ee of 71% upon irradiation of 49b at 4 1C in the presence of 10 equivalents of HSA. Prefoldin (PFD), a chaperone protein from archaeal Pyrococcus horikoshii OT3, has also been used as a chiral protein host for mediating photocyclodimerization of AC (see Scheme 9).79 PFD is

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Scheme 15 Enantiodifferentiating photocyclization of diarylethenes.

a tryptophan-free, jelly fish-like heterohexamer with a semi-cage structure surrounded by hydrophobic amino acid residues on the inside surfaces of the body and tentacles. All of these features are attractive from the supramolecular photochirogenic point of view, since neither non-productive unimolecular binding nor electrontransfer quenching by tryptophan is expected to occur. Circular dichroism spectral examinations suggest that multiple AC molecules are bound to PFD at relatively distant positions without causing any exciton-coupling interactions. Photocyclodimerization of AC is not decelerated even in the presence of an 8-fold excess amount of PFD (indicating weak binding) but is biased toward the HH dimers to afford chiral dimers 21 and 22 in 10% and 16% ee, respectively.79 Chiral variants of amyloid fibrils, which are prepared by agitating acidified solutions of bovine insulin, have recently been applied to the supramolecular photocyclodimerization of AC (see Scheme 9).80 The (+)- and ()-insulin fibrils thus prepared by the chiral bifurcation not only induce quasi-mirror-imaged circular dichroism spectra upon complexation with AC but also afford antiHH cyclodimer 22 of the opposite absolute configurations in 10% and +17% ee, respectively, upon photoirradiation. Although the ee values obtained are not very high, it is important to note that both enantiomers can be obtained by altering the chiral type of the AC-binding amyloid matrix, which is practically unfeasible for usual biological hosts. Supramolecular photochirogenesis with chiral zeolites and mesoporous silica Zeolites attract significant interest as supramolecular hosts for mediating various photoreactions because of their well-defined supercages existing in the mesoporous structures as well as the UV-vis light-transmitting properties. The size, shape and nature of supercage are tunable by exchanging the counter cations that charge-compensate the anionic [AlO4]5 species. Stereochemical consequence of photoreaction conducted in zeolite supercage often differs remarkably from that obtained in isotropic solution.81 Ramamurthy et al. comparatively investigated the photocyclization of tropolone (S)-2-methylbutyl ether 51a to a diastereomeric pair of 51b (and then to 51c upon prolonged irradiation) in hexane and in NaY zeolite (Scheme 16). In contrast to the non-diastereoselective formation of 51b (de = 0%) in hexane, the photoreaction conducted in NaY zeolite affords 51b in 68% de, which is enhanced up to 92% de by

4132 | Chem. Soc. Rev., 2014, 43, 4123--4143

Scheme 16

Photocyclization of tropolone (S)-2-methylbutyl ether.

using ()-norephedrine-modified NaY.82 The confinement imposed by zeolite supercage is important for achieving high diastereoselectivity, since the same reaction conducted on the silica gel surface gives 51b in negligible de. A similar phenomenon has been reported for the photoinduced oxa-di-p-methane rearrangement of 2,2-dimethyl-(2H)naphthalenone-4-carboxylates 52 (Scheme 17). Thus, the photoirradiation of 52b,c in hexane solution or on the silica gel surface gives 53b,c in low de’s, whilst the confinement in the supercage of NaY zeolite leads to much improved 57% and 47% de, respectively. Also, the photolysis of 2,4-cyclohexadienone derivatives 54b–e in trifluoroethanol solution affords 55 in o5% de. However, the photoreaction of 55b,e in NaY zeolite83–85 gives 55b,e in much higher 59% and 73% de, respectively. Interestingly, the stereochemistry of the dominant photoproduct is highly sensitive to the size of the supercage and is tunable by the cation species in zeolite. Thus, the diastereoselectivity can be switched to the epimeric product by exchanging the cation of NaY zeolite with K, Rb or Cs. Zeolite supercage is not chiral by itself, but can be modified by immobilizing chiral inductors on the inside walls. Indeed, modified zeolites, prepared by adsorbing chiral neutral organic molecules or by replacing the zeolite’s counter cations with chiral organic ammonium ions, have been used for the conventional asymmetric syntheses in the ground state.86–90 The enantioand diastereodifferentiating photoisomerizations of diphenylcyclopropane derivatives in chirally modified zeolites have been comprehensively investigated.35,91–94 Upon direct excitation or triplet sensitization, cis-to-trans photoisomerization of 10a is not efficient in the supercage of MY zeolites (M = alkaline metal), due to the cation–p interactions to form a sandwich complex with cis-diphenylcyclopropane, preventing the isomerization to occur. In the case of 56 (Scheme 18), the amide or ester moiety coordinates to the cation and the cis-to-trans


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Scheme 19

Scheme 17 Oxa-di-p-methane rearrangement of naphthalenone and cyclohexadienone derivatives.

photoisomerization becomes more efficient to increase the trans content in the photostationary state from 5–35% for 10a to 42–90% for 56. By using zeolite with immobilized ephedrine as a chiral inductor, 57b was obtained in 20% ee upon photoisomerization of 56b, while the diastereodifferentiating photoisomerizations of 56 give modest de’s of 2–55% in MY zeolites.95,96 Photoisomerization of chiral cis-2,3-diphenyl-1-benzoylcyclopropane derivatives 58 to diastereomeric trans-isomers 59 (Scheme 19) has been examined in zeolite to afford much higher diastereoselectivities than in isotropic solution. In particular, the meta-, rather than para-, substitution leads to better results in the supercage and the highest de of 71% is attained for 59d.97–99 Irradiation period and temperature only slightly influence the de values due to the confinement in zeolite supercage.

Scheme 18

Photoisomerization of chirally modified benzoylcyclopropanes.

The enantiodifferentiating photocyclizations of tropolone ethers 12 and pyridone derivatives 14 (see Scheme 6) have been examined in zeolite supercages chirally modified by ephedrine, norephedrine and pseudoephedrine.100–107 The photocyclization of tropolone 12c in ephedrine-modified zeolite gives 13c in up to 69% ee.106 On the other hand, the enantiodifferentiating photocyclization of pyridone derivative 14e affords cyclization product 15e in 55% ee in norephedrine-modified KY zeolite supercage. These results suggest that organic chiral inductors immobilized in supercages can efficiently transfer the chiral information to the substrate located closely. Turro et al. studied the photolysis of racemic benzoin methyl ether 60 (Scheme 20) in chirally modified zeolites. Photolysis of 60 in solution gives homo-coupling products 61 and 62 in 23% and 70% yields, respectively. However, the photolysis in zeolite affords para-coupled product 63 in 79% yield. Upon irradiation of rac-60 in diethyl tartrate-modified NaY zeolite, enantiomerically enriched 60 (in 9.2% ee) is recovered, which is ascribable to the enantioselective recombination of the geminate radical pair derived from the Norrish type I (a-cleavage) reaction of 60.108

Photoisomerization of benzoylcyclopropane derivatives.


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Scheme 20

Photoreaction of benzoin methyl ether.

Benzonorbornadiene 64 is photo-inert upon direct excitation, but gives di-p-methane rearrangement product 65 upon triplet sensitization (Scheme 21).109,110 In ephedrine-modified TlY zeolite, where the heavy atom accelerates the intersystem crossing of adsorbed substrates, the photorearrangement of 64 proceeds very smoothly to give 65 in 14% ee.111 Intramolecular [2+2] photocycloaddition of 1-cyano-2-(1,5dimethyl-2-oxa-4-hexenyl)naphthalene 66 (Scheme 22) has been performed in NaY zeolite modified with a variety of chiral amines and alcohols.112 Cycloadduct 67 is formed in 10% ee upon irradiation of a cyclohexane slurry of dry NaY zeolite containing 66 and l-(+)-diethyl tartrate, while NaY zeolites modified with enantiopure 2-amino-3-phenyl-propylamine or 2-amino-3-methyl-butylamine give 67 in up to 15% ee. Singlet oxygen (1O2), generated for example by triplet sensitization of molecular oxygen, cycloadds to electron-rich or constrained olefin to form 1,2-dioxetane, which is thermally unstable in general and decomposes to two carbonyl compounds. 1O2 is the smallest possible cycloaddition partner, and hence the stereochemical control of singlet oxygenation is considered to be a challenging task. Recently, Turro et al. have comparatively

Scheme 21 Di-p-methane rearrangement of benzonorbornadiene.

Scheme 22 Intramolecular [2+2] photocycloaddition of 1-cyano-2(5-methyl-2-oxa-4-hexenyl) naphthalene.

Scheme 23

Chem Soc Rev

studied the diastereodifferentiating singlet oxygenations of (E)- and (Z)-isomers of diastereomeric (30 R/S,40 R/S)-enecarbamates 68a (Scheme 23) in solution and in zeolite.113–118 The single oxygenation of (E)-68 is consistently more diastereoselective than that of (Z)-68. In the absence of 1O2-generating sensitizers, the conversion is low (o3%) and the mass balance is poor (o35%) upon photoirradiation of chiral enecarbamates in zeolite.113 However, upon singlet oxygenation in CDCl3 slurry of methylene blue-immobilized NaY zeolite, (Z)-(4R,3 0 R/S)- and (Z)-(4S,3 0 R/S)68c give (R)- and (S)-methyldeoxybenzoin (MDB) in 27% and 11% ee, respectively, while (E)-(4R,3 0 R/S)- and (E)-(4S,30 R/S)-68c afford (R)- and (S)-MDB in much higher 55% and 40% ee, respectively, which are further enhanced to 94% and 88% ee under optimized conditions.116 Mesoporous silica MCM-41 chirally modified by covalently bonded (1R,2S)-trans-1,2-diaminocyclohexane has been employed as a chiral supramolecular host for mediating di-p-methane photorearrangement of 11-formyl-12-methyldibenzobarrelene 70 to give 71 in 24% ee (Scheme 24).119 g-CD-modified mesoporous silica, prepared by co-condensing triethoxylsilane-modified g-CD and triethoxysilane carrying a triblock ethylene oxide–propylene oxide copolymer (EO20PO70EO20), has been used for the enantiodifferentiating photocyclodimerization of AC (see Scheme 9).120 The CD-modified mesoporous silica efficiently adsorbs AC in aqueous solution and the subsequent photoirradiation affords sterically more hindered HH dimers 22 and 23 in 73% combined yield, which is very much in contrast to the dominant formation of HT dimers 20 and 21 upon irradiation of AC in aqueous solution. The inverted selectivity may be rationalized by the favored penetration of two AC anions into the silica wallcapped CD cavity in HH fashion. Although HH dimer 22 becomes the major product (45% relative yield), its ee is modest (24%), probably reflecting the wide pore size of the g-CD modified mesoporous silica. In most of the above studies using zeolite or mesoporous silica, the immobilized chiral compound plays a ‘‘passive’’ role as a chiral inductor for the photochemical transformation occurring in the

Singlet oxygenation of diastereomeric enecarbamates and subsequent decomposition to two carbonyl compounds.

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Scheme 24 barrelene.

Review Article

Di-F-methane rearrangement of 11-formyl-12-methyldibenzo-

supercage. A more active role is played by the chiral sensitizer/ inductor immobilized in zeolite supercage. Thus, in the photosensitized enantiodifferentiating isomerization of (Z)-cyclooctene 1Z (see Scheme 1), chiral alkyl benzoate immobilized in zeolite supercage functions as a chiral sensitizer/inductor to afford (E)-isomer 1E in 4.5% ee.121 Supramolecular photochirogenesis with chiral templates Unlike supramolecular and biomolecular hosts that possess a well-defined three-dimensional space to confine guest substrate(s), chiral templates usually have no cavity for accommodating guest substrate(s), but realize chirality transfer by directly interacting with target substrates through strong and often directional non-covalent interactions, such as hydrogen-bonding and electrostatic interactions. Chiral templates are more ‘‘molecular’’ (or much simpler in structure) and hence easier to design rationally, providing an effective, yet convenient tool for photochirogenesis. Bach et al. employed enantiomeric and diastereomeric Kemp’s acid derivatives 72 and 73 (Fig. 6) as chiral hydrogenbonding templates for mediating a variety of intra- and intermolecular enantiodifferentiating photoreactions. The lactam moiety in 72 and 73 plays dual roles as hydrogen bond donor and acceptor to form an 8-membered hydrogen-bonding network with various lactam substrates, such as 74, 76 and 78 (Scheme 25). It is a clever design to introduce a planar/bulky fence for preventing self-association into a homodimer, while allowing enantiotopic face-selective complexation with planar prochiral lactams (e.g. 74, 76 and 78). The enantiodifferentiating intramolecular [2+2] photocycloaddition of prochiral 2-quinolone allyl ether 74 was studied by using 72 and 73 as chiral templates to find that the lactam moiety of 74 forms stable dual hydrogenbonds with 72, where one of the enantiotopic faces of 74 is shielded by the tetrahydronaphthalene fence, allowing the attack of the allyl group only from the opposite side. Thus, the

Fig. 6

Kemp’s acid derivatives as chiral hydrogen-bonding templates.


Scheme 25 Intramolecular [2+2] photocycloaddition mediated by chiral hydrogen-bonding templates.

photoirradiation of 74 with 72b at 60 1C yields 75 in 93% ee.122,123 Similar intramolecular [2+2] photocycloaddition reactions of 76 and 78 mediated by 72a at 60 1C afford 77 in 59–75% ee and 79 in 74– 92% ee.124 The enantioselectivity increases with the increasing amount of the template, lowering reaction temperature or decreasing solvent polarity as a result of the enhanced complexation of the substrate. The enantiodifferentiating photocyclization of acrylanilides 80 (Scheme 26) was mediated by chiral template 72a to yield 81 and 82 in a ratio ranging from 48 : 52 to 27 : 73 and in up to 57% and 39% ee, respectively, after optimization of the template/ guest ratio and the temperature.125,126 Chiral templates 72 and 73 were used for mediating the Norrish–Yang cyclization of imidazolidinones 83 to endo- and exo-products 84 and 85 (Scheme 27).123,127 Upon photolysis of 83c, the exo/endo ratio is inverted from 38 : 62 in the absence of the chiral template to 90 : 10 in the presence of 73a. The highest ee of 60% is achieved for 84 in the photocyclization of 83 mediated by chiral template 72.123 Diels–Alder reaction of photogenerated dienol intermediates with some dienophiles was performed (Scheme 28) in the presence of 72. Photolysis of aromatic aldehyde 86 affords exocyclic (Z)- and (E)-dienols through intramolecular g-hydrogen abstraction. Although the (Z)-dienol rapidly tautomerizes to the starting material,

Scheme 26

Enantiodifferentiating photocyclization of acrylanilides.

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Scheme 27

Norrish–Yang cyclization of imidazolidinones.

Scheme 28

Photoinduced Diels–Alder reaction of 86.

the (E)-isomer has a lifetime long enough to react with dienophile. Upon photolysis of 86 with chiral template 72a, exo-adduct 87 of up to 94% ee is obtained as the major product.128 Intermolecular [4+4] photocycloaddition of 2-pyridinone to cyclopentadiene gives racemic 89 and 90 in 2 : 3 ratio (Scheme 29). In the presence of 72a as a chiral template, the photocycloaddition affords 89 and 90 in 3 : 2 ratio and in 87% and 84% ee, respectively.129 Cauble et al. have studied the intramolecular [2+2] photocycloaddition of 74 complexed with chiral hydrogen-bonding templates 91a,b (Scheme 30), incorporating the benzophenone chromophore as a triplet sensitizer. At 70 1C, photosensitization with 91b afforded 75 in 22% ee, while template 91a, lacking the hydrogen-bonding aminopyridine moiety, gave the photoproduct as a racemic mixture.130 Bach et al. have also designed chiral templates 92a,b equipped with a sensitizing fence and applied them to the photoinduced electron transfer (PET) cyclization of pyrrolidineappended quinolone 93 (Scheme 30).131,132 The benzophenone moiety of 92a plays dual roles of shielding one of the enantiotopic faces of 93 and sensitizing the PET-induced cyclization of 93. Photoirradiation of 92a complexed with 93 leads to the PET from the pyrrolidine nitrogen to the benzophenone moiety, which is followed by the migration of a hydrogen from the carbon a to the radical cationic pyrrolidine nitrogen to the radical anionic benzophenone. The pyrrolidyl radical thus formed attacks the ipso-carbon from the open face of quinolone to form the spiro skeleton. By applying this strategy, the catalytic photocyclization

Scheme 29

[4+4] Photocycloaddition of 2-pyridinone to cyclopentadiene.

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Scheme 30

Photocyclization sensitized by chiral templates.

of 93 with 0.1 equivalent of chiral template 92a is achieved to give 94 in 52–64% yield and in up to 70% ee. Intramolecular [2+2] photocycloaddition of o-alkenyl(oxy)-2quinolones 95a–f has been mediated by chiral hydrogenbonding templates 72, 92b and 93.133 The photoirradiation of 4-(3 0 -butenyloxy)quinolone 95a in the presence of 0.1 equivalent of 92a gives tricyclic adducts 96a and 97a in 75 : 25 ratio and in 39% and 17% ee, respectively.134 On the other hand, xanthone-bearing template 92b, possessing a higher triplet energy and a more effective shielding ability, affords 96a and 97a in 94% ee. Other substrates 95b–f also afford the corresponding cycloadducts in 72–87% ee under optimized conditions.


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Scheme 31 Intermolecular [2+2] photocycloaddition of 3-(o 0 -alkenyl)and 3-(o 0 -alkenyloxy)-5,6-dihydro-1H-pyridin-2-ones.

The xanthone-based organocatalyst 92b is superior in general to the benzophenone-based 92a. Critically controlling the kinetic factors is essential for achieving good enantioselectivity and the lifetime of the excited supramolecular complex plays a more important role than the photocyclization kinetics. Intramolecular [2+2] photocycloaddition of o-alkenyl- and o-alkenyloxydihydropyridinones 98 (Scheme 31) has been examined in the presence of chiral d-lactam templates 72 (Fig. 6) and 100 (Fig. 7).135 The enantioselectivity of photocycloaddition of 98b is a function of the template concentration and has been shown to reach a maximum ee of 84% in the presence of 2.6 equivalents of 72. Photoreaction of o-alkenyloxysubstrates 98d,e mediated by g-lactam template 100 affords the corresponding cycloadducts in up to 85% ee, while the photoreaction of o-alkenyl-substrates 98a–c with the same template gives lower ee’s. Using 72 as a chiral template, the formal [3+2] photocycloaddition of 2-hydroxy- and 2-amino-1,4-naphthoquinone 101 (Scheme 32) to acyclic and cyclic olefins was studied in various solvents. While the reaction proceeds efficiently to give 102 in up to 81% yield, the ee of 102 remains low (r11%), for which the unselective exo/endo approaches of the alkene to the excited substrate bound to the template and/or the intervention of not only 1 : 1 but also 2 : 1 substrate–template complexes are likely to be responsible.136 More recently, Bach et al. have reported the first enantioselective intermolecular [2+2] photocycloaddition of isoquinolone with alkenes in the presence of the chiral template 72a. The corresponding cyclobutane products were obtained in 86–98% yield with up to 99% ee.137 The photocyclodimerization of AC was examined by using a 2-methoxybenzamide derivative of 4-aminoprolinol TKS159 (104a) with a folded structure, which is known as a gastroprokinetic agent, and its epimer 104b with an extended structure (Fig. 8).

Fig. 7 Chiral g-lactam templates.


Scheme 32 Intermolecular photocycloaddition of alkene to naphthoquinone and isoquinolone.

Fig. 8 Chiral hydrogen-bonding templates: epimeric 2-methoxybenzamide derivatives of 4-aminoprolinol.

The prolinol moiety of the chiral templates binds AC through dual hydrogen bonds with the carboxylic acid in AC, forming a nine-membered network with the prolinol’s amino and hydroxyl groups.138 Upon stacking complexation with 104a, one of the enantiotopic faces of AC is blocked by the 2-methoxybenzamide moiety of 103, while the opposite face is kept open for the attack by free or complexed AC. Photocyclodimerization of AC mediated by chiral template 104a in CH2Cl2 at 50 1C gives HT dimer 21 in 36% ee and HH dimer 22 in 40% ee. In contrast, epimer 104b forms an unstacked complex with AC, which affords the chiral dimers in o3% ee upon irradiation. A general methodology for comprehensively analyzing supramolecular photochirogenic processes was established in this study. Thus, the photophysical and photochemical studies revealed that the re/si ratio of diastereomeric AC-104a complexes is not the only determinant of the enantioselectivity, but the relative lifetime and reaction rate of these diastereomeric complexes are also the essential factors.139 Circular dichroism spectral studies further revealed that AC forms not only 1 : 1 but also novel 2 : 1 HH-oriented hydrogen-bonded/p-stacked complexes with 104a. The 2 : 1 complexation causes an exciton couplet in the circular dichroism spectrum and leads to a significant acceleration of the HH photocyclodimerization.136 More recently, cross-photocyclodimerization of AC with anthracene (AN) was mediated by chiral template 104a (Scheme 33). Interestingly, the cross-, rather than homo-, cyclodimerization is strongly favored upon exclusive excitation of AC to give 105 in 80–84% yield at an initial AC/AN ratio = 1

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Scheme 33

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Cross-photocyclodimerization of AC with anthracene.

and in 98% yield at AC/AN = 10, while the ee is modest at 21–24%. The absolute configuration of 105 was determined by comparing the experimental versus theoretical circular dichroism spectrum. Crucially, the ground-state thermodynamics and the excited-state kinetics are not synergistic but offsetting in enantiotopic-face selectivity, and the latter overwhelms the former to give the homo- and cross-dimers in modest ee. Supramolecular photochirogenesis in other supramolecular systems Besides the supramolecular hosts and templates that have been systematically studied, a variety of novel supramolecular systems with attractive properties and photochirogenic behaviours have recently emerged. Fujita et al. have reported significant rate and stereoselectivity enhancements of several thermal and photochemical reactions performed in M6L4 cage 106 (Scheme 34).140–143 By introducing chiral ligands a–d to the periphery of cage 106, the inside cavity becomes chiral and the photocycloaddition of 107b to 108 in the cavity of 106b gives 109b in 50% ee.141 This is an interesting and encouraging result, revealing that such an apparently trivial outside modification is enough to create a significant chiral environment for the (photo)reaction performed inside the cavity that is originally achiral. The enantiodifferentiating photoisomerization of 1Z to chiral 1E (see Scheme 1) was examined by using homochiral mesoporous metal–organic materials POST-1, prepared from

Scheme 34 Photocycloaddition in the cavity of M6L4 cage incorporating chiral ligands.

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zinc nitrate and isopropylidene-protected N-pyridyltartaric monoamide as building blocks.22,144 Supramolecular photosensitization of 1Z with POST-1 gives 1E in 5.4% ee. The low enantioselectivity may be ascribed to the much larger diameter (13 Å) of the chiral channel than the size of 1Z, leading to less efficient confinement of the guest substrate. Photochirogenesis in organized assemblies, such as gels and liquid crystals (LCs), has also been examined in recent studies. Ishida, Saigo et al. investigated the enantiodifferentiating photocyclodimerization of AC and 1-anthracenecarboxylic acid 110 (Scheme 35) in LC.145 Smectic phase LC was prepared by mixing equimolar amounts of amphiphilic aminoalcohol 115 and AC. Photolysis of the AC-containing LC in the smectic phase leads to the exclusive formation of HH dimers 22 and 23 (see Scheme 9); in particular, the former is obtained in 72% yield and in up to 78% ee upon irradiation at 30 1C, for which the HH alignment of ACs in the chiral LC is responsible. The cyclodimers formed upon photolysis of 110 in the LC are converted to the corresponding methyl esters 111–114, which are then analyzed by chiral HPLC. Although the HH dimers are obtained in 498% combined yield, the enantioselectivity is poor, affording 113 in o2% ee, probably due to less chirally ordered alignment of 110 in the LC. More recently, it turned out that the enantioselectivity of the photoreaction of 2-anthracenecarboxylic acid (AC) (Scheme 9) with 115 is actually a critical function of the annealing period. Thus, photoirradiation of AC in this LC system immediately after preparation proceeded smoothly to give 22 in up to +86% ee,146 while photoirradiation of the same sample after isothermal annealing afforded the same but antipodal product in 94% ee.147 Tung et al. investigated the photocyclization of tropolone ether 12a (see Scheme 6) in chiral inductor-doped lyotropic LCs of sodium dodecyl sulfate and water.148 Photoirradiation of 12a in (1R,2S)-()- or (1S,2R)-(+)-norephedrine-doped hexagonal LC at 10 1C gives 13a in up to 40% ee, for which the hydrogenbonding interaction of the substrate with the inductor is thought to be responsible. When menthol or undoped LCs are used as reaction media, a racemic product is formed. The competitive photoreduction and photocleavage of cyclohexyl phenyl ketone 116 to 117 and 118 via inter- and intramolecular hydrogen abstraction (Scheme 36) have been examined in the same lyotropic LC.149 The photoreaction gives 117 and 118 in 1 : 3 ratio in proline-doped LC and in 12 : 1 in prolinol-doped LC. Only low ee’s of o5% are obtained for 117 upon photolysis in norephedrine-doped LC. The enantiodifferentiating photoisomerization of 1Z (see Scheme 1) has been examined in several lyotropic LCs.150 However, chiral 1E was produced only in low ee’s, indicating that the chiral spatial arrangement of LC is too long to be


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Scheme 35

Enantiodifferentiating photocyclodimerization of 1-anthracenecarboxylic acid and the structure of amphiphilic aminoalcohol.

Scheme 36

Photochemical reduction and cleavage of cyclohexyl phenyl ketone.

Fig. 9

Chiral gelators used for enantio- or diastereodifferentiating photocyclodimerization of AC.

appreciably sensed by the small guest substrate without any specific non-covalent interaction. Shinkai et al. have studied the photocyclodimerization of AC in gels formed by mixing amphiphilic D-alanine derivative 119 (Fig. 9) and AC in nonpolar solvents.151 HH dimers 22 and 23 are formed exclusively upon photocyclodimerization of AC in the gel matrix, and chiral HH dimer 22 is obtained in 10% ee. On the other hand, organogelator 120 (Fig. 9), in which AC is covalently tethered, gives the syn-HT dimer in up to 41% ee and the anti-HH dimer in up to 56% de upon irradiation in the gel state.152 Very recently, Brimioulle and Bach reported the enantiodifferentiating intramolecular [2+2] photocycloaddition of 5,6dihydro-4-pyridone derivatives with alkenyl side chain, e.g. 120, catalyzed by 0.5 equivalent of chiral Lewis acid 122, where the bathochromic shift of >50 nm caused by the ligation of enone to Lewis acid enabled selective excitation of 120–122 complex

Scheme 37 Catalytic enantiodifferentiating intramolecular [2+2] photocycloaddition mediated by chiral Lewis acid.


and subsequent enantioselective cycloaddition to tricyclic compound, e.g. 121, in 48–84% chemical yield and 80–90% ee (Scheme 37).153

2. Conclusions and discussion In the last decade, a wide variety of strategies and chiral hosts/ assemblies have been proposed and examined for supramolecular photochirogenesis. The major advantage of using supramolecular hosts for photochirogenesis over the conventional chiral photochemistry is the confinement of guest substrate(s) in the chiral nanospace throughout the ground-state complexation and the subsequent excited-state reaction. As amply exemplified above, the supramolecular confinement in the chiral cavity can thermodynamically bias the equilibrium of diastereomeric precursor complexes and kinetically differentiate the rates of chirogenic photoreactions, leading to a significant change (often enhancement) in reactivity and a switching of selectivity from those observed in isotropic media. Due to the originally reduced freedom of the guest confined in the chiral cavity, the role of entropy decreases more or less in supramolecular photochirogenesis and the stereochemical outcome becomes a critical function of the host rigidity. Supramolecular photochirogenesis also provides unique and potentially promising tools for manipulating the essential chirogenic processes, which include the wavelength control and the non-sensitizing catalysis.

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Supramolecular photochirogenesis requires rational design and construction of sophisticated chiral architecture or assembly to efficiently and selectively gain the desired chiral product or phenomenon, which is not always feasible to readily achieve but should be greatly assisted by the new designs, approaches, methodologies, concepts and (sometimes unexpected) implications described in this review. As an inherent nature of the supramolecular photochirogenesis, systematic and comprehensive studies on both the ground-state complexation and the excitedstate reaction are indispensable to understand and control the stereochemical consequences of supramolecular photochirogenic reactions. Nevertheless, the qualitative and in particular quantitative prediction of the absolute configuration of the favored product is not necessarily feasible, except for the photochirogenesis mediated by some chiral hydrogen-bonding templates, but will become easier by using the state-of-the-art theoretical and experimental tools. Another important challenge for the near future is the highly efficient photochirogenesis with a catalytic amount of the non-sensitizing supramolecular host. Due to the structural complexity and binding specificity of the (bio)supramolecular host, developing a universal chiral host or template for various substrates seems impractical, but a photochirogenic version of a catalytic antibody or tailor-made catalyst, though not for universal purpose, is much easier to prepare.

Acknowledgements This work was supported by the Setup Foundation of Sichuan University and National Natural Science Foundation of China, No. 21372165 and 23321061 (CY), Japan Science and Technology Agency (CY and YI) and Japan Society for the Promotion of Science (YI).

References 1 H. Nishino and Y. Inoue, Kokagaku, 1997, 24, 54. 2 Y. Inoue, T. Wada, S. Asaoka, H. Sato and J.-P. Pete, Chem. Commun., 2000, 251. 3 Chiral photochemistry, eds. Y. Inoue and V. Ramamurthy, Marcel Dekker, 2004. 4 W. Kuhn and E. Braun, Naturwissenschaften, 1929, 17, 227. 5 C. Yang, Chin. Chem. Lett., 2013, 24, 437. 6 C. Yang and Y. Inoue, in Supramolecular Photochemistry: Controlling Photochemical Processes, ed. V. Ramamurthy and Y. Inoue, John Wiley & Sons Inc., Hoboken, 2011, p. 115. 7 C. Yang and Y. Inoue, in CRC Handbook of Organic Photochemistry and Photobiology 3rd Ed., ed. A. G. Griesbeck, M. Oelgemoller and F. Ghetti, Taylor & Francis Group, Boca Raton, 2012, vol. 1, p. 125. 8 G. S. Hammond and R. S. Cole, J. Am. Chem. Soc., 1965, 87, 3256. 9 Y. Cochez, J. Jespers, V. Libert, K. Mislow and R. Martin, Bull. Soc. Chim. Belg., 1975, 84, 1033. 10 Y. Inoue, T. Yokoyama, N. Yamasaki and A. Tai, J. Am. Chem. Soc., 1989, 111, 6480.

4140 | Chem. Soc. Rev., 2014, 43, 4123--4143

Chem Soc Rev

11 Y. Inoue, T. Yokoyama, N. Yamasaki and A. Tai, Nature, 1989, 341, 225. 12 T. Tamaki and T. Kokubu, J. Incl. Phenom. Macrocyclic Chem., 1984, 2, 815. 13 T. Tamaki, T. Kokubu and K. Ichimura, Tetrahedron Lett., 1987, 43, 1485. 14 Y. Inoue, S. F. Dong, K. Yamamoto, L.-H. Tong, H. Tsuneishi, T. Hakushi and A. Tai, J. Am. Chem. Soc., 1995, 113, 2793. 15 M. Leibovitch, G. Olovsson, G. Sundarababu, V. Ramamurthy, J. R. Scheffer and J. Trotter, J. Am. Chem. Soc., 1996, 118, 1219. 16 Y. Inoue, S. Kosaka, K. Matsumoto, H. Tsuneishi, T. Hakushi, A. Tai, K. Nakagawa and L. Tong, J. Photochem. Photobiol., A, 1993, 71, 61. 17 Y. Inoue, T. Wada, N. Sugahara, K. Yamamoto, K. Kimura, L.-H. Tong, X.-M. Gao, Z.-J. Hou and Y. Liu, J. Org. Chem., 2000, 65, 8041. 18 G. Fukuhara, T. Mori, T. Wada and Y. Inoue, J. Org. Chem., 2006, 71, 8233. 19 R. Lu, C. Yang, Y. Cao, Z. Wang, T. Wada, W. Jiao, T. Mori and Y. Inoue, Chem. Commun., 2008, 374. 20 G. Fukuhara, T. Mori, T. Wada and Y. Inoue, Chem. Commun., 2005, 4199. 21 R. Lu, C. Yang, Y. Cao, Z. Wang, T. Wada, W. Jiao, T. Mori and Y. Inoue, J. Org. Chem., 2008, 7695. 22 Y. Gao, T. Wada, K. Yang, K. Kim and Y. Inoue, Chirality, 2005, 17, S19. 23 Y. Gao, M. Inoue, T. Wada and Y. Inoue, J. Incl. Phenom.Macrocyclic Chem., 2004, 50, 111. 24 Y. Inoue, T. Wada, N. Sugahara, K. Yamamoto, K. Kimura, L.-H. Tong, X.-M. Gao, Z.-J. Hou and Y. Liu, J. Org. Chem., 2000, 65, 8041. 25 Y. Inoue, N. Yamasaki, T. Yokoyama and A. Tai, J. Org. Chem., 1993, 58, 1011. 26 Y. Inoue, H. Ikeda, M. Kaneda, T. Sumimura, S. R. L. Everitt and T. Wada, J. Am. Chem. Soc., 2000, 122, 406. 27 Y. Inoue, Sentan Kagaku Shirizu, 2003, 1, 77. 28 M. Kaneda, Y. Nishiyama, S. Asaoka, T. Mori, T. Wada and Y. Inoue, Org. Biomol. Chem., 2004, 2, 1295. 29 Y. Inoue, Kagaku to Kogyo, 2006, 59, 152. 30 Y. Inoue, H. Tsuneishi, T. Hakushi and A. Tai, J. Am. Chem. Soc., 1997, 119, 472. 31 C. Yang, T. Mori, T. Wada and Y. Inoue, New J. Chem., 2007, 31, 697. 32 W. Liang, C. Yang, M. Nishijima, G. Fukuhara, T. Mori, A. Mele, F. Castiglione, F. Caldera, F. Trotta and Y. Inoue, Beilstein J. Org. Chem., 2012, 8, 1305. 33 W. Liang, C. Yang, D. Zhou, H. Haneoka, M. Nishijima, G. Fukuhara, T. Mori, F. Castiglione, A. Mele and F. Caldera, Chem. Commun., 2013, 49, 3510. 34 K. Vizvardi, K. Desmet, I. Luyten, P. Sandra, G. Hoornaert and E. Van der Eycken, Org. Lett., 2001, 3, 1173. 35 S. Koodanjeri and V. Ramamurthy, Tetrahedron Lett., 2002, 43, 9229. 36 S. Koodanjeri, A. Joy and V. Ramamurthy, Tetrahedron, 2000, 56, 7003.


View Article Online


Chem Soc Rev

37 J. Shailaja, S. Karthikeyan and V. Ramamurthy, Tetrahedron Lett., 2002, 43, 9335. 38 T. Mori, T. Wada and Y. Inoue, Org. Lett., 2000, 2, 3401. 39 T. Mori, Y. Inoue and R. G. Weiss, Org. Lett., 2003, 5, 4661. 40 T. Mori, R. G. Weiss and Y. Inoue, J. Am. Chem. Soc., 2004, 126, 8961. 41 T. Mori, H. Saito and Y. Inoue, Chem. Commun., 2003, 2302. 42 T. Mori, M. Takamoto, T. Wada and Y. Inoue, Photochem. Photobiol. Sci., 2003, 2, 1187. 43 V. P. Rao and N. J. Turro, Tetrahedron Lett., 1989, 30, 4641. 44 A. Nakamura and Y. Inoue, J. Am. Chem. Soc., 2003, 125, 966. 45 A. Wakai, H. Fukasawa, C. Yang, T. Mori and Y. Inoue, J. Am. Chem. Soc., 2012, 134, 4990. 46 H. Ikeda, T. Nihei and A. Ueno, J. Org. Chem., 2005, 70, 1237. 47 C. Yang, G. Fukuhara, A. Nakamura, Y. Origane, K. Fujita, D.-Q. Yuan, T. Mori, T. Wada and Y. Inoue, J. Photochem. Photobiol., A, 2005, 173, 375. 48 C. Yang, A. Nakamura, G. Fukuhara, Y. Origane, T. Mori, T. Wada and Y. Inoue, J. Org. Chem., 2006, 71, 3126. 49 C. Yang, A. Nakamura, T. Wada and Y. Inoue, Org. Lett., 2006, 8, 3005. 50 C. Yang, C. Ke, K. Fujita, D.-Q. Yuan, T. Mori and Y. Inoue, Aust. J. Chem., 2008, 1. 51 C. Ke, C. Yang, T. Mori, T. Wada, Y. Liu and Y. Inoue, Angew. Chem., Int. Ed., 2009, 48, 6675. 52 C. Ke, C. Yang, W. Liang, T. Mori, Y. Liu and Y. Inoue, New J. Chem., 2010, 34, 1323. 53 Q. Wang, C. Yang, G. Fukuhara, T. Mori, Y. Liu and Y. Inoue, Beilstein J. Org. Chem., 2011, 7, 290. 54 C. Yang, A. Nakamura, G. Fukuhara, Y. Origane, T. Mori, T. Wada and Y. Inoue, J. Org. Chem., 2006, 71, 3126. 55 A. Nakamura and Y. Inoue, J. Am. Chem. Soc., 2005, 127, 5338. 56 C. Yang, T. Mori, Y. Origane, Y. H. Ko, N. Selvapalam, K. Kim and Y. Inoue, J. Am. Chem. Soc., 2008, 130, 8574. 57 C. Yang, C. Ke, F. Kahee, D.-Q. Yuan, T. Mori and Y. Inoue, Aust. J. Chem., 2008, 61, 565. 58 C. Ke, C. Yang, T. Mori, T. Wada, Y. Liu and Y. Inoue, Angew. Chem., Int. Ed., 2009, 48, 6675. 59 Q. Wang, C. Yang, C. Ke, G. Fukuhara, T. Mori, Y. Liu and Y. Inoue, Chem. Commun., 2011, 47, 6849. 60 G. Fukuhara, H. Umehara, S. Higashino, M. Nishijima, C. Yang, T. Mori, T. Wada and Y. Inoue, Photochem. Photobiol. Sci., 2014, DOI: 10.1039/C3PP50127B. 61 G.-H. Liao, L. Luo, H.-X. Xu, X.-L. Wu, L. Lei, C.-H. Tung and L.-Z. Wu, J. Org. Chem., 2008, 73, 7345. 62 L. Luo, S.-F. Cheng, B. Chen, C.-H. Tung and L.-Z. Wu, Langmuir, 2010, 26, 782. 63 W. Liang, H.-H. Zhang, J.-J. Wang, Y. Peng, B. Chen, C. Yang, C.-H. Tung, L.-Z. Wu, G. Fukuhara, T. Mori and Y. Inoue, Pure Appl. Chem., 2011, 83, 769. 64 G. Fukuhara, T. Mori, T. Wada and Y. Inoue, Chem. Commun., 2006, 1712.


Review Article

65 G. Fukuhara, T. Mori and Y. Inoue, J. Org. Chem., 2009, 74, 6714. 66 C. Festa, N. Levi-Minzi and M. Zandomeneghi, Gazz. Chim. Ital., 1996, 126, 599. 67 N. Levi-Minzi and M. Zandomeneghi, J. Am. Chem. Soc., 1992, 114, 9300. 68 A. Ouchi, G. Zandomeneghi and M. Zandomeneghi, Chirality, 2002, 14, 1. 69 M. Nishijima, J.-W. Chang, C. Yang, G. Fukuhara, T. Mori and Y. Inoue, Res. Chem. Intermed., 2013, 39, 371. 70 T. Wada, N. Sugahara, M. Kawano and Y. Inoue, Chem. Lett., 2000, 1174. 71 S. Asaoka, T. Wada and Y. Inoue, J. Am. Chem. Soc., 2003, 125, 3008. 72 M. Nishijima, T. C. S. Pace, A. Nakamura, T. Mori, T. Wada, C. Bohne and Y. Inoue, J. Org. Chem., 2007, 72, 2707. 73 M. Nishijima, T. Wada, T. Mori, T. C. S. Pace, C. Bohne and Y. Inoue, J. Am. Chem. Soc., 2007, 129, 3478. 74 C. S. Pace Tamara, M. Nishijima, T. Wada, Y. Inoue and C. Bohne, J. Phys. Chem. B, 2009, 113, 10445. 75 T. Pace, M. Nishijima, T. Wada, Y. Inoue and C. Bohne, J. Phys. Chem. B, 2009, 113, 10445. 76 D. Fuentealba, H. Kato, M. Nishijima, G. Fukuhara, T. Mori, Y. Inoue and C. Bohne, J. Am. Chem. Soc., 2012, 135, 203. 77 M. Nishijima, H. Kato, C. Yang, G. Fukuhara, T. Mori, Y. Araki, T. Wada and Y. Inoue, ChemCatChem, 2013, DOI: 10.1002/cctc.201300160. 78 M. Fukagawa, I. Kawamura, T. Ubukata and Y. Yokoyama, Chem.–Eur. J., 2013, 19, 9401. 79 K. Bando, T. Zako, M. Sakono, M. Maeda, T. Wada, M. Nishijima, G. Fukuhara, C. Yang, T. Mori and T. C. Pace, Photochem. Photobiol. Sci., 2010, 9, 655. 80 M. Nishijima, H. Tanaka, G. Fukuhara, C. Yang, T. Mori, V. Babenko, W. Dzwolak and Y. Inoue, Chem. Commun., 2013, 49, 8916. 81 J. Sivaguru, A. Natarajan, L. S. Kaanumalle, J. Shailaja, S. Uppili, A. Joy and V. Ramamurthy, Acc. Chem. Res., 2003, 36, 509. 82 A. Joy, S. Uppili, M. R. Netherton, J. R. Scheffer and V. Ramamurthy, J. Am. Chem. Soc., 2000, 122, 728. 83 S. Uppili and V. Ramamurthy, Org. Lett., 2002, 4, 87. 84 A. Natarajan, A. Joy, L. S. Kaanumalle, J. R. Scheffer and V. Ramamurthy, J. Org. Chem., 2002, 67, 8339. 85 A. K. Sundaresan, L. S. Kaanumalle, C. L. D. Gibb, B. C. Gibb and V. Ramamurthy, Dalton Trans., 2009, 4003. 86 D. Brunel and M. Lasperas, Nanostruct. Catal., 2003, 157. 87 G. J. Hutchings, Surf. Chem. Catal., 2002, 241. 88 F. Van de Velde, I. W. C. E. Arends and R. A. Sheldon, Top. Catal., 2000, 13, 259. 89 D. S. Shephard, Stud. Surf. Sci. Catal., 2000, 129, 789. 90 G. J. Hutchings, Chem. Commun., 1999, 301. 91 J. Sivaguru, T. Shichi and V. Ramamurthy, Org. Lett., 2002, 4, 4221. 92 J. Sivaguru, T. Wada, Y. Origane, Y. Inoue and V. Ramamurthy, Photochem. Photobiol. Sci., 2005, 4, 119.

Chem. Soc. Rev., 2014, 43, 4123--4143 | 4141

View Article Online


Review Article

93 P. Lakshminarasimhan, R. B. Sunoj, J. Chandrasekhar and V. Ramamurthy, J. Am. Chem. Soc., 2000, 122, 4815. 94 K. Sivasubramanian, L. S. Kaanumalle, S. Uppili and V. Ramamurthy, Org. Biomol. Chem., 2007, 5, 1569. 95 L. S. Kaanumalle, J. Sivaguru, R. B. Sunoj, P. H. Lakshminarasimhan, J. Chandrasekhar and V. Ramamurthy, J. Org. Chem., 2002, 67, 8711. 96 E. Cheung, K. C. W. Chong, S. Jayaraman, V. Ramamurthy, J. R. Scheffer and J. Trotter, Org. Lett., 2000, 2, 2801. 97 K. C. W. Chong, J. Sivaguru, T. Shichi, Y. Yoshimi, V. Ramamurthy and J. R. Scheffer, J. Am. Chem. Soc., 2002, 124, 2858. 98 J. Sivaguru, S. Jockusch, N. J. Turro and V. Ramamurthy, Photochem. Photobiol. Sci., 2003, 2, 1101. 99 L. S. Kaanumalle, J. Sivaguru, N. Arunkumar, S. Karthikeyan and V. Ramamurthy, Chem. Commun., 2003, 116. 100 M. Kaftory, M. Yagi, K. Tanaka and F. Toda, J. Org. Chem., 1988, 53, 4391. 101 F. Toda, Mol. Cryst. Liq. Cryst., 1988, 161, 355. 102 F. Toda and K. Tanaka, Chem. Commun., 1986, 1429. 103 F. Toda, K. Tanaka and M. Yagi, Tetrahedron, 1987, 43, 1495. 104 J. R. Scheffer and L. Wang, J. Phys. Org. Chem., 2000, 13, 531. 105 L. Ma, L.-Z. Wu, L.-P. Zhang and C.-H. Tung, Chin. J. Chem., 2003, 21, 96. 106 A. Joy, L. S. Kaanumalle and V. Ramamurthy, Org. Biomol. Chem., 2005, 3, 3045. 107 A. Joy, J. R. Scheffer and V. Ramamurthy, Org. Lett., 2000, 2, 119. 108 N. A. Kaprinidis, M. S. Landis and N. J. Turro, Tetrahedron Lett., 1997, 38, 2609. 109 J. R. Edman, J. Am. Chem. Soc., 1969, 91, 7103. 110 R. C. Hahn and R. P. Johnson, J. Am. Chem. Soc., 1977, 99, 1508. 111 A. Joy, R. J. Robbins, K. Pitchumani and V. Ramamurthy, Tetrahedron Lett., 1997, 38, 8825. 112 H. Maeda, T. Okumura, Y. Yoshimi and K. Mizuno, Tetrahedron: Asymmetry, 2009, 20, 381. 113 T. Poon, N. Turro, J. Chapman, P. Lakshminarasimhan, X. Lei, S. Jockusch, R. Franz, I. Washington, W. Adam and S. Bosio, Org. Lett., 2003, 5, 4951. 114 W. Adam, S. G. Bosio, N. J. Turro and B. T. Wolff, J. Org. Chem., 2004, 69, 1704. 115 T. Poon, J. Sivaguru, R. Franz, S. Jockusch, C. Martinez, I. Washington, W. Adam, Y. Inoue and N. J. Turro, J. Am. Chem. Soc., 2004, 126, 10498. 116 J. Sivaguru, T. Poon, R. Franz, S. Jockusch, W. Adam and N. Turro, J. Am. Chem. Soc., 2004, 126, 10816. 117 J. Sivaguru, T. Poon, C. Hooper, H. Saito, M. R. Solomon, S. Jockusch, W. Adam, Y. Inoue and N. J. Turro, Tetrahedron, 2006, 62, 10647. 118 J. Sivaguru, H. Saito, M. R. Solomon, L. S. Kaanumalle, T. Poon, S. Jockusch, W. Adam, V. Ramamurthy, Y. Inoue and N. J. Turro, Photochem. Photobiol. Sci., 2006, 82, 123. 119 M. Benitez, G. Bringmann, M. Dreyer, H. Garcia, H. Ihmels, M. Waidelich and K. Wissel, J. Org. Chem., 2005, 70, 2315.

4142 | Chem. Soc. Rev., 2014, 43, 4123--4143

Chem Soc Rev

120 H. Qiu, C. Yang, Y. Inoue and S. Che, Org. Lett., 2009, 11, 1793. 121 T. Wada, M. Shikimi, Y. Inoue, G. Lem and N. J. Turro, Chem. Commun., 2001, 1864. 122 T. Bach, H. Bergmann and K. Harms, Angew. Chem., Int. Ed., 2000, 39, 2302. 123 T. Bach, H. Bergmann, B. Grosch and K. Harms, J. Am. Chem. Soc., 2002, 124, 7982. 124 P. Selig and T. Bach, J. Org. Chem., 2006, 71, 5662. 125 Handbook of Zeolite Science and Technology, ed. S. M. Auerbach, K. A. Carrado and P. K. Dutta, CRC Press, 2003. 126 T. Bach, B. Grosch, T. Strassner and E. Herdtweck, J. Org. Chem., 2003, 68, 1107. 127 T. Bach, H. Bergmann, H. Brummerhop, W. Lewis and K. Harms, Chem.–Eur. J., 2001, 7, 4512. 128 B. Grosch, C. N. Orlebar, E. Herdtweck, M. Kaneda, T. Wada, Y. Inoue and T. Bach, Chem.–Eur. J., 2004, 10, 2179. 129 T. Bach, H. Bergmann and K. Harms, Org. Lett., 2001, 3, 601. 130 D. F. Cauble, V. Lynch and M. J. Krische, J. Org. Chem., 2003, 68, 15. 131 Y. Inoue, Nature, 2005, 436, 1099. 132 A. Bauer, F. Westkaemper, S. Grimme and T. Bach, Nature, 2005, 436, 1139. ¨ller, A. Bauer, M. M. Maturi, M. C. Cuquerella, 133 C. Mu M. A. Miranda and T. Bach, J. Am. Chem. Soc., 2011, 133, 16689. 134 C. Mueller, A. Bauer and T. Bach, Angew. Chem., Int. Ed., 2009, 48, 6640. 135 D. Albrecht, F. Vogt and T. Bach, Chem.–Eur. J, 2010, 16, 4284. 136 Y. Kawanami, S. Katsumata, J. Mizoguchi, M. Nishijima, G. Fukuhara, C. Yang, T. Mori and Y. Inoue, Org. Lett., 2012, 14, 4962. 137 S. C. Coote and T. Bach, J. Am. Chem. Soc., 2013, 135, 14948. 138 J. Mizoguchi, Y. Kawanami, T. Wada, K. Kodama, K. Anzai, T. Yanagi and Y. Inoue, Org. Lett., 2006, 8, 6051. 139 Y. Kawanami, T. C. S. Pace, J. Mizoguchi, T. Yanagi, M. Nishijima, T. Mori, T. Wada, C. Bohne and Y. Inoue, J. Org. Chem., 2009, 74, 7908. 140 T. Furusawa, M. Kawano and M. Fujita, Angew. Chem., Int. Ed., 2007, 46, 5717. 141 Y. Nishioka, T. Yamaguchi, M. Kawano and M. Fujita, J. Am. Chem. Soc., 2008, 130, 8160. 142 M. Yoshizawa, Y. Takeyama, T. Okano and M. Fujita, J. Am. Chem. Soc., 2003, 125, 3243. 143 M. Yoshizawa, M. Tamura and M. Fujita, Science, 2006, 312, 1472. 144 J. S. Seo, D. Whang, H. Lee, S. I. Jun, J. Oh, Y. J. Jeon and K. Kim, Nature, 2000, 404, 982. 145 Y. Ishida, Y. Kai, S.-y. Kato, A. Misawa, S. Amano, Y. Matsuoka and K. Saigo, Angew. Chem., Int. Ed., 2008, 47, 8241.


View Article Online

Chem Soc Rev

149 F. Lv, X. Li, L. Wu and C. Tung, Tetrahedron, 2008, 64, 1918. 150 D. Xiao, T. Wada and Y. Inoue, Chirality, 2008, 21, 110. 151 M. Shirakawa, N. Fujita, T. Tani, K. Kaneko and S. Shinkai, Chem. Commun., 2005, 4149. 152 A. Dawn, T. Shiraki, S. Haraguchi, H. Sato, K. Sada and S. Shinkai, Chem.–Eur. J., 2010, 16, 3676. 153 R. Brimioulle and T. Bach, Science, 2013, 342, 840.


146 Y. Ishida, A. S. Achalkumar, S.-y. Kato, Y. Kai, A. Misawa, Y. Hayashi, K. Yamada, Y. Matsuoka, M. Shiro and K. Saigo, J. Am. Chem. Soc., 2010, 132, 17435. 147 Y. Ishida, Y. Matsuoka, Y. Kai, K. Yamada, K. Nakagawa, T. Asahi and K. Saigo, J. Am. Chem. Soc., 2013, 135, 6407. 148 F.-F. Lv, B. Chen, L.-Z. Wu, L.-P. Zhang and C.-H. Tung, Org. Lett., 2008, 10, 3473.

Review Article


Chem. Soc. Rev., 2014, 43, 4123--4143 | 4143

Understanding photochirogenesis: solvent effects on circular dichroism and anisotropy spectroscopy.

Supramolecular chemistry. Living supramolecular polymerization.

Supramolecular dynamics.

Supramolecular biomaterials.

Self-assembly of a supramolecular hexagram and a supramolecular pentagram.

Supramolecular luminescence from oligofluorenol-based supramolecular polymer semiconductors.

Correction to "Supramolecular Autoregulation".

Supramolecular systems chemistry.

A supramolecular tubular nanoreactor.

Dendronized supramolecular polymers.

Fullerene-porphyrin supramolecular nanocables.

Magnetically aligned supramolecular hydrogels.

Allosteric supramolecular coordination constructs.

Natural supramolecular protein assemblies.

Four-component supramolecular nanorotors.

Supramolecular and dynamic covalent reactivity.

Supramolecular chemistry. New synthetic receptors.

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks.

Glucose Sensing in Supramolecular Chemistry.

Editorial: Supramolecular chemistry in water.

Supramolecular glycodendrimer-based hybrid drugs.

Topological dynamics in supramolecular rotors.

Halogen Bonding in Supramolecular Chemistry.

clusto hybridized supramolecular polymers.