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Supramolecular Photochemistry as a Potential Synthetic Tool: Photocycloaddition Vaidhyanathan Ramamurthy*,† and Jayaraman Sivaguru*,‡ †
Department of Chemistry, University of Miami, Coral Gables, Florida 33146, United States Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108-6050, United States
Chem. Rev. 2016.116:9914-9993. Downloaded from pubs.acs.org by 185.251.71.197 on 08/15/18. For personal use only.
‡
ABSTRACT: Photochemistry, bearing significant applications in natural and man-made events such as photosynthesis, vision, photolithography, photodynamic therapy, etc., is yet to become a common tool during the synthesis of small molecules in a laboratory. Among other rationale, the inability to influence photochemical reactions with temperature, solvent, additives, etc., dissuades chemists from employing light-initiated reactions as a routine synthetic tool. This review highlights how diverse, highly organized structures such as solvent-free crystals and water-soluble host−guest assemblies can be employed to control and manipulate photoreactions and thereby serve as an efficient tool for chemists, including those interested in synthesis. The efficacy of the media in modifying the excited-state behavior of organic molecules is illustrated with photocycloaddition in general and [2 + 2] photocycloaddition in particular, reactions widely employed in the synthesis of complex natural products as well as highly constrained molecules, as exemplars. The reaction media, highly pertinent in the context of green sustainable chemistry, include solvent-free crystals and solids such as silica, clay, and zeolite and water-soluble hosts that can solubilize and preorganize hydrophobic reactants in water. Since no other reagent would be more sustainable than light and no other medium greener than water, we believe that the supramolecular photochemistry expounded here has a momentous role as a synthetic tool in the future.
CONTENTS 1. Introduction 1.1. Scope of the Review 1.2. Choice of Photoreaction: [2 + 2] Photocycloaddition 1.3. Choice of Media: Supramolecular Assemblies 1.4. Model 2. Organic Crystals as a Supramolecular Assembly 2.1. Original Topochemical Postulate 2.2. Modified Topochemical Postulate 2.3. Crystal Engineering: Preorganizing the Olefins toward Reactivity in a Crystal 2.3.1. Intramolecular Functionalization ApproachChlorine and Fluorine as Steering Groups 2.3.2. Preorganization through Acid−Base Salt Formation 2.3.3. Preorganization through Metal Ion Coordination with Olefins 2.3.4. Proton as a Template 2.3.5. Templation through Inclusion within a Diol Host Cavity: Role of Hydrogen Bonding 2.3.6. Hydrogen-Bonding Templates 2.3.7. Urea-Based Nanochannel Templates 2.4. Types of Solid-State Photoreactions 2.4.1. Topochemical Photodimerization 2.4.2. Heterogeneous and Homogeneous Topochemical Photodimerizations © 2016 American Chemical Society
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2.4.3. Single-Crystal to Single-Crystal Photodimerization (SCSC) 2.4.4. Topotactic Photodimerization 2.5. Factors Controlling the Dimer Yield 2.5.1. Effect of Packing 2.5.2. Effect of Temperature 2.5.3. Effect of Wavelength 2.6. Mechanism of Dimerization 2.6.1. Dimerization Probed by Ultrafast Spectroscopy 2.6.2. Concerted vs Stepwise Addition 2.7. Chiral Induction during [2 + 2] Photoaddition in the Solid State 2.8. Solid-State Photodimerization as a Synthetic Tool 2.9. Generalizations on Crystals as Reaction Media Solid Surfaces as Reaction Media: Silica, Clay, and Zeolites Monolayer Assembly and Langmuir−Blodgett Film as a Photoreactive Supramolecular Assembly Water: A Medium That Prompts Supramolecular Aggregation of Hydrophobic Molecules Micelles as Reaction Media
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Special Issue: Photochemistry in Organic Synthesis Received: January 19, 2016 Published: June 2, 2016
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Chemical Reviews 7. Cages, Capsules, and Cavitands as Reaction Containers 7.1. Cyclodextrins (CDs) 7.2. Cucurbiturils (CBs) 7.3. Pd-Nanocages 7.4. Octa Acid 8. H-Bonding Templates 9. Supramolecular Photocatalysis: Organized Assemblies as Catalysts 9.1. Supramolecular Photocatalysis Mediated by Cucurbiturils 9.2. Supramolecular Photocatalysis Mediated by Cyclodextrins 9.3. Supramolecular Photocatalysis Mediated by Hydrogen-Bonding Templates 10. Conclusion and Outlook Author Information Corresponding Authors Notes Biographies Acknowledgments 13. List of Abbreviations References
Review
addition and [2 + 2] and other types of cycloadditions, addition of singlet oxygen to olefins, photocyclizations, di-π methane rearrangement, oxa-di-π methane rearrangement, photodecarbonylation, and electron transfer (SET, PET) initiated reactions are routinely used by synthetic chemists.2,3 Excellent reviews by synthetic chemists on these topics affirm the value of photochemical reactions to this community.5−20 The growth of photochemistry from “molecular” to “supramolecular”21 provides an opportunity to overcome some of the problems encountered by synthetic chemists in employing photochemical reactions in the synthesis of organic molecules.
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1.1. Scope of the Review
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This review highlights the significance of the medium in controlling the outcome of a photoreaction and enunciates the control and prediction of the type and nature (regio- and stereochemical features) of products by choosing an appropriate supramolecular assembly as the reaction medium.22−24 Due to the time-independent and directional interaction between the medium and the reactant the assembly of the reactant and the medium is defined to be “supramolecular”.21 Viewing supramolecular in a much broader context we include all organized and confining media except isotropic organic solvents. We believe the chemistry of the excited molecule in a supramolecular assembly needs to be understood as an ensemble of the reactant and the medium. The unequivocal role of the environment can be tapped to modify the behavior of a molecule in the excited state. Photocycloaddition of two unsaturated molecules yields a product rich in regio- and stereochemistry. Thus, a mixture of isomers could result, and controlling the photochemical outcome could be challenging. Since reactions on excited-state surfaces have very small activation energies and the reacting molecules very short lifetimes, reaction temperature and pressure have little influence. In this context one of the most successful approaches has been preorganization of the reactant molecules through weak interactions and confinement. This review gives more emphasis to the medium than the reaction itself, in other words “the medium is the message”.25 The concepts expounded are general and could be applied to reactions other than the exemplar [2 + 2] photoaddition. As [2 + 2] photoaddition is used extensively in synthesis we have chosen this reaction as the prime example. The media covered include solids and water. Since most organic molecules are not soluble in water, water-soluble assemblies/molecules such as micelles, organic and inorganic cavitands, and capsules are used as hosts to solubilize them in water. With the current emphasis on “sustainability” and “green chemistry” solid and water are appropriate reaction media. No other reagent would be more sustainable than sunlight and greener medium than water (or solid). Given the interdisciplinary nature of the topic, to appreciate and use the chemistry discussed here exposure to both molecular and supramolecular photochemistry is essential.2,3,26−28
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1. INTRODUCTION The importance of the incomparable light-initiated chemistry that has been occurring for hundreds of millions of years is undisputed. Despite the long history only about three centuries ago the first molecule was intentionally irradiated and the products were isolated.1 Although light-induced transformations of organic molecules such as santonin (1830s), anthracene, (1860s), quinone (1870s), etc., were recognized more than a century ago, the mechanistic details of these transformations were not understood until the middle of the last century. Intense research on light and its interaction with materials and molecules during 1940−70 gave birth to a new discipline now known as photochemistry.2,3 As far back as 1912 the importance of light in sustaining life was recognized and that light from the Sun would serve as our energy source predicted.4 Although the prediction is yet to be realized, photochemistry has become an important component of our life. Modern living is made easier by the invention of, among other things, lithographic techniques where light is the key player, which has transformed the printing, electronic, and computer industries. With the discovery of lasers photochemistry is making inroads into health care industry. While the value of photochemistry has been recognized in largescale electronics and the health care industry (e.g., lithography and photodynamic therapy), its utility as a synthetic tool in transforming small molecules is slow in gaining acceptance. Photochemical reactions are mostly used by synthetic organic chemists interested in molecules of pharmaceutical and theoretical importance as a last resort. Though some of the complex and exotic natural products and molecules with extreme strain were made employing photochemical reactions, synthetic chemists are yet to recognize and use them readily. Conviction that photochemical reactions often result in a mixture of products and low yields, the products themselves are easily decomposed by light and, that the reactions cannot be manipulated with heat and/or solvents have dissuaded synthetic chemists from resorting to photochemistry as a primary arsenal in building complex and challenging molecules. However, photochemical reactions such as arene−alkene meta cyclo-
1.2. Choice of Photoreaction: [2 + 2] Photocycloaddition
A few examples where photocycloadditions of various types have played an important role in synthesis are highlighted in Figures 1 and 2.29−32 The photocycloaddition of the CC bond to various chromophores has been employed by synthetic chemists effectively.33−42 To give a flavor of its usefulness an example from each type of cycloaddition is illustrated in Figure 1. These include meta-photocycloaddition,43 [5 + 2] photocycloaddition,44 [3 + 2] photocycloaddition,45 [6 + 2] photocycloaddition,46 [4 + 2] 9915
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Figure 1. Representative molecules synthesized using various types of photocycloaddition as a key step. The kind of photocycloaddition involved is indicated in each case.
Figure 2. Representative molecules synthesized using [2 + 2] photocycloaddition as a key step. 9916
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Figure 3. Cartoon/molecular renditions of various organized/confined/supramolecular assemblies that can serve as reaction containers. Supramolecular assemblies A−F are representative of molecular crystals and porous and nonporous solids that offer one-, two-, or three-dimensional restrictions to the accommodated guest molecules. G−K represent unimolecular or multimolecular (micelle) supramolecular assemblies that can solubilize organic molecules in water. L presents a variety of H-bonding templates that promote efficient phototransformations.
photocycloaddition,47 and [4 + 4] photocycloaddition.48 Among the various photochemical cycloadditions the [2 + 2] photo-
cycloaddition, like the Diels−Alder [4 + 2] thermal addition, has played an important role in the synthesis of constrained and 9917
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the nature of the reaction container (soft, hard, flexible, or inflexible), and the time scale of their existence (time independent or time dependent). Among the supramolecular assemblies listed in Figure 3, crystals,56 zeolites,57 urea clatharates,58 clay,59 silica,60 and L−B film61 on glass surface are solids (Figure 3A−F). The freedom a reactant has within these solid materials varies. For example, in organic crystals (Figure 3A) the molecules have very little translational and rotational freedom, while on a silica surface they can move in two dimensions, and within a clay (Figure 3D) they can do so in one dimension only. Within zeolites (Figure 3E), the interactions between the cations and the guest restrict the mobility of the latter in all three dimensions but lesser than in a crystal. The freedom of molecules on L−B film (Figure 3F) is lesser than on a silica surface (Figure 3E). The superbly organized organic crystals providing very little freedom for their component molecules are ideal for highly selective photoreactions. A major portion of the review discusses photoreactions extensively investigated in this supramolecular assembly. Micelles,62 cyclodextrins,63,64 cucurbiturils,65 Pd-nanocage,66 and octa acid67 (Figure 3G−K) are water-soluble hosts that can solubilize organic molecules in water. In water, mainly hydrophobic forces contribute to the inclusion of guests within these hosts. The binding strength of the host−guest complex depends on the structure of the guest, and therefore, the binding of the various reactant molecules to a given host could vary. To achieve good selectivity it is important to contain all molecules within the host, thus making crucial the right condition for maximum binding. Hosts mentioned above except octa acid (Figure 3K) expose the reactant molecule to aqueous exterior (“open container”). The interface between the exterior water and the hydrophobic interior of micelles and open containers such as cyclodextrins, cucurbiturils, and Pd-nanocage could be used to align polar molecules. The same interface would also lead to the guest’s equilibrium between aqueous exterior and hydrophobic interior. In this context the closed capsular assembly provided by octa acid would allow better manipulation of the excited-state behavior of a reactant molecule it confines. Among the open containers mentioned above, micelles are larger and flexible in size and dynamic in character and can easily accommodate more than one molecule and provide a large interface where the reactants could be aligned. We present examples of [2 + 2] photocycloaddition in these closed and open containers in the following sections. Open containers like cucurbiturils (Figure 3I) are ideal for exploring supramolecular catalysis as they allow for dynamic exchange of reactants and products. The drawback that the above generic hosts that may not be suitable under all conditions has been overcome by tailor-made hosts with specific functions. These hosts by interacting with the reactant molecules, mostly through hydrogen bonding, restrict the latter’s motions and hold them in a specific geometry toward the incoming molecule.68 These hosts generally work in organic solvents that are aprotic with medium to less polarity. A few such hosts are included in Figure 3L. The restriction imposed on the reactant molecule could be transformed into products with excellent regio- and stereoselectivity. Depending on the type of H-bonding host and the guest molecule,68 one can use either stoichiometric or substoichiometric amounts of hosts to control chemical reactivity. In most cases, to achieve good selectivity during photochemical transformations, lower temperature is preferred to maintain interaction between the host and the guest. The ideal situation of carrying out photoreactions in water using catalytic amounts of the host/template rather than molar
naturally occurring molecules. The earliest intramolecular [2 + 2] photocycloaddition leading carvone to camphor was recognized by Ciamician in 1908 and its first synthetic application expounded by Corey and Eaton in 1964 with the syntheses of caryophyllene49 (natural product) and cubane50 (a strained, energy rich molecule), respectively. These reports set the stage for exploitation of [2 + 2] photocycloaddition in the synthesis of natural products as well as highly strained and theoretically interesting molecules. Since construction of the cyclobutane ring by thermal means can be difficult, the [2 + 2] photocycloaddition is recognized to be the tool to synthesize molecules with such structures. One example of [2 + 2] photocycloaddition,51 enone−photocycloaddition,52,53 de Mayo reaction,54 and Paternò−Büchi reaction55 is provided in Figure 2. In this review we focus on [2 + 2] photodimerization of olefins and enones and photocycloaddition of enones with olefins with occasional reference to reaction between carbonyl and olefin and dimerization of aromatics. 1.3. Choice of Media: Supramolecular Assemblies
In the same vein that a “molecule” is a collection of atoms held together by covalent bonds one could define “supramolecule” as a collection of molecules held together by weak contacts such as hydrogen-bonding, C−H----π, cation---π, π---π, and hydrophobic interactions (0.1 M). In aqueous media, in both systems the dimerization was able to compete with geometric isomerization, the only reaction in nonaqueous isotropic solution at low concentrations. In all four examples (Schemes 50 and 51) mentioned there was no clear preference for a single dimer. These results are consistent with the conclusion that the organic molecules tend to aggregate in water, but these aggregates are internally disorganized. Photodimerization of coumarin at high concentrations (>0.3 M) in organic solvents is well investigated (Scheme 52).405 The nature of the dimer obtained varied with the solvent and the concentration. Coumarin 29a could be dimerized at low concentrations (90%). In the absence of the Pd-CNC1 nanocage, cross-photocycloaddition was not observed even at high concentrations. To evaluate chiral induction (Scheme 76), the same group developed chiral nanocages by incorporating chiral ligands around Pd(II).474,476 By replacing the ethylenediamine end-cap ligands on Pd center in Pd-CNC1 with chiral diamines they were able to construct chiral Pd-CNC1c-e. The chiral Pd-CNC1c with (1R,2R)-N,N′-diethyl-1,2-diaminocyclohexane as the capping ligand was found to form a ternary complex with 132 and 133e as guest molecules. Irradiation of the ternary complex resulted in [2 + 2] cross-photocycloaddition leading to the syn heterodimer 134e with an ee of 40% with the major enantiomer having a 1S,2R,2aR,10aR configuration. When 3-methylfluoranthene (133f) was employed for the [2 + 2] cross-photocycloaddition with 132, the corresponding photoproduct 134f
auxiliary was removed by base hydrolysis for ascertaining the stereoselectivity in the corresponding syn-HT and anti-HH photodimer. After the removal of the chiral auxiliary, ee values of 91% and 2% were observed at −20 °C at 210 MPa for the syn-HT and anti-HH dimers, respectively. On the other hand, with CB[8] at −20 °C at 210 MPa ee values of 18% and 8% were observed for the syn-HT and anti-HH dimers, respectively. It was reasoned that the γ-CD with its short cavity and wide openings allowed deep penetration of HT-oriented anthracene moieties enabling photocyclodimerization at the 9,10 positions. On the other hand, CB’s with its narrow portals hindered deep penetration and mutual overlap of two anthracenes moieties thereby suppressing the subsequent photodimerization, allowing only the photodimerization of HH-oriented complex in low ee. 7.3. Pd-Nanocages
The synergetic coalescence of coordination chemistry and supramolecular chemistry has resulted in the advent of a molecular flask known as coordination nanocages (CNC’s) (e.g., Pd-nanocage; Figure 3).66,467 These CNCs are not only water soluble but also effective in controlling chemical transformations. One such flask that has been shown to be effective in controlling photoreactions was developed by Fujita and co-workers.66,467 The CNC’s were constructed around square-planar coordinated Pd(II) and Pt(II) ions with capping ligands such as ethylenediamine derivatives to enforce the 90° cis geometry around the metal center. The self-assembled coordination cages were synthesized by mixing these end-capped metal ions with the tridentate, triangular ligands such as 2,4,6-tris(4-pyridyl)-1,3,5triazine or 2,4,6-tris(3-pyridyl)-1,3,5-triazine. The metal ions anchored the corners of the octahedron with triazine ligands serving as the walls creating a unique cavity that could be employed for controlling chemical transformations.66,467 CNCs have been utilized to promote and control various photo9963
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Scheme 69. CB[8]-Mediated Photodimerization of trans-1,2-Bis(n-pyridyl)ethylenes and Stilbazolesa
a
Single-crystal XRD of CB[8] (E)-117a 1:2 host−guest complex showcase the distance of 4.783 Å between the reactive carbons. XRD structure were reproduced with permission from ref 459. Copyright 2005 The Royal Society of Chemistry.
Scheme 70. Photodimerization of Cationic Styryl Dyes E-100 Mediated by CB[8]a
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Structure based on single-crystal XRD of CB[8] (E)-100f 1:2 host−guest complex is shown at the bottom. XRD structure reproduced with permission from ref 461. Copyright 2014 John Wiley and Sons.
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Scheme 71. CB[8]-Mediated Photodimerization of Cinnamic Acid Derivatives E-102 (eq 1) and 2-Naphthyl-Substituted Derivatives 115 (eq 2)
was observed with an ee value of 50%. Changing the chiral CNC to Pd-CNC 1d and Pd-NC1e for the [2 + 2] crossphotocycloaddition with 132 with 133e resulted in 134e with ee values of 20% and 5%, respectively. The lowering of ee values in Pd-CNC 1d and Pd-NC1e was rationalized based on the distortion of the triazine wall that was inferred by CD spectra.
Scheme 72. CB[7]-Mediated Photodimerization of Aminopyridine Derivative 121
7.4. Octa Acid
Octa acid (OA) as the name implies possesses eight carboxylic acid groups and as expected of a cavitand has an internal cavity of dimensions shown in Figure 3.67 OA is water soluble at pH > 8.5. The top and bottom portals of OA are of different dimensions with the bottom one, too narrow even for the oxygen molecule to diffuse through. In the presence of a guest molecule such as naphthalene and anthracene two molecules of OA form a capsule enclosing two guest molecules. In the context of cycloaddition 2:2 complexes (guest:OA host) are important. As discussed above, in cavitands such as cyclodextrins providing an interface Scheme 73. Photodimerization of α-Cyclodextrin-Appended Anthracene Carboxylic Acid Derivative 124 within CB[8] and γCyclodextrin
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Scheme 74. Pd-Nanocage Mediates Photodimerization of Acenaphthylenes 34 (eq 1), Naphthoquinones 129 (eq 2), and Coumarins 29 (eq 3)a
a
In eq 3 syn-HH is the only product formed.
indene with OA capsule resulted in head−tail 139.479 Thus, within OA the head−tail arrangement that fills the entire cavity is preferred by indene. The need to maximize van der Waals interaction with the host interior probably directed indene to prefer this arrangement, which upon excitation transformed into head−tail dimer. The second example deals with photodimerization of acenaphthylene that forms a 2:2 complex within OA.480 Irradiation of the complex resulted solely in syn dimer (30% yield in 2 h). However, irradiation of acenaphthylene 34a at the same concentration (0.01 M) in either methanol or benzene for over 24 h gave a 5% yield of a mixture of syn-35a and anti-35a dimers (2.5:1 ratio) (Scheme 78). The tremendous increase in yield and selectivity are the result of the local concentration and orientational effects. The inability of the anti-35a dimer to fit within the cage probably also contributed to its elimination as the
like micelles, the selectivity of photoproducts is low due to poor binding. Although the closed OA container lacks a hydrophobic−hydrophilic interface, it has better ability to bind and enclose organic molecules and localize more than one molecule. The localization effect due to high local concentration allows dimerization to proceed efficiently even when the bulk concentration is extremely low. Further, due to the confined nature of the capsule the reactant molecules are forced to accommodate themselves in a specific orientation with very little freedom. Two examples presented below bring out the power of the OA capsule in altering the outcome of photodimerization. Direct excitation, triplet sensitization, and electron transfer sensitization of indene 135 in organic solvents lead to head− head (syn and anti) dimers (136 and 137) as major products (Scheme 77). On the other hand, irradiation of 2:2 complexes of 9966
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Scheme 75. Pd-Nanocage-Promoted Intermolecular [2 + 2] Cross-Photocycloaddition
Scheme 76. Asymmetric Intermolecular [2 + 2] Cross-Photocycloaddition within Chiral Pd-Nanocages
product. While in the case of indene the product that is not formed in solution is favored within OA, in the case of acenaphthylene 34a of the two products formed in solution only one is favored. Dimerizations of styrenes and cyclohexenone are also reported within OA.481,482 These results suggest that the OA host besides bringing the two olefin molecules close enough to react is also capable of preorienting them toward a single dimer. The behavior of OA suggests that it is not essential to have a hydrophobic−hydrophilic interface to orient dimerizing molecules for selective photochemical reactions. In addition to the CDs, CBs, PdCNC, and OA described above, water-soluble calixarenes have been explored as reaction vessels to conduct photodimerization of stilbene, dipyridylethylenes, stilbazoles, and bis(5′-pyrimidyl)ethylene.483−486
However, the generality of this cavitand has not been established yet.
8. H-BONDING TEMPLATES Hydrogen bonding in supramolecules critical in modulating lifesustaining molecular events has provided the inspiration to chemists for employing them to control chemical reactions. The strategy can be extended by incorporating stereodifferentiating unit(s) in the H-bonding template for evaluating asymmetric phototransformations.68 Some of the successful hydrogenbonding templates that have been employed for photochemical transformations are listed in Figure 3. These templates interact with the photoreactive substrate(s) through supramolecular interactions often times in combination with energy transfer 9967
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Scheme 77. Triplet Sensitization and Electron Transfer Sensitization of Indene 135 in the Presence and Absence of Octa Acid
energy sharing between the template and the substrate(s). The molecular architecture of the H-bonding template facilitates facial/stereodifferentiation in the photoreaction of interest.487 A key feature of these H-bonding templates is that they can be employed in substoichiometric amounts to carry out reactions under catalytic conditions (vide infra). This makes H-bonding templates a versatile platform for studying stereoselectivity in small chiral molecules during photoreactions that has presented challenges over the decades. The use of H bonding to preorganize substrates has been extensively studied in crystals (refer to section 2.3.6). One of the earliest attempts to utilize H bonding to control photochemical reactivity in solution was by Beak and co-workers488 (Scheme 79). They utilized H bonding in pyridone functionality to align cinnamoyloxy chromophores 140 to control the [2 + 2] photocycloaddition reaction in benzene solution leading to photoproducts 141 (δ-truxinic product) and 142 (β-truxinic product). In addition to photocycloaddition double-bond isomerization was observed in the reactants and in the photoproducts.
Scheme 78. Photodimerization of Acenaphthylene 34a in the Presence and Absence of Octa Acid
(ET) or electron transfer (eT) or energy-sharing events thereby enhancing chemical reactivity/selectivity in light-initiated reactions. The H-bonding motif serves as a glue to bring the reactive substrate closer to template for efficient interactions. This close proximity enabled by hydrogen bonding assists in enhanced reactivity typically aided by energy/electron transfer or
Scheme 79. Controlling [2 + 2] Photocycloaddition Reaction Pyridone-Functionalized Cinnamoylox Derivative 140 through Hydrogen Bonding
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Scheme 80. Intramolecular [2 + 2] Photocycloaddition Coumarin Functionalization of Kemp Triacid-Based Template KTA1 with Thymine 143
The use of Kemp triacid (KTA) for self-replicating systems enabled its use for molecular recognition events in chemical systems.489 On the basis of this Nakamura and co-workers reported490 the use of Kemp triacid-based template KTA1 as a host molecule that featured a coumarin unit as a light-absorbing motif to initiate the photocycloaddition with thymine 143 (Scheme 80) The host−guest interaction between KTA1 and 143 facilitated by H bonding was reflected in the product selectivity. Due to facial/stereodiscrimination, cis-syn-144 was observed over cis-anti-144. In benzene solution, cis-syn-144:cisanti 144 was 96:4, while in acetonitrile the ratio was 68:32. The formation of cis-syn-144 over cis-anti-144 was rationalized based on the cis-syn complex formed between KTA1 and 143 assisted by H bonding. On the basis of the precedence by Nakamura and coworkers490 on the use of Kemp triacid templates for photoreactions, Bach and co-workers491 extended it by employing optically pure template (+)-KTA2 and (−)-KTA3 for intramolecular [2 + 2] photocycloaddition reactions of 4-substituted2-quinolone 145 (Scheme 81).491 With (−)-KTA3 template, low selectivity was observed in the photoproduct 146a (37% ee, 89% yield, −15 °C) that was rationalized due to the weak association between the reactant 145a and the host template featuring menthol for stereodiscrimination. However, by employing superstoichiometric amounts (2.6 equiv) of the rigid (+)-KTA2 template, high enantioselectivity (93% ee, 77% yield at −60 °C) was observed in 146a. Similarly, carrying out photoreaction with quinolone 145c that featured a longer alkyl chain with 1.2 equiv of chiral host (+)-KTA2 in toluene at −15 °C gave high enantioselectivity (88% ee, 88% yield) in the photoproduct 147c. In spite of employing superstoichiometric amounts of the template, this report showed that Kemp triacid-
Scheme 81. Intramolecular [2 + 2] Photocycloaddition Reactions of 4-Substituted-2-quinolone 145 with Kemp Triacid-Based Template KTA2 and KTA3
based chiral lactam hosts can discriminate enantiotopic faces of the photoreactive substrates. Inoue and co-workers reported enantioselective photocyclodimerization of 148 in the presence of a H-bonding chiral pyrrolidinyl benzamide (PBA) template (Scheme 82).492 The amide and primary alcohol functionalities in pyrrolidinyl benzamide templates PBA1 and PBA2 provided two-point hydrogen-bonding sites to anchor the substrate. Irradiation of 148 in the presence of PBA template at two different temperatures (25 and −50 °C) in dichloromethane yielded photoproducts 149−152. At −50 °C, preferential formation of anti-HT 149 and anti-HH 151 was observed. In the presence of 9969
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Scheme 82. Enantioselective Photocyclodimerization of Anthraceme Carboxylic Acid 148 in the Presence of a H-Bonding Chiral Pyrrolidinyl Benzamide (PBA)
Scheme 83. Photodimerization of Coumarin Derivative 29h with Xanthene-Based Hydrogen-Bonding Receptor PHX
PBA1 and PBA2, a significant difference in the ee values was observed in the chiral photoproducts. Due to the trans geometry between the amide and the alcohol functionalities in PBA2, low enantiomeric excess (
