Supramolecular Photodimerization of Coumarins

Stereoselective photodimerization of coumarin and its derivatives in supra-molecular systems is reviewed. The enantioselective photodimerization of coumarin and thiocoumarin in inclusion crystals with optically active host compounds is also described.


Cucurbituril
Cucurbit [8]uril (8) has a cavity similar to that of cyclodextrins and has been shown to be an effective catalyst for the selective photodimerization of coumarins [7] (Scheme 3). The irradiation of 6-methylcoumarin (9) in water in the absence of 8 affords a mixture of four possible photodimers 10-13 in only 9% conversion. Conversely, in the presence of 8, the reaction was found to be clean and efficient with exclusive formation of syn photodimers (10 + 11) as photoproducts. For example, the photodimerization of 9 in the presence of 50 mol% of 8 resulted in a 72% conversion to photodimers with a syn:anti ratio of >99:1.

Pd-Nanocages
The irradiation of coumarin derivatives 15 within the Pd-nanocage 14 selectively yields the syn-head-head dimers 16, whereas in H 2 O, a mixture of dimers is obtained [8] (Scheme 4). For example, when irradiated as a host-guest complex, 8-methoxycoumarin (15d) exclusively formed the syn-head-head dimer 16d, while 15d itself was not sufficiently soluble to perform the photodimerization directly in water. The selective dimerization is interpreted to mean that coumarin monomers are preorganized by weak intermolecular interactions, such as hydrophobic, π-, and CH- interactions, between the host and guest to afford the syn-head-head dimer within the Pd-nanocage.

β-Cyclodextrin
The photodimerization of coumarin and eight of its derivatives was found to proceed selectively in crystalline inclusion complexes with β-and -cyclodextrins [9] (Scheme 5). For example, the irradiation of a 2:3 inclusion complex of β-cyclodextrin and coumarin in the solid state afforded the syn-head-head dimer in 64% yield, whereas its irradiation in water or as a neat solid provided 2 in low yield (~20%). The X-ray structural analysis of the 2:3 complex showed that the photodimerization likely occurs between coumarin molecules migrating inside a "reaction nano-tube" [10].

Bisurea Macrocycle
The bisurea macrocycle (19) with a diameter of ~9 Å forms a 1:3 inclusion complex with coumarin (1). The photoirradiation of the 1:3 complex for 96 h in the solid state under air afforded the anti-head-head dimer 2 with 96% selectivity and 18% conversion. Interestingly, the reaction under N 2 atmosphere gave a similar high selectivity (96%) with increased conversion (37%). The conversion could be further enhanced under Ar to 55% with no decrease in selectivity (97%) [11] (Scheme 6).

Enantioselective Photodimerization of Coumarins in Crystalline Inclusion Complexes
The single-crystal-to-single-crystal enantioselective photodimerization of 1 or thiocoumarin (25) was found to proceed efficiently in inclusion complexes with (R,R)-(−)-trans-bis(hydroxydiphenylmethyl)-2,2-dimethyl-1,3-dioxacyclopentane (23) or (R,R)-(−)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4dioxaspiro [4.4]nonane (24), respectively [14,15] (Scheme 8). Irradiation of the 1:1 inclusion complex of (−)-23 and 1 in the solid state with a 400-W high-pressure Hg lamp (Pyrex filter, room temperature, 4 h) gave a 2:1 complex of (−)-23 and the optically active anti-head-head dimer (−)-2. The anti-head-head dimer (−)-2 was isolated in 99% yield and 100% ee by recrystallization of the 2:1 complex from DMF/H 2 O (5/1). Optically pure (+)-2 was also obtained when the host compound (+)-23 was used instead of (−)-23. The single-crystal-to-single-crystal nature and the steric course of the enantioselective photodimerization of 1 to the anti-head-head dimer (−)-2 in the inclusion complex were investigated by X-ray crystallographic analysis. The results showed that two molecules of 1 were arranged by forming a hydrogen bond between the C=O of 1 and the O-H of 23 in the direction that gave the anti-head-head dimer (−)-2 by photoirradiation and that the molecular aggregation had distances of 3.59 and 3.42 Å sufficiently short to readily permit topochemical reaction in the crystals. (Figures 1 and 2) After photoirradiation, the bond distances of the cyclobutane ring were 1.6 and 1.57 Å, respectively ( Figure 3). Recently, a new type of C2-symmetric bisphosphine ligand with a cyclobutane backbone has been synthesized starting from enantiopure (−)-2 [16].   The photodimerization of 25 in the solid state gives a complex mixture of four possible dimers, although when irradiated in CH 2 Cl 2 , (±)-26 is obtained [17]. The enantioselective photodimerization of 3.573 Å 3.431 Å 25 to the optically pure anti-head-head dimer (+)-26 in the 1:1 inclusion complex of (−)-24 with 25 was also found to proceed in a single-crystal-to-single-crystal manner [14,15]. The photoirradiation of the 1:1 inclusion complex of (−)-24 with 25 in the solid state (400-W high-pressure Hg lamp, Pyrex filter, room temperature, 2 h) quantitatively gave a 2:1 complex of (−)-24 with (+)-26; (+)-26 was isolated in 73% yield and 100% ee by column chromatography. The single-crystal-to-single-crystal nature and the steric course of the photodimerization of 25 to the anti-head-head dimer (+)-26 in the inclusion crystals were also investigated by X-ray crystallographic analysis. The two molecules of 25 in the 2:1 inclusion complex are related by a pseudo-twofold axis along the c-axis. The C=O of 25 and the O-H of (+)-26 form a hydrogen bond in the direction that gives the anti-head-head dimer of (+)-26. The distances between the two ethylenic double bonds are sufficiently short (3.73 and 3.41 Å) to react easily and topochemically. After photoirradiation, the bond distances of the cyclobutane ring are both 1.60 Å. The crystal data are listed in Table 1.  Recently, thermal [2+2] cycloaddition reactions of coumarin and thiocoumarin were found to occur in the above inclusion crystals [18]. Typically, coumarin and thiocoumarin are thermally unreactive for dimerization according to the Woodward-Hoffmann rules. Interestingly, however, the dimerization of coumarin occurred under high vacuum to form anti-head-head dimers in about 30% yield and 99% ee. For this reaction, both high-vacuum conditions and the presence of the host compound ()-23 were found to be essential.
For example, a 2:1 inclusion complex of (R,R)-()-27 and (S,S,S,S)-(+)-11 was obtained in 60% yield and 95% ee upon photoirradiation of a cyclohexane solution of an equimolar mixture of ()-23 and 9. Treatment of the inclusion complex with DMF/H 2 O gave (S,S,S,S)-(+)-11 of >99% ee in 27% yield. One possible explanation of this reaction is as follows. The photodimerization of coumarin occurs in solvent but is reversible. In hydrocarbon and aromatic solvents, one enantiomer of the dimer complexes with the host, precipitates as inclusion crystals, and is protected from the reverse reaction. The other enantiomer is decomposed to the monomer by further irradiation in solution.