2-Pyridones, photodimerizations

The natural propensity of 2-pyridone photodimerization to favor the head-to-tail [4+4] adducts can be reversed by the use of a tether (Sch. 42). For head-to-head 189, photocycloaddition leads to a 1 1 mixture of the cis and trans adducts [122]. For tail-to-tail isomer 192, a high proportion of the cis adduct 194 is generated, although product mixtures for both reactions change under extended irradiation times, favoring the cis isomers [123]. 

The literature of mechanistic aromatic photochemistry has produced a number of examples of [4 + 4]-photocycloadditions. The photodimerization of anthracene and its derivatives is one of the earliest known photochemical reactions of any type97. More recently, naphthalenes98, 2-pyridones" and 2-aminopyridinium salts100 have all been shown to undergo analogous head-to-tail [4 + 4]-photodimerization. Moreover, crossed [4+4]-photocycloaddition products can be obtained in some cases101. Acyclic 1,3-dienes, cyclohexadienes and furan can form [4 + 4]-cycloadducts 211-214 with a variety of aromatic partners (Scheme 48). 

H-stacking interactions have also been exploited to orientate olefinic moieties in a geometry suitable for photochemical cycloaddition reactions, and have been invoked by Coates et al. to explain the photodimerization and photopolymerization of mono- and diolefins carrying phenyl and perfiuorophenyl groups [43]. Matsumoto et al. reported the photodimerization of 2-pyridone in co-crystals with naphthalene-substituted monocarboxyhc acids, where the stacking of the naphthalene rings provides carbon-carbon distances appropriate for [4+4] cycloaddition [44]. 

The synthesis of cis-1,4 polymers was also tried by e use of monomers with an s-cis conformation. The solid-state photopolymerization of pyridone derivatives, which is a six-membered cyclic diene amide and is a tautomer of 2-hydroxypyridine, was attempted [100]. Pyridones make hydrogen-bonded cocrystals with a carboxylic acid in the crystalline state. Because the cyclic structure fixes its s-cis conformation, if the polymerization proceeds, a cis-2,5 polymer would be obtained. Actually, however, the photopolymerization did not occur, contrary to our expectation, but [4-1-4] photodimerization proceeded when the carbon-to-carbon distance for the dimerization was small (less than 4 A) [101]. A closer stacking distance of the 2-pyridone moieties might be required for the topochemical polymerization of cychc diene monomers. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

Keywords 2-pyridone, inclusion crystal, [2+2]photodimerization, /Mactam... 

Since photochemical reactions in inclusion compounds have been described in one chapter of the previous book [1], enantioselective (3-lactam formation reactions are summarized in this present chapter as a typical application of the inclusion technique for enantioselective photosynthesis. In addition, as a representative enantioselective single-crystal-to-single-crystal photoreaction, the photodimerization reactions of coumarin and thiocoumarin in their inclusion compound with a chiral host are also described. Furthermore, a host-catalyzed photodimerization reaction of chalcone and 2-pyridone in the solid state is also added to this chapter as a unique example of the application of inclusion techniques to selective photoreaction. 

Photodimerization of 2-pyridone (46) in the presence of the 2,2/-biphenyldi-carboxylic acid host (45) also proceeded via a catalytic process. First, irradiation of the 1 2 inclusion complex of 46 and 45 in the solid state gave the trans-anti dimer (47) in 92 % yield [27], The mechanism of this stereoselective photoreaction was investigated through X-ray analysis of this complex. In the complex, two 46 molecules are arranged in ideal positions for yielding 47 by dimerization [27], Secondly, a catalytic dimerization reaction of 46 was carried out. Photoirradiation for 20 h of a 1 4 mixture of powdered 45 and 46 under occasional mixing in the solid state gave 47 in 81 % yield. These data clearly show that molecules of... 

Pyridones can react photochemically along several reaction channels [94]. Besides [4 + 4]-photodimerization and 4jt]-ring closure, [2 + 2]-photocydoaddition reactions are possible in an a,P- or in a y,8-mode relative to the carbonyl carbon atom. With regard to the former reaction pathway, the [2 + 2]-photocydoaddition of olefins to 4-alkoxypyridones appears to be synthetically most useful (vide infra). 

The photodimerization of 2-pyridones is an efficient, regiospecific, and stereoselective [4+ 4]-cycloaddition [56] that converts two achiral aromatics into a highly functionalized tricyclic cyclooctadiene with four stereogenic centers (Scheme 9.34). For tethered pyridones, the trans isomer is usually the major product when one or both pyridine nitrogens are methylated. By contrast, in the unsubstituted systems,... 

Photodimers have been reported as the principal products from irradiation of numerous arene substrates. While there is little selectivity to be considered in most of these reactions, it has been reported that almost all photolyses of 9-substituted anthracenes give head-to-head dimers as depicted in U10). ° An intramolecular version of these photodimerizations has also been reported. Irradiation of di(a-2-naphthylmethyl) ether gave a mixture of the endo cyclomer (111) and the exo cyclomer (112). ° The photodimerization of 2-pyridones has been the subject of extensive investigation for a number of years." "" In most instances the head-to-tail or trans-anti isomer was the major or exclusive product in these reactions. Irradiation of A -methyl-2-pyridone for 15 h provided the trans-anti dimer (113) in 51% yield. This material was accompanied by much smaller quantities of other dimeric species. Vari-... 

Intramolecular photodimerization of 2-pyridones provides a series of primary photoproducts, the structures of which were a function of the chain length comecting the two reactive centers." The initially formed dimers were characterized as being derived from a photochemically allowed [2 + 2] cycloaddition process in each case examined. A particularly interesting example from this study in terms of [4 + 4] cycloaddition chemistry is the conversion of dipyridone (114) into Ae net [4 + 4] dimer (115) via a facile thermal rearrangement. " Further irradiation of the [4 + 4] species (115) produced a second [2 + 2] adduct that was isomeric with the initially formed metastable species. 

As a model reaction for DNA damage by photodimerization of its thymine component, which finally causes a skin cancer, photodimerization reactions of 2-pyridone derivatives are interesting. Photoirradiation of a 1 2 inclusion complex of 66 a and 66 b with the host 67 gives the corresponding rac-cis-anti dimer 68 a and 68 b, respectively [37, 38], Photoirradiations of 66 c and 66 b in their inclusion complexes with 67 and 69, respectively, gives rac-trans-anti dimer 70 c and meso-cis-syn dimer 71 b, respectively [38, 39]. X-ray analysis of these inclusion complexes showed that 2-pyridone molecules are ordered at adequate positions for the corresponding photodimerization reactions in all cases [37-39]. 

An analogous photo-isomer of A -benzyloxycarbonylmethyl-2(l//)-pyridone has been prepared and various transformations of its cyclobutene ring have been explored. The photodimerization of A -methyl-2(l/ )-pyridone in water gives exclusively the products of [4 + 4] addition the yields of trans-anti- (31), trans-syn-, cis-anti-, and cw-jjfn-dimers were 51, 0.6, 11.2, and 6.8%, respectively. In non-aqueous solvents (ethanol or benzene), only a t/-dimers were formed. The thermal cycloaddition of dimethyl acetylenedicarboxylate to 2(l/f)-pyridones also occurs across positions 3 and 6. Reaction is favoured where steric buttressing of the methyl groups in the starting pyridone occurs for example, the cyclo-adduct (32) is... 

A study of the photodimerization of the pyridones (245) in a micellar environment has been reported.The results show that there is an alignment of the molecules in the micelle. The pyrazinone derivative (246) is photochemically unreactive when it is irradiated in solution at room temperature. However when it is irradiated in the solid state at room temperature a [4 + 4]-dimer (247) is formed. 

The photodimerization of 2-pyridones is a [4 -h 4]cycloaddition process, and it is reported that the length of the alkyl chain in A-(co-carboxyalkyl)-2-pyridones (63) governs the ratio of cis trans dimers when the process is carried out in micellar solution. 

Apart from this intramolecular photoelectrocyclization, an intermolecular photodimerization can also occur, e.g. l-methyl-2-pyridone is converted into 20 ... 

Both the [4+4] photodimerization reaction (4 — 6) and the isomerization to give Dewar-pyridone products (4 —> 5) tolerates substitution at every position (Table 1), but certain combinations of substituent and position are notable exceptions. The parent 2-pyridone 4a and N-methyl 4b are typical, yielding either 5 or 6 depending on the starting concentration. - A single additional allyl substituent, represented by l,n-dimethyl examples 4c-4f, all yield at least the [4+4] dimer. Even a /-butyl substituent at C4 (4g) which presents a possible steric impediment, is compatible with the dimerization reaction. Fusion of a cyclohexyl at C5/C6 (4k) or a cyclohexadienyl ring at C4/C5 (41) leads to acceptable yields of the photodimer 6. Chlorine substitution... 

Whereas a 4-alkoxy group (e.g., 12) prevents the photodimerization of 2-pyridones, it does not prevent a photo-[4+4] cycloaddition with other pyridones, such as 20, a typical 2-pyridone dimerization substrate. In this reaction of 2-pyridone mixtures, a simple 1 1 mixture of the two substrates (Figure 7, each 0.25 M in methanol) yields two major products. The yield of dimer 21 dominates that of cross product... 

Photodimerization of 2-pyridones has also been effected in other media. Nakamura reported the result of reactions in micelles and reverse micelles using pyridones bearing aliphatic chains on nitrogen. A high level of abnormal cis and head-to-head photoproducts were observed. ... 

Productive photodimerization and photoisomerization reactions of 2-pyridones in the solid state have been achieved by Toda and Tanaka using asymmetrical hosts (Figure 11). In many cases, the 2-pyridones isomerize to Dewar-pyridone products with complete enantiomeric purity. The symmetrical [4+4] products are achiral and are formed only in what one might anticipate to be the rare circumstances of a crystal structure with the appropriate orientation and distance between pyridones. Nevertheless, this has been accomplished with the two complexes depicted in Figure 11. 

Nakamura s isolation of head-to-head photoproducts from photodimerizations in water (Figure 10) suggested that symmetrical tethering of 2-pyridones at the 3 and 3 positions (head-to-head, 55, Figure 19) or 6 and 6 positions (tail-to-tail, 58, Figure 20), while reversing... 

During nearly forty years of study, the photocycloaddition of 2-pyri-dones has consistently exhibited versatile and reliable [4+4] reactivity. When dimerization is not desired, intramolecular reactions efficiently steer two pyridones to react. Alternatively, intermolecular cross reaction with an excess of another four-electron reactant can be extended to other heterocycles and to simple 1,3-dienes. It is perhaps surprising how few photoreactions of 2-pyridone fail to yield [4+4] products. Failure of the [4+4] reaction can result from a tethering unit that prevents the normal head-to-tail reactivity and introduces strain (Figures 14 and 22) or from steric hindrance caused by excessive substitution at the reacting carbons (Figure 23). A 4-alkoxy substrate shuts down the normally dominant photodimerization reaction and provides opportunities for other [4+-2] or [4+4] reactions (Figures 6 and 7). 

Three common themes for photodimerization reactions in solid organic inclusion compounds are as follows (i) [2- -2] photodimerization involving unsaturated chains (e.g., chal-cone), (ii) [2- -2] photodimerization involving unsaturated rings (e.g., coumarin), and (iii) [4-1-4] photodimerization involving unsaturated rings (e.g., 2-pyridone). We examine briefly each of these classes of reaction, highlighting specific examples in each case. 

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