Pyridones tethered

As mentioned in Section 10.1.2, Padwa and co-workers (40,41) employed the Pummerer reaction to generate and trap isomtinchnones. This group (190,191) has now adapted the intramolecular version of this tactic to the synthesis of several alkaloids of the pyridine, quinolizidine, and clavine classes. In each case, a 2-pyridone serves as the keystone intermediate. For example, Kuethe and Padwa (190) employed this Pummerer reaction of imidosulfoxides that contain tethered iz-bonds in a formal synthesis of the frog alkaloid ( )-pumiliotoxin C. They also used this methodology to synthesize the azafluorenone alkaloid onychine (295) (Scheme 10.42) (191). Generation of the thionium ion 291 under standard... 

Acylium salts undergo aza-Nazarov cyclization under similar conditions to form varied five-membered IV-heterocycles.339 Aryl-tethered pyrrolinones and dihydro-pyridones [Eq. (5.132)] were induced to cyclize with triflic acid to afford tri- and tetracyclic products.340... 

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,... 

When 2-pyridones are symmetrically tethered through nitrogen with a two-carbon chain (95) (Sch. 20), benzophenone-sensitized cycloaddition leads to the [4+2] adduct 96 in good yield. Other tether lengths largely lead to [2+2] products (see Sch. 43 for a [4+4] adduct using a four-carbon tether) [63]. 

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]. 

Several accounts of (4ti + 4tt) intramolecular photodimerisation of tethered pyridones have appeared in recent years and the product from (20), having five stereogenic centres, is reported to have application towards a synthesis of taxanes (Sieburth et al.). A number of examples of intramolecular (2ti + 2k) photocycloadditions involving pyrimidone units have been described within the year. The bichromophore (21) is reported to photoreact with chemo-, stereo- and regio-... 

PhotoreactifHis of Pyridones - Previously Sieburth and his colleagues have demonstrated that the photochemical cyclization of tethered pyridones such as... 

Photocatalysed 2k pins 2k cycloadditions between a pair of tethered d-pyridones can generate spec-tacnlarly complex rings systems easily, as shown. 

Allyltrimethylsilanes react with triplet excited 2,3-dicyano-5,6-dimethylpyra-zine to give diazatricyclooctenes (115), possibly via intermediate (114) formed from ring-opening of an initially-formed [2+2]adduct. Intramolecular [2+2]-cycloaddition yields the pentacyclic compound (116) on irradiation of the corresponding tethered enantiopure bis-2,3-dihydro-4-pyridone. Addition of ethylene to the corresponding a,P-unsaturated-y-lactams in acetone yields (117) and (118) as the major photoproducts. ... 

Irradiation of A -methyl-2-pyridone in aqueous solution produces a mixture of regio- and stereoisomeric dimers such as the one shown above " such 47t plus 47t photo-cycloadditions of 2-pyridones" have also been conducted between two tethered pyridones as illustrated below" and between a side-chain 1,3-diene and a 2-pyridone. ... 

Photocatalysed lir plus lir cycloadditions between a pair of tethered 4-pyridones as shown below, can also generate complex rings systems spectacularly easily. Photocatalysed plus cycloaddition between the 5,6-bond of 2-pyridones and an alkene tethered to nitrogen are also known. 

C. Head-to-Head and Tail-to-Tail Tethered 2-Pyridones. . . 102... 

Loyola University of Chicago), found that Hammond s estimate is accurate, and the fluorescent lifetime of 2 and 40 ate 180 ps. Triplet-sensitized reactions of 2-pyridones have not been extensively studied. However Sharp and Hammond found no evidence for 2-pyri-done photoproducts when xanthone is used as a photosensitizer. Using tethered pyridones, Nakamura found [2+2] and [4+2] cycloaddition products with benzophenone sensitization (see Figure 14). This is consistent with 2-pyrone photochemistry,but the generality of these results await further experimentation. 

Photo-[2+2] reactions of 2-pyridones have been studied, particularly the intramolecular versions. Intermolecular reactions, unbiased by the constraints of tethering are less well studied, in part because of the dominance of the [4+4] cycloaddition. In one simple system, however, acrylonitrile reacts with 2-pyridone to form two products 16 and 17 (Figure 5). The latter has been extensively characterized by both X-ray and NMR techniques. ... 

Intramolecular tethering of 2-pyridones at the 3- and 6 -positions, as shown in Figure 15, reinforces the normal head-to-tail [4+4]... 

Figure 15. Intramolecu lar photocycloaddition of a three-atom tethered bis-2-pyridone and the thermal/photochemical transformation of cis [4+4] product 42 into trans product 41...

Whereas a three atom tether yields a mixture of cis and tmns isomers, a four-atom chain connecting the pyridones is highly trans-selective (Figure 17). One of the first substrates of this type is 49, irradiation of which gives a mixture of two products 50 that can be oxidized, after hydrogenation of the alkenes, to the same ketone. The two products that differ only in the orientation of the hydroxyl group, are formed in a ratio of 3 2 (configuration undetermined). 

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... 

Figure 22. A four-carbon tether symmetrically attached to 2-pyridones does not allow useful [4+4] cycloaddition. ...

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). 

---