Photocycloaddition, , of 2-pyridones

S. M. Sieburth in Advances in Gycloaddition. The Inter- and Intra-Molecular [4+4]-Photocycloaddition of 2-Pyridones and Its Applications to Natural Product Synthesis , M. Harmata, Ed. Jai Press, Greenwich, CT, 1999, vol. 5, p. 85. 

A phase-selective photochemical reaction of 2-pyridones is observed. Irradiation of 225 in benzene gives mainly rearrangement products 226, whereas, in the solid state, [4+4] photocycloaddition to the photodimer 227 occurred in quantitative yield (Scheme 39) <20040L683>. The stereochemistry of the photodimer was exclusively the trans- /+configuration, as shown. This is presumably due to Jt-rt-stacking and dipole-dipole interactions between the pyridones. Intermolecular photocycloaddition of 2-pyridone mixtures can be selective and lead to useful quantities of [4+4] cycloaddition cross-products <1999JOC950>. 

CONTENTS The Synthesis of Seven-Membered-Rings General Strategies and the Design and Development of a New Class of Cycloaddition Reactions, Paul A. Wender and Jennifer A. Love. Recent Advances in Diels -Alder Cycloadditions of 2-Pyrones, Benjamin T. Woodard and Gary H. Posner. The Inter- and Intramolecular [4 + 4] Photocycloaddition of 2-Pyridones and Its Application to Natural Product Synthesis, Scott McN. Sieburth. 3 + 4 Annulations Between Rhodi- J s... 

Sieburth S McN. The inter- and intramolecular [4+4] photocycloaddition of 2-pyridones and its application to natural product synthesis. In Advances of Cycloaddition. Harmata M, ed. Greenwich, CT JAI, 1999 85-118. 

Recently, many investigations have been carried out on the [4 + 4] photocycloaddition of 2-pyridones and its application to organic synthesis. Although the studied reactions involved only racemic materials, high diastereoselectivities have been obtained with chiral substrates. This makes this type of cycloaddition very promising for asymmetric synthesis [93]. 

THE INTER- AND INTRAMOLECULAR [4+4] PHOTOCYCLOADDITION OF 2-PYRIDONES AND ITS APPLICATION TO NATURAL PRODUCT SYNTHESIS... 

Intramolecular [4-1-4]-photocycloaddition of 2-pyridones is accommodated with appropriate tether length and points of attachment (Scheme 5). When the tether is linked at the 3- and 6 - positions (45 and 49), it reinforces the preferred head-to-tail cycloaddition. With a three-atom chain, the cycloaddition of 45 yields a 2 1 mixture of trans- and cis-isomers, similar to the intermolecular reaction. A tether alcohol 45a has little effect on the formation of stereogenic centers during the cycloaddition and yields two diastereomers for both 46 and 47, epimeric at the alcohol carbon. Protection of the alcohol as the sterically demanding t-butyldimethylsilyl (TBS) ether (45h) leads to only 46 and 47. 

SCHEME 9 Photocycloadditions of 2-pyridones with other aromaticsd " ... 

Sieburth, S. McN. and Siegel, B., Tether-enforced reversal of regioselectivity head-to-head [4 -I-4]-photocycloaddition of 2-pyridones,/. Chem. Soc., Chem. Commun., 2249-2250, 1996. 

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]. 

Photo-[4+4] cycloaddition of 2-pyridone is not restricted to reaction with other pyridones. Sato, Ikeda, and Kanaoka found that cyclic and acyclic-1,3-dienes photoreact with 2-pyridones (Figure 8), ° reactions similar to the [4+4] photocycloaddition of 1,3-dienes with other aromatic molecules. Cyclopentadiene is abetter substrate than cyclohexadiene, as it is for the Diels-Alder reaction. A mixture of trans (24) and cis (25) isomers is formed in all cases. Use of acyclic... 

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). 

The photocycloadditions of 2,3-dimethyl-l,3-diene with 4-(alk-l-ynyl)-substituted coumarins (5) produced a mixture of 4 + 2- and 4 + 4-cycloadducts (6) and (7), respectively. However, the corresponding thiocoumarins (8) yielded a single 4 + 2-cycloadduct (9) (Scheme 2)." The intramolecular photocycloadditions (>290nm) of 1,3-enynes with 2-pyridone yielded 2 + 2- and 4 + 4-cycloadducts. The Rh(I)-catalysed formal 5+l-/2 + 2 + 2-cycloaddition of 1-yne-vinylcyclopropanes (10) with two carbon monoxide units produced multifunctional angular tricyclic 5/5/6 compounds (11) in a one-step mechanism (Scheme 3). ... 

Maturi MM, Bach T (2014) Enantioselective catalysis of the intermolecular [2+2] photocycloaddition between 2-pyridones and acetylenedicarboxylates. Angew Chem Int Ed 53 7661-7664... 

Sieburth, S. McN. and Lin, C.-H., Stereocontrol of 2-pyridone [4-1-4]-photocycloaddition a thermal-photochemical cycle to produce exclusively trans cycloadducts, /. Org. Chem., 59, 3597-3599, 1994. 

Nagano, X, Hirobe, M., and Okamoto, X, [4Jls -I- 47ts]-Photocycloadditions of 2-methyl-s-triaz-olo[l,5-a]pyridines to pyridones, Tetrahedron Lett., 3891-3894, 1977. 

Suishu, T, Tsuru, S., Shimo, T, and Somekawa, K., Singlet and triplet photocycloaddition reactions of 2-pyridones with propenoate and 2,4-pentadienoates and the frontier molecular orbital analysis, J. Heterocycl. Chem., 34, 1005-1011,1997. 

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). 

An intramolecular [4+4] photocycloaddition of a 2-pyridone with a furan ring yields the complex 1,5-cyclooctadiene 231 <20060L3367>. The proposed transition state conformation leading to the realized (and desired) f vsy -product is shown (Equation 110). The isopropyl group on the cyclopentane of the pyridone demonstrated stereocontrol and the... 

The photoaddition of methyl acrylate to pyridones (49) gave the three [2 + 2] cycloaddition products (50), (51), and (52).Similar observations have been reported previously.A patent has been lodged which deals with the photoad-dition of alkenes (RCH=CH2 R = H, CN, or MeC02CH2) to the pyridones (53) to yield the adducts (54) and (55). The photocycloaddition of vinyl acetate to the pyridinones (56) affords the head-to-tail adducts (57) preferentially. ... 

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