5,6-Dihydro-4-pyridones (3a-3c) undergo photochemical [2 + 2]-cycloaddition with olefins activated by an electron withdrawing group. Alkyl substituted double bonds could only be brought to react in the intramolecular cases 3d and 3e

Guerry, Philippe

Neier, Reinhard

CHIMIA International Journal for Chemistry

English

Philippe Guerry

Reinhard Neier

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341CHIMIA 41 (1987) Nr. 10 (October)FORSCHUNGPhotochemical Cycloadditions to5,6-Dihydro-4-pyridones**Philippe Guerry and Reinhard Neier** Correspondence; Dr, R. Neier Institut für Organische Chemie Universität Fribourg Pérolles, CH 1700 Fribourg** Financial support of this work by the Swiss National Science Foundation (Project No 2.840-0.85) is grate­fully acknowledged.Abstract: 5,6-Dihydro-4-pyridones (3a-3c) undergo photochemical [2 + 2]-cycloaddi- tion with olefins activated by an electron withdrawing group. Alkyl substituted double bonds could only be brought to react in the intramolecular cases 3d and 3e.The [2 + 2]-cycloaddition has become a popular photochemical reaction for appli­cation in synthetic projects1'1. In contrast to the cyclopentenones and cyclohexenones the corresponding aza-substituted systems have been very scarcely investigated121. Most of the reports dealing with vinylo- gous amides have concentrated on the photochemistry of uracil, thymine131, and derivatives of these bases141. There have been only a few reports dealing with the photochemistry of vinylogous amides as such151.In general the influence of substituents on photochemical reactions is much less predictable than for thermally induced cy­cloadditions161. The lower homologues of the 5,6-dihydro-4-pyridones the 4-pyrro- lin-3-ones have been studied121. No [2 + 2]- cycloaddition could be observed. In the presence of aliphatic ketones a photo­chemical aldol addition, probably induced by an electron transfer, occurred. The goal of our study was therefore to determine if 4-pyridones and the corresponding 5,6- dihydro-4-pyridones can be used for pho­tochemical cycloaddition reactions. In agreement with earlier reports171 neither 4- pyridone (1) nor the l-alkyl-4-pyridones 2a-2c could be brought to react with a number of different olefins under a variety of reaction conditions. Even for the intra­molecular cases 2d, 2e no transformation could be observed.In order to check whether the 5,6-di- hydro-4-pyridones could be used more successfully for photochemical cycloaddi­tion reactions, we needed a series of differ­ently substituted A-alkyl-5,6-dihydro-4- pyridones 3a-3e. The starting materials for these experiments were easily obtained from 4-pyridone (1) via the sequence: sily-lation, A'-alkylation, and reduction18,91 (Scheme 1). Three different reagents were used for the reduction of the aromatic precursors: a) Birch reduction17 81, b) RED- Al181, or c) triethoxy lithium aluminium hy­dride (TELAH)191. The reduction with TE- LAH had only been described on a small scale. The formation of the reagent was very slow when large quantities were used. Long reaction times (12 hours instead of 1 hour) or very efficient mixing (ultrasonic irradiation) was necessary to obtain a re­agent, which could be used reproducibly for the reduction of the A-alkyl-4-pyrido- nes.Scheme 1a) (CH3)3SiCl, N(C2H5)3b) R-XScheme 2R3PyrexOn irradiation the cycloaddition of the 7V-alkyl-5,6-dihydro-4-pyridones with Z- substituted olefins161 occurred readily to provide the bicyclic products 4 6 as mixtu­res of diastereomers in good yield (Scheme 2). In the case of a monosubstituted olefin like acrylonitrile mixtures of diastereomers and regioisomers were obtained. The sepa­ration of these mixtures was difficult. In some cases, e.g. 5, one of the isomers was unstable during chromatography against retro-cycloaddition. Even if after irradia­tion the raw material contained no starting material (checked by 'H-NMR and TLC) up to 30% dihydropyridone 3c and di-methyl fumarate could be isolated after chromatography on silica gel at room tem­perature. The only isolation procedure which allowed to separate the mixtures without losing most of the material wasflash chromatography1101 at low tempera­ture (-20 °C).For the cycloaddition of dimethyl male­ate with 3a three different diastereomers could be isolated. A tentative assignment of the relative configuration based on H-H couplings and 13C shifts showed that in two of the products the ester groups were in trans positions to each other. This result shows that either during or before the photochemical cycloaddition an isome­rization has to take place. Tetracyanoethy­lene was the only olefin studied, which re­acted not in a [2 + 2]-manner but via an addition-elimination process (Scheme 3). The product of the reaction was coloured2 3a;R=CH3 d;R= (CH2)2CH=CH2 bR=CH2C6H5 e.R= (CH2)3CH=CH2 C:R= CH(CbH6)24:R=CH3 z',z2= cooch3 5^R = CH2C6Hb z',z2=cooch3 6; R= CH(C6Hs)2 Z’,Z2 = COOCH3Scheme 3o3 b3 c7:R = CH2C6H58:R = CHtCgHgbFORSCHUNG 342CHIMIA 41 (1987) Nr. 10 (October)due to the extended chromophore (absorp­tion maximum at A = 422 nm).The only cases where the photochemical cycloaddition could be observed with non­activated double bonds, were the intramo­lecular reactions of 3d and 3e (Scheme 4). In both cases good yields of tricyclic pro­ducts could be isolated.Scheme 43 d n = 23e: n= 3hvI pyrexCH3CN9; n = 210 n =3Experimental:13C-NMR spectra: Bruker AM 360; if not mentio­ned CDC13 was used as solvent and TMS as standard. - MS: VG-7070 E. The olefins were commercial pro­ducts. The synthesis of the .V-alkylated 4-pyridones 2a-2e and of the 5,6-dihydro-4-pyridones has been de­scribed®.Typical Procedure for the Photochemical Cycloaddi­tion of 5,6-Dihydro-4-pyridones with Olefins (reaction of 3a with dimethyl maleate): 650 mg (5.8 mmol) 3a and 1.00 g (6.9 mmol, 1.2 equiv.) of dimethyl maleate in 120 mL nitrogen-degazed acetone were irradiated for 3 h by filtering the light of a 125 W mercury lamp through a pyrex filter. The solvent was evaporated in vacuum. The residue was flash-chromatographed'101 at —20 °C with ethyl acetate (cf. Table 1).Received: September 3, 1987 [FC 117][1] a) H. Meier, in Houben- Weyl: Methoden der Orga­nischen Chemie, Noï.4/5b, Thieme, Stuttgart (1975), p.924; b) S.W. Baldwin, Org. Photochem. 5 (1981) 123; c) A. C. Weedon, in W. M. Horspool (Ed.): Synthetic Organic Photochemistry, Plenum, New York (1984), p. 61; d) P. A. Wender, in J. D. Coyle (Ed.): Photochemistry in Organic Synthesis, Spec. Publ. R. Soc. Chem., London (1986), p. 163.[2] M. Beyer, R. Ghaffari-Tabrizi, M. Jung, P. Mar­garetha, Helv. Chim. Acta 67 (1984) 1535.[3] D.G. Whitten, in O. Buchardt (Ed.): Photochem­istry of Heterocyclic Compounds, Wiley, New York (1976), p.558.[4] a) J. S. Swenton, J. A. Hyatt, J. M. Lisy, J. Clardy, J. Am. Chem. Soc. 96 (1974) 4885; b) A. J. Wexler, J.A. Hyatt, P.W. Raynolds, C. Cottrell, J,S. Swenton, ibid. 100 (1978) 512; c) B.A. Pearlman, ibid. 101 (1979) 6398, 6404; d) V.V. Kaminski, R. N. Camber, A. J. Wexler, J. S. Swenton, J. Org. Chem. 48 (1983) 2337.[5] a) K. Wiesner, I. Irvosky, M. Fischman, C.A.J. Williams, Tetrahedron Lett. 8 (1967) 1523; b) Y. Tamura, H. Ishibashi, M. Hirai, Y. Kita, M. Ikeda, J. Org. Chem. 40 (1975) 2702; c) F.M. Schell, P.M. Cook, S.W. Hawkinson, R.E. Cas­sady, W. E. Thiessen, ibid. 44 (1979) 1380; d) T. S. Cameron, R. E. Cordes, B.M. Pinto, W. A. Sza- rek, Can. J. Chem. 59 (1981) 3136; e) C.S. Swin­dell, S.J. deSolms, J.P. Springer, Tetrahedron Lett. 25 (1984) 3797.[6] I. Fleming: Frontier Orbitals and Organic Chemi­cal Reactions, Wiley, New York (1976).[7] a) N. Ishibe, S. Yutaka, J. Org. Chem. 43 (1978) 2138; b) N. Ishibe, S. Yutaka, J. Masui, N. Ihda, ibid. 43 (1978) 2144.[8] P. Guerry, R. Neier. Synthesis (1984) 485.[9] Y. Tamura, M. Kumimato, T. Masui, M. Tera­shima, Chem. Ind. (1972) 168.[10] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 43 (1978)2923.Table 1. Cycloadducts 4-10.Product3) Irradiation time [h] (solvent)Yield [%] (solvent for chromatography)m.p. [°C] 13C-NMRb) MS (70 eV)ô m/z (rel. int. %)44a3 (acetone) 60 (ethyl acetate) 18 oil 207.3 (s, C(5)); 172.8, 170.4 (2s, 2COOCH3); 61.3 (d, C(l)); 255 (2), 111 (100)4b 27 oil52.3, 51.9 (2q, 2H3CO); 51.4 (t, C(3)); 44.9 (d, C(7) or C(8));44.5 (d, C(8) or C(7)); 43.2 (q, CH3-N); 40.3 (d, C(6)); 39.1 (t, C(4))208.2 (s, C(5)); 172.0, 171.3 (2s, 2COOCH3); 62.3 (d, C(l)); . 255 (2), 113 (100)4c 15 oil52.2, 51.9 (2q, 2H3CO); 49.7 (t. C(3)); 45.4 (d, C(7) or C(8));42.5 (d, C(8) or C(7)); 41.2 (q, CH3-N); 40.4 (t, C(4)); 40.1 (d, C(6))270.1 (s, C(5)); 172.7, 171.3 (2s, 2COOCH3); 60.7 (d, C(l)); 255 (3), 111 (100)5e) 4 (acetonitrile) 66 oil52.2, 52.1 (2s, H3CO); 47.8 (t, C(3)); 45.9 (d, C(7) or C(8));41.1 (q, CH3-N); 40.9 (t, C(4)); 40.0 (d, C(7) or C(8)); 38.6 (d, C(6))5a(ether: hexane: dichloromethane =5:4:1)34 115-117 207.4 (s,C(5)); 172.7, 170.3 (2s, 2COOCH3) 137.7 (s, C(l) arom); 331 (3), 113 (100)6e) 2 (acetone) 60(dichloromethane/ hexane)oil128.4, 128.2 (2d, 4C arom); 127.1 (d, C(4)arom); 59.3 (d, C(l));58.8 (t, CH2-Arom); 52.3, 52.0 (2q, 2H3CO); 46.8 (t, C(3));45.2, 44.9 (2d, C(7) and C(8)); 40.1 (d, C(6)); 39.3 (t, C(4))6a(ether: dichloro­methane: hexane = 1:1:2)20 130-131 207.8 (s, C(5)); 172.0, 171.0 (2s, 2COOCH3); 142.0, 140.6 407 (11), 167 (100)7d) 2 (acetonitrile) 75(ether/hexane)175-176(2s, 2C(1) arom); 128.6, 128.5, 128.3, 127.6, 127.3 (6d, aromC);70.4 (d, CH (Arom)2); 56.7 (d, C(l)); 52.1, 51.9 (2q, 2CH3-O);46.4 (d, C(7) or C(8)); 43.1 (t, C(3)); 41.2 (t, C(4)); 40.9 (d, C(6));38.4 (d, C(8) or C(7))185.0 (s, C(4)); 158.7 (d, C(2)); 133.8, 133.4 (2s, C(l) arom and8e) 2 (acetonitrile)(ethyl acetate: hexane = 4:1)80(acetonitrile/ chloroform)195-196C(CN)2); 128.7, 128.3 (2d, arom C); 128.5 (d, C(4) arom);114.5, 114.0, 113.6 (3s, 3CN); 104.4 (s, C(3)); 75.8 (s, C(CN));60.8 (t, CH2-Ph); 46.0 (t, C(6)); 34.3 (t, C(5))185.5 (s, C(4)); 157.3 (d, C(2)); 136.6 (s, 2C(1) arom); 364 (1), 167 (100)9 1.5 (acetonitrile)(ether: hexane: ethanol = 10:9:1)56(acetone/ chloroform)oil136.0 (s, C(CN),); 130.0, 129.6 (2d, arom. C); 129.7 (d, 2C(4) arom);114.6, 114.5, 113.9 (3s, 3CN); 105.4 (s, C(3)); 79.9 (s, C(CN));74.7 (d, CH-Ph); 48.7 (t, C(6)); 35.6 (t, C(5))216.6 (s. C(2)); 62.2 (d, C(9)); 48.4, 45.9 (2t, C(4) and C(6)); 151 (13), 82 (100)10f) 5 (acetonitrile)(dichloromethane: methanol = 19:1) 48 oil41.8 (d, C(l)); 36.0 (d, C(8)); 32.3 (t, C(3)); 30.4 (t, C(10));26.9 (t, C(7))58.7 (d, C(10)); 50.7, 48.8 (2t, C(4) and C(6)); 43.1 (d, C(l)); 165 (25), 96 (100)(ether: hexane: dichloromethane = 6:3:1)39.1 (t, C(3)); 31.0 (t, C(ll)); 22.8, 22.3 (2t, C(7) and C(8))a) The cristalline products 5a, 6a, 7, and 8 gave satisfactory elemental analysis (C ± 0.10, H ± 0.15, N ± 0.10).b) The complex 'H-NMR spectra have been interpreted but for the sake of clarity they have been omitted.c) The oils 5 and 6 were mixtures of two diastereoisomers. In each case one of the isomers could be crystallized.d) The 13C-NMR spectrum has been measured in d6-DMSO.e) The 13C-NMR spectrum has been measured in d6-acetone.f) The signals for C(2) and C(9) could not be unequivocally identified.

Photochemical Cycloadditions to 5,6-Dihydro-4-pyridones

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Photochemical Cycloadditions to 5,6-Dihydro-4-pyridones

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