[3 + 3]-Nucleophilic addition of acyclic enamino ketones to dimethyl 1-Aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates

We previously reported on the reaction of dimethyl 1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates with 3-arylamino-5,5-dimethylcyclohex-2-en-1ones which led to the formation of methyl 1,1′-diaryl4′-hydroxy-6,6-dimethyl-2,4,5′-trioxo-1,1′,2,4,5,5′,6,7octahydrospiro[indole-3,2′-pyrrole]-3′-carboxylates as a result of nucleophilic attack by the β-CH and amino groups of the cyclic enamine on C and ester carbonyl carbon atom on C in the dioxopyrrole, respectively [1, 2]. Reactions of dimethyl 1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates with acyclic enamino ketones have not been described so far. Compounds Ia and Ib reacted with an equimolar amount of 4-aminopent-3-en-2-one (IIa) or 3-amino-1phenylbut-2-en-1-one (IIb) in anhydrous benzene at room temperature (reaction time 2–8 h; until disappearance of the color typical of initial compound I) to give dimethyl 4-benzoyl-1-hydroxy-3-methyl-7-oxo-6phenyl-2,6-diazabicyclo[3.2.1]oct-3-ene-5,8-dicarboxylate (IIIa) and dimethyl 4-acetyl-6-(4-chlorophenyl)1-hydroxy-3-methyl-7-oxo-2,6-diazabicyclo[3.2.1]oct3-ene-5,8-dicarboxylate (IIIb) in good yield. Compounds III are likely to be formed via successive nucleophilic addition of the β-CH and amino groups in acyclic enamine II to the C and C carbon atoms, respectively, in the pyrrole ring of I. The described reaction is the first example of [3 + 3]-nucleophilic addition of acyclic enamines to monocyclic 1Hpyrrol-2,3-diones; it may be regarded as a convenient method of synthesis of 2,6-diazabicyclo[3.2.1]octane derivatives that are representatives of a difficultly accessible bridged heterocyclic system. Dimethyl 4-benzoyl-1-hydroxy-3-methyl-7-oxo6-phenyl-2,6-diazabicyclo[3.2.1]oct-3-ene-5,8-dicarboxylate (IIIa). A solution of 1.0 mmol of compound Ia and 1.0 mmol of IIa in 20 ml of anhydrous benzene was kept for 8 h at room temperature. The precipitate was filtered off and washed with ethyl acetate. Yield 76%, mp 154–156°C. IR spectrum, ν, cm: 3374 br (OH, NH); 1746, 1732 (C=O, ester); 1698 (C=O, 4-C=O). H NMR spectrum, δ, ppm: 1.54 s (3H, Me), 3.37 s (3H, OMe), 3.56 s (1H, 8-H), 3.65 s (3H, OMe), 7.22– 7.52 m (10H, Harom), 7.80 s (1H, NH), 8.43 s (1H, OH). Found, %: C 63.91; H 4.93; N 4.95. C24H22N2O7. Calculated, %: C 64.00; H 4.96; N 4.93. Dimethyl 4-acetyl-6-(4-chlorophenyl)-1-hydroxy3-methyl-7-oxo-2,6-diazabicyclo[3.2.1]oct-3-ene-5,8dicarboxylate (IIIb) was synthesized in a similar way.