Benzoyl-3-[(E)-cyanomethylidene]-5-(methoxycarbonyl)pyrrolidin-2-one (5) was prepared in four steps from l-pyroglutamic acid (1). 1,3-Dipolar cycloadditions of diazomethane ( 6) and 2,4,6-trimethoxybenzonitrile oxide (7) gave substituted 1,2,7-triazaspiro[4.4]non-1-en-6-one 12 and 1-oxa-2,7-diazaspiro [4,4]non-1en-6-one 13 in 38 and 20% de, respectively. On the other hand, reaction of 5 with N-phenylbenzonitrile imines 8 and 9, generated in situ from the corresponding hydrazonoyl chlorides 10 and 11, respectively, and Et 3 N, furnished racemic pyrrolo[3,4-c]pyrazoles 14 and 15 in 61 and 56% de, respectively. Cycloaddition of nitrile oxide 7, when performed in the presence of Et 3 N, led to pyrrolo [3,4-d]isoxazole 16 in 85% de.
1 ) For the preparation of compound 2, see [6]; for the preparation of (S)-5-(alkoxycarbonyl)-3-[(dimethylamino)methylidene]pyrrolidin-2-ones, see [7].
KCN in AcOH to give (5S)-1-benzoyl-3-[(E)-cyanomethylidene]-5-(methoxycarbonyl)pyrrolidin-2-one (5; Scheme 1). The configuration of the exocyclic CC bond in 4 and 5 was determined by NMR. Chemical shifts, coupling constants, and interatomic distances, determined by NOESY experiments, are in agreement with the proposed structure 2 ) (Fig. 1).
Cycloaddition reactions were performed with the following 1,3-dipoles: CH 2 N 2 (6) [9], 2,4,6-trimethoxybenzonitrile oxide (7) [10], N-phenylbenzonitrile imine 8, and Nphenyl-4-chlorobenzonitrile imine 9. Both compounds, 8 and 9, were generated by