A New Route to Cross-Conjugated Bis(enamines) and an Unusual Reaction with DDQ

Abstract

In previous papers, we reported that thiazolidines derived from cysteine methyl ester and aldehydes react with silver carbonate and DBU; the reactions produce transient 1-substituted methyl 2-azadiene-3-carboxylates that act as dienes in the Diels-Alder reaction.1 When we apply the same procedure to the thiazolidines 1a-d we find that the products are isolable cross-conjugated bis(enamines) 3a-d, the more stable tautomers of the azadienes 2a-d (Scheme 1). This is a new versatile route to enamines of this type. The diester 3a is a known compound that has previously been prepared from methyl â-halo-R-aminopropionate hydrohalides by reaction with bases;2 compounds 3b-d are previously unknown. Other cross-conjugated bis(enamines) of this type have been produced by thermal rearrangement of vinylaziridines.3 These compounds undergo an interesting photocyclization to 3,4-dihydropyrroles that can be intercepted, as 1,3-dipoles, in cycloaddition reactions with alkenes and alkynes.2b,3,4 Compound 3a is also reported to react as an electrophile with hydrazines5 and with primary amines,6 giving hydrazones and imines of methyl pyruvate as products. In an attempt to cyclize the diester 3a directly to dimethyl pyrrole-2,5-dicarboxylate by using DDQ as an oxidant, a single product was isolated in high yield. Instead of the pyrrole, it proved to be an interesting 1:1 adduct of the diester and DDQ whose structure 4 was established for the compound by X-ray crystallography (Figure 1). The X-ray analysis clearly shows that the C9-C10N1-C2-C3-C4 and C4-C5-C6-C7-C8-C9 rings are fused cis around the common C4-C9 bond and are furthermore linked by the methylenic bridge C10-C11C5. The conformation of the two above-mentioned rings is intermediate between E1 envelope and H2 half-chair, as shown by the ring puckering parameters7 Q ) 0.662(4) A, θ ) 53.8(3)°, φ ) 13.9(4)° [C9-C10-N1-C2-C3C4], Q ) 0.630(4) A, θ ) 53.8(4)°, φ ) 8.2(5)° [C4-C5C6-C7-C8-C9]. The conformation of the bridging ring C4-C5-C11-C10-C9 is very close to T1 (twisted around the C4-C9 bond), as shown by the puckering parameters Q(2) ) 0.566(4) A, φ(2) ) 163.3(4)°. The H1 atom is shared in a bifurcated intramolecular hydrogen bond [N1-H1‚‚‚O1: 2.714(4) A; N1-H1‚‚‚O4: 2.677(5) A, sum of the valence angles around H1 ) 358.2°]. The methoxycarbonyl group attached to the sp2 C2 atom is almost coplanar with the plane defined by the C10-N1-C2 atoms, whereas the other methoxycarbonyl group that is attached to the tetrahedric C10 atom is twisted by -16.9(5)° around the C10-C12 single bond. The H5 atom of the hydroxyl group is also involved in a bifurcated † Departamento de Quimica. ‡ Departamento de Fisica. (1) (a) Gilchrist, T. L.; Rocha Gonsalves, A. M. d’A.; Pinho e Melo, T. M. V. D. Tetrahedron 1994, 50, 13709-13724. (b) Pinho e Melo, T. M. V. D.; Fausto, R.; Rocha Gonsalves, A. M. d’A.; Gilchrist, T. L. J. Org. Chem. 1998, 63, 5350-5355. (2) (a) Mitsuhashi, K. Asahi Garasu Kogyo Gijutsu Shoreikai Kenkyu Hokoku 1973, 23, 355-362; Chem. Abstr. 1975, 82, 86591. (b) Zaima, T.; Matsunaga, Y.; Mitsuhashi, K. J. Heterocycl. Chem. 1983, 20, 1-4. (3) Gelas-Mialhe, Y.; Mabiala, G.; Vessiere, R. J. Org. Chem. 1987, 52, 5395-5400. (4) (a) Zaima, T.; Matsuno, C.; Matsunaga, Y.; Mitsuhashi, K. J. Heterocycl. Chem. 1984, 21, 445-448. (b) Zaima, T.; Matsuno, C.; Matsunaga, Y.; Mitsuhashi, K. Nippon Kagaku Kaishi 1984, 12931298; Chem. Abstr. 1984, 101, 230340. (5) Zaima, T.; Mitsuhashi, K. Nippon Kagaku Kaishi 1979, 901905; Chem. Abstr. 1979, 91, 140303. (6) Zaima, T.; Matsuno, C.; Mitsuhashi, K. Nippon Kagaku Kaishi 1983, 152-156; Chem. Abstr. 1983, 98, 179141. (7) Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354. Figure 1. X-ray structure of compound 4.