Aza-annulation of enaminones with itaconic anhydride: kinetic preference for exocyclic enamide products

Abstract

Enaminones react with itaconic anhydride in methylene chloride at room temperature to give exocyclic enamides as the major products. These can be readily equilibrated to the thermodynamically more stable endocyclic enamides. In substrates where the exocyclic isomer could not be formed only intractable materials were produced from this reaction. An intermediate in this two step process was detected and identified by proton and ¹³C NMR spectroscopy. In two cases chiral enaminones were employed and the relative stereochemistry at the new chiral centre in the product was established by a crystal structure of compound 27.

References

1. For a review, see J. d'Angelo, D. Desmaele, F. Dumas and A. Guingant, Tetrahedron: Asymmetry, 1992, 3, 459 For recent examples, see J. C. F. Alves, A. B. C. Simas, P. R. R. Costa and J. d'Angelo, Tetrahedron: Asymmetry, 1997, 8, 1963; D. Desmaele, K. Mekouar and J. d'Angelo, J. Org. Chem., 1997, 62, 3890; J. d'Angelo, C. Cave, D. Desmaele, A. Gassama, C. Thominiaux and C. Riche, Heterocycles, 1998, 37, 725.
2. For a review, see J. R. Stille and Nancy S. Barta, Stud. Nat. Prod. Chem., 1996, 18, 315 For recent examples, see K. Paulvannan and J. R. Stille, J. Org. Chem., 1992, 57, 5319; K. Paulvannan and J. R. Stille, J. Org. Chem., 1994, 59, 1613; G. R. Cook, L. G. Beholz and J. R. Stille, J. Org. Chem., 1994, 59, 3575; L. G. Beholz, P. Benovsky, D. L. Ward, N. S. Barta and J. R. Stille, J. Org. Chem., 1997, 62, 1033; A. Guarna, C. Belle, F. Machetti, F. Occhiato, E. G. Payne, C. Cassiani, G. Danza, A. Debellis, S. Dini, A. Marrucci and K. Serio, J. Med. Chem., 1997, 40, 1112; P. Benovsky, G. A. Stephenson and J. R. Stille, J. Am. Chem. Soc., 1998, 120, 2493.
3. L. Ambroise, D. Desmaele and J. d'Angelo, Tetrahedron Lett., 1994, 35, 9705.
4. N. S. Barta, A. Brode and J. R. Stille, J. Am. Chem. Soc., 1994, 116, 6201.
5. H. Matsuyama, Y. Ebisawa, M. Kobayashi and N. Kamigata, Heterocycles, 1989, 29, 449.
6. P. W. Hickmott and G. Sheppard, J. Chem. Soc. C, 1971, 2112; A. Sevin, J. Tortajada and M. Pfau, J. Org. Chem., 1986, 51, 2671.
7. J. H. Robson and E. Marcus, Chem. Ind. (London), 1970, 1022; H. von Bobeneck, E. Brunner, H. Bunke, G. Metzner, R. Schmidt, E. Weil and J. Sonnenbichler, Liebigs. Ann. Chem., 1981, 410.
8. C. Cave, A. Gassama, J. Mahuteau, J. d'Angelo and C. Riche, Tetrahedron Lett., 1997, 38, 4773; J. d'Angelo, C. Cave and D. Desmaele, Isr. J. Chem., 1997, 37, 81.
9. F. G. Fang and S. J. Danishefsky, Tetrahedron Lett., 1989, 28, 3621; T. Nagasaka, H. Inque, M. Ichimura and F. Hamaguchi, Synthesis, 1982, 848.
10. F. Johnston, Chem. Rev., 1968, 68, 375; R. W. Hoffmann, Chem. Rev., 1989, 89, 1841.
11. C. Cave, V. Daley, J. d'Angelo and A. Guingant, Tetrahedron: Asymmetry, 1995, 6, 79.