Nucleophilic cleavage of 1-oxo-2,8-disubstituted-2,5,8-triaza-1λ⁵-phosphabicyclo[3.3.0]octanes: a new route to eight- and five-membered heterocyclic systems

Abstract

Five 1-oxo-2,8-disubstituted-2,5,8-triaza-1λ⁵-phosphabicyclo[3.3.0]octanes 1 have been prepared and the nucleophilic cleavage of one of their P–N bonds has been studied. The acid-catalyzed alcoholysis involves in each case the cleavage of the P–N(5) bond, yielding the eight-membered monocyclic diamides 2. In the base-catalyzed reaction, the N(2),N(8)-dialkyl substituted substrates 1 yielded the same products 2, while for the N(2),N(8)-diaryl derivatives the exclusive cleavage of the P–N(2) (or P–N(8)) bond was observed yielding the isomeric 1,3,2-diazaphospholidine products 3. Products 2 are stable as N(5) ammonium salts or N(5)-acyl derivatives, but as free bases they rearrange spontaneously to products 3 via the intramolecular N(5)→P nucleophilic attack accompanied with the P–N(2) (or P–N(8)) bond cleavage. The effect of the N(2)- and N(8)-substituents in 2 on the rate of the 2→3 rearrangement, as well as on the product distribution for the unsymmetrically disubstituted substrates has been investigated. The mechanism of the formation of products 3 via the rearrangement and via the direct 1→3 nucleophilic cleavage is discussed in terms of the reactivity of the attacking nucleophile, the electrophilicity of the phosphoryl center, and of the basicity of the departing amine in the P–N bond cleavage step.

References

1. H. Wan and T. A. Modro, Synthesis, 1996, 1227.
2. S. A. Bourne, Z. He, T. A. Modro and P. H. van Rooyen, Chem. Commun., 1999, 853.
3. X. Y. Mbianda, T. A. Modro and P. H. van Rooyen, Chem. Commun., 1998, 741.
4. J. Rahil and P. Haake, J. Am. Chem. Soc., 1981, 103, 1723 and references cited therein.
5. A. M. Modro, T. A. Modro, P. Bernatowicz, W. Schilf and L. Stefaniak, Magn. Reson. Chem., 1997, 35, 774.
6. W. von Philipsborn and R. Müller, Angew. Chem., Int. Ed. Engl., 1986, 25, 383.
7. M. J. P. Harger, J. Chem. Soc., Perkin Trans. 1, 1975, 514 See also: B. Krzyzanowska and W. J. Stec, Synthesis, 1982, 270.
8. Conformational Analysis of Medium-Sized Heterocycles, ed. R. S. Glass, VCH, New York, 1988, ch. 3.8.
9. R. K. Sharma and R. Vaidyanathaswamy, J. Org. Chem., 1982, 47, 1741.
10. D. E. C. Corbridge, Phosphorus. An Outline of its Chemistry, Biochemistry and Technology, Elsevier, Amsterdam, 1990, p. 50.
11. M. P. du Plessis, T. A. Modro and L. R. Nassimbeni, J. Org. Chem., 1982, 47, 2313.
12. D. W. J. Cruickshank, Acta Crystallogr., 1964, 17, 671.
13. H. B. Bürgi, Angew. Chem., Int. Ed. Engl., 1975, 14, 460.
14. S. Bauermeister, A. M. Modro, T. A. Modro and A. Zwierzak, Can. J. Chem., 1991, 69, 811.
15. Unpublished result from this laboratory.