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

Five 1-oxo-2,8-disubstituted-2,5,8-triaza-1 lambda(5)-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.