Synthesis of Phosphoproline Derivatives with an Octahydroisoindole Structure

The synthesis of two phosphoproline analogues possessing an octahydroisoindole structure is described for the first time. The new a-aminophosphonic acids can be viewed as the result of fusing a cyclohexane ring to the [c] face of the five-membered pyrrolidine unit. The junction of the bicyclic system is cis in both compounds, but they differ in the relative stereochemistry of the cyclohexane and phosphonate moieties. Using phthalimide as a common precursor and following stereodivergent routes, the target a-aminophosphonic acids, (1R*, 3aR*, 7aS*)- and (1S*, 3aR*, 7aS*)-octahydroisoindole-1-phosphonic acids, have been prepared with complete stereocontrol and in high overall yields. The structurally related isoindoline-1-phosphonic acid, containing a benzene ring [c]-fused to pyrrolidine, has also been obtained.