Synthesis of phosphoproline derivatives with an octahydroisoindole structure

摘要

The synthesis of two phosphoproline analogues possessing an octahydroisoindole structure is described for the first time. The new α-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 α-aminophosphonic acids, (1R*,3aR*,7aS*)-and (1S*,3aR*,7aS*)-octahydroisoindole-1-phosphonic acids, have been prepared with completestereocontrol and in high overall yields. The structurally related isoindoline-1-phosphonic acid, containing a benzene ring [c]-fused to pyrrolidine, has also been obtained.