Asymmetric syntheses of 5- and 6-membered carbocyclic serine analogs via an intramolecular Strecker synthesis

Conformationally restricted analogs of serine possessing a 5- or 6-membered carbocyclic ring, 1 and 2, were synthesized in an optically active form in short steps. The syntheses were started with rac-1, 1-dimethoxy-2-cyclopentanol and rac-trans-1,2-cyclohexanediol, respectively. The key to the present syntheses was a diastereoselective construction of a chiral amino nitrile group onto the ketone group of 5 or 11. This was achieved by the use of an internal Strecker reaction to give optically pure amino nitriles 7a and 13a, respectively. In this reaction, the original chirality derived from phenylalanyl group was efficiently transplanted into both the ketone and α-hydroxyl groups via an imine-enamine equilibrium of the ketimine intermediate 6 or 12. Phenylalanyl moiety of the Strecker adducts was removed by oxidative and hydrolytic treatments of the amino nitriles to give the titled amino acids. Chirality 9:459–462, 1997.