Synthesis of New Enantiopure Bicyclic 1,2-Oxazines by Addition of Lithiated Methoxyallene to Chiral Cyclic Nitrones

A highly diastereoselective addition of lithiated methoxyallene 3 to chiral cyclic nitrones 1 and 2 provided N-hydroxy pyrrolidines 4 and 5, respectively, which cyclized to bicyclic 1,2-oxazines 6 and 7 by simple stirring in dilute CH2Cl2 solution. Storage of 4 in a more concentrated solution led to formation of a 60:40 mixture of 1,2-oxazine 6 and amine oxA highly diastereoselective addition of lithiated methoxyallene 3 to chiral cyclic nitrones 1 and 2 provided N-hydroxy pyrrolidines 4 and 5, respectively, which cyclized to bicyclic 1,2-oxazines 6 and 7 by simple stirring in dilute CH2Cl2 solution. Storage of 4 in a more concentrated solution led to formation of a 60:40 mixture of 1,2-oxazine 6 and amine oxide 8. Hydroboration of 7 furnished the hydroxy-substituted bicyclic 1,2-oxazine 9 with excellent diastereoselectivity. Hydrogenolysis of 6 provided the substituted pyrrolidine derivative 10.