Asymmetric -Dipolar Cycloaddition Reactions: Synthesis of Highly Substituted Proline Derivatives

Article abstract of DOI:10.1021/jo00050a029

The asymmetric <1,3>-dipolar cycloaddition reactions of azomethine ylides derived from (5R,6S)-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one with various aldehydes and dimethyl maleate is described.The reactions prove to be highly endo-selective, installing three contiguous stereogenic centers in the newly formed five-membered ring with essentially complete stereochemical control.In the case of aldehydes higher than formaldehyde, a fourth stereogenic center is created; in most cases, poor stereoselectivity is observed at this center; the diastereomers formed in these cases can be separated by chromatography and separately converted into the amino acids.The bicyclic dipolar adducts can be cleaved with either catalytic hydrogenolysis or hydrolytic ring opening, esterification, and lead tetraacetate removal of the chiral auxiliary.