Synthesis of α-Cyclopropyl-β-homoprolines

1-(2-Pyrrolidinyl)cyclopropanecarboxylic acids (alpha-cyclopropyl-beta-homoprolines) were prepared by 1,3-dipolar cycloadditions of cyclic nitrones onto bicyclopropylidene followed by trifluoroacetic acid induced thermal fragmentative rearrangement. With the use of enantiopure pyrroline N-oxides derived from easily available chiral pool molecules, beta-homoprolines were formed with high stereocontrol. The incorporation of one of these new cyclic beta-amino acids into a simple tripeptide was also evaluated. In particular, the sterically hindered nitrogen atom of the highly substituted pyrrolidine 30 was smoothly acylated through the intermediate formation of a mixed anhydride.