Asymmetric [3 + 2] Cycloaddition of 2,2′-Diester Aziridines To Synthesize Pyrrolidine Derivatives

A highly diastereo- and enantioselective [3 + 2] cycloaddition of 2,2′-diester aziridines with 3,4-dihydropyran derivatives and acyclic enol ethers has been established. Various optically active octahydropyrano[2,3-c]pyrrole and 3-methoxypyrrolidine derivatives were generated in moderate to high yields (up to 94%) and good stereoselectivities (>19:1 dr, up to 95.5:4.5 er). The methodology was also applied in the highly diastereoselective synthesis of d-galactal derivatives. The absolute configuration of the octahydropyrano[2,3-c]pyrroles showed that the reactions using 3,4-dihydropyran and 6-alkyl-substituted ones as substrates gave reversed diastereoselection in the final cyclization step.