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.

本研究成功建立了2,2'-二酯基氮丙啶与3,4-二氢吡喃衍生物及非环状烯醇醚之间的高非对映选择性与对映选择性[3+2]环加成反应。该反应可生成多种具有光学活性的八氢吡喃并[2,3-c]吡咯及3-甲氧基吡咯烷衍生物，产物收率中等至优异（最高达94%），立体选择性优异（非对映选择性比例>19:1，对映选择性比例最高可达95.5:4.5）。此外，该合成方法还可应用于d-半乳糖烯衍生物的高非对映选择性合成。对八氢吡喃并[2,3-c]吡咯的绝对构型分析表明，以3,4-二氢吡喃及6-烷基取代的3,4-二氢吡喃为底物时，最终环化步骤的非对映选择性发生反转。