Asymmetric Redox-Annulation of Cyclic Amines

Cyclic amines such as 1,2,3,4-tetrahydroisoquinoline undergo regiodivergent annulation reactions with 4-nitrobutyraldehydes. These redox-neutral transformations enable the asymmetric synthesis of highly substituted polycyclic ring systems in just two steps from commercial materials. The utility of this process is illustrated in a rapid synthesis of (−)-protoemetinol. Computational studies provide mechanistic insights and implicate the elimination of acetic acid from an ammonium nitronate intermediate as the rate-determining step.诸如1,2,3,4-四氢异喹啉（1,2,3,4-tetrahydroisoquinoline）的环胺（cyclic amines）可与4-硝基丁醛（4-nitrobutyraldehydes）发生区域发散型环化反应（regiodivergent annulation reactions）。这类氧化还原中性（redox-neutral）的转化反应仅需两步即可从商用原料出发，实现高度取代多环环系的不对称合成。该方法的实用性可通过(−)-原伊波蒂宁醇（(−)-protoemetinol）的快速合成得以验证。计算化学研究揭示了该反应的机理，并证实铵硝酸盐中间体（ammonium nitronate intermediate）消除乙酸的步骤为反应的决速步（rate-determining step）。