Molecular Iodine-Mediated α-C–H Oxidation of Pyrrolidines to N,O-Acetals: Synthesis of (±)-Preussin by Late-Stage 2,5-Difunctionalizations of Pyrrolidine

作者：Hao‐Jie Rong, Junjun Yao, Jikun Li, Jin Qu · 发表于：The Journal of Organic Chemistry · 年份：2017 · DOI：10.1021/acs.joc.7b00361 · 被引用次数：28 · 研究领域：Catalytic C–H Functionalization Methods、Oxidative Organic Chemistry Reactions、Synthesis and Catalytic Reactions

We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted pyrrolidines from pyrrolidine by two rounds of redox-triggered α-C-H functionalization. Although this approach can be used to introduce substituents at the 2- and 5-positions, it is lengthy because the redox auxiliary must be removed and then reinstalled. Therefore, we sought to develop a method to oxidize 2-functionalized pyrrolidine to cyclic N,O-acetal which could then react with a nucleophile for introduction of the 5-substituent. In this work, we found that molecular iodine can mediate the preferential oxidation of secondary over tertiary α-C-H bonds of α-substituted pyrrolidines to form cyclic N,O-acetals, improving the step economy of our previously reported method. With this strategy, (±)-preussin and its C(3) epimer were synthesized from (±)-pyrrolidin-3-ol.