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：Rong, Hao-Jie; Yao, Jun-Jun; Li, Ji-Kun; Qu, Jin^*

来源：Journal of Organic Chemistry, 2017, 82(11): 5557-5565.

DOI：10.1021/acs.joc.7b00361

• ENANTIOSELECTIVE TOTAL-SYNTHESIS
• ANTIFUNGAL AGENT (+)-PREUSSIN
• O BOND FORMATION
• STEREOSELECTIVE-SYNTHESIS
• TERTIARY-AMINES
• CATALYZED OXIDATION
• SUBSTITUTED 1,4-BENZOQUINONES
• ELECTROORGANIC CHEMISTRY
• ASYMMETRIC-SYNTHESIS
• CONCISE SYNTHESIS

We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted pyrrolidines from pyrrolidine by two rounds of redox-triggered alpha-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 alpha-C-H bond's of alpha-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.

• 出版日期2017-6-2
• 单位南开大学