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

5 years ago

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

Jin Qu, Ji-Kun Li, Jun-Jun Yao, Hao-Jie Rong

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.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00361

DOI: 10.1021/acs.joc.7b00361