基于电化学阴极还原策略的[1,2]-Wittig重排反应研究

有机电化学合成作为一种绿色、温和、高效的合成方法具有广阔的发展前景。目前对其的研究集中于阳极氧化反应，拓展一类基于碳负离子的阴极还原反应具有重要意义。传统[1,2]-Wittig重排反应需要使用烷基锂试剂脱去质子生成高活性alpha-烷氧基碳负离子，继而引发自由基重组过程得到醇氧负离子。苛刻的反应条件造成其收率低、底物范围受限且立体专一性不佳。本项目拟在电化学温和条件下对alpha-烷氧基NHPI酯进行分步还原，首先产生相应碳自由基，其被二次还原生成碳负离子，以引发[1,2]-Wittig重排反应。我们将全面优化电化学条件下该反应收率、底物范围及立体专一性，拓展氮杂[1,2]-Wittig重排类型，并进行该重排反应的不对称催化尝试。实现电化学[1,2]-Wittig重排反应不仅为合成具有光学活性的醇类及胺类化合物提供了有效方法，而且为探索电化学条件下高活性碳负离子的反应性能开辟了崭新道路。

Organic electrochemical synthesis has demonstrated broad applications in science and industry as a green, mild and efficient synthetic method. Recent progresses in this area mainly occurred in anodic oxidation reactions, further development in cathodic reduction reactions is highly desired. Therefore, exploring new reactivity of carbanion generated under electrochemical conditions will be essential for expanding cathodic reaction patterns. Traditional [1,2]-Wittig rearrangement requires excess organolithium base in order to form a highly reactive alpha-alkoxyl carbanion, which subsequently undergoes radical recombination to generate alcohol anion. Due to such harsh conditions, this reaction usually suffers from moderate yield, limited scope and unsatisfactory stereo-outcome. In this application, we propose to initiate [1,2]-Wittig rearrangement by an electrochemical sequential SET reduction process. An alpha-alkoxyl NHPI ester precursor will be converted into an alpha-alkoxyl radical by the first SET reduction, and then form a corresponding carbanion by the second reduction; this carbanion eventually triggers [1,2]-Wittig rearrangement. The mild electrochemical conditions enable us to carry out detailed optimization to improve the yield, scope and stereo-outcome of this rearrangement. Further endeavors include investigation on related aza-[1,2]-Wittig rearrangement and attempt to accomplish catalytic asymmetric [1,2]-Wittig rearrangement. Achieving electrochemical [1,2]-Wittig rearrangement will not only provide an efficient method to access enantiopure alcohols and amines, but also disclose a novel pathway to study carbanion reactivity under electrochemical conditions.