Regiospecific Alkene Aminofunctionalization via an Electrogenerated Dielectrophile
Regiospecific Alkene Aminofunctionalization via an Electrogenerated Dielectrophile
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DOI：
10.1021/jacs.3c01137
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发表时间：
2023-04-06
影响因子：
15
通讯作者：
Wickens, Zachary K.
中科院分区：
文献类型：
--
作者：
Holst, Dylan E.;Dorval, Celine;Wickens, Zachary K.
快速增加分子复杂性的模块化策略已被证明具有巨大的合成价值。原则上，烯烃转化为介电亲电体提供了在烯烃上递送两种独特亲核试剂的机会。不幸的是，已知的亲电介质的选择性概况在很大程度上排除了这种看似简单的合成方法。在此，我们证明了通过烯烃和噻蒽的电解产生的双阳离子加合物相对于更常规的亲电介质具有独特的选择性。具体而言，这些物质与邻苯二甲酰亚胺盐进行单一且完美的区域选择性取代反应。这一观察结果为氨基官能化反应提供了一个有吸引力的新平台。作为一个说明性的例子，我们实施这种新的反应性范例，以解决一个长期的合成挑战：烯烃二胺化与两个不同的氮亲核试剂。对这一过程的机理的研究揭示了一个关键的烯基噻蒽鎓盐中间体，它控制了该过程的精细区域选择性，并突出了质子源在控制烯基锍盐亲电试剂反应性中的重要性。
Modular strategies to rapidly increase molecular complexity have proven immensely synthetically valuable. In principle, transformation of an alkene into a dielectrophile presents an opportunity to deliver two unique nucleophiles across an alkene. Unfortunately, the selectivity profiles of known dielectrophiles have largely precluded this deceptively simple synthetic approach. Herein, we demonstrate that dicationic adducts generated through electrolysis of alkenes and thianthrene possess a unique selectivity profile relative to more conventional dielectrophiles. Specifically, these species undergo a single and perfectly regioselective substitution reaction with phthalimide salts. This observation unlocks an appealing new platform for aminofunctionalization reactions. As an illustrative example, we implement this new reactivity paradigm to address a longstanding synthetic challenge: alkene diamination with two distinct nitrogen nucleophiles. Studies into the mechanism of this process reveal a key alkenyl thianthrenium salt intermediate that controls the exquisite regioselectivity of the process and highlight the importance of proton sources in controlling the reactivity of alkenyl sulfonium salt electrophiles.