Uncovering Synthetic Potential of Distonic Radical Cations

Distonic自由基阳离子，具有空间分离的自由基部分和阳离子 部分，具有很大的合成潜力，因为它们可以在两个 通过正交地将亲核试剂添加到阳离子部分并截取不同的位点， 自由基部分与自由基受体。然而，捕获双声子的双峰反应性， 自由基阳离子仍然难以捉摸，因为在获得前体方面的限制， 生产条件，并了解它们的反应性，以获得两者的正交控制 反应性部分。我们开发了环丙基-和环丁基-胺的开环， 一般的反应平台，以产生二阶自由基阳离子，但遇到许多挑战， 利用它们的双峰反应性。我们的核心假设是， 开放是可逆的，如何有效地扰动可逆性将是利用开放的关键。 双峰反应性我们确定了两种影响可逆性的策略：使用亲核试剂 和二阶自由基阳离子中阳离子部分的共振稳定。两个具体目标 基于这两种策略开发：1）二阶自由基阳离子的双官能化， 环丙基苯胺和环丁基苯胺; 2）环丙基苯胺和环丁基苯胺的二阶自由基阳离子的官能化， 螺环N，N缩氨基或N，O缩醛。如果能成功利用这种双峰反应性 为了实现二价离子自由基阳离子的双官能化，此类反应可能代表一种 合成化学家利用环烷基胺作为合成结构单元的新方法， 提供了一个指导原则，以发现更有用的方法，利用这些distonic自由基阳离子 在开环过程之外进行访问。这些转变符合一个新兴的主题 在有机合成中：通过碳- 或杂环。强键如碳-碳键的断裂通常用于制备纳米材料。 该方法能够使远程和未活化的碳官能化。

Distonic radical cations, which possess a spatially separated radical moiety and a cation moiety, have great synthetic potential because they can enable difunctionalization at the two distinct sites by orthogonally adding a nucleophile to the cation moiety and intercepting the radical moiety with a radical acceptor. However, capturing the bimodal reactivity of distonic radical cations remains elusive because of the limitations in access to precursors, suitable producing conditions, and understanding of their reactivities to gain orthogonal control of the two reactive moieties. We develop the ring opening of cyclopropyl- and cyclobutyl-amines as a general reaction platform to produce distonic radical cations but encounter many challenges to utilize their bimodal reactivity. Our central hypothesis of the difficulty is that because the ring opening is reversible, how to perturb the reversibility effectively will be critical to harness the bimodal reactivity. We identify two strategies to affect the reversibility: the use of a nucleophile and resonance stabilization of the cation moiety in distonic radical cations. Two specific aims are developed based on these two strategies: 1) difunctionalization of distonic radical cations of cyclopropylanilines and cyclobutylanilines; 2) functionalization of distonic radical cations of spirocyclic N,N aminals or N, O acetals. If this bimodal reactivity can be successfully harnessed to enable the difunctionalization of distonic radical cations, such reactions could represent a new way for synthetic chemists to utilize cycloalkylamines as synthetic building blocks and could provide a guiding principle to discover more useful ways to employ these distonic radical cations accessed beyond the ring opening processes. These transformations fit into an emerging theme in organic synthesis: diversify carbon backbones via deconstructive functionalization of carbo- or hetero-cycles. Cleavage of a strong bond such as carbon-carbon bonds is often employed in this process to enable the functionalization of a remote and unactivated carbon.