IonPairEnantRadical : Transforming Enantioselective Radical Chemistry using Ion Pairing Catalysis

自由基反应是指电子单个而非成对运动的反应，近年来，这种反应取得了巨大的发展。这些令人兴奋的发展，其中许多产生了立体中心，突出了使自由基反应具有对映选择性的持续挑战。虽然许多来自双电子世界的关键对映体控制策略已经被应用，但这些策略在许多情况下是无效的，并且每种策略都具有特定的局限性。我们对一种利用催化剂和底物之间有吸引力的非共价相互作用来拉近两者并更好地进行控制的催化方法非常感兴趣。特别是，离子配对是最基本和最强大的非共价相互作用之一，但由于对方向性和可预测性的关注，合成化学家经常未充分探索其作为一种控制力。然而，我们认为，它们提供了独特的机会，在传统战略失败的地方施加选择性控制。在本提案中，我们概述了一个雄心勃勃的计划，该计划将应用创新和未开发的离子配对策略来控制各种重要的自由基化学中的对映体选择性，这些化学没有或限制了现有的控制方法。在涉及光氧化还原催化的催化循环中，虽然电荷通常适当地指示在中间体上，但在大多数报告中很少描述甚至试图跟踪相关的反离子。我们相信，反离子在控制对映体选择性方面发挥着至关重要的作用——在现有的不对称催化模式几乎没有利用余地的催化循环中，反离子可以提供关键。这项建议包括四个工作计划所界定的四个“挑战领域”。这些代表了重要的和局部的激进转变类别，这些转变很少或没有先例可以使用现有的方法进行不对称。如果可以证明这里概述的方法是可行的，那么还有许多其他反应类型可以应用，我们希望这可能会在该领域开辟新的视野。

Radical reactions, in which electrons move singly rather than in pairs, have seen an immense pace of development in recent years. These exciting developments, many of which produce stereocentres, have served to highlight the ongoing challenge of rendering radical reactions enantioselective. Whilst many of the key enantiocontrol strategies from the two-electron world have been applied, these are ineffective in many situations and each strategy possesses specific limitations. We are broadly interested in an approach to catalysis that utilises attractive non-covalent interactions between catalyst and substrate to draw the two close and better exercise control. Particularly, ion-pairing is one of the most fundamental and powerful non-covalent interactions but is frequently underexplored by synthetic chemists as a controlling force, perhaps due to concerns regarding directionality and predictability. However, we believe that they present unique opportunities to exert selectivity control where conventional strategies fail. In this proposal we outline an ambitious program which will apply innovative and unexplored ion-pairing strategies to control enantioselectivity in a variety of important radical chemistries for which there are no or limited existing methods for imposing control. In catalytic cycles involving photoredox catalysis, whilst charge is usually appropriately indicated on intermediates, the associated counterion is rarely depicted or even attempted to be tracked in most reports. We believe that, far from being insignificant, counterions can play crucial roles in the control of enantioselectivity - in a catalytic cycle where there is little scope for leveraging existing modes of asymmetric catalysis, the counterion can provide the key. This proposal consists of four "challenge areas", as defined in the four Work Plans. These represent important and topical classes of radical transformations that have little or no precedent to be carried out asymmetrically using existing approaches. If the approaches outlined herein can be proven viable then there are numerous other reaction types to which they can be applied and we hope that this may open new horizons in the field.