Merging Photoredox with 1,2-Boronate Rearrangements: New Opportunities for Rapid Increase in Molecular Complexity

在过去的十年中，光氧化还原反应已经成为一种非常多才多艺的有机合成过程，能够在特别温和的条件下(可见光照射)在有机分子的特定位置产生活性自由基物种。在同一个十年里，我们开发了一系列利用硼的基本化学原理的转化，其中许多涉及到1，2-金属硼酸盐络合物的重排。我们现在寻求将合成方法学的这两个主要支柱结合起来，这两个支柱目前是不相连的光氧化还原反应和极性1，2-金属酸盐重排，以创建一个新的领域，我们相信这一领域在有机合成方面具有巨大的潜力。光氧化还原化学可以从缺乏电子的烷基卤化物(溴丙酸)中生成亲电自由基。我们建议将生成的亲电自由基与乙烯基硼酸络合物反应。由于乙烯基硼酸酯富含电子，应该很容易与缺乏电子的自由基反应生成自由基阴离子。富含电子的阴离子在基态氧化光催化剂(再生光催化剂)的作用下容易发生单电子氧化，从而导致1，2-烷基的协同迁移。1，2-金属酸盐重排通常采用在硼附近留下基团，但在这里我们建议氧化靠近硼酸盐的自由基以实现相同的转化，这一过程以前没有报道过。这将提供一种新的工艺，其中两个新的C-C键在一个锅中形成，带有用于进一步转化的多种官能团，初步结果表明这确实是可行的。此外，也有可能使创建三元和四元立体中心的过程不对称。在过去十年中描述的光氧化还原体系的快速指数增长为我们提供了丰富的方法，可以利用我们的1，2-金属重排。我们将采用迄今为止报道的最重要的、具有最大合成潜力的转化，并将它们用于我们的乙烯基硼酸盐。这些包括氟化自由基(如CHF2、CF3、CnF2n+1)、以氮为中心的自由基和芳基自由基的生成。我们还将借此机会看看光氧化还原反应是否可以应用于以前没有探索过的新物种，因为这将扩大这两个领域。使这种化学不对称的可能性尤其具有挑战性，但梅格斯催化剂的使用给了人们一些实现这一目标的希望。通过研究来自天然产物的不寻常的硼酸盐络合物，创造具有生物潜力的高度有趣的结构的新机会变得明显。例如，糖基的硼酸盐络合物可以很容易地制造出来，对它们进行光氧化还原介导的转化将导致一系列带有2-氨基或2-全氟取代基的新型糖。通过保留硼原子，这些物质可以转化为唾液酸类似物和无水糖。通过将两个主要领域结合起来，新的化学将出现具有新性质的新结构，以供开发。

In the last decade photoredox reactions have emerged as tremendously versatile processes for organic synthesis, enabling reactive radical species to be generated at specific positions in an organic molecule under exceptionally mild conditions (visible-light irradiation). Over the same decade we have developed a suite of transformations exploiting the fundamental chemistry of boron, many of which involve 1,2-metallate rearrangement of boronate complexes. We now seek to merge these two major pillars of synthetic methodology, which are currently unconnected, photoredox reactions and polar 1,2-metallate rearrangements, to create a new field, which we believe has significant potential for organic synthesis. Photoredox chemistry enables the generation of electrophilic radicals from e.g. electron-poor alkyl halides (bromomalonate). We propose to react the electrophilic radical generated with a vinyl boronate complex. Being electron rich, vinyl boronates should readily react with electron-deficient radicals leading to radical anions. The radical anions, being electron rich, should undergo facile one-electron oxidation by the ground-state oxidized photocatalyst (which regenerates the photocatalyst) and this will result in concerted 1,2-alkyl migration. 1,2-Metallate rearrangements normally employ leaving groups adjacent to boron but here we are proposing to oxidise a radical adjacent to a boronate to achieve the same transformation, a process that has not been previously reported. This should provide a novel process where two new C-C bonds are formed in one-pot, bearing versatile functional groups for further transformations, and preliminary results have demonstrated that this is indeed feasible. Furthermore, there is also the potential to render the process asymmetric for the creation of both tertiary and quaternary stereogenic centres.The rapid exponential growth of photoredox systems that have been described over the last decade provides us with a cornucopia of methods that can be exploited with our 1,2-metallate rearrangement. We will take the most important transformations reported to date that have the greatest synthetic potential and use them with our vinyl boronates. These include the generation of fluorinated radicals (e.g. CHF2, CF3, CnF2n+1), nitrogen-centred radicals, and aryl radicals. We will also take the opportunity to see if photoredox reactions can be applied to novel species that have not been previously explored as this will expand both fields. The potential to make this chemistry asymmetric is especially challenging but use of Meggers' catalyst gives some hope that this can be achieved. By studying unusual boronate complexes derived from natural products, new opportunities to create highly interesting structures with biological potential become apparent. For example, boronate complexes of glycals can be easily made and subjecting them to photoredox-mediated transformations will lead to a suite of novel sugars with 2-amino or 2-perfluoro substituents. By retaining the boron atom, these can be transformed into sialic acid analogues and anhydro sugars. By combining two major fields of endeavour, novel chemistry will emerge with new structures harbouring novel properties for exploitation.