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

点击翻译按钮获取中文摘要

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.