Catalysis of Tin-Free Radical Reactions Under H2

项目总结/摘要 有机锡试剂通常用于进行产生C-C键或影响C-C键的自由基反应。 还原某些官能团。它们是小规模实验室合成 用于生化评估的分子。不幸的是，这些锡试剂不适合用于 制造业，因为它们很难去除并且毒性很大。生成自由基的另一种方法 中间体是通过氢原子从氢化物络合物转移到不饱和底物， 第一行过渡金属。这些废物是无毒的，它们的使用是可持续的：它们可以再生 因此通过这种方法产生的自由基是催化性的。一个H2分子产生两个 氢原子-和两个自由基-几乎没有浪费。该提案旨在确定哪种氢化物 复合物可以最好地进行这种化学反应，并确定自由基反应的新用途。 首先，各种烯烃和炔烃通过这种方法产生自由基的相对速率将是 测量，并将研究这种自由基在环化中的用途。这些激进分子应该是 特别可用于环化到C=O、C=S和C=N双键上，以及用于构建三- 和通过其它方法不容易获得的四元全碳环。第二，形成 不环化的基团可以在单独的步骤中转移另一个氢原子， 使得H2能够反加成穿过C=C键。该反应应允许合成天然的 传统氢化方法无法获得的产品。第三，这些新方法 自由基生成将在已经通过自由基制备的天然产物靶上进行测试 由已建立的方法生成。目前的合成往往是非最佳的;后期阶段， 将强调多官能基片，以便为该方法提供尽可能有效的基准。 已经开发的方法。然后将成功的催化反应应用于合成 这些天然产物尚未在实验室中制备。 最后，氢化物络合物-特别是阴离子氢化物络合物-也可以能够生成 自由基通过电子转移到适当的卤化物R-X。应该可以再生这些细菌 在氢气和碱的作用下，所以这些反应也可以被催化。我们还将测试这种新方法， 自由基生成的天然产物的目标，已经取得了既定的方法。

PROJECT SUMMARY/ABSTRACT Organotin reagents are routinely used to carry out radical reactions that create C-C bonds or effect the reduction of certain functional groups. They are valuable tools for the small-scale, laboratory synthesis of molecules for biochemical evaluation. Unfortunately, these tin reagents are unsuitable for use in manufacturing, because they are difficult to remove and quite toxic. An alternative way of generating radical intermediates is by the transfer of hydrogen atoms to unsaturated substrates from the hydride complexes of first-row transition metals. Such hydrides are non-toxic and their use is sustainable: they can be regenerated by hydrogen gas, so the generation of radicals by this method is catalytic. One H2 molecule produces two hydrogen atoms — and two radicals — with almost no waste. This proposal seeks to determine which hydride complexes can best do this chemistry and to identify new uses for radical reactions. First, the relative rates at which various alkenes and alkynes give radicals by this method will be measured, and the uses of such radicals in cyclizations will be investigated. These radicals should be particularly useful for cyclizations onto C=O, C=S, and C=N double bonds, and for the construction of three- and four-membered all-carbon rings that are not readily available by other methods. Second, the formation of radicals that do not cyclize can be followed by the transfer of another hydrogen atom in a separate step, enabling the anti addition of H2 across a C=C bond. This reaction should permit the synthesis of natural products that have been unavailable by traditional hydrogenation methods. Third, these new methods of radical generation will be tested on natural product targets that have already been prepared via radicals generated by established methods. The present syntheses have often been non-optimal; late-stage, polyfunctional, substrates will be emphasized, in order to provide as effective a benchmark as possible for the methods that have been developed. Successful catalytic reactions will then be applied to the synthesis of pharmaceutically promising natural products that have not yet been prepared in the laboratory. Finally, hydride complexes — particularly anionic hydride complexes — may also be able to generate radicals by electron transfer to appropriate halides R–X. It should be possible to regenerate these hydrides under hydrogen with base, so these reactions can also be made catalytic. We will also test this new method of radical generation on a natural product target that has been made with established methods.