Development of New Radical Coupling Reactions at Carbon-Heteroatom Multiple Bonds

自由基介导碳碳多键形成碳碳键，如烯烃和炔，由于其通用性，在有机合成中得到了广泛的应用。然而，对于碳杂原子多键，如羰基和亚胺，碳-碳键的形成知之甚少。本研究的目的是在我们最近开发的硅碲化物与碳杂原子多键反应的基础上，开发一种新的碳杂原子多键合成自由基反应。以三甲基硅基苯基碲化物为催化剂，建立了羰基化合物与炔的新偶联反应。反应在温和的热条件下进行，得到相应的具有高立体选择性的含乙烯基碲的烯丙基醇。此外，乙烯基碲化物的自由基和阴离子介导的转化对多取代烯烃的立体选择性合成非常有用。因此，转换后的偶联反应为合成具有明确几何形状的多取代烯烃提供了有力的策略。我们还开发了一类新型的硅基碲化物试剂三乙基氧基苯基碲化物介导的亚胺与异硝基的偶联反应，得到了α-硅基氨基甲酰基碲化物。偶联产物中碳-碲键的转化使α-氨基酸衍生物的收率达到了很高的水平。上述自由基偶联反应以及随后的合成转化对羰基、亚胺、炔和异腈的取代不敏感。因此，我们明确了目前的方法适用于小分子文库的组合合成。

Radical mediated carbon-carbon bond formation at carbon-carbon multiple bonds, such as alkene and alkyne, has been widely utilized in organic synthesis due to its versatilities. However, little is known for the carbon-carbon bond formation at carbon-heteroatom multiple bonds, such as carbonyls and imines. This research was aimed to develop a new synthetic radical reaction at carbon-heteroatom multiple bonds based on the reaction of silyltellurides and carbon-heteroatom multiple bonds, which we have recently developed.A new coupling reaction of carbonyl compounds with alkynes mediated by trimethylsilylphenyltelluride has been developed. The reaction proceeded under mild thermal conditions to give the corresponding E-allylic alcohols bearing vinyltelluride group with high stereoselectivity. Furthermore, radical- and anion-mediated transformations of the vinyltellurides were highly useful for the stereoselective synthesis of multi-substituted alkenes. Therefore, the coupling reaction followed by the transformations provides a powerful strategy for the synthesis of multi-substituted alkenes with defined geometry.We have also developed a new coupling reaction of imines with isonitriles mediated by triethoxysilylphenyltelluride, a new class of silyltelluride reagent, to give α-silylaminomethylimidoyltellurides. The transformation of the carbon- tellurium bond in the coupling products afforded α-amino acid derivatives in good to excellent yields.The above mentioned radical coupling reactions as well as the subsequent synthetic transformations are insensitive to the substitutions of carbonyls, imines, alkynes, and isonitriles. Therefore, we clarified that the current method is suitable for the combinatorial synthesis of small molecule libraries.