二碘化钐参与及二茂钛催化的氮α-位碳自由基偶联反应及其在含氮杂环合成中的应用

SmI_2 and Titanocene-Mediated Coupling Reactions of α-Aminoalkyl Radicals and Applications to the Synthesis of Aza-Heterocycles

氮α-位碳-碳键的构造是含氮有机化合物合成中的基本方法。通过氮α-位的碳正离子(亚胺鎓)、碳负离子和碳自由基中间体是实现这一目标的主要途径。相对而言,通过氮α-位碳自由基中间体构造碳-碳键可在较温和的中性条件下进行,且可实现对亚胺鎓离子的极性反转,因而是对正、负离子极性反应的重要补充。作为温和的单电子还原剂,Kagan试剂(二碘化钐)可还原多种含氮有机物产生氮α-位自由基,进而发生自由基偶联反应,在形成氮α-位碳-碳键的方法学发展中扮演了重要的角色。本文综述了二碘化钐参与的氮α-位自由基偶联反应在有机合成中的研究进展,重点归纳评述了二碘化钐参与的亚胺、硝酮、氮杂半缩醛、酰亚胺和酰胺等底物与醛/酮及与缺电子烯烃的自由基偶联反应,为了探讨、克服二碘化钐在相关反应中的局限性,也介绍了二茂钛催化的氮α-位碳自由基偶联反应的最新进展。此外,还重点评述了这些合成方法在含氮活性化合物、生物碱和中间体的简捷合成中的应用。

Carbon-carbon formation at N-α-carbon is an essential transformation in the synthesis of nitrogen- containing compounds. N-α-Carbocations （iminium ions）, N-α-carbanions, and N-α-aminoalkyl radicals constitute three major classes of intermediates for this goal. The carbon-carbon forming reactions based on N-α- aminoalkyl radicals is advantageous over other two classes of intermediates for being able to run the reactions under mild neutral conditions. Moreover, because N-α-aminoalkyl radicals are umpolung of N-α-carbocations （iminium ions）, the approaches based on these intermediates are complementary. In this regard, Kagan reagent （samarium diiodide, SmI2 ）, a mild single-electron reductant, has emerged as a versatile reagent for the generation and coupling of N-α-aminoalkyl radicals. In this review, recent progresses on the carbon-carbon forming reactions at N-α-carbon via Kagan reagent is summarized. A number of nitrogen-containing substrates including imines, nitrones, hemiaminals, imides and amides have been shown to be valuable precursors to generate α-aminoalkyl radicals. The in situ coupling reactions of the latter with aldehydes/ ketones, or electron- deficient alkenes lead to the formation of N-α-C-C bonds. These methods allow flexible access to diverse N-α-C functionalized compounds. To overcome some limitations of Kagan reagent, methods based on the titanocene- catalyzed generation of N-α-aminoalkyl radicals have also been developed. Many of these methods have been applied to the concise syntheses of medicinal-relevant compounds, alkaloids or key intermediates.