Construction of Polycycles Using Palladium-Catalyzed α-Arylation Reaction toward Carbonyl Group

在过去的十年里，金属有机化学，特别是有机钯化学取得了显著的进展。虽然已经研究了大量钯催化的芳基化和乙烯基化反应，其中大多数涉及到烯烃(Heck反应)、有机锡化合物(Stille反应)或有机硼化合物(Suzuki反应)作为终止剂，开发其他官能团作为终止剂有望扩大应用。最近，美国和日本的三个小组报道了分子间钯催化的酮的α-芳基化反应。同时，我们也独立地报道了它的分子内版本，它使用双(三苯基膦)氯化钯-碳酸铯-有或不有三苯基膦催化体系来形成苯环桥联螺环烷酮。我们的催化体系被发现适用于适当设计的含有甲酰基或硝基端基的底物。根据底物的结构和反应溶剂的不同，对甲酰基的芳基化发生在α-位(α-芳基化)或在羰基碳(羰基-芳基化)。α芳基化的仲硝基部分转化为酮，叔硝基部分消除为苯乙烯类型的烯烃，现在我们可以利用上述分子内芳基化条件得到各种碳环。它们含有有用的官能团，酮、甲酰基和硝基。我们正在利用上述环化反应进行Hetisan型乌头生物碱的合成研究。

In the last decade, organometallic chemistry, especially organopalladium chemistry has made a marked advance. While a great number of palladium-catalyzed arylation and vinylation reactions have been investigated, most of which involve olefins (Heck reaction), organo-tin compounds (Stille reaction), or organo-borane compounds (Suzuki reaction) as terminators.Exploitation of other functional groups as the terminator is expected to enable expanded application. Recently, the intermolecular palladium-catalyzed α-arylation reaction of ketone was reported by three groups of US and Japan. At the same time, we also reported independently its intramolecular version to form benzene-annulated bridged- spirocycloalkanones employing a bis(triphenylphosphine)palladium(II) chloride-cesium carbonate-with or without triphenylphosphine catalyst system.Our catalyst system was found to be applicable to properly designed substrates bearing a formyl or nitro terminating group. Arylation toward the formyl group occurred at the α-position (α-arylation) or at the carbonyl carbon (carbonyl-arylation) depending on the structure of the substrates and on the reaction solvent. The α-arylated secondary nitro group was partially transformed to ketone, whereas the tertiary nitro group was partially eliminated to a styrene type of olefin.Now, we can get various types of carbocycles employing the above intramolecular arylation conditions. They bear the useful functional groups, ketone, formyl, and nitro groups. We are now engaged in the synthetic investigation of Hetisan type of aconite alkaloids using the above cyclization reaction.