Lee S, Hartwig J F
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, CT 06520-8107, USA.
J Org Chem. 2001 May 18;66(10):3402-15. doi: 10.1021/jo005761z.
Catalysts comprised Pd(OAc)(2) and either PCy(3) or sterically hindered N-heterocyclic carbene ligands provide fast rates for a palladium-catalyzed synthesis of oxindoles by amide alpha-arylation. This catalyst system allowed for room-temperature reactions in some cases and reactions of aryl chlorides at 70 degrees C. Most important, reactions occurred in high yields under mild conditions to form the quaternary carbon in alpha,alpha-disubstituted oxindoles. The combined inter- and intramolecular reaction afforded an efficient synthetic method for formation of alpha-aryloxindole derivatives. Surprisingly, catalysts containing tert-butylphosphine ligands, which have been most reactive for ketone arylations, were less active than those containing PCy(3). Use of new, optically active heterocyclic carbene ligands gave substantial enantioselectivity in formation of an alpha,alpha-disubstituted oxindole. In contrast, a variety of optically active phosphine ligands that were tested gave poor enantioselectivity. Mechanistic studies showed that the reaction involves rate-limiting oxidative addition of aryl halide. Base-induced formation of and reductive elimination from an arylpalladium enolate intermediate were both faster than oxidative addition. Deprotonation of the tethered amide appeared to be faster than reductive elimination of the resulting palladium enolate to form the oxindole product.
由醋酸钯（Pd(OAc)₂）与三环己基膦（PCy₃）或空间位阻型氮杂环卡宾配体组成的催化剂，能为钯催化的酰胺α-芳基化合成氧化吲哚提供快速反应速率。在某些情况下，该催化体系可实现室温反应，芳基氯在70℃下也能反应。最重要的是，反应在温和条件下高产率地进行，形成α,α-二取代氧化吲哚中的季碳。分子间和分子内反应相结合，为α-芳基氧化吲哚衍生物的形成提供了一种有效的合成方法。令人惊讶的是，含叔丁基膦配体的催化剂在酮的芳基化反应中活性最高，但在此反应中却不如含PCy₃的催化剂活性高。使用新型光学活性杂环卡宾配体，在α,α-二取代氧化吲哚的形成过程中产生了显著的对映选择性。相比之下，测试的多种光学活性膦配体的对映选择性较差。机理研究表明，该反应涉及芳基卤化物的限速氧化加成。碱诱导的芳基钯烯醇盐中间体的形成和还原消除都比氧化加成快。连接的酰胺的去质子化似乎比所得钯烯醇盐还原消除形成氧化吲哚产物更快。
