Ruthenium-Catalyzed Oxidative Annulation by Cleavage of C-H/N-H Bonds
Ruthenium-Catalyzed Oxidative Annulation by Cleavage of C-H/N-H Bonds
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DOI：
10.1002/anie.201101943
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Hofmann, Nora
中科院分区：
文献类型：
--
作者：
Ackermann, Lutz;Lygin, Alexander V.;Hofmann, Nora
氧化过渡金属催化的C？H键功能化[1]最近引起了人们的极大兴趣，因为这些方法避免了预活化起始材料的多步骤制备，从而允许有机合成的整体流水线。Miura和Satoh，[2]Fagnou，[3]和Jones[4]研究小组的开创性报告显示，特别是Rh催化剂通过螯合辅助实现了炔烃的有效脱氢环化反应，[5，6]这为最近开发的Rh催化异喹诺酮[7]合成奠定了基础。[8]相反，使用价格较低的Ru[9]催化剂通过裂解C±H键进行氧化环化迄今尚未见报道。在对Ru催化的氧化同脱氢芳基化反应的研究中，我们通过C±H和N±H键的化学和位置选择性官能化，观察到了前所未有的Ru催化的炔烃的直接环化[11]，我们希望在这里公布我们的结果。在我们的研究开始时，我们探索了不同的反应参数对酰胺1a对炔2a氧化环化的影响，其中包括使用典型的Ru前体、溶剂、氧化剂和添加剂(支持信息表1和表S1)。在多种Ru络合物中，以[{RuCl2(对伞花烃)}2]为催化剂，以CuOAc(OAc)2·H2O为末端氧化剂，以二氢呋喃(=叔戊基)为溶剂时，产物3a的产率最高。相反，使用银(I)盐作为化学计量比氧化剂会导致催化效率降低。至于反应机理(见下文)，化合物4a在非极性溶剂中的形成是值得注意的。
Oxidative transition-metal-catalyzed CÀH bond functionalizations [1] have attracted significant recent interest, because these methods avoid the multi-step preparation of preactivated starting materials, and hence allow for an overall streamlining of organic synthesis. Pioneering reports by the research groups of Miura and Satoh,[2] Fagnou,[3] and Jones [4] revealed that particularly rhodium catalysts enabled effective dehydrogenative annulation reactions of alkynes through chelation assistance,[5, 6] which have set the stage for very recently developed rhodium-catalyzed isoquinolone [7] syntheses.[8] On the contrary, the use of less-expensive ruthenium [9] catalysts for oxidative annulations through cleavage of CÀH bonds has thus far not been reported. During studies on oxidative ruthenium-catalyzed homodehydrogenative arylations,[10] we observed unprecedented ruthenium-catalyzed direct annulations of alkynes [11] through the chemo-and site-selective functionalization of both CÀH and NÀH bonds, and we wish to disclose our results herein. At the outset of our studies, we explored the effect of different reaction parameters on the oxidative annulation of alkyne 2a by amide 1a, which included the use of representative ruthenium precursors, solvents, oxidants, and additives (Table1, and TableS1 in the Supporting Information). Among a variety of ruthenium complexes, optimal yields of product 3a were obtained with [{RuCl2 (p-cymene)} 2], along with Cu (OAc) 2· H2O as the terminal oxidant, and tAmOH (tAm= tert-amyl) as the solvent. On the contrary, the use of silver (I) salts as stoichiometric oxidants resulted in decreased catalytic efficacy. As to the reaction mechanism (see below), the formation of compound 4a in apolar solvents is noteworthy.[12]