Synthesis of Benzo[b]azocin-2-ones by Aryl Amination and Ring-Expansion of α-(Iodophenyl)-β-oxoesters
Synthesis of Benzo[b]azocin-2-ones by Aryl Amination and Ring-Expansion of α-(Iodophenyl)-β-oxoesters
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DOI：
10.1002/chem.201903139
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发表时间：
2019-10-28
影响因子：
4.3
通讯作者：
Christoffers, Jens
中科院分区：
文献类型：
--
作者：
Dierks, Anna;Toenjes, Jan;Christoffers, Jens
β-氧代酯与PhI（OCOCF 3）（2）的转化产生α-（邻碘苯基）-β-氧代酯。这些原料是通过芳基胺化和环转化合成6-羧基苯并[B]氮杂辛-2-酮的起始原料。该反应顺序开始于在K3 PO 4作为化学计量碱的存在下由碘代芳烃和伯胺铜催化形成N-烷基苯胺。中间产物通过将氮加成到环烷酮的羰基中进行环转化，得到苯并成环的八元环内酰胺。在相同的反应条件下，环己酮和环庚酮衍生物没有生成胺化产物，而是环化生成苯并呋喃衍生物。本研究的标题化合物含有两个进一步多样化的点（内酰胺氮和羧酸酯官能团），因此，通过适当的官能化证明了该化合物类作为支架的适用性。支架的第一系列衍生化通过N-苄基衍生物的氢解脱苄基化来引发，以提供NH-同类物，其可以用LDA去质子化并在氮处烷基化，以给出该化合物类别的其他实例。其次，酯官能团进行皂化，并且所得羧酸可以使用HATU作为偶联剂酰胺化以提供不同的酰胺。
Transformation of beta-oxoesters with PhI(OCOCF3)(2) leads to alpha-(ortho-iodophenyl)-beta-oxoesters. These materials are the starting point for the synthesis of 6-carboxybenzo[b]azocin-2-ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper-catalyzed formation of N-alkyl anilines from the iodoarenes and primary amines in the presence of K3PO4 as stoichiometric base. The intermediate products underwent ring transformation by addition of the nitrogen into the carbonyl group of the cycloalkanone, furnishing benzo-annulated eight-membered ring lactams. Under the same reaction conditions, the cyclohexanone and cycloheptanone derivatives gave no aminated products, but ring-transformed to benzofuran derivatives. The title compounds of this investigation contain two points for further diversification (the lactam nitrogen and the carboxylate function), thus, the suitability of this compound class as a scaffold was proven by appropriate functionalizations. The first series of derivatizations of the scaffold was initiated by hydrogenolytic debenzylation of N-benzyl derivative to provide the NH-congener, which could be deprotonated with LDA and alkylated at nitrogen to give further examples of this compound class. Secondly, the ester function was submitted to saponification and the resulting carboxylic acid could be amidated using HATU as coupling reagent to furnish different amides.