Synthesis of Benzo[b]azocin-2-ones by Aryl Amination and Ring-Expansion of ?-(Iodophenyl)-?-oxoesters.

ABSTRACT: Transformation of ?-oxoesters with PhI(OCOCF₃ )₂ leads to ?-(ortho-iodophenyl)-?-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 K₃ PO₄ 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.

SUBMITTER: Dierks A 

PROVIDER: S-EPMC6899745 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature