Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters

Abstract

Transformation of β‐oxoesters with PhI(OCOCF3)2 leads to α‐(ortho‐iodophenyl)‐β‐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.

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

“…The synthesis of compounds A1–21 starting from intermediate 1 was accomplished as depicted in Scheme 4 . The coupling of the organic acids with amidine 1 to form the corresponding derivatives B1–21 was achieved by common coupling reagents such as N,N' -dicyclohexylcarbodiimide (DCC) or ( O -(7-aza-1 H -benzotriazol-1-yl)- N , N , N ', N '-tetramethyluronium hexafluorophosphate) (HATU) [ 33 ] in DMF or CH 2 Cl 2 with either N,N -diisopropylethylamine (DIPEA) or 4-dimethylaminopyridine (DMAP) as the base. Then, the palladium-catalyzed hydrogenation of compounds B1–21 in THF or EtOAc led to the hydroxy derivatives C1–21 .…”

Preparation of Hexahydrocarbazole Derivatives by Reductive Indolization

“…We relied on a literature procedure applying the hypervalent iodine reagent PhI(OAc) 2 . [ 25 ] First of all, the parent unsubstituted amide 21e was prepared in 93 % yield by activation of the acid 20 with Boc 2 O and conversion of the mixed anhydride with hartshorn salt. The degradation proceeded with PhI(OAc) 2 and the intermediate isocyanate was solvolyzed with MeOH to furnish the carbamate 22 , however, the yield was moderate (44 %).…”

Amidine Derivatives of Avibactam: Synthesis and In Vitro β‐Lactamase Inhibition Activity

“…Synthesis of compounds A1 ‐ A9 starting from intermediate 1 was accomplished as depicted in scheme 2. Coupling of the organic acids with amidine 1 to form the corresponding derivatives B1 ‐ B9 was achieved by coupling reagents such as N,N′ ‐dicyclohexylcarbodiimide (DCC) or ( O ‐(7‐Aza‐ 1H ‐benzotriazol‐1‐yl)‐ N,N,N′,N′ ‐tetramethyluronium hexafluorophosphate) (HATU), [19] in CH 2 Cl 2 or N,N ‐dimethylformamide (DMF) whereas N,N ‐diisopropylethylamine (DIPEA) or 4‐dimethylaminopyridine (DMAP) were used as base. Palladium catalyzed hydrogenation of compounds B1 ‐ B9 in tertrahydrofuran (THF) or EtOAc led to afford hydroxy derivatives C1 ‐ C9 .…”