Copper‐Catalyzed Domino Reaction Involving Nitro as an Unexpected Leaving Group: Construction of Dibenzo‐Fused Azepinone Ring

Abstract

Ac opper-catalyzed newd omino reaction allowed the facile andd irect construction of the dibenzo-fused azepinone ring leading to an array of novel small molecules.T he co-catalyst, ligand or additive free one-pot method afforded au nique class of functionalized derivatives,o ne of which showed encouraging PDE4 inhibition in vitro and apoptosis in vivo.

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…This step was followed by an unusual S N Ar type reaction by which the NO 2 group was displaced, resulting in phosphonylated dibenzo-fused azepinone 857. 429 Fosmidomycin analogues have been synthesized from the tetrahydro-azepinone 858, using as a key step a phosphono-Michael reaction with diethylphosphonate (859) in the presence of tetramethylguanidine (TMG) as a base (Scheme 158). Then, hydrolysis of the phosphonate esters, esterification with chloromethyl pivalate (POMCl), and deprotection with a Pd/C-catalyzed hydrogenation affords the 2-azepanone 863.…”

“…Using diethyl (cyanomethyl)­phosphonate 248 , an Ullmann type C–C coupling evoked a domino reaction through which an N-containing seven-membered ring was formed (Scheme ). This step was followed by an unusual S N Ar type reaction by which the NO 2 group was displaced, resulting in phosphonylated dibenzo-fused azepinone 857 …”

Metal‐Catalyzed Approaches for the Construction of Azepinones

“…In the remarkable report, Pal and research group unveiled an effective methodology for the construction of di‐benzo‐fused azepinone 195 from iodo compound 193 with nitriles 194 via the copper‐catalyzed Domino reaction (Scheme 53). [63] They investigated many ways to couple iodo compound 193 with 194 using Cu‐catalyzed reactions. Remarkably, combining 193 with 194 yielded 195 directly as a single product.…”

Synthesis of Dibenzo[b,e]azepin‐6(11H)‐ones via a Sequential Ugi‐4CR and Sulfur Ylide‐Mediated Rearrangement Reaction

“…The classical reduction (hydrogenation) reactions, [3c,f] intramolecular Friedel–Crafts‐type cyclization reactions, [4a] Beckmamn rearrangement reactions, [4b] reduction‐lactamization reactions [4c] and benzylation of primary benzamides, [4d] are the often used synthetic methods for preparation of dibenzo[b,e]azepin‐6( 11H )‐ones. Some other efficient approaches, including reductive Heck cyclization, [4e] C‐nucleophile insertion reaction [4f] and cascade aryne insertion reaction, [4g] have been developed to access dibenzo[b,e]azepin‐6( 11H )‐ones (Figure 1). Although effective for the synthesis of dibenzo[b,e]azepin‐6( 11H )‐ones, these methods are self‐limiting because of severe reaction conditions, use of expensive transition metal catalysts, multistep substrate preparation, and lack of functional group tolerance in some cases.…”