New Short Strategy for the Synthesis of the Dibenz[b,f]oxepin Scaffold

Abstract

Abstract:In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework through intramolecular S N Ar and McMurry reactions is described. The diaryl ethers required for the McMurry reaction have been obtained in good yields under microwave-assisted conditions of the reaction of salicylaldehydes with fluorobenzaldehydes without catalysts. Application of an intramolecular McMurry reaction to the synthesized diarylethers using TiCl 4 /Zn in THF gave the target dibenzo [b,f]oxepin system in 53%-55% yields.

Exciting progress in the transition metal‐catalyzed synthesis of oxepines, benzoxepines, dibenzoxepines, and other derivatives

“…[ 130 ] Moreno et al in 2013 demonstrated synthesis of the dibenz[ b , f ]oxepines 373 through S N Ar reaction of salicylaldehydes 49 with fluorobenzaldehydes 47 and then intramolecular McMurry reaction of the prepared 2,2′‐oxybis(benzaldehyde) compounds 372 using TiCl 4 /Zn (Scheme 88). [ 131 ]…”

“…[130] McMurry reaction of the prepared 2,2 0 -oxybis(benzaldehyde) compounds 372 using TiCl 4 /Zn (Scheme 88). [131] Tamura et al in 2010 reported a multistep way for the synthesis of bauhinoxepin J 379 from 2,5-dihydroxyp-benzoquinone 374 as starting material. [132] In this synthetic method, Ti-Zr McMurry coupling of tetramethoxybenzaldehyde 375 with salicylaldehyde 49 followed by hydrogenation, DDQ oxidative dearomatization, and final cyclization reaction afforded the dibenzo[b,f]oxepine scaffold (Scheme 89).…”

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives

“…Very few MW-assisted syntheses of dibenzoxazepines have been reported. Nevertheless, two very interesting approaches, based (i) on an intramolecular SNAr; and (ii) on a McMurry reaction, each occurring with MW-activation, have been described by Moreno and co-workers [29] (Scheme 10A). The dibenz [b,f ]oxepines are characterized by an oxepane fused with two aromatic moieties: this is a relevant pharmacophore present in the structure of numerous therapeutic agents which can be used for several therapeutic applications such as antidepressant, antipsychotic and anti-inflammatory indications ( Figure 5) [24][25][26][27][28].…”

“…Very few MW-assisted syntheses of dibenzoxazepines have been reported. Nevertheless, two very interesting approaches, based (i) on an intramolecular SNAr; and (ii) on a McMurry reaction, each occurring with MW-activation, have been described by Moreno and co-workers [29] (Scheme 10A). Very few MW-assisted syntheses of dibenzoxazepines have been reported.…”

“…Very few MW-assisted syntheses of dibenzoxazepines have been reported. Nevertheless, two very interesting approaches, based (i) on an intramolecular SNAr; and (ii) on a McMurry reaction, each occurring with MW-activation, have been described by Moreno and co-workers [29] (Scheme 10A). The SNAr strategy requires the synthesis of a multi-functionalized Z-stilbene 61, which is obtained in 87% yield through a conventional Wittig reaction involving o-bromobenzyltriphenylphosphonium salt 60 and 2-formylphenyl-4-methylbenzene sulfonate 59.…”