FeCl₃-catalyzed synthesis of functionally diverse dibenzo[b,f]oxepines and benzo[b]oxepines via alkyne–aldehyde metathesis

Abstract

An efficient synthesis of dibenzo[b,f]oxepines and benzo[b]oxepines via FeCl3-catalyzed alkyne-aldehyde metathesis reaction is described. Structurally diverse dibenzo[b,f]oxepines and benzo[b]oxepines have been achieved in good yields with high regio- and chemoselectivity under mild conditions. Notably, among the various catalysts such as Fe(III), Au(III), In(III), Zn(II), Ag(I) and triflic acid, the alkyne-aldehyde metathesis reaction of 2-(2'-phenylethynyl-phenyloxy)-benzaldehyde is only catalyzed by environmentally friendly and sustainable iron(III) chloride.

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

“…Bera et al developed an efficient, simple, mild, atom‐economical, and regioselective and chemoselective method for the synthesis of substituted dibenzo[ b , f ]oxepines 49 (Scheme 14) and benzo[ b ]oxepines 53 (Scheme 15) in good yields. [ 61 ] This transformation involved an S N Ar reaction of o ‐fluorobenzaldehyde derivatives 47 with ortho ‐halo phenols 32 followed by palladium‐catalyzed Sonogashira coupling and then FeCl 3 ‐catalyzed alkyne–aldehyde metathesis reaction to afford dibenzoxepine analog. Generally, so far, several methods and strategies have been developed for the synthesis of dibenzo[ b , f ]oxepines such as intramolecular C–O ether bond formation of 2‐styrylphenols, [ 62 ] Friedel–Crafts, [ 27 ] Wagner–Meerwein, [ 62 ] Heck reaction, [ 56 ] Os‐catalyzed hydroxylation of aromatic alkynols, [ 63 ] and Rh‐catalyzed olefin hydroacylation.…”

“…[ 64 ] But these protocols were subject to some limitations, such as low chemical yield, harsh reaction condition, lack of generality, non‐availability of starting materials, and the use of expensive and toxic reagents. In the mentioned method, [ 61 ] the construction of seven‐membered oxygen heterocycles employing alkyne‐carbonyl metathesis is reported for the first time with high efficiency, easy availability precursors, and use of FeCl 3 as inexpensive and environmentally friendly catalyst. In addition, this reaction was not successful in the presence of NaAuCl 4 , InCl 3 , AgOTf, and TfOH as catalyst.…”

Iron-Catalyzed Carbonyl–Alkyne and Carbonyl–Olefin Metathesis Reactions

“…The discovery of the reaction being catalyzed by AgSbF 5 led the focus to less expensive Lewis acids [24]. Even though the reaction has also been described to occur with other Lewis acids, iron-based Lewis acids have been found to be one of the most favorable, which can be explained by the HSAB theory: [25] Fe III can be considered as a "harder" Lewis acid than e.g., In III , as it has a smaller ionic radius and, therefore, a more concentrated charge, which can be beneficial for interaction, resulting in better catalytic performance [26].…”

Crystal structures of methyl 3-phenyl-4,5-dihydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxylate and methyl 1-methyl-3-phenyl-4,5-dihydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxylate

“…This principle has inspired decades of research into the pathways of angiogenesis (the formation of new blood vessels), leading to the identification of a family of vascular endothelial growth factors (VEGFs) that stimulate this process (Edwards et al, 2011). Sevenmembered oxygen heterocycles are ubiquitous in natural products and show a wide spectrum of biological activity (Bera et al, 2014).…”