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

Abstract

From the past decade so far, the synthesis of seven‐membered oxacycles especially natural monocyclic oxepines and their annulated derivatives has received considerable attention. Due to the importance of these valuable scaffolds in natural products, pharmaceuticals, and prospective drugs, as well as their strong potential for use in the biosynthesis and metabolism of monocyclic and polycyclic aromatic compounds, a variety of synthesis strategies have been proposed to afford oxepine moiety. Among the versatile and attractive approaches, this review article focuses on the exciting developments in transition metal‐mediated reactions as the key step in the synthesis of oxepine derivatives from 2010 to early 2021.

Advances in the synthesis of rearranged homoisoflavonoids

“…Since their isolation in the mid-1980s, 26 the 8-membered bridge biaryl skeleton protosappanin A ( 18 ) was synthesized only in 2016 by Chu and coworkers (Scheme 29). 96 The researchers obtained this natural product via palladium-catalyzed intramolecular ortho arylation by a Csp 2 –H activation/C–C coupling reaction of biaryls, 97,98 followed by ring-expansion through Tiffeneau–Demjanov rearrangement. 99,100…”

Base-promoted cyclization ofortho-hydroxyacetophenones within situgenerated cyclopropenes: diastereoselective access to spirobenzo[b]oxepines and related precursors

“…Highly efficient design and assembly of functionalized benzo[ b ]oxepine backbones involving simple substances are given special priority in organic synthesis 1 because these medium-sized fused cyclic ethers are widely distributed in many bioactive natural products, 2 medicinally useful synthetic products, 3 pharmaceuticals, 3,4 and natural herbicides (Fig. 1).…”

“…This may be due to the unfavorable entropic penalties and the unavoidable transannular interactions during their formation. 6 In view their pharmacological importance and synthetic challenges, chemists have made great efforts to search for straightforward techniques for obtaining a large molecular diversity of functionalized benzo[ b ]oxepines, 1–5,7–18 for example, the intramolecular Mitsunobu reaction of phenols, 8 the Friedel–Crafts cyclization of aryloxybutanoic acid 9 and ring-closing metathesis (RCM) of dienes 10 have been traditionally used for the construction of these hybrid frameworks. However, the described methods have one or more critical shortcomings, such as narrow substrate scope, difficult-to-access starting materials, poor yields, etc ., which limit the progression of the field.…”

Direct Access to Trifluoromethylated Benzo[d]oxepines from o-Alkynylaryl Aldehydes and Trifluorodiazoethane

“…Consequently, exceptional advances have been made for the syntheses of highly sought-after benzo­[ b ]- and benzo­[ c ]­oxepine scaffolds using transition-metal-catalyzed inter- and intramolecular cyclization reactions . Despite the notable progress reported for the construction of these analogues of benzoxepine, the availability of general methods for the synthesis of benzo­[ d ]­oxepines lags behind, and this may be attributed to the limited source of reaction partners. As of now, only a handful of reports are documented in the literature for their synthesis.…”