Total Synthesis of (±)‐Dihydroisosubamol

Abstract

We herein report the first total synthesis of the dibenzocycloheptanoide (AE)-dihydroisosubamol. The key step includes a recently developed gold-catalysed hydroarylation reaction for the construction of the dibenzocycloheptene motif. Additional steps are a Suzuki-Miyaura cross coupling, a palladium-catalysed hydroxylation and an allylic oxidation. To access the saturated seven-membered ring system an iridium-catalysed hydrogenation proved to be successful.

Abnormal Nucleophilic Substitution on Methoxytropone Derivatives: Steric Strategy to Synthesize 5‐Substituted Azulenes

“…Machiguchia nd co-workersi n their report [18] provided detailed theoretical and experimental insight of the mechanism of the azulene synthesis from at roponoid precursor (2-methoxytropone) and an active methylene compound (Scheme 3). As described, [18] the process consists of the following elementary steps:1 )The initial step includes the nucleophilic attack of the malononitrile anion (HC(CN) 2 À )o n the troponoid substrate, 2-methoxy tropone (4)t of orm the (10). Ab ase attacks the imine 10,w hich results in the generation of ac onjugate base of the final product azulene ( 11).…”

“…[9] Hashmi and group reported the synthesis of several naturalp roducts bearing the active unsaturated seven-memberedr ing. [10] Aw ide variety of cycloaddition reactions, photochemical transformations, and nucleophilic substitutions on tropolone, 2-methoxytropone, and other substituted tropolones have been carriedo ut for the synthesis of biologically active compounds. [11][12][13][14] Yamamoto andc o-workersh ave studied the regioselectivity of nucleophilic substitution on 5-bromo-2-methoxytropone with various nucleophiles, where soft Sn ucleophiles preferred the 5-position andt he harder Oa nd Nn ucleophiles preferred the 2-position for the substitution.…”

“…Their pharmacological properties, in turn, are determined by the nature and position of functional groups in the tropolone ring . Hashmi and group reported the synthesis of several natural products bearing the active unsaturated seven‐membered ring …”

Gold-catalyzed hydroarylation reactions: a comprehensive overview

“…Hashmi's group proposed the total synthesis of (±)-dihydroisosubamol (Scheme 11). 26 For this synthesis, the initial compound was 22 and a gold-catalyzed hydroarylation reaction occurred in the fourth step of the total synthesis of (±)-dihydroisosubamol. The hydroarylation reaction proceeded with alkyne 23 with 2 mol% [L 7 Au(SbF 6 )] catalyst, 2 mol% AgSbF 6 in dichloromethane at room temperature for 1 h to form the tricyclic compound 24 in 84% yields, which leads to the formation of the final (±)-dihydroisosubamol 25 .…”

Regio- and Diastereoselective Construction of Functionalized Benzo[b]oxepines and Benzo[b]azepines via Recyclable Gold(I)-Catalyzed Cyclizations

“…During the recent decades, gold-catalyzed organic transformations have attracted much attention due to their high efficiency, mild reaction conditions, and excellent functional group compatibility and have been developed into powerful tools for the synthesis of numerous bioactive molecules, natural products, and pharmaceuticals . Gold catalysis easily leads to five- and six-membered rings, but it is much more difficult to construct seven-membered rings by gold catalysis . In recent years, gold-catalyzed transformations have been successfully applied for constructing seven-membered hetero- or carbocycles.…”