Synthesis of Benzothiophene-3-carboxylic Esters by Palladium Iodide-Catalyzed Oxidative Cyclization–Deprotection–Alkoxycarbonylation Sequence under Aerobic Conditions

Abstract

A palladium-catalyzed carbonylative approach to benzothiophene-3-carboxylic esters, starting from simple and readily available building blocks [2-(methylthio)phenylacetylenes, CO, an alcohol, and O 2 (from air)], is reported. The process is catalyzed by the simple PdI 2 /KI catalytic system to give the desired products in fair to high yields (57−83%). Interestingly, the reaction also works nicely in the ionic liquid BmimBF 4 as the solvent, with the possibility to recycle the catalytic system several times without appreciable loss of activity.

Palladium Iodide‐Catalyzed Selective Carbonylative Double Cyclization of 4‐(2‐Aminophenyl)‐3‐yn‐1‐ols to Dihydrofuroquinolinone Derivatives

“…We have recently reported that the simple catalytic system PdI 2 /KI, [ 7 ] proposed by our research group as an efficient catalyst for the oxidative carbonylation of alkynes in 1992 [8] and since then used for promoting many carbonylative heterocyclization processes, [ 7,9‐10 ] is able to catalyze the sequential oxidative heterocyclization – cyclocarbonylation of different suitably difunctionalized acetylenic derivatives with formation of carbonylated polycyclic heterocycles. [ 11 ] In particular, we were able to synthesize high value added 3,4‐dihydro‐1 H ‐furo[3,4‐ b ]indol‐1‐ones 2 in one step starting from 3‐(2‐aminophenyl)‐2‐yn‐1‐ols 1 , as shown in Scheme 1.…”

Metal‐Catalysed Synthesis of Benzofused Five‐Membered N/O/S‐Heterocycles, a Progressive Area in Synthetic Organic Chemistry

“…On this basis, the same group developed a Pd‐catalysed carbonylation of 2‐(methylthio)‐phenylacetylenes 85 to synthesize benzothiophene‐3‐carboxylic esters 91 at good yields (Scheme 31). [127] The reaction utilizes readily accessible starting materials, CO, alcohol, atmospheric oxygen, and a PdI 2 /KI catalytic system. The active catalytic species was conveniently recycled using an ionic liquid (BmimBF 4 ) as the reaction solvent in which the catalyst was perfectly soluble and no significant loss of activity was found even after up to five runs.…”

Synthesis of benzothiophenes via sulfonium-[3,3]-rearrangement of aryl sulfoxides with allenenitriles

“…1,2 For example, the benzothiophene scaffold, serving as a privileged structural motif, is prominently featured in several marketed drugs, such as zileuton, 3 raloxifene 4 and arzoxifene. 5 The well-developed methods for the synthesis of benzothiophenes include the Willgerodt–Kindler reaction, 6,7 electrophilic cyclization of alkynes, 8,9 annulation of thiophenol with active internal alkynes, 10,11 etc . In this context, Procter and coworkers developed a sulfonium-rearrangement for the synthesis of benzothiophenes (Scheme 1a).…”