Regioselective Synthesis of Isochromenones by Iron(III)/PhSeSePh-Mediated Cyclization of 2-Alkynylaryl Esters

Abstract

A series of 4-Se-(Te, S)-isochromenones and 3-substituted isochromenones were synthesized in good yields via FeCl(3)-mediated cyclization of alkynylaryl esters with different diorganyl dichalcogenides. This methodology was carried out at room temperature, using inexpensive and environmentally friendly iron salts as metallic source and under air atmosphere. The reaction showed to be tolerant to a range of substituents bonded into the aromatic ring of the diorganyl dichalcogenides as well as to alkyl groups directly bonded to the chalcogen atom. Alternatively, the cyclization reaction of 2-alkynylaryl esters with FeCl(3), in the absence of diorganyl dichalcogenide, gave the isochromenones without the chalcogen moiety in the structure. This approach proved to be highly regioselective, providing only six-membered ring products, once the possible five-membered products were not observed in any experiments.

Design and Synthesis of Metabolically Stable tRNA Synthetase Inhibitors Derived from Cladosporin

“…As shown in Scheme , our pivotal starting material, methyl 2‐bromo‐4,6‐dimethoxybenzoate ( 18 ) is subsequently engaged in a Sonogashira coupling reaction with prop‐2‐yn‐1‐ylcyclohexane ( 26 ) in the presence of a catalytic amount of copper iodide and trimethylamine, leading to alkynylaryl ester 27 in 80 % yield. FeCl 3 ‐mediated cyclization of 27 selectively generated the expected six‐membered ring product, which was subjected to BBr 3 treatment, to afford analogue 28 ready for biological evaluation (Scheme ) …”

Construction of 4‐(Methylthio)isochromenones Skeleton through Regioselective Intramolecular Cyclization of 2‐Alkynylbenzoate Mediated by DMSO/[D6]DMSO and SOCl2

“…Isochromenones, known as a privileged class of lactones, are widely distributed in natural products and have exhibited a great variety of pharmacological properties involving antimicrobial, antifungal, immunomodulatory, cytotoxic,, anti‐inflammatory,, and antimalarial activities Considerable efforts have focused on synthetic method development for this class of biologically interesting heterocycles . Among them, the intramolecular cyclization of the 2‐alkynylbenzoates or 2‐alkynylbenzic acids has emerged as an effective and powerful process for the construction of isochromenone framework , . Meanwhile, diverse substituents can be introduced at the 4‐position of the isochromenones , .…”

Vinylic Tellurides

“…11 The reaction occured in the presence iron(III) under mild conditions and in air. The methodology was regioselective, providing only the six-membered ring as the product.…”