Iron-Catalyzed Synthesis of Functionalized 2H-Chromenes via Intramolecular Alkyne−Carbonyl Metathesis

Abstract

An iron-catalyzed intramolecular alkyne-aldehyde metathesis strategy of the alkynyl ether of salicylaldehyde derivatives has been developed which works under mild reaction conditions to produce the functionalized 2H-chromene derivatives. This protocol is compatible toward a wide range of functional groups, such as methoxy, fluoro, chloro, bromo, and phenyl groups. This method provides an atom-economical and environmentally friendly approach for the synthesis of a series of substituted 2H-chromenes.

Catalytic Synthesis of 2H-Chromenes

“…Unlike the mechanism proposed by Jana et al, 7 this reaction mechanism involves the initial activation of the alkyne by FeCl 3 followed by nucleophilic attack of the carbonyl on the activated alkyne. This leads to the formation of intermediate 1.2.2-B (Scheme 7).…”

“…Ramachary et al reported 56 a new method for the synthesis of highly substituted (Z)-2-(buta-1,3-dienyl)phenols from highly substituted dienes by a combination of ring-closing metathesis (i) and base-induced ring-opening (ii). The corresponding phenol then transformed to the desired 2-methyl-2H-chromenes via a [1,7]-sigmatropic H-shift reaction followed by electrocyclic ring closure (Scheme 96). Two different reaction conditions were employed: heating at 120− 140°C and treatment with silica at room temperature.…”

“…The mechanism of these reactions involves the formation of the ortho-quinone methide intermediates 2.23B from a [1,7]sigmatropic H-shift followed by an electrocyclic ring closure to give the desired chromene products (Scheme 98). …”

Iron Catalysis in Organic Synthesis

“…1317 This method has been utilized for the conversion of O-propargylsalicylaldehydes into 2H-chromenes in the presence of catalytic amounts of iron(III) chloride. A series of such products could be obtained in good to high yields.…”

Strong base- or acid-mediated chemoselectivity shifts in the synthesis of 2H-chromene or coumarin derivatives from common Baylis-Hillman adducts

“…Synthetic 2H-chromene-3-carboxamide derivatives have also been shown to act as COX-2 inhibitors, 7 central muscle relaxants, 8 analgesics and anti-inflammatories, 9 and as dopamine-D3 ligands. 10 2H-Chromene derivatives have also been accessed via ring-closing metathesis methods, 11,12 while Zhang et al 13 have recently reported the synthesis of 2-trifluoromethyl-6-trimethylsilyl-2H-chromene-3-carboxylic acid derivatives as potential COX-2 inhibitors. 2H-Chromene-3-carboxylic acids have also been obtained efficiently via alkaline hydrolysis of 3-cyano-2H-chromenes which, in turn, were afforded by Baylis-Hillman reactions of 2-hydroxybenzaldehydes with acrylonitrile.…”