Synthesis of 2,3-Disubstituted Benzo[b]furans by the Palladium-Catalyzed Coupling ofo-Iodoanisoles and Terminal Alkynes, Followed by Electrophilic Cyclization

Abstract

Abstract2,3-Disubstituted benzo [b]furans are readily prepared under very mild reaction conditions by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization using I 2 , PhSeCl or p-O 2 NC 6 H 4 SCl. Aryl-and vinylic-substituted alkynes undergo electrophilic cyclization in excellent yields. Biologically important furopyridines can be prepared by this approach in high yields.

Highly Potent Naphthofuran‐Based Retinoic Acid Receptor Agonists

“…[16,[31][32][33] Common electrophiles [31,34] activate the alkyne for intramolecular addition of the oxygen lone pair. Iodine has been most useful in this regard, [31] but other activators such as NIS, ICl, and PhSeCl [31,33] work equally well. This reactivity pattern is also observed upon activation of the alkyne with transition metals.…”

“…[35][36][37] We first selected the conditions reported by Arcadi et al, [16,17] which use solutions of I 2 in alcohols (ethanol, methanol) in the presence of sodium bicarbonate. Using methyl ethers such as 7, the substrates favored by Larock and colleagues, [31] starting materials were recovered. Compared with the electron-rich substrates used elsewhere, [31] the lack of reactivity of 7, even after heating for 16 h at 80 8C or microwave irradiation for 5 min at 200 W, must be traced back to the electron deficiency induced on the alkyne by the p-carbethoxyphenyl group.…”

Metalated Heterocycles in Organic Synthesis: Recent Applications

“…409 Other 6-stannylated 3,4-dihydro-2H-pyrans have also been used recently in Stille couplings, as in the total synthesis of the neurotoxin azaspirazid-1 410 or in the synthesis of spiroketals. 411 These organotin derivatives have also been employed as a source of organolithiums in a total synthesis of the marine sponge metabolite (+)-mycalamide A, 412 415 respectively. In the case of selanylated pyridines, another synthetic method is the use of selenoates in a substitution reaction starting from halopyridines.…”

A novel one-pot three-step synthesis of 2-(1-Benzofuran-2-yl)quinoline-3-carboxylic acid derivatives

“…Among these, the most widely used approach for the synthesis of 2-substituted benzo [b] furans involves the palladium-catalyzed heteroannulation of 2-halophenols with a terminal alkyne via a tandem Sonogashira coupling-5-endo-dig-cyclization, largely based on the methods of Larock and his co-workers. [7][8][9][10] Recently, other less popular approaches for the synthesis of 2-substituted benzo [b]furans include p-toluenesulfonic acid-mediated cyclization of o- (1-alkynyl)anisoles to obtain 2-arylsubstituted benzofurans, 11 rearrangement and cyclization reactions of 2-hydroxybenzophenones with Corey-Chaykovsky reagent, 12 cyclization of 2-acyloxy-1-bromomethylarenes with Cr(II)Cl 2 /BF 3 -OEt 2 catalyt, 13 boron tribromide-promoted tandem deprotection-cyclization of 2-methoxyphenylacetones, 14 (2-methoxyphenyl) methanols, 15 and 2-hydroxy-3-arylpropenoic acids 16 leading respectively to 2-methyl, 2-carboxy, and 2-arylbenzo [b] furans. However, these methods often require expensive catalysts and/or multi-step synthesis.…”