Gold(I)‐Catalyzed Cycloisomerization of 2‐Fluoroalk‐3‐yn‐1‐ones: Synthesis of 2,5‐Substituted 3‐Fluorofurans

Abstract

Fluorination of 1,4-disubstituted tert-butyldimethylsilyl but-1-en-3-yn-1-yl ethers with Selectfluor gives 2-mono-fluorobut-3-yn-1-ones. Subsequent 5-endo-dig cyclization in the presence of chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (both 5 mol%, dichloromethane) under ambient conditions, provides a facile method for the generation of mainly 2,5-diaryl-substituted 3-fluorofurans in high yields (89-96%). The structure of 2-(4-bromophenyl)-3-fluoro-5-(4-methylphenyl)furan was confirmed by X-ray crystallography.

Electrophilic Cyclizations of 2‐Fluoroalk‐3‐yn‐1‐ones: Room‐Temperature Synthesis of Diversely 2,5‐Disubstituted 3,4‐Fluorohalofurans

“…Although the conversion of alk-3-yn-1-ones to furans may be quantitatively accomplished at room temperature within minutes by using simple Lewis acids such as zinc chloride or other transition metals, [18,19] the analogous reaction of 2-fluoroalk-3-yn-1-ones requires the use of a gold catalyst. [10] Alkyne activation with the use of acids, iodine, or gold complexes was reviewed recently. [20] Especially gold(I) complexes have proved to be excellent π-electrophilic Lewis acids.…”

“…[10] This method is essentially limited to the synthesis of trisubstituted furans. [11] Upon considering the pharmaceutical potential, as well as the limitations of available synthetic methods for 2,4,5-trisubstituted 3-fluorofurans, we decided to pursue the development of their synthesis.…”

Metal-catalyzed Furan Synthesis. A Review

“…47 The α-fluoroketone substrates are prepared by fluorination of the tert-butylsilyl enol ether of the corresponding aryl(alkyl)-3-yn-1-ones. This procedure compares very favorably to other methods to prepare fluorinated furans as Selectfluor is used as the fluorine source rather than Freon gas (CBr 2 F 2 ).…”

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

“…In the last decade, gold catalysts with their carbophilic character have emerged as a new tool for furan preparation. As summarized in Scheme 1, furans could now be obtained by either gold(I) or gold(III) catalysis from various types of substrates such as allenyl ketones [8–14], enynes or diynes [15–17], alkynes and sulfur ylides [18–19], alkynyl oxiranes [20–26], alkynyl ketones [27–35], alkynyl alcohols [36–46], and alkynyl ethers [47–48]. Very recently, a three-component coupling reaction toward furans catalyzed by gold(III) has been reported starting from terminal alkenes, glyoxal derivatives and secondary amines [49].…”