Synthesis of Highly Substituted 3‐Formylfurans by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

Abstract

3-Formylfuran derivatives are core structures of a variety of bioactive natural products. However, procedures for their preparation are still rare and generally inefficient in terms of atom economy: These methods require multiple steps or harsh reaction conditions and show selectivity problems. An efficient gold(I)-catalyzed cascade reaction that leads to 3-formylfurans from easily accessible starting materials is now described. A wide variety of 3-formylfurans were obtained from the corresponding symmetric and unsymmetric 1,4-diyn-3-ols in the presence of an N-oxide in good to excellent yields. Isotope-labeling experiments as well as DFT calculations support a mechanism in which, after an initial oxygen transfer, a 1,2-alkynyl migration is favored over a hydride shift; a cyclization ensues to afford the desired functionalized furan core.

Gold‐Catalyzed Transformations of Propargyl Alcohols and Propargyl Amines

“…In the case of gold carbenes, 1,2‐H, alkyl, aryl and alkenyl migrations have been particularly described. In 2014, Hashmi and co‐workers reported a gold(I)‐catalyzed oxidation/1,2‐alkynyl migration/cyclization cascade for the synthesis of 3‐formyl furans, in which a 1,2‐alkynyl migration onto gold carbene center was believed to be involved (Scheme ) . The reaction started from 1,4‐diyn‐3‐ols and pyridine N ‐oxides, affording a large array of 3‐formyl furans in good to excellent yields under mild conditions.…”

Gold(III) Chloride Catalyzed Synthesis of Chiral Substituted 3‐Formyl Furans from Carbohydrates: Application in the Synthesis of 1,5‐Dicarbonyl Derivatives and Furo[3,2‐c]pyridine

“…19 Common protecting groups such as COCH 3 (acetyl), CH 2 Ph (benzyl), and TBDMS ( tert ‐butyldimethylsilyl) were used for hydroxyl‐group protection in monosaccharides. 2‐Alkynylated sugars ( 3 a – p ) were synthesized by the [Pd(PPh 3 ) 2 Cl 2 ]/CuI‐catalyzed standard Sonogashira coupling reaction (Scheme ) 16c. 20…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…1327) to 3-formylfurans (e.g. 1330) [1222]. In the proposed mechanism the initially-formed carbene complex intermediate (e.g.…”