Oxidative Cleavage of Furans

Abstract

Oxidative ring cleavage reactions of furans constitute a group of important transformations that have found wide utility in synthetic organic chemistry. These processes have been used to prepare a variety of 1,4‐dicarbonyl compounds including 1,4‐dioxoalkenes, 4‐oxoalkenals, 4‐oxoalkenoic acids, and their derivatives such as 4‐hydroxybutenolides and 2,5‐dialkoxydihydrofurans. Oxidations of furfuryl alcohols (Achmatowicz reaction) and furfuryl amines (aza‐Achmatowicz reaction) provide access to highly functionalized heterocyclic structures that have been employed as intermediates in synthetic routes for the preparation of complex molecules including carbohydrates and alkaloids. Complete oxidative degradation of the furan ring affords carboxylic acids; thus the oxygen heterocycle has served as a masked carboxyl group in many synthetic studies. These transformations and their applications in total syntheses are covered in this chapter.

Asymmetric Total Synthesis of (−)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A

“…With compound 55 in hand, we next proceeded to complete the synthesis of 13­( R )-demethyl spirochensilide A [ 57 (Scheme )]. Initially, we attempted a direct oxidative spiroketalization of the furan motif in 55 using reported oxidants, such as NBS, NaClO 2 , and m -CPBA . However, we failed to obtain the desired product 56 , presumably because furyl alcohol 55 contained an allylic alcohol motif that did not tolerate harsh conditions.…”

Modular Synthesis of Functionalized Butenolides by Oxidative Furan Fragmentation

“…Because furans are inexpensive, readily available, and highly reactive, they are versatile synthons and have frequently been used to access a wide array of valuable building blocks. 21 Typical transformations of furans include Diels-Alder reactions to afford butenolides and 1,4-diketones, Achmatowicz reactions to furnish pyranones and pyridones, and Mukaiyama Aldol reactions to form butenolides (Figure 1c). Despite the frequent application of these classic transformations in natural product synthesis and medicinal chemistry, the use of furans to rapidly generate molecular complexity via C-C bond fragmentation has rarely been reported.…”

Oxidative Furan-to-Indole Rearrangement. Synthesis of 2-(2-Acylvinyl)indoles and Flinderole C Analogues

“…Otherwise, azaheterocycles can be formed as a result of the intramolecular reaction of a nitrogen nucleophile, with a single latent ketone function while a second masked carbonyl group evolves in a free form (Butin reaction, Scheme b). Moreover, under oxidative conditions, furan can react as synthetic equivalent of 2-ene-1,4-dione; corresponding reactions of furfurylamines afford pyridine derivatives (Scheme c, aza-Achmatowicz reaction) . In the last process, the nitrogen nucleophile, separated from the furan ring by a single carbon atom, can react with the remote masked carbonyl group only.…”