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

Abstract

Oxidative rearrangement of 2-(2-aminobenzyl)furans affording 2-(2-acylvinyl)indoles in a stereocontrolled manner in good-to-excellent yields has been developed. Thus, (2-aminobenzyl)furans with electron-releasing alkoxy substituents in the phenyl group form only E-isomers of 2-(2-acylvinyl)indoles. Conversely, substrates without such substituents produce target products as Z-isomers exclusively. A short diastereoselective method for the transformation of the obtained 2-(2-acylvinyl)indoles into antimalarial bisindole alkaloid flinderole A-C analogues has been developed.

Cycloamination strategies for renewable N-heterocycles

“…229,230 With respect to upgrading "furan platform", various N-heterocycles (e.g., pyrroles and indoles) can be synthesized via respective processes like Yuriev, Butin, and Achmatowicz reactions (Scheme 27A-C). 231 Specifically, biomass-derived 2-(2-aminobenzyl)furans 98 undergoes oxidative rearrangement successively with m-chloroperbenzoic acid (m-CPBA) at 0°C and then application of trifluoroacetic acid (TFA) at room temperature gives 2-(2-acylvinyl)indoles 99 (up to >90% yield) in exclusive E-or Z-isomers, closely dependent on the presence or absence of electron-donating alkoxy substituents in the phenyl ring, respectively (Scheme 27D). 231 Zeolite HZSM-5 (Si/Al = 25) was illustrated to efficiently catalyze direct gas-phase conversion of furfural via cascade thermal conversion and ammonization with NH 3 to give indoles (yield 20.79%) at 650°C with a weight hourly space velocity (WHSV) of 1.0 h −1 and NH 3 /furfural molar ratio of 2.…”

“…231 Specifically, biomass-derived 2-(2-aminobenzyl)furans 98 undergoes oxidative rearrangement successively with m-chloroperbenzoic acid (m-CPBA) at 0°C and then application of trifluoroacetic acid (TFA) at room temperature gives 2-(2-acylvinyl)indoles 99 (up to >90% yield) in exclusive E-or Z-isomers, closely dependent on the presence or absence of electron-donating alkoxy substituents in the phenyl ring, respectively (Scheme 27D). 231 Zeolite HZSM-5 (Si/Al = 25) was illustrated to efficiently catalyze direct gas-phase conversion of furfural via cascade thermal conversion and ammonization with NH 3 to give indoles (yield 20.79%) at 650°C with a weight hourly space velocity (WHSV) of 1.0 h −1 and NH 3 /furfural molar ratio of 2. It was proposed that the reaction between furfural and ammonia gives furfuryl imine 100, followed by cracking reaction to furan 101 which is considered as the key intermediate leading to pyrrole 102 and ultimately to indoles 103, with pyridines, aniline, and benzenes being concurrently generated as byproducts (Scheme 28).…”

Rhodium‐Catalyzed Amination and Annulation of Arenes with Anthranils: C‐H Activation Assisted by Weakly Coordinating Amides

“…Treatment with m-CPBA and TFA afforded the transannulated product 7 in overall moderate yield (eq 2). [21] Reduction of 3 ja with LAH led to reduction of both the amide and the ketone functional groups (eq 3). To further display the synthetic utility, a 2 mmol-scale reaction has been performed and the product 3 ba was obtained in 83% yield (eq 4).…”

Efficient Synthesis of Arylated Furans by a Sequential Rh‐Catalyzed Arylation and Cycloisomerization of Cyclopropenes

“…[8] Thes ynthetic utility of this protocol was subsequently examined (Scheme 3). In the presence of m-CPBA, the products 3a and 3q undergo an oxidative rearrangement, [11] affording the corresponding products 4a and 4q in good yields.T hese products include ab enzofuran-3(2H)-one unit which is an important structural motif prevalently present in many natural products and biologically interesting compounds. [12] Thep roposed pathway includes an epoxidation of the furan ring encouraged by m-CPBA, followed by an intramolecular attack of the phenol unit.…”