An Efficient Approach for 3,3-Disubstituted Oxindoles Synthesis: Aryl Iodine Catalyzed Intramolecular C–N Bond Oxidative Cross-Coupling

Abstract

Herein, we report the first intramolecular C−N bond formation of phenylpropanamide derivatives via organocatalytic oxidative reactions, affording 3,3-disubstituted oxindole derivatives with up to 99% yield. The high efficiency of this reaction is exemplified by the transition metal-free mild conditions and the ability to perform the reaction on a gram scale. Meanwhile, the DFT calculation of the catalytic oxidative transformation pathway has also been studied.O xindole scaffolds, especially 3,3-disubstituted oxindole derivatives, exist in many privileged natural products and biologically active compounds such as the alkaloid horsfiline, the antibacterial agent arundaphine, etc. (Figure 1). 1 Therefore, novel methods to obtain oxindoles are worthy of further investigation in synthetic organic chemistry.

Hypervalent iodine-promoted twofold oxidative coupling of amines with amides and thioamides: chemoselective pathway to oxazoles and thiazoles

“…A tentative mechanism is proposed in Scheme 5 . The reaction commences with electrophilic activation of the C S and C O bonds by the hypervalent iodine reagent, 21 which is followed by the nucleophilic addition of amine. Subsequently, the first oxidation takes place to give thiourea 15 or urea 12.…”

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…Wang et al reported an organocatalytic oxidative system for the intramolecular amination of C(sp 2 )–H bonds for the formation of 3,3-disubstituted oxindoles including spirocyclic derivatives. 33 Thus, an intramolecular C–N cross-coupling reaction of phenylacetamide 27 bearing cyclic alkyl substituents at the α-position afforded structurally diverse spirooxindoles 28 in 74–98% yields. The reaction employed m CPBA as the oxidant and an aryl iodide C 3 as a catalyst and was facile with N -alkoxy substituents on substrate 27 .…”

PyBroP-mediated nucleophilic addition of oxindoles with pyridine N-oxides to access 3-pyridyl-3,3-disubstituted oxindoles

“…9 Consequently, the development of efficient protocols to access these scaffolds is an active area of research in organic chemistry. The available classical synthetic routes involve: (1) C–C bond formation reactions of oxindole derived nucleophiles or electrophiles such as Michael addition between C3-substituted oxindoles and α,β-unsaturated carbonyl compounds 10 or conjugated dienes, 11 allylic substitution between C3-substituted oxindoles and allylic electrophiles, 12 Mannich reaction of isatin imines 13 and Friedel–Crafts reactions of 3-hydroxy-xyindoles with arenes; 14 (2) oxidative arylation of oxindoles; 15 (3) intramolecular annulation reaction by transition-metal-catalyzed C–H amination 16 and carbon–halogen cross-couplings of N -arylacrylamide derivatives. 17 Despite these advancements made in this research area, to exploit a new convenient process to access C3-aromatic 3,3-disubstituted oxindoles remains highly desirable and is still a challenging topic.…”