Palladium‐Catalyzed Intramolecular ipso‐Friedel–Crafts Alkylation of Phenols and Indoles: Rearomatization‐Assisted Oxidative Addition

Abstract

Inspiroierend: Eine neuartige Synthese von Spirocyclen basierend auf einer Palladium‐katalysierten intramolekularen ipso‐Friedel‐Crafts‐Alkylierung von Phenolen (siehe Schema; dba=Dibenzylidenaceton) und Indolen wird beschrieben. Mechanistische Studien belegen, dass die Reaktion über eine präzedenzlose Rearomatisierungs‐unterstützte oxidative Addition verläuft.

Rhodium‐Catalyzed Intramolecular Difluoromethylenative Dearomatization of Phenols

“…Furthermore, this catalytic system was also effective for difluoromethylenative dearomatization of indoles 3c,4. When indole derivative 4 was treated under the optimized reaction conditions, aza‐spirocyclic adduct 5 was obtained in good yield [Equation (2)].…”

“…In the same year, You et al developed a procedure for iridium‐catalyzed asymmetric allylic dearomatization of phenols with excellent yields and enantioselectivities (Scheme , b) 3f. More recently, Hamada's group discovered a palladium‐catalyzed approach to ipso ‐Friedel–Crafts alkylation of phenols (Scheme , c); this kind of method can also be applied to dearomatization of indoles 3c…”

Gold‐Catalyzed Carbocyclization of Phenols with a Terminal Alkyne via an Intramolecular ipso‐Friedel–Crafts Alkenylation

“…We recently reported a novel method for synthesizing spiro[4.5]cyclohexadienones based on a Pd‐catalyzed intramolecular ipso ‐Friedel–Crafts allylic alkylation of phenols 6. The present reaction mode could be further extended to the synthesis of spiro[5.5]cyclohexadienones using η 3 ‐propargyl‐palladium(II) complexes as electrophiles7 (Scheme ). Based on this background, we hypothesized that an analogous spirocyclization should proceed through an intramolecular ipso ‐Friedel–Crafts‐type addition of phenols to alkynes activated by electrophilic gold catalysts, affording spirocyclohexadienones with an exo ‐cyclic olefin unit.…”

Platinum‐Catalyzed Friedel–Crafts‐Type C−H Coupling–Allylic Amination Cascade to Synthesize 3,4‐Fused Tricyclic Indoles

“…We recently demonstrated that h 3 -propargylpalladium(II) intermediates coulds erve as effective electrophilicp artnersi n ap alladium-catalyzedi ntramolecular ipso-Friedel-Crafts alkylation of para-substituted phenols. [8,9] We hypothesized that this reactionm ode could be applicable to the synthesis of 3,4fused tricyclic indoles (Scheme 1b). If meta-substituted aniline derivatives are utilized as substrates, aF riedel-Crafts-type CÀH coupling with h 3 -propargylpalladium(II) intermediates would occur at the ortho-position to the aniline to give p-allylpalladium(II) species.T he following CÀNb ond formation would afford 3,4-fusedt ricyclic 3-alkylidene indolines.E xtensive efforts based on this workingh ypothesis illustrated the overwhelming advantage of platinum catalysts for this reaction.…”

“…[11] Asimilar rapid palladacycle formation/reductive elimination process was also observed in our previousi ntramolecular ipso-Friedel-Crafts alkylation of phenols, reasonablys upporting this mechanistic consideration. [8] Sequential 6-endo or 5-exo cyclization of 5a proceeded under the reaction conditions, producing compound 2a or 3a,r espectively. [12] To make the desired pathway operative, selective promotion of the Friedel-Craft-type process from the h 3 -propargylpalladium(II) intermediate III is required.…”