Palladium-Catalyzed Dearomative Allylic Alkylation of Indoles with Alkynes To Synthesize Indolenines with C3-Quarternary Centers

Abstract

A palladium-catalyzed dearomative allylic alkylation of indoles with alkynes to construct indolenines with C3-quarternary centers was reported. The in situ formed arylallene intermediate omitted the need to install leaving groups on the allylic compounds and employ extra oxidants to oxidize the allylic C-H bonds. The reaction exhibited good functional group tolerance and high atom economy. Moreover, the reaction was further expanded to synthesize pyrroloindolines and furanoindolines.

Alkynes as Electrophilic or Nucleophilic Allylmetal Precursors in Transition‐Metal Catalysis

“…In a concurrent study, Lin, Yao, and co‐workers reported the dearomatizing allylic alkylation of indoles with aryl propynes to furnish indolines bearing C3‐quaternary stereocenters. Again, carboxylic acid co‐catalysts were required as additives (Scheme ) …”

A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

“…The synthetic route to access 1 is shown in Scheme 3. From readily available 2bromo-6-hydroxybenzaldehyde (7), an initial Sonogashira coupling [15,16] with propyne was accomplished to afford 11 at a 69% yield. Initial attempts to form the isoquinoline scaffold from 10 were unsuccessful both via conversion of 10 into the corresponding tertbutylimine followed by a copper-catalyzed imino-annulation [17] or attempting a tandem imine formation and subsequent ethynyl-imino cyclization reaction with ammonia [18].…”

Allylic and Allenylic Dearomatization of Indoles Promoted by Graphene Oxide by Covalent Grafting Activation Mode

“…In particular, Tamaru ([Pd 0 ]/BEt 3 ), Trost ([Pd 0 ]/9‐BBN‐C 6 H 13 ), You ([Ru II ]/ p TsOH), You ([Ir I ]/Fe(OTf) 2 ) and Bisai ([Pd 0 /BEt 3 /KO t Bu]) documented very elegant methodologies (Figure ). Additionally, Pd‐mediated allylic C−H activations and site‐selective insertion into C−C triple bonds deserve particular mention as parallel methodologies in the indole allylative dearomatization realm.…”