Palladium-catalyzed oxidative cyclization of aniline-tethered alkylidenecyclopropanes with O₂: a facile protocol to selectively synthesize 2- and 3-vinylindoles

Abstract

A novel palladium-catalyzed oxidative cyclization of aniline-tethered alkylidenecyclopropanes using molecular oxygen as the terminal oxidant through β-carbon elimination of aminopalladation intermediates is disclosed. The reaction opens up an effective way to obtain a series of 2- and 3-vinylindoles which are important synthetic intermediates in many natural indole derivatives.

The Construction of Molecular Complexity from Functionalized Alkylidenecyclopropanes (FACPs)

“…However,3 -vinylindoles were produced when the ACPs were substituted by a hydrogena tom (Scheme 16 a). [22] From the mechanistic analysis, we concluded that the reaction pathways all underwent b-carbone limination to cleave the proximal CÀCb ond of the ACPs and b-hydride elimination to form the vinyl group. As for the formation of 3-vinylindoles,4 -exo-aminopalladationa nd b-aryl elimination insteado f5 -endo-aminopalladationmight occur successively,w hich assisted the shift of the alkylidenecyclopropanes to the aniline nitrogen atom, giving intermediate 71.T he detailedm echanism is outlined in Scheme 16 b.…”

“…The reaction underwent two different pathways relying on the substituents on the alkylidenecyclopropanes: When ACPs have substituents including aryl, alkyl, or heteroaromatic groups, 2‐vinylindoles were obtained. However, 3‐vinylindoles were produced when the ACPs were substituted by a hydrogen atom (Scheme a) . From the mechanistic analysis, we concluded that the reaction pathways all underwent β‐carbon elimination to cleave the proximal C−C bond of the ACPs and β‐hydride elimination to form the vinyl group.…”

Palladium‐Catalyzed Cascade Reductive and Carbonylative Cyclization of Ortho‐Iodo‐Tethered Methylenecyclopropanes (MCPs) Using N‐Formylsaccharin as CO Source

“…[14g,h] In 2013, Manabe's group reported a novel and practical method for palladium-catalyzed reductive carbonylation of aryl halides with N-formylsaccharin to produce aromatic aldehyde derivatives in good yields. [17] Very recently, our group also developed a novel palladium-catalyzed cascade cyclization of MCPs via a cyclopropene intermediate and a vinylÀ palladium carbene species, furnishing spirocyclic compounds in an unprecedented ring-opening pattern of MCPs (Scheme 1d). [14b] Due to the highly strained small ring and excellent reactivity, methylenecyclopropanes (MCPs) can undergo various ring-opening reactions in the presence of transition metal catalyst such as palladium catalyst.…”

“…UPDATES asc.wiley-vch.de 70°C or 75°C, the conversion of 1 g was improved and the yield of 3 g was raised to 48% (Table 1, entries 2-3). The phosphine ligands such as dppe, dppb and Xantphos, base and solvents were also examined respectively, but all affording 3 g in lower yields (Table 1, entries [14][15][16][17][18]. Next, when the amount of the transfer carbonylation reagent NFS and Et 3 SiH were increased from 1.5 to 2.0 eq, both of the conversion of 1 g and the yield of 3 g were increased, affording 3 g in 53% yield ( [7][8][9][10][11][12][13].…”

“…[16] In 2017, our group developed a palladium-catalyzed cyclization of aniline-tethered MCPs under oxidative conditions, in which the insertion of palladium into the proximal CÀ C bond took place, giving 2-and 3-vinylindole derivatives (Scheme 1c). [17] Very recently, our group also developed a novel palladium-catalyzed cascade cyclization of MCPs via a cyclopropene intermediate and a vinylÀ palladium carbene species, furnishing spirocyclic compounds in an unprecedented ring-opening pattern of MCPs (Scheme 1d). [18] On the basis of previous research work, herein, we aimed to develop a tandem reductive and carbonylative cyclization of MCPs using N-formylsaccharin as CO source under the catalysis of palladium via a new ringopening pattern.…”