Revisiting the Intermolecular Fujiwara Hydroarylation of Alkynes

Abstract

The Fujiwara hydroarylation of alkynes was reinvestigated using the addition of indole to methyl or ethyl phenylpropiolate catalyzed by Pd(OAc)2 as a model reaction. Reactions were monitored by both 1H NMR spectroscopy and electrospray ionization mass spectrometry (ESI/MS), and also through reactions carried out in the gas phase using MS/MS experiments. Contrary to the original suggestion for exclusive heteroarene activation, the data supports the coexistence of both heteroarene activation (C–H activation) and alkyne activation (Friedel–Crafts‐type pathway). Under the reaction conditions used in this work, intermediates for both mechanisms were detected by NMR spectroscopy and MS, but alkyne activation seems to be predominant according to 1H NMR spectroscopic studies and theoretical predictions. Alkyne activation is promoted by the coordination of an electrophilic palladium species to the C–C triple bond, followed by nucleophilic attack of the heteroaryl counterpart. Two previously undetected equilibria in this reaction involving the vinylpalladium intermediates and the final products were also found to be critical to the stereoselectivity of the reaction.

Regioselective Direct C‐Alkenylation of Indoles

“…Av ery recent mechanistic investigation made on the reaction of indole with ethyl phenylpropiolate catalyzed by Pd(OAc) 2 has demonstrated that both processes depicted in Scheme 28 are operative with am arked preference for the alkyne activation at least in the adopted reaction conditions. [80] On the other hand, ap revious study on the intramolecular hydroarylation of aryl phenylpropiolates using the same catalyst in TFAh as shown as imilar trend consisting in ap reliminary alkyne activation followed by aF riedel-Crafts reaction. [81] The alkyne activation is particularly operative with Brønsted acids or metal derivatives having ar emarkable Lewis acidity.C onversely, CÀHa ctivation of indoles is very likely using some Pd II complexes or other transition metals( Ru, Rh) in the presence of ad irecting group at the nitrogen atom of the indole as previously discussed for the C-2 alkenylationsusing olefins.…”

“…A very recent mechanistic investigation made on the reaction of indole with ethyl phenylpropiolate catalyzed by Pd(OAc) 2 has demonstrated that both processes depicted in Scheme are operative with a marked preference for the alkyne activation at least in the adopted reaction conditions . On the other hand, a previous study on the intramolecular hydroarylation of aryl phenylpropiolates using the same catalyst in TFA has shown a similar trend consisting in a preliminary alkyne activation followed by a Friedel–Crafts reaction .…”

The Intermediates in Lewis Acid Catalysis with Lanthanide Triflates

“…[7] Examples of reactions catalysed by these metals include Friedel-Crafts acylations, [8] Michael additions, [9,10] aldol condensations [11] and cycloadditions. [18,19,28,29,[20][21][22][23][24][25][26][27] Electrospray ionization mass spectrometry (ESI-MS) is a highly sensitive technique for monitoring complex reaction mixtures. [17] The growing use and applications of lanthanides as catalysts calls for detailed understanding of their speciation in solution and their reactivity modes.…”

One‐Pot Synthesis of 3‐(2‐Fluoroalkenyl)indoles

“…Apparently this is related to elusive unstable nature of fluoroacetylenes that could be precursors for synthesis of the such structures by hydroarylation of alkynes with indoles; a commonly used method for preparation of 3‐alkenylindoles (Scheme ). [19a], In this context, formal result of the sequence herein proposed looks like the potential reaction of indoles with fluoroacetylenes.…”