Friedel–Crafts Addition of Indoles to Nitrones Promoted by Trimethylsilyl Trifluoromethanesulfonate

Abstract

N-Alkylindoles undergo Friedel−Crafts addition to aryl and secondary alkyl nitrones in the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine to produce 3-(1-(silyloxyamino)alkyl)indoles. Spontaneous conversion to bisindolyl(aryl)methanes, which is thermodynamically favored for nitrones derived from aromatic aldehydes, is suppressed under the reaction conditions. The silyloxyamino group can be deprotected with tetrabutylammonium fluoride to yield hydroxylamines. Note pubs.acs.org/joc

Titanocene Lewis Acid Complexes with Diversified N,O-Ligands: Selectivity toward Three-Component Friedel–Crafts Reactions of Indoles

“…The Friedel–Crafts reaction of indoles with aldehydes or imines is a synthetically outstanding C–C/N bond-forming thoroughfare that provides an important architecture of key structural motifs of natural products, pharmaceuticals, agrochemicals, photochromic agents, and dendrimers. − As a result of its synthetic and theoretical significance, a range of Lewis acid and Brønsted acid catalysts have been developed in these transformations. − These methods constitute a valuable synthetic scheme for indoles. However, the controllable aza-Friedel–Crafts reaction into benzylamine adducts by acids seems to be restricted to highly electrophilic substrates and prefunctionalized imines that are not readily available, costly, and often unstable. − The three-component aza-Friedel–Crafts reaction of indoles with amines and aldehydes represents a convenient and green way. − Unfortunately, the formation of water in the three-component system tends to inactivate Lewis acid catalysts.…”

Catalytic Enantioselective Alkyne Addition to Nitrones Enabled by Tunable Axially Chiral Imidazole-Based P,N-Ligands

“…Additionally, in most highly enantioselective A 3 coupling reactions, the amine features symmetrical or very bulky alkyl groups to avoid isomerism or to minimize size differences; however, this strategy is not applicable to nitrones. Consequently, we envisioned that an activating reagent for nitrone such as TMSOTf would silylate the oxygen atom on nitrone, facilitating Cu-acetylide addition and also blocking the potential coordination with Cu-catalyst to prevent formation of the Kinugasa product and other 1,3-dipolar cycloaddition side reactions . To test this hypothesis, nitrone 1a and alkyne 2a were selected as the model substrates with the Cu-StackPhos catalyst.…”