The Aminomethylation of Electron-Rich Aromatics with an N-Silyl-N,O-Acetal Catalyzed by a Metal Triflate-TMSCl System:  Facile Synthesis of Aromatic Primary Amines, 1-Aryl-trichloroethylamines

Abstract

The copper(II) triflate- and hafnium(IV) triflate-catalyzed aminomethylation of indole (2) with an N-silyl-N,O-acetal 1 containing a trichloromethyl group provides the primary amine derivative (3a) in modest yield. When 1 equiv of trimethylchlorosilane (TMSCl) was added to the reaction mixture, the reaction proceeded smoothly, and the yield of 3a was dramatically improved (>90%). The use of this catalytic system permitted the introduction of an aminomethyl group onto indoles 2a-h bearing a variety of functional groups, which appears to deactivate the Lewis acid, in 52-92% yields. Hf(OTf)4-doped TMSCl catalyzed the successful aminomethylation of various electron-rich aromatic compounds 4a-j to produce 1-aryl-trichloroethylamine derivatives 5a-j.

A General One-Pot, Three-Component Mono N-Alkylation of Amines and Amine Derivatives in Lithium Perchlorate/Diethyl Ether Solution

“…Since the 3-position in indoles is the preferred site for electrophilic substitution, an efficient catalyst is desirable for Friedel-Crafts reaction of indoles. Although a considerable number of the Lewis or protic acid-mediated aminomethylation of aromatic compounds or heterocycles using imine or iminium intermediates have been reported, 12 the Lewis acid catalyzed N-hydroxyaminoalkylation of indole(s) with an Otrimethylsilyloxime has not been studied. In this connection we describe the use of 5.0 M LPDE solution, as reaction medium for these reactions.…”

Innovative Catalytic Protocols for the Ring‐Closing Friedel–Crafts‐Type Alkylation and Alkenylation of Arenes

“…However, the use of stoichiometric amounts of Lewis or Brønsted acids are often required in order to guarantee reasonable conversions in acceptable times. Herein, allylic iminium ions are known to be valuable transient electrophilic species for both inter- [80] and intramolecular alkylation of aromatics. [81] In this context, Hiemstra, Rutjes and co-workers very recently reported the use of low loadings of Sn(OTf) 2 (2 %) as a catalyst for the formation of α-vinyl-substituted isoquinolines and β-carbolines in good yields via the allylic Nsulfonyliminium intermediate 100 (Scheme 32).…”

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

“…b When the reaction was performed using 2.5 equiv of SnCl 4 , 3.6 equiv of HMDS, and TMSCl and 2.1 equiv of 5-FU, at rt using CH 2 Cl 2 as the solvent, no formation of the products was observed. c No reaction was detected when 1.04 equiv of Sc(OTf) 3 was used, although there is evidence of effective activation of acetals, bearing a nitro group, by catalytic metal triflates (see ref ). d When the reaction temperature varies from 40 to 50 °C these conditions could be considered similar.…”