Iron-Catalyzed Oxidative Coupling of Alkylamides with Arenes through Oxidation of Alkylamides Followed by Friedel−Crafts Alkylation

Abstract

FeCl(3) in combination with t-BuOOt-Bu as an oxidant was found to be an efficient catalyst for oxidation of alkylamides to α-(tert-butoxy)alkylamides. FeCl(2) and CuCl showed, respectively, almost the same and slightly lower activities compared with FeCl(3) in the tert-butoxylation of N-phenylpyrrolidone (1a), whereas no tert-butoxylated product was obtained by use of Fe(OTf)(3), RuCl(3), or Zr(OTf)(4). FeCl(3) was found to be effective also as a catalyst for the Friedel-Crafts alkylation with thus obtained α-(tert-butoxy)alkylamides. The Friedel-Crafts alkylation proceeded smoothly also in the presence of a catalytic amount of Fe(OTf)(3), RuCl(3), or Zr(OTf)(4). In contrast, FeCl(2) and CuCl, which showed certain activity toward the tert-butoxylation, failed to promote the Friedel-Crafts alkylation. Among the transition metal complexes thus far examined, only FeCl(3) showed high catalytic activities for both the oxidation and the Friedel-Crafts alkylation. The bifunctionality of FeCl(3) was utilized for the oxidative coupling of alkylamides with arenes through a tandem reaction consisting of oxidation of alkylamides to α-(tert-butoxy)alkylamides and the following Friedel-Crafts alkylation. The FeCl(3)-catalyzed oxidative coupling is applicable to a wide variety of alkylamides and arenes, though a combination of FeCl(3) with Fe(OTf)(3) was found to be effective for the reaction of arenes with low nucleophilicity. A Fe(II)-Fe(III) catalytic cycle is concerned with the tert-butoxylation, whereas a Fe(III) complex as a Lewis acid catalyzes the Friedel-Crafts alkylation.

Iron Catalysis in Organic Synthesis

“…75 A FriedelÀCrafts alkylation step is also involved in the following iron(III) triflate catalyzed three-component reaction for the synthesis of indenoquinolines (Scheme 86). 182 Damavandi and Sandaroos treated aryl aldehydes with arylamines and 1,3-indanedione under solvent-free conditions at 183 Alkylamines could be coupled with arenes in an analogous way (cf. Scheme 288).…”

“…An intramolecular variant of this transformation has been exploited for the construction of the pyrrolo[2,1-a]isoquinoline alkaloids (()-crispine A and (()-trolline. 183,551 You and co-workers reported the coupling of N-(pyridin-2-ylcarbonyl)-substituted α-amino acid derivatives with indoles (Scheme 287). 552 This direct CÀH/CÀH coupling was achieved in the presence of catalytic amounts of iron(III) chloride hexahydrate and di-tert-butyl peroxide as oxidant.…”

Transition-Metal-Catalyzed Functionalization of C(sp3)&singleBond;H Bonds of Amines

“…[22,23] The reaction is rationalized by assuming a cytochrome P-450 type mechanism, as shown in Scheme 3. The ruthenium(II) complex undergoes reaction with tert-butyl hydroperoxide to generate ruthenium(II) tert-butyl peroxide species 3, which is converted into the ruthenium(IV) oxide species 4 by protonolysis and O-O bond cleavage.…”

“…[20] An example is the development of an efficient method for the oxidation of a-C-H bonds of tertiary N-methylamines. [21][22][23] 40.1.1.5.6.1.1…”

“…The transformation can occur via two reaction paths: (1) oxidation to the (a-alkoxyalkyl)amides and subsequent S E Ar reaction, or (2) tandem combination of direct oxidative coupling of alkylamides and S E Ar reaction to give the products (Scheme 39). [23] Scheme 39 Iron(III) Chloride Catalyzed Tandem Reaction [23] Ar Among the transition metal complexes examined, only iron(III) chloride shows high catalytic activities for both oxidation of alkylamides and S E Ar reaction with the resulting a-(alkoxy)alkylamides. Treatment of 1-phenyl-1H-indole (1 equiv) and 1-phenylpyrrolidin-2one (6 equiv) with iron(III) chloride (3 mol%) and di-tert-butyl peroxide (3 equiv) in 1,2-dichloroethane at 90 8 8C for 7 hours generates the coupling product in 72% yield (Table 15, entry 1).…”