Efficient Iron‐Catalyzed Reductive N‐Alkylation of Aromatic Amines with Carboxylic Acid and Phenylsilane

Abstract

The development of efficient catalysts for the alkylation of amines with carboxylic acids is attracting much attention. Herein, we would like to report an earthabundant iron-catalyzed protocol for the N-alkylation of anilines using carboxylic acid as alkyl source and phenylsilane as reducing agent. With Fe 2 (CO) 9 as a catalyst, a broad range of primary and secondary anilines are successfully converted to the corresponding tertiary anilines. Furthermore, this N-alkylation mainly goes through the amide pathway; while the aldehyde pathway can not be ruled out.

Direct N‐Alkylation/Fluoroalkylation of Amines Using Carboxylic Acids via Transition‐Metal‐Free Catalysis

“…Consequently, development of new synthetic tools for selective construction of sp 3 C−N bonds still remains at the center stage of current organic research. Several elegant catalytic systems using an air‐sensitive Lewis acid (B(C 6 F 5 ) 3 ) and transition metal complexes (Fe, Co, Ni, Ru, Pt, Rh, and Ir) with silane or H 2 have been developed for DNACA recently, together with one catalyst free system employing ammonia borane as the reductant . However, the mechanisms of all these systems involve the reactive metal‐hydride or boron‐hydride species, leading to relatively limited functional group tolerance (Scheme b).…”

An overview of iron‐catalyzed N‐alkylation reactions

“…A new and efficient strategy was proposed by Li et al for the iron-catalyzed reductive N-alkylation of aromatic amines with carboxylic acids through amide pathway. [32] Phenyl silane was used as the reducing agent, and primary and secondary anilines were converted to the S C H E M E 2 N-Alkylation of aniline with benzyl alcohol S C H E M E 3 N-Alkylation of aniline using benzyl alcohol via Fe catalysis S C H E M E 4 Substrate scope for the N-alkylation reaction of aniline with alcohol corresponding tertiary anilines (Scheme 6). A series of amines were examined to identify the versatility of the newly developed catalyst.…”

“…A new and efficient strategy was proposed by Li et al for the iron‐catalyzed reductive N‐alkylation of aromatic amines with carboxylic acids through amide pathway. [ 32 ] Phenyl silane was used as the reducing agent, and primary and secondary anilines were converted to the corresponding tertiary anilines (Scheme 6). A series of amines were examined to identify the versatility of the newly developed catalyst.…”

Metal-Free Hydroxymethylation of Indole Derivatives with Formic Acid as an Alternative Way to Indirect Utilization of CO2

“…In most cases, transition-metal catalysts are essential to the aforementioned conversions, and the alkylation reagents are limited to carboxylic acids. With our continuing interest in the valorization of formic acid (HCOOH) and considering the high efficiency of reductive amination, ,, we envisaged to develop the hydroxymethylation of indole derivatives using HCOOH as the alkylation reagent. Thus, this protocol could achieve the selective indole N-alkylation and utilization of the renewable resource HCOOH as a C1 synthon for reductive amination simultaneously.…”

“…According to the above mechanistic studies as well as the former reports, a possible reaction mechanism is conceived involving the participation of the formoxysilane intermediate as depicted in Scheme . Initially, the deprotonation of N–H in indole assisted by TBD furnishes the indole nitrogen anion A integrated with the bulkier cation, that is, TBD-H + .…”