Ligand‐free Iron(II)‐Catalyzed N‐Alkylation of Hindered Secondary Arylamines with Non‐activated Secondary and Primary Alcohols via a Carbocationic Pathway

Abstract

Secondary benzylic alcohols represent a challenging class of substrates for N-alkylation of amines. Herein, we describe an iron(II)-catalyzed eco-friendly protocol for N-alkylation of secondary arylamines with secondary benzyl alcohols through a carbocationic pathway instead of the known borrowing hydrogen transfer (BHT) approach. Transiently generated carbocations, produced from alcohols via self-condensation, were coupled with arylamines to provide highly functionalized amine products. The scope of this methodology involves N-alkylation of primary, secondary and heterocyclic amines with primary/secondary benzylic, allylic and heterocyclic alcohols, which are common key structures in numerous pharmaceuticals drugs. The method can also be easily adopted for the amination of various natural products.

Lewis‐Acid‐Catalyzed Direct Nucleophilic Substitution Reaction of Alcohols for the Functionalization of Aromatic Amines

“…Further, this complex A protonates B to form the benzylic cation ( D ) via desilylation of intermediate C . Next, carbocation D is trapped by various nucleophile such as thiol ( 1 bb ), and N ‐methylaniline ( 2 ) (Scheme c). Further, tin(II) amide attacks the cationic centre of D to form E .…”

TBN‐Catalyzed Dehydrative N‐Alkylation of Anilines with 4‐Hydroxybutan‐2‐one

“…In 1981, Grigg and Watanabe reported the first examples of alcohol substitution by N‐nucleophiles in the presence of rhodium, iridium, and ruthenium compounds. Since then, many efficient catalytic methods for the N ‐alkylation of amines as well as the related reactions by activating alcohols were developed using metal catalysts (Ag, Au, Ir, Pd, Re, Ru, Co, Cu, Fe, Mn and Ni), bimetallic catalysts and non‐metal catalysts etc (Scheme a). Most of these catalyst systems needed high temperatures and strong alkalis to work.…”

An overview of iron‐catalyzed N‐alkylation reactions

“…Maurya et al proposed an efficient protocol for the N‐alkylation of secondary aryl amines with secondary benzyl alcohols using Fe (II) catalyst through a carbocationic pathway, instead of conventional borrowing hydrogen transfer (BHT) method (Scheme 9). [ 35 ] In this study, they tested the scope of a wide variety of substrates. Both electron‐rich and electron‐deficient secondary benzylic alcohols gave good yields of the targeted tertiary arylamine products.…”