Iron catalysed direct alkylation of amines with alcohols

Abstract

The selective conversion of carbon-oxygen bonds into carbon-nitrogen bonds to form amines is one of the most important chemical transformations for the production of bulk and fine chemicals and pharma intermediates. An attractive atom-economic way of carrying out such C-N bond formations is the direct N-alkylation of simple amines with alcohols by the borrowing hydrogen strategy. Recently, transition metal complexes based on precious metals have emerged as suitable catalysts for this transformation; however, the crucial change towards the use of abundant, inexpensive and environmentally friendly metals, in particular iron, has not yet been accomplished. Here we describe the homogeneous, iron-catalysed, direct alkylation of amines with alcohols. The scope of this new methodology includes the monoalkylation of anilines and benzyl amines with a wide range of alcohols, and the use of diols in the formation of five, six-and seven-membered nitrogen heterocycles, which are privileged structures in numerous pharmaceuticals.

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

“…Interestingly, when natural alcohol bearing pyrone skeleton such as maltol (16) was used as an alkylating agent for N-alkylation of 17, an unexpected rearranged product 19 was obtained instead of desired product 18 (Scheme 12). In future, we will explore the surprising reactivity pattern of this type of moieties with amines via specific structural rearrangement.…”

“…[11,12] For example, Zeng, [13] Shimizu, [14] Saito, [15] Feringa [16] and other groups [17] reported metal catalyzed mono-N-alkylation of primary amines with alcohols by a borrowing hydrogen transfer (BHT) methodology. Noteworthy, highly abundant and bio-relevant homogeneous transition metal catalysts such as Fe, Co and Mn which were used in the mono alkylation of primary amines with primary as well as secondary alcohols.…”

Yeni Ru-NHC Komplekslerinin Sentezi, Karakterizasyonu ve Aminlerin Alkilasyonundaki Uygulamaları

“…Daha sonra farklı ligantlar içeren birçok Ru [8,9], iridyum (Ir) [10,11] ve demir (Fe) [12] kompleksleri bu katalitik sistemde kullanılmıştır.…”

A Step into an eco‐Compatible Future: Iron‐ and Cobalt‐catalyzed Borrowing Hydrogen Transformation

“…[8] This exceptional toler-ance was exemplified in the direct synthesis of Piribedil, an anti-Parkinson drugp repared in one step from two functionalized startingm aterials (Scheme 4). first reportedt hat cat2 catalyzed this process with av ery broad scope andf unctional group tolerance in terms of halogenated aromatics or heteroaromatics, allowing an efficient borrowing hydrogen reaction of diversely functionalized substrates except for secondary alcohols, which rendered moderate yields (Scheme 3, bottom left).…”