Efficient Copper(II)‐Catalyzed Transamidation of Non‐Activated Primary Carboxamides and Ureas with Amines

Abstract

Carboxamides represent an important class of compounds found in numerous bioactive products, [1] such as top-sold medicines (i.e., Lipitor, Lidoderm, Vyvanse), [2] as well as in biological and synthetic polymers (i.e., proteins and nylons). [3] In addition, amides serve as versatile building blocks for the preparation of pharmaceuticals, agrochemicals, polymers, etc. [4] In general, substituted amides are prepared by substitution reactions of carboxylic acid derivatives with amines [14] [Scheme 1, Eq. (1)], or by the coupling of aryl/ alkyl halides with primary amides [15] [Scheme 1, Eq. (2)]. Alternatively, well-established name reactions (i.e., Ritter, [5] Schmidt, [6] Beckmann, [7] Ugi, [8] Wolff, [9] etc.) and more recently established approaches [10][11][12][13][14][15] are applied for their synthesis.

Benzoic Acid‐Catalyzed Transamidation Reactions of Carboxamides, Phthalimide, Ureas and Thioamide with Amines

“…[17] Fortunately, all types of substituted ureas could be reacted with aromatic amines in good to excellent yields with our developed protocol (Table 6). The transamidation of ureas needed copper as catalyst in previous documents.…”

“…[14] However, they always suffer from some limitations, such as stoichiometric amounts of activating agents, tedious work-up procedures and low reactivity. Bertrand, [16] Beller (Scheme 1, ii), [17] Myers, [18] Akamanchi, [19] Shimizu (Scheme 1, i), [20] Stahl, [21] and Williams [22] have reported a series of metal-catalyzed methods of transamidation. Unfortunately, because of the high stability of amided, transamidation usually requires harsh conditions, such as long reaction times, high temperatures (> 250 8C) or stoichiometric amounts of activating Scheme 1.…”

Self-coupling of benzylamines over a highly active and selective supported copper catalyst to produce N-substituted amines by the borrowing hydrogen method

“…With alcohols as the initial source of the electrophile, this reaction sequence can be initialized by several catalysts such as Pd [5], Pt [6], Ru [7], Ir [8], Ag [9], Au [10] and CuAg bimetallic catalysts [11]. The same methodology has also been applied for N-alkylation of nitroaromatics [12], N-alkylation of amines [5,7,9,10], transamidation of carboxyamides and ureas [13], and CAC bond formation [14]. Compared to the use of alcohols as the source of electrophiles, the alkylation of amines with other amines is much less developed.…”

“…Instead of alcohols, amines can also serve as alkylating agent, and the oxidative coupling of a primary amine to the corresponding secondary imine and water has recently been reported over graphite oxide (GO) [15] and Cu-based catalysts [13]. However, the one-pot transformation of primary amines to secondary amines with return of the 'borrowed' hydrogen is still a challenge.…”

Theoretical Insight into the Mechanism of an Efficient ʟ-Proline-catalyzed Transamidation of Acetamide with Benzylamine

“…7 Alternatively, the transamidation process is an attractive tool in the field of synthetic organic chemistry and represents an excellent unusual route for the functionalization of a given carboxamide. 8 So far, elegant methods for transamidation reactions (i.e., transamidation processes catalyzed by copper, 9 cerium, 10 hydroxylamine hydrochloride, 11 ammonium bromide, 12 and boric acid,…”